Women who are diagnosed accurately with hypoactive sexual desire dysfunction (HSDD) and female sexual arousal disorder (FSAD), could benefit from testosterone supplementation. Testosterone therapy appears to be helpful and safe when the dose does not exceed premenopausal physiological levels. For more details, refer to the Global Position Statement published in JCEM in October 2019.

Also see:

Sex hormones

Women health

J C E M

Global Statement

October 2019

Testosterone treatment of naturally or surgically postmenopausal women with HSDD, with/or without concurrent estrogen therapy

Testosterone therapy, in doses, that approximate physiological testosterone concentrations for premenopausal women, exerts a beneficial effect on sexual function including increases, above the effects of placebo/comparator therapy, of an average of one satisfying sexual event per month, and increases in the subdomains of sexual desire, arousal, orgasmic function, pleasure, and sexual responsiveness, together with a reduction in sexual concerns including sexual distress.
Because the majority of studies reporting on sexual function recruited women assessed as having HSDD or generalized FSD, these recommendations cannot be generalized to other subtypes of FSD or women without sexual dysfunction (Expert Opinion).
The first recommendations above do not apply to injectables, pellets, or formulations that result in supraphysiological blood concentrations of testosterone, or compounded preparations (Expert Opinion).
- Systemic dehydroepiandrosterone is not associated with significant improvement in libido or sexual function in postmenopausal women with normal adrenal function and cannot be recommended for women with HSDD.
- In the absence of vulvovaginal atrophy, vaginal dehydroepiandrosterone has not been tested and thus cannot be recommended for the treatment of HSDD (Expert Opinion).
Recommendations regarding the design of future trials of physiologically dosed testosterone (Expert Opinion for all)
- More adequately powered, double-blind RCTs, without selection bias and with consistent reporting of standardized outcomes, are needed to comprehensively establish the benefits and risks of testosterone therapy for women.
- For studies of testosterone and FSD disorder:
  - Relief of the distress associated with sexual dysfunction is a primary aim of FSD treatment.
  - Presently, no questionnaire covers all domains of female sexual function such that a combination of domains from different questionnaires should be used.
  - Satisfying sexual events should no longer be used as a primary efficacy measure in clinical trials of women with FSD.
  - A set of clearly defined core outcomes needs to be established.
  - There is a need for an instrument to assess sexual function with the following characteristics: general applicability; not disease-specific; high discriminant validity between women diagnosed with FSD and sexually functional women; validated, to measure FSD per se and as an instrument to screen for and diagnose FSD and demonstrating clinically meaningful response to intervention; cover different domains, with each domain comprising several items; translated and back-translated in a variety of languages, satisfies the most stringent assessment to gain approval by regulatory agencies.
- There is a need for adequately powered RCTs of the effects of testosterone on the musculoskeletal health of women with normal bone mass, low bone mass, osteopenia/osteoporosis, and sarcopenia, with outcomes including vertebral and total hip and femoral neck bone mineral density, trabecular bone score, serum biomarkers, fracture risk, body composition, and muscle strength.
- There is a need for adequately powered RCTs of the effects of testosterone on cognitive performance.
- Studies must be undertaken to establish the longer-term cardiometabolic and breast safety of testosterone therapy for women
- The only evidence-based indication for the use of testosterone in women is for the treatment of postmenopausal women who have been diagnosed as having HSDD after formal biopsychosocial assessment.
- There is an unmet need for the provision and approval of testosterone treatments specific to women, formulated with the aim of approximating physiological testosterone concentrations for premenopausal women (Expert Opinion).
- Where an appropriate approved female testosterone preparation is not available, off-label, prescribing of an approved male formulation is reasonable, provided hormone concentrations are maintained in the physiologic female range (Expert Opinion).
- Compounded “bioidentical” testosterone therapy cannot be recommended for the treatment of HSDD because of the lack of evidence for efficacy and safety unless an authorized equivalent preparation is not available (Expert Opinion). In the absence of an available approved product, if a compounded product is needed, the compounding pharmacy should be compliant with the purity of Active Pharmaceutical Ingredients and Good Manufacturing Practice to meet industry standards for quality and safety. Dosing should be limited to achieving testosterone concentrations in the physiologic premenopausal range.
- The use of any testosterone preparation that results in supraphysiologic concentrations of testosterone, including pellets and injections, is not recommended (Expert Opinion).
- Should a trial of testosterone therapy be given for HSDD, a baseline total testosterone concentration should be measured before commencement, with a repeat level 3–6 weeks after treatment initiation.
- Patients should be monitored for their clinical response to treatment and assessed for signs of androgen excess with a serum total testosterone level every 6 months, to screen for overuse (Expert Opinion).
- If no benefit is experienced by 6 months, treatment should be ceased
Recommendations regarding other androgenic preparations
- Systemic dehydroepiandrosterone is not associated with significant improvement in libido or sexual function in postmenopausal women with normal adrenal function and cannot be recommended for women with HSDD.
- In the absence of vulvovaginal atrophy, vaginal dehydroepiandrosterone has not been tested and thus cannot be recommended for the treatment of HSDD (Expert Opinion).
Recommendations regarding the design of future trials of physiologically dosed testosterone (Expert Opinion for all)
- More adequately powered, double-blind RCTs, without selection bias and with consistent reporting of standardized outcomes, are needed to comprehensively establish the benefits and risks of testosterone therapy for women.
- For studies of testosterone and FSD disorder:
  - Relief of the distress associated with sexual dysfunction is a primary aim of FSD treatment.
  - Presently, no questionnaire covers all domains of female sexual function such that a combination of domains from different questionnaires should be used.
  - Satisfying sexual events should no longer be used as a primary efficacy measure in clinical trials of women with FSD.
  - A set of clearly defined core outcomes needs to be established.
  - There is a need for an instrument to assess sexual function with the following characteristics: general applicability; not disease-specific; high discriminant validity between women diagnosed with FSD and sexually functional women; validated, to measure FSD per se and as an instrument to screen for and diagnose FSD and demonstrating clinically meaningful response to intervention; cover different domains, with each domain comprising several items; translated and back-translated in a variety of languages, satisfies the most stringent assessment to gain approval by regulatory agencies.
- There is a need for adequately powered RCTs of the effects of testosterone on the musculoskeletal health of women with normal bone mass, low bone mass, osteopenia/osteoporosis, and sarcopenia, with outcomes including vertebral and total hip and femoral neck bone mineral density, trabecular bone score, serum biomarkers, fracture risk, body composition, and muscle strength.
- There is a need for adequately powered RCTs of the effects of testosterone on cognitive performance.
- Studies must be undertaken to establish the longer-term cardiometabolic and breast safety of testosterone therapy for women
- FSD including HSDD, FSAD, and orgasmic disorder/dysfunction have multiple etiologies including biopsychosocial factors such as neuroendocrine imbalance, physical ill-health or disease, interpersonal difficulties, psychological distress, and sexually repressive cultural or religious values.
- Treatments should follow this biopsychosocial model and include pharmacologic options (hormone therapies and other pharmacologic agents), psychotherapy, or multimodal treatments that combine both.
Current testosterone therapy and postmenopausal women
- The only evidence-based indication for the use of testosterone in women is for the treatment of postmenopausal women who have been diagnosed as having HSDD after formal biopsychosocial assessment.
- There is an unmet need for the provision and approval of testosterone treatments specific to women, formulated with the aim of approximating physiological testosterone concentrations for premenopausal women (Expert Opinion).
- Where an appropriate approved female testosterone preparation is not available, off-label, prescribing of an approved male formulation is reasonable, provided hormone concentrations are maintained in the physiologic female range (Expert Opinion).
- Compounded “bioidentical” testosterone therapy cannot be recommended for the treatment of HSDD because of the lack of evidence for efficacy and safety unless an authorized equivalent preparation is not available (Expert Opinion). In the absence of an available approved product, if a compounded product is needed, the compounding pharmacy should be compliant with the purity of Active Pharmaceutical Ingredients and Good Manufacturing Practice to meet industry standards for quality and safety. Dosing should be limited to achieving testosterone concentrations in the physiologic premenopausal range.
- The use of any testosterone preparation that results in supraphysiologic concentrations of testosterone, including pellets and injections, is not recommended (Expert Opinion).
- Should a trial of testosterone therapy be given for HSDD, a baseline total testosterone concentration should be measured before commencement, with a repeat level 3–6 weeks after treatment initiation.
- Patients should be monitored for their clinical response to treatment and assessed for signs of androgen excess with a serum total testosterone level every 6 months, to screen for overuse (Expert Opinion).
- If no benefit is experienced by 6 months, treatment should be ceased
Recommendations regarding other androgenic preparations
- Systemic dehydroepiandrosterone is not associated with significant improvement in libido or sexual function in postmenopausal women with normal adrenal function and cannot be recommended for women with HSDD.
- In the absence of vulvovaginal atrophy, vaginal dehydroepiandrosterone has not been tested and thus cannot be recommended for the treatment of HSDD (Expert Opinion).
Recommendations regarding the design of future trials of physiologically dosed testosterone (Expert Opinion for all)
- More adequately powered, double-blind RCTs, without selection bias and with consistent reporting of standardized outcomes, are needed to comprehensively establish the benefits and risks of testosterone therapy for women.
- For studies of testosterone and FSD disorder:
  - Relief of the distress associated with sexual dysfunction is a primary aim of FSD treatment.
  - Presently, no questionnaire covers all domains of female sexual function such that a combination of domains from different questionnaires should be used.
  - Satisfying sexual events should no longer be used as a primary efficacy measure in clinical trials of women with FSD.
  - A set of clearly defined core outcomes needs to be established.
  - There is a need for an instrument to assess sexual function with the following characteristics: general applicability; not disease-specific; high discriminant validity between women diagnosed with FSD and sexually functional women; validated, to measure FSD per se and as an instrument to screen for and diagnose FSD and demonstrating clinically meaningful response to intervention; cover different domains, with each domain comprising several items; translated and back-translated in a variety of languages, satisfies the most stringent assessment to gain approval by regulatory agencies.
- There is a need for adequately powered RCTs of the effects of testosterone on the musculoskeletal health of women with normal bone mass, low bone mass, osteopenia/osteoporosis, and sarcopenia, with outcomes including vertebral and total hip and femoral neck bone mineral density, trabecular bone score, serum biomarkers, fracture risk, body composition, and muscle strength.
- There is a need for adequately powered RCTs of the effects of testosterone on cognitive performance.
- Studies must be undertaken to establish the longer-term cardiometabolic and breast safety of testosterone therapy for women

