Biomedical Therapy - International Academy of Homotoxicology
Biomedical Therapy - International Academy of Homotoxicology
Biomedical Therapy - International Academy of Homotoxicology
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Journal <strong>of</strong><br />
<strong>Biomedical</strong><br />
<strong>Therapy</strong><br />
Female<br />
Disorders<br />
Volume 5, Number 1 ) 2011<br />
Integrating Homeopathy<br />
and Conventional Medicine<br />
• Current Trends in Women’s Health<br />
• Which Came First: Insulin Resistance or Inflammation?
) 2<br />
)<br />
Cover © Sebastian Kaulitzki/medicstock.com<br />
© fixerOO/Fotolia.de<br />
© iStockphoto.com/Rosemarie © Gearhart iStockphoto.com/© Anatoliy Samara<br />
© iStockphoto.com/© DNY59<br />
Contents<br />
In Focus<br />
Current Trends in Women’s Health . . . . . . . . . . . . . . . . . . . . . . 4<br />
What Else Is New? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12<br />
From the Practice<br />
Uterine Fibroids: A Clinical Case Report . . . . . . . . . . . . . . . . . . 14<br />
Refresh Your <strong>Homotoxicology</strong><br />
Which Came First: Insulin Resistance or Inflammation? . . . . 16<br />
Practical Protocols<br />
Genital Human Papilloma Virus Infection<br />
Bioregulatory Management . . . . . . . . . . . . . . . . . . . . . . . . 20<br />
Specialized Applications<br />
Contributions <strong>of</strong> Biological Medicine in Infertility . . . . . . . . . 22<br />
Meet the Expert<br />
Dr. Mónica Lucia Name Guerra . . . . . . . . . . . . . . . . . . . . . . . . . 25<br />
Expand Your Research Knowledge<br />
Purpose-Orientated Clinical Research . . . . . . . . . . . . . . . . . . . 26<br />
Around the Globe<br />
Fifth <strong>International</strong> Congress on<br />
Complementary Medicine Research . . . . . . . . . . . . . . . . . . . . 29<br />
Research Highlights<br />
Traumeel for the Treatment <strong>of</strong><br />
Pain Associated With Breast Cancer . . . . . . . . . . . . . . . . . . . . . 30<br />
Published by/Verlegt durch: <strong>International</strong> <strong>Academy</strong> for <strong>Homotoxicology</strong> GmbH, Bahnackerstraße 16,<br />
76532 Baden-Baden, Germany, www.iah-online.com, e-mail: journal@iah-online.com<br />
Editor in Chief/verantwortlicher Redakteur: Dr. Alta A. Smit<br />
Editor: Dr. David W. Lescheid<br />
Managing Editor: Silvia Bartsch<br />
Print/Druck: Dinner Druck GmbH, Schlehenweg 6, 77963 Schwanau, Germany<br />
© 2011 <strong>International</strong> <strong>Academy</strong> for <strong>Homotoxicology</strong> GmbH, Baden-Baden, Germany<br />
© iStockphoto.com/Milena Lachowicz
Female Health in the 21st Century<br />
The woman <strong>of</strong> today lives in a<br />
changed environment, which<br />
plays a decisive role in the development<br />
<strong>of</strong> disease. The sociocultural<br />
environment has changed through<br />
shifting roles <strong>of</strong> women in society,<br />
who are <strong>of</strong>ten late parents and also<br />
support aging parents on top <strong>of</strong><br />
their own families and work. 1 The<br />
psychological stresses normal for<br />
our modern lives are <strong>of</strong>ten amplified<br />
by the dual role <strong>of</strong> career woman<br />
and housewife.<br />
The physical environment also has a<br />
substantial influence on women’s<br />
health. Environmental toxins have<br />
been implicated as so-called endocrine<br />
disruptors and as triggers for<br />
metabolic syndrome, which in itself<br />
is closely associated with female diseases,<br />
such as polycystic ovary syndrome<br />
and infertility. 2,3<br />
Thus, the triad <strong>of</strong> chronic psychological<br />
stress, environmental toxicity,<br />
and obesity with the concomitant<br />
systemic inflammation forms the<br />
background for many female disorders.<br />
This triad <strong>of</strong>ten becomes a circulus<br />
vitiosus.,<br />
)<br />
Dr. Alta A. Smit<br />
The eating patterns <strong>of</strong> modern<br />
women have changed, with stress<br />
eating being the order <strong>of</strong> the day. 4<br />
This is combined with a change in<br />
the activity <strong>of</strong> the hypothalamic-pituitary-adrenal<br />
axis. The resultant<br />
obesity increases systemic inflammation<br />
and increases the storage <strong>of</strong><br />
fat-soluble toxins, such as the organochlorides,<br />
noted endocrine disruptors.<br />
5,6<br />
In this issue, Dr. Michael Greer, a<br />
gynecologist, examines the current<br />
trends in women’s health and suggests<br />
possible treatment strategies.<br />
Dr. Olga García reports on a case <strong>of</strong><br />
uterine fibroids, treated with bioregulatory<br />
medicine, while Dr. Gaston<br />
Orellana has two contributions,<br />
one on infertility and one on the<br />
treatment <strong>of</strong> chronic postmastectomy<br />
pain, which won him the Reckeweg<br />
Incentive Award in 2008.<br />
As mentioned earlier, we see an increasing<br />
link between inflammation<br />
and metabolic disturbance. Dr. David<br />
Lescheid examines this phenomenon<br />
in his cutting-edge article on<br />
the link between insulin resistance<br />
and inflammation.<br />
Dr. Robbert van Haselen continues<br />
the series on research methodologies,<br />
and Dr. Konstantin Cesnulevicius<br />
reports on a complementary<br />
research congress in Tromsø, Norway.<br />
Journal <strong>of</strong> <strong>Biomedical</strong> <strong>Therapy</strong> 2011 ) Vol. 5, No. 1<br />
Last, we introduce an expert wellknown<br />
to many as an excellent<br />
lecturer with a beautiful voice:<br />
Dr. Mónica Name.<br />
Dr. Alta A. Smit<br />
References<br />
1. Ron P. Daughters as caregivers <strong>of</strong> aging<br />
parents: the shattering myth. J Gerontol Soc<br />
Work. 2009;52(2):135-153.<br />
2. Desvergne B, Feige JN, Casals-Casas C.<br />
PPAR-mediated activity <strong>of</strong> phthalates: a link<br />
to the obesity epidemic? Mol Cell Endocrinol.<br />
2009;304(1-2):43-48.<br />
3. Mendola P, Messer LC, Rappazzo K. Science<br />
linking environmental contaminant exposures<br />
with fertility and reproductive health<br />
impacts in the adult female. Fertil Steril.<br />
2008;89(suppl 2):e81-e94.<br />
4. Torres SJ, Nowson CA. Relationship between<br />
stress, eating behavior, and obesity. Nutrition.<br />
2007;23(11-12):887-894.<br />
5. Elobeid MA, Padilla MA, Brock DW, Ruden<br />
DM, Allison DB. Endocrine disruptors and<br />
obesity: an examination <strong>of</strong> selected persistent<br />
organic pollutants in the NHANES 1999-<br />
2002 data. Int J Environ Res Public Health.<br />
2010;7(7):2988-3005.<br />
6. Müllerová D, Kopecký J. White adipose tissue:<br />
storage and effector site for environmental<br />
pollutants. Physiol Res. 2007;56(4):375-<br />
381.<br />
) 3
) 4<br />
) In Focus<br />
Current Trends<br />
in Women’s Health<br />
Introduction<br />
After World War II, modern life<br />
brought special challenges for women’s<br />
health and family planning. Today,<br />
there is a growing trend for<br />
women to delay having their first<br />
baby until later in life to establish a<br />
career before embarking on parenthood;<br />
in addition, middle-aged<br />
women who remarry may want to<br />
add to their existing family with<br />
their new partner. Many epidemiological<br />
data investigating maternal<br />
age and fetal loss have confirmed<br />
that older age strongly increases a<br />
woman’s chances <strong>of</strong> stillbirth, miscarriage,<br />
and ectopic pregnancy. 1<br />
Older women carry risks <strong>of</strong> conceiving<br />
a trisomic oocyte and <strong>of</strong><br />
having a less efficient uterus. 2 Conversely,<br />
women who chose to have<br />
children early in life are returning to<br />
work and working longer into the<br />
perimenopausal and menopausal<br />
years (the so-called baby boomers<br />
turned zoomers). It is generally accepted<br />
that susceptibility to stress<br />
and stress-related illness can be affected<br />
by hormonal changes and<br />
that common menopausal symptoms<br />
(eg, tiredness and night sweats)<br />
can make women temporarily more<br />
susceptible to fatigue and stress at<br />
work. In addition to these trends in<br />
culture, the options for controlling<br />
fertility have grown during the past<br />
50 years, affecting the age at which<br />
women bear children. 2 Specifically,<br />
By Michael E. Greer, MD<br />
Obstetrician/Gynecologist<br />
“pills” or oral contraceptives (OCs)<br />
contain hormones that suppress<br />
ovulation, thicken the cervical mucous<br />
to block sperm passage, and/or<br />
cause abortion by making the uterine<br />
lining hostile to implantation.<br />
Oral contraceptives have been used<br />
in the management <strong>of</strong> premenstrual<br />
symptoms 3 and, although not sufficiently<br />
substantiated, endometriosis.<br />
4 Combined OCs have a significant<br />
protective effect on the risk <strong>of</strong><br />
ovarian and endometrial cancer,<br />
which increases with duration <strong>of</strong><br />
use, and can be used as chemoprevention<br />
in young women who are<br />
breast cancer gene (BRCA) mutation<br />
carriers. 5 Indeed, none <strong>of</strong> the large<br />
prospective cohort studies with prolonged<br />
follow-up has indicated an<br />
increased overall risk <strong>of</strong> cancer incidence<br />
or mortality among women<br />
that have ever used OCs. 5 However,<br />
OC use has been associated with an<br />
increased risk <strong>of</strong> venous thromboembolism.<br />
6 There is also a slightly<br />
increased breast cancer risk among<br />
current OC users that disappears 5<br />
to 10 years after discontinuation, an<br />
increased cervical cancer risk with<br />
long-term OC use, and an increased<br />
risk <strong>of</strong> benign liver tumors and liver<br />
cancer. 5<br />
However, the options surrounding<br />
fertility are not always a matter <strong>of</strong><br />
choice. Among the many chemicals<br />
and toxins released into the environment<br />
during the past decades, the<br />
endocrine disruptors can interfere<br />
Journal <strong>of</strong> <strong>Biomedical</strong> <strong>Therapy</strong> 2011 ) Vol. 5, No. 1<br />
with the endocrine system through<br />
their binding to intracellular receptor<br />
proteins for steroid hormones. 7<br />
In particular, endocrine disruptors<br />
have a strong impact on the normal<br />
functioning <strong>of</strong> the reproductive system.<br />
7,8 They ultimately interfere<br />
with the effects <strong>of</strong> endogenous steroid<br />
hormones, evoking hormonal<br />
effects in animals, humans, and cell<br />
cultures. 8 For example, bisphenol A,<br />
used in the manufacture <strong>of</strong> plastics,<br />
has been associated with many different<br />
malformations <strong>of</strong> the female<br />
reproductive tract, including cystic<br />
ovaries, in animal models. 7 Moreover,<br />
the detrimental effects on reproductive<br />
physiological features in<br />
animals by other medicines, such as<br />
nonsteroidal anti-inflammatory<br />
drugs, after long-term inhibition <strong>of</strong><br />
prostaglandins in humans remain<br />
unknown. 9 However, the most dramatic<br />
effects <strong>of</strong> endocrine disruptors<br />
may be the many reproductive organ<br />
dysfunctions observed in women<br />
exposed in utero to diethylstilbestrol.<br />
8<br />
Disorders <strong>of</strong> the female reproductive<br />
system (Figure 1) have a wide<br />
range <strong>of</strong> etiologies, including infections<br />
and hormonal problems. Primary<br />
symptoms can vary from vaginal<br />
discomfort and discharge to<br />
chronic debilitating pain. Although<br />
the pa tho physiological characteristics<br />
<strong>of</strong> some conditions are wellknown,<br />
others are more enigmatic,<br />
with multiorgan involvement and
Ovary<br />
multiple potential targets for treatment,<br />
and require a comprehensive<br />
approach to patient management.<br />
This article reviews current thinking<br />
on some <strong>of</strong> the more challenging<br />
conditions affecting female health.<br />
Inflammatory Disorders<br />
Fallopian tube<br />
Cervix<br />
Vagina<br />
Figure 1. Female Reproductive System<br />
Vaginitis<br />
Vaginitis is one <strong>of</strong> the most common<br />
reasons for women to present to a<br />
family physician. 10 In the United<br />
States each year, an estimated 10<br />
million health care <strong>of</strong>fice visits to<br />
gynecologists are because <strong>of</strong> vulvovaginitis.<br />
11 Vulvovaginitis is a term<br />
encompassing a variety <strong>of</strong> inflammatory<br />
lower genital tract disorders.<br />
11 In addition to infection, other<br />
causes <strong>of</strong> vaginal itching, burning,<br />
irritation, or discharge include allergy<br />
to latex condoms, contact dermatitis,<br />
and atrophic vaginitis. 10<br />
Although the causes <strong>of</strong> vulvovaginitis<br />
are many and varied, women fre-<br />
) In Focus<br />
Uterus<br />
quently assume they are the result <strong>of</strong><br />
a yeast infection or an allergy to a<br />
new product. Consequently, the use<br />
<strong>of</strong> over-the-counter medications is<br />
very high for this condition. This<br />
can lead to considerable delay between<br />
the onset <strong>of</strong> symptoms and<br />
consultation with a clinician and establishment<br />
<strong>of</strong> a definitive diagnosis.<br />
12<br />
Infectious vaginitis can be caused by<br />
several organisms. The most common<br />
<strong>of</strong> these organisms are Gardnerella<br />
vaginalis and Mycoplasma hominis,<br />
causing bacterial vaginosis<br />
(22%-50%); Candida albicans, causing<br />
vulvovaginal candidiasis (17%-<br />
39%); and Trichomonas vaginalis<br />
causing vaginitis and/or urethritis<br />
(4%-35%). However, coinfections<br />
can exist, and the exact cause <strong>of</strong><br />
vaginal symptoms may remain undiagnosed<br />
in many women. 10<br />
Approximately 75% <strong>of</strong> women will<br />
have an episode <strong>of</strong> vulvovaginal<br />
candidiasis within their lifetime;<br />
Journal <strong>of</strong> <strong>Biomedical</strong> <strong>Therapy</strong> 2011 ) Vol. 5, No. 1<br />
Endometrial<br />
(uterine) lining<br />
Myometrium<br />
© fixerOO/Fotolia.de<br />
40% to 45% will have 2 or more<br />
episodes. 10 However, many women<br />
with symptoms <strong>of</strong> recurrent vaginitis<br />
do not have candidiasis; consequently,<br />
self-treatment with overthe-counter<br />
antifungal agents is<br />
ineffective. 12 Trichomoniasis is estimated<br />
to be responsible for 25% <strong>of</strong><br />
vaginitis cases in the United States<br />
and is the most common nonviral<br />
sexually transmitted infection. 12<br />
Patients with infectious vaginitis<br />
commonly present with vaginal or<br />
perineal vulvar irritation and abnormal<br />
vaginal discharge. 10 However,<br />
women with bacterial vaginosis and<br />
trichomonas can be asymptomatic. 10<br />
Etiology cannot be confirmed without<br />
examination <strong>of</strong> the discharge<br />
specimen. The gold standard for the<br />
diagnosis <strong>of</strong> candidiasis is visualization<br />
<strong>of</strong> pseudohyphae (mycelia)<br />
and/or budding yeast on a 10% potassium<br />
hydroxide wet preparation;<br />
for bacterial vaginosis, vaginal Gram<br />
stain (Nugent or Spiegel criteria);<br />
) 5
) 6<br />
) In Focus<br />
Figure 2. Endoscopic Image<br />
<strong>of</strong> a Ruptured Endometrial Cyst<br />
(“Chocolate Cyst”)<br />
and for T vaginalis, culture (Diamond<br />
media or InPouch TV). 13 The<br />
treatment <strong>of</strong> infectious vaginitis depends<br />
on the causative organism:<br />
antifungals are used to treat candidiasis;<br />
antibiotics, such as metronidazole<br />
and clindamycin, are effective<br />
against anaerobic bacteria and<br />
are used to treat bacterial vaginosis;<br />
and either metronidazole or tinidazole<br />
are usually used to treat T vaginalis,<br />
a protozoan. 10 In conventional<br />
treatment for candidiasis, topical<br />
azoles are the mainstay <strong>of</strong> treatment,<br />
achieving complete relief <strong>of</strong> symptoms<br />
in 80% to 90% <strong>of</strong> patients.<br />
However, oral agents are more acceptable<br />
