Clinical Trial: Androgen Excess as a Mechanism for Adipogenic Dysfunction in PCOS Women
Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional
Official Title: Androgen Excess as a Mechanism for Adipogenic Dysfunction in PCOS Women
Brief Summary:
The purpose of this research study is to collect specimen samples and study medical information from women with Polycystic Ovary Syndrome (PCOS) and women without PCOS. The goal is to learn more about the changes that take place in the body that result in PCOS.
We anticipate that 59 women will take part in this study (15 without PCOS and 44 with PCOS). All patients will undergo a physical exam, blood tests, and ultrasound of their ovaries. If they meet the criteria for this study, they will then undergo additional blood tests, removal of a small amount of subcutaneous abdominal fat, measurement of regional body fat (i.e., MRI, DXA scan), a modified frequently-sampled intravenous glucose tolerance test (FSIGTT), and determination of ovarian function (via a follicle stimulating hormone [FSH] test). The women without PCOS will be complete the study at this point.
The women with PCOS will be randomized to receive the drug flutamide 125 mg/day or placebo. They will take the drug every day for six 28-day cycles. They will be asked to collect and store a urine sample once a week. They will also be asked to complete a pill diary and menstrual diary. Once a month while they are taking the flutamide/placebo, they will return to the clinic and bring their frozen urine samples. At that time they will undergo a physical exam, toxicity assessment, and blood draw.
Quality of Life assessments will be done at the beginning of the study for all participants. Women with PCOS who are taking the flutamide or placebo will be asked to repeat the Quality of Life assessments during the study and at the end of the study.
Six months following the completion of protocol procedures, participants who received flutamide/placebo will be contacted by phone
Detailed Summary:
Aim 1. Compare differences in SC abdominal adipogenesis of lean PCOS women vs. age- and BMI-matched controls Subjects and clinical assessment: We will recruit 36 lean (18.5-25 kg/M2) PCOS subjects and 12 age- and BMI-matched controls. Subjects will complete a standardized questionnaire emphasizing menstrual dating, abnormal hair growth and acne. The questionnaire also will annotate age, smoking status, medications, surgical history and family histories of excess hair growth in female relatives and of diabetes in parents or siblings for exclusion criteria and for inclusion of some basic traits as covariates. Subjects also will undergo a physical examination; hirsutism will be scored by the modified Ferriman-Gallwey (mFG) method. Transvaginal sonography (TVUS) will be performed to determine the presence or absence of polycystic ovaries. A screening blood sample will be obtained for determinations of steroid hormones, SHBG, TSH, and prolactin.
Non-Hispanic Caucasian women between the ages of 18 and 35 years will be recruited to avoid confounding differences as a function of race. PCOS patients will be diagnosed by 1990 NIH criteria. Controls will have regular menstrual cycles at 21 to 35 day intervals, a luteal phase progesterone (P4) level > 3 ng/mL, and no evidence of hirsutism, acne, alopecia, polycystic ovaries or endocrine dysfunction. Exclusion criteria are: present/past history (<5 years) of smoking, cancer, alcohol abuse, drug addiction, severe depression, or post traumatic stress; diabetes; uncontrolled hypertension (≥ 165/100); clinically significant hepatic or renal disease, or other major medical illness; signs or symptoms of infection; recent (within 30 days) use of an experimental device; recent (within 6 months) use of androgens, anabolic steroids or non-steroidal anti-inflammatory drugs; recent (within 3 months) use of hormonal agents (including b
Sponsor: University of California, Los Angeles
Current Primary Outcome:
- Six-month flutamide (antiandrogen) administration to lean women with polycystic ovary syndrome (PCOS) will improve impaired glucose tolerance by glucose tolerance testing and normalize the size of enlarged subcutaneous (SC) fat cells by fat biopsy. [ Time Frame: 6 months ]Women with PCOS exhibit impaired glucose tolerance that correlates with enlarged subcutaneous (SC) abdominal adipocytes. Since a common denominator to these abnormalities is hyperandrogenism, we hypothesize that 6-month flutamide (antiandrogen) administration to lean PCOS women will improve glucose tolerance by glucose tolerance testing and reduce subcutaneous (SC) abdominal adipocyte size, as determined by SC abdominal fat biopsy.
- Six-month flutamide (antiandrogen) administration to lean women with polycystic ovary syndrome (PCOS) will establish ovulatory menstrual cycles, as determined by menstrual diaries and weekly urinary progesterone (metabolite) determinations. [ Time Frame: 6 months ]Women with PCOS exhibit oligo-ovulation, in part due to hyperandrogenism. We hypothesize that 6-month flutamide (antiandrogen) administration to lean PCOS women will establish ovulatory menstrual cycles, as determined by menstrual diaries and weekly urinary progesterone (metabolite) determinations.
Original Primary Outcome:
- Six-month flutamide (antiandrogen) administration to lean women with polycystic ovary syndrome (PCOS) will improve impaired glucose tolerance by glucose tolerance testing and normalize the size of enlarged subcutaneous (SC) fat cells by fat biopsy. [ Time Frame: 6 months ]Women with PCOS exhibit impaired glucose tolerance that correlates with enlarged subcutaneous (SC) abdominal adipocytes. Since a common denominator to these abnormalities is hyperandrogenism, we hypothesize that 6-month flutamide (antiandrogen) administration to lean PCOS women will improve glucose tolerance by oral glucose tolerance testing and reduce subcutaneous (SC) abdominal adipocyte size, as determined by SC abdominal fat biopsy.
- Six-month flutamide (antiandrogen) administration to lean women with polycystic ovary syndrome (PCOS) will establish ovulatory menstrual cycles, as determined by menstrual diaries and weekly urinary progesterone (metabolite) determinations. [ Time Frame: 6 months ]Women with PCOS exhibit oligo-ovulation, in part due to hyperandrogenism. We hypothesize that 6-month flutamide (antiandrogen) administration to lean PCOS women will establish ovulatory menstrual cycles, as determined by menstrual diaries and weekly urinary progesterone (metabolite) determinations.
Current Secondary Outcome: Quality of Life Questionnaires [ Time Frame: 6 months ]
Original Secondary Outcome: Same as current
Information By: University of California, Los Angeles
Dates:
Date Received: June 20, 2013
Date Started: April 2013
Date Completion: March 2018
Last Updated: October 27, 2016
Last Verified: October 2016