A full assessment of FSD before commencing testosterone therapy

FSD including HSDD, FSAD, and orgasmic disorder/dysfunction have multiple etiologies including biopsychosocial factors such as neuroendocrine imbalance, physical ill-health or disease, interpersonal difficulties, psychological distress, and sexually repressive cultural or religious values.
Treatments should follow this biopsychosocial model and include pharmacologic options (hormone therapies and other pharmacologic agents), psychotherapy, or multimodal treatments that combine both.

Current testosterone therapy and postmenopausal women

The only evidence-based indication for the use of testosterone in women is for the treatment of postmenopausal women who have been diagnosed as having HSDD after formal biopsychosocial assessment.
There is an unmet need for the provision and approval of testosterone treatments specific to women, formulated with the aim of approximating physiological testosterone concentrations for premenopausal women (Expert Opinion).
Where an appropriate approved female testosterone preparation is not available, off-label, prescribing of an approved male formulation is reasonable, provided hormone concentrations are maintained in the physiologic female range (Expert Opinion).
Compounded “bioidentical” testosterone therapy cannot be recommended for the treatment of HSDD because of the lack of evidence for efficacy and safety unless an authorized equivalent preparation is not available (Expert Opinion). In the absence of an available approved product, if a compounded product is needed, the compounding pharmacy should be compliant with the purity of Active Pharmaceutical Ingredients and Good Manufacturing Practice to meet industry standards for quality and safety. Dosing should be limited to achieving testosterone concentrations in the physiologic premenopausal range.
The use of any testosterone preparation that results in supraphysiologic concentrations of testosterone, including pellets and injections, is not recommended (Expert Opinion).
Should a trial of testosterone therapy be given for HSDD, a baseline total testosterone concentration should be measured before commencement, with a repeat level 3–6 weeks after treatment initiation.
Patients should be monitored for their clinical response to treatment and assessed for signs of androgen excess with a serum total testosterone level every 6 months, to screen for overuse (Expert Opinion).
If no benefit is experienced by 6 months, treatment should be ceased

Recommendations regarding other androgenic preparations

Systemic dehydroepiandrosterone is not associated with significant improvement in libido or sexual function in postmenopausal women with normal adrenal function and cannot be recommended for women with HSDD.
In the absence of vulvovaginal atrophy, vaginal dehydroepiandrosterone has not been tested and thus cannot be recommended for the treatment of HSDD (Expert Opinion).

Recommendations regarding the design of future trials of physiologically dosed testosterone (Expert Opinion for all)

More adequately powered, double-blind RCTs, without selection bias and with consistent reporting of standardized outcomes, are needed to comprehensively establish the benefits and risks of testosterone therapy for women.
For studies of testosterone and FSD disorder:
- Relief of the distress associated with sexual dysfunction is a primary aim of FSD treatment.
- Presently, no questionnaire covers all domains of female sexual function such that a combination of domains from different questionnaires should be used.
- Satisfying sexual events should no longer be used as a primary efficacy measure in clinical trials of women with FSD.
- A set of clearly defined core outcomes needs to be established.
- There is a need for an instrument to assess sexual function with the following characteristics: general applicability; not disease-specific; high discriminant validity between women diagnosed with FSD and sexually functional women; validated, to measure FSD per se and as an instrument to screen for and diagnose FSD and demonstrating clinically meaningful response to intervention; cover different domains, with each domain comprising several items; translated and back-translated in a variety of languages, satisfies the most stringent assessment to gain approval by regulatory agencies.
There is a need for adequately powered RCTs of the effects of testosterone on the musculoskeletal health of women with normal bone mass, low bone mass, osteopenia/osteoporosis, and sarcopenia, with outcomes including vertebral and total hip and femoral neck bone mineral density, trabecular bone score, serum biomarkers, fracture risk, body composition, and muscle strength.
There is a need for adequately powered RCTs of the effects of testosterone on cognitive performance.
Studies must be undertaken to establish the longer-term cardiometabolic and breast safety of testosterone therapy for women

Testosterone therapy and serious adverse events

Testosterone therapy for postmenopausal women, in doses, that approximate physiological testosterone concentrations for premenopausal women, is not associated with serious adverse events.
Because RCTs of testosterone therapy have excluded women at high cardiometabolic disease risk, and most have included women taking concurrent estrogen therapy, recommendation 10 (a) is not generalizable to a more “at-risk” population (Expert Opinion).
Safety data for testosterone in physiologic doses are not available beyond 24 months of treatment

A full assessment of FSD before commencing testosterone therapy

FSD including HSDD, FSAD, and orgasmic disorder/dysfunction have multiple etiologies including biopsychosocial factors such as neuroendocrine imbalance, physical ill-health or disease, interpersonal difficulties, psychological distress, and sexually repressive cultural or religious values.
Treatments should follow this biopsychosocial model and include pharmacologic options (hormone therapies and other pharmacologic agents), psychotherapy, or multimodal treatments that combine both.

Current testosterone therapy and postmenopausal women

The only evidence-based indication for the use of testosterone in women is for the treatment of postmenopausal women who have been diagnosed as having HSDD after formal biopsychosocial assessment.
There is an unmet need for the provision and approval of testosterone treatments specific to women, formulated with the aim of approximating physiological testosterone concentrations for premenopausal women (Expert Opinion).
Where an appropriate approved female testosterone preparation is not available, off-label, prescribing of an approved male formulation is reasonable, provided hormone concentrations are maintained in the physiologic female range (Expert Opinion).
Compounded “bioidentical” testosterone therapy cannot be recommended for the treatment of HSDD because of the lack of evidence for efficacy and safety unless an authorized equivalent preparation is not available (Expert Opinion). In the absence of an available approved product, if a compounded product is needed, the compounding pharmacy should be compliant with the purity of Active Pharmaceutical Ingredients and Good Manufacturing Practice to meet industry standards for quality and safety. Dosing should be limited to achieving testosterone concentrations in the physiologic premenopausal range.
The use of any testosterone preparation that results in supraphysiologic concentrations of testosterone, including pellets and injections, is not recommended (Expert Opinion).
Should a trial of testosterone therapy be given for HSDD, a baseline total testosterone concentration should be measured before commencement, with a repeat level 3–6 weeks after treatment initiation.
Patients should be monitored for their clinical response to treatment and assessed for signs of androgen excess with a serum total testosterone level every 6 months, to screen for overuse (Expert Opinion).
If no benefit is experienced by 6 months, treatment should be ceased

Recommendations regarding other androgenic preparations

Systemic dehydroepiandrosterone is not associated with significant improvement in libido or sexual function in postmenopausal women with normal adrenal function and cannot be recommended for women with HSDD.
In the absence of vulvovaginal atrophy, vaginal dehydroepiandrosterone has not been tested and thus cannot be recommended for the treatment of HSDD (Expert Opinion).

