Ovarian Response to Recombinant Follicle Stimulating Hormone in Women With PCOS
Condition: Polycystic Ovary Syndrome; Healthy; Anovulation; Hyperandrogenism
MeSH terms: Polycystic Ovary Syndrome; Hyperandrogenism; Anovulation; Syndrome
Study type: Interventional
Phase: Phase 4

Summary: 
      Women with PCOS suffer from anovulation and, as a result, infertility. Efforts to clinically
      induce ovulation in these women using follicle stimulating hormone (FSH) administered
      subcutaneously seemingly requires prolonged administration compared to that of ovulatory
      women without PCOS. The apparent differing ovarian responsiveness to FSH between PCOS and
      normal women has not been carefully studied. We propose to address this issue by performing a
      dose-response study and examine ovarian follicle (estrogen, E2) responses to FSH administered
      subcutaneously in women with PCOS compared to responses observed in normal women.
    

Detailed description: 
      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.
    

Intervention name(s): Recombinant Follicle Stimulating Hormone
Intervention type(s): Drug
Intervention description(s): A modified dose-response study will be done using recombinant FSH (r-FSH), injected sc for 3 days at any one dose. r-FSH will be administered at weight-adjusted doses equivalent to 37.5, 75, and 150 IU based on an average weight of 70 kg, which approximates the weight of the average woman in the United States according to the Centers for Disease Control. Therefore, the actual dose of r-FSH will be 0.53 IU/kg for the 37.5 dose group. Accordingly, r-FSH will be repeated at doses of 1.1 IU/kg and 2.2 IU/kg that are equivalent to 75 and 150 IU for a 70 kg subject. Each FSH stimulation test will be assigned randomly and be separated by an interval of 8 weeks.
Intervention MeSH terms: Hormones; Follicle Stimulating Hormone
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Other
Keywords: polycystic ovary syndrome; anovulation; hyperandrogenism