Steroid Hormone Action In Female Reproduction

National Institute Of Diabetes And Digestive And Kidney Diseases

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Abstract

To evaluate reproductive health, we contacted thirty-nine women with fibrous dysplasia/McCune-Albright syndrome and obtained detailed menstrual and reproductive histories. In addition, ovarian ultrasound results were reviewed to evaluate for the presence of a spontaneous cyst, and biochemical data were reviewed. We found that 77% (30/39) of the women reported abnormal uterine bleeding that caused severe anemia requiring blood transfusion in 3 cases. Nine women underwent hysterectomy for management of bleeding, including 67% (6/9) at the unusually young age of less than age 35years. Infertility affected 43% of women (9/21), including 2 women who developed primary ovarian insufficiency after undergoing surgical resection of ovarian cysts. Of 25 spontaneous pregnancies in 14 women, 35% (8) were unplanned. Among the 14 pregnancies, pregnancy was associated with no change in bone pain in 7 subjects (53%), increased bone pain in 4 subjects (31%), and decreased bone pain in 2 subjects (15%). No additional skeletal complications were reported during pregnancies. We conclude that women with fibrous dysplasia/McCune-Albright syndrome report a high prevalence of gynecologic morbidity and reduced fertility. There is no clear association between pregnancy and poor skeletal outcomes in this population. In this pilot, double-blind, placebo-controlled trial, women with PPD were randomized to receive transdermal 17-estradiol (100 mcg/day) or placebo patch. Over 6 weeks, women completed weekly ratings on the Beck Depression Inventory (BDI), Edinburgh Postnatal Depression Scale (EPDS), and Hamilton Depression Scale (HAM-D). Primary outcome measures were treatment response (>50% decrease from baseline BDI) and remission (BDI <10) at 6 weeks, and secondary outcome measures included severity on all scales at weeks 3 and 6. Of 12 recruited women, 6 received TE and 6 received placebo. By week 6, 5 women receiving TE responded to treatment and 4 showed symptom remission, compared to 2 responders and 1 remitter in the placebo group. This difference was not significant (p=0.24). In a mixed-model of BDI ratings, TE was associated with a 9.2 point decrease at 3 weeks (95%CI -19.5 to +1.0, p=0.074) and a 10.5 point decrease at 6 weeks (95%CI -21.0-0.0, p=0.049) compared to placebo, though these differences did not survive multiple comparisons correction. Analogous effects were found for HAM-D but not EPDS scores. Interestingly, no significant difference in plasma estradiol levels existed between groups. We were unable to demonstrate a significant therapeutic benefit of TE compared with placebo in PPD. Although limited by under-recruitment and loss to follow-up, our results suggest TE is a feasible option for outpatient PPD management, with preliminary evidence (based on secondary outcomes) for efficacy. Therapeutic effects may be seen as early as 3 weeks and may not directly depend on peripheral measures of estradiol. We speculate that TE may provide more consistent estrogen exposure than pulsatile endogenous estrogen as the normal pituitary-ovarian axis resumes after delivery, and that a more consistent estrogenic mileau may underlie the improvements in the women who received TE.