Often women are prescribed hormone replacement therapy (HRT) during the perimenopause or
Hormone replacement therapy includes both estrogen and progesterone. The estrogen component
of HRT helps to relieve the symptoms and has a beneficial effect on the heart and bones, but
estrogen also increases the risk of uterine cancer. The progesterone component of the HRT
(progestin) works to prevent the increased risk of uterine cancer.
There is evidence that some women experience unpleasant mood symptoms (such as irritability,
depressed mood and anxiety) while receiving hormone replacement therapy (HRT) while taking
the progestin / progesterone component of the HRT.
This study is designed to evaluate the ability of progestins to produce negative mood
symptoms in women. Researchers intend on doing this by comparing the effects of
medroxyprogesterone acetate (Provera) and a placebo inactive sugar pill. Patient's moods
will be monitered based on their response to questionnaires answered in the outpatient
clinic and at home.
This research will attempt to answer the following questions:
1. Are progestins associated with changes in mood during hormone replacement therapy?
2. If progestins are associated with mood disturbance, is it because they are blocking the
beneficial effects of estrogen?
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?
The subjects in this study will be women who meet the following criteria:
1. history of mood and/or behavioral symptoms associated with hormone replacement
2. age 40 to 65;
3. in good medical health.
Any subject with significant physical, EKG, mammogram or laboratory abnormalities will not
participate in this protocol. Additionally prior to participation all subjects will be
examined for any contradictions to estrogen therapy (as determined by a pelvic exam and
mammogram) within the past year by a gynecologist of their choice. In those patients who
are unable to independently arrange this exam, we have arranged for a consultant
gynecologist to be available through our collaboration with NICHD.