The Estrogen Controversy: It's Not Just for Women

Abstract & Commentary

By Eileen C. West, MD, Director, Primary Care Women's Health, Clinical Assistant Professor, Internal Medicine/Obstetrics and Gynecology; University of Oklahoma Health Sciences Center, Oklahoma City. Dr. West reports no financial relationship to this field of study.

Synopsis: A total of 2084 men from two Framingham Heart Study cohorts had endogenous levels of total serum estrogen, testosterone and dehydroepiandrosterone sulfate (DHEA-S) measured. Testosterone and DHEA-S levels were not associated with CVD risk, but those with the highest natural estrogen levels had the lowest cardiovascular risk.

Source: Arnlov, J et al. Endogenous sex hormones and cardiovascular disease incidence in men. Ann Intern Med. 2006;145:176-184.

Scientists have suggested that one reason cardiovascular disease (CVD) develops 5-10 years later for men than for women has to do with endogenous levels of sex hormones.1 These sex hormones, produced naturally by the body, appear to influence CVD risk factors.2 Men with genetic defects of estrogen synthesis develop premature atherosclerosis,3 and genetic variation in estrogen-receptor alpha has been associated with CVD.4 Androgen and estrogen receptors are located in coronary arteries and have been reported to influence atherosclerosis in men.5

In a recent article published in the Annals of Internal Medicine, Arnlov and colleagues present a prospective cohort study begun in the 1980s to study levels of endogenous sex hormones and the development of cardiovascular disease in men. In this study, 2084 men from the original Framingham Heart Study cohort as well as their offspring had labs drawn at one of the visits. Serum total testosterone, estrogen and DHEA-S levels were measured, then the men were followed for ten years for the occurrence of any CVD events or deaths. Events included coronary heart disease, cerebrovascular disease including stroke or transient ischemic attack, congestive heart failure, or peripheral vascular disease including intermittent claudication. The results were then analyzed in several ways.

Each hormone result was divided into four groups, from low to high. For each quartile the following characteristics of the men were recorded: age, systolic blood pressure, diastolic blood pressure, cholesterol ratio and medication use, diabetes status and medication use, body mass index, and smoking status. In general, men with high testosterone levels were younger, more likely to have high cholesterol, somewhat lower in BMI, and more likely to be smokers. Men with higher DHEA-S levels were younger, had lower blood pressure readings, and were more likely to smoke. Men with the highest estradiol levels were more likely to take blood pressure medication.

Results showed that after ten years, factoring out all other cardiovascular risk factors, men in the highest quartile for estradiol suffered fewer cardiovascular events over 10 years (relative risk, 0.68; 95% CI, 0.50-0.92). Testosterone and DHEA-S levels were not associated with CVD risk. The authors conclude that endogenous estrogen has vasculoprotective influences in men.

Commentary

The findings of this cohort study suggest that natural circulating estrogen in a man's body can help protect his heart. The weaknesses of the study include the single draw of blood hormone levels, the lack of use of free hormone levels which are generally considered to be more reliable, and that only white men were studied. Further studies looking at endogenous hormones may help to answer some of the many questions about sex hormones and cardiovascular health, both in men and women.

References

1. Phillips GB. Is atherosclerotic cardiovascular disease an endocrinological disorder? The estrogen-androgen paradox. J Clin Endocrinol Metab. 2005;90:2708-2711.

2. Muller M, et al. Endogenous sex hormones and cardiovascular disease in men. J Clin Endocrinol Metab. 2003;88:5076-5086.

3. Maffei L, et al. Dysmetabolic syndrome in a man with a novel mutation of the aromatase gene: effects of testosterone, alendronate, and estradiol treatment. J Clin Endocrinol Metab. 2004;89:61-70.

4. Schuit SC, et al. Estrogen receptor alpha gene polymorphisms and risk of myocardial infarction. JAMA. 2004;291:2969-2677.

5. Liu PY, et al. Correlating androgen and estrogen steroid receptor expression with coronary calcification and atherosclerosis in men without known coronary artery disease. J Clin Endocrinol Metab. 2005;90:1041-1046.