Recommendations regarding the design of future trials of physiologically dosed testosterone (Expert Opinion for all)

More adequately powered, double-blind RCTs, without selection bias and with consistent reporting of standardized outcomes, are needed to comprehensively establish the benefits and risks of testosterone therapy for women.
For studies of testosterone and FSD disorder:
- Relief of the distress associated with sexual dysfunction is a primary aim of FSD treatment.
- Presently, no questionnaire covers all domains of female sexual function such that a combination of domains from different questionnaires should be used.
- Satisfying sexual events should no longer be used as a primary efficacy measure in clinical trials of women with FSD.
- A set of clearly defined core outcomes needs to be established.
- There is a need for an instrument to assess sexual function with the following characteristics: general applicability; not disease-specific; high discriminant validity between women diagnosed with FSD and sexually functional women; validated, to measure FSD per se and as an instrument to screen for and diagnose FSD and demonstrating clinically meaningful response to intervention; cover different domains, with each domain comprising several items; translated and back-translated in a variety of languages, satisfies the most stringent assessment to gain approval by regulatory agencies.
There is a need for adequately powered RCTs of the effects of testosterone on the musculoskeletal health of women with normal bone mass, low bone mass, osteopenia/osteoporosis, and sarcopenia, with outcomes including vertebral and total hip and femoral neck bone mineral density, trabecular bone score, serum biomarkers, fracture risk, body composition, and muscle strength.
There is a need for adequately powered RCTs of the effects of testosterone on cognitive performance.
Studies must be undertaken to establish the longer-term cardiometabolic and breast safety of testosterone therapy for women

There is insufficient evidence to support the use of testosterone to enhance cognitive performance, or to delay cognitive decline, in postmenopausal women.
Available data show no effect of testosterone therapy on general wellbeing.
Testosterone may improve wellbeing in premenopausal women, but data are inconclusive.
Available data do not show an effect of testosterone on depressed mood.

Musculoskeletal effects of testosterone

Few studies have evaluated the musculoskeletal effects of testosterone.
Of the studies that have reported musculoskeletal outcomes, the number of included participants has been small, all participants were taking concurrent estrogen therapy, and no studies have been in women with osteoporosis.
The available data do not support an effect of testosterone treatment on bone mineral density at the spine, total hip, or femoral neck at 12 months.
No statistically significant effect of testosterone administered in physiologic doses has been demonstrated on lean body mass, total body fat, or muscle strength.
There is a need for clinical trials to evaluate the impact of testosterone treatment on musculoskeletal tissues (Expert Opinion).

Testosterone therapy and serious adverse events

Testosterone therapy for postmenopausal women, in doses, that approximate physiological testosterone concentrations for premenopausal women, is not associated with serious adverse events.
Because RCTs of testosterone therapy have excluded women at high cardiometabolic disease risk, and most have included women taking concurrent estrogen therapy, recommendation 10 (a) is not generalizable to a more “at-risk” population (Expert Opinion).
Safety data for testosterone in physiologic doses are not available beyond 24 months of treatment

A full assessment of FSD before commencing testosterone therapy

FSD including HSDD, FSAD, and orgasmic disorder/dysfunction have multiple etiologies including biopsychosocial factors such as neuroendocrine imbalance, physical ill-health or disease, interpersonal difficulties, psychological distress, and sexually repressive cultural or religious values.
Treatments should follow this biopsychosocial model and include pharmacologic options (hormone therapies and other pharmacologic agents), psychotherapy, or multimodal treatments that combine both.

Current testosterone therapy and postmenopausal women

The only evidence-based indication for the use of testosterone in women is for the treatment of postmenopausal women who have been diagnosed as having HSDD after formal biopsychosocial assessment.
There is an unmet need for the provision and approval of testosterone treatments specific to women, formulated with the aim of approximating physiological testosterone concentrations for premenopausal women (Expert Opinion).
Where an appropriate approved female testosterone preparation is not available, off-label, prescribing of an approved male formulation is reasonable, provided hormone concentrations are maintained in the physiologic female range (Expert Opinion).
Compounded “bioidentical” testosterone therapy cannot be recommended for the treatment of HSDD because of the lack of evidence for efficacy and safety unless an authorized equivalent preparation is not available (Expert Opinion). In the absence of an available approved product, if a compounded product is needed, the compounding pharmacy should be compliant with the purity of Active Pharmaceutical Ingredients and Good Manufacturing Practice to meet industry standards for quality and safety. Dosing should be limited to achieving testosterone concentrations in the physiologic premenopausal range.
The use of any testosterone preparation that results in supraphysiologic concentrations of testosterone, including pellets and injections, is not recommended (Expert Opinion).
Should a trial of testosterone therapy be given for HSDD, a baseline total testosterone concentration should be measured before commencement, with a repeat level 3–6 weeks after treatment initiation.
Patients should be monitored for their clinical response to treatment and assessed for signs of androgen excess with a serum total testosterone level every 6 months, to screen for overuse (Expert Opinion).
If no benefit is experienced by 6 months, treatment should be ceased

Recommendations regarding other androgenic preparations

Systemic dehydroepiandrosterone is not associated with significant improvement in libido or sexual function in postmenopausal women with normal adrenal function and cannot be recommended for women with HSDD.
In the absence of vulvovaginal atrophy, vaginal dehydroepiandrosterone has not been tested and thus cannot be recommended for the treatment of HSDD (Expert Opinion).

Recommendations regarding the design of future trials of physiologically dosed testosterone (Expert Opinion for all)

More adequately powered, double-blind RCTs, without selection bias and with consistent reporting of standardized outcomes, are needed to comprehensively establish the benefits and risks of testosterone therapy for women.
For studies of testosterone and FSD disorder:
- Relief of the distress associated with sexual dysfunction is a primary aim of FSD treatment.
- Presently, no questionnaire covers all domains of female sexual function such that a combination of domains from different questionnaires should be used.
- Satisfying sexual events should no longer be used as a primary efficacy measure in clinical trials of women with FSD.
- A set of clearly defined core outcomes needs to be established.
- There is a need for an instrument to assess sexual function with the following characteristics: general applicability; not disease-specific; high discriminant validity between women diagnosed with FSD and sexually functional women; validated, to measure FSD per se and as an instrument to screen for and diagnose FSD and demonstrating clinically meaningful response to intervention; cover different domains, with each domain comprising several items; translated and back-translated in a variety of languages, satisfies the most stringent assessment to gain approval by regulatory agencies.
There is a need for adequately powered RCTs of the effects of testosterone on the musculoskeletal health of women with normal bone mass, low bone mass, osteopenia/osteoporosis, and sarcopenia, with outcomes including vertebral and total hip and femoral neck bone mineral density, trabecular bone score, serum biomarkers, fracture risk, body composition, and muscle strength.
There is a need for adequately powered RCTs of the effects of testosterone on cognitive performance.
Studies must be undertaken to establish the longer-term cardiometabolic and breast safety of testosterone therapy for women

Effects of testosterone on wellbeing, mood, and cognition in postmenopausal women

There is insufficient evidence to support the use of testosterone to enhance cognitive performance, or to delay cognitive decline, in postmenopausal women.
Available data show no effect of testosterone therapy on general wellbeing.
Testosterone may improve wellbeing in premenopausal women, but data are inconclusive.
Available data do not show an effect of testosterone on depressed mood.

Musculoskeletal effects of testosterone

Few studies have evaluated the musculoskeletal effects of testosterone.
Of the studies that have reported musculoskeletal outcomes, the number of included participants has been small, all participants were taking concurrent estrogen therapy, and no studies have been in women with osteoporosis.
The available data do not support an effect of testosterone treatment on bone mineral density at the spine, total hip, or femoral neck at 12 months.
No statistically significant effect of testosterone administered in physiologic doses has been demonstrated on lean body mass, total body fat, or muscle strength.
There is a need for clinical trials to evaluate the impact of testosterone treatment on musculoskeletal tissues (Expert Opinion).

Testosterone therapy and serious adverse events

Testosterone therapy for postmenopausal women, in doses, that approximate physiological testosterone concentrations for premenopausal women, is not associated with serious adverse events.
Because RCTs of testosterone therapy have excluded women at high cardiometabolic disease risk, and most have included women taking concurrent estrogen therapy, recommendation 10 (a) is not generalizable to a more “at-risk” population (Expert Opinion).
Safety data for testosterone in physiologic doses are not available beyond 24 months of treatment

A full assessment of FSD before commencing testosterone therapy

FSD including HSDD, FSAD, and orgasmic disorder/dysfunction have multiple etiologies including biopsychosocial factors such as neuroendocrine imbalance, physical ill-health or disease, interpersonal difficulties, psychological distress, and sexually repressive cultural or religious values.
Treatments should follow this biopsychosocial model and include pharmacologic options (hormone therapies and other pharmacologic agents), psychotherapy, or multimodal treatments that combine both.

