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.
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
144
University of Virginia
Charlottesville, Virginia, United States
RECRUITINGChange in calculated free testosterone concentrations
pg/mL
Time frame: baseline, 30 mininutes and 1 hour after adrenocorticotropic hormone (ACTH), 24 hours after recombinant human chorionic gonadotropin (rhCG).
Mean luteinizing hormone (LH) concentrations
IU/L
Time frame: overnight frequent blood sampling (every 10 mininutes for 12 hours)
Change in ovarian 17-hydroxyprogesterone to r-hCG
ng/mL
Time frame: baseline, and 24 hours after receiving rhCG
Change in adrenal 17-hydroxyprogesterone to ACTH
ng/mL
Time frame: baseline, 30 minutes, and 60 minutes after ACTH
Mean insulin level during oral glucose tolerance test
uIU/mL
Time frame: during 2 hours of oral glucose tolerance test
Matsuda index
It is an index calculated by using glucose and insulin levels
Time frame: during 2 hours of glucose tolerance test
LH pulse frequency
pulses/hour
Time frame: overnight frequent blood sampling (every 10 minutes for 12 hours)
Change in dehydroepiandrosterone (DHEA) to r-hCG
ng/mL
Time frame: baseline, and 24 hours after r-hCG
Change in DHEA to ACTH
ng/mL
Time frame: baseline, 30 minutes and 1 hour after ACTH
Change in androstenedione to r-hCG
ng/mL
Time frame: baseline, and 24 hours after r-hCG
Change in androstenedione to ACTH
ng/mL
Time frame: baseline, 30 minutes and 1 hour after ACTH
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