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A large retrospective study found higher rates of cardiovascular events among postmenopausal women who started testosterone therapy than among matched women who did not. The researchers say the association does not prove the treatment caused the events, and the study lacked details on dose and formulation.
A retrospective study of 3,164 postmenopausal women who started testosterone therapy found higher rates of cardiovascular events than among a matched group not exposed to the treatment, researchers reported at the Menopause Society annual meeting. The results point to a possible safety concern, but the study cannot show that testosterone caused the events.
At five years, the study recorded a composite cardiovascular outcome in 3.8% of women in the testosterone group, compared with 0.5% of matched controls. The outcome included coronary artery disease, cerebrovascular disease and heart failure. The researchers reported a hazard ratio of 8.08 (95% confidence interval 4.72–13.83) for the five-year analysis.
The association was also reported in longer follow-up analyses. At 10 years, events occurred in 5.3% of the testosterone group and 0.5% of controls; the reported hazard ratio was 11.50 (95% CI 6.78–19.50). In an unrestricted follow-up analysis, the figures were 6.2% and 1%, respectively, with a hazard ratio of 5.92 (95% CI 4.09–8.56). These percentages are observed rates, while the hazard ratios are the study’s comparative estimates.
The study used the TriNetX electronic health record network to compare women aged 45 and older who initiated testosterone with women who did not receive it. Researchers excluded people with prior cardiovascular disease and certain other conditions, then used propensity score matching to create two groups of 3,164. Mean follow-up was 2.6 years, despite analyses reporting outcomes over longer periods. A sensitivity analysis also found an association when comparing women taking testosterone plus menopausal hormone therapy with women taking menopausal hormone therapy alone.
How the Finding Affects Treatment Decisions
The results add a cardiovascular safety question to decisions about testosterone use for menopause-related concerns. They do not establish that the treatment is harmful, but they suggest that clinicians and patients may need better evidence about long-term risks, especially because the study reported a marked difference in observed event rates.
Testosterone is sometimes prescribed off-label to women, including for low sexual desire, but there are no FDA-approved testosterone products for women, according to the source report. Evidence that testosterone relieves menopausal symptoms is limited; some research suggests a benefit for women with low libido. The study does not settle whether an individual patient should use treatment. Its findings instead underscore the need to weigh uncertain benefits against safety information that remains incomplete.
External biostatistician Stephen Burgess said the reported difference was concerning, while cautioning that the study could not prove treatment caused it. The results should be read as a signal for further research, not as a definitive estimate of risk for every patient or every prescribing approach.
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Why Long-Term Safety Evidence Is Limited
Research into testosterone therapy for menopause has often involved small samples or short follow-up, and trials were generally not designed to measure major cardiovascular events. That makes it difficult to use trial data to establish long-term safety for less common outcomes. The study authors said they turned to a large, multicenter health-record database to examine the question.
However, database studies have limits of their own. The retrospective design means researchers examined existing records rather than assigning treatment and tracking outcomes prospectively. Records may misclassify exposure or diagnoses, and differences between treated and untreated patients can remain even after statistical matching. The study also did not record the testosterone dose, formulation, delivery route or reason for prescribing it, limiting conclusions about specific treatment regimens.
“Our findings suggest that testosterone use is associated with a higher risk of cardiovascular events in postmenopausal women.”
— Xuezhi (Daniel) Jiang, MD, PhD, of Drexel University College of Medicine and Reading Hospital
What the Study Cannot Establish
The findings do not establish a causal link between testosterone and cardiovascular disease. Because the analysis was observational, unmeasured differences between groups may have influenced the results. The researchers also noted possible misclassification, residual confounding, a relatively short mean follow-up and few cardiovascular events overall.
It is also unclear whether the association applies to particular doses, formulations, routes of delivery or reasons for treatment: those details were not available in the database. The authors cautioned that the results should not be generalized to all menopausal women receiving guideline-concordant, physiologic-dose transdermal testosterone. The study does not identify which individual cardiovascular outcomes accounted for the observed pattern.
Prospective Studies Needed to Verify Risk
Jiang said the results should be validated in prospective studies, which could follow participants under a planned research design and collect more detailed treatment information. Future work should also examine individual cardiovascular outcomes rather than relying only on the composite measure.
Until further evidence is available, the study provides a reason for continued scrutiny, not a definitive ruling on testosterone therapy. The source report does not describe a specific next trial or timetable for new results. Further research will need to clarify whether the association persists when dose, formulation, route and treatment indication are accounted for.
Key Questions
Does this study prove testosterone causes heart disease?
No. It was a retrospective observational study and found an association. Its design cannot establish that testosterone caused the cardiovascular events.
How many women were included?
After propensity score matching, the study included 3,164 women in each group: one group that initiated testosterone and a control group not exposed to it.
What cardiovascular outcomes did researchers count?
The primary composite outcome included coronary artery disease, cerebrovascular disease and heart failure.
Does the finding apply to every form of testosterone treatment?
That is not known. The database did not include dose, formulation or delivery route, and the study authors cautioned against generalizing the results to all women receiving guideline-concordant, physiologic-dose transdermal testosterone.
What research is needed next?
The authors called for prospective studies to validate the association and for research that examines individual cardiovascular outcomes and captures more detail about treatment.
Source: rss
