For adult women requiring testosterone replacement for hypoactive sexual desire disorder or menopausal androgen deficiency, is transdermal testosterone (gel or patch) a better option than intramuscular testosterone injections?

Transdermal Testosterone is the Superior Choice for Women

For adult women requiring testosterone therapy for hypoactive sexual desire disorder (HSDD) or menopausal androgen deficiency, transdermal testosterone (gel, patch, or cream) is strongly preferred over intramuscular injections due to superior safety, more physiologic hormone delivery, and proven efficacy in multiple high-quality randomized controlled trials. 1, 2

Evidence Supporting Transdermal Testosterone in Women

Efficacy Data from High-Quality Trials

• Large randomized, double-blind, placebo-controlled Phase III trials demonstrate that 300 µg/day transdermal testosterone significantly improves sexual function in postmenopausal women with HSDD, including increased satisfying sexual episodes, enhanced sexual desire, and reduced personal distress 1, 3, 2

• The APHRODITE trial specifically examined testosterone alone (without concurrent estrogen therapy) and confirmed increased sexual desire with only mild adverse events, establishing efficacy as monotherapy 3

• Five high-quality randomized controlled trials (GRADE scores 4-6 out of 6) consistently show effectiveness of 300 µg/day transdermal testosterone for both surgically and naturally menopausal women, with or without concomitant estrogen/progestin therapy 2

• Women report meaningful clinical benefit that translates to real-world continuation of therapy, as demonstrated in clinical relevance studies showing patients only continue treatment when experiencing subjectively important improvements 3

Pharmacokinetic Advantages of Transdermal Delivery

• Transdermal administration delivers testosterone at a controlled rate into systemic circulation, avoiding hepatic first-pass metabolism and reproducing physiologic diurnal rhythm, unlike injections which create supraphysiologic peaks followed by subtherapeutic troughs 4

• The stable day-to-day testosterone levels achieved with patches and gels eliminate the mood, energy, and sexual function fluctuations that occur with injectable testosterone's peak-and-trough pattern 5, 4

• Transdermal preparations allow rapid discontinuation if adverse effects occur, which is particularly important in women over 50 when monitoring for unexpected reactions becomes critical 4

Safety Profile

• Short-term safety data from multiple trials show the main side effects are mild: increased hair growth and acne, with no serious adverse events at therapeutic doses 1, 3

• Available cardiovascular, breast, and endometrial safety data are reassuring, though not conclusive, with interim long-term phase III safety trial data showing continued low rates of cardiovascular events and breast cancer in postmenopausal women at increased cardiovascular risk 1

• One long-term study showed a trend toward higher breast cancer risk (0.37%) with extended use, indicating the need for ongoing surveillance but not contraindication to therapy 2

• Androgens may actually suppress the proliferative effects of estrogen and progesterone on breast tissue, potentially offering protective rather than harmful effects 3

Why Injections Are Inappropriate for Women

Lack of Evidence Base

• All high-quality efficacy and safety data in women come from transdermal formulations (patches, gels, creams)—there are no comparable randomized controlled trials establishing safety or efficacy of intramuscular testosterone injections in women 1, 3, 2, 6

Dosing Challenges

• No testosterone injection product is designed for women, meaning clinicians would need to use male-formulated preparations with concentrations far exceeding female physiologic needs 6

• Injectable testosterone formulations for men (typically 100-200 mg every 2 weeks) deliver doses 30-60 times higher than the proven effective female dose of 300 µg/day transdermal, making accurate dosing nearly impossible 7, 6

• The risk of supraphysiologic testosterone exposure with injections in women is unacceptably high, potentially causing irreversible virilization (voice deepening, clitoral enlargement, male-pattern baldness) 6

Pharmacokinetic Mismatch

• Injectable testosterone in men produces peak levels 2-5 days post-injection with return to baseline by days 10-14, creating dramatic fluctuations incompatible with female physiology 8

• Women require steady-state testosterone levels in the low physiologic range (total testosterone 20-70 ng/dL), which cannot be achieved with injectable formulations designed for male replacement (targeting 500-600 ng/dL) 8, 6

Safety Concerns Specific to Women

• Injectable testosterone carries a 43.8% risk of erythrocytosis in men (versus 15.4% with transdermal), and this risk would be amplified in women who have lower baseline hemoglobin and are more vulnerable to polycythemia complications 5

• The cardiovascular event risk associated with injectable testosterone in men (due to time spent in both supratherapeutic and subtherapeutic ranges) would pose unacceptable risk in postmenopausal women who already face elevated cardiovascular risk 5, 9

