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Female Testosterone for HSDD — Off-Label Transdermal Therapy

Testosterone is not approved in North America for the treatment of hypoactive sexual desire disorder (HSDD) in women, but it has been prescribed off-label for this indication since the 1940s. An international task force concluded that transdermal testosterone, dosed to restore serum testosterone to approximately premenopausal concentrations, is moderately effective for postmenopausal HSDD — currently the only evidence-based indication for testosterone therapy in women per the 2019 Global Consensus Position Statement (endorsed by 11 international societies).[1][2] Both flibanserin and bremelanotide are FDA-approved for premenopausal HSDD, but no pharmacotherapy is approved for postmenopausal HSDD in North America, making testosterone the primary off-label option for this population.[1]

For the male testosterone-replacement framework (TRAVERSE 2023, hypogonadism, prostate-cancer safety) see Testosterone Replacement. For the clinical-conditions framework on female sexual dysfunction see Sexual Dysfunction (Women's Health). For the FDA-approved premenopausal options see Flibanserin and Bremelanotide.

Regulatory Landscape​

RegionStatus
United States / CanadaNo FDA-approved female testosterone formulation. All female testosterone use is off-label.
EuropeTransdermal testosterone patch (Intrinsa) was previously approved for surgically postmenopausal women with HSDD despite adequate estrogen therapy. Manufacturer withdrew Intrinsa when approval was not extended to naturally menopausal women — despite clinical-trial data showing similar efficacy in both populations.[1]
AustraliaTransdermal 1% testosterone cream (AndroFeme) approved by the TGA for postmenopausal HSDD.[1]

More than 2 million testosterone prescriptions are written annually for women in the US — most are likely for compounded preparations.[1] Compounded formulations are not subject to pharmacokinetic-profiling requirements, and their uncertain absorption may cause overdose and harm.

Indication and Diagnostic Framework​

The only evidence-based indication for testosterone therapy in women is postmenopausal HSDD — distress about decreased sexual desire that is not better explained by:

  • Coexisting medical / psychiatric condition.
  • Relationship factors.
  • Effects of a medication (especially SSRIs / SNRIs).
  • Genitourinary syndrome of menopause (GSM) — which should first be addressed with vaginal estrogen / DHEA / ospemifene.

Per the 2019 Global Consensus Position Statement (Davis 2019, endorsed by IMS, ESM, ISSM, ISSWSH, NAMS, RANZCOG, FSPS, RCOG, FIGO, AAGL, ACOG-supportive): testosterone therapy in postmenopausal women is not recommended for any other indication — including general well-being, cognitive performance, cardiovascular protection, bone density, or musculoskeletal benefit.[2]

Diagnosis is clinical. Testosterone levels do not correlate with HSDD symptoms, and a low testosterone level should NOT be used to diagnose HSDD. A full biopsychosocial assessment should be completed before initiating testosterone, addressing relationship factors, psychological distress, medications, and medical conditions.[2][10]

Mechanism and Rationale​

Endogenous testosterone in women is produced by the ovaries and adrenal glands; circulating levels decline gradually with age and decline more abruptly after surgical menopause / bilateral oophorectomy. The causal contribution of low testosterone to HSDD is unproven — there is no validated serum-testosterone threshold below which HSDD is more likely. The clinical decision is symptom-driven, not biomarker-driven.[1][2]

Efficacy​

Islam 2019 Lancet Diabetes Endocrinol meta-analysis — the foundational evidence base​

Meta-analysis of 36 RCTs / 8,480 participants of testosterone in women, mostly postmenopausal.[3]

  • Satisfying sexual events (SSEs) — significant increase of approximately +0.85 / month over placebo.
  • FSFI — significant improvement in desire, arousal, orgasm, and pleasure domains.
  • Distress — significantly reduced.
  • Effects on responsiveness, self-image, and reduced concerns about sexual function — all significantly improved.
  • No effect on serious adverse events, lipid profile (with non-oral routes), or anthropometric measures when delivered transdermally.

Achilli 2017 Fertil Steril SR/meta-analysis​

Systematic review of 7 RCTs enrolling 3,035 postmenopausal women with HSDD specifically evaluating the 300 µg/day transdermal testosterone patch (TTP).[4]

  • Significant increases in satisfying sexual episodes, sexual activity, orgasms, and desire vs placebo.
  • No increase in serious adverse events.

