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Introduction

Testosterone is a normal female hormone that exerts important physiological effects in multiple tissues. It plays a vital role in female fertility, specifically in supporting ovarian oocyte development, as well as in other tissues throughout the body.

Testosterone has been prescribed for women with low libido since the 1940’s.(1) Clinical trials of over recent years have consistently shown testosterone therapy can be effective for the treatment of postmenopausal HSDD.(2) Based on the cumulative data from these studies,(3) postmenopausal HSDD is presently the only evidence-based indication for testosterone supplementation for women. The global consensus is that, where possible, testosterone therapy for women should be by a female-specific formulation.(4) In Australia, a female-specific transdermal testosterone formulation was approved by the Therapeutic Goods Administration (TGA) for postmenopausal HSDD in 2020,5 with subsequent approval in several other countries. The global consensus also concluded that further research is needed before presently testosterone be prescribed for the treatment of any other symptoms or medical condition, or for any disease prevention.(4)

Testosterone physiology overview

Testosterone physiology in women is complex and is still poorly understood. During the premenopausal years testosterone is primarily secreted by the ovaries, and made in non-ovarian tissues from the ovarian and adrenal precursors, dehydroepiandrosterone (DHEA) and androstenedione (A4), and adrenally derived DHEA-sulphate. The adrenal glands secrete very little testosterone directly into the circulation.(6) After menopause the primary source of testosterone is from non-ovarian production. Large studies have consistently shown that testosterone blood levels decline in women from the age of about 20 years,(7-10) do not change at natural menopause,7,9 but steadily decline until the age of about 60 years,(7,9,10) after which levels appear to gradually, slightly increase.(7,9-11)

As much of the testosterone made in peripheral tissues acts within these tissues,12 blood testosterone concentrations are spill-over from peripheral production and correlate weakly, or not at all, with clinical variables in healthy women. In premenopausal women, testosterone blood concentrations have been weakly positively associated with orgasm and sexual self-image,13 and DHEA/DHEAS and A4 with sexual desire,(13,14) but no blood cut-off level of these hormones distinguishes women with these symptoms from those without. Hence, there is no blood testosterone concentration below which a woman can be classified as having testosterone deficiency.

Identifying HSDD

Sexual difficulties are the subjective experience of symptoms whereas “sexual dysfunction” indicates the symptom causes substantial concern to the affected person. While the understanding of female sexual dysfunction (FSD) is primarily informed by research involving cis-gender women, much of what is known is applicable to transgender women. There is no normative standard by which to assess FSD, which also has no age limit, and people do not need to be partnered to be negatively impacted by FSD.

The most recent classification of FSD has been provided by the 11th International Classification of Disease (ICD-11).(15) Each of the described dysfunctions, namely desire dysfunction, arousal dysfunction and anorgasmia, are not mutually exclusive, and may be life-long or acquired, as well as generalised or situation specific.

The ICD-11 definition of HSDD, provided is not gender specific, but defines HSDD as,
the absence or marked reduction in desire or motivation to engage in sexual activity as manifested by any of the following:

1. reduced or absent spontaneous desire (sexual thoughts or fantasies);
2. reduced or absent responsive desire to erotic cues and stimulation; or
3. inability to sustain desire or interest in sexual activity once initiated.

The pattern of diminished or absent spontaneous or responsive desire or inability to sustain desire / interest in sexual activity has occurred, episodically or persistently over a period at least several months, and is associated with clinically significant distress.

Unlike older definitions of HSDD, the ICD-11 does not require symptoms to have been present for a specific number of months but rather be “episodic or persistent over a period at least several months”. The ICD-11 recognises an array of factors might contribute to HSDD. It also does not specify HSDD as a diagnosis of exclusion which allows affected women to be treated in the context of having contributing factors identified, for example diabetes or depression. Nonetheless, the clinical assessment of women presenting with loss of sexual desire/ responsiveness that is of concern to them should include the identification of potentially modifiable contributing factors, such as relationship issues, current or prior physical, sexual or emotional abuse, fear, anxiety poor body image, and untreated menopausal symptom. Dyspareunia not due to estrogen insufficiency, generally requires further gynaecological evaluation. In screening women for HSDD it is important to establish whether, in the past, their level of sexual desire/responsiveness was good and satisfying, whether there has been a decrease in their level of sexual desire or responsiveness, and if yes, whether this bothers them, and whether they would like to look into this further in terms of treatment. Life-long lack of sexual desire or interest is unlikely to be responsive to pharmacotherapy.

