Recruiting

Early Phase 1

Observational StudyHyperandrogenemia and Altered Day-night LH Pulse Patterns

Sponsor:

University of Virginia

Code:

NCT03068910

Conditions

Hyperandrogenism

Polycystic Ovary Syndrome

Puberty

Eligibility Criteria

Sex: Female

Age: 10 - 17

Healthy Volunteers: Accepted

Interventions

Micronized progesterone

Spironolactone

Placebo

Study Details

Brief summary:

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).

Conditions

Hyperandrogenism

Polycystic Ovary Syndrome

Puberty

Study ID

NCT03068910

Start date

Jul 21, 2016

Status verified date

Jul, 2025

Completion date

Dec 1, 2025

Anticipated

Primary completion date

Oct 1, 2025

Anticipated

Eligibility Criteria

Sex: Female

Age: 10 - 17

Healthy Volunteers: Accepted

Inclusion Criteria:

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

Exclusion Criteria:

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).

Study Design

Enrollment

32 participants

Anticipated

Allocation

Randomized

Intervention Model

Crossover

Primary purpose

Basic Science

Interventions and Outcome Measures

Arms

experimental: Spironolactone

Prior to the first or the second admission (randomly determined), participants will be pretreated for 2 weeks with spironolactone (50 mg twice daily).

placebo comparator: Placebo

Prior to the first or the second admission (randomly determined), participants will be pretreated for 2 weeks with placebo (twice daily).

Interventions

Micronized progesterone

Micronized progesterone 0.8 mg/kg at 0700, 1500, 2300 and 0700 h. Progesterone is a natural hormone.

Spironolactone

Spironolactone is an androgen-receptor blocker commonly used (off-label) for hyperandrogenism. The spironolactone dose will be 50 mg taken orally twice daily (for two weeks before admission to the Clinical Research Unit).

Placebo

Placebo contains only inert ingredients and is not expected to exert any direct physiological effects.

Primary outcome measure

Luteinizing hormone (LH) pulse frequency [ Time Frame: During first CRU admission and during the second CRU admission (which occurs at least 2 months after the first) ]

Central Contacts and Locations

Central contacts

Melissa Gilrain, MS

434-243-6911 mg7zb@uvahealth.org

Christine Burt Solorzano, M.D.

434-243-6911 cmb6w@uvahealth.org

Locations

University of Virginia Clinical Research Unit

Recruiting

Charlottesville, Virginia, United States, 22908

Contacts

Melissa Gilrain, BS

434-243-6911 mg7zb@uvahealth.org

Christine Burt Solorzano, M.D.

434-243-6911 cmb6w@virginia.edu

Principal Investigator:

Christine Burt Solorzano, M.D.

More Information

Sponsor

University of Virginia

Last update posted

Aug 5, 2025

Last verified

Jul, 2025

Keywords

Hyperandrogenism
Polycystic ovary syndrome
Puberty

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-11. This information was provided to ClinicalTrials.gov by University of Virginia on 2025-08-05.