APHRODITE — Davis 2008 N Engl J Med (landmark trial in non-estrogen-using women)​

Double-blind, placebo-controlled trial randomized 814 naturally or surgically menopausal women with HSDD not taking estrogen to 300 µg/day testosterone patch or placebo for 24 weeks.[5]

  • Mean SSE increase +2.12/month with testosterone vs +0.73 with placebo.
  • Reported orgasms — > 115% increase vs 38% with placebo.
  • All Profile of Female Sexual Function domains and the Personal Distress Scale significantly improved at week 24.

Braunstein 2005 Arch Intern Med — surgically menopausal women​

In two large trials of surgically menopausal women on oral estrogen, SSEs improved from ~ 3 to ~ 5 per month with testosterone vs ~ 4 with placebo — a statistically significant median increase of approximately one additional satisfying sexual event per month. Personal distress declined by 65–68% with testosterone vs 40–48% with placebo. All domains of sexual function (arousal, pleasure, orgasm, self-image, responsiveness) improved significantly.[6]

Subsequent reviews​

The 2025 Obstet Gynecol expert update (Kling) confirms consistent efficacy of transdermal testosterone in postmenopausal HSDD and notes that two clinical guidelines now provide expert guidance on testosterone treatment and monitoring for HSDD in women.[11]

Dosing and Formulations​

FormulationStatusRecommendation
Transdermal 1% cream / gel — AndroFeme (Australia)TGA-approved for postmenopausal HSDD0.5 mL daily to thigh / abdomen — delivers ~ 5 mg testosterone
Intrinsa transdermal patchWithdrawn from European market300 µg/day (no longer commercially available)
Fractionated dose of male transdermal product (e.g., AndroGel, Testim)Off-label US practice~ 1/10 of male dose (~ 5 mg/day from a 50 mg/day male product); aim for ~ 300 µg/day absorbed
Compounded transdermal testosteroneNot regulator-approvedGlobal Consensus recommends against due to lack of PK profiling and uncertain absorption[2]
Oral testosteroneNot recommendedAdverse effects on lipoprotein levels (HDL ↓, LDL ↑) and inconsistent absorption[1][2]
Testosterone implants / pelletsNot recommendedSupraphysiologic peaks; difficult to titrate or remove; virilization risk
Testosterone injectionsNot recommendedSupraphysiologic levels; lacks safety data in women
Systemic DHEANot effective; not recommended for HSDD per ACOG Level A and Davis 2024 NEJMDHEA has not improved sexual dysfunction in RCTs of women with intact adrenals or adrenal insufficiency[1][8]

Target. Achieve and maintain total testosterone within the premenopausal physiological range (upper end of the female reference range, not the male range).[2]

Practical US off-label dosing — Heald 2026 PK variability​

A pharmacokinetic study of postmenopausal women using Testogel 16.2 mg/g pump (20.25 mg applied every 3–4 days) found substantial interindividual variability in testosterone levels — Cmax range 1.3–26.1 nmol/L — underscoring the importance of monitoring serum levels rather than assuming a fixed-dose / fixed-level relationship.[12]

Monitoring Protocol​

Per the Global Consensus and ACOG.[2][8]

StepAction
BaselineMeasure total testosterone before initiation; complete biopsychosocial assessment
3–6 weeksRepeat total testosterone to confirm levels remain in the premenopausal physiological range
Every 6 monthsClinical assessment for androgen excess + total testosterone
6 monthsDiscontinue if no clinical response
OngoingNote that safety data are not available beyond 24 months

Adverse Effects​

Androgenic effects​

  • Mild increases in acne and body / facial hair growth are expected at physiologic doses; these are generally reversible.[1][2]
  • Alopecia, clitoromegaly, and voice change have not been observed at recommended doses.[2]
  • Virilization effects at supraphysiologic doses (voice deepening, clitoromegaly) may be irreversible.[8]
  • Mild weight gain reported in some series.[1]

Lipid effects​

  • Oral testosterone adversely affects HDL and LDL cholesterol — one of the central rationales for the transdermal-only recommendation.[1][3]
  • Non-oral / transdermal routes have a neutral lipid profile in short-term RCTs.[3]

Cardiovascular​

The cardiovascular safety data are conflicting, and long-term outcomes remain uncertain.