The estimated prevalences of HSDD amongst premenopausal women and perimenopausal women, aged 40 years or older, are 9.1% and 18.8% respectively, with no meaningful increase in prevalence amongst postmenopausal women up to the age of 69 years.(16) Other independent risk factors for HSDD include being married or de facto, having vaginal dryness, having moderate-severe depressive symptoms, and using an anti-depressant or anxiolytic medication.(16,17)

Evidence for efficacy of testosterone for HSDD

Clinical trials have consistently demonstrated benefits of testosterone therapy on several domains of sexual function for postmenopausal women with low sexual desire causing substantial personal concern. A systematic review and meta-analysis found that testosterone therapy, at doses that restore blood testosterone levels to approximately the levels seen in premenopausal women, improves desire, arousal, orgasm, and sexual satisfaction, and reduces sexually-related distress, in postmenopausal women with HSDD.(3) The global consensus task force that evaluated the prescribing of testosterone for women concluded in 2019 that there was insufficient evidence to support the use of testosterone therapy for premenopausal sexual dysfunction, or for the use of isolated arousal disorder or anorgasmia.(2) There have been no studies since that would likely change these recommendations.

Large studies of testosterone for HSDD that imbedded wellbeing and menopausal symptom questionnaires in their design found no benefit of testosterone, compared with placebo, on psychological and general wellbeing or menopausal symptoms.(18,19) Other studies have found no evidence of improvement in depressive symptoms with testosterone in women with known depression.(20,21) A hallmark of all the studies of testosterone reporting the aforementioned outcomes include the very large placebo effect.

Studies of the effects of testosterone on bone, muscle and cognition have generated inconsistent findings, reflecting the heterogeneity in their designs, and having mostly been too small and of too short durations too provide conclusive data.(3)

Consequently, there is insufficient evidence to support the prescribing of testosterone for low mood, fatigue, brain fog, muscle weakness, or to prevent or treat bone loss or sarcopenia. Nonetheless these benefits, which remain unsubstantiated, are being widely promoted on social media and via the internet.

Measuring testosterone in women

The mainstay of measurement of testosterone is with high through-put immunoassays. These are adequate to evaluate testosterone in men, and to identify testosterone excess in women. However, immunoassays lack precision to evaluate testosterone blood levels in the healthy female reference range, or for research. Liquid chromatography with tandem mass spectrometry (LC-MS/MS) is considered the gold standard for measurement of testosterone in women, and is becoming increasingly available. While LC-MS/MS is essential for research studies, most immunoassays are adequate for their main uses in women:

1. To investigate women with clinical androgen excess
2. Before commencing testosterone therapy, primarily to identify women with an unexpectedly high baseline testosterone level
3. To monitor for biochemical excess in women receiving testosterone therapy

Measurement of sex hormone binding globulin (SHBG) is essential to interpret testosterone blood levels. SHBG binds about 66% of testosterone in the circulation. Women with low SHBG tend to have lower testosterone blood levels and will more likely clear a given dose of testosterone more rapidly from their blood stream. It may even appear as though they are not even absorbing the treatment effectively. Conversely, women with very high SHBG levels, will tend to have a higher blood testosterone concentration, for a given dose of testosterone, and thus may be incorrectly assessed as being over treated. In both instances the mainstay of management is by clinical assessment.

Measurement of “free testosterone” is not of additional value as free testosterone is not measured, but calculated by various equations.(22) These equations were developed before the binding dynamics of testosterone to both SHGB and albumin were well understood. The accuracy of calculated free testosterone also depends on the precise measurement of testosterone, which immunoassay does not provide.(22) Additionally, calculated free testosterone provides poor estimations when SHBG is either very high or very low. The free androgen index, reported by some laboratories, is even less accurate and should not be used.

Prescribing testosterone for women

Testosterone can be considered for postmenopausal women with HSDD after modifiable components have been identified and appropriately addressed. Pretreatment total testosterone should be measured to identify women with an unexpectedly high testosterone who may not be candidates for treatment, and SHBG to further guide treatment; women with a high SHBG level may be less responsive to testosterone therapy(2,23)

Oral testosterone preparations have adverse effects on lipid profiles and should not be prescribed.(3) Where available a regulator approved non-oral testosterone for women should be used. A 1% testosterone cream for women (AndroFeme1) has been approved in several countries for postmenopausal women with HSDD.

