Testosterone Replacement Therapy in Women: Current Evidence and Guidelines
Critical Limitation: No FDA-Approved Products for Women
There is currently no testosterone preparation specifically approved by the FDA for the treatment of androgen insufficiency or sexual dysfunction in women, and the available evidence-based guidelines focus exclusively on male testosterone deficiency. 1, 2, 3
Off-Label Use Context
While testosterone has been used off-label to treat low libido and sexual dysfunction in women for over 40 years, this practice lacks formal guideline support and FDA approval. 2
Potential Candidates for Off-Label Testosterone Therapy
Postmenopausal women with decreased sexual desire associated with personal distress and no other identifiable cause may be candidates for testosterone therapy, but only when used concomitantly with estrogen therapy. 3
Diagnostic Considerations:
Rule out non-hormonal causes first: physical factors, psychosocial factors, medications, and relationship issues must be excluded before considering testosterone therapy 3
Ensure physiologic cause for low testosterone: bilateral oophorectomy, hypopituitarism, adrenal insufficiency, glucocorticoid therapy, or use of oral contraceptives/estrogens 4, 3
Clinical symptoms to assess: diminished sense of well-being, persistent unexplained fatigue, decreased sexual desire, sexual receptivity, and pleasure in an estrogen-replete woman 4
Laboratory testing limitations: Clinically available assays do not accurately detect testosterone at concentrations typically found in women, and no specific testosterone level has been clearly linked to a clinical syndrome of testosterone insufficiency 3
Testing should only monitor for supraphysiologic levels during therapy, not to diagnose deficiency 3
Treatment Approach (When Considered)
Transdermal patches and topical gels or creams are strongly preferred over oral formulations due to first-pass hepatic effects and adverse lipid profile changes documented with oral testosterone. 5, 3
Dosing Strategy:
Aim for serum testosterone levels at the upper portion or slightly above the reference range for reproductive-aged women 5
Use the lowest dose for the shortest time that meets treatment goals 3
Custom-compounded products should be used with extreme caution due to inconsistent dosing 3
Testosterone products formulated for men carry risk of excessive dosing, though some clinicians use lower doses off-label 3
Evidence for Efficacy
Randomized controlled trials up to 2 years demonstrate positive effects on sexual desire, arousal, and orgasmic response in postmenopausal women after spontaneous or surgical menopause 3
Data are inadequate to support testosterone use for any other indication including bone mineral density, hot flashes, lean body mass, or general well-being 3
Safety Profile (Short-Term Data Only)
Short-term studies up to 2 years show acceptable safety when testosterone levels are maintained at physiologic ranges: 5
Mild and reversible acne and hirsutism are the most common side effects 5, 3
No hepatotoxicity, endometrial hyperplasia, or behavioral hostility at physiologic doses 5
No adverse cardiovascular effects including blood pressure changes, blood viscosity alterations, or polycythemia 5
Breast cancer risk data are mixed and inconclusive - some experimental studies suggest decreased estrogen-induced breast epithelial proliferation with low-dose testosterone 5
Absolute Contraindications
Testosterone therapy is contraindicated in women with: 3
- Breast cancer (current or history)
- Uterine cancer (current or history)
- Cardiovascular disease
- Liver disease
Monitoring Requirements
Measure testosterone levels before and during therapy to monitor for supraphysiologic levels (not to diagnose deficiency) 3
Assess subjective sexual response, desire, and satisfaction at regular intervals 3
Evaluate for adverse effects: acne, hirsutism, voice changes, clitoral enlargement 3
Duration of safety data is limited to 6 months in most studies 3
Critical Knowledge Gaps
Long-term safety beyond 2 years has not been established for testosterone therapy in women, and conclusive evidence regarding cardiovascular disease, breast cancer risk, and thromboembolic events is lacking. 5, 3
Testosterone therapy without concomitant estrogen cannot be recommended due to lack of evidence. 3
Clinical Pitfall to Avoid
The AUA guidelines 1 and related materials 6, 7, 8 address testosterone deficiency exclusively in men, with specific warnings about accidental transference to women and children causing virilization, precocious puberty, and hyperandrogenism. 1 These male-focused guidelines should not be extrapolated to female patients.