Hyperandrogenemia and Altered Day-night LH Pulse Patterns

Recruiting now · Early Phase 1 · Has a placebo group

Conditions studied: Hyperandrogenism, Polycystic Ovary Syndrome, Puberty

In brief

The purpose of this study is to determine if, in mid- to late pubertal girls with hyperandrogenism, androgen-receptor blockade (spironolactone) improves the ability of progesterone to acutely reduce waking luteinizing hormone pulse frequency (primary endpoint).

Key facts

Study ID: NCT03068910
Run by: University of Virginia
People needed: 32
Starts: 2016-07-21
Expected to finish: 2025-12-01
Last updated by the study team: 2025-08-05

Who can join

Age: 10 and older, up to 17. Sex: female. Healthy volunteers: accepted.

You may qualify if…

Mid- to late pubertal adolescent girl (at least Tanner breast stage 3, but no more than 2 years postmenarcheal)
Hyperandrogenism, defined as a serum (calculated) free testosterone concentration greater than the Tanner stage-specific reference range and/or unequivocal evidence for hirsutism
General good health (excepting overweight, obesity, hyperandrogenism, and adequately-treated hypothyroidism)
Capable of and willing to provide informed assent (adolescents under age 16 years) and/or consent (adolescents over age 16 years; custodial parents or guardians of all adolescent volunteers)
Willing to strictly avoid pregnancy with use of reliable non-hormonal methods during the study period

You may not qualify if…

Inability/incapacity to provide informed consent
Males will be excluded (hyperandrogenism is unique to females)
Obesity resulting from a well-defined endocrinopathy or genetic syndrome
Positive pregnancy test or current lactation
Evidence for non-physiologic or non-PCOS causes of hyperandrogenism and/or anovulation
Evidence of virilization (e.g., rapidly progressive hirsutism, deepening of the voice, clitoromegaly)
Total testosterone > 150 ng/dl, which suggests the possibility of virilizing ovarian or adrenal tumor
DHEA-S elevation > 1.5 times the upper reference range limit. Mild elevations may be seen in adolescent HA and in PCOS, and will be accepted in these groups.
Early morning 17-hydroxyprogesterone > 200 ng/dl measured in the follicular phase, which suggests the possibility of congenital adrenal hyperplasia (if elevated during the luteal phase, the 17-hydroxyprogesterone will be repeated during the follicular phase). NOTE: If a 17-hydroxyprogesterone > 200 ng/dl is confirmed on repeat testing, an ACTH stimulated 17-hydroxyprogesterone < 1000 ng/dl will be required for study participation.
Abnormal thyroid stimulating hormone (TSH): Note that subjects with stable and adequately treated primary hypothyroidism, reflected by normal TSH values, will not be excluded.
Hyperprolactinemia > 20% higher than the upper limit of normal. Mild prolactin elevations may be seen in adolescents and women with HA/PCOS, and elevations within 20% higher than the upper limit of normal will be accepted in this group.
History and/or physical exam findings suggestive of Cushing's syndrome, adrenal insufficiency, or acromegaly
History and/or physical exam findings suggestive of hypogonadotropic hypogonadism (e.g., symptoms of estrogen deficiency) including functional hypothalamic amenorrhea (which may be suggested by a constellation of symptoms including restrictive eating patterns, excessive exercise, psychological stress, etc.)
Persistent hematocrit < 36% and hemoglobin < 12 g/dl.
Severe thrombocytopenia (platelets < 50,000 cells/microliter) or leukopenia (total white blood count < 4,000 cells/microliter)
Previous diagnosis of diabetes, fasting glucose > or = 126 mg/dl, or a hemoglobin A1c > or = 6.5%
Persistent liver panel abnormalities, with two exceptions. Mild bilirubin elevations will be accepted in the setting of known Gilbert's syndrome. Also, mild transaminase elevations may be seen in obesity/HA/PCOS; therefore, elevations < 1.5 times the upper limit of normal will be accepted in this group.
Significant history of cardiac or pulmonary dysfunction (e.g., known or suspected congestive heart failure, asthma requiring intermittent systemic corticosteroids, etc.)
Decreased renal function evidenced by GFR < 60 ml/min/1.73m2
A personal history of breast, ovarian, or endometrial cancer
History of any other cancer diagnosis and/or treatment (with the exception of basal cell or squamous cell skin carcinoma) unless they have remained clinically disease free (based on appropriate surveillance) for five years
History of allergy to micronized progesterone or spironolactone
Body mass index (BMI)-for-age percentile < 5% (underweight)
Due to the amount of blood being drawn, adolescent volunteers with body weight < 25 kg will be excluded.
Restrictions on use of other drugs or treatments: No medications known to affect the reproductive system, glucose metabolism, lipid metabolism, or blood pressure can be taken in the 2 months prior to the screening visit and in the 3 months prior to the start of the study medications. Such medications include oral contraceptive pills, progestins, metformin, systemic glucocorticoids, some antipsychotic medications, and sympathomimetics/stimulants (e.g., methylphenidate).

Where it is running

University of Virginia Clinical Research Unit — Charlottesville, Virginia, United States (enrolling)

Full record on ClinicalTrials.gov

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