Progesterone Treatment for Pubertal Girls with Hormone Issues
Acute Progesterone Suppression of Wake vs. Sleep Luteinizing Hormone Pulse Frequency in Pubertal Girls With and Without Hyperandrogenism
Recruiting
Early Phase 1Interventional Study
PubertyHyperandrogenism
Healthy Volunteers Welcome
You do not need to have the condition being studied to take part.
Ready to participate?
Review the details below, then apply to join this clinical trial.
At a Glance
Age
10 – 17
Sex
Female
Trial phase
Early Phase 1
Study type
Interventional
Purpose
Basic Science
Participants needed
36 (estimated)
Sponsor
University of Virginia · Other
Who this trial is looking for
This trial is looking for mid- to late pubertal girls with or without hormone issues called hyperandrogenism. Participants will take progesterone and undergo tests to measure certain hormone levels during waking and sleeping hours.
Are You a Good Fit for This Trial?
Must not be takingHormonal contraceptivesMetforminGlucocorticoidsAntipsychoticsStimulants
Rules you outCushing's syndromeAdrenal insufficiencyAcromegalyHypogonadotropic hypogonadism
You may be able to join if
I am a mid- to late pubertal girl and not more than 2 years after my first period.
I am in good health except for being overweight or having hyperandrogenism.
I can provide consent if I’m over 16, or assent if I’m younger.
I will use reliable non-hormonal methods to avoid pregnancy during the trial.
You may not be able to join if
I cannot provide informed consent.
I am male.
I have a positive pregnancy test or am currently breastfeeding.
I have a significant history of heart or lung problems.
I have had specific cancers or treatments in the past.
I have a personal history of severe menstrual issues or hormonal disorders.
I weigh less than 25 kg.
I have had severe blood-related issues like low platelets.
Summarized in plain language from this trial's official eligibility criteria.
The full criteria are further down this page — only the research team can
confirm whether you qualify.
Think this trial could be right for you?
Answer a few quick questions to see if you may meet the eligibility requirements.
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 …
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.
Trial Locations
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Eligibility Criteria
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 hirsutis…
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).
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