Plasma Estradiol in Premenopausal Women: The Framingham Offspring Study

Abstract

The conspicuous protection of premenopausal women from coronary heart disease is one of the remaining puzzles of cardiovascular disease epidemiology. The measurement of plasma estradiol levels in Framingham Offspring Study participants was undertaken to improve the understanding of the relationship of endogenous female hormones, which have long been suspected as the principle source of women's protection from coronary risk. Menstruating women aged 30 to 54 years who were not taking oral contraceptive medication and were free of cardiovascular disease were studied. Estradiol levels were found to show average decline of about 0.4% per year of age from age 30 to age 54. This decline was found to be attributable to cigarette smoking; cigarette smokers exhibited lower estradiol levels, particularly after age 40. As expected, women with larger subscapular skinfolds measurements had higher average estradiol and women who had higher levels of fitness had lower levels. Weak, not statistically significant, negative associations between self-reported measures of physical activity and estradiol levels generally supported the findings for fitness. The estimated impact of fitness on estradiol levels appears to be modest (0.3% decrease for every 1 min of additional treadmill time). Alcohol consumption, tubal ligation, and number of live births were not significantly related to estradiol levels. Variation in high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and very-low-density lipoprotein cholesterol could be explained by body fatness and cigarette smoking but not by plasma estradiol levels. Only fasting plasma glucose level was found to be associated (inversely) with estradiol. This study, while adding to the wealth of data that document the adverse health consequences of cigarette smoking, does not support suggestions that naturally occurring variation in estradiol levels is a major determinant of lipoprotein metabolic function.