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

NCT ID: NCT01428245

Last Updated: 2020-12-30

Study Results

Results available

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

NA

Total Enrollment

3 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-04-22

Study Completion Date

2013-05-14

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Hyperandrogenemia Polycystic Ovary Syndrome

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

NONE

Study Groups

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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

Group Type EXPERIMENTAL

Progesterone

Intervention Type DRUG

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

Estrace (estrogen)

Intervention Type DRUG

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

Interventions

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Progesterone

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

Intervention Type DRUG

Estrace (estrogen)

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

Intervention Type DRUG

Other Intervention Names

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estradiol

Eligibility Criteria

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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
Minimum Eligible Age

8 Years

Maximum Eligible Age

14 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

Yes

Sponsors

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

NIH

Sponsor Role collaborator

University of Virginia

OTHER

Sponsor Role lead

Responsible Party

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John Marshall

Director, Center for Research in Reproduction

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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John C. Marshall, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Virginia

Locations

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Center for Research in Reproduction, University of Virginia

Charlottesville, Virginia, United States

Site Status

Countries

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United States

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

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U54HD028934

Identifier Type: NIH

Identifier Source: secondary_id

View Link

P50HD028934

Identifier Type: NIH

Identifier Source: secondary_id

View Link

14100

Identifier Type: -

Identifier Source: org_study_id