TDSM- Testosterone Dose Response in Surgically Menopausal Women
TDSM will study the physiology of testosterone in women ages 21-60 who have had surgical menopause (uterus and both ovaries removed). Testosterone is commonly thought of as a "male hormone" thus being that it is the male's primary hormone. Women produce testosterone in much smaller amounts and despite this, testosterone still plays a significant role. Fifty percent of a women's testosterone is made in her adrenal glands (glands that sit on top of the kidneys) and fifty percent is made in her ovaries. When a woman has her ovaries removed it is thought that her testosterone levels decrease rapidly and significantly. This study will be examining testosterone's role in sexual function, general well being, muscle performance, cognitive function, carbohydrate metabolism and muscle and fat distribution.
The study is 14 months long with weekly to monthly visits. The subjects will be placed on the estrogen patch for the duration of the study. They will also be given weekly injections of testosterone or placebo for 6 months. During the testosterone treatment phase the women will be separated into 5 groups. The groups include a dose of testosterone that is very low, low, medium, high and placebo. A placebo looks and feels similar to testosterone; however it does not have testosterone in it. We use this to test if the subject is having a response to the testosterone itself or the thought of receiving testosterone. Neither the subject nor the investigators will know the dose until the end of the study.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Testosterone Dose Response in Surgically Menopausal Women|
- Physical Function [ Time Frame: 14 months ] [ Designated as safety issue: No ]
- Muscle mass [ Time Frame: 14 months ] [ Designated as safety issue: No ]
- Lipids, glucose, HOMA [ Time Frame: 14 months ] [ Designated as safety issue: No ]
|Study Start Date:||January 2009|
|Study Completion Date:||December 2009|
|Primary Completion Date:||December 2009 (Final data collection date for primary outcome measure)|
|Active Comparator: 1||
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In healthy women the primary hormones produced by the ovaries are estrogens and progesterone, but they also produce testosterone both before and after menopause. Although normal blood levels of testosterone in women are much lower than in men, testosterone is thought to have important physiologic effects in women, particularly on muscle function, body composition, sexual function and cognitive function. When women require bilateral oophorectomy (removal of ovaries), they subsequently have a significant drop in serum testosterone levels. They also frequently experience a decreased sense of well being, and decreased sexual function.
While treatment with testosterone and other androgens has been widely promoted for women with low serum levels, there is little available data on the effects of such treatment particularly when given in physiologic doses (doses resulting in normal blood levels for women). Studies that have demonstrated benefits of testosterone in women have often used doses of testosterone which resulted in higher than normal serum testosterone levels. At such doses, testosterone and other androgens can produce virilizing side effects such as increased facial and body hair, acne, increased size of the clitoris and changes in the voice.
It is not known whether physiologic testosterone replacement can provide the benefits seen with higher doses in women with androgen deficiency without the limiting, virilizing side effects. It has been assumed that testosterone dose-response relationships are different in women than in men, and that clinically significant effects on psycho-sexual function, body composition, muscle performance, cognitive function, and other health-related outcomes can be achieved at testosterone doses and concentrations that are substantially lower than those required to produce similar effects in men; however, these assumptions have not been tested rigorously.
Therefore, the primary objective of this study is to establish testosterone dose-response relationships in surgically menopausal women with low testosterone concentrations for a range of androgen-dependent outcomes, including sexual function, fat-free mass, thigh muscle strength and leg power, several domains of neurocognitive function, plasma lipids, apolipoproteins and lipoprotein particles, and insulin sensitivity.
The secondary objective is to determine the range of testosterone doses and subsequent plasma testosterone concentrations that are associated with improvements in sexual, physical and neurocognitive functions and that can be safely administered to women without significant adverse effects on hair growth, voice, sebum production, clitoral size, and cardiovascular risk factors.
- Testosterone administration in surgically menopausal women with low testosterone concentrations is associated with dose- and concentration-dependent improvements in sexual function and sexual activity scores, specific domains of cognitive function, fat-free mass, thigh muscle strength, and leg power.
- Testosterone dose-response relationships are different for different androgen dependent processes. While some domains of sexual function are normalized by testosterone concentrations at the upper end of the normal range for healthy, young women, significant gains in fat-free mass, thigh muscle strength and power would require higher testosterone doses than those required to induce changes in sexual function.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00494208
|United States, Massachusetts|
|Boston University Medical Center|
|Boston, Massachusetts, United States, 02118|
|Principal Investigator:||Shalender Bhasin, MD||Boston Univeristy Medical Center|
|Study Director:||Shehzad Basaria, M.D.||Boston University|