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Time Course of Waking Versus Sleep-associated Luteinizing Hormone (LH) Pulse Frequency Suppression in Response to Progesterone in Late Pubertal Girls With and Without Hyperandrogenemia

Information source: University of Virginia
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Hyperandrogenemia

Intervention: Micronized progesterone suspension (Drug); Placebo (Drug)

Phase: N/A

Status: Recruiting

Sponsored by: University of Virginia

Official(s) and/or principal investigator(s):
Christopher R McCartney, M D, Principal Investigator, Affiliation: University of Virginia

Overall contact:
Jessica Robic, Phone: 434-243-6911, Email: pcos@virginia.edu


The purpose of this study is to determine if in late pubertal girls without hyperandrogenemia (HA), progesterone (P) will acutely reduce waking lutenizing hormone (LH) frequency to a greater extent than sleep-associated LH frequency. We hypothesize that in late pubertal girls with HA: (a) waking and sleep-associated LH frequency will be elevated (compared to controls); and (b) P will suppress waking LH frequency to a lesser degree than it does in girls without HA.

Clinical Details

Official title: Time Course of Waking vs. Sleep-associated LH Pulse Frequency Suppression in Response to Progesterone in Late Pubertal Girls With and Without Hyperandrogenemia

Study design: Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Supportive Care

Primary outcome: Luteinizing hormone pulse frequency

Secondary outcome:




Luteinizing hormone pulse amplitude

Sleep parameters (e.g., sleep stages)

Detailed description: During early puberty, LH frequency increases during sleep; but in late puberty, LH frequency decreases overnight. Nonetheless, nocturnal LH frequency is similar (~0. 5 pulses per hour) in early and late pubertal girls. Preliminary data in early pubertal girls suggests that progesterone acutely slows waking LH frequency, but does not acutely change nocturnal LH frequency. We hypothesize that daytime LH frequency is regulated primarily by sex steroid negative feedback, while sleep-associated LH frequency is not; and that androgens interfere with sex steroid suppression of daytime LH frequency. We propose to assess this further using a protocol in which short-term Progesterone and placebo is given to late pubertal girls (in a cross-over fashion), with subsequent assessment of LH pulse frequency (with sampling occurring while awake and while asleep). We propose that any effect of Progesterone will be blunted or absent in late pubertal girls with hyperandrogenemia.


Minimum age: 10 Years. Maximum age: 17 Years. Gender(s): Female.


Inclusion Criteria: 1. Late pubertal girls (Tanner breast stage 3, 4, or 5) 2. Postmenarcheal, but no more than 4 y postmenarcheal 3. Age 10-17 y Exclusion Criteria: 1. Age < 10 or > 17 y 2. BMI-for-age < 5th percentile 3. Inability to comprehend what will be done during the study or why it will be done 4. Being a study of GnRH pulse regulation in adolescent girls with and without HA, boys are excluded 5. Obesity associated with a diagnosed (genetic) syndrome (e. g., Prader-Willi syndrome, leptin deficiency), obesity related to medications (e. g., glucocorticoids), etc. 6. Pregnancy or lactation 7. Virilization 8. Total testosterone > 150 ng/dl 9. DHEAS > upper limit of age-appropriate normal range (mild elevations may be seen in adolescent HA, and elevations < 1. 5 times the age-appropriate upper limit of normal will be accepted in such girls) 10. 17-hydroxyprogesterone > 250 ng/dl, which suggests the possibility of congenital adrenal hyperplasia (if postmenarcheal, the 17-hydroxyprogesterone will be collected during the follicular phase, or >60 if oligomenorrheic). NOTE: If a 17-hydroxyprogesterone > 250 ng/dl is confirmed on repeat testing, an ACTH stimulated 17-hydroxyprogesterone < 1000 ng/dl will be required for study participation 11. History of premature adrenarche (i. e., appearance of pubic and/or axillary hair before age 8) 12. A previous diagnosis of diabetes 13. Fasting glucose ≥ 126 mg/dl, or a hemoglobin A1c > 6. 5% (confirmed on repeat) 14. Abnormal TSH (confirmed on repeat) (subjects with adequately treated hypothyroidism, reflected by normal TSH values, will not be excluded) 15. Abnormal prolactin (confirmed on repeat) (mild elevations may be seen in HA girls, and elevations < 1. 5 times the upper limit of normal will be accepted in this group) 16. Evidence of Cushing's syndrome by history or physical exam (e. g., history of impaired growth in children, striae) 17. Hematocrit < 36% and hemoglobin < 12 g/dl (specifically, documentation of a hematocrit >= 36% or a hemoglobin >= 12 g/dl in the month prior to GCRC admission is required for the frequent sampling protocol in the GCRC) 18. Significant history of cardiac or pulmonary dysfunction (e. g., known or suspected congestive heart failure; asthma requiring intermittent systemic corticosteroids; etc.) 19. Persistent liver test abnormalities (confirmed on repeat), with the exception that mild bilirubin elevations will be accepted in the setting of known Gilbert's syndrome 20. Persistently abnormal sodium, potassium, or elevated creatinine concentration (confirmed on repeat) 21. Bicarbonate concentrations < 20 or > 30 (confirmed on repeat) 22. No medications known to affect the reproductive system, glucose metabolism, lipid metabolism, or blood pressure can be taken in the 3 months prior to the first inpatient GCRC study (or in the 2 months prior to screening). Such medications include oral contraceptive pills, progestins, metformin, glucocorticoids, psychotropics, and sympathomimetics/stimulants (e. g., methylphenidate). Patients taking restricted medications will be excluded unless written permission (for the subjects to discontinue the medication) is received from the subject's physician. 23. Weight < 22 kg is an absolute exclusion criterion (to ensure safe blood withdrawal) 24. Personal history of deep venous thrombosis (DVT) 25. Personal history of ovarian, endometrial, or breast neoplasia

Locations and Contacts

Jessica Robic, Phone: 434-243-6911, Email: pcos@virginia.edu

University of Virginia, Charlottesville, Virginia 22908, United States; Recruiting
Jessica Robic, Phone: 434-243-6911, Email: pcos@virginia.edu
Christopher McCartney, MD, Principal Investigator
Additional Information

Starting date: June 2008
Last updated: December 1, 2014

Page last updated: August 23, 2015

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