Subcutaneous Testosterone Injection for Postmenopausal HSDD: Not Recommended
Subcutaneous testosterone pellets are explicitly not recommended for treating hypoactive sexual desire disorder in postmenopausal women due to risks of supraphysiological dosing and insufficient safety evidence; transdermal formulations are the preferred route of administration. 1
Why Subcutaneous Administration Is Contraindicated
The Latin American Association of Gynecological Endocrinology position statement (2025) specifically advises against subcutaneous testosterone pellets because they carry significant risk of delivering supraphysiological doses that cannot be easily titrated or reversed. 1
Subcutaneous pellets release testosterone in an uncontrolled manner over months, making it impossible to adjust dosing if adverse effects develop or if serum levels exceed the premenopausal physiological range. 1
Unlike transdermal preparations that can be discontinued immediately if problems arise, pellet implants continue releasing testosterone for 3–6 months after insertion, creating a prolonged exposure risk. 1
Recommended Treatment Algorithm for HSDD
Step 1: Confirm Diagnosis Through Formal Biopsychosocial Evaluation
HSDD diagnosis requires a comprehensive biopsychosocial assessment that excludes relationship problems, psychiatric disorders, medication side effects, and other medical causes of low desire before considering testosterone therapy. 1
Do not rely on serum testosterone measurements for diagnosis—routine androgen levels are not recommended to establish HSDD, though baseline testosterone should be checked before initiating therapy to exclude pre-existing elevated concentrations. 1
Step 2: Counsel on Off-Label Use and Alternative FDA-Approved Options
Patients must be informed that testosterone therapy for women is off-label in the United States, as no FDA-approved testosterone formulation exists for female HSDD. 1, 2
The American College of Obstetricians and Gynecologists recommends considering FDA-approved alternatives first, specifically flibanserin or bremelanotide, both of which have established safety profiles for postmenopausal HSDD. 3
Step 3: Initiate Transdermal Testosterone (If Proceeding After Counseling)
Transdermal testosterone formulations (patches or gels) are the only recommended delivery method because they allow dose titration, maintain physiologic levels, and can be discontinued immediately if adverse effects occur. 1, 4, 5
Large randomized controlled trials demonstrate that transdermal testosterone patches improve sexual function, desire, and satisfying sexual events in postmenopausal women with HSDD, with favorable short-term safety profiles showing mainly mild androgenic side effects (increased hair growth, acne). 4, 5
Transdermal testosterone has been studied both as monotherapy and in combination with estrogen/progestin therapy, showing efficacy in surgically and naturally menopausal women. 4, 5
Step 4: Monitor Within 3–6 Weeks and Maintain Physiologic Levels
Follow-up assessment should occur within 3–6 weeks of initiating therapy to evaluate symptom response and check serum testosterone levels. 1
Testosterone concentrations must be maintained within the premenopausal physiological range—supraphysiological levels increase risks of cardiovascular events, virilization, and potential long-term harms. 1
Clinical practice guidelines emphasize that women will only continue therapy if they experience meaningful benefit, providing a natural checkpoint for efficacy assessment. 5
Critical Safety Considerations
Formulations to Avoid
Compounded "bioidentical" testosterone preparations are not recommended due to lack of quality control, inconsistent dosing, and insufficient evidence of safety or efficacy. 1
Oral DHEA is not advised for systemic treatment of sexual symptoms—evidence does not support its effectiveness for HSDD, though vaginal DHEA (prasterone) is approved specifically for genitourinary syndrome of menopause, not desire disorders. 1
Long-Term Safety Gaps
No testosterone product has been FDA-approved for women primarily because long-term safety data (particularly regarding cardiovascular outcomes and breast cancer risk) remain incomplete despite ongoing Phase III trials. 4, 2
Interim data from long-term testosterone gel trials show continued low rates of cardiovascular events and breast cancer in postmenopausal women at increased cardiovascular risk, providing some reassurance but not definitive evidence. 4
Available data suggest androgens may suppress proliferative effects of estrogen and progesterone on breast tissue, but this protective hypothesis requires further validation. 5
Alternative Approaches When Testosterone Is Not Appropriate
Intravaginal DHEA (prasterone) may improve sexual function in women with concurrent dyspareunia related to vaginal atrophy, addressing a mechanical barrier to sexual activity rather than desire itself. 3
Vaginal testosterone cream represents a potential safer alternative to systemic administration for some patients, particularly cancer survivors, though its primary indication is local genitourinary symptoms rather than central desire. 3
The North American Menopause Society supports considering these local therapies when systemic testosterone is contraindicated or when vaginal symptoms contribute significantly to sexual dysfunction. 3
Common Pitfalls to Avoid
Prescribing testosterone without formal biopsychosocial evaluation—many cases of low desire stem from relationship issues, depression, or medication side effects that testosterone will not address. 1
Using subcutaneous pellets for convenience—the inability to reverse supraphysiological dosing outweighs any perceived benefit of less frequent administration. 1
Failing to check baseline testosterone levels—starting therapy in a woman with already-elevated androgens increases virilization risk and suggests an alternative diagnosis. 1
Monitoring testosterone levels too infrequently—waiting longer than 6 weeks for initial follow-up may allow supraphysiological levels to persist, increasing adverse effect risk. 1