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

NCT00929006 | Recruiting Early Phase 1 DMC FDA Drug

• 1 other identifier: 13717
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

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

Keywords

hyperandrogenemia; pubertal; polycystic ovary syndrome

Outcome Measures

Primary Outcomes (1)

• Luteinizing hormone (LH) pulse frequency

  LH pulse frequency while awake vs. while asleep pulse frequency

  During first CRU admission and during the second CRU admission (which occurs at least 2 months after the first)

Study Arms (2)

Micronized progesterone suspension

EXPERIMENTAL

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

Drug: Micronized progesterone suspension

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Micronized progesterone suspension DRUG

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

Also known as: Progesterone

Micronized progesterone suspension

Placebo DRUG

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

Placebo

Eligibility Criteria

• Age: 10 Years - 17 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• University of Virginia: lead
• National Institutes of Health (NIH): collaborator

Study Sites (1)

University of Virginia

Charlottesville, Virginia, 22908, United States

RECRUITING

Related Publications (1)

• Kim SH, Lundgren JA, Bhabhra R, Collins JS, Patrie JT, Burt Solorzano CM, Marshall JC, McCartney CR. Progesterone-Mediated Inhibition of the GnRH Pulse Generator: Differential Sensitivity as a Function of Sleep Status. J Clin Endocrinol Metab. 2018 Mar 1;103(3):1112-1121. doi: 10.1210/jc.2017-02299.

  PMID: 29300925 DERIVED

MeSH Terms

Conditions

Hyperandrogenism; Polycystic Ovary Syndrome

Interventions

Progesterone

Condition Hierarchy (Ancestors)

46, XX Disorders of Sex Development; Disorders of Sex Development; Urogenital Abnormalities; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Adrenogenital Syndrome; Male Urogenital Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Gonadal Disorders; Endocrine System Diseases; Ovarian Cysts; Cysts; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Genital Diseases

Intervention Hierarchy (Ancestors)

Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Corpus Luteum Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Progesterone Congeners; Gonadal Steroid Hormones

Study Officials

• Christine M Burt Solorzano, MD

  University of Virginia

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Melissa Gilrain

CONTACT

434-243-6911; pcos@virginia.edu

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Pediatrics

Model Details: Randomized, placebo-controlled, crossover study

Study Record Dates

• First Submitted: June 23, 2009
• First Posted: June 26, 2009
• Study Start: June 1, 2008
• Primary Completion: October 1, 2025
• Study Completion: December 1, 2025
• Last Updated: August 5, 2025

Record last verified: 2025-07

Locations

US (1)