Sleep-wake Changes of Luteinizing Hormone Frequency in Pubertal Girls With and Without High Testosterone (CRM005)

Comparison of Sleep-wake LH Frequency in Peripubertal Girls With and Without Hyperandrogenemia

The purpose of this study is to determine whether sleep-wake changes of luteinizing hormone pulse frequency are different in early pubertal girls with high testosterone levels compared to early pubertal girls with normal testosterone levels.

Study Overview

• Status: Active, not recruiting
• Conditions: Hyperandrogenism
• Intervention / Treatment: Other: Blood sampling

Detailed Description

During early puberty, luteinizing hormone (LH) pulse frequency normally increases during sleep. In contrast, preliminary data suggest that obese girls (who have high testosterone levels in general) demonstrate low LH frequency during the day and night during early puberty; but at mid puberty rapidly transition to a high LH frequency during the day and night. We hypothesize that in early pubertal girls with high testosterone levels, overnight increases of LH frequency are less prominent than those observed in early pubertal girls with normal testosterone levels. We will assess this using a frequent sampling protocol for assessment of LH pulse frequency (with sampling occurring while awake and while asleep) in early pubertal girls with and without high testosterone levels. Sleep will be formally evaluated.

• Study Type: Observational
• Enrollment (Anticipated): 90

Contacts and Locations

Study Locations

• United States
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years to 15 years (Child)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

Community sample and patients from local clinics

Description

Inclusion Criteria:

• Early to midpubertal girls (late Tanner 1 [i.e., estradiol > 20 pg/ml] to Tanner 3)
• Premenarcheal
• Approximate ages, 8-15 years

Exclusion Criteria:

• BMI-for-age < 5th percentile
• Inability to comprehend what will be done during the study or why it will be done
• Being a study of GnRH pulse regulation in adolescent girls with and without HA, boys are excluded
• Obesity associated with a diagnosed (genetic) syndrome (e.g., Prader-Willi syndrome, leptin deficiency), obesity related to medications (e.g., glucocorticoids), etc.
• Pregnancy or lactation
• Virilization
• Total testosterone > 150 ng/dl (confirmed on repeat)
• DHEAS > upper limit of age-appropriate normal range (confirmed on repeat) (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)
• Follicular phase 17-hydroxyprogesterone > 250 ng/dl (for girls < 12 years old) or > 300 ng/dl (for girls 12 and older) (confirmed on repeat), which suggests the possibility of congenital adrenal hyperplasia. NOTE: If an elevated follicular 17-hydroxyprogesterone is confirmed on repeat testing, an ACTH stimulated 17-hydroxyprogesterone < 1000 ng/dl will be required for study participation
• History of premature adrenarche (i.e., appearance of pubic and/or axillary hair before age 8)
• A previous diagnosis of diabetes
• Fasting glucose ≥ 126 mg/dl, or a hemoglobin A1c > 6.5% (confirmed on repeat)
• Abnormal TSH (confirmed on repeat) (subjects with adequately treated hypothyroidism, reflected by normal TSH values, will not be excluded)
• 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)
• Evidence of Cushing's syndrome by history or physical exam (e.g., history of impaired growth in children, striae)
• Hematocrit < 36% and hemoglobin < 12 g/dl (confirmed on repeat)
• Significant history of cardiac or pulmonary dysfunction (e.g., known or suspected congestive heart failure; asthma requiring intermittent systemic corticosteroids; etc.)
• 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
• Persistently abnormal sodium, potassium, or elevated creatinine concentration (confirmed on repeat)
• Bicarbonate concentrations < 20 or > 30 (confirmed on repeat)

• 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
• Weight < 22 kg is an absolute exclusion criterion (to ensure safe blood withdrawal)

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Hyperandrogenemic; Girls with elevated free testosterone concentrations	Other: Blood sampling; Blood sampling for later hormone measurements
Controls; Girls with normal free testosterone concentrations	Other: Blood sampling; Blood sampling for later hormone measurements

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Luteinizing hormone pulse frequency (while awake and while asleep)	Baseline (time zero)

Secondary Outcome Measures

Outcome Measure	Time Frame
Progesterone concentration	Baseline (time zero)
Estradiol concentration	Baseline (time zero)
Testosterone concentrations	Baseline (time zero)
Luteinizing hormone amplitude	Baseline (time zero)
Sleep stage parameters	Baseline (time zero)

Collaborators and Investigators

• Sponsor: University of Virginia
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Study record dates

Study Major Dates

• Study Start: October 1, 2008
• Primary Completion (Anticipated): May 1, 2023
• Study Completion (Anticipated): August 1, 2023

Study Registration Dates

• First Submitted: June 24, 2009
• First Submitted That Met QC Criteria: June 29, 2009
• First Posted (Estimate): June 30, 2009

Study Record Updates

• Last Update Posted (Actual): May 18, 2022
• Last Update Submitted That Met QC Criteria: May 16, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: Puberty; Luteinizing hormone
• Additional Relevant MeSH Terms: Endocrine System Diseases; Gonadal Disorders; 46, XX Disorders of Sex Development; Disorders of Sex Development; Urogenital Abnormalities; Adrenogenital Syndrome; Congenital Abnormalities; Hyperandrogenism
• Other Study ID Numbers: 13950

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: We do not have current plans to share IPD

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No