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Sex hormones fail to influence all-cause, CVD mortality in middle-aged men
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Mortality and cardiovascular disease outcomes are not influenced by testosterone, dihydrotestosterone or estradiol in predominantly middle-aged men, study data show.
These data differ from previously reported findings revealing a link between hormones and CVD, the researchers wrote.
Bu B. Yeap, PhD, MBBS, FRACP, professor in the school of medicine and pharmacology at the University of Western Australia in Perth, and colleagues evaluated data from the 1994-1995 Busselton Health Survey on 1,804 men (mean age, 50.3 years) to determine the relationships between endogenous sex hormones and mortality and CVD events. The mean follow-up period from baseline was until death or 14.9 years.
Researchers found 319 deaths overall, 141 CVD deaths and 399 fatal or nonfatal CVD events. At baseline, 1,501 participants were free of CVD; 191 of this group died (71 from CVD) and 234 experienced CVD events. Among participants with testosterone levels less than 8 nmol/L, 54 died (23 from CVD) and 60 experienced CVD events. Participants who died had lower testosterone, free testosterone and dihydrotestosterone levels and higher estradiol, sex hormone-binding globulin and luteinizing hormone compared with those who did not die.
In an age-adjusted analysis, an inverse relationship was found between testosterone and overall mortality (HR = 0.81; 95% CI, 0.71-0.93) and CVD events (HR = 0.88; 95% CI, 0.79-0.98), but in the fully adjusted model these associations were not significant. No association was found between CVD death and testosterone.
Among participants without CVD, the risks for death, CVD death and CVD events were not influenced by testosterone.
When dihydrotestosterone and estradiol were analyzed as continuous levels, according to quartiles or when the highest quartile was compared with the rest of the quartiles, there were no associations with all-cause or CVD mortality.
“Neither higher nor lower concentrations of [testosterone], [dihydrotestosterone] or [estradiol were associated with CV events and mortality in this cohort of men ranging from 17 to 97 years,” Yeap told Endocrine Today. “Neutral associations imply neither benefit nor risk in having higher or lower circulating sex hormones. These findings do contrast with other research in older men where lower circulating androgens have been associated with poorer outcomes.” – by Amber Cox
For more information:
Bu B. Yeap, PhD, MBBS, FRACP, can be reached at bu.yeap@uwa.edu.au.
Disclosure: Yeap reports various financial ties with Bayer, Besins, Eli Lilly, Lawley Pharmaceuticals and Weight Watchers.
Perspective
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Paul L. Douglass
Chan and colleagues have added significant fuel to the debate regarding the risk of low testosterone levels in men. However, the impact on clinical practice will likely remain negligible. The investigators demonstrate that a cohort of Australian men of predominantly Anglo–Celtic origin when surveyed in this epidemiological study have neutral associations of sex hormones linked to excessive cardiovascular morbidity and mortality. This study adds to the ongoing debate regarding the risks/benefits of testosterone replacement therapy. The authors suggest that baseline CV risk factors, ie, hyperlipidemia, inflammation, and renal function, play a significant confounder role. The medical community now is able to search the medical literature and find mostly observational studies and a few underpowered randomized controlled trials to support whichever side of this argument that one sits. The only certainty is that direct to consumer marketing has increased the prescriptions for testosterone from 1.3 million in 2010 to 2.3 million in 2013. This, with significant numbers of men not having baseline levels drawn, but only complaining of low libido, fatigue, and loss of muscle mass. The authors were careful to accurately assess the sex hormone levels using mass spectrometry, but this was only a single measurement. Also this was a homogenous population which probably cannot be extrapolated to countries with more diverse populations. So this observational study with a large population adds to the debate, but does not answer the cause and effect question. Only a large randomized controlled trial will do that. In the meantime, I feel that the most prudent advice to the medical community with the conflicting data currently available, is to avoid therapy of low testosterone when it represents the aging process and only supplement testosterone in men with primary or secondary hypogonadism. Focus on CV risk factors which often contribute to the symptoms.
Disclosure:Douglass reports no relevant financial disclosures.
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