Practical Implementation Algorithm

Step 1: Confirm Diagnosis

• Establish HSDD diagnosis: persistent decreased sexual desire causing personal distress, not explained by relationship issues, psychiatric conditions, or medications 1, 3
• Document menopausal status: either natural menopause or surgical (bilateral oophorectomy) 1, 2
• Note: There is no clear correlation between circulating testosterone levels and sexual desire in women, so diagnosis is clinical, not laboratory-based 6

Step 2: Select Transdermal Formulation

• First-line: Transdermal testosterone patch 300 µg/day (if available in your region), as this has the most robust Phase III trial data 1, 2
• Alternative: Transdermal testosterone gel or cream 5 mg daily or less (compounded or off-label use of male formulations with careful dosing), as no female-specific product is available in Europe or the US 6
• Application site: Non-genital skin (upper arms, shoulders, abdomen) for gels/creams; rotate sites for patches to minimize skin irritation 4

Step 3: Initiate Therapy

• Start with 300 µg/day (patch) or 5 mg/day (gel/cream) 2, 6
• Can be used with or without concurrent estrogen/progestin therapy, as efficacy is proven in both scenarios 1, 2
• Counsel patient on application technique: apply to clean, dry skin; allow to dry completely before dressing; wash hands after application to prevent transfer to others 4

Step 4: Monitor Response and Safety

• Assess clinical response at 8-12 weeks: improvement in sexual desire, satisfying sexual episodes, and reduction in personal distress using validated tools (Sexual Activity Log, Profile of Female Sexual Function, Personal Distress Scale) 2
• Monitor for androgenic side effects: increased facial/body hair, acne, voice changes, clitoral enlargement 1, 3
• Check total testosterone level at 3-6 months: target low-normal female range (20-70 ng/dL total testosterone); if levels are elevated, reduce dose** 6
• Annual monitoring: breast examination, cardiovascular risk assessment, hemoglobin/hematocrit (though polycythemia risk is minimal with appropriate female dosing)** 1

Step 5: Long-Term Management

• Continue therapy only if patient reports meaningful subjective benefit—women self-select for continuation based on perceived improvement 3
• Reassess need annually: HSDD may improve with time, relationship changes, or other interventions 3
• Discontinue if no benefit after 6 months of adequate dosing, as non-responders will not benefit from prolonged exposure 3

Critical Pitfalls to Avoid

Never Use Injectable Testosterone in Women

• Do not attempt to use male testosterone injections (cypionate, enanthate, undecanoate) in women, as there is zero evidence supporting this practice and substantial risk of harm from overdosing and virilization 7, 6

Do Not Rely on Testosterone Levels for Diagnosis

• Do not measure baseline testosterone levels to diagnose HSDD, as sexual desire does not correlate with circulating androgen levels in women 6
• Only measure testosterone after initiating therapy to ensure levels remain in the safe female physiologic range and to detect overdosing 6

Avoid Compounding Errors

• When using compounded testosterone cream/gel (necessary due to lack of FDA-approved female products), verify the concentration carefully—prescribe in milligrams per day, not percentage strength, to prevent 10-fold dosing errors 6
• Educate patients that male testosterone gels (AndroGel, Testim, etc.) contain 50-100 mg per application, which is 10-20 times the appropriate female dose; if using these off-label, instruct on fractional dosing (e.g., 1/20th of a packet) 7, 6

Do Not Ignore Virilization Signs

• If voice deepening, significant clitoral enlargement, or male-pattern baldness occur, discontinue testosterone immediately, as these changes may be irreversible 6
• Mild acne and increased hair growth are acceptable and manageable side effects; severe virilization indicates overdosing 1, 3

Why This Recommendation Prioritizes Morbidity, Mortality, and Quality of Life

• Quality of life improvement is the primary outcome: HSDD causes significant personal distress, and transdermal testosterone demonstrably improves sexual function, desire, and distress scores in validated instruments 1, 2

• Morbidity prevention: Transdermal delivery avoids the erythrocytosis, cardiovascular events, and virilization risks associated with injectable testosterone or inappropriate dosing 5, 1

• Mortality considerations: While no mortality benefit is expected from treating HSDD, avoiding cardiovascular complications from injectable testosterone in postmenopausal women (who already face elevated CV risk) is paramount 5, 9

• Evidence-based safety: The reassuring short- and intermediate-term safety data for transdermal testosterone (low rates of breast cancer, cardiovascular events, and endometrial effects) support its use, whereas injections have no safety data in women 1, 2