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

NCT01428245 | Terminated Results

• 3 other identifiers: 14100U54HD028934P50HD028934
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

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.

Conditions

Hyperandrogenemia; Polycystic Ovary Syndrome

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (1)

Progesterone, estrace

EXPERIMENTAL

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; Drug: Estrace (estrogen)

Interventions

Progesterone DRUG

oral progesterone suspension (20 mg/ml, 25-100 mg) three times a day at 0700, 1500, and 2300 hr for seven days

Progesterone, estrace

Estrace (estrogen) DRUG

oral estrace, 0.5-1 mg once a day for seven days

Also known as: estradiol

Progesterone, estrace

Eligibility Criteria

• Age: 8 Years - 14 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (1)

Center for Research in Reproduction, University of Virginia

Charlottesville, Virginia, 22908, United States

Location

MeSH Terms

Conditions

Polycystic Ovary Syndrome

Interventions

Progesterone; Estradiol; Estrogens

Condition Hierarchy (Ancestors)

Ovarian Cysts; Cysts; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Gonadal Disorders; Endocrine System 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; Estrenes; Estranes; Estradiol Congeners; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses

Results Point of Contact

• Title: Clinical Research Coordinator
• Organization: University of Virginia

pcos@virginia.edu

434-243-6911

Study Officials

• John C. Marshall, MD, PhD

  University of Virginia

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Center for Research in Reproduction

Study Record Dates

• First Submitted: August 31, 2011
• First Posted: September 2, 2011
• Study Start: April 22, 2011
• Primary Completion: May 14, 2013
• Study Completion: May 14, 2013
• Last Updated: December 30, 2020
• Results First Posted: December 30, 2020

Record last verified: 2020-12

Locations

US (1)