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For post menopausal women, higher ratios of testosterone to estradiol hormones were associated with elevated cardiovascular risk, an observational analysis showed.

Each standard deviation greater log-transformed testosterone/estradiol ratio was associated with increased likelihood of experiencing incident cardiovascular disease (CVD), coronary heart disease (CHD), and heart failure (HF) over a median 12.1 years of follow-up:

• CVD: HR 1.19 (95% CI 1.02 to 1.40)
• CHD: HR 1.45 (95% CI 1.19 to 1.78)
• HF: HR 1.31 (95% CI 1.01 to 1.70)

Additionally, according to Di Zhao, PhD, of Johns Hopkins University Bloomberg School of Public Health in Baltimore, and colleagues: women had greater risks for CVD events (HR 1.14, 95% CI 1.01 to 1.29) and CHD (HR 1.20, 95% CI 1.03 to 1.40) per standard deviation in total testosterone.

However, those with higher estradiol levels saw a significantly lower risk for experiencing CHD (HR 0.77 per standard deviation, 95% CI 0.63 to 0.95), they wrote in the .

Both sex hormone binding globulin and dehydroepiandrosterone levels were not significantly tied to any specific cardiovascular outcomes.

"A woman's sex hormone levels and ratios of them isn't something that physicians regularly check," noted senior study author Erin Michos, MD, also of Johns Hopkins University School of Medicine in a statement. "Because an imbalance in the proportion of testosterone to estrogen may affect heart disease risk, physicians may want to think about adding hormone tests to the toolbox of screenable risk factors, like blood pressure or cholesterol, to identify women who may be at higher risk of heart or vascular disease."

The analysis included 2,834 women from the Multi-Ethnic Study of Atherosclerosis, which included white, black, Hispanic, and Chinese postmenopausal women, all of whom were free from cardiovascular disease at baseline. The final analysis was adjusted for demographic factors, lifestyle factors, and intermediate CVD risk, some of which included systolic blood pressure, cholesterol, use of antihypertensive and lipid lowering medications, diabetes, and renal function.

During the follow-up period, 283 women developed incident CVD, 171 developed CHD, and 103 developed an HF event.

In regards to specific HF subtype, a higher risk for HF and reduced ejection fraction (HFrEF) was associated with a higher testosterone to estradiol ratio (HR 1.65, 95% CI 1.07 to 2.54), congruent with the overall analysis. Also, higher estradiol levels were tied to a lower risk for HFrEF (HR 0.60, 95% CI 0.39 to 0.93). However, no hormone levels had any significant association with the risk for heart failure with preserved ejection fraction (HFpEF) -- a finding authors Virginia M. Miller, PHD, and Rekha Mankad, MD, both of the Mayo Clinic in Rochester, Minn., called unexpected.

"By addressing a set of defined incident events, this study provides new information needed to develop mechanistic hypotheses of causal relationships of hormones with specific aspects of cardiac function," they wrote.

Miller and Mankad also suggested that clinicians engaging in "precision medicine" should assess individual CVD risk by accounting for "individualized profiles of genetic variants in enzymes associated with steroids metabolism, uptake, and receptors in conjunction with risk for specific cardiovascular pathologies."

Although this study builds on prior literature linking sex hormone levels to heart risks, Zhao's group explained, it remains "unclear what the best intervention is to modify sex hormone levels for risk reduction." In regards to hormone therapy, previous randomized clinical trials have "failed to conclusively show" effectiveness as primary prevention for CHD risk or CVD mortality in postmenopausal women. However, the group added these trials did not assess compounds besides conjugated equine estrogen and medroxyprogesterone acetate and may therefore be limited in their conclusions.

To further assess this, the group conducted a sensitivity analysis excluding all women who were taking hormone therapy, which yielded similar results to the primary analysis. A higher testosterone/estradiol ratio was tied to a larger risk for CHD (HR 1.55, 95% CI 1.20 to 2.00) and HF (HR 1.51, 95% CI 1.10 to 2.06), while higher estradiol levels were tied to a lower risk for CHD (HR 0.76, 95% CI 0.58 to 0.99).