Current testosterone therapy and postmenopausal women

The only evidence-based indication for the use of testosterone in women is for the treatment of postmenopausal women who have been diagnosed as having HSDD after formal biopsychosocial assessment.
There is an unmet need for the provision and approval of testosterone treatments specific to women, formulated with the aim of approximating physiological testosterone concentrations for premenopausal women (Expert Opinion).
Where an appropriate approved female testosterone preparation is not available, off-label, prescribing of an approved male formulation is reasonable, provided hormone concentrations are maintained in the physiologic female range (Expert Opinion).
Compounded “bioidentical” testosterone therapy cannot be recommended for the treatment of HSDD because of the lack of evidence for efficacy and safety unless an authorized equivalent preparation is not available (Expert Opinion). In the absence of an available approved product, if a compounded product is needed, the compounding pharmacy should be compliant with the purity of Active Pharmaceutical Ingredients and Good Manufacturing Practice to meet industry standards for quality and safety. Dosing should be limited to achieving testosterone concentrations in the physiologic premenopausal range.
The use of any testosterone preparation that results in supraphysiologic concentrations of testosterone, including pellets and injections, is not recommended (Expert Opinion).
Should a trial of testosterone therapy be given for HSDD, a baseline total testosterone concentration should be measured before commencement, with a repeat level 3–6 weeks after treatment initiation.
Patients should be monitored for their clinical response to treatment and assessed for signs of androgen excess with a serum total testosterone level every 6 months, to screen for overuse (Expert Opinion).
If no benefit is experienced by 6 months, treatment should be ceased

Recommendations regarding other androgenic preparations

Systemic dehydroepiandrosterone is not associated with significant improvement in libido or sexual function in postmenopausal women with normal adrenal function and cannot be recommended for women with HSDD.
In the absence of vulvovaginal atrophy, vaginal dehydroepiandrosterone has not been tested and thus cannot be recommended for the treatment of HSDD (Expert Opinion).

Recommendations regarding the design of future trials of physiologically dosed testosterone (Expert Opinion for all)

More adequately powered, double-blind RCTs, without selection bias and with consistent reporting of standardized outcomes, are needed to comprehensively establish the benefits and risks of testosterone therapy for women.
For studies of testosterone and FSD disorder:
- Relief of the distress associated with sexual dysfunction is a primary aim of FSD treatment.
- Presently, no questionnaire covers all domains of female sexual function such that a combination of domains from different questionnaires should be used.
- Satisfying sexual events should no longer be used as a primary efficacy measure in clinical trials of women with FSD.
- A set of clearly defined core outcomes needs to be established.
- There is a need for an instrument to assess sexual function with the following characteristics: general applicability; not disease-specific; high discriminant validity between women diagnosed with FSD and sexually functional women; validated, to measure FSD per se and as an instrument to screen for and diagnose FSD and demonstrating clinically meaningful response to intervention; cover different domains, with each domain comprising several items; translated and back-translated in a variety of languages, satisfies the most stringent assessment to gain approval by regulatory agencies.
There is a need for adequately powered RCTs of the effects of testosterone on the musculoskeletal health of women with normal bone mass, low bone mass, osteopenia/osteoporosis, and sarcopenia, with outcomes including vertebral and total hip and femoral neck bone mineral density, trabecular bone score, serum biomarkers, fracture risk, body composition, and muscle strength.
There is a need for adequately powered RCTs of the effects of testosterone on cognitive performance.
Studies must be undertaken to establish the longer-term cardiometabolic and breast safety of testosterone therapy for women

Hypoactive sexual desire disorder/dysfunction (HSDD) and female sexual arousal disorder (FSAD) are distinct conditions that should be categorized separately when considering the impact of androgens on their clinical presentation and response to treatment
Although HSDD and FSAD overlap, they have distinct etiologies, risk factors, clinical features, and responses to psychological and biological interventions.
Traditional specifiers (i.e., lifelong vs acquired; generalized vs situational) should be retained and used to further categorize and stratify treatments for HSDD and other female sexual disorders/dysfunctions.
The diagnosis of HSDD in clinical practice should be based on thorough clinical assessment guided by available diagnostic criteria such as the International Society for the Study of Women’s Sexual Health or the International Classification of Diseases, 11th edition (Expert Opinion).

Associations between endogenous androgen concentrations and female sexual function

The associations between endogenous androgen concentrations and sexual function in women remain uncertain because of issues relating to the sensitivity and specificity of androgen assays in some studies and insufficient data.
The physiology of androgens is complex because of their conversion in tissues and possible intracrine metabolism in multiple tissues.
No cutoff blood level can be used for any measured circulating androgen to differentiate women with and without sexual dysfunction.

Effects of testosterone on wellbeing, mood, and cognition in postmenopausal women

There is insufficient evidence to support the use of testosterone to enhance cognitive performance, or to delay cognitive decline, in postmenopausal women.
Available data show no effect of testosterone therapy on general wellbeing.
Testosterone may improve wellbeing in premenopausal women, but data are inconclusive.
Available data do not show an effect of testosterone on depressed mood.

Musculoskeletal effects of testosterone

Few studies have evaluated the musculoskeletal effects of testosterone.
Of the studies that have reported musculoskeletal outcomes, the number of included participants has been small, all participants were taking concurrent estrogen therapy, and no studies have been in women with osteoporosis.
The available data do not support an effect of testosterone treatment on bone mineral density at the spine, total hip, or femoral neck at 12 months.
No statistically significant effect of testosterone administered in physiologic doses has been demonstrated on lean body mass, total body fat, or muscle strength.
There is a need for clinical trials to evaluate the impact of testosterone treatment on musculoskeletal tissues (Expert Opinion).

Testosterone therapy and serious adverse events

Testosterone therapy for postmenopausal women, in doses, that approximate physiological testosterone concentrations for premenopausal women, is not associated with serious adverse events.
Because RCTs of testosterone therapy have excluded women at high cardiometabolic disease risk, and most have included women taking concurrent estrogen therapy, recommendation 10 (a) is not generalizable to a more “at-risk” population (Expert Opinion).
Safety data for testosterone in physiologic doses are not available beyond 24 months of treatment

A full assessment of FSD before commencing testosterone therapy

FSD including HSDD, FSAD, and orgasmic disorder/dysfunction have multiple etiologies including biopsychosocial factors such as neuroendocrine imbalance, physical ill-health or disease, interpersonal difficulties, psychological distress, and sexually repressive cultural or religious values.
Treatments should follow this biopsychosocial model and include pharmacologic options (hormone therapies and other pharmacologic agents), psychotherapy, or multimodal treatments that combine both.

Current testosterone therapy and postmenopausal women

The only evidence-based indication for the use of testosterone in women is for the treatment of postmenopausal women who have been diagnosed as having HSDD after formal biopsychosocial assessment.
There is an unmet need for the provision and approval of testosterone treatments specific to women, formulated with the aim of approximating physiological testosterone concentrations for premenopausal women (Expert Opinion).
Where an appropriate approved female testosterone preparation is not available, off-label, prescribing of an approved male formulation is reasonable, provided hormone concentrations are maintained in the physiologic female range (Expert Opinion).
Compounded “bioidentical” testosterone therapy cannot be recommended for the treatment of HSDD because of the lack of evidence for efficacy and safety unless an authorized equivalent preparation is not available (Expert Opinion). In the absence of an available approved product, if a compounded product is needed, the compounding pharmacy should be compliant with the purity of Active Pharmaceutical Ingredients and Good Manufacturing Practice to meet industry standards for quality and safety. Dosing should be limited to achieving testosterone concentrations in the physiologic premenopausal range.
The use of any testosterone preparation that results in supraphysiologic concentrations of testosterone, including pellets and injections, is not recommended (Expert Opinion).
Should a trial of testosterone therapy be given for HSDD, a baseline total testosterone concentration should be measured before commencement, with a repeat level 3–6 weeks after treatment initiation.
Patients should be monitored for their clinical response to treatment and assessed for signs of androgen excess with a serum total testosterone level every 6 months, to screen for overuse (Expert Opinion).
If no benefit is experienced by 6 months, treatment should be ceased

Recommendations regarding other androgenic preparations

Systemic dehydroepiandrosterone is not associated with significant improvement in libido or sexual function in postmenopausal women with normal adrenal function and cannot be recommended for women with HSDD.
In the absence of vulvovaginal atrophy, vaginal dehydroepiandrosterone has not been tested and thus cannot be recommended for the treatment of HSDD (Expert Opinion).

