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Female Testosterone for HSDD — Off-Label Transdermal Therapy

Testosterone remains off-label in the US for hypoactive sexual desire disorder (HSDD) in women. Transdermal testosterone has moderate efficacy for postmenopausal HSDD, the only evidence-based indication for testosterone therapy in women in the 2019 Global Consensus Position Statement. Use physiologic female dosing and serum levels to avoid excess, not to correct a presumed laboratory deficiency.[1][2][21] Flibanserin has FDA approval for women younger than 65, including postmenopausal women.[20]

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). See Flibanserin and Bremelanotide for their distinct FDA-approved populations.

Regulatory Landscape​

RegionStatus
United StatesNo FDA-approved female testosterone formulation. Treatment of female HSDD is off-label.
Europe — historical productTransdermal testosterone patch (Intrinsa) was previously approved for surgically menopausal women receiving estrogen. The product was subsequently withdrawn. This historical approval does not establish current availability.[21]
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) — assess and treat pain and dryness with an appropriate GSM strategy.

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. There is no serum-testosterone threshold that diagnoses HSDD; a low level should NOT be used to diagnose it. A full biopsychosocial assessment should precede treatment, 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.
  • Short-term non-oral lipid findings were reassuring; a nonsignificant serious-adverse-event comparison does not prove long-term safety. Testosterone treatment was associated with increased weight overall, so a blanket claim of no anthropometric effect is inappropriate.[21]

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 statistically significant serious-adverse-event difference was detected during the trials; this does not establish long-term safety.

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

Double-blind trial randomized 814 postmenopausal women with HSDD not taking estrogen to 150 µg/day, 300 µg/day or placebo. Efficacy was assessed at 24 weeks and safety through 52 weeks, with a subgroup followed longer.[5]

  • At 24 weeks, satisfying sexual episodes increased 2.1 per four weeks with 300 µg/day versus 0.7 with placebo; the 150-µg dose did not significantly improve this primary outcome.
  • Androgenic adverse events were more frequent with 300 µg/day. Four breast cancers were diagnosed in testosterone recipients and none with placebo; timing complicates attribution, and the trial did not resolve long-term breast safety.[5]

Braunstein 2005 Arch Intern Med — surgically menopausal women​

This was one 24-week dose-ranging trial, with 447 women randomized to placebo or 150, 300 or 450 µg/day patches while taking oral estrogen. 318 (71%) completed it. The 300-µg group improved sexual desire and satisfying sexual activity compared with placebo; higher dosing did not establish greater benefit.[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 — approximately 5 mg applied; follow the formulation’s application instructions
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 practiceApproximately 1/10 of the product's male starting dose; distinguish milligrams applied from micrograms delivered by a patch. Absorption is formulation-dependent.[21]
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]

Monitoring ceiling, not a numerical target. Use levels to avoid excess: remain within the laboratory’s premenopausal range. Do not escalate toward its upper end when symptoms fail to improve.[21]

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​

Based on the Global Consensus and ISSWSH guidance.[2][21]

StepAction
BaselineTotal testosterone, SHBG, fasting lipids and liver tests; complete biopsychosocial assessment
3–6 weeksRepeat total testosterone to confirm levels remain in the premenopausal physiological range
Dose change / excess levelRecheck within 6 weeks after an increase; reduce excessive dosing and recheck in 2–3 weeks
Every 4–6 months once stableClinical assessment for androgen excess + total testosterone
6 monthsDiscontinue if no clinical response
OngoingLong-term safety remains unestablished; limited observational follow-up is not equivalent to randomized safety evidence

Adverse Effects​

Androgenic effects​

  • Mild increases in acne and body / facial hair growth are expected at physiologic doses; these are generally reversible.[1][2]
  • Short-term physiologic-dose trials did not demonstrate an increase in alopecia, clitoromegaly or voice change; monitor for androgen excess rather than treating these effects as impossible.[2][21]
  • 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.[15]
  • 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.[16]
  • 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.[17]

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.[18]
  • 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.[19]

Exclusions and safety assessment​

Do not derive an estradiol-equivalent contraindication list from aromatization alone. The cited 2025 Cochrane item concerns a planned review of menopausal genitourinary/vasomotor symptoms, not completed HSDD safety evidence.[13]

  • Pregnancy or potential pregnancy: avoid testosterone because of fetal androgen exposure.
  • Androgen excess or concurrent antiandrogen therapy: ISSWSH advises against treatment in these circumstances.
  • Liver disease or hyperlipidemia: listed as contraindications in ISSWSH guidance; assess before prescribing.
  • Hormone-dependent neoplasia: consult the treating cancer specialist. High cardiovascular or thrombotic risk requires individualized assessment; short trials in selected patients do not establish safety.[2][21]

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.[14]

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​

  • Strongest evidence is in postmenopausal HSDD. ISSWSH also discusses selected late-reproductive-age women, but that evidence is limited.[21]
  • Address GSM-related pain and dryness; treatment of contributing conditions may proceed alongside HSDD therapy when appropriate.[21]
  • Address relevant psychosocial and medical contributors; psychological and pharmacologic treatment can be combined.[21]
  • Diagnosis is clinical — a low testosterone level does not diagnose HSDD.
  • Set realistic expectations — meta-analysis effect size is +0.85 SSE/month vs placebo, a within-evidence-base estimate that does not establish superiority over other HSDD drugs.
  • Transdermal route only. Oral testosterone is not recommended.
  • Use testosterone levels to prevent excessive dosing, not to target the upper end of the female range.[21]
  • 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 (a locally available female formulation or fractionated doses of approved male transdermal products with careful monitoring).
  • Women with prior breast cancer were excluded from RCTs. Small uncontrolled reports do not establish safety; involve the treating oncology specialist.[19]

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. Review protocol. Cochrane Database Syst Rev. 2025;6:CD016052. doi:10.1002/14651858.CD016052

14. 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

15. 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

16. 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

17. 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

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

19. 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

20. Sprout Pharmaceuticals. Addyi prescribing information, revised December 2025. Accessed September 11, 2026.

21. 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. J Sex Med. 2021;18:849–867.