TDSM- Testosterone Dose Response in Surgically Menopausal Women

• Status: Completed
• Trial end date: 2009-12-01
• Target enrollment: 0
• Participant gender: Female

Summary

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.

• Phase: N/A
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Treatments: Methyltestosterone; Testosterone; Testosterone 17 beta-cypionate; Testosterone enanthate; Testosterone undecanoate

Criteria

Inclusion Criteria

• Medically stable, ambulatory, surgically menopausal women, 21-60 years of age, who have undergone bilateral salpingo-oophorectomy and hysterectomy at least 6 months before study entry

• Serum total testosterone concentrations less than 31 ng/dL or free testosterone less than 3.5 pg/ml (less than the median for healthy, young women

• Able to understand and give informed consent.

• The women will have been on a stable regimen of transdermal estrogen replacement for at least three months. Those who are not on estrogen replacement or are taking a different mode of estrogen replacement will be included only if they are willing to switch to transdermal estradiol patch (see below).

• A normal PAP smear (if subject has a cervix) and mammogram in the preceding 12 months.

Exclusion Criteria:

• Significant depression, as assessed by Beck's Depression Scale.

• Any acute or chronic illness, malignant disease or fever of known or unknown origin will be excluded.

• Poorly controlled diabetes mellitus (hemoglobin A1c greater than 8.5%)

• Uncontrolled hypertension defined as blood pressure of greater than 160/100

• Severe obesity defined as body mass index of greater than 40 kg/m2

• Current or recent (last 6 months) users of illicit drugs (which may affect appetite, food intake, metabolism, and/or compliance with the protocol)

• Any one planning to initiate a weight-reduction diet in the subsequent six months

• Alcohol or drug dependence currently or in the preceding 6 month.

• Significant liver function abnormalities, defined as SGOT, SGPT or alkaline phosphatase value of greater than three times the upper limit of normal in our Clinical Pathology Laboratory or serum bilirubin levels of greater than 1.5 mg/dl will be excluded.

• History of breast, ovarian, endometrial or cervical cancer

• History of hyperandrogenic disorders such as hirsutism, grade 2 or 3 acne, and polycystic ovary disease. Testosterone administration to these patients may exacerbate the underlying disorder.

• Intolerance to other transdermal formulations

• Women with abnormal PAP smears or mammograms will not be included unless they have been evaluated by their gynecologists and breast and uterine/cervical cancers have been excluded by appropriate tests.

• Women with dementia as assessed by the mini-mental state examination

• Women with depression, assessed by Beck's Depression Scale.

• Those with disabilities that would prevent them from participating in strength testing (e.g., amputation of limbs, blindness, severe arthritis, neurologic disorders such as Parkinson's disease, stroke, or myopathy).

• Women with any heart disease, including angina, congestive heart failure, or history of myocardial infarction or coronary artery angioplasty or bypass surgery in the previous year will be excluded.

• Subjects planning to initiate a weight-reduction diet in the subsequent six months

• Other Medications. Women who have received in the preceding three months drugs known to affect testosterone production or metabolism such as ketoconazole, Megace, and/or anabolic/androgenic steroids will be excluded. We will also exclude women who are taking or have taken in the past three months medication that include sexual dysfunction (e.g., spironolactone, SSRIs, GnRH agonists). Women who are using any medication, device or dietary supplement known to enhance sexual function will not be included. Women receiving thyroid hormone replacement therapy may participate in the study only if they have been on a stable replacement dose of L-thyroxine for at least three months.

• Intolerance to estrogen products or skin patches

• Undiagnosed vaginal or vulvar bleeding

• History of deep vein thrombosis, pulmonary embolism, or other thromboembolic disorder