Recommendations regarding the design of future trials of physiologically dosed testosterone (Expert Opinion for all)

More adequately powered, double-blind RCTs, without selection bias and with consistent reporting of standardized outcomes, are needed to comprehensively establish the benefits and risks of testosterone therapy for women.
For studies of testosterone and FSD disorder:
- Relief of the distress associated with sexual dysfunction is a primary aim of FSD treatment.
- Presently, no questionnaire covers all domains of female sexual function such that a combination of domains from different questionnaires should be used.
- Satisfying sexual events should no longer be used as a primary efficacy measure in clinical trials of women with FSD.
- A set of clearly defined core outcomes needs to be established.
- There is a need for an instrument to assess sexual function with the following characteristics: general applicability; not disease-specific; high discriminant validity between women diagnosed with FSD and sexually functional women; validated, to measure FSD per se and as an instrument to screen for and diagnose FSD and demonstrating clinically meaningful response to intervention; cover different domains, with each domain comprising several items; translated and back-translated in a variety of languages, satisfies the most stringent assessment to gain approval by regulatory agencies.
There is a need for adequately powered RCTs of the effects of testosterone on the musculoskeletal health of women with normal bone mass, low bone mass, osteopenia/osteoporosis, and sarcopenia, with outcomes including vertebral and total hip and femoral neck bone mineral density, trabecular bone score, serum biomarkers, fracture risk, body composition, and muscle strength.
There is a need for adequately powered RCTs of the effects of testosterone on cognitive performance.
Studies must be undertaken to establish the longer-term cardiometabolic and breast safety of testosterone therapy for women

Testosterone may act directly via the androgen receptor/nongenomic androgenic action, or by reduction to the more potent androgen dihydrotestosterone and/or aromatization to estradiol and their metabolites.
Testosterone concentrations decline during the reproductive years.
Testosterone concentrations appear to be maintained in women beyond the age of 65 years, but whether this confers a benefit is yet to be understood.
Total testosterone can be measured with high accuracy and reproducibility using liquid/gas chromatography and tandem mass spectrometry assays.
Direct assays for the measurement of total and free testosterone are highly unreliable in the female range.
Reference laboratories should be “harmonized” with biological standards in coordination with the US Centers for Disease Control and Prevention.
Measurement of testosterone using direct assays in clinical practice is appropriate, if liquid/gas chromatography and tandem mass spectrometry assay is not available, to exclude high baseline concentrations and also to exclude supraphysiological concentrations during treatment (Expert Opinion).
Current research into testosterone physiology and clinical effects should mainly focus on measuring total testosterone as the main biomarker rather than “free” testosterone because evidence that “free” testosterone is the biologically active testosterone fraction is lacking (Expert Opinion).

Terminology for female sexual dysfunction (FSD)

Hypoactive sexual desire disorder/dysfunction (HSDD) and female sexual arousal disorder (FSAD) are distinct conditions that should be categorized separately when considering the impact of androgens on their clinical presentation and response to treatment
Although HSDD and FSAD overlap, they have distinct etiologies, risk factors, clinical features, and responses to psychological and biological interventions.
Traditional specifiers (i.e., lifelong vs acquired; generalized vs situational) should be retained and used to further categorize and stratify treatments for HSDD and other female sexual disorders/dysfunctions.
The diagnosis of HSDD in clinical practice should be based on thorough clinical assessment guided by available diagnostic criteria such as the International Society for the Study of Women’s Sexual Health or the International Classification of Diseases, 11th edition (Expert Opinion).

Associations between endogenous androgen concentrations and female sexual function

The associations between endogenous androgen concentrations and sexual function in women remain uncertain because of issues relating to the sensitivity and specificity of androgen assays in some studies and insufficient data.
The physiology of androgens is complex because of their conversion in tissues and possible intracrine metabolism in multiple tissues.
No cutoff blood level can be used for any measured circulating androgen to differentiate women with and without sexual dysfunction.

Effects of testosterone on wellbeing, mood, and cognition in postmenopausal women

There is insufficient evidence to support the use of testosterone to enhance cognitive performance, or to delay cognitive decline, in postmenopausal women.
Available data show no effect of testosterone therapy on general wellbeing.
Testosterone may improve wellbeing in premenopausal women, but data are inconclusive.
Available data do not show an effect of testosterone on depressed mood.

Musculoskeletal effects of testosterone

Few studies have evaluated the musculoskeletal effects of testosterone.
Of the studies that have reported musculoskeletal outcomes, the number of included participants has been small, all participants were taking concurrent estrogen therapy, and no studies have been in women with osteoporosis.
The available data do not support an effect of testosterone treatment on bone mineral density at the spine, total hip, or femoral neck at 12 months.
No statistically significant effect of testosterone administered in physiologic doses has been demonstrated on lean body mass, total body fat, or muscle strength.
There is a need for clinical trials to evaluate the impact of testosterone treatment on musculoskeletal tissues (Expert Opinion).

Testosterone therapy and serious adverse events

Testosterone therapy for postmenopausal women, in doses, that approximate physiological testosterone concentrations for premenopausal women, is not associated with serious adverse events.
Because RCTs of testosterone therapy have excluded women at high cardiometabolic disease risk, and most have included women taking concurrent estrogen therapy, recommendation 10 (a) is not generalizable to a more “at-risk” population (Expert Opinion).
Safety data for testosterone in physiologic doses are not available beyond 24 months of treatment

A full assessment of FSD before commencing testosterone therapy

FSD including HSDD, FSAD, and orgasmic disorder/dysfunction have multiple etiologies including biopsychosocial factors such as neuroendocrine imbalance, physical ill-health or disease, interpersonal difficulties, psychological distress, and sexually repressive cultural or religious values.
Treatments should follow this biopsychosocial model and include pharmacologic options (hormone therapies and other pharmacologic agents), psychotherapy, or multimodal treatments that combine both.

Current testosterone therapy and postmenopausal women

The only evidence-based indication for the use of testosterone in women is for the treatment of postmenopausal women who have been diagnosed as having HSDD after formal biopsychosocial assessment.
There is an unmet need for the provision and approval of testosterone treatments specific to women, formulated with the aim of approximating physiological testosterone concentrations for premenopausal women (Expert Opinion).
Where an appropriate approved female testosterone preparation is not available, off-label, prescribing of an approved male formulation is reasonable, provided hormone concentrations are maintained in the physiologic female range (Expert Opinion).
Compounded “bioidentical” testosterone therapy cannot be recommended for the treatment of HSDD because of the lack of evidence for efficacy and safety unless an authorized equivalent preparation is not available (Expert Opinion). In the absence of an available approved product, if a compounded product is needed, the compounding pharmacy should be compliant with the purity of Active Pharmaceutical Ingredients and Good Manufacturing Practice to meet industry standards for quality and safety. Dosing should be limited to achieving testosterone concentrations in the physiologic premenopausal range.
The use of any testosterone preparation that results in supraphysiologic concentrations of testosterone, including pellets and injections, is not recommended (Expert Opinion).
Should a trial of testosterone therapy be given for HSDD, a baseline total testosterone concentration should be measured before commencement, with a repeat level 3–6 weeks after treatment initiation.
Patients should be monitored for their clinical response to treatment and assessed for signs of androgen excess with a serum total testosterone level every 6 months, to screen for overuse (Expert Opinion).
If no benefit is experienced by 6 months, treatment should be ceased

Recommendations regarding other androgenic preparations

Systemic dehydroepiandrosterone is not associated with significant improvement in libido or sexual function in postmenopausal women with normal adrenal function and cannot be recommended for women with HSDD.
In the absence of vulvovaginal atrophy, vaginal dehydroepiandrosterone has not been tested and thus cannot be recommended for the treatment of HSDD (Expert Opinion).

Recommendations regarding the design of future trials of physiologically dosed testosterone (Expert Opinion for all)

More adequately powered, double-blind RCTs, without selection bias and with consistent reporting of standardized outcomes, are needed to comprehensively establish the benefits and risks of testosterone therapy for women.
For studies of testosterone and FSD disorder:
- Relief of the distress associated with sexual dysfunction is a primary aim of FSD treatment.
- Presently, no questionnaire covers all domains of female sexual function such that a combination of domains from different questionnaires should be used.
- Satisfying sexual events should no longer be used as a primary efficacy measure in clinical trials of women with FSD.
- A set of clearly defined core outcomes needs to be established.
- There is a need for an instrument to assess sexual function with the following characteristics: general applicability; not disease-specific; high discriminant validity between women diagnosed with FSD and sexually functional women; validated, to measure FSD per se and as an instrument to screen for and diagnose FSD and demonstrating clinically meaningful response to intervention; cover different domains, with each domain comprising several items; translated and back-translated in a variety of languages, satisfies the most stringent assessment to gain approval by regulatory agencies.
There is a need for adequately powered RCTs of the effects of testosterone on the musculoskeletal health of women with normal bone mass, low bone mass, osteopenia/osteoporosis, and sarcopenia, with outcomes including vertebral and total hip and femoral neck bone mineral density, trabecular bone score, serum biomarkers, fracture risk, body composition, and muscle strength.
There is a need for adequately powered RCTs of the effects of testosterone on cognitive performance.
Studies must be undertaken to establish the longer-term cardiometabolic and breast safety of testosterone therapy for women

Testosterone therapy and breast health

Testosterone therapy does not increase mammographic breast density.
Available data suggest that short-term transdermal testosterone therapy does not impact breast cancer risk.

