Ovarian Response to Recombinant Follicle Stimulating Hormone in Women With PCOS
Primary Purpose
Polycystic Ovary Syndrome, Healthy, Anovulation
Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Recombinant Follicle Stimulating Hormone
Sponsored by
About this trial
This is an interventional other trial for Polycystic Ovary Syndrome focused on measuring polycystic ovary syndrome, anovulation, hyperandrogenism
Eligibility Criteria
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:
- Women with hemoglobin less than 11 gm/dl at screening evaluation
- Women with untreated thyroid abnormalities
- Pregnant women or women who are nursing
- Women with BMI > 37
- Women with known sensitivity to the agents being used
- Women with diabetes, or renal, liver, or heart disease
- Women with any hormonal therapy or metformin for at least 2 months prior to study start.
Sites / Locations
- University of California, San Diego
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Active Comparator
Arm Label
Women with normal menses
Women with Polycystic Ovary Syndrome
Arm Description
Outcomes
Primary Outcome Measures
Change in granulosa cell function in 24 hours intervals following FSH administration
Granulosa function will be assessed using estradiol and inhibin levels
Change in follicle count in following FSH administration
Number of ovarian follicles will be assessed by pelvic ultrasound
Change in follicular size in following FSH administration
Size of ovarian follicles will be assessed by pelvic ultrasound
Secondary Outcome Measures
Full Information
NCT ID
NCT03252223
First Posted
August 8, 2017
Last Updated
September 6, 2021
Sponsor
University of California, San Diego
Collaborators
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
1. Study Identification
Unique Protocol Identification Number
NCT03252223
Brief Title
Ovarian Response to Recombinant Follicle Stimulating Hormone in Women With PCOS
Official Title
Ovarian Function in Women With Polycystic Ovary Syndrome
Study Type
Interventional
2. Study Status
Record Verification Date
September 2021
Overall Recruitment Status
Completed
Study Start Date
October 2, 2017 (Actual)
Primary Completion Date
June 30, 2021 (Actual)
Study Completion Date
June 30, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of California, San Diego
Collaborators
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Polycystic Ovary Syndrome, Healthy, Anovulation, Hyperandrogenism
Keywords
polycystic ovary syndrome, anovulation, hyperandrogenism
7. Study Design
Primary Purpose
Other
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
33 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Women with normal menses
Arm Type
Active Comparator
Arm Title
Women with Polycystic Ovary Syndrome
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
Recombinant Follicle Stimulating Hormone
Intervention Description
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.
Primary Outcome Measure Information:
Title
Change in granulosa cell function in 24 hours intervals following FSH administration
Description
Granulosa function will be assessed using estradiol and inhibin levels
Time Frame
Serum levels will be assessed daily during each 3 day FSH stimulation test and for five days following the initial FSH administration
Title
Change in follicle count in following FSH administration
Description
Number of ovarian follicles will be assessed by pelvic ultrasound
Time Frame
With each dose tested, a pelvic ultrasound will be done before and 3 days after commencing FSH
Title
Change in follicular size in following FSH administration
Description
Size of ovarian follicles will be assessed by pelvic ultrasound
Time Frame
With each dose tested, a pelvic ultrasound will be done before and 3 days after commencing FSH
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
37 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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:
Women with hemoglobin less than 11 gm/dl at screening evaluation
Women with untreated thyroid abnormalities
Pregnant women or women who are nursing
Women with BMI > 37
Women with known sensitivity to the agents being used
Women with diabetes, or renal, liver, or heart disease
Women with any hormonal therapy or metformin for at least 2 months prior to study start.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
R. Jeffrey Chang, MD
Organizational Affiliation
University of California, San Diego
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of California, San Diego
City
La Jolla
State/Province
California
ZIP/Postal Code
92037
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
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Ovarian Response to Recombinant Follicle Stimulating Hormone in Women With PCOS
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