and convenient for many<br />
women, although they are associated<br />
with adverse effects, such as<br />
headache and gastrointestinal upset,<br />
and are more costly. A single 150mg<br />
fluconazole dose will achieve<br />
clearance in approximately two<br />
thirds <strong>of</strong> patients, whereas a second<br />
dose, given on day 3, will yield an<br />
80% clearance rate. In women with<br />
recurrent infections, longer courses<br />
may be needed to suppress Candida.<br />
Treatment failure may indicate infection<br />
with Candida glabrata, which<br />
does not respond well to azoles, in<br />
which case intravaginal boric acid<br />
capsules may be effective. 10<br />
Bacterial vaginosis is usually treated<br />
with metronidazole or macrolide<br />
antibiotics, such as clindamycin. 12<br />
Although treatment <strong>of</strong> bacterial<br />
vaginosis reduces symptoms, recur-<br />
rences are common: 23% <strong>of</strong> women<br />
will have a recurrence at 1 month,<br />
and 58% will experience a recurrence<br />
within 1 year. 10<br />
Trichomonas is usually treated with<br />
oral nitroimidazoles, such as metronidazole.<br />
12 In trichomonas, abstinence<br />
from alcohol is recommended<br />
for 24 hours after starting metronidazole<br />
treatment and for 72 hours<br />
after taking tinidazole because <strong>of</strong><br />
the potential for a disulfiram-like reaction,<br />
which may include flushing,<br />
nausea, vomiting, thirst, palpitations,<br />
chest pain, vertigo, and hypotension.<br />
10<br />
Because trichomonas is a sexually<br />
transmitted infection, and carriers<br />
may be asymptomatic, sexual partners<br />
should also be treated to prevent<br />
reinfection. Indeed, recurrences<br />
<strong>of</strong> trichomonas are commonly reinfections<br />
or may be a consequence <strong>of</strong><br />
nonadherence to medical treatment.<br />
10 However, there are cases <strong>of</strong><br />
resistance to metronidazole. 10<br />
Pelvic Inflammatory Disease<br />
Pelvic inflammatory disease (PID) is<br />
defined as an ascending infection<br />
that spreads from the vagina or cervix<br />
to the fallopian tubes, endometrium,<br />
ovaries, and peritoneum. It<br />
can lead to any combination <strong>of</strong> endometritis,<br />
salpingitis, tubo-ovarian<br />
abscess, and pelvic peritonitis. 14 Pelvic<br />
inflammatory disease has the potential<br />
for fallopian tube scarring,<br />
chronic pelvic pain, ectopic preg-<br />
Journal <strong>of</strong> <strong>Biomedical</strong> <strong>Therapy</strong> 2011 ) Vol. 5, No. 1<br />
http://en.wikipedia.org/wiki/File:Perforierte_<br />
Endometriosezyste.jpg<br />
nancies, and infertility. 10,15 Indeed,<br />
approximately 25% <strong>of</strong> women who<br />
experience a single episode <strong>of</strong> PID<br />
experience tubal infertility, chronic<br />
pelvic pain, or an ectopic pregnancy;<br />
after a third episode <strong>of</strong> PID, half<br />
<strong>of</strong> the women will experience infertility.<br />
14<br />
In the developed world, 8% to 15%<br />
<strong>of</strong> women may be diagnosed as having<br />
PID in their lifetime, whereas<br />
much higher rates (up to 32%) are<br />
reported in the developing world. 16<br />
Chlamydia trachomatis and Neisseria<br />
gonorrhoeae are the organisms most<br />
commonly implicated in PID. 14-16<br />
Swabs <strong>of</strong> the cervix identify gonorrhea<br />
in 30% to 80% <strong>of</strong> patients and<br />
chlamydia in 20% to 40% <strong>of</strong> patients.<br />
14 There are concerns that recent<br />
increases in the incidence <strong>of</strong><br />
chlamydia and gonorrhea may be<br />
associated with an increase in the<br />
incidence <strong>of</strong> PID. 15 Pelvic inflammatory<br />
disease may develop in up to<br />
40% <strong>of</strong> women with untreated chlamydia<br />
infection and in most women<br />
with untreated gonorrhea. 10<br />
Gonorrhea and chlamydia may initiate<br />
a polymicrobial infection, including<br />
Gram-positive and Gramnegative<br />
bacteria and anaerobes.<br />
<strong>Therapy</strong> requires multiple antibiotic<br />
regimens to ensure that all organisms<br />
are treated. 10,15,16 Treatment<br />
may be oral or intravenous, depending<br />
on the status <strong>of</strong> the patient and<br />
the patient’s ability and/or willingness<br />
to take oral medication. 10
Adequate antibiotic coverage for anaerobic<br />
organisms is difficult to<br />
achieve, with metronidazole appearing<br />
to have limited efficacy, possibly<br />
because poor tolerability limits<br />
compliance. 16 Microbial resistance<br />
to other antibiotics also is a problem.<br />
15-17<br />
As a consequence <strong>of</strong> the prevalence<br />
<strong>of</strong> antibiotic resistance, modulation<br />
<strong>of</strong> the innate immune system to protect<br />
against infection has been discussed<br />
as an attractive alternative to<br />
antibiotic therapies in the medical<br />
literature. 18 Study <strong>of</strong> the innate immune<br />
response has indicated that<br />
there is variation in host immunity,<br />
possibly because <strong>of</strong> genetic differences.<br />
Thus, a suboptimal innate immune<br />
response may result in a permissive<br />
environment for pathogen<br />
colonization, whereas an excessive<br />
response will result in disproportionate<br />
levels <strong>of</strong> inflammation and<br />
tissue damage. An investigation <strong>of</strong><br />
modulation <strong>of</strong> the innate immune<br />
response in the reproductive tract<br />
could provide significant advances<br />
in the management <strong>of</strong> PID and its<br />
sequelae. 18<br />
Endometriosis<br />
Endometriosis can have a pr<strong>of</strong>ound<br />
impact on a woman’s life, potentially<br />
affecting her education, career,<br />
and ability to have children. 19 The<br />
cost <strong>of</strong> endometriosis to both the individual<br />
and society, including delayed<br />
diagnosis and ineffective treatments,<br />
is considerable and poorly<br />
quantified. 19 The results <strong>of</strong> a health<br />
survey in the United States indicated<br />
that half <strong>of</strong> women reporting endometriosis<br />
required at least a day <strong>of</strong><br />
bed rest within the past year, as a<br />
consequence <strong>of</strong> the condition, with<br />
the average number <strong>of</strong> days <strong>of</strong> bed<br />
rest being 17.8. 20 More than 8% <strong>of</strong><br />
women reported that endometriosis<br />
limited their activity, and nearly 5%<br />
reported that it limited them in their<br />
) In Focus<br />
work; only cancer and prolapse provided<br />
greater levels <strong>of</strong> limitation in<br />
this survey. 20 Confirming these findings,<br />
the first Global Study <strong>of</strong> Women’s<br />
Health reporting the societal<br />
impact <strong>of</strong> endometriosis found a<br />
significant loss <strong>of</strong> work productivity<br />
among 1459 women (aged 18-45<br />
years) who have the condition. Loss<br />
<strong>of</strong> work productivity (not caused by<br />
absence from work) was approximately<br />
10 hours per week vs 7<br />
hours per week for those with other<br />
disorders. Non–work-related activities,<br />
such as housework, exercise,<br />
and child care, were also significantly<br />
impaired. 21<br />
Endometriosis remains an enigmatic<br />
disorder: the etiology, natural history,<br />
and mechanisms by which it<br />
causes pain are not completely understood.<br />
22,23 Endometriosis is a<br />
condition in which tissue with the<br />
characteristics <strong>of</strong> endometrial tissue<br />
is located outside the endometrial<br />
cavity. 19,22 The most commonly<br />
acepted theory regarding the pathophysiological<br />
features <strong>of</strong> endometriosis<br />
is that desquamated<br />
en do metrial cells are transported<br />
into the peritoneal cavity after retrograde<br />
menstruation, with viable<br />
cells subsequently implanting and<br />
growing. 19,24-27<br />
For some patients, endometriosis is<br />
not significant; for others, it is aggressive<br />
and invasive, causing incapacitating<br />
pain. 22 The pain associated<br />
with endometriosis commonly<br />
manifests as dysmenorrhea, dyspareunia,<br />
and chronic pelvic pain<br />
(noncyclic nonmenstrual pelvic<br />
pain). 22<br />
The true prevalence and incidence<br />
<strong>of</strong> endometriosis are difficult to determine<br />
because diagnosis requires<br />
surgical biopsy with histological<br />
confirmation. 22 The disorder is more<br />
common in women <strong>of</strong> reproductive<br />
age, 24 with the prevalence estimated<br />
to be between 6% and 15%. 19,26,27<br />
Journal <strong>of</strong> <strong>Biomedical</strong> <strong>Therapy</strong> 2011 ) Vol. 5, No. 1<br />
The annual incidence <strong>of</strong> surgically<br />
diagnosed disease is 1.6 per 1000<br />
women aged 15 to 49 years. 26 It is<br />
estimated that 5% to 21% <strong>of</strong> women<br />
with pelvic pain experience endometriosis,<br />
25 increasing to approximately<br />
75% <strong>of</strong> women with chronic<br />
pelvic pain. 26 Endometriosis is the<br />
third leading cause <strong>of</strong> gynecologic<br />
hospitalization in the United<br />
States. 26 Approximately half <strong>of</strong><br />
women with endometriosis are infertile,<br />
25 and endometriosis represents<br />
the leading cause <strong>of</strong> infertility.<br />
26<br />
Incomplete knowledge regarding<br />
the pathogenesis and pathophysiological<br />
features <strong>of</strong> endometriosis is a<br />
major obstacle to effective treatment.<br />
19 There are several factors that<br />
may be implicated in the pathogenesis<br />
<strong>of</strong> endometriosis, including hormonal<br />
dysfunction, aberrant gene<br />
expression, immunoinflammatory<br />
chan ges, abnormal growth (Figure<br />
2), remodeling, and angiogenesis. It<br />
is believed that all these dysfunctions<br />
play a role in the underlying<br />
multifactorial molecular events leading<br />
to the development <strong>of</strong> endometriosis<br />
and its symptoms. 25<br />
Oxidative stress has been implicated<br />
in endometriosis and infertility. An<br />
imbalance in the generation <strong>of</strong> reactive<br />
oxygen species and the scavenging<br />
capacity <strong>of</strong> antioxidants in the<br />
reproductive tract provides an environment<br />
for the development <strong>of</strong><br />
oxidative stress. 24 Indeed, studies<br />
have shown that oxidative stress and<br />
antioxidant biomarkers are present<br />
in both serum and peritoneal fluid<br />
<strong>of</strong> women with endometriosis. 24<br />
Women with endometriosis may exhibit<br />
altered expression <strong>of</strong> the enzymes<br />
involved in the defense<br />
against oxidative stress in the endometrium.<br />
24<br />
Antioxidants, such as vitamin E, can<br />
play an important role in protecting<br />
biological membranes by preventing<br />
) 7
) 8<br />
) In Focus<br />
Figure 3. Ultrasound Showing<br />
Typical Ovarian Cysts in Polycystic<br />
Ovary Syndrome<br />
the activation <strong>of</strong> pathways implicated<br />
in abnormal cell proliferation and<br />
inflammatory response. However,<br />
the role <strong>of</strong> antioxidants in endometriosis<br />
is not clear. Although some<br />
studies have found that they can afford<br />
some protection against the development<br />
<strong>of</strong> endometriosis, others<br />
have found no improvement. 24<br />
There is evidence that endometriosis<br />
is a pelvic inflammatory process. 22,26<br />
Indeed, there is emerging evidence<br />
that women with endometriosis are<br />
more likely to have other inflammatory<br />
diseases, such as fibromyalgia<br />
and rheumatoid arthritis, than the<br />
general population. 26 Endometriosis<br />
generates significant inflammatory<br />
responses, suggesting that much <strong>of</strong><br />
the pain associated with endometriosis<br />
is inflammatory. 22 A theory is<br />
that the presence <strong>of</strong> inflammation<br />
activates silent nociceptors and significantly<br />
enhances both the sensitivity<br />
and severity <strong>of</strong> visceral pain. 22<br />
Visceral cross sensitization is<br />
thought to be a factor in the common<br />
co-occurrence <strong>of</strong> other visceral<br />
pain syndromes, such as dyspareunia,<br />
interstitial cystitis, and irritable<br />
bowel syndrome. 22 It is believed to<br />
be the result <strong>of</strong> increased persistent<br />
nociceptive input from inflamed reproductive<br />
system organs that sensitize<br />
neurons, particularly at the dorsal<br />
root ganglion; they also receive<br />
input from unaffected visceral organs<br />
(eg, bladder and colon). This<br />
phenomenon may underlie comor-<br />
bidity in many functional visceral<br />
pain syndromes. 22<br />
Surgery is the first-line treatment<br />
option for endometriosis. Conservative<br />
surgical removal <strong>of</strong> endometriosis<br />
provides pain relief and increases<br />
the chances <strong>of</strong> pregnancy. 19 However,<br />
this approach is far from ideal.<br />
Although surgery may alleviate pelvic<br />
pain in the short-term, it usually<br />
recurs within 2 years. Furthermore,<br />
the spontaneous pregnancy rate after<br />
surgery is generally lower than<br />
50%. 19 In addition, there are risks<br />
associated with surgery and repeated<br />
use <strong>of</strong> this modality increases the<br />
risk <strong>of</strong> complications. 19 Thus, medical<br />
treatment is generally used to<br />
prevent recurrences.<br />
Despite a paucity <strong>of</strong> evidence, nonsteroidal<br />
anti-inflammatory drugs<br />
are <strong>of</strong>ten used to treat symptoms. 19<br />
Hormonal treatments, such as OCs,<br />
are frequently used with some success,<br />
although symptoms <strong>of</strong>ten return<br />
and may even worsen on cessation.<br />
19 An obvious drawback <strong>of</strong><br />
hormonal approaches is that they<br />
disrupt the menstrual cycle and do<br />
not <strong>of</strong>fer an option for women who<br />
want to conceive. 27 Although research<br />
into new treatment options is<br />
ongoing, surgical and medical treatment<br />
<strong>of</strong> endometriosis is far from<br />
satisfactory. 19,26,27 Ideally, treatment<br />
should alleviate the pain and address<br />
the subfertility associated with<br />
the disease, while not interfering<br />
with ovulation and menstruation. In<br />
Journal <strong>of</strong> <strong>Biomedical</strong> <strong>Therapy</strong> 2011 ) Vol. 5, No. 1<br />
addition, treatment should be well<br />
tolerated and have no significant adverse<br />
effects or teratogenicity. 27<br />
Bioregulatory Treatment<br />
© iStockphoto.com/Amanda Rohde<br />
Vaginitis and PID<br />
The bioregulatory treatment <strong>of</strong> vaginitis<br />
and PID is directed toward the<br />
terrain and especially toward the<br />
epithelial barrier and the restoration<br />
<strong>of</strong> symbiotic micr<strong>of</strong>lora. As previously<br />
mentioned, it is <strong>of</strong>ten difficult<br />
to contain the conditions with only<br />
antimicrobial treatment and it is difficult<br />
to deal with recurrences. Treatment<br />
options include Gynäcoheel;<br />
because <strong>of</strong> the low-dose ingredients,<br />
this agent is thought to have an action<br />
on inflammatory conditions <strong>of</strong><br />
the female genital tract. 28 Furthermore,<br />
the addition <strong>of</strong> Mucosa compositum<br />
to support the epithelial<br />
barrier is useful. For bacterial infections,<br />
Echinacea compositum is used<br />
in an adjuvant fashion, and Metro-<br />
Adnex-Injeel is added in the case <strong>of</strong><br />
PID. Last, if the situation is recurrent,<br />
the patient should undergo a<br />
basic detoxification, as described in<br />
previous issues <strong>of</strong> this journal. 29<br />
Probiotics form an essential part <strong>of</strong><br />
the treatment <strong>of</strong> vaginitis and may<br />
even have a preventative role. 30,31 It<br />
is essential to restore the flora after<br />
antimicrobial treatment and to ensure<br />
a healthy genital tract environment.
