Effects of Androgen Blockade on Sensitivity of the GnRH Pulse Generator to Suppression by Estradiol and Progesterone
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| ClinicalTrials.gov Identifier: NCT01428193 |
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Recruitment Status :
Terminated
(Haven't enrolled participants since 2010)
First Posted : September 2, 2011
Results First Posted : June 4, 2018
Last Update Posted : June 4, 2018
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Polycystic Ovary Syndrome Hyperandrogenism | Drug: Flutamide Drug: Progesterone Drug: estrace | Not Applicable |
Similar to women with PCOS, girls with hyperandrogenemia have an increased frequency of LH pulses when compared to age matched controls. An ongoing study by our group is investigating whether the progesterone insensitivity of the GnRH pulse generator in adult women with PCOS is also seen in adolescent girls with hyperandrogenemia. Analysis of the data to date suggests that the hyperandrogenic adolescent girls have decreased hypothalamic progesterone sensitivity when compared to adolescent controls, with a subgroup (consisting of approximately half of the hyperandrogenic girls) having marked progesterone insensitivity similar to that seen in adult women with PCOS. These data have recently been published.
Given that androgens mediate hypothalamic progesterone insensitivity in adult women with PCOS, we hypothesize that androgens play a similar role in adolescent girls with hyperandrogenemia and that progesterone sensitivity can be restored with the use of the androgen receptor blocker flutamide.
Better understanding the effects of hyperandrogenemia in adolescence and its role in the development of PCOS will hopefully lead to improved prevention and treatment strategies for PCOS. This may prove increasingly important if the current epidemic in childhood obesity results in a growing number of girls with elevated androgen levels.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 4 participants |
| Allocation: | N/A |
| Intervention Model: | Single Group Assignment |
| Masking: | None (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 Hyperandrogenic Adolescent Girls (JCM021) |
| Actual Study Start Date : | September 2006 |
| Actual Primary Completion Date : | August 2017 |
| Actual Study Completion Date : | August 2017 |
| Arm | Intervention/treatment |
|---|---|
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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 0.5-1 mg once a day for seven days
Other Name: (estradiol) |
- Slope of the Percent Change in Luteinizing Hormone (LH) Pulses as a Function of Day 7 Progesterone Level [ Time Frame: 3 weeks after flutamide treatment ]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.
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| Ages Eligible for Study: | 13 Years to 17 Years (Child) |
| Sexes Eligible for Study: | Female |
| Accepts Healthy Volunteers: | No |
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 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
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 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01428193
| United States, Virginia | |
| Center for Research in Reproduction, University of Virginia | |
| Charlottesville, Virginia, United States, 22908 | |
| Principal Investigator: | Christopher R. McCartney, MD | University of Virginia |
Documents provided by John Marshall, University of Virginia:
| Responsible Party: | John Marshall, Principal investigator Center for Research in Reproduction, University of Virginia |
| ClinicalTrials.gov Identifier: | NCT01428193 |
| Other Study ID Numbers: |
12632 U54HD028934-18 ( U.S. NIH Grant/Contract ) |
| First Posted: | September 2, 2011 Key Record Dates |
| Results First Posted: | June 4, 2018 |
| Last Update Posted: | June 4, 2018 |
| Last Verified: | May 2018 |
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PCOS hyperandrogenemia |
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Polycystic Ovary Syndrome Hyperandrogenism Ovarian Cysts Cysts Neoplasms Ovarian Diseases Adnexal Diseases Gonadal Disorders Endocrine System Diseases 46, XX Disorders of Sex Development Disorders of Sex Development Urogenital Abnormalities Adrenogenital Syndrome |
Congenital Abnormalities Flutamide Estradiol Progesterone Estrogens Hormones Hormones, Hormone Substitutes, and Hormone Antagonists Physiological Effects of Drugs Progestins Androgen Antagonists Hormone Antagonists Antineoplastic Agents, Hormonal Antineoplastic Agents |