DOES THE LOW LEVEL OF DEHYDROEPIANDROSTERONE SULFATE (DHEA-S) INDEPENDENTLY INFLUENCE RISK OF DEATH AT AGE 55 YEARS AND OLDER?

Aim. To investigate on the possible associations of dehydroepiandrosterone sulfate (DHEA-S) levels in blood serum, with cardiovascular diseases (CVD), risk factors (RF) and all-case mortality, as CV mortality, and to assess the specifics.

Material and methods. The results analyzed, of the prospective cohort study “Stress, ageing and health”, that included 1876 persons at age 55 years and older. According to the protocol, all participants were assessed on the RF and CVD. Mortality was assessed based on the continuous death registry, with the standard methods. During 8-year observation, 473 deaths registered, including CVD — 286. Statistics was done with SAS software.

Results. Mean DHEA-S levels were 1,5 times higher in men than in women. A significant decline of concentration was found with the age, and decrease gradient was 2 times faster in men. Prevalence of the low DHEA-S level in 55 and older was 17,4%, increased from 7,0% among 55-64 y. o. to 46,2% at age 85 and older (p<0,0001). There were no significant relations with ischemic heart disease (CHD), diabetes and chronic heart failure in men and women. Mean level of DHEA-S was significantly higher in male smokers, and prevalence of low DHEA-S levels in male smokers was lower than in non-smokers. Low concentrations of the studied parameter decreased with the raise of compression force in dynamometry. Similarly, C-reactive protein (CRP) and total cholesterol (TC) in the 1st quintile significantly predicted lower level of DHEA-S. Application of the multiple logistic regression made it to evaluate the independent associations of low DHEA-S and RF, similar for both sexes: age, smoking, low dynamometry, cholesterol level outside the 2-4 quintiles, low CRP. In multiple model of prognostic significance of DHEA-S for all-cause mortality and CV mortality in men there were no significant relations (HR 1,13 13 (0,86-1,50), р=0,38; and HR 1,18 (0,84-2,67), р=0,34, respectively). In female cohort, on the contrary, death risk in low DHEA-S was 1,5 times higher, than in higher concentrations (HR 1,58, 95% CI 1,12-2,24, p=0,009). The significance of differences remained with correction for the age, raised BP, CHF, low dynamometry and TC levels outside 2-4 quintiles. For CV mortality in women the low DHEA-S was significant at 9%.

Conclusion. Low DHEA-S is independent predictor of all-cause mortality in women 55 years and older, but does not significantly associate with mortality in men of the same age.

1. Labrie F. Adrenal androgens and intracrinology. Semin Reprod Med, 2004; 22: 299-309.

2. Parker CR, Slayden SM, Azziz R, Crabbe SL, et al. Effects of aging on adrenal function in the human: responsiveness and sensitivity of adrenal androgens and cortisol to adrenocorticotropin in premenopausal and postmenopausal women. J. Clin. Endocrinol., 2000; 85: 48-54.

3. Nafziger AN, Bowlin SJ, Jenkins PL, Pearson TA. Longitudinal changes in dehydroepiandrosterone concentrations in men and women. J Lab Clin Med, 1998; 131: 316-23.

4. Bhagra S, Nippoldt TB, Nair KS. Dehydroepiandrosterone in adrenal insufficiency and ageing. Curr Opin Endocrinol Diabetes Obes, 2008; 15: 239-43.

5. Tchernof A, Labrie F. Dehydroepiandrosterone, obesity and cardiovascular disease risk: a review of human studies. Eur J Endocrinol, 2004; 151: 1-14.

6. Valenti G, Denti L, Maggio M, et al. Effect of DHEA-S on skeletal muscle over the life span: the InCHIANTI study. J Gerontol A Biol Sci Med Sci, 2004; 59A: 466-72.

7. Zhu G, Yin Y, Xiao CL, et al. Serum DHEA-S levels are associated with the development of depression. Psychiatry Res, 2015; 30; 229 (1-2): 447-53.

8. Nair KS, Rizza RA, O’Brien P, et al. DHEA in Elderly Women and DHEA or Testosterone in Elderly Men. N Engl J Med, 2006; 355: 1647-59.

9. Haring R, Teng Z, Xanthakis V, et al. Association of sex steroids, gonadotrophins, and their trajectories with clinical cardiovascular disease and all-cause mortality in elderly men from the Framingham Heart Study. Clin Endocrinol, 2013; 78(4): 629-34.

10. Cappola AR, Xue QL, Walston JD, et al. DHEA-S levels and mortality in disabled older women: the Women’s Health and Aging Study I. J Gerontol A Biol Sci Med Sci, 2006; 61(9): 957-62.

11. Shkolnikova M, Shalnova S, Shkolnikov VM, et al. Biological mechanisms of disease and death in Moscow: rationale and design of the survey on Stress Aging and Health in Russia (SAHR). BMC Public Health 2009; 9: 293.

12. Goncharov NP, Katsiya GV. Dehydroepiandrosterone biosynthesis, metabolism, biological effects, and clinical use (analytical review). Andrology and genital surgery, 2015; 1: 13-22.

13. Russian (Гончаров Н. П., Кация Г. В. Дегидроэпиандростерон: биосинтез, метаболизм, биологическое действие и клиническое применение (аналитический обзор). Андрология и генитальная хирургия, 2015; 1: 13-22).

14. Salvini S, Stampfer MJ, Barbieri Rl, Hennekens CH. Effects of Age, Smoking and Vitamins on Plasma DHEAS Levels: A Cross-Sectional Study in Men. Journal of Clinical Endocrinology and Metabolism, 1992; 74; 1: 139-43.

15. Glei DA, Goldman N, Weinstein M, Liu I-W. Dehydroepiandrosterone sulfate (DHEAS) and health:does the relationship differ by sex? Experimental Gerontology, 2004; 39: 321-31.

16. Tannenbaum С, Barrett-Connor E, Laughlin GA, Platt RW. A longitudinal study of dehydroepiandrosterone sulphate (DHEAS) change in older men and women: the Rancho Bernardo Study. European Journal of Endocrinology, 2004; 151: 717-25.

17. Khaw KT, Tazuke S, Barrett-Connor E. Cigarette smoking and levels of adrenal androgens in postmenopausal women. New England Journal of Medicine, 1988; 318: 1705-9.

18. Tivesten A, Vandenput L, Carlzon D, et al. Dehydroepiandrosterone and its sulfate predict the 5-Year Risk of Coronary Heart Disease Events in Elderly Men. J Am Coll Cardiol, 2014; 64: 1801-10.

19. Stork S, Bots ML, Grobbee DE, van der Schouw YT. Endogenous sex hormones and C-reactive protein in healthy postmenopausal women. J Intern Med, 2008; 264: 245-53.

20. Ohlsson С, Labrie F, Barrett-Connor E, et al. Low serum levels of dehydroepiandrosterone sulfate predict all-cause and cardiovascular mortality in elderly Swedish men. J Clin Endocrinol Metab, 2010; 95; 9: 4406-14.

21. Trivedi DR, Khaw KT, Dehydroepiandrosterone sulfate and mortality in elderly men and women, J Clin Endocrinol Metab, 2001; 86; 9: 4171-7.

22. Baulieu EE, Thomas G, Legrain S, et al. Dehydroepiandrosterone (DHEA), DHEA sulfate, and aging: contribution of the DHEAge Study to a sociobiomedical issue. Proc Natl Acad Sci USA. 2000; 97; 8: 4279-84.