• The commencement dose of the TGA-approved AndroFeme1, is 0.5 ml (5 mg) as a cream which is applied to the upper outer thigh or buttock daily. Patients should be advised to wash their hands after each application to avoid transfer to children, other women or pets.
• The first on-treatment testosterone level should ideally be performed 3 weeks after commencing treatment, or any change to dose, in order to ensure overuse is identified before unwanted androgenic side effects might emerge. A testosterone concentration more than 50% above the upper limit of the premenopausal reference range for the given pathology laboratory signals overuse and a need for dose reduction after reviewing application procedures which might have caused an artifactually high level.
• Patients should be advised that a treatment effect may not emerged for 4 to 6 weeks. Therefore, it is recommended patients be re-assessed after 12 weeks, for their treatment response and to check for any androgenic side effects.
• The maximum recommended dose of AndroFeme 1 is 1.0 ml (10 mg) daily
• If no clinically meaningful improvement has occurred by six months of continuous treatment, it should be ceased.
• Women who continue therapy should have a 6-montly check of their testosterone and SHBG, and clinical review. (2)

With the availability of a female-specific option, the prescription of male testosterone gels cannot be justified. The risk of inadvertent overuse with male formulations is substantial due to the inaccuracy of measuring the small amount of a male gel needed for a woman. Also, the dosing of male gel preparations is not equivalent to AndroFeme1, as the male gels have skin penetration enhancers. So a 5 mg dose of male gel will result in higher blood levels than 5mg of AndroFeme1. Compounded testosterone preparations are not recommended as they lack evidence for their absorption, safety and effectiveness.2

Who should not be prescribed testosterone therapy

Women with clinical androgen excess (e.g. acne, hirsutism or androgenic alopecia) or receiving anti-androgen therapy should not be treated with testosterone. Testosterone should not be co-prescribed with tibolone, a synthetic steroid with oestrogenic, progestogenic and androgenic effects. The safety of testosterone for women with a history of breast cancer is unknown and requires further research. AndroFeme1 is contra-indicated in people with tree nut allergy as this preparation contains almond oil.

Side effects and safety

Doses that result in blood levels that approximate the premenopausal reference range may occasionally cause acne, increased hair growth, and weight gain.(3) Female-appropriate doses of non-oral testosterone do not adversely impact glucose, insulin, haemoglobin or blood pressure.(3) Alopecia or virilising features, such as voice deepening and clitoromegaly are signs of overtreatment. Judicious dosing with regulator-approved testosterone and biochemical and clinical monitoring minimises the likelihood of this occurring.

