Baseline Sexual Function, Cognitive Function, Body Composition and Muscle Parameters and Pharmacokinetics of Transdermal Testosterone Gel in Women With Hypopituitarism
Recruitment status was: Recruiting
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Baseline Sexual Function, Cognitive Function, Body Composition and Muscle Parameters and Pharmacokinetics of Transdermal Testosterone Gel in Women With Hypopituitarism|
- The purpose of this study is to determine the pharmacokinetics of testosterone gel 2 mg/d administered for a week to women with hypopituitarism and determine if this leads to testosterone replacement in a physiologic range. [ Time Frame: 6 weeks ] [ Designated as safety issue: Yes ]
- An additional objective is to determine the baseline laboratory abnormalities and physical, cognitive, emotional and sexual symptomatology of these women with hypopituitarism. [ Time Frame: 6 weeks ] [ Designated as safety issue: Yes ]
|Study Start Date:||August 2002|
|Estimated Study Completion Date:||December 2010|
|Estimated Primary Completion Date:||December 2010 (Final data collection date for primary outcome measure)|
Pharmacokinetic study of transdermal testosterone gel-study groups of (8 pumps, 12 pumps, 16 pumps)
Drug: Transdermal Testosterone Gel
2.0 mg per pump of testosterone gel (8 pumps, 12 pumps, 16 pumps). Pharmacokinetic study
The ovaries and the adrenal glands contribute to the daily production of 300 micrograms of testosterone in healthy, menstruating women. The physiologic role of testosterone in women, however, remains poorly understood. Previous studies of testosterone supplementation, largely in surgically or naturally menopausal women, have reported improvements in subjective measures of sexual function, sense of well being, and variable changes in markers of bone formation and resorption. However, many of these previous studies used supraphysiologic doses of testosterone, and insensitive assays for the measurement of total and free testosterone levels that lacked precision and accuracy in the low range prevalent in women. The effects of testosterone in women on body composition, muscle performance and physical function have not been studied. Therefore, the clinical significance of androgen deficiency in women remains unclear. Thus, we do not know whether physiologic testosterone replacement of women with androgen deficiency can produce clinically meaningful improvements in sexual and cognitive functions, fat-free mass, and muscle performance, without virilizing side effects.
Women with hypopituitarism represent an excellent model to study the effects of physiologic replacement as these patients have severely diminished androgen production from both the adrenal glands and the ovaries. Estrogen administration, by increasing sex hormone binding globulin (SHBG) in these women leads to further reduction in free testosterone concentrations. In fact, a recent study demonstrated very low levels of total and free testosterone, dehydroepiandrosterone sulfate (DHEAS), its parent steroid dehydroepiandrosterone (DHEA), and androstenedione in women with hypopituitarism. Therefore, it is postulated that many women with hypopituitarism suffer from decreased libido, altered body composition, and impaired quality of life, symptoms possibly related to androgen deficiency. However, these parameters have not been properly studied in a well-defined group of women with hypopituitarism. These baseline studies are needed prior to undertaking a study on treating women with hypopituitarism with a testosterone preparation.
Prior to investigating testosterone replacement in a large study of women with hypopituitarism, we must first determine in this pilot study the amount and interval of testosterone administration.
Currently, the only FDA-approved drug for testosterone in women is Estratest, which contains methyl testosterone, a compound that when given orally is associated with liver toxicity in animals and humans. Until recently, most hypogonadal men received biweekly intramuscular injections of testosterone. This regimen gives variable serum testosterone levels depending on the time of the blood sampling compared to the time of injection. Many male hypogonadal patients now receive their testosterone replacement via either transdermal testosterone gel or patch, with much more uniform serum testosterone levels. We have chosen transdermal testosterone gel for use in this study for several reasons:
- Recent studies have shown that stable, reproducible levels of serum testosterone can be obtained irrespective of application site in hypogonadal men. No skin irritation (which can be problematic with the testosterone patch) was observed.
- Graded Double-blinded dosing can easily be implemented.
Thus, we will use transdermal testosterone gel as it provides predictable and physiologic levels of testosterone.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00144404
|United States, California|
|Charles R. Drew University|
|Los Angeles, California, United States, 90059|
|Principal Investigator:||Ted C Friedman, M.D., Ph.D.||Charles Drew University of Medicine and Science|