  • The Global Consensus Position Statement found that non-oral testosterone at physiologic doses showed no statistically significant adverse effects on lipid profiles over the short term, and no association with increases in blood pressure, blood glucose, or HbA1c. A nonsignificant trend for increased DVT risk was noted; RCTs excluded women at high cardiometabolic risk.[2]
  • Lopez 2023 (claims database, n = 25,796 cisgender women) — testosterone therapy associated with a 24% increased CVD risk (HR 1.24, 95% CI 1.15–1.34), 26% increased CAD risk, and 29% increased stroke risk.[16]
  • Agrawal 2024 (claims database) — testosterone therapy associated with a lower MACE risk (RR 0.64, 95% CI 0.51–0.81) and lower DVT, PE, and breast-cancer risk vs propensity-matched controls.[17]
  • Viana 2026 systematic review — no cardiovascular deaths in 13 RCTs of transdermal testosterone in cisgender women (n = 2,628; 8–52 weeks); the absence of deaths in short-term trials does not allow inference regarding long-term safety.[18]

Breast cancer​

  • Short-term transdermal testosterone does not increase mammographic breast density, and available RCT data suggest no increase in breast-cancer risk.[2]
  • Gompel 2026 Lancet Diabetes Endocrinol review confirmed that subsequent observational studies support these findings, though long-term high-quality studies remain absent.[19]
  • Women with prior breast cancer were excluded from RCTs. Glynne 2026 Menopause small retrospective open-label study of breast-cancer survivors using transdermal testosterone showed significant improvement in menopausal symptoms with no reported adverse events — but placebo-controlled trials are needed before this can be recommended.[20]

Contraindications​

Due to peripheral conversion of androgens to estrogens, absolute contraindications align with those of estradiol.[13][14]

  • Hormone-dependent cancers (breast, meningioma, endometrial).
  • Thromboembolic disease, recent myocardial infarction, recent stroke.
  • Pregnancy — potential fetal harm.

Guideline Recommendations​

Society / guidelinePosition
2019 Global Consensus Position Statement (Davis 2019; endorsed by 11 international societies)[2]The only evidence-based indication for testosterone in women is postmenopausal HSDD; moderate therapeutic effect; transdermal only; physiologic doses; recommends against compounded preparations; recommends fractionated dose of regulator-approved male formulation if no female-specific product is available
ACOG 2019 (Practice Bulletin 213)[8]Short-term transdermal testosterone can be considered for postmenopausal women with HSDD; insufficient evidence for premenopausal women; 3–6 month trial recommended
Endocrine Society 2014[7]Recommends against general use of testosterone for women; short-term trial may be reasonable in postmenopausal HSDD with informed consent; against compounded or supraphysiologic formulations
AAFP 2025 (Dalrymple)[9]Transdermal testosterone off-label in postmenopausal women; discontinue if no benefit at 6 months; insufficient evidence for compounded testosterone; systemic / pellet forms not recommended
ISSWSH 2018 Process of Care (Clayton)[10]Hormonal therapy includes off-label testosterone in postmenopausal HSDD; guided by menopausal status within a biopsychosocial framework

Premenopausal Women​

There are insufficient data to recommend testosterone for premenopausal women with HSDD.[2][8] The Global Consensus Position Statement explicitly states that no recommendations can be made regarding testosterone use in premenopausal women for sexual function or any other outcome.[2]

Despite this, a 2024 claims-database analysis (Agrawal) found that testosterone prescriptions for HSDD are increasing, with the highest rate of increase in women aged 41–55 years; only 2.54% of women diagnosed with HSDD received a testosterone prescription.[15]

For premenopausal HSDD, the FDA-approved options are Flibanserin (daily PO) and Bremelanotide (on-demand SC) — see those pages for the full prescribing frameworks.

Counseling and Prescribing Pearls​

  • Postmenopausal HSDD only. No evidence base for premenopausal use.
  • GSM-driven dyspareunia and arousal symptoms should be addressed first with vaginal estrogen / DHEA / ospemifene before considering systemic testosterone.
  • Psychological interventions (CBT, mindfulness-based therapy, sex therapy) are first-line before pharmacotherapy.[9]
  • Diagnosis is clinical — testosterone levels do not correlate with HSDD symptoms; a low level should not be used to diagnose HSDD.
  • Set realistic expectations — meta-analysis effect size is +0.85 SSE/month vs placebo, the strongest effect size of any HSDD pharmacotherapy.
  • Transdermal route only. Oral testosterone is not recommended.
  • Aim for the upper end of the female reference range — never the male range.
  • Counsel explicitly on the off-label status in the US and the lack of long-term safety data as part of informed consent.
  • Discontinue at 6 months if no symptomatic response.
  • Heald 2026 PK data underscore substantial interindividual variability — monitor serum levels, do not assume fixed-dose / fixed-level relationships.[12]
  • Compounded products vary in concentration / quality — when possible, use a regulator-approved formulation (Australian AndroFeme for women between regulatory jurisdictions, or fractionated doses of FDA-approved male transdermal products with careful monitoring).
  • Women with prior breast cancer were excluded from RCTs — exercise caution; placebo-controlled data are awaited (Glynne 2026 pilot suggests possible safety).[20]

