Medical Risks of Testosterone Supplementation in Menopausal Women
Testosterone therapy in menopausal women carries several documented risks, most notably HDL cholesterol reduction (particularly with oral formulations), along with androgenic side effects like acne and hirsutism, while long-term safety data regarding breast cancer, cardiovascular disease, and thromboembolic events remain insufficient. 1, 2
Established Risks with Good Evidence
Lipid Profile Changes
- HDL cholesterol reduction is the most consistent and well-documented risk, especially with oral methyltestosterone formulations 1
- Transdermal testosterone appears to have less impact on lipid profiles compared to oral preparations 1, 3
- Oral testosterone causes first-pass hepatic effects that worsen the lipid profile, making transdermal formulations preferable 2
Androgenic Side Effects
- Acne and hirsutism are common but generally mild and reversible 3, 2
- These effects are dose-dependent and should be monitored during therapy 2
Risks with Insufficient Long-Term Data
Breast Cancer
- The relationship between testosterone therapy and breast cancer risk remains unclear and controversial 3, 2
- Some experimental studies suggest testosterone may actually decrease estrogen-induced breast epithelial proliferation at low doses 3
- Women with existing breast cancer should not receive testosterone therapy 2
Cardiovascular Disease
- Short-term studies (up to 2 years) have not shown adverse cardiovascular effects including changes in blood pressure, arterial vascular reactivity, hypercoagulable states, or polycythemia 3
- However, long-term cardiovascular safety has not been established 2
- Women with cardiovascular disease should not receive testosterone therapy 2
Thromboembolic Events
- The risk of venous thromboembolism with testosterone therapy in women is unknown 2
- This contrasts with the documented increased risk in men receiving testosterone 4
Endometrial Safety
- Short-term studies (up to 2 years) have not shown increased risk of endometrial hyperplasia when testosterone levels are maintained at or slightly above the upper reference range for reproductive-aged women 3
- Women with uterine cancer should not receive testosterone therapy 2
Formulation-Specific Risks
Oral Testosterone
- Carries higher risk of hepatotoxicity due to first-pass hepatic metabolism 2
- Causes more pronounced HDL cholesterol reduction compared to transdermal forms 1, 2
- Should be avoided in favor of transdermal preparations 2
Transdermal Preparations
- Preferred route due to avoidance of first-pass hepatic effects 2
- Lower risk of lipid abnormalities compared to oral formulations 1, 3
Products Formulated for Men
- Carry risk of excessive dosing when used in women 2
- Custom-compounded products may have inconsistent dosing 2
Critical Safety Gaps
The most significant limitation is the lack of long-term safety data beyond 6 months to 2 years 3, 2. This means:
- Breast cancer risk cannot be definitively assessed 2
- Long-term cardiovascular effects remain unknown 2
- Cumulative effects on bone, liver, and other organ systems are unclear 2
Monitoring Requirements
When testosterone therapy is used, close surveillance must include:
- HDL cholesterol levels (most important given consistent risk) 1
- Testosterone levels to avoid supraphysiologic dosing 2
- Clinical assessment for acne and hirsutism 2
- Subjective assessments of sexual response and satisfaction 2
Absolute Contraindications
Testosterone therapy should not be used in women with: 2
- Breast cancer
- Uterine cancer
- Cardiovascular disease
- Liver disease
Clinical Context
Testosterone therapy should be administered at the lowest effective dose for the shortest time that meets treatment goals 2. The only evidence-based indication is decreased sexual desire with personal distress in postmenopausal women, and even this indication requires concomitant estrogen therapy, as testosterone without estrogen cannot be recommended due to lack of evidence 2, 5.