Premenstrual Syndromes : PMS and PMDD - Rutuja :: The site ...

are improved. Luteal phase danazol is a very effective
treatment for breast symptoms and with virtual elimination
of symptomatic side effects.
GONADOTROPIN-RELEASING
HORMONE AGONISTS
Gonadotropin-releasing hormone (GnRH) agonists are
an example of a group of drugs that suppress ovarian
function, which is believed to be the trigger for PMDD. 47
GnRH agonists down-regulate the gonadotropin receptors
in the pituitary gland to create a hypogonadotropic
state whereby ovarian function is suppressed to menopausal
levels and amenorrhea is induced. 47 Due to the
low serum estradiol concentrations induced by GnRH
agonists, side effects are common and, because of
potential bone demineralization, 48 treatment with these
compounds is usually restricted to 6 months. 49 In order
to lengthen the period that GnRH agonists can be
administered, several studies have used concomitant ‘addback’
hormone replacement therapy. GnRH agonists are
not frequently prescribed in primary care because of
cost and side effects.
Recently, a meta-analysis of published randomized
placebo-controlled trials was conducted to evaluate the
efficacy of GnRH agonists with and without ‘add-back’
therapy in women with a diagnosis of PMS. 47 Five
trials without add-back therapy (71 women on active
treatment) met inclusion criteria. The equivalent odds
ratio (OR) was 8.66 in favor of GnRH agonists. GnRH
agonists were more efficacious for physical than behavioral
symptoms, although the difference was not statistically
significant. Women were three times more likely
to experience side effects on treatment compared with
placebo, which included hot flashes, aches, night sweats,
and nausea. Of the five included trials, three used depot
GnRH agonists, 4,6,50 one used daily injection, 51 and
another gave GnRH agonists as a nasal spray. 52
However, the efficacy of individual GnRH types and
routes of administration could not be assessed in the
meta-analysis, owing to the small number of trials and
participants.
Three randomized controlled trials (64 patients in
total) compared the efficacy of add-back therapy
and GnRH agonists � placebo in the management
of PMS. 5,50,53 There was no significant reduction in
effectiveness of GnRH agonists with the addition of
add-back therapy. These finding were confirmed in a
subsequent study of leuprolide acetate with and
without add-back. 54 However, women were more likely
to drop out of the trial while on add-back therapy.
Future studies on GnRH agonists in PMDD should
include those which assess the safety of long-term
combined therapy particularly in relation to lipid profiles
and bone mineral densities. Additionally, cost and
the need for long-term repeated injections needs
consideration. Nevertheless, in patients unresponsive
to successive trials of OCPs, GnRH agonists �
add-back therapy should be considered second-line
treatment.
DIETARY SUPPLEMENTATION
Some dietary supplements are thought to interact with
steroid activity and are therefore considered here.
Chasteberry
Chasteberry, the fruit of the chaste tree (Vitex agnuscastus),
is commonly used for treating premenstrual
symptoms. Active constituents in chasteberries are the
essential oils, iridoid glycosides, and the flavonoids. 55
The mechanism of action is unclear, but it may involve
decreasing estrogen, and increasing progesterone, prolactin,
and dopamine levels. 56 A 3-month, randomized
double-blind placebo-controlled study of 217 PMS/
PMDD subjects found chasteberry (600 mg three times
daily) only alleviated restlessness. 57 Another study
showed that chasteberry and vitamin B 6 had similar
reductions in PMS scores (77% and 66%, respectively).
58 In general, the data show conflicting results
but appear promising.
Black cohosh
The majority of studies looking at black cohosh
(Cimicifuga racemosa) have been in the treatment of
menopausal symptoms. The mechanism of action
remains somewhat unclear, but may involve suppressing
luteinizing hormone secretion. 56 A number of
studies using Remifemin, a proprietary extract of black
cohosh, show efficacy in treating menopausal symptoms
(hot flashes, profuse sweating, sleep disturbance,
and depressive moods). 59 Because these symptoms often
present in women with PMDD, many clinicians have
recommended the use of black cohosh in this population.
Further clinical studies are needed to determine
the efficacy of black cohosh in PMDD. The recommended
dose is 40–80 mg of a standardized extract
twice daily, providing 4–8 mg of triterpine glycosides. 59
CONCLUSIONS
HORMONAL THERAPIES OVERVIEW 113
The ideal choice of a hormonal treatment in PMS/ PMDD
would be based on randomized, placebo-controlled