Effects of Androgen Blockade on Sensitivity of the GnRH Pulse Generator to Suppression by Estradiol and Progesterone

NCT01428193 | Terminated Results

• 2 other identifiers: 12632U54HD028934-18
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to understand the effects of elevated male hormones in adolescent girls and how they effect the development of polycystic ovary syndrome (PCOS). If the investigators understand the effects of elevated male hormones levels in girls, the investigators may be able to better treat girls with elevated male hormone levels and perhaps even learn how to prevent the development of PCOS. Females with elevated levels of male hormones respond differently to estrace (estradiol) and progesterone than females with normal male hormone levels. The investigators will be giving you estrogen and progesterone to see how you respond after the male hormone has been blocked by a medication called flutamide.

Conditions

Polycystic Ovary Syndrome; Hyperandrogenism

Keywords

PCOS; hyperandrogenemia

Outcome Measures

Primary Outcomes (1)

• Slope of the Percent Change in Luteinizing Hormone (LH) Pulses as a Function of Day 7 Progesterone Level

  The primary outcome variable for the study is the slope of the percent change in LH pulses as a function of day 7 progesterone level.

  3 weeks after flutamide treatment

Study Arms (1)

Flutamide, estrace, progesterone

EXPERIMENTAL

For flutamide, subjects weighing \> 50 kg will receive 250 mg orally twice a day, and subjects weighing \< 50 kg will receive 125 mg orally twice a day for approximately 3 weeks. Subjects will be given oral estrace, 0.5-1 mg once a day for 7 days following the first overnight study admission. Subjects will be given oral progesterone suspension (20 mg/ml, 25-100 mg) three times a day at 0700, 1500, and 2300 hr for seven days following the first overnight study admission.

Drug: Flutamide; Drug: Progesterone; Drug: estrace

Interventions

Flutamide DRUG

Subjects weighing \> 50 kg will receive 250 mg orally twice a day, and subjects weighing \< 50 kg will receive 125 mg orally twice a day.

Flutamide, estrace, progesterone

Progesterone DRUG

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

Flutamide, estrace, progesterone

estrace DRUG

0.5-1 mg once a day for seven days

Also known as: (estradiol)

Flutamide, estrace, progesterone

Eligibility Criteria

• Age: 13 Years - 17 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Girls ages 13 to 17
• Tanner IV or V stage of puberty
• Post-menarche
• Hyperandrogenemic (total testosterone \> 0.4 ng/mL or free testosterone \> 35 pmol/L) with or without hirsutism
• Normal aspartate aminotransferase/alanine aminotransferase (AST/ALT) (AST \< 35 U/L, ALT \< 55 U/L)
• Hemoglobin \> 12 mg/dL or Hematocrit \> 36%
• Normal screening labs (with exception of the expected hormonal abnormalities inherent in hyperandrogenemia)
• Sexually active subjects must agree to abstain or use double barrier contraception during the study
• Subjects must agree not to take any other medications during the course of the study without approval by the study investigators

You may not qualify if:

• Abnormal screening labs (with the exception of the expected hormonal abnormalities inherent in hyperandrogenemia)
• Elevated AST/ALT (AST \> 35 U/L, ALT \> 55 U/L)
• Hemoglobin \<12 mg/dL or hematocrit \< 36%
• Weight \< 32 kg
• History of liver disease, peanut allergy, deep venous thrombosis, breast cancer, endometrial cancer, or cervical cancer
• Pregnant or breastfeeding
• On medications known to affect the reproductive axis within 3 months of the study (including oral contraceptive pills, metformin, and spironolactone)
• On medications known or likely to inhibit or induce CYP1A2 or CYP3A4 (please see "Restrictions on use of other drugs or treatments" section below for common examples of such drugs)
• Are currently participating in another study or have been in one in the last 30 days.

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; Hyperandrogenism

Interventions

Flutamide; Progesterone; Estradiol

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; 46, XX Disorders of Sex Development; Disorders of Sex Development; Urogenital Abnormalities; Adrenogenital Syndrome; Male Urogenital Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; 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

Results Point of Contact

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

pcos@virginia.edu

434-243-6911

Study Officials

• Christopher R. McCartney, MD

  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: Principal investigator Center for Research in Reproduction

Study Record Dates

• First Submitted: August 29, 2011
• First Posted: September 2, 2011
• Study Start: September 1, 2006
• Primary Completion: August 1, 2017
• Study Completion: August 1, 2017
• Last Updated: June 4, 2018
• Results First Posted: June 4, 2018

Record last verified: 2018-05

Locations

US (1)