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

This study is currently recruiting participants.
Verified June 2012 by University of Virginia
Sponsor:
Collaborator:
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Information provided by (Responsible Party):
John Marshall, University of Virginia
ClinicalTrials.gov Identifier:
NCT01428193
First received: August 29, 2011
Last updated: June 12, 2012
Last verified: June 2012
History of Changes
  Purpose

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.


Condition Intervention
Polycystic Ovary Syndrome
Hyperandrogenism
 Drug: Flutamide
Drug: Progesterone
Drug: estrace (estradiol)

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: Effect of Androgen Blockade on Sensitivity of the GnRH Pulse Generator to Suppression by Estradiol and Progesterone in Hyperandrogeneic Adolescent Girls (JCM021)

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by University of Virginia:

Primary Outcome Measures:
  • Slope of the percent change in Leuteinizing hormone pulses as a function of day 7 progesterone level [ Time Frame: 3 weeks after flutamide treatment ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 13
Study Start Date: September 2006
Estimated Study Completion Date: April 2015
Estimated Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Flutamide, estrace, progesterone

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
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.
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 (estradiol)
0.5-1 mg once a day for seven days

  Eligibility

Ages Eligible for Study:   13 Years to 17 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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 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

Exclusion Criteria:

  • 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 breast feeding
  • 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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01428193

Contacts
Contact: Michelle Y. Abshire, PhD 434-243-6911 pcos@virginia.edu
Contact: John C. Marshall, MD, PhD 434-243-6911 pcos@virginia.edu

Locations
United States, Virginia
Center for Research in Reproduction, University of Virginia Recruiting
Charlottesville, Virginia, United States, 22908
Contact: Michelle Y. Abshire, PhD     434-243-6911     pcos@virginia.edu    
Principal Investigator: John C. Marshall, MD, PhD            
Sub-Investigator: Christine M Burt Solorzano, MD            
Sponsors and Collaborators
University of Virginia
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
  More Information

No publications provided

Responsible Party: John Marshall, Director, Center for Research in Reproduction, University of Virginia
ClinicalTrials.gov Identifier: NCT01428193     History of Changes
Other Study ID Numbers: 12632, U54HD028934-18
Study First Received: August 29, 2011
Last Updated: June 12, 2012
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by University of Virginia:
PCOS
hyperandrogenemia

Additional relevant MeSH terms:
Polycystic Ovary Syndrome
Hyperandrogenism
Ovarian Cysts
Cysts
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Gonadal Disorders
Endocrine System Diseases
46, XX Disorders of Sex Development
Disorders of Sex Development
Urogenital Abnormalities
Adrenogenital Syndrome
Congenital Abnormalities
 Androgens
Estradiol
Polyestradiol phosphate
Progesterone
Flutamide
Estradiol valerate
Estradiol 3-benzoate
Estradiol 17 beta-cypionate
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Estrogens
Contraceptive Agents
Reproductive Control Agents

ClinicalTrials.gov processed this record on May 23, 2013