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Sexual Dimorphism in the Influence of Advanced Aging on Adrenal Hormone Levels: The Rancho Bernardo Study¹

Department of Family and Preventive Medicine, Division of Epidemiology, University of California–San Diego, School of Medicine, La Jolla, California 92093-0607

Address correspondence to: Dr. Elizabeth Barrett-Connor, Professor, Department of Family and Preventive Medicine, Division of Epidemiology, School of Medicine, University of California–San Diego, La Jolla, California 92093-0607.

In recent years, adrenal function and aging has been the subject of intense interest. This cross-sectional study examines age and gender differences in plasma levels of cortisol, dehydroepiandrosterone (DHEA), DHEA-sulfate (DHEAS), and the molar ratio of cortisol/DHEAS in 50–89-yr-old community-dwelling adults. Plasma hormone levels were assayed in samples obtained between 0730 h and 1100 h from 857 men and 735 nonestrogen-using, postmenopausal women. Hormone levels were stratified by 10-yr age groups and compared by two-factor (gender and age) ANOVA.

Overall, age and BMI-adjusted DHEA and DHEAS [collectively DHEA(S)] levels were 40% lower and cortisol levels 10% higher in women than men, resulting in a 1.7-fold higher cortisol/DHEAS molar ratio for women (both, P < 0.001). Cortisol levels increased progressively (20% overall) with age in both men and women (both, P < 0.01). Although DHEA(S) levels declined 60% and the cortisol/DHEAS ratio increased 3-fold across the 40-yr age range for both men and women (all P < 0.001), the pattern of the change differed (all P < 0.01 for interaction). For men, DHEA(S) fell in a curvilinear fashion, with the degree of change decreasing with each decade. In contrast, DHEA(S) levels in women fell 40% from the 50s to 60s, were unvarying from 60–80 yr of age, and declined an additional 18% in the 80s. The cortisol/DHEAS ratio increased in a linear fashion for men, but was flat during the 60–80-yr age range for women. Despite these differences in the effect of aging, levels of DHEA(S) remained lower and cortisol and the cortisol/DHEAS ratio higher, in women than men throughout the 50–89-yr age range. These results were independent of adiposity, smoking, and alcohol consumption.

In summary, among older, healthy adults DHEA(S) levels are lower and cortisol levels higher in women than men. The age-related decline in adrenal androgens persists into advanced age for both men and women, but exhibits a sexually dimorphic pattern. In contrast, cortisol levels in men and women show a parallel, linear increase with aging. These findings may have important implications for a host of age-related processes that exhibit gender differences, including brain function, bone metabolism, and cardiovascular disease.

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