Endometriosis<br />
Bioregulatory therapy has a significant<br />
role to play in the treatment <strong>of</strong><br />
endometriosis because the condition<br />
presents like a typical dysregulation<br />
syndrome. The immune and neuroendocrine<br />
systems, and local tissue<br />
cycles, are involved, making linear<br />
intervention difficult; therefore, endometriosis<br />
lends itself to the multitargeted<br />
approach that is used in<br />
homotoxicology.<br />
The basic treatment for endometriosis<br />
is the inflammation-regulating<br />
drug Traumeel. Ovarium compositum<br />
is added, along with Coenzyme<br />
compositum for metabolic support.<br />
Ovarium compositum also contains<br />
hypophysis suis, which supports the<br />
hypothalamic-pituitary-ovarian-adrenal<br />
axis. The immunomodulator,<br />
Tonsilla compositum, is used to support<br />
the immune system. In addition,<br />
Tonsilla compositum contains<br />
hypothalamus suis and glandula suprarenalis<br />
suis that further support<br />
the hypothalamic-pituitary-adrenal<br />
axis; and a primitive tissue, funiculus<br />
umbilicalis suis, that is postulated to<br />
support the connective tissue. 28<br />
Traumeel is given daily, whereas the<br />
other medications are prescribed in<br />
cycles <strong>of</strong> 5 weeks, with 4 weeks’ rest<br />
in between (2 ampoules <strong>of</strong> each are<br />
given orally or subcutaneously twice<br />
a week). The number <strong>of</strong> cycles needed<br />
depends on the response <strong>of</strong> the<br />
patient.<br />
Metabolic Disorders:<br />
Polycystic Ovary Syndrome<br />
Polycystic ovary syndrome (PCOS)<br />
is the most frequent endocrinopathy<br />
in women <strong>of</strong> reproductive age, 32 occurring<br />
in approximately 5% to 10%<br />
<strong>of</strong> these women. 33,34 The Rotterdam<br />
criteria for the diagnosis <strong>of</strong> PCOS<br />
require 2 <strong>of</strong> the following 3 criteria<br />
to be met: irregular or no ovulation,<br />
clinical/paraclinical hyperandro-<br />
) In Focus<br />
genemia, and polycystic ovaries<br />
(Figure 3). Other causes <strong>of</strong> hyperandrogenemia<br />
also need to be excluded.<br />
32 Interestingly, confirmation <strong>of</strong><br />
the presence <strong>of</strong> polycystic ovaries is<br />
not necessary for diagnosis. 33<br />
Polycystic ovary syndrome can affect<br />
women in many different<br />
ways. 33 Common manifestations <strong>of</strong><br />
PCOS include hirsutism, infertility,<br />
insulin resistance, and menstrual irregularities.<br />
33 Other conditions that<br />
may be associated with PCOS include<br />
hypertension, dyslipidemia,<br />
and type 2 diabetes mellitus, which<br />
all increase the risk <strong>of</strong> cardiovascular<br />
events, with associated morbidity<br />
and mortality. 34,35 Thus, PCOS is<br />
recognized as having a major impact<br />
throughout life on the gynecological<br />
and metabolic health <strong>of</strong><br />
women. 34<br />
Treatment <strong>of</strong> PCOS is frequently<br />
targeted at specific manifestations.<br />
For example, insulin-sensitizing<br />
agents, such as metformin, may be<br />
used to treat insulin resistance; eflornithine<br />
may be used to treat hirsutism;<br />
and OCs may be used to address<br />
menstrual irregularities or,<br />
alternatively, clomiphene may be<br />
used to address infertility. 33 Treatment<br />
should aim to break the vicious<br />
cycle <strong>of</strong> abdominal obesity<br />
and inflammation that lead to increased<br />
testosterone levels and, thus,<br />
promote the abdominal obesity/inflammation<br />
cycle. 32<br />
The prevalence <strong>of</strong> insulin resistance<br />
is much higher in women with<br />
PCOS compared with an age- and<br />
weight-matched population <strong>of</strong><br />
women. 33 Insulin resistance is <strong>of</strong>ten<br />
a precursor to the development <strong>of</strong><br />
diabetes and is a component <strong>of</strong> the<br />
metabolic syndrome, conferring an<br />
increased cardiovascular risk. 33 Approximately<br />
50% to 70% <strong>of</strong> women<br />
with PCOS have some degree <strong>of</strong> insulin<br />
resistance. 35 However, the precise<br />
mechanism <strong>of</strong> insulin resistance<br />
Journal <strong>of</strong> <strong>Biomedical</strong> <strong>Therapy</strong> 2011 ) Vol. 5, No. 1<br />
is not clear. It seems most likely that<br />
this is a result <strong>of</strong> impaired glucose<br />
metabolism, rather than a difference<br />
in the number and affinity <strong>of</strong> insulin<br />
receptors, making the mechanism <strong>of</strong><br />
insulin resistance in PCOS unique. 32<br />
In the ovaries, high insulin levels<br />
stimulate the conversion <strong>of</strong> progesterone<br />
to androstenedione, which is<br />
then converted to testosterone. The<br />
theory that hyperinsulinemia may<br />
stimulate hyperandrogenemia in<br />
PCOS is supported by the efficacy<br />
<strong>of</strong> insulin-sensitizing agents, such as<br />
metformin. 32 However, studies using<br />
glitazones suggest that this relationship<br />
may be more complex. 32 High<br />
testosterone levels in women with<br />
PCOS promote abdominal obesity<br />
that, in turn, promotes insulin resistance,<br />
leading to increased testosterone<br />
activity; thus, the vicious circle<br />
ensues. 32 Polycystic ovary syndrome<br />
is a multiorgan disease: abdominal<br />
obesity and increased activation <strong>of</strong><br />
the inflammatory system, seen in<br />
both normal-weight and obese patients<br />
with PCOS, lead to an increased<br />
risk <strong>of</strong> dyslipidemia, diabetes,<br />
and cardiovascular disease. 32<br />
Hormonal imbalance caused by<br />
PCOS can lead to hyperandrogenism<br />
that can manifest as hirsutism<br />
and/or acne. 33 Hirsutism occurs in<br />
5% to 25% <strong>of</strong> women <strong>of</strong> reproductive<br />
age. 32 Between 70% and 90% <strong>of</strong><br />
women with hirsutism are diagnosed<br />
as having PCOS. 32 Although<br />
many treatments for hirsutism are<br />
nonpharmacological, antiandrogens,<br />
such as spironolactone and finasteride,<br />
are sometimes used. However,<br />
OCs are among the most commonly<br />
used medications for hirsutism and<br />
acne. 33<br />
The elevated levels <strong>of</strong> androgens in<br />
women with PCOS can also cause<br />
menstrual irregularities with associated<br />
infertility. Although OCs are<br />
<strong>of</strong>ten used to address menstrual irregularities,<br />
they obviously cannot<br />
) 9
) 10<br />
) In Focus<br />
help with infertility. 33 Clomiphene,<br />
an ovulation-induction agent, may<br />
be used, with the risks <strong>of</strong> multiple<br />
pregnancies, ovarian hyperstimulation,<br />
thromboembolism, and visual<br />
disturbances. Alternatively, insulinsensitizing<br />
agents, such as metformin,<br />
have shown benefit in the<br />
treatment <strong>of</strong> infertility associated<br />
with PCOS. 33<br />
Obesity is prevalent in women with<br />
PCOS. 35 Approximately 60% to<br />
70% <strong>of</strong> patients with PCOS are<br />
obese. Furthermore, the fat is distributed<br />
around the central body;<br />
such visceral obesity is associated<br />
with insulin resistance (Figure 4). 35<br />
However, although the obesity<br />
found in PCOS contributes to the<br />
level <strong>of</strong> insulin resistance observed,<br />
the levels <strong>of</strong> insulin resistance are<br />
greater than those that can be explained<br />
purely by the higher levels<br />
<strong>of</strong> fat. 35 The obesity rate has increased<br />
considerably in women with<br />
PCOS during the past decades,<br />
whereas the prevalence <strong>of</strong> PCOS<br />
has increased only minimally. This<br />
suggests that genetic factors may<br />
play a more important role than environmental<br />
factors in the development<br />
<strong>of</strong> PCOS. 34<br />
Obesity is associated with lowgrade<br />
inflammation and increased<br />
inflammatory cytokine levels. Although<br />
obesity-related inflammation<br />
is <strong>of</strong>ten considered a disorder<br />
<strong>of</strong> innate immunity, there is significant<br />
cross talk between the innate<br />
Figure 4. Central obesity is common<br />
in patients with polycystic ovary<br />
syn drome. Increased visceral fat<br />
is associated with a higher risk<br />
<strong>of</strong> heart disease, hypertension,<br />
insulin resistance, and diabetes<br />
mellitus type 2.<br />
and adaptive immune systems.<br />
Moreover, disorders <strong>of</strong> both innate<br />
and adaptive immunity have<br />
been implicated in obesity-related<br />
inflammation. 35 In addition, the inflammatory<br />
process associated with<br />
obesity could underlie comorbidities,<br />
such as atherosclerosis, diabetes,<br />
and fatty liver disease. 35 Indeed, up<br />
to 50% <strong>of</strong> women with PCOS fulfill<br />
the criteria <strong>of</strong> the metabolic syndrome.<br />
32 Furthermore, the incidence<br />
<strong>of</strong> diabetes is increased, with an estimated<br />
5- to 8-fold increase in risk<br />
compared with age- and weightmatched<br />
controls. 32<br />
Weight loss is an important component<br />
<strong>of</strong> PCOS management. Lifestyle<br />
modification and weight loss<br />
improve ovulation rate and fertility<br />
and decrease testosterone levels.<br />
Greater than 5% to 10% weight loss<br />
can improve fertility and menstrual<br />
cycles in women with PCOS, although<br />
no specific diet has been<br />
identified as particularly effective.<br />
32,34<br />
Bioregulatory Treatment:<br />
PCOS<br />
In patients with obesity and PCOS,<br />
the most important intervention is<br />
weight loss because central obesity<br />
significantly contributes to the<br />
whole syndrome.<br />
Bioregulatory treatment includes<br />
Gynäcoheel and Cutis compositum<br />
for symptomatic relief and Ovarium<br />
Journal <strong>of</strong> <strong>Biomedical</strong> <strong>Therapy</strong> 2011 ) Vol. 5, No. 1<br />
compositum, Placenta compositum,<br />
Coenzyme compositum, and Ubichinon<br />
compositum for organ and<br />
tissue support. Additional supportive<br />
treatment with Hepar compositum,<br />
Thyreoidea compositum, and<br />
Solidago compositum is also used to<br />
promote the restoration <strong>of</strong> autoregulatory<br />
pathways.<br />
Conclusion<br />
© iStockphoto.com/© hartphotography1<br />
The management <strong>of</strong> many female<br />
disorders remains challenging, with<br />
a need to address many different<br />
components. As understanding <strong>of</strong><br />
the pathophysiological characteristics<br />
<strong>of</strong> these conditions grows,<br />
hopefully more effective treatments<br />
will follow. In the meantime, recognition<br />
<strong>of</strong> the multiorgan involvement<br />
in many <strong>of</strong> these diseases emphasizes<br />
the importance <strong>of</strong> a<br />
comprehensive approach to patient<br />
management.|
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ovary syndrome. Am Fam Physician.<br />
2009;79(8):671-676.<br />
34. Hirschberg AL. Polycystic ovary syndrome,<br />
obesity and reproductive implications.<br />
Womens Health (Lond Engl). 2009;5(5):529-<br />
540.<br />
35. Sathyapalan T, Atkin SL. Mediators <strong>of</strong> inflammation<br />
in polycystic ovary syndrome<br />
in relation to adiposity. Mediators Inflamm.<br />
2010;2010:758656.<br />
) 11
) 12<br />
Walking Reduces Stroke Risk<br />
in Women<br />
Moderate walking makes a difference<br />
in women’s health. A recent<br />
study indicates that walking is associated<br />
with lower risks <strong>of</strong> different<br />
types <strong>of</strong> stroke, including total, ischemic,<br />
and hemorrhagic strokes.<br />
Physical activity has been shown to<br />
modify risk factors for stroke, such<br />
as obesity and hypertension, by decreasing<br />
blood pressure and atherosclerosis<br />
and improving lipid pr<strong>of</strong>ile<br />
and insulin sensitivity. The study<br />
included 39,315 healthy US women,<br />
aged 45 years or older, from the<br />
Women’s Health Study. These women<br />
reported overall physical activity<br />
at baseline (1992-1995) and then<br />
36, 72, 96, 125, and 149 months<br />
later. During this lengthy period,<br />
579 women developed incident<br />
stroke: 473 ischemic strokes, 102<br />
hemorrhagic strokes, and 4 strokes<br />
<strong>of</strong> unknown type. Although intense<br />
physical activity was not associated<br />
with stroke risk (P = .50 for trend),<br />
walking time and pace were inversely<br />
related to total, ischemic, and<br />
hemorrhagic stroke risks (P = .002<br />
through P = .07). Thus, all women<br />
should be encouraged to try walking<br />
as a way to prevent stroke (and<br />
other illnesses).<br />
Stroke. 2010;41(6):12431250.<br />
© Siggi/Fotolia.de<br />
) What Else Is New?<br />
Moderate physical activity, in particular<br />
walking, may prevent stroke in women.<br />
Melatonin Helps<br />
Prevent Cancer in Women<br />
In a recent study, the effect <strong>of</strong> melatonin<br />
on breast and endometrial<br />
cancers in women was examined.<br />
Based on decades <strong>of</strong> scientific evidence,<br />
melatonin (N-acetyl-5-methoxytryptamine)<br />
is a hormone that<br />
might protect against cancer development.<br />
Melatonin has antioxidant,<br />
antimitotic, and antiangiogenic<br />
properties. In addition, melatonin<br />
alters fat metabolism and may regulate<br />
tumor growth. In terms <strong>of</strong> breast<br />
cancer, melatonin may block an estrogen<br />
receptor (ie, ERα) and affect<br />
aromatase (ie, an enzyme that produces<br />
estradiol). Epidemiologic<br />
studies have examined the interaction<br />
between night shift work and<br />
varied sleep duration and melatonin<br />
concentration at night. The evidence<br />
indicates lower melatonin<br />
concentration in those who work<br />
the night shift. Case-control and<br />
prospective cohort studies have indicated<br />
that the risk <strong>of</strong> breast and<br />
endometrial cancers is affected by<br />
night shift work. Overall, night shift<br />
work may become a public health<br />
concern if additional data indicate<br />
its negative effect on cancer. More<br />
studies should determine the exact<br />
advantageous effects <strong>of</strong> melatonin<br />
for the prevention <strong>of</strong> cancer.<br />
Cancer Lett. 2009;281(1):17.<br />
doi:10.1016/j.canlet.2008.11.002.<br />
Journal <strong>of</strong> <strong>Biomedical</strong> <strong>Therapy</strong> 2011 ) Vol. 5, No. 1<br />
Antihomotoxic <strong>Therapy</strong><br />
for Autoimmune Thyroiditis<br />
Thyreoidea compositum, an antihomotoxic<br />
agent, may treat chronic<br />
lymphocytic thyroiditis (autoimmune<br />
thyroiditis) in women who experience<br />
habitual miscarriage. In<br />
this study, the therapeutic effectiveness<br />
<strong>of</strong> Thyreoidea compositum was<br />
estimated in 28 women <strong>of</strong> reproductive<br />
age who had autoimmune thyroiditis<br />
and experienced habitual<br />
loss <strong>of</strong> a fetus. The mean±SD age <strong>of</strong><br />
the women was 27.14±0.69 years,<br />
and the mean±SD duration <strong>of</strong> the<br />
disease was 1.57±0.16 years. Patients<br />
were divided into 3 groups:<br />
(1) 9 women for whom L-thyroxin<br />
was prescribed (control group); (2) 9<br />
women who took Thyreoidea compositum,<br />
2.2 mL, intramuscularly<br />
once in 3 days (monotherapy); and<br />
(3) 10 women for whom L-thyroxin,<br />
50 to 100 μg/d, plus Thyreoidea<br />
compositum (combination therapy)<br />
was prescribed. The researchers determined<br />
that Thyreoidea compositum,<br />
used as both a monotherapy<br />
and as part <strong>of</strong> a complex treatment,<br />
leads to decreased levels <strong>of</strong> antibodies<br />
to thyroglobulin and thyro tropin,<br />
an increased level <strong>of</strong> free thyroxine,<br />
and goiter reduction. There fore, this<br />
antihomotoxic agent has immunecorrecting,<br />
anti-inflammatory, and<br />
regenerative effects.<br />
Azerbaijan Med J. 2010;2:2529.
