Recruiting

Early Phase 1

Progesterone vs. Luteinizing HormoneAcute Progesterone Suppression of Wake vs. Sleep Luteinizing Hormone Pulse Frequency in Pubertal Girls With and Without Hyperandrogenism

Sponsor:

University of Virginia

Code:

NCT00929006

Conditions

Puberty

Hyperandrogenism

Eligibility Criteria

Sex: Female

Age: 10 - 17

Healthy Volunteers: Accepted

Interventions

Micronized progesterone suspension

Placebo

Study Details

Brief summary:

The purpose of this study is two-fold. (1) We will determine if in mid- to late pubertal girls without hyperandrogenism (HA), progesterone (P4) acutely reduces waking luteinizing hormone (LH) frequency to a greater extent than sleep-associated LH frequency. (2) We will determine if in mid- to late pubertal girls with HA, P4 will acutely suppress waking LH frequency to a lesser degree than it does in girls without HA.

Conditions

Puberty

Hyperandrogenism

Study ID

NCT00929006

Start date

Jun, 2008

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)
For girls without hyperandrogenism: serum (calculated) free testosterone concentration within the Tanner stage-specific reference range and the absence of hirsutism
For girls with hyperandrogenism: 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: Mild prolactin elevations may be seen in 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.)
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 such girls.
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.
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

36 participants

Anticipated

Allocation

Randomized

Intervention Model

Crossover

Primary purpose

Basic Science

Interventions and Outcome Measures

Arms

experimental: Micronized progesterone suspension

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

placebo comparator: Placebo

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

Interventions

Micronized progesterone suspension

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

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

434-243-6911 pcos@virginia.edu

Locations

University of Virginia

Recruiting

Charlottesville, Virginia, United States, 22908

Contacts

Melissa Gilrain

434-243-6911 pcos@virginia.edu

Principal Investigator:

Christopher McCartney, MD

More Information

Sponsor

University of Virginia

Last update posted

Aug 5, 2025

Last verified

Jul, 2025

Keywords

hyperandrogenemia
pubertal
polycystic ovary syndrome

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by University of Virginia on 2025-08-05.