Is testosterone cream indicated for a postmenopausal woman with low libido, sexual dissatisfaction, fatigue, and loss of muscle mass unresponsive to estrogen therapy, and what are the appropriate dosing, contraindications, baseline evaluations, and monitoring?

Testosterone Cream for Menopause

Testosterone therapy is indicated for postmenopausal women with hypoactive sexual desire disorder (HSDD) who have failed non-hormonal interventions, but it is absolutely contraindicated in women with current or prior breast cancer, and no FDA-approved testosterone preparation exists for women—requiring off-label use of male formulations at reduced doses or compounded creams. 1, 2, 3

Indications and Patient Selection

Testosterone therapy should be reserved for postmenopausal women with persistent HSDD who have not responded to addressing underlying causes (relationship issues, depression, anxiety, vaginal atrophy) and who have no contraindications. 1, 4

Specific Clinical Criteria

• The patient must have hypoactive sexual desire disorder characterized by absent or greatly diminished sexual motivation, desire, or libido that causes personal distress 5, 4
• Symptoms should include persistent unexplainable fatigue, lack of energy, and diminished sense of well-being 5
• The patient must be in a stable relationship and not clinically depressed 6
• Non-hormonal interventions (pelvic floor physical therapy, cognitive behavioral therapy, addressing vaginal atrophy) must have been attempted first 1

Absolute Contraindications

Testosterone therapy is absolutely prohibited in the following situations: 1, 2

• Current or prior breast cancer or other hormone-dependent malignancies 1
• Active or recent pregnancy 2
• Active liver disease 2
• History of thromboembolic disease (DVT, PE, stroke) 2

Dosing and Formulations

Available Options (All Off-Label)

No FDA-approved testosterone preparation exists for women; all use represents off-label prescribing. 3, 4

• Compounded testosterone cream 10 mg daily (2 cm application) has demonstrated efficacy in clinical trials 6
• Reduced-dose male-approved transdermal testosterone gel can be used at approximately 1/10th the male dose to achieve premenopausal physiologic testosterone ranges 3
• Testosterone injections or pellets are NOT recommended because they cause supraphysiological testosterone levels 3

Practical Dosing Algorithm

• Start with testosterone cream 10 mg applied daily to non-genital skin (inner thigh or lower abdomen) 6
• Target serum testosterone levels within the premenopausal physiologic range (not supraphysiological) 3, 4
• Reassess response at 3 months; meaningful improvement includes approximately 1 additional satisfying sexual episode per month 3, 4

Baseline Evaluation

Before initiating testosterone therapy, obtain: 4

• Serum total and free testosterone levels (though measurement accuracy is limited with commonly used techniques) 7
• Lipid panel 6
• Liver function tests 2
• Blood pressure and weight 6
• Screen for depression using validated tools 6
• Assess for contraindications including breast cancer history and thromboembolic disease 1, 2

Monitoring Requirements

During testosterone therapy, monitor: 6, 4

• Serum testosterone levels to avoid supraphysiological dosing and maintain levels within premenopausal physiologic range 3, 4
• Lipid panel (testosterone did not adversely affect lipids in 3-month trials) 6
• Blood pressure and weight 6
• Clinical response using validated sexual function questionnaires 6
• Androgenic side effects (hirsutism, acne, voice deepening) 7, 3

Monitoring Schedule

• Reassess at 3 months for efficacy and side effects 6
• Continue monitoring every 6-12 months if therapy is continued 4
• Use the lowest effective dose for the shortest duration necessary 4

Expected Benefits and Timeline

Women receiving testosterone therapy can expect: 6, 3, 4

• Significant improvement in sexual desire, frequency of sex, receptivity, and initiation 6
• Approximately 1 additional satisfying sexual episode per month 3, 4
• Improvement in arousal, orgasm, pleasure, and responsiveness 3
• Reduction in sexual distress 3
• Improvement in mood, energy, and sense of well-being 5
• Response typically occurs within 3 months of consistent therapy 6

Safety Profile and Adverse Effects

Short-Term Safety (Up to 2 Years)

Testosterone therapy in low-dose regimens is well-tolerated with no serious side effects in controlled trials up to 2 years duration. 5, 6

• Common reversible side effects include hirsutism and acne, which resolve with discontinuation 7, 3
• No adverse effects on lipids, blood pressure, or weight in 3-month trials 6
• No change in mood or energy levels (beyond improvement in sexual function) 6

Long-Term Safety Concerns

Critical safety data are lacking: 3, 4

• No long-term data on cardiovascular safety 3
• No long-term data on breast cancer risk 3
• No long-term data on cognitive effects 3
• Patients must be counseled about the absence of long-term safety data, particularly regarding cardiovascular outcomes and breast cancer incidence 1

Special Populations

Breast Cancer Survivors

Systemic testosterone therapy is absolutely contraindicated in women with current or prior breast cancer. 1

• The NCCN guidelines explicitly list active or prior breast cancer as an absolute contraindication to testosterone therapy 1
• Intravaginal testosterone cream (not systemic) has demonstrated safety and efficacy for vaginal atrophy in breast cancer patients on aromatase inhibitors, but this is a different indication and route than systemic therapy for libido 1
• Vaginal DHEA should be used with extreme caution in women on aromatase inhibitors because it raises circulating androgens and may interfere with inhibitor activity 1

Women on Estrogen Therapy

Testosterone can be added to existing estrogen therapy for women with persistent HSDD. 5, 6

• Most clinical trials demonstrating efficacy used testosterone added to estrogen therapy 5
• The combination significantly improved multiple facets of sexual functioning including libido, desire, arousal, frequency, and satisfaction 5
• Women already on transdermal estrogen can add testosterone cream 6

Common Pitfalls to Avoid

• Using testosterone injections or pellets, which cause supraphysiological levels and are not recommended 3
• Prescribing testosterone without first addressing vaginal atrophy, which may be the primary cause of sexual dysfunction 8, 1
• Failing to screen for depression and relationship issues, which are common contributors to low libido 1, 6
• Not counseling patients about the lack of FDA-approved formulations and the off-label nature of all testosterone use in women 3, 4
• Inadequate monitoring of serum testosterone levels, risking supraphysiological dosing 3, 4
• Prescribing to women with breast cancer history, which is an absolute contraindication 1

Alternative Therapies When Testosterone Is Contraindicated

For women with contraindications to testosterone or who prefer non-androgen options: 1

• Flibanserin 100 mg at bedtime (FDA-approved for premenopausal HSDD, used off-label postmenopausally) results in approximately 1 extra satisfying sexual event per 2 months 1
• Bremelanotide (FDA-approved for premenopausal low sexual desire) has shown statistically significant increases in sexual desire 1
• Off-label bupropion or buspirone may be considered despite limited data 1
• Address vaginal atrophy with vaginal estrogen, DHEA, or ospemifene if dyspareunia is contributing to low libido 8, 1