ClinicalTrials.gov record NCT00929006

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

Record copied from ClinicalTrials.gov: Oct 10, 2026AI summaries generated: Sep 17, 2026

Study to Assess Acute Progesterone Suppression of Wake vs. Sleep Luteinizing Hormone Pulse Frequency in Pubertal Girls With and Without Hyperandrogenism

StatusRecruitingThe study is currently enrolling participants. Only the study team can say whether a particular person can join.
Study typeInterventionalA study in which researchers assign participants to one or more interventions, such as a drug, procedure, device, behavioural programme or other approach, to measure their effects.
PhaseEarly phase 1A very early study, usually in a small number of people, to learn how the body handles a treatment. It is not designed to show whether the treatment works.
Healthy volunteersAcceptedPeople who do not have the condition being studied who are allowed to take part. Some studies include both people with the condition and healthy volunteers; others may enrol only healthy volunteers.
Age10 years old to 17 years old
SexFemale
LocationUnited States
AI summaryWhat this study is about, in plain languageShow ▾Hide ▴

AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.

This randomized, quadruple-masked, placebo-controlled crossover study gives mid- to late-pubertal girls oral micronized progesterone or placebo during two separate 18-hour inpatient stays. Blood will be sampled frequently to measure luteinizing hormone (LH) pulse frequency while awake and asleep. The study compares results in girls with and without hyperandrogenism.

What it is studying. The study tests whether a short course of oral micronized progesterone acutely reduces luteinizing hormone (LH) pulse frequency more during waking hours than during sleep in mid‑ to late‑pubertal girls without hyperandrogenism, and whether that acute suppression of waking LH is reduced in girls who have hyperandrogenism.

What the researchers hope to learn. To determine (1) whether progesterone acutely suppresses waking versus sleep LH pulse frequency in mid‑ to late‑pubertal girls without hyperandrogenism, and (2) whether this acute suppression of waking LH is impaired in pubertal girls with hyperandrogenism. The primary outcome is LH pulse frequency while awake.

What this study is about

The study's own summary, as published on ClinicalTrials.gov. Underlined terms have a short explanation.

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.

Interventions being studied

Being studied in this trial does not mean the treatment or procedure is approved or available for this condition.

Drug
  • Micronized progesterone suspension
  • Placebo

Eligibility

The criteria exactly as listed on ClinicalTrials.gov. Only the study team can say whether they apply to you.

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 description and what participation involves

The study's detailed description, as published on ClinicalTrials.gov.

Show the detailed description from the registry

This is a randomized, placebo-controlled, double-blinded crossover study to test the following hypotheses: (1) In normal mid- to late pubertal girls without hyperandrogenism (HA), progesterone acutely suppresses waking LH pulse frequency more than sleep-associated LH pulse frequency; and (2) compared to normal mid- to late pubertal girls without HA, acute progesterone suppression of waking LH pulse frequency is impaired in mid- to late pubertal girls with HA. Studies will be performed in mid- to late pubertal girls (at least Tanner breast stage 3 but no more than 2 years postmenarcheal). Subjects will complete two 18-hour Clinical Research Unit (CRU) admissions in separate menstrual cycles. Immediately before and during the first CRU admission, either oral micronized progesterone (0.8 mg/kg/dose) or placebo (randomized) will be given at 0700, 1500, 2300, and 0700 h. During the CRU admission, blood will be obtained every 10 minutes through an indwelling iv catheter from 1800 to 1200 h. This will allow full characterization of pulsatile LH secretion in addition to other hormone measurements. A second CRU admission (performed at least 2 months later given blood withdrawal limits) will be identical to the first except that placebo will exchanged for progesterone or vice versa (treatment crossover). The primary endpoint is LH pulse frequency while awake. (LH pulse frequency while asleep is an important secondary endpoint.) Results in pubertal girls without HA were recently published (Kim et al, J Clin Endocrinol Metab 2018;103:1112-1121). Data from girls with HA will be compared to recently-published results in girls without HA. Mean LH pulse frequency while awake will be analyzed via a hierarchical linear mixed model (HLMM). HA status (HA vs. non-HA), sleep status (wake vs. sleep), and treatment (progesterone vs. placebo) will represent fixed-effects, along with all associated interactions. Random effects will be used to account for hierarchical variance-covariance structure of the crossover study design. With regard to hypothesis testing, the association between HA status and wake LH pulse frequency will be evaluated via linear contrasts of HLMM least squares pulse frequency means. The differential impact of exogenous progesterone on wake LH pulse frequency in pubertal girls with and without HA (primary analysis) will be evaluated via the same testing method. Using published and preliminary data, we determined that, if 16 pubertal girls with HA complete both admissions, we should have at least an 80% chance of detecting a 0.2 pulse/hour differential effect of P4 on wake LH pulse frequency between the HA and the non-HA groups with a two-sided false positive rejection rate of no more than 0.05.

AI summaryWhat participation may involve, in plain languageShow ▾Hide ▴

AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.

