Status:
RECRUITING
Acute Progesterone Suppression of Wake vs. Sleep Luteinizing Hormone Pulse Frequency in Pubertal Girls With and Without Hyperandrogenism
Lead Sponsor:
University of Virginia
Collaborating Sponsors:
National Institutes of Health (NIH)
Conditions:
Puberty
Hyperandrogenism
Eligibility:
FEMALE
10-17 years
Phase:
EARLY_PHASE1
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) frequenc...
Detailed Description
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...
Eligibility Criteria
Inclusion
- 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
- 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).
Key Trial Info
Start Date :
June 1 2008
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
December 1 2025
Estimated Enrollment :
36 Patients enrolled
Trial Details
Trial ID
NCT00929006
Start Date
June 1 2008
End Date
December 1 2025
Last Update
August 5 2025
Active Locations (1)
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1
University of Virginia
Charlottesville, Virginia, United States, 22908