Assessment of Sensitivity of the Hypothalamic GnRH Pulse Generator to Estradiol and Progesterone Inhibition (JCM026)

Assessment of Sensitivity of the Hypothalamic GnRH Pulse Generator to Estradiol and Progesterone Inhibition in Early Pubertal Girls (JCM026)

Gonadotropin-releasing hormone (GnRH) is a hormone that regulates the ability of the pituitary to secrete two hormones, luteinizing hormone (LH) and follicle-stimulating hormone (FSH). LH and FSH control the production of female hormones (such as estrogen and progesterone) and the development of eggs by the ovary. Progesterone and estrogen then decrease the number of GnRH pulses produced by the brain (and therefore the number of LH pulses from the pituitary). The ability to decrease GnRH pulses seems to be very important for normal menstrual function in adult women. The purpose of this study is to learn more about how GnRH and LH pulses are controlled during puberty. The information gathered in this study will hopefully allow us to learn more about how menstrual cycles are normally established in girls during puberty.

Study Overview

• Status: Terminated
• Conditions: Polycystic Ovary Syndrome; Hyperandrogenemia
• Intervention / Treatment: Drug: Progesterone; Drug: Estrace (estrogen)

Detailed Description

In this study, the investigators will aim to discover the effect of 7 days of estrogen and progesterone on GnRH pulses in girls in early and mid puberty. Ultimately, if the investigators understand these normal processes, the investigators may be able to better understand abnormalities of puberty.

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • Center for Research in Reproduction, University of Virginia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years to 14 years (CHILD)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Girls ages 8 to 14
• Tanner 1-3 pubertal stage
• Pre-menarchal
• Normal screening labs

Exclusion Criteria:

• Abnormal screening labs
• Congenital adrenal hyperplasia
• Hyperandrogenism (e.g., hirsutism, elevated free testosterone level)
• Hemoglobin <12 mg/dL or hematocrit < 36% (Subjects will be offered the opportunity to take iron supplementation for 60 days if their hematocrit is slightly low (33-36%) (suggestive of iron deficiency anemia) and will then return for retesting of their hemoglobin/hematocrit.)
• Weight < 31 kg
• History of peanut allergy, deep venous thrombosis, breast cancer, endometrial cancer, or cervical cancer
• On hormonal medications (including oral contraceptive pills) or on medications known to affect the reproductive axis within 3 months of the study
• Pregnant or breast feeding
• Participation in a research study within the past 30 days that involved taking a study drug.
• Participation in a research study that involved taking up to or greater than 473 ml's of blood within the past 60 days.
• Cigarette smoking
• History of surgery that required bedrest within the past 30 days
• Family history of hypercoagulability or unexplained thromboembolic disease (not in setting of bedrest, surgery, or malignancy)
• In order to ensure an adequate number of younger girls, no more than 4 enrolled subjects will be Tanner stage 3

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Progesterone, estrace; oral progesterone suspension (20 mg/ml, 25-100 mg) three times a day at 0700, 1500, and 2300 hr to achieve mean plasma concentrations over the range of 2-8 ng/ml for seven days oral estrace, 0.5-1 mg once a day for seven days	Drug: Progesterone; oral progesterone suspension (20 mg/ml, 25-100 mg) three times a day at 0700, 1500, and 2300 hr for seven days; Drug: Estrace (estrogen); oral estrace, 0.5-1 mg once a day for seven days; Other Names: estradiol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
LH Pulse Frequency as a Function of Day 7 Progesterone	number of LH pulses per 11 hours on Day 7 of progesterone	7 days following oral estrace and progesterone administration

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 (ACTUAL): April 22, 2011
• Primary Completion (ACTUAL): May 14, 2013
• Study Completion (ACTUAL): May 14, 2013

Study Registration Dates

• First Submitted: August 31, 2011
• First Submitted That Met QC Criteria: September 1, 2011
• First Posted (ESTIMATE): September 2, 2011

Study Record Updates

• Last Update Posted (ACTUAL): December 30, 2020
• Last Update Submitted That Met QC Criteria: December 3, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Endocrine System Diseases; Ovarian Cysts; Cysts; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Polycystic Ovary Syndrome; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Progestins; Estradiol; Progesterone; Estrogens
• Other Study ID Numbers: 14100; P50HD028934 (U.S. NIH Grant/Contract); U54HD028934 (NIH)