Effects of Androgen Blockade on Sensitivity of the GnRH Pulse Generator to Suppression by Estradiol and Progesterone
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT01428193|
Recruitment Status : Active, not recruiting
First Posted : September 2, 2011
Last Update Posted : June 1, 2017
|Condition or disease||Intervention/treatment|
|Polycystic Ovary Syndrome Hyperandrogenism||Drug: Flutamide Drug: Progesterone Drug: estrace|
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 :||13 participants|
|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|
|Estimated Primary Completion Date :||August 2018|
|Estimated Study Completion Date :||August 2018|
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.Drug: Progesterone
oral progesterone suspension (20 mg/ml, 25-100 mg) three times a day at 0700, 1500, and 2300 hr for seven daysDrug: 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.
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|