Can low-dose testosterone therapy help improve sex drive in postmenopausal women?

Testosterone Therapy for Low Sex Drive in Postmenopausal Women

Yes, low-dose testosterone therapy can effectively improve sex drive in postmenopausal women with hypoactive sexual desire disorder (HSDD), particularly those who have undergone surgical menopause, though it remains off-label in most countries and requires careful patient counseling about risks and benefits.

Evidence for Efficacy

Testosterone therapy has demonstrated clear benefits for sexual function in postmenopausal women with HSDD:

• Transdermal testosterone significantly increases satisfying sexual activity by 51-74% compared to placebo in surgically menopausal women receiving concomitant estrogen therapy 1
• All domains of sexual function improve, including desire, arousal, orgasm, and overall satisfaction, with corresponding decreases in personal distress 1
• The magnitude of benefit is clinically meaningful to patients, with 85% of treated women indicating they would continue therapy 1
• Testosterone therapy improves sexual desire, arousal, pain, and overall sexual function in postmenopausal women, though the effect size is modest 2, 3

Clinical Context and Indications

The sole evidence-based indication for testosterone therapy is HSDD in postmenopausal women 3. This is particularly relevant for:

• Surgically menopausal women (bilateral oophorectomy), where up to 50% experience decreased sexual desire due to loss of ovarian testosterone production 1
• Women who have failed other therapeutic strategies for low libido, as testosterone should not be first-line therapy 4
• Patients without biologic or psychosocial causes unrelated to decreased androgen levels 5

Regulatory Status and Formulation Challenges

There are currently no testosterone formulations approved for women by the FDA, Brazilian regulatory agencies, or most other countries 4. This creates important clinical considerations:

• Male testosterone formulations are not recommended for women due to dosing concerns and lack of safety data in female populations 4
• Transdermal patches and topical gels are preferred when used off-label, as they bypass hepatic first-pass metabolism 5
• Intravaginal testosterone cream has shown safety and efficacy for vaginal atrophy and sexual function in postmenopausal breast cancer survivors on aromatase inhibitors 2

Safety Profile and Monitoring

The available safety data, while limited in duration, is reassuring:

• Most adverse events are application site reactions that are well-tolerated and reversible upon discontinuation 1, 5
• No increased risk for mortality, cardiovascular events, or prostate cancer has been observed in observational studies, though long-term safety data beyond 10 years is lacking 2
• Concerns about breast cancer risk may be overstated, as androgens may actually suppress the proliferative effects of estrogen and progesterone 6
• A large cohort study of nearly 50,000 breast cancer patients followed for up to 20 years showed no increased breast cancer-specific mortality with vaginal estrogen use 2

Practical Prescribing Approach

When considering testosterone therapy for postmenopausal women with HSDD:

1. Confirm the diagnosis of HSDD with validated instruments and rule out other causes of sexual dysfunction (relationship issues, medications like SSRIs, depression, anxiety) 4, 3

2. Discuss risks and benefits thoroughly with the patient, emphasizing the off-label nature of treatment and limited long-term safety data 4

3. Consider testosterone only after other strategies have failed, including addressing vaginal dryness with lubricants, pelvic physical therapy, and treating underlying mood disorders 4

4. Use transdermal formulations when possible (patches or gels) to avoid hepatic metabolism 5

5. Testosterone is typically administered with estrogen therapy in postmenopausal women, though the APHRODITE trial showed efficacy with testosterone alone 6

6. Monitor for clinical improvement and adverse reactions at regular intervals, with patients discontinuing if no meaningful benefit is experienced 1, 6

Important Caveats

The magnitude of effect is modest, and patient selection is critical for success 4. No direct correlation has been established between endogenous testosterone levels and sexual dysfunction, so measuring baseline testosterone is not necessarily predictive of treatment response 5.

For cancer survivors, particularly those with hormone-sensitive cancers, the decision becomes more complex. While vaginal testosterone has shown safety in breast cancer survivors on aromatase inhibitors 2, systemic testosterone therapy safety has not been firmly established in survivors of estrogen-dependent cancers 2. The NCCN guidelines note that vaginal DHEA should be used with caution in survivors receiving aromatase inhibitor therapy due to potential impacts on AI activity 2.

Alternative options should be considered first, including flibanserin (FDA-approved for HSDD in premenopausal women but with some postmenopausal data), bupropion, or buspirone for low desire 2, and ospemifene for dyspareunia in women without estrogen-dependent cancer history 2.