Trial Information

The Phenomenology and Biophysiology of Progestin-Induced Dysphoria

There is evidence in the literature that some women experience dysphoric symptoms while
receiving hormone replacement therapy (HRT) and that this disturbance in mood is related to
the progestin component of the HRT. The bulk of this evidence is anecdotal. While some
authors have attempted to examine this putative problem in a more systematic fashion, there
are no controlled studies that attempt to identify the mechanism through which the
perturbation in mood occurs. Adverse effects of progestins might be mediated directly
through the progesterone or androgen receptor. Alternatively, the effects of progestins
might be consequent to the antiestrogen effects of progesterone. This latter possibility is
in part supported by our observation in previous studies of the beneficial effects of
estradiol on mood and the possible precipitation of mood disturbance following acute
estrogen withdrawal. Finally, despite the popular lore that progesterone causes mood
disturbances, a placebo effect cannot be ruled out, since women taking HRT know when they
are receiving the progestin component of the regimen. Our research questions therefore are
as follows: 1) Are progestins associated with changes in mood during HRT, and 2) If
progestins are associated with mood disturbance, is it because they are blocking the
beneficial effects of estrogen?