Does Treatment of Androgen Excess Using Spironolactone Improve Ovulatory Rates in Girls With Androgen Excess?
Does Treatment of Androgen Excess Using Spironolactone Improve Ovulatory Rates in Girls With Androgen Excess?
Adolescent girls with androgen excess have a higher rate of irregular periods and decreased
 ovulation rates compared to normal girls, and are considered at-risk for developing
 polycystic ovary syndrome (PCOS). This pilot study will look at whether giving spironolactone
 might improve ovulation rates in girls with androgen excess, ages 13-19. If this is true,
 spironolactone treatment to young girls might prevent PCOS from developing and avoid future
 infertility.
This is a non-randomized, clinical pilot study testing whether 16 weeks of spironolactone
 improves ovulation rates in post-menarcheal girls with androgen excess. The investigators
 will recruit girls ages 13-19 with clinical or biochemical androgen excess (defined as
 hirsutism and/or elevated Tanner stage-specific free testosterone concentrations) who are 4
 to 6 years post-menarche. Girls will keep a menstrual diary and collect twice weekly saliva
 samples for progesterone and estradiol for 16 weeks before and for 16 weeks during
 spironolactone (if ≤ 60 kg, 50 mg twice daily; if > 60 kg, 100 mg twice daily [1.7-3.3
 mg/kg/24 hr]) use. Girls will be asked to continue to collect saliva twice weekly for
 progesterone and estradiol testing for an additional 16 weeks after discontinuation of
 spironolactone and to continue menstrual diaries off of study medication for 12 additional
 months to assess persistence of any spironolactone effect. Ovulation events will be counted
 per 100 days based on definitive rises in salivary progesterone. The primary outcome will be
 changes in ovulation rate during spironolactone use compared to baseline. Changes in
 menstrual regularity via inter-menstrual interval will also be assessed as a secondary
 outcome of spironolactone administration. Another secondary outcome will be changes in acne
 and/or hirsutism.
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.