Ovarian Contribution to Androgen Production in Adolescent Girls

• Girls age 7-18 years
• Normal weight (BMI 5-85%-ile for age) or overweight (>85%-ile)
• With or without signs of excess androgen
• Screening labs within age-appropriate normal range, with the exception of a mildly low hematocrit (see below) and the hormonal abnormalities inherent in obesity which could include mildly elevated luteinizing hormone (LH), lipids, testosterone, prolactin, DHEAS, E2, glucose, and insulin; and decreased follicle-stimulating hormone (FSH) and/or sex hormone-binding globulin (SHBG)

Exclusion Criteria:

• Patients currently enrolled in another research protocol will be excluded, except for those enrolled in IRB-HSR #12702/JCM022. This protocol is designed to allow subjects enrolling in IRB-HSR #12702/JCM022 to simultaneously participate in this companion protocol.
• Inability to comprehend what will be done during the study or why it will be done
• BMI-for-age \< 5th percentile
• Weight \< 27 kg if simultaneously participating in IRB-HSR #12702/JCM022 due to blood volume limits
• Obesity associated with a diagnosed genetic syndrome (e.g. Prader-Willi syndrome)
• Since the study involves looking at ovarian function, boys will be excluded.
• Positive pregnancy test or lactation. Subjects with a positive pregnancy test will be informed of the result by the screening physician. Under Virginia law, parental notification is not required for minors. However, the screening physician will encourage them to tell their parent(s) and counsel them about the importance of appropriate prenatal care and counseling. We will arrange follow-up for them at the Teen Health Clinic at the University of Virginia or their primary care physician's office in a timely manner.
• Abnormal laboratory studies will be confirmed by repeat testing to exclude laboratory error.
• Morning cortisol \< 3 microgram/dL or history of Cushing syndrome or adrenal insufficiency
• History of congenital adrenal hyperplasia or 17-hydroxyprogesterone > 300 ng/dL, which suggests the possibility of congenital adrenal hyperplasia (if postmenarchal, the 17-hydroxyprogesterone will be collected during the follicular phase, or ≥ 40 days since last menses if oligomenorrheic). NOTE: If a 17-hydroxyprogesterone >300 mg/dL is confirmed on repeat testing, an adrenocorticotropic hormone-stimulated 17-hydroxyprogesterone \<1000 ng/dL will be required for study participation.
• Total testosterone > 150 ng/dL
• Previous diagnosis of diabetes, fasting glucose ≥126 mg/dL, or a hemoglobin A1c >6.5%
• Abnormal thyroid stimulating hormone (TSH) for age. Subjects with adequately treated hypothyroidism, reflected by normal TSH values, will not be excluded.
• Abnormal prolactin. Mild elevations may be seen in overweight girls, and elevations \<1.5 times the upper limit of normal will be accepted in this group.
• Persistent hematocrit \<36% and hemoglobin \<12 g/dL. Subjects with a mildly low hematocrit (33-36%) will be asked to take iron in the form of ferrous gluconate for up to 60 days. Subjects weighing ≤ 36 kg will take one 300-325 mg tablet oral ferrous gluconate daily (containing 36 mg elemental iron); subjects weighing >36 kg will take two 300-325 mg tablets oral ferrous gluconate daily (containing 36 mg elemental iron each). They will return to the Clinical Research Unit (CRU) or alternate UVA clinical unit after 30-60 days of iron therapy to have their hemoglobin or hematocrit rechecked and will proceed with the remainder of the study if it is ≥12 g/dL or ≥36%, respectively.
• Persistent liver test abnormalities, with the exception that mild bilirubin elevations will be accepted in the setting of known Gilbert's syndrome. Mild elevations may be seen in overweight girls, so elevations \<1.5 times the upper limit of normal will be accepted in this group.