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

Muse et al (IM [D-Trp-ProNEt-GnRH 50 µg daily)
Freeman et al (depot leuprolide 3.75 mg monthly)
Brown et al (depot leuprolide 3.75 mg monthly)
Leather et al (depot goserelin 3.6 mg monthly)
Overall anovulatory GnRH analogue doses
Non-ovulatory dosing regimens
Sundstrom et al (100 µg nasal buserelin daily)
Favors GnRH analogue
Overall GnRH doses (anovulatory and non-anovulatory)
Add-back hormone therapy
Menopausal symptoms and osteoporosis limit the use
of GnRH analogues. The use of add-back hormonal
therapy may reduce these side effects and prolong their
use. There has been some debate as to what the best
form of add-back hormone therapy is for women on
long-term GnRH analogues, both from the point of view
of maintaining efficacy and avoiding osteoporosis. Data
show that bone mineral density can be maintained by
use of standard preparations of both cyclical and continuous
HRT. Continuous combined therapy or tibolone
is preferable to sequential combined therapy if one is to
minimize the risks of symptom resurgence during the
progestogen phase from PMDD-like progestogenic side
effects. 20,21 Overall, the meta-analysis favored neither
GnRH alone or GnRH with add-back � 0.12 (CI �0.34
to 0.59), 18 which means that the highly beneficial effect
of the analogues is not diminished by the addition of
add-back therapy, particularly for tibolone.
Practical aspects
Because symptoms recur with the return of ovarian
function, therapy may have to be continued indefinitely;
this is precluded by significant trabecular bone loss,
which can occur by 6 months’ therapy. The use of GnRH
analogues with add-back estrogen or tibolone can be
protective to the skeleton, but bone density should be
monitored in women using analogues for more than 6
months, as bone loss may still occur in some individuals.
22 There is little published evidence to guide management.
It seems likely that bone density scanning is
MANAGEMENT BY OVARIAN CYCLE SUPPRESSION 125
–10 –8 –6 –4 –2 0 2
Standard mean differences
unnecessary for short-term therapy. If therapy is prolonged,
then it would seem safest to undertake bone
density scans (ideally by dual energy X-ray absorptiometry)
annually throughout therapy, even when add-back
is used. Treatment should be stopped if bone density
declines significantly in scans performed 1 year apart.
PROGESTERONE AND PROGESTOGENS
The efficacy of progestogens and progesterone in the
treatment of PMS/PMDD remains questionable. Progestogens
(synthetic progesterone) produce PMDD-like
side effects due to competition for the mineralocorticoid,
androgen, and central nervous system (CNS) receptors.
It is therefore not surprising that the data for their efficacy
is poor. On the other hand, progesterone is diuretic,
natriuretic, and is a CNS anxiolytic. As such, there is
some logic to using a progesterone preparation for treatment
of PMD/PMDD. 13 However, we have seen that no
evidence exists to demonstrate progesterone deficiency
(see Chapter 10) and so if progesterone was effective it
would be pharmacotherapeutic rather than replacement
therapy.
Possible mechanism of action
Favors placebo
Figure 14.3 Meta-analysis of studies using GnRH analogue therapy for PMDD. (Adapted from Wyatt et al
2004, 18 with permission.)
One of the theories regarding the genesis of PMS/
PMDD symptoms was that symptoms were due to a
progesterone deficiency in the luteal phase. It is known
that progesterone does produce CNS depression and in
very large doses can be anesthetic. It follows that, in
theory, women with symptoms of irritability and agitated