Inclusion Criteria:
- Girls age 13 - 19 years, with clinical or biochemical HA (defined as hirsutism and/or elevated Tanner stage-specific free testosterone concentrations) that are 4-6 years post-menarche
- Screening labs within age-appropriate normal range
- Volunteers who are 18-19 y old must be willing and able to provide written informed consent.
- When the subject is a minor (i.e., age < 18 y), the subject and custodial parents must be willing and able to provide written informed assent and consent, respectively.
- Willingness to strictly avoid pregnancy (using non-hormonal methods) during the time of study.
Exclusion Criteria:
- Age < 13 or > 19 y
- Girls ≤ 3 years and ≥ 7 years post-menarche will be excluded
- Being a study of androgen excess in adolescent girls with HA, men and boys are excluded
- Inability to comprehend what will be done during the study or why it will be done
- Precocious puberty (breast development before age 7)
- Primary amenorrhea (no menses by age 16)
- BMI-for-age < 5th percentile
- Patients currently enrolled in another research protocol will be excluded, except for those enrolled in IRB-HSR 17633 DENND1A
- Obesity due to genetic syndrome (e.g. Prader-Willi syndrome)
- Cushing syndrome
- 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.
- Diabetes mellitus
- History of congenital adrenal hyperplasia or 17-hydroxyprogesterone > 300 ng/dL in the follicular phase, which suggests the possibility of congenital adrenal hyperplasia. NOTE: If a 17-hydroxyprogesterone > 300 ng/dL is confirmed on repeat testing, and ACTH-stimulated 17-hydroxyprogesterone < 1000 ng/dL will be required for study participation.
- Total testosterone > 150 ng/dL
- Abnormal thyroid stimulating hormone (TSH) for age. Subjects with adequately treated hypothyroidism, reflected by normal TSH values, will not be excluded.
- Abnormal sodium, potassium, or bicarbonate concentrations, or elevated creatine concentration (confirmed on repeat)
- Subjects must not take exogenous steroids or any medications known to affect the reproductive axis or glucose metabolism for 3 months prior to the study (or in the 2 months prior to screening). Such medications include oral contraceptives, progestins, metformin, glucocorticoids, and antipsychotic medications
- If sexually active, subjects will be required to abstain and/or use barrier forms of contraception during the study.
Note: Abnormal laboratory studies may be confirmed by repeat testing to exclude laboratory error.