Participants complete two 18-hour admissions to a Clinical Research Unit in separate menstrual cycles (at least 2 months apart). During each admission they receive, in random order and blinded, oral micronized progesterone or placebo given at 07:00, 15:00, 23:00 and 07:00, and an indwelling IV catheter is used for intensive blood sampling every 10 minutes from 18:00 to 12:00 to measure luteinizing hormone pulses and other hormones. The study involves repeated blood draws and close monitoring; timing and frequency of visits and blood-volume limits are part of the protocol.

How the study is structured. Participants are randomly assigned to receive either oral micronized progesterone (0.8 mg/kg at 07:00, 15:00, 23:00 and 07:00) or matching placebo during a first 18-hour Clinical Research Unit admission. Each participant crosses over to the other treatment in a second, identical admission at least two months later. The study is quadruple-masked (blinded) and placebo-controlled; blood is drawn every 10 minutes from 18:00 to 12:00 during each admission to measure LH pulses.

Questions you could ask

These questions are suggestions for a conversation with the study team or your own clinician, not advice.

  • The registry lists this study under Puberty; Hyperandrogenism. Does it apply to my diagnosis?
  • Some participants receive a placebo. How is that decided, and what happens for placebo-group participants when the study ends?
  • This is an early-phase study, mainly about safety and dose. What is already known about this treatment?
  • The listed sites are in United States. Is any of them reachable for me, and does the study help with travel?
  • Which of the eligibility criteria would need to be checked with tests before I could join?

More on congenital adrenal hyperplasia

Clinical trials43 trials listed for congenital adrenal hyperplasiaEvery trial the registry lists for congenital adrenal hyperplasia, with recruitment status, phase and sites, updated from ClinicalTrials.gov.See all trials →Research updatesWhat changed in congenital adrenal hyperplasia researchLatest monthly update: September 2026. Includes: Bedtime hydrocortisone. New research summarized each month in plain language, with links to every source paper.Read the latest update →

Important dates

Study start
June 2008
Primary completion
Oct 1, 2025 (estimated)
Study completion
Dec 1, 2025 (estimated)
Target enrollment
36 participants (estimated)
Last updated on registry
Aug 5, 2025
Data verified
Oct 10, 2026

Sponsor and research team

The lead sponsor funds and oversees the trial. A pharmaceutical or biotech company sponsor typically means the study is testing that company's drug or device; a hospital, university, or government agency usually indicates investigator-initiated or publicly funded research.

Lead sponsor
University of Virginia
Principal investigator
Christine Burt Solorzano, Professor of Pediatrics
University of Virginia
Collaborators
  • National Institutes of Health (NIH)

Central study contact

If you're interested in participating, the central contact can answer general questions about the study — including eligibility requirements and how to find a recruiting site near you. Actual eligibility is determined by the site's medical team.

Participating sites (1)

  • University of VirginiaRecruiting

    Charlottesville, Virginia, 22908 · United States

Terms used on this page · explanations by MedicalUpdates.ai

assent
A child's or dependent adult's agreement to take part, given alongside the formal consent of a parent or legal representative.
informed consent
The process of explaining a study, including its risks and what participation involves, so that a person can decide freely whether to take part. Consent is usually documented in writing, and a participant can choose to leave the study later.
upper limit of normal
The highest value of a blood test that a laboratory considers normal. Criteria such as '≤ 3 × ULN' mean the result must be no more than three times that value.
corticosteroids
Steroid medicines, such as prednisone, that reduce inflammation. Studies often require a stable dose at entry or measure whether the study treatment allows the dose to be reduced.
GFR
A blood-test estimate of how well the kidneys are filtering. Lower numbers mean reduced kidney function; many studies set a minimum value.
screening visit
The checks done before enrolment to see whether a person qualifies, such as tests, scans or a review of medical history.
Inclusion Criteria
The conditions a person must meet to be considered for the study, for example a confirmed diagnosis, an age range or a test result.
Exclusion Criteria
The conditions that rule a person out even if they meet the inclusion criteria, for example other illnesses, certain medicines or pregnancy.
randomized
Participants are assigned to the study groups by chance, like a coin toss, rather than chosen by the doctor or the participant. This is done so the groups are comparable.
placebo-controlled
A study design in which one group receives a placebo so that the study treatment's effects can be compared with no active treatment.
blinded
Who does not know which intervention a participant is receiving. It can apply to participants, the people giving the treatment, those assessing results, or those analysing the data.
crossover
Each participant receives more than one intervention, one after the other, usually with a gap (a washout) in between. Participants act as their own comparison.
placebo
A treatment that looks like the study treatment but contains no active ingredient. Some participants receive it instead of the study treatment, usually without knowing which they got.
primary endpoint
The main result the study is designed to measure and report on. Other results, called secondary outcomes, are also collected.
secondary endpoint
An additional result the study measures alongside the primary outcome, for example quality of life or a laboratory value.

The study record on this page is reproduced from ClinicalTrials.gov, a database of the U.S. National Library of Medicine, where it was submitted by the study sponsor. MedicalUpdates.ai does not own this content, is not affiliated with or endorsed by ClinicalTrials.gov, NIH, or the U.S. Government, and does not verify the record. Plain-language notes, the glossary and the questions above are added by this site; text in the boxes marked "AI summary" was written by an AI model and may contain errors. Registry records change over time. Check the original record for the current version and discuss eligibility or participation with a qualified healthcare professional.

← Back to clinical trials