What are the adverse risks of testosterone therapy in a 60‑year‑old postmenopausal woman?

Adverse Risks of Testosterone Therapy in a 60-Year-Old Postmenopausal Woman

Testosterone therapy in postmenopausal women carries significant risks including virilization, unfavorable lipid changes, cardiovascular concerns, and lacks FDA approval for use in women—making it inappropriate for routine use outside of carefully selected cases of hypoactive sexual desire disorder with close monitoring. 1, 2

Regulatory Status and Approved Indications

• No testosterone product is FDA-approved for use in women; all currently marketed testosterone formulations are approved only for male hypogonadism. 1, 2
• The FDA explicitly contraindicates testosterone use in women through its labeling, stating warnings about secondary exposure and lack of approved indications for female patients. 1
• Any testosterone use in a 60-year-old postmenopausal woman would be strictly off-label, and patients must be counseled accordingly before initiation. 2

Androgenic and Dermatologic Risks

• Hirsutism and acne are the most consistent adverse effects of testosterone therapy in women, though the actual incidence rates are not well-defined in long-term studies. 3, 4
• These androgenic effects are generally mild and reversible with discontinuation, but can cause significant distress and cosmetic concerns. 5
• The risk of virilization increases with supraphysiologic dosing, which is particularly concerning with compounded preparations that show considerable batch-to-batch variability. 2, 4

Cardiovascular and Metabolic Risks

• Oral testosterone formulations consistently reduce HDL cholesterol levels (good evidence), which theoretically increases cardiovascular risk, though long-term cardiovascular outcomes remain unknown. 3, 4
• Transdermal testosterone does not appear to adversely affect HDL cholesterol, making it the preferred route if therapy is pursued. 3, 5
• Short-term studies (up to 2 years) have not demonstrated adverse effects on blood pressure, blood viscosity, arterial vascular reactivity, hypercoagulable states, or polycythemia in women. 5
• However, the absence of long-term safety data means cardiovascular risk cannot be definitively excluded, and testosterone therapy should be contraindicated in women with existing cardiovascular disease. 4

Hematologic Effects

• Unlike in men, where erythrocytosis is a common side effect (3-44% depending on formulation), polycythemia has not been demonstrated in short-term studies of women receiving physiologic testosterone doses. 6, 5
• Nevertheless, monitoring for hematologic changes remains prudent given the known effects in men. 6

Breast Cancer Risk

• The relationship between testosterone therapy and breast cancer risk in women remains uncertain and controversial, with mixed experimental data. 5, 4
• Some experimental studies suggest that low-dose testosterone may actually decrease estrogen-induced breast epithelial proliferation. 5
• Women with polycystic ovarian syndrome (a model of chronic supraphysiologic androgen exposure) have not shown increased breast cancer risk in observational studies. 5
• Despite these potentially reassuring signals, the lack of long-term randomized controlled trials means breast cancer risk cannot be excluded, and testosterone therapy is contraindicated in women with breast cancer. 4

Endometrial and Uterine Safety

• Short-term studies up to 2 years have not shown increased risk of endometrial hyperplasia with testosterone therapy when serum levels are maintained at the upper portion or slightly above the reference range for reproductive-aged women. 5
• Testosterone therapy is contraindicated in women with uterine cancer. 4

Hepatotoxicity

• Hepatotoxicity is primarily limited to oral testosterone preparations due to first-pass hepatic metabolism. 6, 3
• Transdermal formulations avoid this risk, making them strongly preferred over oral products. 4
• Testosterone therapy is contraindicated in women with active liver disease. 4

Thromboembolic Risk

• Short-term data have not shown increased risk of thromboembolic events in women receiving physiologic testosterone doses. 5, 4
• However, testosterone therapy should be contraindicated in women with a history of thromboembolic disease given the theoretical risk and lack of long-term safety data. 4

Behavioral and Psychological Effects

• Short-term studies have not demonstrated increased behavioral hostility with testosterone therapy in women. 5
• Data on effects on well-being are mixed, with fair evidence for improvement with transdermal testosterone but insufficient data to recommend testosterone for this indication. 3, 4

Limitations of Available Safety Data

• The most critical limitation is the absence of long-term safety studies beyond 2 years, making it impossible to definitively assess risks of breast cancer, cardiovascular disease, or other chronic conditions. 3, 5, 4
• Most studies have evaluated testosterone in combination with estrogen therapy; data for testosterone alone in postmenopausal women are insufficient. 4
• Clinically available laboratory assays do not accurately detect testosterone concentrations at the values typically found in women, complicating both diagnosis and monitoring. 4

Specific Risks with Compounded Preparations

• Compounded "bioidentical" testosterone preparations are not recommended due to risks of supraphysiological dosing and insufficient evidence of safety or efficacy. 2
• Subcutaneous testosterone pellets carry particular risk of supraphysiologic dosing and should be avoided. 2
• Custom-compounded products show more inconsistent dosing than government-approved products. 4

Monitoring Requirements if Therapy is Pursued

• Baseline testosterone levels should be checked before therapy to exclude elevated concentrations, though routine measurement is not recommended for diagnosis. 2
• Treatment monitoring should occur within 3-6 weeks, maintaining testosterone within the premenopausal physiological range. 2
• Monitoring should include assessment for hirsutism, acne, HDL cholesterol changes (particularly with oral formulations), and subjective evaluation of sexual response. 3, 4
• Laboratory testing should be used only to monitor for supraphysiologic levels, not to diagnose testosterone insufficiency. 4

Contraindications Summary

Absolute contraindications to testosterone therapy in women include: 4

• Breast cancer
• Uterine cancer
• Cardiovascular disease
• Liver disease
• History of thromboembolic events

Critical Clinical Pitfalls

• Never prescribe testosterone for indications other than hypoactive sexual desire disorder confirmed through formal biopsychosocial evaluation—there is inadequate evidence to support use for bone density, hot flashes, lean body mass, or general well-being. 2, 4
• Avoid using testosterone products formulated for men, as they carry risk of excessive dosing despite some clinicians using lower doses off-label. 4
• Do not prescribe oral DHEA systemically, as evidence does not support its effectiveness for sexual symptoms. 2
• Never initiate testosterone without first ruling out physical and psychosocial causes of sexual dysfunction unrelated to androgen levels. 4

Risk-Benefit Context for a 60-Year-Old Woman

• At age 60, a postmenopausal woman is already at increased baseline risk for cardiovascular disease and breast cancer compared to younger women. 6
• The lack of long-term safety data is particularly concerning in this age group, where cumulative exposure to potential risks would be substantial. 5, 4
• The only evidence-based indication (hypoactive sexual desire disorder) must be weighed against unknown long-term risks in an age group where competing health priorities typically take precedence. 2, 4