More recommendations

Measurement of testosterone in women

Testosterone may act directly via the androgen receptor/nongenomic androgenic action, or by reduction to the more potent androgen dihydrotestosterone and/or aromatization to estradiol and their metabolites.
Testosterone concentrations decline during the reproductive years.
Testosterone concentrations appear to be maintained in women beyond the age of 65 years, but whether this confers a benefit is yet to be understood.
Total testosterone can be measured with high accuracy and reproducibility using liquid/gas chromatography and tandem mass spectrometry assays.
Direct assays for the measurement of total and free testosterone are highly unreliable in the female range.
Reference laboratories should be “harmonized” with biological standards in coordination with the US Centers for Disease Control and Prevention.
Measurement of testosterone using direct assays in clinical practice is appropriate, if liquid/gas chromatography and tandem mass spectrometry assay is not available, to exclude high baseline concentrations and also to exclude supraphysiological concentrations during treatment (Expert Opinion).
Current research into testosterone physiology and clinical effects should mainly focus on measuring total testosterone as the main biomarker rather than “free” testosterone because evidence that “free” testosterone is the biologically active testosterone fraction is lacking (Expert Opinion).

Terminology for female sexual dysfunction (FSD)

Hypoactive sexual desire disorder/dysfunction (HSDD) and female sexual arousal disorder (FSAD) are distinct conditions that should be categorized separately when considering the impact of androgens on their clinical presentation and response to treatment
Although HSDD and FSAD overlap, they have distinct etiologies, risk factors, clinical features, and responses to psychological and biological interventions.
Traditional specifiers (i.e., lifelong vs acquired; generalized vs situational) should be retained and used to further categorize and stratify treatments for HSDD and other female sexual disorders/dysfunctions.
The diagnosis of HSDD in clinical practice should be based on thorough clinical assessment guided by available diagnostic criteria such as the International Society for the Study of Women’s Sexual Health or the International Classification of Diseases, 11th edition (Expert Opinion).

Associations between endogenous androgen concentrations and female sexual function

The associations between endogenous androgen concentrations and sexual function in women remain uncertain because of issues relating to the sensitivity and specificity of androgen assays in some studies and insufficient data.
The physiology of androgens is complex because of their conversion in tissues and possible intracrine metabolism in multiple tissues.
No cutoff blood level can be used for any measured circulating androgen to differentiate women with and without sexual dysfunction.

Effects of testosterone on wellbeing, mood, and cognition in postmenopausal women

There is insufficient evidence to support the use of testosterone to enhance cognitive performance, or to delay cognitive decline, in postmenopausal women.
Available data show no effect of testosterone therapy on general wellbeing.
Testosterone may improve wellbeing in premenopausal women, but data are inconclusive.
Available data do not show an effect of testosterone on depressed mood.

Musculoskeletal effects of testosterone

Few studies have evaluated the musculoskeletal effects of testosterone.
Of the studies that have reported musculoskeletal outcomes, the number of included participants has been small, all participants were taking concurrent estrogen therapy, and no studies have been in women with osteoporosis.
The available data do not support an effect of testosterone treatment on bone mineral density at the spine, total hip, or femoral neck at 12 months.
No statistically significant effect of testosterone administered in physiologic doses has been demonstrated on lean body mass, total body fat, or muscle strength.
There is a need for clinical trials to evaluate the impact of testosterone treatment on musculoskeletal tissues (Expert Opinion).

Testosterone therapy and serious adverse events

Testosterone therapy for postmenopausal women, in doses, that approximate physiological testosterone concentrations for premenopausal women, is not associated with serious adverse events.
Because RCTs of testosterone therapy have excluded women at high cardiometabolic disease risk, and most have included women taking concurrent estrogen therapy, recommendation 10 (a) is not generalizable to a more “at-risk” population (Expert Opinion).
Safety data for testosterone in physiologic doses are not available beyond 24 months of treatment

A full assessment of FSD before commencing testosterone therapy

FSD including HSDD, FSAD, and orgasmic disorder/dysfunction have multiple etiologies including biopsychosocial factors such as neuroendocrine imbalance, physical ill-health or disease, interpersonal difficulties, psychological distress, and sexually repressive cultural or religious values.
Treatments should follow this biopsychosocial model and include pharmacologic options (hormone therapies and other pharmacologic agents), psychotherapy, or multimodal treatments that combine both.

Current testosterone therapy and postmenopausal women

The only evidence-based indication for the use of testosterone in women is for the treatment of postmenopausal women who have been diagnosed as having HSDD after formal biopsychosocial assessment.
There is an unmet need for the provision and approval of testosterone treatments specific to women, formulated with the aim of approximating physiological testosterone concentrations for premenopausal women (Expert Opinion).
Where an appropriate approved female testosterone preparation is not available, off-label, prescribing of an approved male formulation is reasonable, provided hormone concentrations are maintained in the physiologic female range (Expert Opinion).
Compounded “bioidentical” testosterone therapy cannot be recommended for the treatment of HSDD because of the lack of evidence for efficacy and safety unless an authorized equivalent preparation is not available (Expert Opinion). In the absence of an available approved product, if a compounded product is needed, the compounding pharmacy should be compliant with the purity of Active Pharmaceutical Ingredients and Good Manufacturing Practice to meet industry standards for quality and safety. Dosing should be limited to achieving testosterone concentrations in the physiologic premenopausal range.
The use of any testosterone preparation that results in supraphysiologic concentrations of testosterone, including pellets and injections, is not recommended (Expert Opinion).
Should a trial of testosterone therapy be given for HSDD, a baseline total testosterone concentration should be measured before commencement, with a repeat level 3–6 weeks after treatment initiation.
Patients should be monitored for their clinical response to treatment and assessed for signs of androgen excess with a serum total testosterone level every 6 months, to screen for overuse (Expert Opinion).
If no benefit is experienced by 6 months, treatment should be ceased

Recommendations regarding other androgenic preparations

Systemic dehydroepiandrosterone is not associated with significant improvement in libido or sexual function in postmenopausal women with normal adrenal function and cannot be recommended for women with HSDD.
In the absence of vulvovaginal atrophy, vaginal dehydroepiandrosterone has not been tested and thus cannot be recommended for the treatment of HSDD (Expert Opinion).

Recommendations regarding the design of future trials of physiologically dosed testosterone (Expert Opinion for all)

More adequately powered, double-blind RCTs, without selection bias and with consistent reporting of standardized outcomes, are needed to comprehensively establish the benefits and risks of testosterone therapy for women.
For studies of testosterone and FSD disorder:
- Relief of the distress associated with sexual dysfunction is a primary aim of FSD treatment.
- Presently, no questionnaire covers all domains of female sexual function such that a combination of domains from different questionnaires should be used.
- Satisfying sexual events should no longer be used as a primary efficacy measure in clinical trials of women with FSD.
- A set of clearly defined core outcomes needs to be established.
- There is a need for an instrument to assess sexual function with the following characteristics: general applicability; not disease-specific; high discriminant validity between women diagnosed with FSD and sexually functional women; validated, to measure FSD per se and as an instrument to screen for and diagnose FSD and demonstrating clinically meaningful response to intervention; cover different domains, with each domain comprising several items; translated and back-translated in a variety of languages, satisfies the most stringent assessment to gain approval by regulatory agencies.
There is a need for adequately powered RCTs of the effects of testosterone on the musculoskeletal health of women with normal bone mass, low bone mass, osteopenia/osteoporosis, and sarcopenia, with outcomes including vertebral and total hip and femoral neck bone mineral density, trabecular bone score, serum biomarkers, fracture risk, body composition, and muscle strength.
There is a need for adequately powered RCTs of the effects of testosterone on cognitive performance.
Studies must be undertaken to establish the longer-term cardiometabolic and breast safety of testosterone therapy for women

Testosterone therapy and cardiovascular health

Oral testosterone therapy is associated with adverse lipid profiles with negative effects on high-density lipoprotein-cholesterol and low-density lipoprotein-cholesterol levels and is not recommended.
Studies of non-oral testosterone therapies (percutaneous and injectable), in doses that approximate physiological testosterone concentrations for premenopausal women have shown no statistically significant adverse effects on lipid profiles over the short term.
Testosterone therapy has not been associated with increases in blood pressure, blood glucose, or HbA1c levels.
A nonsignificant trend for an increased risk of deep venous thrombosis has been seen with testosterone therapy; however, the role of concurrent estrogen therapy in possible venous thrombosis risk cannot be excluded.

