Does Treatment of Androgen Excess Using Spironolactone Improve Ovulatory Rates in Girls With Androgen Excess?

Inclusion Criteria:

• Girls age 13 - 19 years, with clinical or biochemical HA (defined as hirsutism and/orelevated Tanner stage-specific free testosterone concentrations) that are 4-6 yearspost-menarche
• Screening labs within age-appropriate normal range
• Volunteers who are 18-19 y old must be willing and able to provide written informedconsent.
• When the subject is a minor (i.e., age < 18 y), the subject and custodial parents mustbe willing and able to provide written informed assent and consent, respectively.
• Willingness to strictly avoid pregnancy (using non-hormonal methods) during the timeof 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 areexcluded
• 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 forthose 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 beinformed of the result by the screening physician. Under Virginia law, parentalnotification is not required for minors. However, the screening physician willencourage them to tell their parent(s) and counsel them about the importance ofappropriate prenatal care and counseling. We will arrange follow-up for them at theTeen Health Clinic at the University of Virginia or their primary care physician'soffice in a timely manner.
• Diabetes mellitus
• History of congenital adrenal hyperplasia or 17-hydroxyprogesterone > 300 ng/dL in thefollicular phase, which suggests the possibility of congenital adrenal hyperplasia.NOTE: If a 17-hydroxyprogesterone > 300 ng/dL is confirmed on repeat testing, andACTH-stimulated 17-hydroxyprogesterone < 1000 ng/dL will be required for studyparticipation.
• Total testosterone > 150 ng/dL
• Abnormal thyroid stimulating hormone (TSH) for age. Subjects with adequately treatedhypothyroidism, reflected by normal TSH values, will not be excluded.
• Abnormal sodium, potassium, or bicarbonate concentrations, or elevated creatineconcentration (confirmed on repeat)
• Subjects must not take exogenous steroids or any medications known to affect thereproductive axis or glucose metabolism for 3 months prior to the study (or in the 2months 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 ofcontraception during the study. Note: Abnormal laboratory studies may be confirmed by repeat testing to exclude laboratoryerror.