Clinical Research Directory

Inclusion Criteria: * PCOS group: post-pubertal (\> 4 years post-menarche) adult woman aged 18-30 years with PCOS, defined as clinical and/or laboratory evidence of hyperandrogenism (hirsutism and/or elevated serum \[calculated\] free testosterone concentration) plus ovulatory dysfunction (irregular menses, fewer than 9 per year), but without evidence for other potential causes of hyperandrogenism and/or ovulatory dysfunction * Control group: post-pubertal (\> 4 years post-menarche) adult woman aged 18-30 years with regular menstrual periods (every 26-35 days) and no evidence of hyperandrogenism (i.e., no hirsutism, normal serum \[calculated\] free testosterone concentration) * General good health (excepting overweight, obesity, PCOS, and adequately-treated hypothyroidism) * Capable of and willing to provide informed consent * Willing to strictly avoid pregnancy with use of reliable non-hormonal methods during the study period Exclusion Criteria: * Inability/incapacity to provide informed consent * Males will be excluded (hyperandrogenism is unique to females) * Age \< 18 years (we do not propose to study children because we have no preliminary data that would support this particular study in children) * Age \> 30 years (since ovarian reserve may decrease beyond age 30) * Obesity resulting from a well-defined endocrinopathy or genetic syndrome * Positive pregnancy test or current lactation * Evidence for non-physiologic or non-PCOS causes of hyperandrogenism and/or anovulation * Evidence of virilization (e.g., rapidly progressive hirsutism, deepening of the voice, clitoromegaly) * Total testosterone \> 150 ng/dl, which suggests the possibility of virilizing ovarian or adrenal tumor * DHEA-S greater than upper reference range limit for controls; and DHEA-S elevation \> 1.5 times the upper reference range limit for PCOS. Mild elevations may be seen in PCOS, and will be accepted in this group. * Early morning 17-hydroxyprogesterone \> 200 ng/dl measured in the follicular phase, which suggests the possibility of congenital adrenal hyperplasia (if elevated during the luteal phase, the 17-hydroxyprogesterone will be repeated during the follicular phase). NOTE: If a 17-hydroxyprogesterone \> 200 ng/dl is confirmed on repeat testing, an ACTH stimulated 17-hydroxyprogesterone \< 1000 ng/dl will be required for study participation. * Abnormal thyroid stimulating hormone (TSH): Note that subjects with stable and adequately treated primary hypothyroidism, reflected by normal TSH values, will not be excluded. * Hyperprolactinemia: Any degree of hyperprolactinemia (confirmed on repeat) will be grounds for exclusion for subjects without PCOS. Hyperprolactinemia \> 20% higher than the upper limit of normal will be grounds for exclusion for subjects without PCOS. Mild prolactin elevations may be seen in PCOS, and elevations within 20% higher than the upper limit of normal will be accepted in this group. * History and/or physical exam findings suggestive of Cushing's syndrome, adrenal insufficiency, or acromegaly * History and/or physical exam findings suggestive of hypogonadotropic hypogonadism (e.g., symptoms of estrogen deficiency) including functional hypothalamic amenorrhea (which may be suggested by a constellation of symptoms including restrictive eating patterns, excessive exercise, psychological stress, etc.) * Persistent hematocrit \< 36% and hemoglobin \< 12 g/dl * Severe thrombocytopenia (platelets \< 50,000 cells/microliter) or leukopenia (total white blood count \< 4,000 cells/microliter) * Previous diagnosis of diabetes, fasting glucose \> or = 126 mg/dl, or a hemoglobin A1c \> or = 6.5% * Persistent liver panel abnormalities, with two exceptions. Mild bilirubin elevations will be accepted in the setting of known Gilbert's syndrome. Also, mild transaminase elevations may be seen in obesity/PCOS; therefore, elevations \< 1.5 times the upper limit of normal will be accepted in these groups. * Significant history of cardiac or pulmonary dysfunction (e.g., known or suspected congestive heart failure, asthma requiring intermittent systemic corticosteroids, etc.) * Decreased renal function evidenced by GFR \< 60 ml/min/1.73m2 * A personal history of breast, ovarian, or endometrial cancer * History of any other cancer diagnosis and/or treatment (with the exception of basal cell or squamous cell skin carcinoma) unless they have remained clinically disease free (based on appropriate surveillance) for five years * History of allergy to transdermal estradiol patches * BMI \< 18 or \> 40 kg/m2; BMI \< 18 kg/m2 is considered to be underweight, while \> 40 kg/m2 is considered to be class 3 obesity -- both may have marked confounding effects for the outcomes of interest * Menstrual cycles lasting fewer than 26 days: Cycle frequency \< 26 days suggest the possibility of relatively short follicular phases (e.g., \< 12 days). If a subject with a follicular phase shorter than 12 days participates in Aim 1c, they could experience an endogenous gonadotropin surge under surveillance. Since we wish to capture only experimentally-induced surges, we will exclude such subjects.