(029) The Use of Testosterone in Patients With History of Estrogen-Responsive Cancers

Abstract Introduction Testosterone has recently garnered interest for its demonstrated therapeutic benefits in treating female hypoactive sexual desire disorder (HSDD). However, the safety profile of testosterone has been under-researched in the female cancer patient population, specifically in those with possibly estrogen-responsive breast and gynecologic malignancies, who tend to have high rates of reported sexual dysfunction. Because testosterone aromatases into estrogen, there is concern that use of testosterone in these patients may lead to increased risk for life-threatening events or cancer recurrence. Objective To identify whether there are increased rates of life-threatening events associated with the use of testosterone therapy in patients with a history of malignancies linked with estrogen sensitivity. Methods Cross-sectional analysis of available records from the TriNetX database was performed on 11/1/25 to calculate risk ratios in outcomes of pulmonary embolism, thrombotic events, acute kidney injury, stroke, and osteoporosis between cohorts of females aged 18 and older with history of breast or gynecologic cancer with and without subsequent testosterone use. Patients were followed for approximately 6 years, on average, from the time of testosterone prescription. Results Using ICD-10 codes, 792 individuals were identified for inclusion in Cohort 1, which consisted of patients with a history of malignant neoplasm of the cervix uteri (C53), breast (C50), uterus (C55), ovary (C56), or corpus uteri (C54) with subsequent prescription testosterone use (RxNorm-10 379) for sexual dysfunction (F52) or menopausal/perimenopausal disorders (N95). Using the same codes (C50, C53-56), 1 192 307 controls who were not prescribed testosterone were included in Cohort 2. After propensity-score matching for age, ethnicity, hypertension, baseline coronary artery disease, chronic ischemic heart disease, smoking/tobacco use, nicotine dependence, diabetes, hyperlipidemia, and chronic kidney disease, Cohorts 1 and 2 each included 677 patients. After applying a Bonferroni correction to account for multiple comparisons (α = 0.01), risk of stroke (RR = 1.083 with respect to the control group; p = 0.8400), osteoporosis (RR = 0.841; p = 0.2851), pulmonary embolism (RR = 0.689; p = 0.3329), and thrombotic events (RR = 0.677; p = 0.2167) were not significantly different in patients with a history of testosterone use compared to those without. Interestingly, risk of acute kidney injury (RR = 0.519; p = 0.0025) was significantly lower in patients with testosterone use compared to those without. Conclusions Taken together, these results suggest that use of testosterone therapy in females with a history of breast or gynecologic cancers does not appear to be associated with significantly increased risk for adverse, potentially life-threatening outcomes. There are several important limitations to this study. As a database study, it is inherently reliant on ICD-10 codes, which may not capture all patients with a given condition. Additionally, due to database limitations, we could not determine the duration or age of initiation of testosterone therapy among patients, or devise a reliable measure to capture recurrence. As recurrence is a major outcome of interest, further study in this area is needed to more fully assess the safety profile of testosterone in the estrogen-responsive cancer population. Disclosure No.