Is testosterone replacement therapy recommended for a 52-year-old postmenopausal woman with fatigue and a testosterone level of 0.6 micromoles per liter (hypotestosteronemia)?

Testosterone Replacement Therapy for Postmenopausal Women with Fatigue

Testosterone replacement therapy is not recommended for a 52-year-old postmenopausal woman with fatigue and a testosterone level of 0.6 micromoles per liter, as there is insufficient evidence supporting its use for fatigue in women and potential safety concerns exist.

Evidence on Testosterone Use in Women

• Current clinical guidelines primarily address testosterone therapy in men with age-related low testosterone, not women 1
• The evidence for testosterone therapy in postmenopausal women is limited, with most studies focusing on sexual function rather than fatigue 2, 3
• Short-term studies (up to 2 years) suggest testosterone therapy may be relatively safe when maintaining levels at the upper portion or slightly above the reference range for reproductive-aged women 4
• However, long-term safety data for testosterone use in women is lacking, particularly regarding cardiovascular effects, breast cancer risk, and cognitive impacts 5

Fatigue Management in Postmenopausal Women

• For fatigue in postmenopausal women, guidelines recommend assessing for and treating any underlying causes including anemia, thyroid dysfunction, and cardiac dysfunction 1
• Non-pharmacological approaches such as regular physical activity and cognitive behavioral therapy are recommended first-line treatments for fatigue in postmenopausal women 1
• In men, testosterone treatment showed only a less-than-small improvement in vitality and fatigue (SMD 0.17 higher) in clinical trials, suggesting limited efficacy even in the population where it's more established 1, 6

Risks and Safety Considerations

• Common side effects of testosterone therapy in women include mild and reversible acne and hirsutism 4
• Oral testosterone can adversely affect lipid profiles, though transdermal formulations may have less impact 4
• No approved testosterone preparation is specifically available for women; using compounded testosterone creams or reduced dosing of male-approved therapies represents off-label use 5
• Injections or pellets can cause supraphysiological testosterone levels and are not recommended for women 5

Alternative Approaches for Fatigue Management

• Assess for reversible contributing factors to fatigue, such as anemia, thyroid dysfunction, cardiac dysfunction, mood disorders, sleep disturbance, and pain 1
• Counsel patients to engage in regular physical activity, which has demonstrated benefits for fatigue management 1
• Consider referral for cognitive behavioral therapy, which has shown efficacy for fatigue management 1
• For menopausal symptoms affecting quality of life, conventional hormone replacement therapy with estrogen (with or without progestin) may be more appropriate than testosterone 1

Important Caveats

• Most research on testosterone therapy has been conducted in men, with limited data on its use in premenopausal or postmenopausal women 7, 3
• The diagnosis of "hypotestosteronemia" in women is problematic as there are no clear guidelines regarding the diagnosis of androgen insufficiency in women 2
• If sexual dysfunction is the primary concern rather than fatigue, a more focused discussion about testosterone therapy could be warranted, as this is where most evidence for benefit exists 2, 3