TDSM- Testosterone Dose Response in Surgically Menopausal Women

NCT00494208 | Completed

• 1 other identifier: U54HD041748
• Study Type: interventional
• Target: 270
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Hysterectomy; Ovariectomy; Menopause; Testosterone Deficiency

Keywords

androgens; testosterone; testosterone deficiency; women; menopause; surgical Menopause; hysterectomy; oophorectomy; ovariectomy; sexual dysfunction; sexual function; muscle function; insulin sensitivity; body composition

Outcome Measures

Primary Outcomes (1)

• Physical Function

  14 months

Secondary Outcomes (2)

• Muscle mass

  14 months

• Lipids, glucose, HOMA

  14 months

Study Arms (5)

1

ACTIVE COMPARATOR

Drug: Testosterone

2

ACTIVE COMPARATOR

Drug: Testosterone

3

ACTIVE COMPARATOR

Drug: Testosterone

4

ACTIVE COMPARATOR

Drug: Testosterone

5

ACTIVE COMPARATOR

Drug: Testosterone

Interventions

Testosterone DRUG

Testosterone ester

1; 2; 3; 4; 5

Eligibility Criteria

• Age: 21 Years - 60 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): lead

Study Sites (1)

Boston University Medical Center

Boston, Massachusetts, 02118, United States

Location

Related Publications (4)

• Tapper J, Huang G, Pencina KM, Li Z, Arver S, Martling A, Blomqvist L, Buchli C, Travison TG, Storer TW, Bhasin S, Basaria S. The effects of testosterone administration on muscle areas of the trunk and pelvic floor in hysterectomized women with low testosterone levels: proof-of-concept study. Menopause. 2019 Dec;26(12):1405-1414. doi: 10.1097/GME.0000000000001410.

  PMID: 31479032 DERIVED

• Huang G, Pencina KM, Coady JA, Beleva YM, Bhasin S, Basaria S. Functional Voice Testing Detects Early Changes in Vocal Pitch in Women During Testosterone Administration. J Clin Endocrinol Metab. 2015 Jun;100(6):2254-60. doi: 10.1210/jc.2015-1669. Epub 2015 Apr 15.

  PMID: 25875779 DERIVED

• Huang G, Tang E, Aakil A, Anderson S, Jara H, Davda M, Stroh H, Travison TG, Bhasin S, Basaria S. Testosterone dose-response relationships with cardiovascular risk markers in androgen-deficient women: a randomized, placebo-controlled trial. J Clin Endocrinol Metab. 2014 Jul;99(7):E1287-93. doi: 10.1210/jc.2013-4160. Epub 2014 Apr 8.

  PMID: 24712568 DERIVED

• Huang G, Basaria S, Travison TG, Ho MH, Davda M, Mazer NA, Miciek R, Knapp PE, Zhang A, Collins L, Ursino M, Appleman E, Dzekov C, Stroh H, Ouellette M, Rundell T, Baby M, Bhatia NN, Khorram O, Friedman T, Storer TW, Bhasin S. Testosterone dose-response relationships in hysterectomized women with or without oophorectomy: effects on sexual function, body composition, muscle performance and physical function in a randomized trial. Menopause. 2014 Jun;21(6):612-23. doi: 10.1097/GME.0000000000000093.

  PMID: 24281237 DERIVED

MeSH Terms

Conditions

Sexual Dysfunction, Physiological; Insulin Resistance

Interventions

Testosterone

Condition Hierarchy (Ancestors)

Genital Diseases; Urogenital Diseases; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Androstenols; Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Testosterone Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Shalender Bhasin, MD

  Boston Univeristy Medical Center

  PRINCIPAL INVESTIGATOR

• Shehzad Basaria, M.D.

  Boston University

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 28, 2007
• First Posted: June 29, 2007
• Study Start: January 1, 2009
• Primary Completion: December 1, 2009
• Study Completion: December 1, 2009
• Last Updated: May 1, 2013

Record last verified: 2009-01

Locations

US (1)