Effects of Androgen Blockade on Sensitivity of the GnRH Pulse Generator to Suppression by Estradiol and Progesterone
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.
Polycystic Ovary Syndrome
|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 Hyperandrogenic Adolescent Girls (JCM021)|
- 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 ] [ 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.
|Study Start Date:||September 2006|
|Study Completion Date:||August 2015|
|Primary Completion Date:||August 2015 (Final data collection date for primary outcome measure)|
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.
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.
Other Name: flutamideDrug: Progesterone
oral progesterone suspension (20 mg/ml, 25-100 mg) three times a day at 0700, 1500, and 2300 hr for seven days
Other Name: ProgesteroneDrug: estrace
0.5-1 mg once a day for seven days
Other Name: (estradiol)
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.
Please refer to this study by its ClinicalTrials.gov identifier: 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|