HysterectomyNCT00494208
TDSM- Testosterone Dose Response in Surgically Menopausal Women
A study testing Testosterone in people with Hysterectomy and Ovariectomy, run by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 21 to 60 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Hysterectomy, Ovariectomy, Menopause
- What is being tested?
- Testosterone
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 270 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2009to Dec 2009
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 60 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
Who cannot join
- 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)
Show all 22Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Boston University Medical Center
Boston, Massachusetts, 02118
About this study
Official title: 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.
Read the detailed description
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.
Hypotheses
- 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.
- Conditions
- Hysterectomy, Ovariectomy, Menopause, Testosterone Deficiency
- Being tested
- Testosterone
- Keywords
- androgens, testosterone, testosterone deficiency, women, menopause, surgical Menopause, hysterectomy, oophorectomy, ovariectomy, sexual dysfunction, sexual function, muscle function, insulin sensitivity, body composition
- Medical subject headings
- Sexual Dysfunction, Physiological, Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TestosteroneDrug
Testosterone ester
| Study group | Role | What they receive |
|---|---|---|
| 1 | Active comparator | Not described Receives: Drug: Testosterone |
| 2 | Active comparator | Not described Receives: Drug: Testosterone |
| 3 | Active comparator | Not described Receives: Drug: Testosterone |
| 4 | Active comparator | Not described Receives: Drug: Testosterone |
| 5 | Active comparator | Not described Receives: Drug: Testosterone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Physical Function
Measured: 14 months
Secondary outcomes (2)
Muscle mass
Measured: 14 months
Lipids, glucose, HOMA
Measured: 14 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jun 2007 (estimated)
- Study startJan 2009
- Primary completionDec 2009
- Study completionDec 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for HysterectomyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 270 participants (actual)
Sponsor and investigators
- Lead sponsor
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Shalender Bhasin, MD, Principal investigator, Boston Univeristy Medical CenterShehzad Basaria, M.D., Study director, Boston University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00494208
- Sponsor's protocol ID
- U54HD041748
- Status last verified
- Jan 2009
- First submitted
- 28 Jun 2007
- Last updated
- 1 May 2013
- Results posted
- No
Publications
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.
PubMed 31479032Huang 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.
PubMed 25875779Huang 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.
PubMed 24712568Huang 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.
PubMed 24281237
Study at a glance
From the registry record, last updated by the sponsor on 1 May 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Testosterone Dose Response in Surgically Menopausal Women
- ClinicalTrials.gov ID
- NCT00494208
- Acronym / sponsor ID
- U54HD041748
- Conditions
- Hysterectomy, Ovariectomy, Menopause, Testosterone Deficiency
- Keywords
- androgens, testosterone, testosterone deficiency, women, menopause, surgical Menopause, hysterectomy, oophorectomy
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 270 participants (actual)
- Lead sponsor
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)US National Institutes of Health
- Study start
- Jan 2009
- Primary completion
- Dec 2009 (actual)
- Study completion
- Dec 2009 (actual)
- First posted
- 29 Jun 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Hypotheses
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| 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 |
Who may qualify
- Ages
- 21 to 60 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (22 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TestosteroneTestosterone ester | Drug | 1, 2, 3, 4, 5 |
Primary outcome
Physical Function
Time frame: 14 months
2 secondary outcomes
Muscle mass
Time frame: 14 months
Lipids, glucose, HOMA
Time frame: 14 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 May 2013.
- Derived from this study: PubMed 31479032Tapper 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.
- Derived from this study: PubMed 25875779Huang 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.
- Derived from this study: PubMed 24712568Huang 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.
- Derived from this study: PubMed 24281237Huang 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Shalender Bhasin, MD principal investigator
Boston Univeristy Medical Center
Shehzad Basaria, M.D. study director
Boston University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Testosterone in people with Hysterectomy and Ovariectomy, run by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 May 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Physical Function (time frame: 14 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00494208, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 May 2013.