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
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OBJECTIVE: This study aims to determine the dose-dependent effects of testosterone on sexual function, body composition, muscle performance, and physical function in hysterectomized women with or without oophorectomy. METHODS: Seventy-one postmenopausal women who previously underwent hysterectomy with or without oophorectomy and had total testosterone levels less than 31 ng/dL or free testosterone levels less than 3.5 pg/mL received a standardized transdermal estradiol regimen during the 12-week run-in period and were randomized to receive weekly intramuscular injections of placebo or 3, 6.25, 12.5, or 25 mg of testosterone enanthate for 24 weeks. Total and free testosterone levels were measured by liquid chromatography-tandem mass spectrometry and equilibrium dialysis, respectively. The primary outcome was change in sexual function measured by the Brief Index of Sexual Functioning for Women. Secondary outcomes included changes in sexual activity, sexual distress, Derogatis Interview for Sexual Functioning, lean body mass, fat mass, muscle strength and power, and physical function. RESULTS: Seventy-one women were randomized; five groups were similar at baseline. Sixty-two women with analyzable data for the primary outcome were included in the final analysis. The mean on-treatment total testosterone concentrations were 19, 78, 102, 128, and 210 ng/dL in the placebo, 3-mg, 6.25-mg, 12.5-mg, and 25-mg groups, respectively. Changes in composite Brief Index of Sexual Functioning for Women scores, thoughts/desire, arousal, frequency of sexual activity, lean body mass, chest-press power, and loaded stair-climb power were significantly related to increases in free testosterone concentrations; compared with placebo, changes were significantly greater in women assigned to the 25-mg group, but not in women in the lower-dose groups. Sexual activity increased by 2.7 encounters per week in the 25-mg group. The frequency of androgenic adverse events was low. CONCLUSIONS: Testosterone administration in hysterectomized women with or without oophorectomy for 24 weeks was associated with dose and concentration-dependent gains in several domains of sexual function, lean body mass, chest-press power, and loaded stair-climb power. Long-term trials are needed to weigh improvements in these outcomes against potential long-term adverse effects.
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In a study of postmenopausal women, increasing testosterone to a mean nadir concentration of 7.3 nmol/L produced significant increases in muscle mass and strength, ranging from 4.4% for muscle (lean) mass to between 12% and 26% for measures of muscle strength.
“The women whose testosterone concentrations were increased to 7.3 nmol/L achieved significant increases in muscle mass and strength (Table 4), ranging from 4.4% for muscle (lean) mass to between 12% and 26% for measures of muscle strength (chest and leg press, loaded stair climb).”
From Circulating Testosterone as the Hormonal Basis of Sex Differences in Athletic Performance (2018) · cites this paper as [112]
In postmenopausal women, the highest testosterone dose (25 mg weekly), which increased mean serum testosterone to 7.3 nmol/L, had the largest increase (3%) in blood hemoglobin and hematocrit.
“Analogous findings were reported for testosterone treatment effects in postmenopausal women where the highest dose (25 mg weekly) of testosterone, which increased mean serum testosterone to 7.3 nmol/L, had the largest increase (3%) in blood hemoglobin and hematocrit (112).”
From Circulating Testosterone as the Hormonal Basis of Sex Differences in Athletic Performance (2018) · cites this paper as [112]
The basis for the sex difference in muscle mass and strength is the sex difference in circulating testosterone.
“The basis for the sex difference in muscle mass and strength is the sex difference in circulating testosterone as clearly shown (for example) by (1) the enhanced athletic performance of men compared with prepubertal boys and women (8); (2) the close correspondence of muscle growth (muscle size) with muscle strength in ascending dose studies in men by Bhasin et al. (111, 117–119) and Finkelstein et”
From Circulating Testosterone as the Hormonal Basis of Sex Differences in Athletic Performance (2018) · cites this paper as [112]
In a randomized placebo-controlled study of testosterone administration in postmenopausal women, the highest dose (the only one causing circulating testosterone levels to exceed the normal female range) produced an increase in muscle mass (4.4%) and a strikingly greater increase in muscle strength (12% to 26%).
“In a randomized placebo-controlled study of testosterone administration in postmenopausal women (112), in case of those receiving the highest dose (the only one causing circulating testosterone levels to exceed the normal female range), there was not only an increase in muscle mass (4.4%) but a strikingly greater increase in muscle strength (12% to 26%), suggesting an enhanced mental motivational”
From Circulating Testosterone as the Hormonal Basis of Sex Differences in Athletic Performance (2018) · cites this paper as [112]
The greater increase in muscle strength than muscle mass with the highest testosterone dose suggests an enhanced mental motivational effect of testosterone on effort-dependent tests of muscle strength.
“In a randomized placebo-controlled study of testosterone administration in postmenopausal women (112), in case of those receiving the highest dose (the only one causing circulating testosterone levels to exceed the normal female range), there was not only an increase in muscle mass (4.4%) but a strikingly greater increase in muscle strength (12% to 26%), suggesting an enhanced mental motivational”
From Circulating Testosterone as the Hormonal Basis of Sex Differences in Athletic Performance (2018) · cites this paper as [112]
With the exception of one interventional study administering a relatively low testosterone dose to women, the available evidence comprises observational studies that can only examine effects of serum testosterone within physiological female limits or sparse and mostly uncontrolled data from intersex/DSD athletes.