Infant Sensitivity to Peanut<br />
Associated with Maternal<br />
Ingestion<br />
Peanut allergies can be lifelong and<br />
severe. In a recent study <strong>of</strong> 503 infants<br />
(age range, 3-15 months; mean<br />
age, 9.4 months), maternal ingestion<br />
<strong>of</strong> peanuts during pregnancy and<br />
lactation affected the sensitivity <strong>of</strong><br />
infants to peanuts. The risk to the<br />
infant increased with increased peanut<br />
intake by the mother. The infants<br />
studied had already experienced<br />
allergic reactions to other<br />
products: 308 had an immediate reaction<br />
to cow’s milk and/or egg,<br />
and 204 had atopic dermatitis and a<br />
positive allergy test result to milk<br />
and/or egg. Other significant factors<br />
that affected infant peanut allergy<br />
included male sex (P = .02)<br />
and nonwhite race (P = .02).<br />
J Allergy Clin Immunol.<br />
2010;126(6):11911197.<br />
© iStockphoto.com/Karen Sarraga<br />
) What Else Is New?<br />
Symptoms <strong>of</strong> peanut allergy usually<br />
appear rapidly and tend to be severe.<br />
Exposure to urban air pollution may<br />
increase breast cancer risk.<br />
Endometriosis and<br />
Leiomyomata Linked to<br />
Phthalate Exposure<br />
Phthalates, chemicals in commercial<br />
products, include mono(2-ethylhexyl)<br />
phthalate (MEHP), monobutyl<br />
phthalate (MBP), monoethyl phthalate<br />
(MEP), and monobenzyl phthalate<br />
(MBzP). In this cross-sectional<br />
study, mono(2-ethyl-5-hydroxyhexyl)<br />
phthalate (MEHHP) and<br />
mono(2-ethyl-5-oxohexyl) phthalate<br />
were also examined. When a<br />
population <strong>of</strong> women (aged 20-54<br />
years) was studied to determine urinary<br />
phthalate levels, 7% and 12%<br />
reported endometriosis and leiomyomata,<br />
respectively. The odds ratios<br />
for MBP were as follows: 1.36 for<br />
endometriosis, 1.56 for leiomyomata,<br />
and 1.71 for both conditions<br />
combined.<br />
Environ Health Perspect.<br />
2010;118(6):825832.<br />
doi:10.1289/ehp.0901543.<br />
FOR PROFESSIONAL USE ONLY<br />
The information contained in this journal is meant for pr<strong>of</strong>essional use only, is meant to convey general and/or specific worldwide scientific information relating to the<br />
products or ingredients referred to for informational purposes only, is not intended to be a recommendation with respect to the use <strong>of</strong> or benefits derived from the<br />
products and/or ingredients (which may be different depending on the regulatory environment in your country), and is not intended to diagnose any illness, nor is it<br />
intended to replace competent medical advice and practice. IAH or anyone connected to, or participating in this publication does not accept nor will it be liable<br />
for any medical or legal responsibility for the reliance upon or the misinterpretation or misuse <strong>of</strong> the scientific, informational and educational content <strong>of</strong> the<br />
articles in this journal.<br />
The purpose <strong>of</strong> the Journal <strong>of</strong> <strong>Biomedical</strong> <strong>Therapy</strong> is to share worldwide scientific information about successful protocols from orthodox and complementary practitioners.<br />
The intent <strong>of</strong> the scientific information contained in this journal is not to “dispense recipes” but to provide practitioners with “practice information” for a better<br />
understanding <strong>of</strong> the possibilities and limits <strong>of</strong> complementary and integrative therapies.<br />
Some <strong>of</strong> the products referred to in articles may not be available in all countries in which the journal is made available, with the formulation described in any article or<br />
available for sale with the conditions <strong>of</strong> use and/or claims indicated in the articles. It is the practitioner’s responsibility to use this information as applicable<br />
and in a manner that is permitted in his or her respective jurisdiction based on the applicable regulatory environment. We encourage our readers to share<br />
their complementary therapies, as the purpose <strong>of</strong> the Journal <strong>of</strong> <strong>Biomedical</strong> <strong>Therapy</strong> is to join together like-minded practitioners from around the globe.<br />
Written permission is required to reproduce any <strong>of</strong> the enclosed material. The articles contained herein are not independently verified for accuracy or truth. They have<br />
been provided to the Journal <strong>of</strong> <strong>Biomedical</strong> <strong>Therapy</strong> by the author and represent the thoughts, views and opinions <strong>of</strong> the article’s author.<br />
Journal <strong>of</strong> <strong>Biomedical</strong> <strong>Therapy</strong> 2011 ) Vol. 5, No. 1<br />
Air Pollution Affects<br />
Breast Cancer Risk<br />
An association was found between<br />
the risk <strong>of</strong> breast cancer in postmenopausal<br />
women and exposure to<br />
urban air pollution by measuring<br />
concentrations <strong>of</strong> nitrogen dioxide<br />
(NO 2). The results <strong>of</strong> this case-control<br />
study conducted in Montreal,<br />
Quebec, Canada, indicated that an<br />
increase <strong>of</strong> 5-parts-per-billion NO 2<br />
produced an approximately 25% increased<br />
risk <strong>of</strong> breast cancer. The<br />
NO 2 is most likely part <strong>of</strong> a complex<br />
mixture derived from combustion<br />
and is not necessarily the causal factor<br />
but a marker <strong>of</strong> level <strong>of</strong> air pollution.<br />
Additional research is needed<br />
to determine the possible critical periods<br />
<strong>of</strong> exposure to air pollution in<br />
relation to breast cancer development.<br />
Environ Health Perspect.<br />
2010. doi:10.1289/ehp.1002221.<br />
) 13<br />
© iStockphoto.com/Don Bayley
) 14<br />
) From the Practice<br />
Uterine Fibroids<br />
Fibroids or leiomyomas are the<br />
most common form <strong>of</strong> benign<br />
uterine tumor in women. 1 Although<br />
fibroids are found relatively rarely in<br />
women younger than 20 years, statistically,<br />
1 in 5 women <strong>of</strong> childbearing<br />
age will have this disorder. 2<br />
From the standpoint <strong>of</strong> conventional<br />
medicine, the formation <strong>of</strong> fibroids<br />
is considered a hormonal disturbance<br />
or the result <strong>of</strong> a genetic predisposition.<br />
Studies have also shown<br />
that fibroids have different distributions<br />
among the various races. 3 Fibroids<br />
are the result <strong>of</strong> increased<br />
growth <strong>of</strong> smooth muscle tissue<br />
within the uterus and its outer mucosa.<br />
The frequency distribution <strong>of</strong><br />
fibroid sites is as follows: subserous,<br />
55%; intramural, 40%; and submucous,<br />
5%. 2<br />
The symptoms <strong>of</strong> fibroids include<br />
unusually heavy bleeding during<br />
and between periods and nonspecific<br />
pressure in the lower abdomen,<br />
associated with a frequent urge to<br />
urinate and general bowel movement<br />
difficulties. 4 In contrast, routine<br />
examinations sometimes reveal<br />
fibroids that cause no symptoms.<br />
The possibility that a fibroid will<br />
follow a degenerative course is relatively<br />
rare. If fibroids become so<br />
large that their blood supply is no<br />
longer adequate, they may become<br />
necrotic. In subserous fibroids, necrosis<br />
may also occur when fibroids<br />
become twisted in on themselves<br />
because <strong>of</strong> their abnormal size. 2<br />
A Clinical Case Report<br />
By Olga García Domínguez, MD<br />
Gynecologist<br />
Conventional medicine suggests<br />
various treatment possibilities and<br />
methods for use in fibroid therapy<br />
that, as a rule, carry the risk <strong>of</strong> adverse<br />
effects. Surgical or drug treatment<br />
methods are used. The most<br />
commonly used surgical procedures<br />
are myomectomy, hysterectomy, and<br />
drug-induced embolization via the<br />
uterine artery. Pharmaceutical hormone<br />
treatments are also used (eg,<br />
administration <strong>of</strong> a gonadotropinreleasing<br />
hormone analogue) to<br />
trigger early menopause in the patient.<br />
The placement <strong>of</strong> intrauterine<br />
devices that release hormones is another<br />
treatment method. 5<br />
From the standpoint <strong>of</strong> homotoxicology,<br />
fibroids are a chronic disease<br />
that is classified in the deposition<br />
phase and belongs to the germinodermal<br />
layer. It is assumed that the<br />
disease is caused by multiple factors<br />
and that psychological factors play a<br />
particular role in this gynecological<br />
disease. As an expert with long-term<br />
experience in biological medicine, I<br />
try, in my daily practice, to treat fibroid<br />
diseases primarily from a correspondingly<br />
different viewpoint.<br />
Of course, every physician knows<br />
that health is to be understood as an<br />
unstable equilibrium state that is<br />
constantly striving to balance itself<br />
and that the neuroendocrine system<br />
is involved in both human emotions<br />
and the hormone cascade. Physicians<br />
can come closer to treating fibroid<br />
disease by carefully observing<br />
Journal <strong>of</strong> <strong>Biomedical</strong> <strong>Therapy</strong> 2011 ) Vol. 5, No. 1<br />
the patient and getting to know<br />
about her life history. This begins<br />
with birth and includes dietary habits,<br />
emotional life, and physical activities.<br />
All <strong>of</strong> these individual characteristics<br />
are to be compiled in a<br />
thorough history so that physicians<br />
can successfully identify the factor<br />
that caused the disturbance and led<br />
to the disease.<br />
I attempt to convey to the patient<br />
that a fibroid constitutes an organic<br />
enlargement in which nutrition<br />
plays a role; therefore, I recommend<br />
a diet according to the principles <strong>of</strong><br />
Traditional Chinese Medicine. I<br />
combat the physical imbalance by<br />
using homeopathically prepared<br />
hormones and therapy with organ<br />
extracts, which normalize the functions<br />
<strong>of</strong> the pituitary and thyroid.<br />
Clinical Case<br />
In 2009, a 43-year-old patient presented<br />
to my practice with massive<br />
menstrual bleeding caused by an intramural<br />
fibroid measuring 8.1 x 6.6<br />
cm (Figure 1). Her medical history<br />
showed the following: menarche at<br />
the age <strong>of</strong> 12 years, nullipara, 1 miscarriage,<br />
and no major diseases. Her<br />
first fibroid symptoms had appeared<br />
in 1994 at the age <strong>of</strong> 28 years. A<br />
myomectomy was performed. In<br />
January 2003, the fibroid symptoms<br />
recurred. To counteract the renewed<br />
heavy bleeding, which was having a<br />
serious effect on her daily life, the<br />
patient was treated with a hormonal
Figure 1. Transabdominal Echography (2009)<br />
An anteverted uterus, measuring 11.7 x 7.8 cm, is shown. A<br />
subserous intramural fibroid on the anterior surface and right<br />
border is clearly submucosal, measuring 8.1 x 6.6 cm.<br />
intrauterine system. However, her<br />
heavy bleeding continued, and the<br />
fibroid continued to grow. According<br />
to the ultrasonographic examination<br />
results from 2007, the fibroid<br />
had reached a size <strong>of</strong> 5.5 x 4.6 cm.<br />
The severe bleeding persisted, and<br />
the ultrasonographic examination<br />
from 2008 showed that the fibroid<br />
had grown to 7.0 x 5.4 cm. I immediately<br />
began homotoxicological<br />
treatment and recommended the dietary<br />
adjustment, as discussed before.<br />
<strong>Therapy</strong><br />
The patient received Cinnamomum-<br />
Homaccord in drop form (maximum<br />
dosage, 70 drops daily) to counteract<br />
the heavy bleeding. For tissue<br />
support, I administered Mucosa<br />
com positum ampoules (1 twice a<br />
week). To reduce inflammation, she<br />
was given Traumeel drops (10 drops<br />
3-5 times a day). To slow the fibroid<br />
growth and counteract obsessive<br />
thoughts, I prescribed Thuja granules<br />
(5 granules daily); and for hormonal<br />
balance, I prescribed Agnus<br />
) From the Practice<br />
castus granules (5 granules daily).<br />
The latter medication is used to restore<br />
the balance between estrogens<br />
and progesterone.<br />
In the follow-up examination conducted<br />
by a colleague in February<br />
2010, 6 months after the beginning<br />
<strong>of</strong> treatment, the fibroid had decreased<br />
to 6.6 x 4.5 cm (Figure 2).<br />
To date, the patient has remained<br />
symptom free, and her menstrual<br />
bleeding has become completely<br />
normal. She continues to be treated<br />
with the same medication. We await<br />
the results <strong>of</strong> future regular ultrasonographic<br />
examinations <strong>of</strong> the<br />
shrunken fibroid.|<br />
References<br />
1. Stewart EA. Uterine fibroids. Lancet.<br />
2001;357(9252):293-298.<br />
2. Katz VL. Benign gynecologic lesions: vulva,<br />
vagina, cervix, uterus, oviduct, ovary. In:<br />
Katz VL, Lentz GM, Lobo RA, Gershenson<br />
DM, eds. Comprehensive Gynecology. 5th ed.<br />
Philadelphia, PA: Mosby Elsevier; 2007:chap<br />
18.<br />
3. Blake RE. Leiomyomata uteri: hormonal and<br />
molecular determinants <strong>of</strong> growth. J Natl<br />
Med Assoc. 2007;99(10):1170-1184.<br />
Journal <strong>of</strong> <strong>Biomedical</strong> <strong>Therapy</strong> 2011 ) Vol. 5, No. 1<br />
Figure 2. Transvaginal Echography (2010)<br />
An anteflected, large, and globular uterus.<br />
The bilobular fi broid on the anterior surface is reduced,<br />
measuring 6.6 x 4.5 cm.<br />
4. Levy BS. Modern management <strong>of</strong> uterine<br />
fibroids. Acta Obstet Gynecol Scand.<br />
2008;87(8):812-823.<br />
5. Viswanathan M, Hartmann K, McKoy N, et<br />
al. Management <strong>of</strong> uterine fibroids: an update<br />
<strong>of</strong> the evidence. Evid Rep Technol Assess (Full<br />
Rep). 2007;(154):1-122.<br />
Further reading<br />
1. Cónill Montobbio V. Tratado de Ginecología<br />
y de Técnica Terapéutica Ginecológica.<br />
5th ed. Barcelona, Spain: Labor;<br />
1967.<br />
2. Kushi M. Alimentacion Macrobiotica.<br />
Madrid, Spain: EDAF; 2004.<br />
3. Kyank H, Sommer K. Lehrbuch der<br />
Gynäkologie. 3rd ed. Leipzig, Germany:<br />
Thieme; 1978.<br />
4. Ordinatio Antihomotoxica et Materia<br />
Medica: Tratado Práctico de Terapia<br />
Antihomotóxica. 9th Rev ed. Baden-<br />
Baden, Germany: Biologische Heilmittel<br />
Heel GmbH; 2007.<br />
5. Pommier L. Diccionario Homeopático<br />
de Urgencia. 2nd ed. Barcelona, Spain:<br />
Paidotribo; 2002.<br />
6. Schmid F, Rimpler M, Wemmer U.<br />
Medicina Antihomotóxica: Principios,<br />
Clínica, Práctica. Vol 1. 2nd ed. Baden-<br />
Baden, Germany: Aure lia; 2004.<br />
7. Vannier L. La Típologia y sus Aplicaciones<br />
Terapéuticas. Madrid, Spain: Mandala;<br />
2001.<br />
) 15
) 16<br />
) Refresh Your <strong>Homotoxicology</strong><br />
Which Came First:<br />
Insulin Resistance or Inflammation?<br />
It is well established that persistently<br />
elevated levels <strong>of</strong> inflammatory<br />
cytokines play a significant role<br />
in the development <strong>of</strong> chronic disease.<br />
For example, persistently high<br />
levels <strong>of</strong> 1 or more <strong>of</strong> the proinflammatory<br />
cytokines (ie, interleukins 1<br />
and 6 and tumor necrosis factor α)<br />
are common to the pathogenesis <strong>of</strong><br />
diseases such as cardiovascular disease,<br />
cancers, inflammatory bowel<br />
disease, chronic fatigue syndrome,<br />
and neurological disorders (eg, depression,<br />
Parkinson disease, and<br />
Alz heimer disease). 1<br />
The elevation <strong>of</strong> these cytokines has<br />
become such a common thread for<br />
the development <strong>of</strong> these diseases<br />
that the term sickness behavior2,3 has<br />
recently been proposed to describe<br />
the associated signs and symptoms<br />
<strong>of</strong> fever, anorexia, fatigue, sleepiness,<br />
and social withdrawal. Additional<br />
support for the paramount<br />
importance <strong>of</strong> inflammation in disease<br />
development has recently come<br />
from the Justification for the Use <strong>of</strong><br />
Statins in Primary Prevention: An<br />
Intervention Trial Evaluating Rosuvastatin<br />
(JUPITER). The results <strong>of</strong><br />
this trial suggest that the proposed<br />
benefit <strong>of</strong> statin drugs in the prevention<br />
<strong>of</strong> cardiovascular disease was<br />
more likely because <strong>of</strong> their ability<br />
to reduce levels <strong>of</strong> high-sensitivity<br />
C-reactive protein (a nonspecific inflammatory<br />
marker) than their effects<br />
on lowering cholesterol. 4<br />
By David W. Lescheid, PhD, ND<br />
Although there are some similarities,<br />
the inflammatory component <strong>of</strong><br />
chronic diseases is different from the<br />
inflammatory response associated<br />
with tissue repair and recovery that<br />
follows acute injury or infection.<br />
This subclass <strong>of</strong> inflammation may<br />
be termed metainflammation (metabolic<br />
inflammation), because <strong>of</strong> its<br />
initiation by nutrients and metabolic<br />
surplus 5 ; or parainflammation, because<br />
it shares intermediate characteristics<br />
between the basal and acute<br />
inflammatory state. 6<br />
Chronic inflammation does play an<br />
important role in disease processes.<br />
An important question to ask is as<br />
follows: Why has the inflammation<br />
occurred in the first place (ie, what is<br />
the nature <strong>of</strong> the inflammatory inducer<br />
or trigger)? There are several<br />
different theories and proposed<br />
mechanisms; however, one <strong>of</strong> the<br />
most promising current models suggests<br />
that dysregulated cell metabolism,<br />
particularly from nutrient excess<br />
and the associated altered<br />
insulin signaling, 7 is one <strong>of</strong> the most<br />
important initiating events. This article<br />
will discuss the roles <strong>of</strong> hyperinsulinemia<br />
and <strong>of</strong> a few potential<br />
triggers <strong>of</strong> excess insulin in the development<br />
<strong>of</strong> disease, with some examples<br />
<strong>of</strong> the effect on women’s<br />
health issues.<br />
Men and women have substantial<br />
differences in body composition,<br />
such as distribution <strong>of</strong> visceral and<br />
hepatic adipose tissue and lean body<br />
Journal <strong>of</strong> <strong>Biomedical</strong> <strong>Therapy</strong> 2011 ) Vol. 5, No. 1<br />
mass, and in sex hormone and adipokine<br />
levels. These differences tend<br />
to improve insulin sensitivity in<br />
women compared with men 8 and<br />
suggest that sex differences must be<br />
considered when preventing and<br />
treating diseases associated with insulin<br />
resistance.<br />
There is no question that obesity has<br />
reached epidemic proportions in<br />
many parts <strong>of</strong> the world. In many<br />
countries, particularly those <strong>of</strong> industrialized<br />
and developed nations,<br />
there is a regular excess intake <strong>of</strong><br />
calories from increasingly caloriedense<br />
but nutrient-poor foods and<br />
drinks. The excess <strong>of</strong> calories, combined<br />
with an increasingly less<br />
physically active society, creates a<br />
daily energy surplus that eventually<br />
leads to a dysregulation <strong>of</strong> the<br />
body’s key storage hormone, insulin<br />
(Figure). 9 With cells no longer sensitive<br />
to insulin and a surplus <strong>of</strong> blood<br />
glucose triggering the continued release<br />
<strong>of</strong> insulin from the pancreas,<br />
hyperinsulinemia develops.<br />
Adipose tissue is an endocrine organ<br />
releasing many different signaling<br />
molecules, some <strong>of</strong> which have direct<br />
localized and systemic inflammatory<br />
effects. 10 The development<br />
<strong>of</strong> adipose tissue is preceded by an<br />
impairment <strong>of</strong> energy balance that is<br />
primarily associated with the inability<br />
<strong>of</strong> the cells to respond to insulin,<br />
either through inadequacy <strong>of</strong> insulin<br />
receptor signaling or some other<br />
defect in the biochemical pathway.
