Hormones and Cardiovascular Risk: More Unknowns than Knowns

By Rina Mauricio, M.D.

Assistant Professor of Internal Medicine

It is not uncommon for practitioners to care for patients on exogenous hormones, from hormone replacement therapy post menopause, during assisted reproductive technology, or as part of gender-affirming care. At the recent #AHA23, we reviewed data on the associations between hormone therapy and cardiovascular disease – and concluded that far more is unknown than known.

The session started with a review on the known associations between assisted reproductive technology (ART) and cardiovascular disease (CVD). Due to the hemodynamic and hemostatic changes of ART, practitioners must keep in mind acute complications such as ovarian hyperstimulation syndrome (OHSS), thromboembolism, and bleeding when counseling their patients with CVD or cardiovascular risk factors who are contemplating ART. ART has been associated with an elevated risk of the hypertensive disorders of pregnancy, which includes preeclampsia, and thromboembolism. Currently, there are no data confirming an elevated risk of future cardiovascular disease after ART, though studies are lacking.

The session then pivoted to hormone replacement therapy (HRT) and what to do after a patient on HRT has a myocardial infarction. Multiple studies have looked at the relationship between HRT and cardiovascular disease with mixed results, likely due to differences in study population, timing of HRT initiation, and formulation of HRT used, among other factors. However, when taking the sum of available data, none suggest benefit of HRT for the primary or secondary prevention of atherosclerotic cardiovascular disease, a finding reiterated in the 2011 update to the Guidelines for the Prevention of Cardiovascular Disease in Women. It is important to acknowledge that data in this field are from older studies conducted at a time when primary and secondary prevention of ASCVD and the epidemiology of cardiovascular risk factors were different. Thus, it may be time for updated data in a more contemporary cohort.

Testosterone-replacement therapy has been on the rise, either for diagnosed hypogonadism or, more commonly, for symptoms that have been attributed to low testosterone with or without documented low testosterone levels. The recently published TRAVERSE trial found no elevated risk for cardiovascular disease in men with documented hypogonadism and either established CVD or at risk for CVD. All study participants in this trial had to have documented low fasting testosterone levels, and testosterone levels were monitored carefully throughout. Such careful monitoring must be kept in mind when applying these trial results to individual patients.

The need for more research on the association between exogenous hormone therapy and cardiovascular disease was reiterated several times during this session, particularly on the question of gender-affirming hormone therapy and possible cardiovascular disease risk. While epidemiologic studies have demonstrated an association between estrogen or testosterone and future CVD risk, these studies are limited, lack longitudinal follow-up, and are mainly observational. Thus, more studies on hormone therapy, for all uses discussed above, are needed.

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