Testosterone linked to higher composite cardiovascular risk in postmenopausal women

A retrospective, propensity-matched cohort study of more than 6,300 postmenopausal women found that initiating testosterone therapy was associated with a higher hazard of incident composite cardiovascular disease than having no testosterone exposure. During nearly three years of mean follow-up, the composite event rate was 3.8% in the testosterone group and 0.5% in the comparison group, corresponding to a hazard ratio of 8.08 (95% confidence interval, 4.72–13.82). Although the absolute event rates were low, the researchers reported that the association remained consistent across multiple cohort definitions.

Sensitivity analyses comparing women receiving testosterone plus hormone therapy with women receiving hormone therapy alone also showed the same association. The study used data from the TriNetX US Collaborative Network and included postmenopausal women aged 45 years and older. Participants who initiated testosterone therapy were matched one to one with women without testosterone exposure.

The researchers applied a 12-month washout period, excluding women with any testosterone exposure during the 12 months before the index date, and they also excluded patients with prior cardiovascular disease. Mean follow-up was nearly three years. Propensity-score matching was used to balance measured characteristics, including demographics, smoking status, obesity, hysterectomy status, surgical menopause, baseline use of menopause hormone therapy or vaginal estrogen, vasomotor symptoms, premature ovarian insufficiency, diabetes, hypertension, dyslipidemia and other comorbidities associated with cardiovascular risk.

The composite outcome was broad: coronary artery disease, including angina, myocardial infarction and acute or chronic ischemic heart disease; cerebrovascular disease, including ischemic stroke or arterial occlusive disease; and heart failure. Qualifying events could occur from 30 days to five years after the index date. Because the analysis combined several cardiovascular conditions, its hazard ratio describes the association with the composite endpoint rather than the risk of each individual condition.

The findings also came from an observational cohort, so they demonstrate an association rather than establishing that testosterone therapy caused the cardiovascular events. Mean follow-up of nearly three years and the study design limit conclusions about longer-term risk. The findings identify a potential cardiovascular safety signal for a treatment whose long-term safety in postmenopausal women remains poorly characterized.

Testosterone therapy is sometimes prescribed off-label to address low libido and has proven effective for hypoactive sexual desire disorder, a persistent and distressing loss of interest in sex that is estimated to affect about 10% to 15% of postmenopausal women. There are currently no FDA-approved testosterone products for women in the United States, so healthcare professionals prescribing them for women generally use very low doses of male formulations, usually as a cream or gel. Higher doses have been associated with acne, increased facial hair, scalp hair thinning and a deepening of the voice.

Insufficient evidence also remains regarding testosterone for managing several other menopause symptoms, including fatigue, memory loss, weight gain and loss of bone density. Lead author Xuezhi Daniel Jiang, professor of obstetrics and gynecology at Drexel University College of Medicine, said the low absolute event rates and consistency across analyses warrant further prospective investigation. Stephanie Faubion, medical director for The Menopause Society, said studies of this kind are important because long-term safety data on testosterone use in women are lacking and clinicians must balance individualized risks and benefits when prescribing it.

The research did not evaluate a treatment strategy or demonstrate a clinical benefit from avoiding or discontinuing testosterone therapy.

Subject of Research: Association between testosterone therapy and incident composite cardiovascular disease in postmenopausal women

Article Title: Testosterone therapy may increase risk of cardiovascular disease in postmenopausal women

Article References: Testosterone therapy may increase risk of cardiovascular disease in postmenopausal women. Original publication (Bibliographic details unavailable.)

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Keywords: testosterone therapy, postmenopausal women, cardiovascular disease, composite outcomes, hazard ratio, propensity matching, retrospective cohort, TriNetX, menopause, hypoactive sexual desire disorder, Testosterone, therapy