Hyperinsulinemia<br />
and Female Health<br />
Figure. Human<br />
Insulin Molecule<br />
High insulin levels can modulate the<br />
activity <strong>of</strong> gonadotropin-releasing<br />
hormone in the hypothalamus (at<br />
least in lean healthy controls) and,<br />
therefore, interfere with the pattern<br />
<strong>of</strong> release <strong>of</strong> luteinizing hormone<br />
(LH). 11 These data suggest that reproductive<br />
cycles, ovulation, and<br />
fertility could be affected. Indeed,<br />
recent evidence suggests that fasting<br />
insulin levels, fasting serum levels <strong>of</strong><br />
sex hormone–binding globulin<br />
(SHBG), and the free androgen index<br />
had strong negative influences<br />
on the regularity <strong>of</strong> menstrual cycles<br />
in young women. 12 Furthermore,<br />
women with insulin resistance and<br />
hyperinsulinemia (and upper body<br />
obesity, which is also termed android<br />
or truncal obesity) had a greater risk<br />
<strong>of</strong> anovulatory cycles 13 that could be<br />
reversed through the use <strong>of</strong> insulinsensitizing<br />
drugs. 14<br />
Glucose intolerance, including insulin<br />
resistance and impaired fasting<br />
glucose level, 15 is an important part<br />
<strong>of</strong> the pathophysiological characteristics<br />
<strong>of</strong> polycystic ovary syndrome<br />
(PCOS). 16,17 However, insulin infusions<br />
to women with PCOS had no<br />
effect on the secretion <strong>of</strong> LH, suggesting<br />
that the inappropriate secretion<br />
<strong>of</strong> LH observed in this disease<br />
might not be directly due to insulin<br />
resistance and hyperinsulinemia. 18<br />
Furthermore, there was no change<br />
) Refresh Your <strong>Homotoxicology</strong><br />
in the altered pattern <strong>of</strong> LH secretion<br />
in women with PCOS after insulin<br />
infusion despite an improvement<br />
in insulin sensitivity after<br />
treatment with pioglitazone, a thiazolidinedione<br />
type <strong>of</strong> drug known<br />
to modulate transcription <strong>of</strong> insulinsensitive<br />
genes in the muscle, liver,<br />
and adipose tissue. 19 This suggests<br />
that the dysregulated gonadotropin<br />
release in PCOS is caused by a<br />
mechanism that is not directly related<br />
to insulin levels.<br />
High insulin levels in the ovaries<br />
help stimulate the production <strong>of</strong> steroid<br />
hormones, such as androstenedione<br />
and testosterone, 20 that are<br />
associated with some <strong>of</strong> the signs<br />
and symptoms <strong>of</strong> disease in women<br />
if they are in excess for a long time.<br />
Higher levels <strong>of</strong> testosterone, but<br />
not androstenedione, are correlated<br />
with higher levels <strong>of</strong> insulin resistance<br />
in women (but not in men). In<br />
particular, women with PCOS that<br />
are also insulin resistant have the<br />
highest circulating levels <strong>of</strong> testosterone,<br />
suggesting that their ovaries<br />
are more sensitive to the testosterone-stimulating<br />
effects <strong>of</strong> insulin. 21<br />
Insulin is a key regulator <strong>of</strong> the synthesis<br />
<strong>of</strong> SHBG in the liver. 22 Elevated<br />
levels <strong>of</strong> insulin down regulate<br />
the production <strong>of</strong> SHBG and, therefore,<br />
increase the amount <strong>of</strong> bioavailable<br />
estrogen; this increases the<br />
risk <strong>of</strong> diseases associated with estrogen<br />
excess. Furthermore, a decreased<br />
serum level <strong>of</strong> SHBG would<br />
Journal <strong>of</strong> <strong>Biomedical</strong> <strong>Therapy</strong> 2011 ) Vol. 5, No. 1<br />
result in an excess <strong>of</strong> free testosterone<br />
and, therefore, the associated<br />
signs and symptoms, such as hirsutism<br />
and acne. High testosterone and<br />
low SHBG levels are also associated<br />
with a higher risk <strong>of</strong> cardiovascular<br />
disease in postmenopausal women. 23<br />
Elevated levels <strong>of</strong> insulin increase<br />
the bioavailability <strong>of</strong> insulinlike<br />
growth factor 1, by directly increasing<br />
its synthesis and decreasing several<br />
<strong>of</strong> its binding proteins (eg, insulinlike<br />
growth factor-binding pro -<br />
teins 1 and 2). 24 Insulinlike growth<br />
factor 1 is a hormone that is involved<br />
in several different conditions,<br />
including certain types <strong>of</strong> carcinogenesis,<br />
25 cognitive decline, 26<br />
dysregulation <strong>of</strong> the immune system,<br />
and autoimmune diseases, 27<br />
and in the development <strong>of</strong> female<br />
disorders, including breast cancer in<br />
premenopausal women. 28<br />
High insulin, but not insulinlike<br />
growth factor 1, levels are independent<br />
risk factors for the development<br />
<strong>of</strong> breast cancer in postmenopausal<br />
women 29 and for endome trial<br />
adenocarcinoma. 30,31<br />
Possible Triggers <strong>of</strong><br />
Dysregulated Insulin Levels<br />
© iStockphoto.com/Martin McCarthy<br />
The interconnectivity between female<br />
pathophysiological features<br />
and insulin has been further substantiated<br />
with recent reports demonstrating<br />
that estrogen is important<br />
in glucose homeostasis. For exam-<br />
) 17
) 18<br />
) Refresh Your <strong>Homotoxicology</strong><br />
ple, both is<strong>of</strong>orms <strong>of</strong> estrogen receptor<br />
(α and β) are present in pancreatic<br />
beta cells. The insulin content<br />
<strong>of</strong> pancreatic beta cells was increased<br />
after long-term exposure to physiological<br />
levels <strong>of</strong> 17β-estradiol, most<br />
likely by binding with estrogen receptor<br />
α. 32<br />
It is becoming increasingly evident<br />
that environmental chemicals from<br />
plastics and common household<br />
products, such as bisphenol A (BPA)<br />
and phthalates, have the potential to<br />
trigger dysregulated metabolic<br />
events that could lead to insulin resistance<br />
and contribute to the obesity<br />
epidemic. 33 For example, there<br />
is evidence that the environmental<br />
estrogen mimetic BPA significantly<br />
binds and activates estrogen receptor<br />
α in pancreatic beta cells at serum<br />
levels that are plausible, suggesting<br />
that this could be one <strong>of</strong> the<br />
early triggers <strong>of</strong> dysregulated insulin<br />
levels. The putative role <strong>of</strong> BPA<br />
in disrupting the normal physiological<br />
regulation <strong>of</strong> glucose has been<br />
reported and reviewed elsewhere.<br />
34,35 It is interesting to note<br />
that in mouse models, when pregnant<br />
mice are exposed to environmentally<br />
relevant levels <strong>of</strong> BPA, glucose<br />
homeostasis is affected and<br />
insulin resistance develops not only<br />
in the mothers themselves, but also<br />
in the male <strong>of</strong>fspring. These negative<br />
effects initiated in utero persisted<br />
until adulthood, suggesting that<br />
exposure to BPA early in development<br />
could influence the development<br />
<strong>of</strong> chronic disease later in<br />
life. 36<br />
Phthalates, widely found in plastic<br />
products, are additional environmental<br />
pollutants that disrupt cellular<br />
metabolism and, therefore, contribute<br />
to the development <strong>of</strong> insulin<br />
resistance and obesity (at least in<br />
men). 37 This dysregulation <strong>of</strong> cell<br />
metabolism was the result <strong>of</strong> the<br />
ability <strong>of</strong> phthalates to interfere<br />
with the function <strong>of</strong> peroxisome<br />
proliferative receptors, 38 transcription<br />
factors known to function at a<br />
critical intercellular junction between<br />
lipid and glucose metabolism<br />
and, therefore, storage or usage <strong>of</strong><br />
nutrients.<br />
A cellular event that might even precede<br />
insulin resistance and inflammation<br />
is endoplasmic reticulum<br />
(ER) stress. This organelle can be<br />
negatively affected by hypoxia, viral<br />
infections, toxins, energy, and nutrient<br />
fluctuations (both deprivation<br />
and excess <strong>of</strong> nutrients will stress<br />
the ER), imbalances <strong>of</strong> calcium levels<br />
within the organelle, excess demands<br />
on host cell synthetic biochemical<br />
machinery, inflammatory<br />
mediators, and accumulation <strong>of</strong> improperly<br />
processed proteins. 11 The<br />
ER responds to these stressors by a<br />
complex response, known as the unfolded<br />
protein response, that ultimately<br />
initiates pathways that negatively<br />
affect insulin signaling and<br />
promote the inflammatory response.<br />
5,7 The presence <strong>of</strong> chronic<br />
oxidative stress, possibly from mitochondrial<br />
dysfunction, inadequate<br />
cell antioxidant networks, or ER<br />
stress, can promote insulin resistance<br />
and inflammation and can impair insulin<br />
secretion from pancreatic beta<br />
cells. 5 Furthermore, persistent nutrient<br />
excess (and, ultimately, obesity)<br />
increases the levels <strong>of</strong> excess free<br />
fatty acids (that can activate inflammatory<br />
responses through binding<br />
with toll-like receptors 11 ), reduces<br />
glucose availability (as the result <strong>of</strong><br />
cellular insulin resistance), and augments<br />
the demands for protein synthesis.<br />
These variables all induce ER<br />
stress and the unfolded protein response.<br />
39 The ER might be the important<br />
sensory link between nutrient-associated<br />
signals and the<br />
development <strong>of</strong> insulin resistance<br />
and inflammation. 11<br />
Journal <strong>of</strong> <strong>Biomedical</strong> <strong>Therapy</strong> 2011 ) Vol. 5, No. 1<br />
It has recently been proposed that a<br />
combination <strong>of</strong> nutrient excess and<br />
physical inactivity, occurring against<br />
a background <strong>of</strong> genetic predisposition,<br />
could lead to the persistent hyperglycemia<br />
associated with the development<br />
<strong>of</strong> oxidative stress.<br />
Ultimately, this may trigger inflammatory<br />
pathways that contribute to<br />
the development <strong>of</strong> chronic disease.<br />
There are many different points<br />
along this “oxidative inflammatory”<br />
cascade that can be modulated to<br />
prevent any pathological consequences;<br />
however, reducing the persistent<br />
hyperglycemia (by improving<br />
insulin sensitivity) appears to be a<br />
critical first step. 40<br />
In conditions <strong>of</strong> nutrient excess,<br />
which are common in industrialized<br />
nations, it is more likely that a dysregulation<br />
<strong>of</strong> metabolic signals, such<br />
as insulin resistance, precedes the<br />
promotion <strong>of</strong> the inflammatory response.<br />
These metabolic signals<br />
could have been disrupted by stress<br />
on intercellular organelles, such as<br />
the ER, or, alternately, by external<br />
stressors, such as the environmental<br />
toxins BPA and phthalates. An increased<br />
understanding <strong>of</strong> some <strong>of</strong><br />
the key initiators <strong>of</strong> the process <strong>of</strong><br />
chronic disease can assist with the<br />
development <strong>of</strong> prevention and<br />
treatment plans that address the root<br />
cause and, therefore, have a more<br />
pr<strong>of</strong>ound and persistent therapeutic<br />
effect.|
References<br />
1. Handschin C, Spiegelman BM. The<br />
role <strong>of</strong> exercise and PGC1α in inflammation<br />
and chronic disease. Nature.<br />
2008;454(7203):463-469.<br />
2. Dantzer R, Kelley KW. Twenty years <strong>of</strong> research<br />
on cytokine-induced sickness behavior.<br />
Brain Behav Immun. 2007;21(2):153-<br />
160.<br />
3. Myers JS. Proinflammatory cytokines and<br />
sickness behavior: implications for depression<br />
and cancer-related symptoms. Oncol<br />
Nurs Forum. 2008;35(5):802-807.<br />
4. Mora S, Ridker PM. Justification for the Use<br />
<strong>of</strong> Statins in Primary Prevention: an Intervention<br />
Trial Evaluating Rosuvastatin (JU-<br />
PITER): can C-reactive protein be used to<br />
target statin therapy in primary prevention?<br />
Am J Cardiol. 2006;97(2A):33A-41A.<br />
5. Hotamisligil GS, Erbay E. Nutrient sensing<br />
and inflammation in metabolic diseases. Nat<br />
Rev Immunol. 2008;8(12):923-934.<br />
6. Medzhitov R. Inflammation 2010: new adventures<br />
<strong>of</strong> an old flame. Cell. 2010;140(6):<br />
771-776.<br />
7. Hotamisligil GS. Inflammation and metabolic<br />
disorders. Nature. 2006;444(7121):860-<br />
867.<br />
8. Geer EB, Shen W. Gender differences in insulin<br />
resistance, body composition and energy<br />
balance. Gend Med. 2009;6(suppl 1):60-75.<br />
9. Fair AM, Montgomery K. Energy balance,<br />
physical activity, and cancer risk. In: Verma<br />
M, ed. Cancer Epidemiology. New York, NY:<br />
Humana Press; 2009. Methods in Molecular<br />
Biology; vol 472.<br />
10. Wozniak SE, Gee LL, Wachtel MS, Frezza EE.<br />
Adipose tissue: the new endocrine organ? A<br />
review article. Dig Dis Sci. 2009;54(9):1847-<br />
1856.<br />
11. Moret M, Stettler R, Rodieux F, et al. Insulin<br />
modulation <strong>of</strong> luteinizing hormone secretion<br />
in normal female volunteers and lean polycystic<br />
ovary syndrome patients. Neuroendocrinology.<br />
2009;89(2):131-139.<br />
12. Wei S, Schmidt MD, Dwyer T, Norman RJ,<br />
Venn AJ. Obesity and menstrual irregularity:<br />
associations with SHBG, testosterone, and<br />
insulin. Obesity. 2009;17(5):1070-1076.<br />
13. Morán C, Hernández E, Ruíz JE, Fonseca<br />
ME, Bermúdez JA, Zárate A. Upper body<br />
obesity and hyperinsulinemia are associated<br />
with anovulation. Gynecol Obstet Invest.<br />
1999;47(1):1-5.<br />
14. Ibáñez L, Valls C, Ferrer A, Ong K, Dunger<br />
DB, De Zegher F. Additive effects <strong>of</strong> insulin-sensitizing<br />
and anti-androgen treatment<br />
in young, nonobese women with hyperinsulinism,<br />
hyperandrogenism, dyslipidemia,<br />
and anovulation. J Clin Endocrinol Metab.<br />
2002;87(6):2870-2874.<br />
15. Salley KE, Wickham EP, Cheang KI, Essah<br />
PA, Karjane NW, Nestler JE. Glucose intolerance<br />
in polycystic ovary syndrome: a position<br />
statement <strong>of</strong> the Androgen Excess Society.<br />
J Clin Endocrinol Metab. 2007;92(12):4546-<br />
4556.<br />
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16. Moran LJ, Misso ML, Wild RA, Norman<br />
RJ. Impaired glucose tolerance, type 2 diabetes<br />
and metabolic syndrome in polycystic<br />
ovary syndrome: a systematic review<br />
and meta-analysis. Hum Reprod Update.<br />
2010;16(4):347-363.<br />
17. Teede H, Deeks A, Moran L. Polycystic ovary<br />
syndrome: a complex condition with psychological,<br />
reproductive and metabolic manifestations<br />
that impacts on health across the<br />
lifespan. BMC Med. 2010;8:41.<br />
18. Patel K, C<strong>of</strong>fler MS, Dahan MH, et al. Increased<br />
luteinizing hormone secretion in<br />
women with polycystic ovary syndrome is<br />
unaltered by prolonged insulin infusion.<br />
J Clin Endocrinol Metab. 2003;88(11):5456-<br />
5461.<br />
19. Mehta RV, Patel KS, C<strong>of</strong>fler MS, et al. Luteinizing<br />
hormone secretion is not influenced<br />
by insulin infusion in women with polycystic<br />
ovary syndrome despite improved insulin<br />
sensitivity during pioglitazone treatment.<br />
J Clin Endocrinol Metab. 2005;90(4):2136-<br />
2141.<br />
20. Franks S, Gilling-Smith C, Watson H, Willis<br />
D. Insulin action in the normal and polycystic<br />
ovary. Endocrinol Metab Clin North Am.<br />
1999;28(2):361-378.<br />
21. Asagami T, Holmes TH, Reaven G. Differential<br />
effects <strong>of</strong> insulin sensitivity on androgens<br />
in obese women with polycystic ovary<br />
syndrome or normal ovulation. Metabolism.<br />
2008;57(10):1355-1360.<br />
22. Franks S, Kiddy DS, Hamilton-Fairley D,<br />
Bush A, Sharp PS, Reed MJ. The role <strong>of</strong> nutrition<br />
and insulin in the regulation <strong>of</strong> sex<br />
hormone binding globulin. J Steroid Biochem<br />
Mol Biol. 1991;39(5B):835-838.<br />
23. Brand JS, van der Schouw YT. Testosterone,<br />
SHBG and cardiovascular health in<br />
postmenopausal women. Int J Impot Res.<br />
2010;22(2):91-104.<br />
24. Kaaks R. Nutrition, insulin, IGF-1 metabolism<br />
and cancer risk: a summary <strong>of</strong> epidemiological<br />
evidence. Novartis Found Symp.<br />
2004;262:247-260.<br />
25. Renehan AG, Zwahlen M, Minder C,<br />
O’Dwyer ST, Shalet SM, Egger M. Insulinlike<br />
growth factor (IGF)-I, IGF binding<br />
protein-3, and cancer risk: systematic review<br />
and meta-regression analysis. Lancet.<br />
2004;363(9418):1346-1353.<br />
26. Sonntag WE, Ramsey M, Carter CS. Growth<br />
hormone and insulin-like growth factor-1<br />
(IGF-1) and their influence on cognitive aging.<br />
Ageing Res Rev. 2005;4(2):195-212.<br />
27. Smith TJ. Insulin-like growth factor-I regulation<br />
<strong>of</strong> immune function: a potential therapeutic<br />
target in autoimmune diseases? Pharmacol<br />
Rev. 2010;62(2):199-236.<br />
28. Key TJ, Appleby PN, Reeves GK, et al; Endogenous<br />
Hormones and Breast Cancer Collaborative<br />
Group. Insulin-like growth factor<br />
1 (IGF1), IGF binding protein 3 (IGFBP3),<br />
and breast cancer risk: pooled individual data<br />
analysis <strong>of</strong> 17 prospective studies. Lancet Oncol.<br />
2010;11(6):530-542.<br />
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29. Gunter MJ, Hoover DR, Yu H, et al. Insulin,<br />
insulin-like growth factor-I, and risk <strong>of</strong><br />
breast cancer in postmenopausal women.<br />
J Natl Cancer Inst. 2009;101(1):48-60.<br />
30. Gunter MJ, Hoover DR, Yu H, et al. A prospective<br />
evaluation <strong>of</strong> insulin and insulin-like<br />
growth factor-I as risk factors for endometrial<br />
cancer. Cancer Epidemiol Biomarkers<br />
Prev. 2008;17(4):921-929.<br />
31. Kaaks R, Lukanova A, Kurzer MS. Obesity,<br />
endogenous hormones, and endometrial cancer<br />
risk: a synthetic review. Cancer Epidemiol<br />
Biomark Prev. 2002;11(12):1531-1543.<br />
32. Alonso-Magdalena P, Ropero AB, Carrera<br />
MP, et al. Pancreatic insulin content regulation<br />
by the estrogen receptor ERα. PLoS One.<br />
2008;3(4):e2069.<br />
33. Desvergne B, Feige JN, Casals-Casas C.<br />
PPAR-mediated activity <strong>of</strong> phthalates: a link<br />
to the obesity epidemic? Mol Cell Endocrinol.<br />
2009;304(1-2):43-48.<br />
34. Alonso-Magdalena P, Morimoto S, Ripoll C,<br />
Fuentes E, Nadal A. The estrogenic effect <strong>of</strong><br />
bisphenol A disrupts pancreatic β-cell function<br />
in vivo and induces insulin resistance.<br />
Environ Health Perspect. 2006;114(1):106-<br />
112.<br />
35. Alonso-Magdalena P, Ropero AB, Soriano<br />
S, Quesada I, Nadal A. Bisphenol-A: a new<br />
diabetogenic factor? Hormones (Athens).<br />
2010;9(2):118-126.<br />
36. Alonso-Magdalena P, Vieira E, Soriano S, et<br />
al. Bisphenol A exposure during pregnancy<br />
disrupts glucose homeostasis in mothers and<br />
adult male <strong>of</strong>fspring. Environ Health Perspect.<br />
2010;118(9):1243-1250<br />
37. Stahlhut RW, van Wijngaarden E, Dye TD,<br />
Cook S, Swan SH. Concentrations <strong>of</strong> urinary<br />
phthalate metabolites are associated with<br />
increased waist circumference and insulin<br />
resistance in adult US males. Environ Health<br />
Perspect. 2007;115(6):876-882.<br />
38. Hurst CH, Waxman DJ. Activation <strong>of</strong> PPARα<br />
and PPARγ by environmental phthalate<br />
monoesters. Toxicol Sci. 2003;74(2):297-<br />
308.<br />
39. Gregor MF, Hotamisligil GS. Adipocyte<br />
stress: the endoplasmic reticulum and metabolic<br />
disease. J Lipid Res. 2007;48(9):1905-<br />
1914.<br />
40. Lamb RE, Goldstein BJ. Modulating an oxidative-inflammatory<br />
cascade: potential new<br />
treatment strategy for improving glucose<br />
metabolism, insulin resistance, and vascular<br />
function. Int J Clin Pract. 2008;62(7):1087-<br />
1095.<br />
) 19
) 20<br />
) Practical Protocols<br />
Genital Human<br />
Papilloma Virus Infection<br />
Bioregulatory Management<br />
Of the 100 strains that exist,<br />
only 40 have an affinity for<br />
genital sites, being primarily sexually<br />
transmitted. These can be classified<br />
into 2 general categories: highand<br />
low-risk HPV. The low-risk<br />
strains, especially types 6 and 11,<br />
are responsible for genital warts and<br />
respiratory papillomatosis. Of the<br />
15 high-risk types, 2 strains (16 and<br />
18) are responsible for approximately<br />
70% <strong>of</strong> the cervical cancers<br />
worldwide. 2 Cervical cancer is the<br />
second most frequent cancer <strong>of</strong><br />
women and is the first cancer caused<br />
solely by virological agents. 3<br />
Human papilloma virus infection is<br />
common, and most women will be<br />
infected with 1 <strong>of</strong> the HPV subtypes<br />
in their sexual lifetime. In most individuals,<br />
the infection is transient<br />
and asymptomatic and will resolve<br />
within 2 years. 4 Only a subset <strong>of</strong><br />
women infected with high-risk carcinogenic<br />
HPV will develop invasive<br />
cervical cancer, and several c<strong>of</strong>actors<br />
have been associated with<br />
HPV persistence and HPV-related<br />
By Alta A. Smit, MD<br />
The burden <strong>of</strong> human papilloma virus (HPV) infections<br />
and their consequences is a major health concern worldwide<br />
in terms <strong>of</strong> the cost to society and suffering. It is<br />
estimated that 360 million persons worldwide are infected<br />
with HPV. 1<br />
disease progression. These factors<br />
include the following: (1) viral factors,<br />
such as genotype (eg, HPV<br />
16) 5 ; (2) lifestyle factors, such as tobacco<br />
smoke 6 and long-term oral<br />
contraceptive use 7 ; and (3) genetic<br />
and immunological host factors,<br />
such as innate immunity. 8<br />
Prophylactic HPV vaccines have<br />
proved to be highly effective in preventing<br />
HPV infection, despite concerns<br />
regarding their long-term<br />
safety. 9-11 However, even the rigorous<br />
vaccination program in industrialized<br />
countries will not obliterate<br />
the need for cervical screening because<br />
the vaccine does not contain<br />
all the carcinogenic viral types and<br />
women already infected have no<br />
benefit from the primary intervention.<br />
Secondary prevention with cervical<br />
screening has been extremely effective<br />
in reducing the serious sequelae<br />
from HPV infection. In the future,<br />
HPV screening (with or without cytological<br />
testing) may be used as the<br />
primary screening test in women<br />
older than 30 years. 12<br />
Journal <strong>of</strong> <strong>Biomedical</strong> <strong>Therapy</strong> 2011 ) Vol. 5, No. 1<br />
From a bioregulatory perspective,<br />
the emphasis in treating HPV infection<br />
should be on the factors implicated<br />
in persistence and disease progression;<br />
the immunomodulatory<br />
aspect and the tissue terrain should<br />
be addressed in a primary fashion.<br />
This type <strong>of</strong> treatment lends itself to<br />
a classic 3-pillar approach (Table).<br />
Lifestyle adjustment is <strong>of</strong> major importance,<br />
and smoking cessation<br />
should especially be encouraged.<br />
Protective sexual intercourse with<br />
condoms is advised, especially in<br />
women younger than 21 years because<br />
this is the age at which there is<br />
a peak incidence and because the<br />
presence <strong>of</strong> other sexually transmitted<br />
diseases concurrently has been<br />
implicated in the persistence <strong>of</strong><br />
high-risk HPV types.|<br />
References<br />
1. Diaz ML. Human papilloma virus: prevention<br />
and treatment. Obstet Gynecol Clin North Am.<br />
2008;35(2):199-217, vii-viii.<br />
2. Wheeler CM. Natural history <strong>of</strong> human papillomavirus<br />
infections, cytologic and histologic<br />
abnormalities, and cancer. Obstet Gynecol<br />
Clin North Am. 2008;35(4):519-536, vii.<br />
3. Garland SM, Hernandez-Avila M, Wheeler<br />
CM, et al. Quadrivalent vaccine against human<br />
papillomavirus to prevent anogenital<br />
diseases. N Engl J Med. 2007;356(19):1928-<br />
1943.<br />
4. Steben M, Duarte-Franco E. Human papillomavirus<br />
infection: epidemiology and pathophysiology.<br />
Gynecol Oncol. 2007;107(2)<br />
(suppl 1):S2-S5.
