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Temporal changes in sex hormones linked to increased mortality in older men
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In older men, all-cause and cause-specific mortality are associated with temporal changes in serum testosterone, calculated free testosterone, dihydrotestosterone and estradiol, study findings show.
“The present study extends our understanding of the contemporaneous longitudinal relationship between distinct patterns of progressive change in circulating androgens and estrogens with subsequent death in older men,” the researchers wrote.
David J. Handelsman, MBBS, PhD, FRACP, foundation professor and director of the ANZAC Research Institute in Sydney, and colleagues evaluated data from the CHAMP study on men aged at least 70 years at baseline (2005-2007; n = 1,705), 2 years (n = 1,367) and 5 years of follow-up (n = 958). Researchers sought to determine the association between progressive changes in circulating reproductive hormones over time with all-cause and cause-specific mortality in older men.
Increased risk for all-cause mortality was associated with progressive declines in serum testosterone (RR = 1.18 per 1 standard deviation [SD] decline; 95% CI, 1.05-1.32), dihydrotestosterone (RR = 1.17 per 1 SD decline; 95% CI, 1.05-1.32), calculated free testosterone (RR = 1.27 per 1 SD decline; 95% CI, 1.13-1.41) and estradiol (RR = 1.46 per 1 SD decline; 95% CI, 1.3-1.63). A lower risk for all-cause mortality was seen with declining sex hormone-binding globulin (RR = 0.8 per 1 SD decline; 95% CI, 0.73-0.88), luteinizing hormone (LH; RR = 0.81 per 1 SD decline; 95% CI, 0.77-0.89) and follicle-stimulating hormone (FSH; RR = 0.85 per 1 SD decline; 95% CI, 0.77-0.94). Significant interactions were found between all-cause mortality and serum testosterone and serum estradiol levels (P = .02). Compared with intermediate/high testosterone and estradiol, combined low testosterone and low estradiol were linked to an increased risk for all-cause mortality (RR = 1.35; 95% CI, 1.06-1.72).
Progressive declines in serum testosterone, dihydrotestosterone, calculated free testosterone, estradiol and LH/testosterone were linked to cancer-specific mortality, whereas SHBG, LH and FSH were not.
Increased risk for cardiovascular-specific mortality was linked to declining serum testosterone, dihydrotestosterone, calculated free testosterone and estradiol, as well as increasing SHBG, LH, FSH and LH/testosterone.
“Men with declining androgen status whether measured by serum [testosterone] or [calculated free testosterone], over time showed a greater risk of dying from all causes and cancer-related causes over 7 years even after adjusting for age, obesity, smoking and comorbidities,” the researchers wrote. “The increased age-related mortality associated with [CV] or other causes was explained by concurrent covariables for serum [testosterone] and [calculated free testosterone]. Progressive changes in serum LH ... were also shown to be associated with all-cause and cancer-specific mortality.” – by Amber Cox
Disclosure: Handelsman reports no relevant financial disclosures. Please see the full study for a list of all other authors’ relevant financial disclosures.
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