Testosterone therapy and breast health

Testosterone therapy does not increase mammographic breast density.
Available data suggest that short-term transdermal testosterone therapy does not impact breast cancer risk.

More recommendations

Measurement of testosterone in women

Testosterone may act directly via the androgen receptor/nongenomic androgenic action, or by reduction to the more potent androgen dihydrotestosterone and/or aromatization to estradiol and their metabolites.
Testosterone concentrations decline during the reproductive years.
Testosterone concentrations appear to be maintained in women beyond the age of 65 years, but whether this confers a benefit is yet to be understood.
Total testosterone can be measured with high accuracy and reproducibility using liquid/gas chromatography and tandem mass spectrometry assays.
Direct assays for the measurement of total and free testosterone are highly unreliable in the female range.
Reference laboratories should be “harmonized” with biological standards in coordination with the US Centers for Disease Control and Prevention.
Measurement of testosterone using direct assays in clinical practice is appropriate, if liquid/gas chromatography and tandem mass spectrometry assay is not available, to exclude high baseline concentrations and also to exclude supraphysiological concentrations during treatment (Expert Opinion).
Current research into testosterone physiology and clinical effects should mainly focus on measuring total testosterone as the main biomarker rather than “free” testosterone because evidence that “free” testosterone is the biologically active testosterone fraction is lacking (Expert Opinion).

Terminology for female sexual dysfunction (FSD)

Hypoactive sexual desire disorder/dysfunction (HSDD) and female sexual arousal disorder (FSAD) are distinct conditions that should be categorized separately when considering the impact of androgens on their clinical presentation and response to treatment
Although HSDD and FSAD overlap, they have distinct etiologies, risk factors, clinical features, and responses to psychological and biological interventions.
Traditional specifiers (i.e., lifelong vs acquired; generalized vs situational) should be retained and used to further categorize and stratify treatments for HSDD and other female sexual disorders/dysfunctions.
The diagnosis of HSDD in clinical practice should be based on thorough clinical assessment guided by available diagnostic criteria such as the International Society for the Study of Women’s Sexual Health or the International Classification of Diseases, 11th edition (Expert Opinion).

Associations between endogenous androgen concentrations and female sexual function

The associations between endogenous androgen concentrations and sexual function in women remain uncertain because of issues relating to the sensitivity and specificity of androgen assays in some studies and insufficient data.
The physiology of androgens is complex because of their conversion in tissues and possible intracrine metabolism in multiple tissues.
No cutoff blood level can be used for any measured circulating androgen to differentiate women with and without sexual dysfunction.

Effects of testosterone on wellbeing, mood, and cognition in postmenopausal women

There is insufficient evidence to support the use of testosterone to enhance cognitive performance, or to delay cognitive decline, in postmenopausal women.
Available data show no effect of testosterone therapy on general wellbeing.
Testosterone may improve wellbeing in premenopausal women, but data are inconclusive.
Available data do not show an effect of testosterone on depressed mood.

Musculoskeletal effects of testosterone

Few studies have evaluated the musculoskeletal effects of testosterone.
Of the studies that have reported musculoskeletal outcomes, the number of included participants has been small, all participants were taking concurrent estrogen therapy, and no studies have been in women with osteoporosis.
The available data do not support an effect of testosterone treatment on bone mineral density at the spine, total hip, or femoral neck at 12 months.
No statistically significant effect of testosterone administered in physiologic doses has been demonstrated on lean body mass, total body fat, or muscle strength.
There is a need for clinical trials to evaluate the impact of testosterone treatment on musculoskeletal tissues (Expert Opinion).

Testosterone therapy and serious adverse events

Testosterone therapy for postmenopausal women, in doses, that approximate physiological testosterone concentrations for premenopausal women, is not associated with serious adverse events.
Because RCTs of testosterone therapy have excluded women at high cardiometabolic disease risk, and most have included women taking concurrent estrogen therapy, recommendation 10 (a) is not generalizable to a more “at-risk” population (Expert Opinion).
Safety data for testosterone in physiologic doses are not available beyond 24 months of treatment

A full assessment of FSD before commencing testosterone therapy

FSD including HSDD, FSAD, and orgasmic disorder/dysfunction have multiple etiologies including biopsychosocial factors such as neuroendocrine imbalance, physical ill-health or disease, interpersonal difficulties, psychological distress, and sexually repressive cultural or religious values.
Treatments should follow this biopsychosocial model and include pharmacologic options (hormone therapies and other pharmacologic agents), psychotherapy, or multimodal treatments that combine both.

Current testosterone therapy and postmenopausal women

The only evidence-based indication for the use of testosterone in women is for the treatment of postmenopausal women who have been diagnosed as having HSDD after formal biopsychosocial assessment.
There is an unmet need for the provision and approval of testosterone treatments specific to women, formulated with the aim of approximating physiological testosterone concentrations for premenopausal women (Expert Opinion).
Where an appropriate approved female testosterone preparation is not available, off-label, prescribing of an approved male formulation is reasonable, provided hormone concentrations are maintained in the physiologic female range (Expert Opinion).
Compounded “bioidentical” testosterone therapy cannot be recommended for the treatment of HSDD because of the lack of evidence for efficacy and safety unless an authorized equivalent preparation is not available (Expert Opinion). In the absence of an available approved product, if a compounded product is needed, the compounding pharmacy should be compliant with the purity of Active Pharmaceutical Ingredients and Good Manufacturing Practice to meet industry standards for quality and safety. Dosing should be limited to achieving testosterone concentrations in the physiologic premenopausal range.
The use of any testosterone preparation that results in supraphysiologic concentrations of testosterone, including pellets and injections, is not recommended (Expert Opinion).
Should a trial of testosterone therapy be given for HSDD, a baseline total testosterone concentration should be measured before commencement, with a repeat level 3–6 weeks after treatment initiation.
Patients should be monitored for their clinical response to treatment and assessed for signs of androgen excess with a serum total testosterone level every 6 months, to screen for overuse (Expert Opinion).
If no benefit is experienced by 6 months, treatment should be ceased

Recommendations regarding other androgenic preparations

Systemic dehydroepiandrosterone is not associated with significant improvement in libido or sexual function in postmenopausal women with normal adrenal function and cannot be recommended for women with HSDD.
In the absence of vulvovaginal atrophy, vaginal dehydroepiandrosterone has not been tested and thus cannot be recommended for the treatment of HSDD (Expert Opinion).

Recommendations regarding the design of future trials of physiologically dosed testosterone (Expert Opinion for all)

More adequately powered, double-blind RCTs, without selection bias and with consistent reporting of standardized outcomes, are needed to comprehensively establish the benefits and risks of testosterone therapy for women.
For studies of testosterone and FSD disorder:
- Relief of the distress associated with sexual dysfunction is a primary aim of FSD treatment.
- Presently, no questionnaire covers all domains of female sexual function such that a combination of domains from different questionnaires should be used.
- Satisfying sexual events should no longer be used as a primary efficacy measure in clinical trials of women with FSD.
- A set of clearly defined core outcomes needs to be established.
- There is a need for an instrument to assess sexual function with the following characteristics: general applicability; not disease-specific; high discriminant validity between women diagnosed with FSD and sexually functional women; validated, to measure FSD per se and as an instrument to screen for and diagnose FSD and demonstrating clinically meaningful response to intervention; cover different domains, with each domain comprising several items; translated and back-translated in a variety of languages, satisfies the most stringent assessment to gain approval by regulatory agencies.
There is a need for adequately powered RCTs of the effects of testosterone on the musculoskeletal health of women with normal bone mass, low bone mass, osteopenia/osteoporosis, and sarcopenia, with outcomes including vertebral and total hip and femoral neck bone mineral density, trabecular bone score, serum biomarkers, fracture risk, body composition, and muscle strength.
There is a need for adequately powered RCTs of the effects of testosterone on cognitive performance.
Studies must be undertaken to establish the longer-term cardiometabolic and breast safety of testosterone therapy for women

Possible androgenic side effects of testosterone therapy

Systemic testosterone therapy for postmenopausal women, in doses, that approximate physiological testosterone concentrations for premenopausal women, is associated with mild increases in acne and body/facial hair growth in some women, but not with alopecia, clitoromegaly, or voice change.