Table. Three-Pillar Approach for the Treatment <strong>of</strong> HPV Infection<br />
DET-Phase Basic and/or<br />
Symptomatic<br />
Mucodermal<br />
Urogenital<br />
Impregnation<br />
• Gynäcoheel<br />
(inflammation)<br />
) Practical Protocols<br />
Regulation <strong>Therapy</strong> a<br />
D&D • Advanced supportive detoxification and drainageb (for 6 weeks) followed by<br />
• Basic detoxification and drainage: Detox-Kitc (for 6 weeks)<br />
IM • Engystol<br />
• Tonsilla compositum<br />
(if persistence is not cleared by<br />
a regimen with Engystol only)<br />
COS • Mucosa compositum<br />
(vaginal and cervical)<br />
• Cutis compositum<br />
(external genital warts)<br />
• Coenzyme compositum<br />
• Ubichinon compositum<br />
(if not cleared by the initial regimen)<br />
Note: Persistent HPV is classified as being in the impregnation phase and, therefore, should be addressed aggressively. Engystol has been<br />
shown to have antiviral properties in several viruses, including the DNA viruses, 13 and can increase interferon production. 14 Thus, it is used<br />
as a supportive measure. However, if the virus is still persistent at the first follow-up after initiating treatment, a course <strong>of</strong> Tonsilla compositum<br />
(supportive <strong>of</strong> the immune system) and Ubichinon compositum (for deep cellular detoxification) should be added (3 times a<br />
week for 6 weeks) and Engystol should be continued after this period with follow-up.<br />
In patients who are seen with persistence <strong>of</strong> the same strain for longer than 2 years, these 2 organ regulators should be the first intervention<br />
for the first cycle, followed by Engystol.<br />
Dosages: Gynäcoheel, 10 drops 3 times daily. Regulation therapy: tablets, 1 tablet 3 times daily; ampoules, 1 ampoule <strong>of</strong> each medication,<br />
1 to 3 times per week; Detox-Kit, 30 drops <strong>of</strong> each medication in 1.5 L <strong>of</strong> water (drink throughout the day).<br />
Abbreviations: COS, cell and organ support; D&D, detoxification and drainage; DET, Disease Evolution Table; HPV, human papilloma virus; IM,<br />
immunomodulation.<br />
aAntihomotoxic regulation therapy consists <strong>of</strong> a 3-pillar approach: D&D, IM, and COS.<br />
bAdvanced supportive detoxification and drainage consists <strong>of</strong> Hepar compositum (liver), Solidago compositum (kidney), and Thyreoidea<br />
compositum (connective tissue).<br />
cThe Detox-Kit consists <strong>of</strong> Lymphomyosot, Nux vomica-Homaccord, and Berberis-Homaccord.<br />
5. Schiffman M, Herrero R, Desalle R, et al.<br />
The carcinogenicity <strong>of</strong> human papillomavirus<br />
types reflects viral evolution. Virology.<br />
2005;337(1):76-84.<br />
6. McIntyre-Seltman K, Castle PE, Guido R,<br />
Schiffman M, Wheeler CM. Smoking is a risk<br />
factor for cervical intraepithelial neoplasia<br />
grade 3 among oncogenic human papillomavirus<br />
DNA-positive women with equivocal or<br />
mildly abnormal cytology. Cancer Epidemiol<br />
Biomarkers Prev. 2005;14(5):1165-1170.<br />
7. Marks M, Gravitt PE, Gupta SB, et al. The<br />
association <strong>of</strong> hormonal contraceptive use<br />
and HPV prevalence [published online ahead<br />
<strong>of</strong> print October 26, 2010]. Int J Cancer.<br />
doi:10.1002/ijc.25628.<br />
8. Einstein MH, Schiller JT, Viscidi RP, et al.<br />
Clinician’s guide to human papillomavirus<br />
immunology: knowns and unknowns. Lancet<br />
Infect Dis. 2009;9(6):347-356.<br />
9. Haug C. The risks and benefits <strong>of</strong> HPV vaccination.<br />
JAMA. 2009;302(7):795-796.<br />
10. Slade BA, Leidel L, Vellozzi C, et al. Postlicensure<br />
safety surveillance for quadrivalent<br />
human papillomavirus recombinant vaccine.<br />
JAMA. 2009;302(7):750-757.<br />
11. Gold MS, McIntyre P. Human papillomavirus<br />
vaccine safety in Australia: experience to<br />
date and issues for surveillance. Sex Health.<br />
2010;7(3):320-324.<br />
Journal <strong>of</strong> <strong>Biomedical</strong> <strong>Therapy</strong> 2011 ) Vol. 5, No. 1<br />
12. Waxman AG, Zsemlye MM. Preventing cervical<br />
cancer: the Pap test and the HPV vaccine.<br />
Med Clin North Am. 2008;92(5):1059-<br />
1082, x.<br />
13. Oberbaum M, Glatthaar-Saalmüller B, Stolt<br />
P, Weiser M. Antiviral activity <strong>of</strong> Engystol:<br />
an in vitro analysis. J Altern Complement Med.<br />
2005;11(5):855-862.<br />
14. Roeska K, Seilheimer B. Antiviral activity<br />
<strong>of</strong> Engystol and Gripp-Heel: an in-vitro<br />
assessment. J Immune Based Ther Vaccines.<br />
2010;8:6. doi:10.1186/1476-8518-8-6.<br />
) 21
) 22<br />
) Specialized Applications<br />
Contributions <strong>of</strong><br />
Biological Medicine in Infertility<br />
Although it is debatable whether<br />
this figure has increased, it appears<br />
reasonably certain that women<br />
have been increasingly postponing<br />
their first pregnancy because <strong>of</strong><br />
their studies, work, or, simply, personal<br />
fulfillment. As we will see in<br />
the following text, this produces a<br />
complex situation that is <strong>of</strong> great<br />
significance for biological medicine.<br />
2 Broadly speaking, the causes<br />
<strong>of</strong> infertility can be summarized as<br />
shown in the Figure.<br />
Study centers specializing in infertility<br />
have developed well-designed<br />
Figure. Causes <strong>of</strong> Infertility 3<br />
By Gaston Orellana Alvarellos, MD<br />
Obstetrician/Gynecologist<br />
Infertility, defined as the inability to complete a pregnancy<br />
within a reasonable period (usually 12 months) in cases in<br />
which no contraceptives are used, is a problem that affects<br />
1 in every 6 couples. 1<br />
10%<br />
20%<br />
diagnostic methods, treatment protocols,<br />
and follow-up criteria that<br />
are generally free <strong>of</strong> controversy.<br />
Nevertheless, from the standpoint <strong>of</strong><br />
homotoxicology, which presupposes<br />
a more holistic consideration <strong>of</strong><br />
each pathological event, 4 I believe a<br />
different light can be cast on this<br />
particular subject. First, attention<br />
must be focused on the 10% <strong>of</strong> cases<br />
in which infertility is <strong>of</strong> unexplained<br />
etiology, while remaining cognizant<br />
<strong>of</strong> the fact that these considerations<br />
are valid for all cases. In addition,<br />
there is another area that has unex-<br />
10%<br />
30%<br />
30%<br />
Journal <strong>of</strong> <strong>Biomedical</strong> <strong>Therapy</strong> 2011 ) Vol. 5, No. 1<br />
pectedly come to the forefront in<br />
my personal experience; therefore, it<br />
will be necessary to discuss this area<br />
from a personal standpoint.<br />
In Chile, a forum has been set up for<br />
women being treated for infertility<br />
to share their experiences on the Internet.<br />
5 In this forum, members have<br />
mentioned the recurrent appearance<br />
<strong>of</strong> studies promoting treatment referred<br />
to as “alternative” concurrently<br />
with conventional treatment. Because<br />
my name has appeared in<br />
connection with successful cases, I<br />
have had to assume responsibility<br />
and consider, from both theoretical<br />
and practical standpoints (in combination<br />
with acupuncture), the concepts<br />
I would like to share.<br />
Most, if not all, <strong>of</strong> my patients have<br />
been aged between 30 and 40 years.<br />
This is what I mean when I say that<br />
women have postponed pregnancy<br />
until they have reached the age <strong>of</strong><br />
Uterotubal factors<br />
Male factors<br />
Ovulatory factors<br />
Sperm mobility factors<br />
Unexplained factors
approximately 35 years, a critical<br />
point statistically with respect to<br />
fertility. 6<br />
These are urban women, with sedentary<br />
jobs, working under artificial<br />
light, eating the diet imposed by the<br />
cafeteria at their company, in an environment<br />
that is overpopulated and<br />
exposed to all <strong>of</strong> the toxins in a<br />
modern building. The stress <strong>of</strong> modern<br />
life must be added, resulting<br />
from a job in which one’s survival<br />
depends on performance; this is<br />
only one <strong>of</strong> the factors that contribute<br />
toward maintaining the body’s<br />
alarm system on continual alert.<br />
Relevant <strong>Biomedical</strong> Factors<br />
1. Natural light. Circadian rhythms<br />
and the role <strong>of</strong> melatonin must<br />
be addressed. Melatonin is a hormone<br />
that was formerly paid little<br />
attention but whose study is<br />
attracting ever-increasing interest,<br />
particularly with respect to a<br />
scenario that is essentially cyclic.<br />
7<br />
2. Physical exercise. Surprisingly, I<br />
have been faced with the need<br />
to recommend exercise and to<br />
occasionally restrict it. Highper<br />
formance physical exercise<br />
causes severe disruption <strong>of</strong> the<br />
hypo thalamic-pituitary axis. 8<br />
3. Use <strong>of</strong> medicines. In particular,<br />
medicines acting on the central<br />
nervous system, which common-<br />
) Specialized Applications<br />
ly cause hyperprolactinemia,<br />
should be examined.<br />
4. Use <strong>of</strong> recreational drugs.<br />
5. Nutrition.<br />
• The consumption <strong>of</strong> complex<br />
car abohydrates, which are rich<br />
in fiber and have a low glyce mic<br />
index, should be recommen ded. 9<br />
There is increasing impor tance<br />
attributed to insulin in fertility.<br />
10,11<br />
• The consumption <strong>of</strong> proteins <strong>of</strong><br />
vegetable origin and white meat<br />
is important. There is no need to<br />
expand herein, but it is clear that<br />
excessive amounts <strong>of</strong> arachidonic<br />
acid must be avoided. This ingredient<br />
is found in red meat and<br />
contributes to the synthesis <strong>of</strong><br />
“bad eicosanoids.” 12<br />
• For the same reasons, with a<br />
view to recommend the “good<br />
eicosanoids”, 12 the use <strong>of</strong> extravirgin<br />
and cold-pressed vegetable<br />
oils should be emphasized.<br />
Journal <strong>of</strong> <strong>Biomedical</strong> <strong>Therapy</strong> 2011 ) Vol. 5, No. 1<br />
• Incidentally, when I speak <strong>of</strong><br />
good and bad eicosanoids, I am<br />
drawing attention, in an extremely<br />
general manner, to factors<br />
that play a role in persistent<br />
inflammatory syndrome and impaired<br />
endothelial function.<br />
Bioregulatory Treatment<br />
From the beginning <strong>of</strong> therapy, patients<br />
require the first pillar <strong>of</strong> treatment,<br />
4 detoxification and drainage,<br />
using Nux vomica-Homaccord, Berberis-Homaccord,<br />
and Lymphomyosot.<br />
However, in practice, I have had<br />
to administer the 2 other pillars earlier<br />
than planned because <strong>of</strong> the urgent<br />
nature <strong>of</strong> the patient’s situation.<br />
<strong>Homotoxicology</strong> involves acceptance<br />
<strong>of</strong> the concept that there is a<br />
minimum persistent inflammatory<br />
syndrome behind every pathological<br />
situation. In practice, this implies<br />
the use <strong>of</strong> Traumeel from the outset.<br />
© Monart Design/Fotolia.de<br />
) 23
) 24<br />
) Specialized Applications<br />
Table. Medications Used in the Treatment <strong>of</strong> Infertility<br />
DET-Phase Basic and/or<br />
Symptomatic<br />
Impregnation or<br />
degeneration<br />
Clinicians are faced with a problem<br />
in which there is no clarity about<br />
the specific organ that requires support.<br />
From a simplistic point <strong>of</strong><br />
view, the ovary must be considered<br />
as the main organ responsible; however,<br />
infertility is a problem <strong>of</strong> unknown<br />
origin. From this perspective,<br />
what I propose and use, in<br />
addition to Ovarium compositum, is<br />
Hepar compositum because the metabolism<br />
<strong>of</strong> steroids requires a<br />
healthy liver. If the dysfunctional<br />
tissue is unknown, I propose Coenzyme<br />
compositum and Ubichinon<br />
compositum as a second step.<br />
There are 2 resources that also must<br />
be mentioned. The first is Sepia in<br />
potency chords, as is seen in China-<br />
Homaccord, which meets the needs<br />
<strong>of</strong> a depressed and hopeless patient<br />
who requires support.<br />
The second is Placenta compositum.<br />
I have the highest opinion <strong>of</strong> its ca-<br />
Regulation <strong>Therapy</strong> a Optional<br />
• Gynäcoheel D&D • Basic detoxification and<br />
drainage: Detox Kit b<br />
IM • Traumeel<br />
COS • Ovarium compositum<br />
• Hepar compositum<br />
• Coenzyme compositum<br />
• Ubichinon compositum<br />
pacity to increase microcirculation<br />
at any level, including the ovaries; if<br />
applicable, this capacity should be<br />
considered.<br />
The bioregulatory treatment <strong>of</strong><br />
infertility is summarized in the<br />
Table.|<br />
References<br />
1. Lim AS, Tsakok MF. Age-related decline in<br />
fertility: a link to degenerative oocytes? Fertil<br />
Steril. 1997;68(2):265-271.<br />
2. Cruz JR, Gind<strong>of</strong>f PR. Age and reproduction.<br />
Reprod Med Rev. 1999;7(1):61-69.<br />
3. Edwards RG, Risquez F, eds. Modern Assisted<br />
Conception. Cambridge, England: Reproductive<br />
Healthcare Ltd; 2003.<br />
4. Ordinatio Antihomotoxica et Materia Medica:<br />
Tratado Práctico de Terapia Antihomotóxica.<br />
6th Rev ed. Baden-Baden, Germany: Biologische<br />
Heilmittel Heel GmbH; 2002.<br />
Journal <strong>of</strong> <strong>Biomedical</strong> <strong>Therapy</strong> 2011 ) Vol. 5, No. 1<br />
• China-Homaccord<br />
(if patient has a depressed mood)<br />
• Placenta compositum<br />
• Aesculus compositum<br />
Dosages: Gynäcoheel, 10 drops 3 times daily. Regulation therapy: tablets, 1 tablet 3 times daily; ampoules, 1 ampoule <strong>of</strong> each medication, 1<br />
to 3 times per week; Detox-Kit, 30 drops <strong>of</strong> each medication in 1.5 L <strong>of</strong> water (drink throughout the day). Optional therapy: ampoules, 1<br />
ampoule 1 to 3 times per week; drops, 10 drops 3 times daily.<br />
Abbreviations: COS, cell and organ support; D&D, detoxification and drainage; DET, Disease Evolution Table; IM, immunomodulation.<br />
a Antihomotoxic regulation therapy consists <strong>of</strong> a 3-pillar approach: D&D, IM, and COS.<br />
b The Detox-Kit consists <strong>of</strong> Lymphomyosot, Nux vomica-Homaccord, and Berberis-Homaccord.<br />
5. Foro Del Zócalo–Infertilidad–Adopción. Zócalo<br />
Web site. http://www.forodelzocalo.cl/.<br />
Accessed May 2, 2011.<br />
6. Age and Fertility: A Guide to Patients. American<br />
Society <strong>of</strong> Reproductive Medicine Web<br />
site. http://www.asrm.org/uploadedFiles/<br />
ASRM_Content/Resources/Patient_Resources/Fact_Sheets_and_Info_Booklets/<br />
agefertility.pdf. Accessed May 2, 2011.<br />
7. Lewy AJ. Melatonin and human chronobiology.<br />
Cold Spring Harb Symp Quant Biol.<br />
2007;72:623-636.<br />
8. Stafford DE. Altered hypothalamic-pituitary-ovarian<br />
axis function in young female<br />
athletes: implications and recommendations<br />
for management. Treat Endocrinol.<br />
2005;4(3):147-154.<br />
9. Chavarro JE, Rich-Edwards JW, Rosner BA,<br />
Willett WC. A prospective study <strong>of</strong> dietary<br />
carbohydrate quantity and quality in relation<br />
to risk <strong>of</strong> ovulatory infertility. Eur J Clin Nutr.<br />
2009;63(1):78-86.<br />
10. Kasturi SS, Tannir J, Brannigan RE. The<br />
metabolic syndrome and male infertility.<br />
J Androl. 2008;29(3):251-259.<br />
11. Porte D Jr, Baskin DG, Schwartz MW. Insulin<br />
signaling in the central nervous system:<br />
insulin and the control <strong>of</strong> reproduction and<br />
lifespan in mammals. Medscape Today Web<br />
site. http://www.medscape.com/viewarticle/504336_13.<br />
Accessed May 2, 2011.<br />
12. Sears B. The Antiaging Zone. New York, NY:<br />
Regan Books; 1999.
