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

• ClinicalTrials.gov Identifier: NCT01428245
• Recruitment Status: Terminated
• First Posted: September 2, 2011
• Results First Posted: December 30, 2020
• Last Update Posted: December 30, 2020
• Sponsor: University of Virginia
• Collaborator: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Information provided by (Responsible Party): John Marshall, University of Virginia

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Hyperandrogenemia; Polycystic Ovary Syndrome	Drug: Progesterone; Drug: Estrace (estrogen)	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 3 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: Assessment of Sensitivity of the Hypothalamic GnRH Pulse Generator to Estradiol and Progesterone Inhibition in Early Pubertal Girls (JCM026)
• Actual Study Start Date: April 22, 2011
• Actual Primary Completion Date: May 14, 2013
• Actual Study Completion Date: May 14, 2013

Arms and Interventions

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 Name: estradiol

Outcome Measures

Primary Outcome Measures :

1. LH Pulse Frequency as a Function of Day 7 Progesterone [ Time Frame: 7 days following oral estrace and progesterone administration ]
   number of LH pulses per 11 hours on Day 7 of progesterone

Eligibility Criteria

• Ages Eligible for Study: 8 Years to 14 Years (Child)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

Criteria

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

Contacts and Locations

Locations

United States, Virginia

Center for Research in Reproduction, University of Virginia

Charlottesville, Virginia, United States, 22908

Sponsors and Collaborators

University of Virginia

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Investigators

• Principal Investigator: John C. Marshall, MD, PhD; University of Virginia

  Study Documents (Full-Text)

Documents provided by John Marshall, University of Virginia:

Study Protocol and Statistical Analysis Plan  [PDF] February 29, 2012

Informed Consent Form  [PDF] July 1, 2011

More Information

• Responsible Party: John Marshall, Director, Center for Research in Reproduction, University of Virginia
• ClinicalTrials.gov Identifier: NCT01428245
• Other Study ID Numbers: 14100; U54HD028934 ( U.S. NIH Grant/Contract ); P50HD028934 ( U.S. NIH Grant/Contract )
• First Posted: September 2, 2011
• Results First Posted: December 30, 2020
• Last Update Posted: December 30, 2020
• Last Verified: December 2020

Additional relevant MeSH terms:

Polycystic Ovary Syndrome; Ovarian Cysts; Cysts; Neoplasms; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine System Diseases; Estradiol; Estrogens; Progesterone; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Progestins