“With the exception of one interventional study administering a relatively low testosterone dose (i.e., low for males) to women (112), the available evidence comprises observational studies that can only examine the effects of serum testosterone within physiological female limits or sparse and mostly uncontrolled data from intersex/DSD athletes.”
From Circulating Testosterone as the Hormonal Basis of Sex Differences in Athletic Performance (2018) · cites this paper as [112]
In the Huang et al. study, the highest testosterone dose (weekly injections of 25 mg testosterone enanthate) increased mean circulating testosterone from 0.9 nmol/L to 7.3 nmol/L, equivalent to circulating testosterone of boys in early to middle puberty.
“In this study the highest testosterone dose (weekly injections of 25 mg of testosterone enanthate) increased mean circulating testosterone from 0.9 nmol/L to 7.3 nmol/L, which is equivalent to the circulating testosterone of boys in early to middle puberty.”
From Circulating Testosterone as the Hormonal Basis of Sex Differences in Athletic Performance (2018) · cites this paper as [112]
The only well-designed, placebo-controlled study of testosterone in otherwise healthy postmenopausal women was restricted to relatively low testosterone doses that were only 20% to 25% of male testosterone replacement doses.
“The only well-designed, placebo-controlled study of testosterone in otherwise healthy postmenopausal women was restricted to relatively low testosterone doses that, although clearly supraphysiological for women, were only 20% to 25% of male testosterone replacement doses (112).”
From Circulating Testosterone as the Hormonal Basis of Sex Differences in Athletic Performance (2018) · cites this paper as [112]
After 24 weeks of testosterone treatment, the increase in circulating testosterone concentrations led to significant increases in muscle size of 4.4% and in muscle strength of 12% to 26%.
“After 24 weeks of testosterone treatment, the increase in circulating testosterone concentrations led to significant increases in muscle size of 4.4% and in muscle strength of 12% to 26%.”
From Circulating Testosterone as the Hormonal Basis of Sex Differences in Athletic Performance (2018) · cites this paper as [112]
According to the Huang et al. study, reducing circulating testosterone to a mean of 7.3 nmol/L would still deliver a 4.4% increase in muscle size and a 12% to 26% increase in muscle strength compared with circulating testosterone at the normal female mean value of 0.9 nmol/L.
“For example, according to the Huang et al. (112) study, reducing circulating testosterone to a mean of 7.3 nmol/L would still deliver a 4.4% increase in muscle size and a 12% to 26% increase in muscle strength compared with circulating testosterone at the normal female mean value of 0.9 nmol/L.”
From Circulating Testosterone as the Hormonal Basis of Sex Differences in Athletic Performance (2018) · cites this paper as [112]
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Self-citationEvans, S. F., Kwok, Y., Solterbeck, A., Pyragius, C., Hull, M. L., Hutchinson, M. R., & Rolan, P. (2021) · Journal of Pain Research · doi:10.2147/jpr.s279253 · Cited by 21 · see citing works
- Authors
- Huang, G., Basaria, S., Travison, T. G., Ho, M. H., Davda, M., Mazer, N. A., Miciek, R., Knapp, P. E., Zhang, A., Collins, L., Ursino, M., Appleman, E., Dzekov, C., Stroh, H., Ouellette, M., Rundell, T., Baby, M., Bhatia, N. N., Khorram, O., Friedman, T., Storer, T. W., & Bhasin, S.
- Affiliations
- Boston University (US)
- University of California, Los Angeles (US)
- Charles R. Drew University of Medicine and Science (US)
- Corresponding author
- Ho, Matthew H.
- Bhasin, Shalender
- ORCID
- Venue
- Menopause
- Published
- 2014-06
- Volume
- 21
- Issue
- 6
- Pages
- 612-623
- ISSN
- 1072-3714 (ISSN-L)
- PMC
- PMC4701202
- OpenAlex
- W2079399680
- Cited by
- 119
- References
- 56
- Citations by year
- 2026: 11 · 2025: 11 · 2024: 7 · 2023: 11 · 2022: 10 · 2021: 15 · 2020: 12 · 2019: 8 · 2018: 5 · 2017: 10 · 2016: 5 · 2015: 6 · 2014: 7
- FWCI
- 4.72
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Menopause The Journal of The North American Menopause Society (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institutes of Health (5p30ag031679-15)
- National Institute on Aging (5 P30 AG031679, P30-AG031679)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (U54HD041748)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Menopause: Health Impacts and Treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Sexual function and dysfunction studies
- Keywords
- testosterone enanthate, dose-response relationship, testosterone replacement therapy, hysterectomy, oophorectomy, postmenopausal women, sexual function, free testosterone, lean body mass, muscle strength, physical function, transdermal estradiol, sexual activity
- MeSH terms
- Androgens, Arousal, Body Composition, Dose-Response Relationship, Drug, Female, Humans, Hysterectomy, Middle Aged, Ovariectomy, Sexual Behavior, Testosterone, Postmenopause, Muscle, Skeletal, Sexuality, Muscle Strength
About these checks
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