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

126 THE PREMENSTRUAL SYNDROMES
depression may therefore respond favorably to progesterone.
However, the most plausible mechanism of
action is that at high doses, particularly when used
through the whole cycle, progestogens and progesterone
can have an ovulation suppressant effect which
can improve symptoms. However, what often happens
when preparations such as depot medroxyprogesterone
acetate are used is that cyclical symptoms are replaced
by lower-grade continuous PMDD-type side effects.
Most studies have shown no benefit. One prospective
randomized study undertaken and published by a pharmaceutical
company did show ‘a benefit for both psychological
and physical symptoms in the pre-menstruum
with absence of symptoms in the post-menstruum’. 23
Patients were randomized to use either progesterone
pessaries (400 mg twice a day) or matching placebo, by
vaginal or rectal administration, from 14 days before
the expected onset of menstruation until onset of vaginal
bleeding for four consecutive cycles; 45 general practitioners
identified a total of 281 patients. The main
outcome variables were change in the severity of each
patient’s most severe symptoms and in the average score
of all the patients’ symptoms. The response to progesterone
was greater than to placebo during each cycle;
the difference was clinically and statistically significant.
Adverse events of irregularity of menstruation, vaginal
pruritus, and headache were reported more frequently
by patients taking active therapy.
A recent meta-analysis of all published studies meeting
strict methodological criteria for the treatment of PMS/
PMDD failed to confirm benefit with either progesterone
or progestogens in the management of PMS. 24 The
objective of this meta-analysis was to evaluate the efficacy
of progesterone and progestogens in the management
of premenstrual syndrome. Ten trials of progestogen
therapy (531 women) and four trials of progesterone
therapy (378 women) were reviewed. The main outcome
measure was a reduction in overall symptoms of PMS.
All the trials of progesterone (by both routes of administration)
showed no clinically significant difference
between progesterone and placebo. For progestogens,
the overall SMD for reduction in symptoms showed a
slight non-significant difference in favor of progestogen
with the mean difference being �0.036 (95% CI �0.059
to �0.014). The meta-analysis of this systematic review
therefore suggested that there was no published evidence
to support the use of either progesterone or progestogen
therapy in the management of premenstrual syndrome.
The evidence for the use of progesterone and progestogens
is poor and does not support their continued use for
PMS. There is some justification for undertaking betterdesigned
studies in patients with well-defined PMDD
for the established progestogens and progesterone and
for looking at the newer progestogens: for instance,
etonorgestrel, as found in some modern ovulation suppressant
progestogen-only contraceptives (e.g. Cerazette,
Organon Laboratories). Whether study of the so-called
natural progesterone preparations should be undertaken
is more debatable and should not be conducted
before there are formulations which give rise to consistent
elevation of blood progesterone levels.
HYSTERECTOMY AND BILATERAL
SALPINGO-OOPHORECTOMY
A historical perspective
Henry Maudlsey was the first to recognize the association
of physical and emotional symptoms with the
woman’s cycle and with great prescience noted the
association of behavioral changes with ovarian cycles:
‘the monthly activity of the ovaries which marks
the advent of puberty in women has a notable
effect upon the mind and body wherefore it may
become an important cause of mental and physical
derangement.’
Thus it was clear that the cyclical symptoms of insanity
or menstrual madness were believed to be due to
ovarian function rather than menstruation, and treatment
took the form of removal of ovaries. Thus
evolved the original form of ‘ovarian cycle suppression’.
It was not until 1872 that normal ovariotomy – i.e.
removal of normal ovaries – was performed for a disorder
or malady which was not essentially gynecological.
25 The first surgeon to perform this was Alfred
Hegar of Freiberg, to be followed 7 days later by Lawson
Tait of Birmingham and Robert Battey of Georgia, USA.
At the latter’s insistence, it became known as Battey’s
operation, 26 but in Britain, ‘Tait’s operation’ was used,
particularly by his enemies. Battey believed that insanity
was, ‘not infrequently caused by uterine and ovarian
disease’. He describes how he had a Southern girl, of
more than unusual beauty, as a patient with cyclical
vomiting and hysteria. If we regard menstrual madness
as severe PMDD, and ovarian ablation by GnRH analogues
as a medical castration equivalent to oophorectomy,
then there is ample evidence that removing the
ovarian cycle in this way will improve all of the symptom
groups of severe PMDD. These historical events have
recently been reviewed by Studd and found to have great
relevance to our current medical treatment of PMDD.
Although the procedure would have had the desired
effect of curing cyclical monthly symptoms, if the
surgeon had correctly selected his patients, the 19th
century surgeons had no concept of menopausal symptoms
or osteoporosis. Thus, this operation would