References

1. Greenblatt RB. Testosterone proprionate pellet implanation in gyneic disorders. JAMA 1943;121(1):17-24.
2. Davis SR, Baber R, Panay N, et al. Global Consensus Position Statement on the Use of Testosterone Therapy for Women. Climacteric 2019;22(5):429-434. DOI: 10.1080/13697137.2019.1637079.
3. Islam RM, Bell RJ, Green S, Page MJ, Davis SR. Safety and efficacy of testosterone for women: a systematic review and meta-analysis of randomised controlled trial data. Lancet Diabetes and Endocrinol 2019;7(10):754-766. DOI: 10.1016/S2213-8587(19)30189-5.
4. Davis SR, Baber R, Panay N, et al. Global Consensus Position Statement on the Use of Testosterone Therapy for Women. J Clin Endocrinol Metab 2019;104(10):4660-4666. DOI: 10.1210/jc.2019-01603.
5. Public Summary: ANDROFEME 1 testosterone 1% w/v (10 mg/mL) cream tube. Australian Government. Department of Health, Disability and Ageing. Theapeutic Goods Administration, 2020. (https://www.ebs.tga.gov.au/servlet/xmlmillr6?dbid=ebs/PublicHTML/pdfStore.nsf&docid=324274&agid=%28PrintDetailsPublic%29&actionid=1).
6. Nakamura Y, Hornsby PJ, Casson P, et al. Type 5 17beta-hydroxysteroid dehydrogenase (AKR1C3) contributes to testosterone production in the adrenal reticularis. J Clin Endocrinol Metab 2009;94(6):2192-8. DOI: 10.1210/jc.2008-2374.
7. Davison SL, Bell R, Donath S, Montalto JG, Davis SR. Androgen levels in adult females: changes with age, menopause, and oophorectomy. J Clin Endocrinol Metab 2005;90(7):3847-53.
8. Skiba MA, Bell RJ, Islam RM, Handelsman DJ, Desai R, Davis SR. Androgens during the reproductive years, what's normal for women? J Clin Endocrinol Metab 2019;104(11):5382-5392. DOI: 10.1210/jc.2019-01357.
9. Wang Y, Islam MR, Bond M, Davis SR. Testosterone and pre-androgens by age and menopausal stage at midlife: findings from a cross-sectional study. EBioMedicine 2025;121. DOI: 10.1016/j.ebiom.2025.105972. .
10. Haring R, Hannemann A, John U, et al. Age-specific reference ranges for serum testosterone and androstenedione concentrations in women measured by liquid chromatography-tandem mass spectrometry. J Clin Endocrinol Metab 2012;97(2):408-15. (In eng). DOI: 10.1210/jc.2011-2134.
11. Davis SR, Bell RJ, Robinson PJ, et al. Testosterone and estrone increase from the age of 70 years; findings from the Sex Hormones in Older Women Study. J Clin Endocrinol Metab 2019;104(12):6291-6300. DOI: 10.1210/jc.2019-00743.
12. Labrie F. Extragonadal synthesis of sex steroids: intracrinology. Ann Endocrinol (Paris) 2003;64(2):95-107.
13. Zheng J, Islam RM, Skiba MA, Bell RJ, Davis SR. Associations between androgens and sexual function in premenopausal women: a cross-sectional study. Lancet Diabetes and Endocrinol 2020;8(8):693-702. DOI: 10.1016/S2213-8587(20)30239-4.
14. Davis SR, Davison SL, Donath S, Bell RJ. Circulating androgen levels and self-reported sexual function in women. JAMA 2005;294(1):91-6.
15. HA00 Hypoactive sexual desire dysfunction. 2025 (https://icd.who.int/browse/2025-01/mms/en#1189253773).
16. Wang Y, Islam MR, Bond M, Skiba M, Davis SR. Sexual dysfunction in women at midlife: cross-sectional findings from the Australian Women’s Midlife Years Study. Lancet Obstet Gynaecol Women’s Health 2025;1:3:E198-208.
17. Worsley R, Bell RJ, Gartoulla P, Davis SR. Prevalence and Predictors of Low Sexual Desire, Sexually Related Personal Distress, and Hypoactive Sexual Desire Dysfunction in a Community-Based Sample of Midlife Women. J Sex Med 2017;14(5):675-686. DOI: 10.1016/j.jsxm.2017.03.254.
18. Davis SR, Moreau M, Kroll R, et al. Testosterone for Low Libido in Menopausal Women Not Taking Estrogen Therapy. N Eng J Med 2008;359:2005-17.
19. Simon J, Braunstein G, Nachtigall L, et al. Testosterone patch increases sexual activity and desire in surgically menopausal women with hypoactive sexual desire disorder. J Clin Endocrinol Metab 2005;90(9):5226-33. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16014407).
20. Dichtel LE, Carpenter LL, Nyer M, et al. Low-Dose Testosterone Augmentation for Antidepressant-Resistant Major Depressive Disorder in Women: An 8-Week Randomized Placebo-Controlled Study. Am J Psychiatry 2020;177(10):965-973. DOI: 10.1176/appi.ajp.2020.19080844.
21. Fooladi E, Bell RJ, Jane F, Robinson PJ, Kulkarni J, Davis SR. Testosterone improves antidepressant-emergent loss of libido in women: findings from a randomized, double-blind, placebo-controlled trial. J Sex Med 2014;11(3):831-9. (Research Support, Non-U.S. Gov't) (In eng). DOI: 10.1111/jsm.12426.
22. Goldman AL, Bhasin S, Wu FCW, Krishna M, Matsumoto AM, Jasuja R. A Reappraisal of Testosterone's Binding in Circulation: Physiological and Clinical Implications. Endocr Rev 2017;38(4):302-324. DOI: 10.1210/er.2017-00025.
23. Parish SJ, Simon JA, Davis SR, et al. International Society for the Study of Women's Sexual Health Clinical Practice Guideline for the Use of Systemic Testosterone for Hypoactive Sexual Desire Disorder in Women. Climacteric 2021;24(6):533-550. DOI: 10.1080/13697137.2021.1891773.

Authorship

Professor Susan R Davis AO

MBBS, FRACP, PhD, FAHMS

NHMRC Investigator

Professor and Director, Women's Health Research Program Monash University, and Head, Women's Endocrine Clinic, Alfred Hospital, Bayside Health, Melbourne.

April 2026