Testosterone therapy and cardiovascular health

Oral testosterone therapy is associated with adverse lipid profiles with negative effects on high-density lipoprotein-cholesterol and low-density lipoprotein-cholesterol levels and is not recommended.
Studies of non-oral testosterone therapies (percutaneous and injectable), in doses that approximate physiological testosterone concentrations for premenopausal women have shown no statistically significant adverse effects on lipid profiles over the short term.
Testosterone therapy has not been associated with increases in blood pressure, blood glucose, or HbA1c levels.
A nonsignificant trend for an increased risk of deep venous thrombosis has been seen with testosterone therapy; however, the role of concurrent estrogen therapy in possible venous thrombosis risk cannot be excluded.

Testosterone therapy and breast health

Testosterone therapy does not increase mammographic breast density.
Available data suggest that short-term transdermal testosterone therapy does not impact breast cancer risk.

More recommendations

Measurement of testosterone in women

Testosterone may act directly via the androgen receptor/nongenomic androgenic action, or by reduction to the more potent androgen dihydrotestosterone and/or aromatization to estradiol and their metabolites.
Testosterone concentrations decline during the reproductive years.
Testosterone concentrations appear to be maintained in women beyond the age of 65 years, but whether this confers a benefit is yet to be understood.
Total testosterone can be measured with high accuracy and reproducibility using liquid/gas chromatography and tandem mass spectrometry assays.
Direct assays for the measurement of total and free testosterone are highly unreliable in the female range.
Reference laboratories should be “harmonized” with biological standards in coordination with the US Centers for Disease Control and Prevention.
Measurement of testosterone using direct assays in clinical practice is appropriate, if liquid/gas chromatography and tandem mass spectrometry assay is not available, to exclude high baseline concentrations and also to exclude supraphysiological concentrations during treatment (Expert Opinion).
Current research into testosterone physiology and clinical effects should mainly focus on measuring total testosterone as the main biomarker rather than “free” testosterone because evidence that “free” testosterone is the biologically active testosterone fraction is lacking (Expert Opinion).

Terminology for female sexual dysfunction (FSD)

Hypoactive sexual desire disorder/dysfunction (HSDD) and female sexual arousal disorder (FSAD) are distinct conditions that should be categorized separately when considering the impact of androgens on their clinical presentation and response to treatment
Although HSDD and FSAD overlap, they have distinct etiologies, risk factors, clinical features, and responses to psychological and biological interventions.
Traditional specifiers (i.e., lifelong vs acquired; generalized vs situational) should be retained and used to further categorize and stratify treatments for HSDD and other female sexual disorders/dysfunctions.
The diagnosis of HSDD in clinical practice should be based on thorough clinical assessment guided by available diagnostic criteria such as the International Society for the Study of Women’s Sexual Health or the International Classification of Diseases, 11th edition (Expert Opinion).

Associations between endogenous androgen concentrations and female sexual function

The associations between endogenous androgen concentrations and sexual function in women remain uncertain because of issues relating to the sensitivity and specificity of androgen assays in some studies and insufficient data.
The physiology of androgens is complex because of their conversion in tissues and possible intracrine metabolism in multiple tissues.
No cutoff blood level can be used for any measured circulating androgen to differentiate women with and without sexual dysfunction.

Effects of testosterone on wellbeing, mood, and cognition in postmenopausal women

There is insufficient evidence to support the use of testosterone to enhance cognitive performance, or to delay cognitive decline, in postmenopausal women.
Available data show no effect of testosterone therapy on general wellbeing.
Testosterone may improve wellbeing in premenopausal women, but data are inconclusive.
Available data do not show an effect of testosterone on depressed mood.

Musculoskeletal effects of testosterone

Few studies have evaluated the musculoskeletal effects of testosterone.
Of the studies that have reported musculoskeletal outcomes, the number of included participants has been small, all participants were taking concurrent estrogen therapy, and no studies have been in women with osteoporosis.
The available data do not support an effect of testosterone treatment on bone mineral density at the spine, total hip, or femoral neck at 12 months.
No statistically significant effect of testosterone administered in physiologic doses has been demonstrated on lean body mass, total body fat, or muscle strength.
There is a need for clinical trials to evaluate the impact of testosterone treatment on musculoskeletal tissues (Expert Opinion).

Testosterone therapy and serious adverse events

Testosterone therapy for postmenopausal women, in doses, that approximate physiological testosterone concentrations for premenopausal women, is not associated with serious adverse events.
Because RCTs of testosterone therapy have excluded women at high cardiometabolic disease risk, and most have included women taking concurrent estrogen therapy, recommendation 10 (a) is not generalizable to a more “at-risk” population (Expert Opinion).
Safety data for testosterone in physiologic doses are not available beyond 24 months of treatment

A full assessment of FSD before commencing testosterone therapy

FSD including HSDD, FSAD, and orgasmic disorder/dysfunction have multiple etiologies including biopsychosocial factors such as neuroendocrine imbalance, physical ill-health or disease, interpersonal difficulties, psychological distress, and sexually repressive cultural or religious values.
Treatments should follow this biopsychosocial model and include pharmacologic options (hormone therapies and other pharmacologic agents), psychotherapy, or multimodal treatments that combine both.

Current testosterone therapy and postmenopausal women

The only evidence-based indication for the use of testosterone in women is for the treatment of postmenopausal women who have been diagnosed as having HSDD after formal biopsychosocial assessment.
There is an unmet need for the provision and approval of testosterone treatments specific to women, formulated with the aim of approximating physiological testosterone concentrations for premenopausal women (Expert Opinion).
Where an appropriate approved female testosterone preparation is not available, off-label, prescribing of an approved male formulation is reasonable, provided hormone concentrations are maintained in the physiologic female range (Expert Opinion).
Compounded “bioidentical” testosterone therapy cannot be recommended for the treatment of HSDD because of the lack of evidence for efficacy and safety unless an authorized equivalent preparation is not available (Expert Opinion). In the absence of an available approved product, if a compounded product is needed, the compounding pharmacy should be compliant with the purity of Active Pharmaceutical Ingredients and Good Manufacturing Practice to meet industry standards for quality and safety. Dosing should be limited to achieving testosterone concentrations in the physiologic premenopausal range.
The use of any testosterone preparation that results in supraphysiologic concentrations of testosterone, including pellets and injections, is not recommended (Expert Opinion).
Should a trial of testosterone therapy be given for HSDD, a baseline total testosterone concentration should be measured before commencement, with a repeat level 3–6 weeks after treatment initiation.
Patients should be monitored for their clinical response to treatment and assessed for signs of androgen excess with a serum total testosterone level every 6 months, to screen for overuse (Expert Opinion).
If no benefit is experienced by 6 months, treatment should be ceased

Recommendations regarding other androgenic preparations

Systemic dehydroepiandrosterone is not associated with significant improvement in libido or sexual function in postmenopausal women with normal adrenal function and cannot be recommended for women with HSDD.
In the absence of vulvovaginal atrophy, vaginal dehydroepiandrosterone has not been tested and thus cannot be recommended for the treatment of HSDD (Expert Opinion).

Recommendations regarding the design of future trials of physiologically dosed testosterone (Expert Opinion for all)

More adequately powered, double-blind RCTs, without selection bias and with consistent reporting of standardized outcomes, are needed to comprehensively establish the benefits and risks of testosterone therapy for women.
For studies of testosterone and FSD disorder:
- Relief of the distress associated with sexual dysfunction is a primary aim of FSD treatment.
- Presently, no questionnaire covers all domains of female sexual function such that a combination of domains from different questionnaires should be used.
- Satisfying sexual events should no longer be used as a primary efficacy measure in clinical trials of women with FSD.
- A set of clearly defined core outcomes needs to be established.
- There is a need for an instrument to assess sexual function with the following characteristics: general applicability; not disease-specific; high discriminant validity between women diagnosed with FSD and sexually functional women; validated, to measure FSD per se and as an instrument to screen for and diagnose FSD and demonstrating clinically meaningful response to intervention; cover different domains, with each domain comprising several items; translated and back-translated in a variety of languages, satisfies the most stringent assessment to gain approval by regulatory agencies.
There is a need for adequately powered RCTs of the effects of testosterone on the musculoskeletal health of women with normal bone mass, low bone mass, osteopenia/osteoporosis, and sarcopenia, with outcomes including vertebral and total hip and femoral neck bone mineral density, trabecular bone score, serum biomarkers, fracture risk, body composition, and muscle strength.
There is a need for adequately powered RCTs of the effects of testosterone on cognitive performance.
Studies must be undertaken to establish the longer-term cardiometabolic and breast safety of testosterone therapy for women