Dr. Mónica Lucia<br />
Name Guerra<br />
By Edda Medina, MD<br />
Born in Sincelejo, Colombia,<br />
Mónica grew up with her parents,<br />
Judith and Assad, and at the<br />
side <strong>of</strong> her three brothers. Music,<br />
poetry, and medicine were the constant<br />
components <strong>of</strong> her surroundings<br />
and predicted her successful<br />
life. From a very early age, and<br />
thanks to her father, a psychiatrist,<br />
and her uncle, a plastic surgeon,<br />
Mónica was in close contact with<br />
medicine, the pr<strong>of</strong>ession to which<br />
she was to devote all her energy.<br />
After graduating with a medical degree<br />
from the Universidad del Norte<br />
in Barranquilla, and with the firm<br />
intention <strong>of</strong> specializing in plastic<br />
surgery, she found her life taking an<br />
unexpected turn. She witnessed the<br />
return to health <strong>of</strong> her father, who<br />
had been treated with alternative<br />
therapy by a friend from his university<br />
days, Armando Rojas, who had<br />
dedicated himself to antihomotoxic<br />
medicine. The biological physician<br />
invited her to spend her vacation at<br />
the Center for Biological Medicine<br />
in Cali (founded by Dr. Arturo<br />
) Meet the Expert<br />
O’Byrne), and Mónica<br />
gladly accepted.<br />
During this period,<br />
her contact with the world <strong>of</strong> integrative<br />
biological medicine gave her<br />
the opportunity to witness not only<br />
the results achieved in patients, but<br />
also the possibility <strong>of</strong> practicing<br />
medicine in a holistic and integrative<br />
manner. What was planned as a<br />
brief vacation turned into a 5-year<br />
stay, beginning in 1991, during<br />
which she was trained in biological<br />
medicine and homotoxicology.<br />
Mónica came to realize the diagnostic<br />
and therapeutic benefits <strong>of</strong> electroacupuncture<br />
under the supervision<br />
<strong>of</strong> Dr. O’Byrne. Her interest<br />
and research led her to write a book<br />
in 2000, entitled Electroacupuntura<br />
de Voll (Electroacupuncture After<br />
Voll), promoting the appropriate use<br />
and interpretation <strong>of</strong> this diagnostic<br />
and therapeutic method.<br />
Thanks to the support <strong>of</strong> her husband,<br />
William Rincón, with whom<br />
she has shared her life since 1999,<br />
she began a successful medical career,<br />
resulting in the founding <strong>of</strong> her<br />
clinic in Bogota, which serves as a<br />
center <strong>of</strong> integrative biological medicine.<br />
The young couple fulfilled their<br />
lives with the birth <strong>of</strong> their son,<br />
William David, who became Mónica’s<br />
central inspiration, driving her<br />
to be more creative, dynamic, and<br />
enterprising. She enrolled at the National<br />
University <strong>of</strong> Colombia in<br />
2000, where she completed a vari-<br />
Journal <strong>of</strong> <strong>Biomedical</strong> <strong>Therapy</strong> 2011 ) Vol. 5, No. 1<br />
ety <strong>of</strong> additional courses in cellular<br />
and molecular biology, osteopathy,<br />
neural therapy, and acupuncture.<br />
She completed her studies and obtained<br />
a master’s degree in homeopathy<br />
in 2009.<br />
Mónica’s interest in academia has<br />
led her to develop accredited programs<br />
in molecular biology, with a<br />
specialty in homotoxicology, at several<br />
nationally and internationally<br />
recognized universities in various<br />
cities in Colombia.<br />
Mónica’s versatility and dedication<br />
are also reflected in her choice <strong>of</strong><br />
pastime activities. She is an accomplished<br />
singer and has mastered<br />
both the piano and the guitar. In addition,<br />
she enjoys painting and<br />
practicing her most daring hobby:<br />
riding the unicycle.|<br />
) 25
) 26<br />
) Expand Your Research Knowledge<br />
Purpose-Orientated<br />
Clinical Research<br />
In terms <strong>of</strong> research design, clinical<br />
studies can be interventional<br />
(clinical trials) or noninterventional<br />
(various types <strong>of</strong> observational studies).<br />
Clinical trials are experiments in<br />
which patients are usually allocated<br />
to groups at random (ie, randomized)<br />
and exposed to different treatments,<br />
with the goal <strong>of</strong> obtaining an<br />
unbiased comparison. Clinical trials<br />
can be either single blind (the nature<br />
<strong>of</strong> treatment is “masked” only for<br />
the patient) or double blind (the treatment<br />
is masked for both physicians<br />
and patients). Sometimes, reference<br />
is made to triple blind (usually this<br />
means that all the principal statistical<br />
analyses are completed on a<br />
blinded basis before the treatment<br />
allocation code is broken). In cases<br />
in which blinding <strong>of</strong> treatment is<br />
not possible, the term open label is<br />
<strong>of</strong>ten used.<br />
There are many types <strong>of</strong> observational<br />
studies. The key design characteristic<br />
is that these studies are<br />
noninterventional. The most basic<br />
type <strong>of</strong> observational study is a case<br />
report. Further types <strong>of</strong> observation-<br />
By Robbert van Haselen, MSc<br />
In the previous article in this series, I provided an over-<br />
view <strong>of</strong> the different medical study formats. Reference was<br />
made to an “evidence mosaic” as a multifaceted evidence<br />
base. In this article, I will delve a bit deeper into the role<br />
<strong>of</strong> clinical research as part <strong>of</strong> the evidence base.<br />
al studies are case series, case-control<br />
studies, and cohort studies. Cohorts<br />
can be defined in different<br />
ways (eg, on the basis <strong>of</strong> exposure to<br />
toxic substances, such as tobacco<br />
smoke, or treatment[s] received).<br />
The latter studies are sometimes referred<br />
to as postmarketing surveillance<br />
studies. Such cohort studies are useful<br />
for collecting information on the<br />
safety and effectiveness <strong>of</strong> particular<br />
medicines or therapeutic approaches<br />
in routine clinical practice. In summary,<br />
the key feature that distinguishes<br />
observational studies from<br />
clinical trials is the absence <strong>of</strong> an<br />
experimental intervention.<br />
A postauthorization safety study (PASS)<br />
is defined as a pharmacoepidemiological<br />
study performed in accordance<br />
with the terms <strong>of</strong> the marketing<br />
authorization, conducted with<br />
the aim <strong>of</strong> identifying or quantifying<br />
a safety hazard related to an<br />
authorized medicinal product. 1<br />
Therefore, a PASS is primarily characterized<br />
by its objective and not by<br />
its design. For instance, there is a<br />
PASS using an interventional design<br />
that confirms the safety <strong>of</strong> Traumeel<br />
Journal <strong>of</strong> <strong>Biomedical</strong> <strong>Therapy</strong> 2011 ) Vol. 5, No. 1<br />
tablets. 2 On the other hand, there<br />
are numerous noninterventional<br />
(PASS) cohort studies, including approximately<br />
9000 patients, that<br />
confirm the excellent tolerability <strong>of</strong><br />
Traumeel in its various galenic<br />
forms. 3 Therefore, PASSs are important<br />
for further substantiating the<br />
excellent safety pr<strong>of</strong>ile <strong>of</strong> biotherapeutic<br />
medicines. It is <strong>of</strong>ten forgotten<br />
that the utility <strong>of</strong> a treatment is<br />
not only determined by its effectiveness<br />
but also by its safety, <strong>of</strong>ten referred<br />
to as the riskbenefit ratio.<br />
Therefore, the relative safety <strong>of</strong> bioregulatory<br />
compared with conventional<br />
medicine is an important factor<br />
in conveying the overall utility<br />
<strong>of</strong> the therapeutic approach.<br />
The characteristics <strong>of</strong> the previously<br />
mentioned study designs are summarized<br />
in the Table.<br />
Dimensions <strong>of</strong> Research Design<br />
The purposes <strong>of</strong> clinical research on<br />
products can be categorized in various<br />
dimensions. The main types <strong>of</strong><br />
clinical studies are positioned somewhere<br />
in a space with the dimensions<br />
reality (real world vs ideal<br />
world), comparativeness (absolute<br />
effects vs relative effects), and level<br />
<strong>of</strong> confirmation (hypothesis generation<br />
vs hypothesis confirmation).<br />
Real World vs Ideal World<br />
This dimension is illustrated by contrasting<br />
the determination <strong>of</strong> relative<br />
efficacy <strong>of</strong> a treatment vs place-
) Expand Your Research Knowledge<br />
Table. Characteristics <strong>of</strong> Clinical Study Designs<br />
Study Design Characteristics<br />
Randomized<br />
clinical trial<br />
Postauthorization<br />
safety<br />
study<br />
bo in the “ideal world” <strong>of</strong> highly<br />
preselected patients who are willing<br />
to participate in a clinical trial vs determining<br />
the effectiveness <strong>of</strong> a<br />
treatment in patients in the “naturalistic”<br />
setting <strong>of</strong> routine clinical practice<br />
in observational studies. This<br />
dimension is weighted differently<br />
depending on the perspective. For<br />
health economists, real-world costeffectiveness<br />
data are more valuable<br />
than placebo-controlled clinical trial<br />
data. On the other hand, for a competent<br />
authority (ie, government<br />
regulatory body) that needs to decide<br />
on allowing a new drug on the<br />
market for a particular indication,<br />
placebo-controlled data will <strong>of</strong>ten<br />
be preferred. Most clinicians will<br />
usually want to know the effectiveness<br />
<strong>of</strong> a proposed new treatment<br />
compared with existing treatments.<br />
Absolute vs Relative Effects<br />
As an example, a clinical case report<br />
ranks the highest on the scale <strong>of</strong><br />
“absolute effectiveness”; on the other<br />
hand, a clinical trial comparing<br />
the new treatment <strong>of</strong> interest with<br />
the best available alternative treat-<br />
This is an interventional study in which participants are randomly (ie, by chance) assigned to 1 <strong>of</strong> 2 or more<br />
treatment arms. The reference treatment can be a placebo and/or an active treatment.<br />
A pragmatic clinical trial aims to assess the effectiveness <strong>of</strong> a treatment as much as possible under “realworld”<br />
conditions (ie, “Does it work?”).<br />
An explanatory clinical trial aims to assess the efficacy <strong>of</strong> a treatment under ideal conditions (ie, “Can it<br />
work?”)<br />
This is a pharmacoepidemiological study performed in accordance with the terms <strong>of</strong> the marketing authorization,<br />
conducted with the aim <strong>of</strong> identifying or quantifying a safety hazard related to an authorized<br />
medicinal product.<br />
Cohort study This type <strong>of</strong> study involves the identification <strong>of</strong> 2 or more cohorts <strong>of</strong> patients, one receiving the exposure/<br />
treatment <strong>of</strong> interest and the other(s) not, and following up these cohorts with regard to the outcome <strong>of</strong><br />
interest.<br />
Case-control<br />
study<br />
This type <strong>of</strong> study involves the identification <strong>of</strong> patients who have the outcome <strong>of</strong> interest and control<br />
patients who do not have the outcome <strong>of</strong> interest and then looking back to see if they had the exposure/<br />
treatment <strong>of</strong> interest.<br />
ment ranks the highest on the scale<br />
<strong>of</strong> “relative efficacy.”<br />
Hypothesis Generation vs<br />
Hypothesis Confirmation<br />
Most observational studies are excellent<br />
hypothesis-generating tools.<br />
In such cases, a “pro<strong>of</strong>-<strong>of</strong>-concept”<br />
clinical pilot trial could be a next<br />
step in identifying the most promising<br />
hypotheses, which can then be<br />
confirmed in larger-scale “confirmatory<br />
trials.”<br />
The Figure illustrates how different<br />
study designs fit into these dimensions.<br />
As can be seen from the positioning<br />
on the top-to-bottom axis,<br />
clinical case reports represent maximally<br />
the “real world” <strong>of</strong> clinical<br />
practice. When looking at the horizontal<br />
axes, it can be seen from the<br />
positioning on the left-to-right axis<br />
that case reports primarily represent<br />
“absolute” rather than “relative” effects.<br />
The reason for this is obvious:<br />
in a single case, clinicians are only<br />
interested in the effect in that particular<br />
patient and not in comparing<br />
it with effects in other patients.<br />
Journal <strong>of</strong> <strong>Biomedical</strong> <strong>Therapy</strong> 2011 ) Vol. 5, No. 1<br />
From the positioning on the frontto-back<br />
axis, it is clear that clinical<br />
case reports are primarily hypothesis<br />
generating. The reason for this is<br />
that a single case report can rarely<br />
be a definite pro<strong>of</strong>. A case series,<br />
pointing in the direction <strong>of</strong> a particular<br />
outcome, is still primarily hypothesis<br />
generating, but compared<br />
with a single case report, similar observations<br />
in repeated cases can be a<br />
first step toward confirmation <strong>of</strong> a<br />
particular hypothesis. The latter is<br />
represented by a shift in the direction<br />
<strong>of</strong> hypothesis confirmation on<br />
the front-to-back axis.<br />
All the clinical trial designs are on<br />
the horizontal axes, firmly placed<br />
toward hypothesis confirmation and<br />
relative effects. The reason is related<br />
to the primary objective <strong>of</strong> clinical<br />
trials: to make comparisons between<br />
different treatments to confirm or<br />
refute a particular predefined hypothesis.<br />
The main variation occurs<br />
on the vertical axis. A trial with a<br />
“surrogate” marker (eg, a particular<br />
laboratory value deemed to be predictive<br />
<strong>of</strong> a particular outcome) is<br />
less representative <strong>of</strong> the real world<br />
) 27
) 28<br />
) Expand Your Research Knowledge<br />
Absolute Effects<br />
Clinical<br />
Case Report<br />
Figure. Positioning <strong>of</strong> Clinical Study Designs<br />
on 3 Key Research Design Dimensions<br />
than a placebo-controlled trial with<br />
a clinical outcome measure (eg,<br />
pain). Also, placebo-controlled trials<br />
are less representative <strong>of</strong> the real<br />
world compared with trials in which<br />
the treatment <strong>of</strong> interest is compared<br />
with a well-established active treatment.<br />
In between case reports and clinical<br />
trials, which are positioned toward<br />
the extremes <strong>of</strong> the 3-dimensional<br />
space in the Figure, there are several<br />
further study types, such as casecontrol<br />
studies, cohort studies, and<br />
PASSs.<br />
Postauthorization<br />
Safety Study:<br />
Interventional<br />
Hypothesis Generation<br />
Case Series<br />
Postauthorization<br />
Safety Study:<br />
Noninterventional<br />
Ideal World<br />
Case<br />
Control<br />
Studies<br />
Real World<br />
Irrespective <strong>of</strong> whether a clinical<br />
study is a clinical trial or a case report,<br />
from a scientific perspective,<br />
the value <strong>of</strong> a study is determined by<br />
the appropriateness <strong>of</strong> the chosen<br />
design and the quality <strong>of</strong> its reporting.|<br />
Journal <strong>of</strong> <strong>Biomedical</strong> <strong>Therapy</strong> 2011 ) Vol. 5, No. 1<br />
Hypothesis Confirmation<br />
Cohort<br />
Studies<br />
Clinical Trial vs Placebo<br />
Surrogate Marker<br />
Clinical Trial vs Placebo<br />
Clinical Outcome<br />
Relative Effects<br />
Pragmatic Clinical Trial<br />
Active Control<br />
© iStockphoto.com/Kheng Guan Toh<br />
References<br />
1. EudraLex - Volume 9 Pharmacovigilance<br />
guide lines. European Commission Web site.<br />
http://ec.europa.eu/health/documents/eudralex/vol-9/index_en.htm.<br />
Accessed May<br />
2, 2011.<br />
2. Arora S, Harris T, Scherer S. Clinical safety<br />
<strong>of</strong> a homeopathic preparation. Biomed Ther.<br />
2000;18(2):222-225.<br />
3. Data on file. Baden-Baden, Germany: Biologische<br />
Heilmittel GmbH.
