Who may be eligible for the Hyperandrogenemia and Altered Day-night LH Pulse Patterns trial?

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 \ 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 \ 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).

ClinicalTrials.gov record NCT03068910

Hyperandrogenemia and Altered Day-night LH Pulse Patterns

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

Study to Evaluate if Androgen-receptor Blockade (Spironolactone) Improves Progesterone-suppression of Wake Luteinizing Hormone Pulse Frequency in Pubertal Girls With Hyperandrogenism

About this page. This page shows the study's official ClinicalTrials.gov record ↗, with added help to make it easier to understand. We explain medical terms, highlight key details in plain language, and suggest questions you may want to ask the study team.

The record is periodically copied from ClinicalTrials.gov and may lag behind changes. AI summaries are checked by software, not a clinician.Read moreShow less

The official record is written by the study sponsor and published on ClinicalTrials.gov. It may not always reflect the latest changes. Before making any decisions, please confirm important information with the study team and your own healthcare team.

Where you see "AI summary", AI was used to create a plain-language explanation and software checked it against the source. It has not been reviewed by a clinician, so it may contain mistakes or leave out important details.

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, placebo-controlled, double-blinded crossover study tests whether 2 weeks of spironolactone changes how well progesterone acutely reduces waking luteinizing hormone (LH) pulse frequency in mid- to late pubertal girls with hyperandrogenism. Each participant completes two 18-hour clinical research unit admissions (one after spironolactone pretreatment, one after placebo), with progesterone given during the admissions and frequent blood sampling plus a sleep study. The two admissions are performed in separate menstrual cycles and are at least two months apart to meet blood-draw limits.

What it is studying. The study compares LH pulse frequency while awake (primary) and while asleep (secondary) after exogenous progesterone given during two hospital admissions. One admission follows two weeks of oral spironolactone (50 mg twice daily) and the other follows two weeks of placebo, with the order assigned randomly.

What the researchers hope to learn. Scientific goals: measure whether androgen-receptor blockade with spironolactone alters the acute suppression of waking LH pulse frequency by progesterone in mid- to late pubertal girls with hyperandrogenism. The study is designed to compare wake and sleep LH pulse patterns between spironolactone and placebo admissions and is powered to detect a specified within-subject difference in LH pulse frequency.

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 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).

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
Spironolactone
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)
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 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 hypothesis: In mid- to late pubertal girls with hyperandrogenism (HA), acute progesterone suppression of waking LH pulse frequency is greater after 2 weeks of spironolactone pretreatment compared to after 2 weeks of placebo pretreatment. We will only study mid- to late pubertal girls with HA (i.e., girls who would be candidates for therapeutic spironolactone use). Subjects will complete two 18-hour Clinical Research Unit (CRU) admissions in separate menstrual cycles. Subjects will be randomized to be pretreated for 2 weeks with either oral spironolactone (50 mg twice daily) or placebo prior to the first CRU admission. Immediately before and during each CRU admission, oral micronized progesterone (0.8 mg/kg/dose) will be given at 0700, 1500, 2300, and 0700 h. During each 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. Formal polysomnography will be performed during CRU admissions. A second CRU admission (performed at least 2 months later given blood withdrawal limits) will be identical to the first except that placebo pretreatment will exchanged for spironolactone pretreatment or vice versa (treatment crossover). The primary endpoint is LH pulse frequency while awake. (LH pulse frequency while asleep is an important secondary endpoint.) The wake LH pulse frequency data from the spironolactone and placebo admissions will be analyzed via a hierarchical linear mixed model (HLMM). The admission (spironolactone vs. placebo) will represent the fixed effect factor of the HLMM. Random effects will be utilized to account for the hierarchical variance-covariance structure of the two-period cross-over design. Wake LH pulse frequency in response to exogenous progesterone will be compared between the spironolactone admission and the placebo admission via a linear contrast of the HLMM least squares LH pulse frequency means. A similar analysis will be performed for sleep-related LH pulse frequency. Using published and preliminary data, we determined that, if 16 mid- to late pubertal girls with HA complete both admissions, we should have at least an 80% chance of detecting a 0.35 pulse/hour mean within-subject difference in wake LH pulse frequency between the spironolactone and placebo admissions 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 will take spironolactone or matching placebo twice daily for two weeks before each test admission (randomized, double-blind, crossover). They will have two 18-hour inpatient Clinical Research Unit admissions in separate menstrual cycles; during each admission they will receive oral micronized progesterone at scheduled times and undergo formal sleep monitoring (polysomnography). An indwelling IV catheter will be used for very frequent blood sampling (every 10 minutes from 18:00 to 12:00) during each admission. A medication washout before screening/start and agreement to avoid pregnancy during the study are required, and the second admission occurs at least two months after the first because of blood-draw limits.

How the study is structured. Interventional, randomized, quadruple‑masked crossover study. Each participant receives two pretreatment periods (spironolactone and placebo) in random order; during each period they have an 18‑hour admission when progesterone is given and blood is sampled every 10 minutes via an indwelling IV catheter; formal polysomnography is performed during admissions.

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 Hyperandrogenism; Polycystic Ovary Syndrome; Puberty. 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: Jul 21, 2016
Primary completion: Oct 1, 2025 (estimated)
Study completion: Dec 1, 2025 (estimated)
Target enrollment: 32 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, Dr., MD
University of Virginia
Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

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.

Melissa Gilrain, MS 📞 434-243-6911 ✉ mg7zb@uvahealth.org
Christine Burt Solorzano, M.D. 📞 434-243-6911 ✉ cmb6w@uvahealth.org

Participating sites (1)

University of Virginia Clinical Research UnitRecruiting
Charlottesville, Virginia, 22908 · United States
- Melissa Gilrain, BS · 434-243-6911 · mg7zb@uvahealth.org
- Christine Burt Solorzano, M.D. · 434-243-6911 · cmb6w@virginia.edu
- Christine Burt Solorzano, M.D.
- Christopher R McCartney, M.D.

Terms used on this page · explanations by MedicalUpdates.ai

primary endpoint: The main result the study is designed to measure and report on. Other results, called secondary outcomes, are also collected.
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.
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.

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