Suppression of Daytime and Nighttime LH Frequency by Progesterone in Early Pubertal Girls With and Without Hyperandrogenemia (JCM024)

Studies will be performed in early pubertal (late Tanner 1 [estradiol level > 20 pg/ml] to Tanner 3, premenarcheal) girls with and without hyperandrogenemia (HA). After a potential subject is identified by the Pediatric, Teen, or Endocrine clinics, she will come to the CRU or alternate UVA clinical unit for an outpatient screening exam. The goals and procedures of the study will be explained to the potential subjects and their custodial parents, and they will be given the opportunity to ask questions. A subject and her custodial parent(s) will be asked to sign the assent and consent forms. A physician will record a family and personal medical history and perform a physical exam. The physical exam will include height, weight, and determination of pubertal stage (Tanner scale). Since adiposity is a potential confounder in this study, measures of adiposity will be recorded. This will include measurement of waist circumference (using standard technique) to provide an estimate of abdominal adiposity. Hip circumference will also be measured. Additionally, BOD POD® will be used to measure total fat mass, fat free mass, and percent body fat. Blood tests will include CBC, Chem17, prolactin, LH, FSH, E2, P, total testosterone, SHBG, DHEA-S, 17-OHP, TSH, insulin, beta-hCG, and cytoadipokines. Bone age (simple x-ray of left hand and wrist) will be measured.

If safety labs are abnormal during screening (e.g., abnormal liver tests, abnormal TSH), subjects will be asked to return once for repeat (confirmatory) labs to exclude lab error, especially when values are only slightly abnormal. Repeat testing will generally occur within one month of the original screening lab draw. If exclusionary lab values are confirmed on such repeat testing, subjects will be excluded from participation. If the subject has a low hemoglobin (<11.5 g/dL for non-African American subjects; Hemoglobin < 11.0 g/dL for African American subjects ) at the time of screening, we will offer the option of taking oral iron supplementation at a dose of 1-2 mg/kg for 30 days. Subjects weighing ≤ 36 kg will be given 300-325 mg oral ferrous gluconate daily (containing 36 mg of elemental iron); subjects weighing >36 kg will be given 300-325 mg oral ferrous gluconate twice daily. Following the course of iron supplementation, the subject will then return to the CRU for a repeat hemoglobin, and will only be able to proceed with the study if her hemoglobin is greater than or equal to 11.0 g/dL for African American subjects or greater than or equal to 11.5 g/dL for non-African American subjects. If the subject's hemoglobin remains low after repeat testing, we will recommend that they follow up with their primary physician.

If three months have elapsed between an admission and the subject's most recent safety labs, then safety labs (CBC, chemistry and liver panel) will be obtained prior to the overnight admission (or on admission) to exclude anemia and any other exclusion criteria.

Subjects who meet all inclusion criteria will then be scheduled for an inpatient admission. They will begin taking iron supplementation for a maximum of 30 days prior to admission. Girls 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 tablets oral ferrous gluconate daily (containing 36 mg elemental iron). The inpatient admission can occur at any time during this period of iron supplementation.

Inpatient Admission: