Time Course of Waking Versus Sleep-associated Luteinizing Hormone (LH) Pulse Frequency Suppression in Response to Progesterone in Late Pubertal Girls With and Without Hyperandrogenemia (CRM003)

Inclusion Criteria:

1. Late pubertal girls (Tanner breast stage 3, 4, or 5)
2. Postmenarcheal, but no more than 4 y postmenarcheal
3. Age 10-17 y

Exclusion Criteria:

1. Age < 10 or > 17 y
2. BMI-for-age < 5th percentile
3. Inability to comprehend what will be done during the study or why it will be done
4. Being a study of GnRH pulse regulation in adolescent girls with and without HA, boys are excluded
5. Obesity associated with a diagnosed (genetic) syndrome (e.g., Prader-Willi syndrome, leptin deficiency), obesity related to medications (e.g., glucocorticoids), etc.
6. Pregnancy or lactation
7. Virilization
8. Total testosterone > 150 ng/dl
9. DHEAS > upper limit of age-appropriate normal range (mild elevations may be seen in adolescent HA, and elevations < 1.5 times the age-appropriate upper limit of normal will be accepted in such girls)
10. 17-hydroxyprogesterone > 250 ng/dl, which suggests the possibility of congenital adrenal hyperplasia (if postmenarcheal, the 17-hydroxyprogesterone will be collected during the follicular phase, or >60 if oligomenorrheic). NOTE: If a 17-hydroxyprogesterone > 250 ng/dl is confirmed on repeat testing, an ACTH stimulated 17-hydroxyprogesterone < 1000 ng/dl will be required for study participation
11. History of premature adrenarche (i.e., appearance of pubic and/or axillary hair before age 8)
12. A previous diagnosis of diabetes
13. Fasting glucose ≥ 126 mg/dl, or a hemoglobin A1c > 6.5% (confirmed on repeat)
14. Abnormal TSH (confirmed on repeat) (subjects with adequately treated hypothyroidism, reflected by normal TSH values, will not be excluded)
15. Abnormal prolactin (confirmed on repeat) (mild elevations may be seen in HA girls, and elevations < 1.5 times the upper limit of normal will be accepted in this group)
16. Evidence of Cushing's syndrome by history or physical exam (e.g., history of impaired growth in children, striae)
17. Hematocrit < 36% and hemoglobin < 12 g/dl (specifically, documentation of a hematocrit >= 36% or a hemoglobin >= 12 g/dl in the month prior to GCRC admission is required for the frequent sampling protocol in the GCRC)
18. Significant history of cardiac or pulmonary dysfunction (e.g., known or suspected congestive heart failure; asthma requiring intermittent systemic corticosteroids; etc.)
19. Persistent liver test abnormalities (confirmed on repeat), with the exception that mild bilirubin elevations will be accepted in the setting of known Gilbert's syndrome
20. Persistently abnormal sodium, potassium, or elevated creatinine concentration (confirmed on repeat)
21. Bicarbonate concentrations < 20 or > 30 (confirmed on repeat)
22. No medications known to affect the reproductive system, glucose metabolism, lipid metabolism, or blood pressure can be taken in the 3 months prior to the first inpatient GCRC study (or in the 2 months prior to screening). Such medications include oral contraceptive pills, progestins, metformin, glucocorticoids, psychotropics, and sympathomimetics/stimulants (e.g., methylphenidate). Patients taking restricted medications will be excluded unless written permission (for the subjects to discontinue the medication) is received from the subject's physician.
23. Weight < 22 kg is an absolute exclusion criterion (to ensure safe blood withdrawal)
24. Personal history of deep venous thrombosis (DVT)
25. Personal history of ovarian, endometrial, or breast neoplasia