See Also​

References​

1. Davis SR. Sexual dysfunction in women. N Engl J Med. 2024;391(8):736–745. doi:10.1056/NEJMcp2313307

2. 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

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 Endocrinol. 2019;7(10):754–766. doi:10.1016/S2213-8587(19)30189-5

4. Achilli C, Pundir J, Ramanathan P, et al. Efficacy and safety of transdermal testosterone in postmenopausal women with hypoactive sexual desire disorder: a systematic review and meta-analysis. Fertil Steril. 2017;107(2):475–482.e15. doi:10.1016/j.fertnstert.2016.10.028

5. Davis SR, Moreau M, Kroll R, et al. Testosterone for low libido in postmenopausal women not taking estrogen. N Engl J Med. 2008;359(19):2005–2017. doi:10.1056/NEJMoa0707302

6. Braunstein GD, Sundwall DA, Katz M, et al. Safety and efficacy of a testosterone patch for the treatment of hypoactive sexual desire disorder in surgically menopausal women: a randomized, placebo-controlled trial. Arch Intern Med. 2005;165(14):1582–1589. doi:10.1001/archinte.165.14.1582

7. Wierman ME, Arlt W, Basson R, et al. Androgen therapy in women: a reappraisal: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2014;99(10):3489–3510. doi:10.1210/jc.2014-2260

8. American College of Obstetricians and Gynecologists' Committee on Practice Bulletins—Gynecology. Female sexual dysfunction: ACOG Practice Bulletin Number 213. Obstet Gynecol. 2019;134(1):e1–e18. doi:10.1097/AOG.0000000000003324

9. Dalrymple SN, Hoeg L, Thacker H. Female sexual dysfunction: common questions and answers. Am Fam Physician. 2025;111(5):433–442.

10. Clayton AH, Goldstein I, Kim NN, et al. The International Society for the Study of Women's Sexual Health process of care for management of hypoactive sexual desire disorder in women. Mayo Clin Proc. 2018;93(4):467–487. doi:10.1016/j.mayocp.2017.11.002

11. Kling JM. Testosterone for the treatment of hypoactive sexual desire disorder in perimenopausal and postmenopausal women. Obstet Gynecol. 2025. doi:10.1097/AOG.0000000000006015

12. Heald A, Illangasekera Y, Rehman H, et al. A single-centre study to describe the changes in serum testosterone concentration following application of testosterone gel in postmenopausal women with hypoactive sexual desire disorder already receiving this as part of usual care in conjunction with oestrogen-containing HRT. Clin Endocrinol (Oxf). 2026. doi:10.1111/cen.70119

13. Lara LA, Cartagena-Ramos D, Cantelli D, et al. Androgens for genitourinary and vasomotor symptoms associated with menopause. Cochrane Database Syst Rev. 2025;6:CD016052. doi:10.1002/14651858.CD016052

14. Pinkerton JV, Blackman I, Conner EA, Kaunitz AM. Risks of testosterone for postmenopausal women. Endocrinol Metab Clin North Am. 2021;50(1):139–150. doi:10.1016/j.ecl.2020.10.007

15. Agrawal P, Lee YS, Grutman AJ, et al. Characteristics of systemic testosterone therapy for female hypoactive sexual desire disorder — a claims database analysis. J Sex Med. 2024;21(4):288–293. doi:10.1093/jsxmed/qdae013

16. Lopez DS, Mulla JS, El Haddad D, et al. Testosterone replacement therapy in relation with cardiovascular disease in cisgender women and transgender people. J Clin Endocrinol Metab. 2023;108(12):e1515–e1523. doi:10.1210/clinem/dgad388

17. Agrawal P, Singh SM, Hsueh J, et al. Testosterone therapy in females is not associated with increased cardiovascular or breast-cancer risk: a claims database analysis. J Sex Med. 2024;21(5):414–419. doi:10.1093/jsxmed/qdae032

18. Viana DPDC, Câmara LC, Alto LSM. Cardiovascular mortality associated with testosterone therapy in cisgender women and transgender men: a systematic review. Front Endocrinol (Lausanne). 2026;17:1789504. doi:10.3389/fendo.2026.1789504

19. Gompel A, Simcock R. Menopausal hormone treatment and breast cancer. Lancet Diabetes Endocrinol. 2026. doi:10.1016/S2213-8587(25)00394-8

20. Glynne S, Kamal A, Neville A, et al. Use of transdermal testosterone to treat menopausal symptoms in women with a history of breast cancer: a small, retrospective, open-label study. Menopause. 2026. doi:10.1097/GME.0000000000002777