Polycystic Ovary Syndrome
Conditions
Keywords
Polycystic Ovary Syndrome
Brief summary
The objective of the study is to determine the relative contributions of four established predictors of hyperandrogenism (luteinizing hormone \[LH\] secretion, ovarian response to recombinant human chorionic gonadotropin \[r-hCG\] administration, adrenal response to adrenocorticotropic hormone \[ACTH\] administration, and hyperinsulinemia) in older vs. young women with Polycystic Ovary Syndrome (PCOS) in a cross-sectional, physiological study. The investigators hypothesize that hyperinsulinemia is a stronger independent predictor of free testosterone (T) in older reproductive aged (vs. young) women with PCOS.
Detailed description
PCOS is a highly prevalent reproductive disorder characterized by hyperandrogenism (HA) and oligo/anovulation. PCOS is also associated with metabolic syndrome, obesity and insulin resistance. In young women with PCOS, several factors contribute to HA: a) excess LH secretion, b) abnormal ovarian steroidogenesis, c) abnormal adrenal steroidogenesis, and d) hyperinsulinemia/ insulin resistance. Of interest, HA (and menstrual function) improves with age in PCOS. However, the relative contributions of the aforementioned HA-related factors in young adult vs. late reproductive-aged women with PCOS are not known. Identifying the most important predictor(s) of HA in older women with PCOS will be critically important for devising the most relevant therapeutic strategies for older women with PCOS. The investigators propose to determine the relative contributions of four established predictors of HA (LH secretion, ovarian response to r-hCG administration, adrenal response to ACTH administration, and hyperinsulinemia) in older vs. young women with PCOS in a physiological study. The investigators hypothesize that hyperinsulinemia is a stronger independent predictor of free testosterone (T) in older reproductive aged (vs. young) women with PCOS. In addition, the investigators hypothesize that, in older vs. young women with PCOS: a) ovarian response to r-hCG will be a weaker independent predictor of free T; b) mean LH will be a stronger independent predictor of free T; and c) the predictive ability of adrenal response to ACTH will be similar. This will be a cross-sectional physiological study. Ordinary Least Square (OLS) regression will be utilized to determine the relative contributions of 4 established predictors of HA in older vs. young women with PCOS. Statistical plans include intra-age group hypothesis testing, inter-age group hypothesis testing, and a ranking of the importance of predictors in each age group.
Interventions
Sponsors
University of Virginia
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Masking description
No masking is involved in this study.
Intervention model description
This is a cross-sectional physiological observational study.
Eligibility
Sex/Gender
FEMALE
Age
20 Years to 49 Years
Healthy volunteers
Yes
Inclusion criteria
* Women with PCOS aged 20-30 years and 40-49 years. Subject is considered to have PCOS if she has current or verifiable history of: a) clinical and/or biochemical evidence of hyperandrogenism plus b) oligomenorrhea (average menstrual cycle length \>45 days or fewer than 9 menses/year) or irregular menstruation (substantially inconsistent menstrual cycle length). Note: For subjects aged 40-49 years, they will be allowed to participate if they have fewer than 10 menses/year (average menstrual cycle length \>35 days) as long as they have a compelling past history of oligomenorrhea or irregular menstruation. * Screening safety labs within normal reference ranges although mild abnormalities that are common in obesity and/or hyperandrogenism will not be grounds for exclusion (see
Exclusion criteria
). * Subjects must be willing and able to provide written informed consent. * Willingness to strictly avoid pregnancy (using non-hormonal methods) during the time of the study * Willingness and ability to comply with scheduled visits and study procedures
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in calculated free testosterone concentrations | baseline, 30 mininutes and 1 hour after adrenocorticotropic hormone (ACTH), 24 hours after recombinant human chorionic gonadotropin (rhCG). | pg/mL |
| Mean luteinizing hormone (LH) concentrations | overnight frequent blood sampling (every 10 mininutes for 12 hours) | IU/L |
| Change in ovarian 17-hydroxyprogesterone to r-hCG | baseline, and 24 hours after receiving rhCG | ng/mL |
| Change in adrenal 17-hydroxyprogesterone to ACTH | baseline, 30 minutes, and 60 minutes after ACTH | ng/mL |
| Mean insulin level during oral glucose tolerance test | during 2 hours of oral glucose tolerance test | uIU/mL |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Matsuda index | during 2 hours of glucose tolerance test | It is an index calculated by using glucose and insulin levels |
| Change in androstenedione to ACTH | baseline, 30 minutes and 1 hour after ACTH | ng/mL |
| LH pulse frequency | overnight frequent blood sampling (every 10 minutes for 12 hours) | pulses/hour |
| Change in dehydroepiandrosterone (DHEA) to r-hCG | baseline, and 24 hours after r-hCG | ng/mL |
| Change in DHEA to ACTH | baseline, 30 minutes and 1 hour after ACTH | ng/mL |
| Change in androstenedione to r-hCG | baseline, and 24 hours after r-hCG | ng/mL |
Countries
United States
Contacts
Primary ContactMelissa G Gilrain, BS
Outcome results
None listed