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14
The management of PMS/PMDD through
ovarian cycle suppression
Nick Panay and John WW Studd
INTRODUCTION
We have seen in previous chapters that the underlying
cause of premenstrual syndrome/premenstrual dysphoric
disorder (PMS/PMDD) remains unknown, although
cyclical ovarian activity appears to be a key factor. 1 A
logical treatment, therefore, is to suppress ovulation
and thus prevent the neuroendocrine changes that cause
the distressing symptoms. The current therapy for PMS/
PMDD is varied and includes psychotherapeutic, cognitive,
or hormonal. However, the cornerstone of hormonal
treatment relies upon suppression of ovulation
and removal of the hormonal changes that follow ovulation
in the luteal phase. When there are no cyclical
hormonal changes during pregnancy, not only are there
no cyclical mood symptoms but also depression is uncommon.
There then often follows an episode of postpartum
depression when there is a fall of levels of placental
hormones, with a recurrence of symptoms when the
periods return. 2
There are now many placebo-controlled studies
showing that suppression of ovulation by increasing
plasma estradiol levels or by down-regulation results in
an improvement in PMS/PMDD. A number of drugs
are capable of achieving this but they are not without
their own side effects, and this may influence the efficacy
of the treatment and the duration for which they may be
given. The purpose of this chapter will be to review the
evidence for the available therapies and offer some
practical advice as to how these preparations can be
incorporated into day-to-day clinical practice.
THE COMBINED ORAL
CONTRACEPTIVE PILL
Although able to suppress ovulation and used commonly
to improve PMS/PMDD symptoms, the combined oral
contraceptive pill (COCP) was initially not shown to be
of benefit in randomized prospective trials. 3 This is
probably because the daily progestogen in the secondgeneration
pills caused PMDD-type symptoms of its own
accord. A new combined contraceptive pill (Yasmin,
Schering Corporation) contains an antimineralocorticoid
and antiandrogenic progestogen, drospirenone.
This has shown considerable promise in the treatment
of PMS/PMDD, as it is devoid of progestogenic side
effects and provides additional benefits from the mild
diuretic and antiandrogenic effect. There are now both
observational and small randomized trial data supporting
its efficacy; these data require confirmation with
larger studies. 4
More recently, a lower-dose version of this COCP
(Yaz, Schering Corporation) with 20 �g ethinylestradiol
and 3 mg drospirenone (24 active, 4 inactive tablets, per
cycle) has been shown to be effective for treating PMDD
in a moderately sized randomized controlled trial of 450
subjects over three treatment cycles. 5 There was a significantly
greater improvement of the total Daily Record
of Severity of Problems (DRSP) for active treatment compared
with placebo (�37.49 vs �29.99, p � 0.001).
Specifically, mood symptoms improved significantly
(�19.2 vs �15.3, p � 0.003). There was a reduction in
daily symptoms of 48% for active vs 36% for placebo
(RR � 1.7, p � 0.015).
Practical aspects
If the COCP is used to treat PMS/PMDD, pill packets
should be used back to back (bicycling/tricycling or
continuously) and a break only introduced if erratic
bleeding occurs. Recognizing the benefits of longer
cycle regimens, a four bleed per year COCP has already
been licensed and a no-bleed regimen is planned. Data
are required to confirm the superiority of these regimens
in comparison to traditional regimens.