) Around the Globe<br />
Fifth <strong>International</strong> Congress on<br />
Complementary Medicine Research<br />
The <strong>International</strong> Congress on<br />
Complementary Medicine Research<br />
in Tromsø, Norway, was an<br />
intensive 4-day event involving 6<br />
keynote, 160 oral, and 110 poster<br />
presentations, as well as 5 symposia.<br />
The <strong>International</strong> Congress on<br />
Complementary Medicine Research<br />
2010 was the fifth congress <strong>of</strong> the<br />
<strong>International</strong> Society for Complementary<br />
Medicine Research; these<br />
congresses take place on a yearly rotating<br />
basis in Europe, Australasia,<br />
and the Americas. The fact that so<br />
many complementary and alternative<br />
medicine (CAM) researchers<br />
from throughout the world were<br />
willing to travel such long distances<br />
further underlined the rapid increase<br />
<strong>of</strong> CAM research activity on a global<br />
scale. Dominant CAM treatment<br />
modalities were Chinese medicine,<br />
acupuncture, body-mind techniques,<br />
and homeopathy.<br />
Several basic research studies on homeopathy<br />
were presented, including<br />
data from Kerstin Röska, PhD, suggesting<br />
that Engystol stimulates antiviral<br />
interferon type I production<br />
in cells <strong>of</strong> the innate immune system<br />
in vitro and that it might have a potent<br />
antiviral effect. Stephan<br />
Baumgartner, PhD, presented studies<br />
that suggested there were biological<br />
effects <strong>of</strong> potentized substances,<br />
including rosy apple aphid<br />
and Arsenicum album.<br />
Jim Rogers gave an interesting presentation<br />
on the methods <strong>of</strong> homeo-<br />
Tromsø, Norway, May 18 to 21, 2010<br />
By Konstantin Cesnulevicius, MD, PhD<br />
pathic pathogenetic trials (provings).<br />
He recommended developing methods<br />
for screening participants for<br />
sensitivity to the medicine used and<br />
establishing standards <strong>of</strong> planning,<br />
conducting, reporting, and communicating<br />
provings.<br />
Rainer Lüdtke presented the results<br />
<strong>of</strong> a systematic review that compared<br />
placebo effects in clinical trials<br />
on homeopathy with placebo effects<br />
in trials using conventional<br />
therapies. Results showed that, contrary<br />
to what is <strong>of</strong>ten assumed, placebo<br />
effects in randomized controlled<br />
trials using classical<br />
homeopathy were no larger than<br />
placebo effects using conventional<br />
medicine. This means that all<br />
schools <strong>of</strong> homeopathy can, in principle,<br />
be investigated in placebocontrolled<br />
studies. This study has<br />
been published in Homeopathy. 1<br />
Many presentations focused on<br />
“comparative effectiveness research”<br />
and the methodological challenges<br />
in CAM research. Issues that were<br />
discussed intensively during the<br />
congress included the “atypical” patient<br />
populations used in CAM research<br />
(compared with patients seen<br />
in routine CAM practice), blinding<br />
issues (eg, in acupuncture), the need<br />
for sensitive and appropriate outcome<br />
measures, and highly “context-specific”<br />
results <strong>of</strong> clinical studies.<br />
Josephine Briggs, MD, director <strong>of</strong><br />
the US National Center for Comple-<br />
Journal <strong>of</strong> <strong>Biomedical</strong> <strong>Therapy</strong> 2011 ) Vol. 5, No. 1<br />
mentary and Alternative Medicine,<br />
gave a keynote lecture on CAM research.<br />
She highlighted that there is<br />
a need for “pharmacological signatures”<br />
<strong>of</strong> natural products to evaluate<br />
them properly in clinical trials.<br />
These pharmacological signatures<br />
are important for demonstrating and<br />
explaining changes in actual pathophysiological<br />
mechanisms.<br />
The quality and pr<strong>of</strong>essionalism <strong>of</strong><br />
CAM research are rapidly evolving<br />
further; the fifth congress <strong>of</strong> the <strong>International</strong><br />
Society for Complementary<br />
Medicine Research has illustrated<br />
and confirmed this trend.<br />
Abstracts <strong>of</strong> the conference can be<br />
downloaded from the <strong>International</strong><br />
Congress on Complementary Medicine<br />
Research 2010 web site. 2<br />
The congress also confirmed that<br />
more basic and clinical research is<br />
needed in homeopathy. The sixth<br />
congress <strong>of</strong> the <strong>International</strong> Society<br />
for Complementary Medicine<br />
Research will take place in Chengdu,<br />
China, from May 7 to 9,<br />
2011.|<br />
References<br />
1. Nuhn T, Lüdtke R, Geraedts M. Placebo<br />
effect sizes in homeopathic compared to<br />
conventional drugs: a systematic review <strong>of</strong><br />
randomised controlled trials. Homeopathy.<br />
2010;99(1):7682.<br />
2. ICCMR 2010 Abstract Book. Rev ed. ICC-<br />
MR 2010 Web site. http://www.iccmr2010.<br />
com/Media/Files/ICCMR-2010-Abstract-<br />
Book-Revised-Edition. Accessed May 2,<br />
2010.<br />
) 29
) 30<br />
) Research Highlights<br />
Traumeel for the Treatment <strong>of</strong> Pain<br />
Associated With Breast Cancer<br />
Summary<br />
Introduction<br />
Breast cancer is a worldwide problem<br />
because <strong>of</strong> its high incidence.<br />
The pain associated with breast cancer<br />
treatment, including surgery, radiotherapy,<br />
and chemotherapy, <strong>of</strong>ten<br />
remains a long-term problem for<br />
many patients. The pain can be a result<br />
<strong>of</strong> scars after surgery or the adverse<br />
effects <strong>of</strong> radiotherapy and<br />
chemotherapy. This pain can definitely<br />
affect the quality <strong>of</strong> life <strong>of</strong> patients.<br />
Therefore, effective pain<br />
treatments are important.<br />
The World Health Organization<br />
lists the following conventional<br />
treatments for pain associated with<br />
breast cancer: acetylsalicylic acid,<br />
paracetamol, naproxen, metamizol,<br />
and dicl<strong>of</strong>enac (step 1 nonsteroidal<br />
anti-inflammatory drugs); and tramadol,<br />
codeine, and dihydrocodeine<br />
(step 2 opioid analgesic agents).<br />
However, these conventional treatments<br />
may not be effective for all<br />
patients who experience pain associated<br />
with breast cancer. Therefore,<br />
the following complementary and<br />
alternative therapies may also be<br />
used (especially for short-term pain<br />
relief ): acupuncture, hypnosis, relaxation/imagery,<br />
music, massage,<br />
and herbal supplements. Finally, homotoxicological<br />
treatments, such as<br />
Traumeel (Heel GmbH, Baden-<br />
Baden, Germany), can be used to<br />
treat resistant pain associated with<br />
breast cancer.<br />
In the study by Orellana Alvarellos<br />
et al, 1 a Traumeel injection was used<br />
By Gaston Orellana Alvarellos, MD<br />
Obstetrician/Gynecologist<br />
to alleviate the pain associated with<br />
breast cancer for patients who continued<br />
to experience pain after treatment<br />
with conventional medications.<br />
This study showed the<br />
advantages <strong>of</strong> Traumeel injection<br />
therapy for the relief <strong>of</strong> pain in those<br />
with breast cancer.<br />
Methods<br />
The study by Orellana Alvarellos et<br />
al 1 included case observations <strong>of</strong> 9<br />
women with unilateral breast cancer.<br />
The study was performed to assess<br />
pain relief and health-related quality<br />
<strong>of</strong> life after use <strong>of</strong> Traumeel injection<br />
therapy.<br />
The 9 women in this study were<br />
aged 52 to 81 years (mean, 69.7<br />
years). The cancer treatment these<br />
women received included surgery<br />
(conservative in 6 women and radical<br />
in 3 women), radiotherapy (all 9<br />
women), and chemotherapy (only 3<br />
women). Some <strong>of</strong> the women experienced<br />
pain immediately after treatment,<br />
whereas others only experienced<br />
pain between 2 and 12<br />
months after surgery plus radiotherapy.<br />
The conventional pain medications<br />
that the women received after<br />
treatment included paracetamol,<br />
pregabalin, ibupr<strong>of</strong>en, and ketopr<strong>of</strong>en.<br />
(One woman did not receive<br />
any <strong>of</strong> these medications.).<br />
A combination Traumeel and procaine<br />
injection was administered to<br />
all 9 women, who were then observed<br />
from August 2007 to April<br />
2008. The Traumeel injection solu-<br />
Journal <strong>of</strong> <strong>Biomedical</strong> <strong>Therapy</strong> 2011 ) Vol. 5, No. 1<br />
tion contained the following active<br />
ingredients: Arnica montana, Calendula<br />
<strong>of</strong>ficinalis, Chamomilla recutita,<br />
Symphytum <strong>of</strong>ficinale, Achillea millefolium,<br />
Atropa belladonna, Aconitum<br />
napellus, Bellis perennis, Hypericum<br />
perforatum, Echinacea angustifolia,<br />
Echinacea purpurea, Hamamelis virginiana,<br />
Mercurius solubilis Hahnemanni,<br />
and Hepar sulfuris. The injection<br />
was given once weekly (1 ampoule<br />
[2.2 mL] <strong>of</strong> Traumeel given subcutaneously<br />
with 2% procaine [5.0 mL]).<br />
Procaine was added to the Traumeel<br />
injection to relieve the pain associated<br />
with the injection. There were<br />
a maximum <strong>of</strong> 20 sites for injection<br />
(based on Oriental acupuncture), including<br />
the breast, ipsilateral shoulder,<br />
and ipsilateral scapula.<br />
The 9 women received from 3 to 10<br />
injections, until the pain was reduced.<br />
Injections were administered<br />
weekly. After the last injection, the<br />
patients were observed for 3- and<br />
6-month periods. Of the 9 patients,<br />
7 completed 6 months <strong>of</strong> observation<br />
and 2 completed 3 months <strong>of</strong><br />
observation.<br />
Pain was assessed by the 9 women<br />
as follows: before injection, immediately<br />
after injection, and at the 3-<br />
and 6-month observations. The<br />
sites, type, and occurrence <strong>of</strong> pain<br />
were assessed by questionnaire.<br />
Pain level was determined on a scale<br />
from 1 to 10, as on a visual analog<br />
pain scale. Patients also rated their<br />
health-related quality <strong>of</strong> life, including<br />
physical disability, insomnia,
© iStockphoto.com/motorolka<br />
and psychological distress. Finally,<br />
use <strong>of</strong> conventional analgesic agents<br />
before and after the Traumeel injection<br />
was noted.<br />
Results<br />
Three months after the final Traumeel<br />
injection, the mean±SD pain<br />
score was 3.3±2.2 points (range,<br />
1-7 points). This indicated a slight<br />
overall increase in pain when compared<br />
with the level immediately<br />
after the Traumeel injection. However,<br />
at 3 months after the final<br />
treatment, the effects <strong>of</strong> Traumeel<br />
injection therapy tended to vary<br />
from patient to patient. For example,<br />
1 patient experienced further pain<br />
relief, from 4 to 2 points; 3 patients<br />
maintained their pain relief (between<br />
1 and 3 points); and 5 patients<br />
experienced increased levels<br />
<strong>of</strong> pain (between 2 and 7 points).<br />
Overall, all 9 women still had lower<br />
levels <strong>of</strong> pain than they had before<br />
the Traumeel injection was first administered.<br />
Six months after the final Traumeel<br />
injection, the mean±SD pain score<br />
was 4.1±2.5 points (range, 1-7<br />
points). For 5 <strong>of</strong> the women, the<br />
pain score remained the same; only<br />
2 women experienced increased<br />
pain (this increase did not require<br />
treatment). Overall, the pain score<br />
was lower than before treatment,<br />
even after a lengthy period without<br />
any further therapy. Finally, even 12<br />
months after the last Traumeel injection,<br />
some <strong>of</strong> the women noted that<br />
their pain had not been exacerbated.<br />
In terms <strong>of</strong> physical disability, insomnia,<br />
and psychological distress<br />
symptoms, all 9 women experienced<br />
improvement after Traumeel injection<br />
therapy. At the 3-month obser-<br />
) Research Highlights<br />
The active ingredients <strong>of</strong> Traumeel<br />
include two species <strong>of</strong> the purple<br />
coneflower (Echinacea angustifolia and<br />
Echinacea purpurea, left) and the<br />
common daisy (Bellis perennis, right).<br />
vation, this improvement was sustained<br />
and even further increased in<br />
most <strong>of</strong> the women. However, 2<br />
women experienced a deterioration<br />
in these quality-<strong>of</strong>-life variables (to<br />
levels before the Traumeel injection).<br />
At the 6-month observation, 7<br />
women continued to sustain a good<br />
quality <strong>of</strong> life, as determined by the<br />
physical and psychological symptoms.<br />
The patients were asked about the<br />
effectiveness <strong>of</strong> Traumeel injection<br />
therapy. Of the 9 women, 8 indicated<br />
high effectiveness and 1 indicated<br />
good effectiveness. No patients<br />
reported low effectiveness.<br />
Overall, Traumeel injection therapy<br />
in these 9 women with breast cancer<br />
produced a sustained reduction in<br />
pain. <strong>Therapy</strong> also helped these<br />
women improve their management<br />
<strong>of</strong> daily work and reduce their psychological<br />
distress. Finally, the<br />
women experienced improved sleep<br />
as well.<br />
Discussion<br />
Traumeel has been used in Germany<br />
since 1937 to treat injuries and trauma.<br />
Research has indicated that<br />
Traumeel has analgesic and anti-inflammatory<br />
properties “by inhibiting<br />
the release <strong>of</strong> proinflammatory<br />
cytokines” (ie, interleukin 1β and<br />
tumor necrosis factor α) and a chemokine<br />
(ie, interleukin 8) in vitro. 2<br />
Other indications for which Traumeel<br />
has been used include chemotherapy-induced<br />
stomatitis, pain,<br />
and inflammation.<br />
The pilot study performed by Orellana<br />
Alvarellos et al 1 determined the<br />
effect <strong>of</strong> Traumeel injection therapy<br />
on 9 women with breast cancer. It<br />
was an open-label study and was<br />
Journal <strong>of</strong> <strong>Biomedical</strong> <strong>Therapy</strong> 2011 ) Vol. 5, No. 1<br />
not blinded. Each <strong>of</strong> the 9 women<br />
had taken various analgesic agents<br />
before the injection therapy, and the<br />
dosages <strong>of</strong> these agents were variable.<br />
This study is the first to show the<br />
effectiveness <strong>of</strong> Traumeel injection<br />
therapy for pain associated with<br />
breast cancer. For example, 1 <strong>of</strong> the<br />
9 women reduced her pain level<br />
from 10 points before the Traumeel<br />
injection to 5 points at 6 months after<br />
the last injection. Traumeel is effective<br />
because it contains neuralgia-alleviating<br />
substances used in<br />
homeopathy and homotoxicology.<br />
In conclusion, Traumeel injection<br />
therapy should be considered as an<br />
alternative therapy for pain in patients<br />
with breast cancer. Because<br />
breast cancer remains a worldwide<br />
health issue, and patients continue<br />
to experience resistant pain, effective<br />
pain medications are important.<br />
Traumeel provided tremendous pain<br />
relief immediately after final administration.<br />
This pain relief was long<br />
lasting (without using additional<br />
therapeutic agents). Therefore, because<br />
the results with Traumeel were<br />
good in this study, further clinical<br />
trials <strong>of</strong> this effective and tolerable<br />
homotoxicological agent should be<br />
planned and conducted.|<br />
References<br />
1. Orellana Alvarellos G, Ruiz de Viñaspre<br />
Alvear P, Kaszkin-Bettag M. A series <strong>of</strong><br />
case reports: clinical evaluation <strong>of</strong> a complex<br />
homeopathic injection therapy in the<br />
management <strong>of</strong> pain in patients after breast<br />
cancer treatment. Altern Ther Health Med.<br />
2010;16(1):54-59.<br />
2. Porozov S, Cahalon L, Weiser M, Branski<br />
D, Lider O, Oberbaum M. Inhibition <strong>of</strong> IL-<br />
1beta and TNF-alpha secretion from resting<br />
and activated human immunocytes by the<br />
homeopathic medication Traumeel S. Clin<br />
Dev Immunol. 2004;11(2):143-149.<br />
© iStockphoto.com/cunfek<br />
) 31
) 32<br />
IAH Abbreviated<br />
1 Access the IAH website at www.iah-online.com.<br />
Select your language.<br />
2 Click on Login and register.<br />
3 Go to Education Program.<br />
4 Click on The IAH abbreviated course.<br />
5 When you have finished the course, click on Examination.<br />
After completing it successfully, you will receive your<br />
certificate by mail.<br />
For MDs and licensed healthcare practitioners only<br />
Free <strong>of</strong> charge<br />
www.iah-online.com<br />
Course<br />
An e-learning course leading to<br />
certification in homotoxicology<br />
from the <strong>International</strong> <strong>Academy</strong> for<br />
<strong>Homotoxicology</strong> in just 40 hours.