Ovarian Response to Recombinant Follicle Stimulating Hormone in Women With PCOS

In women with polycystic ovary syndrome (PCOS) androgen excess is fundamental to the clinical
and physiological alterations of this disorder. In particular, androgen overproduction
induces distinctive PCO morphology and appears to influence follicle function. Studies
conducted in animals and nonhuman primates have demonstrated that androgens increase follicle
number and in small antral follicles enhance granulosa cell (GC) responsiveness to
gonadotropin stimulation. However, androgens also have been shown to clearly inhibit GC
aromatase activity, and in PCOS follicular fluid, androgen content is abnormally increased.
Efforts to reconcile these differences are nonexistent. Moreover, appropriate clinical
studies to examine the effects of androgen on follicle health in women are lacking. Excessive
androgen exposure in women due to functional tumors or high-dose testosterone treatment in
F-M transsexuals has been associated with PCO morphology. Use of androgen therapy to promote
follicle growth prior to ovarian hyperstimulation in women undergoing in vitro fertilization
has not provided consistent results. However, in these studies GC responses to FSH were not
carefully assessed, study populations were exclusively women with previously poor ovarian
responses to FSH, and women with PCOS were not included. In fact, there are essentially no
clinical studies that have addressed in detail the impact of androgen on follicle function in
normal or PCOS women. We hypothesize that androgen facilitates GC responses to FSH in normal
women and androgen excess further amplifies follicle growth and function in women with PCOS.
We propose to study the effect of increased ovarian androgen on follicle function by
increasing intraovarian androgen accumulation using aromatase inhibition followed by FSH
stimulation. The experiments in this project are designed to provide insight into whether
androgen excess facilitates or interferes with follicle function and ovulation in women with
PCOS.

Inclusion Criteria:

- Subjects determined to have PCOS based on clinical history of irregular menses and
clinical or laboratory evidence of hyperandrogenism and polycystic ovaries on
ultrasound OR

- Subjects determined to have a clinical history of regular periods.

Exclusion Criteria:

1. Women with hemoglobin less than 11 gm/dl at screening evaluation

2. Women with untreated thyroid abnormalities

3. Pregnant women or women who are nursing

4. Women with BMI > 37

5. Women with known sensitivity to the agents being used

6. Women with diabetes, or renal, liver, or heart disease

7. Women with any hormonal therapy or metformin for at least 2 months prior to study
start.