Can testosterone therapy increase the growth of breast fibroids (uterine leiomyomas)?

Testosterone's Effect on Breast Fibroids

The relationship between testosterone therapy and breast fibroids is complex, with conflicting evidence suggesting both potential growth-promoting and growth-inhibiting effects, though current clinical guidelines indicate no definitive evidence that testosterone increases fibroid growth in breast tissue.

Testosterone's Effects on Breast Tissue

• Testosterone's impact on breast tissue is variable, with some preclinical studies suggesting that androgen receptor activation may actually prevent or reduce hormonally driven breast changes 1
• Early preclinical studies suggested that testosterone in high concentrations might increase the risk for estrogen-dependent growth because testosterone can be aromatized to estrogen 1
• Other preclinical studies indicate that androgen receptor activation by exogenous testosterone may promote breast tissue growth 1
• Recent genomic profiling data from Cedars-Sinai Medical Center suggests that androgen receptor activation may actually have protective effects against hormonally driven breast changes 1

Conflicting Evidence in Research

• In experimental studies, testosterone action is generally anti-proliferative and pro-apoptotic in breast tissue, mediated via the androgen receptor, despite testosterone's potential for aromatization to estrogen 2
• Animal studies suggest testosterone may serve as a natural, endogenous protector of the breast and limit mitogenic and cancer-promoting effects of estrogen on mammary epithelium 2, 3
• Results from studies in rhesus monkeys suggest that testosterone may protect the breast and limit estrogen's mitogenic effects on mammary epithelium 3
• The effects appear to be dose-dependent and influenced by the presence of specific coregulatory proteins at the receptor level 3

Clinical Implications

• There are no prospective clinical data to definitively inform or estimate the risk of hormone therapy on the progression of hormone-sensitive tissue growth 1
• For patients with hormone-sensitive conditions, a tailored conversation about hormone therapy should be informed by individual patient factors and preferences 1
• Testosterone therapy alone is not recommended for estrogen-depleted women due to the potential risk of enhanced aromatization to estrogen 2
• When testosterone is used therapeutically, monitoring for potential tissue changes is advisable, particularly in patients with pre-existing fibroids or other hormone-sensitive conditions 1

Special Considerations

• Implanted testosterone pellets used for vasomotor or sexual symptoms are often combined with aromatase inhibitors and have not been shown to increase tissue growth risk, though these preparations use much lower doses than those used in gender-affirming hormone therapy 1
• It remains unclear whether breast tissue-directed hormone therapy, such as tamoxifen or aromatase inhibitors, may block the effects of therapeutic testosterone and its aromatization to estrogen 1
• The measurement of pulsatility index of uterine arteries has been suggested as a possible screening tool before initiating hormone therapy in women with fibroids, as low resistance index in these arteries is associated with increased risk of fibroid growth 4

Conclusion

• While the relationship between testosterone and breast fibroids is complex, current evidence does not definitively establish that testosterone therapy increases fibroid growth in breast tissue 1
• Translational trials examining hormone therapy in diverse patient populations remain critical to advance understanding of optimal treatment approaches 1