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J Clin Endocrinol Metab. 2014 Jan;99(1):E9-18. doi: 10.1210/jc.2013-3272. Epub 2013 Dec 20.

In older men an optimal plasma testosterone is associated with reduced all-cause mortality and higher dihydrotestosterone with reduced ischemic heart disease mortality, while estradiol levels do not predict mortality.

Author information

1
School of Medicine and Pharmacology (B.B.Y., S.A.P.C., G.J.H., L.F.), University of Western Australia, Perth, Western Australia 6009, Australia; Department of Endocrinology and Diabetes (B.B.Y.), Fremantle Hospital, Fremantle, Western Australia 6160, Australia; Western Australian Centre for Health and Ageing (H.A., O.P.A., L.F.), Centre for Medical Research, University of Western Australia, Perth, Western Australia 6009, Australia; PathWest Laboratory Medicine (S.A.P.C.), Fremantle and Royal Perth Hospitals, Perth, Western Australia 6009, Australia; ANZAC Research Institute (D.J.H.), University of Sydney, Sydney, New South Wales 2139, Australia; School of Psychiatry and Clinical Neurosciences (O.P.A.), University of Western Australia, Perth, Western Australia 6009, Australia; Vascular Biology Unit (J.G.), Queensland Research Centre for Peripheral Vascular Disease, School of Medicine, James Cook University, Townsville, Queensland 4811, Australia; and School of Surgery (P.E.N.), University of Western Australia, Perth, Western Australia 6009, Australia.

Abstract

CONTEXT:

Testosterone (T) levels decline with age and lower T has been associated with increased mortality in aging men. However, the associations of its metabolites, dihydrotestosterone (DHT) and estradiol (E2), with mortality are poorly defined.

OBJECTIVE:

We assessed associations of T, DHT, and E2 with all-cause and ischemic heart disease (IHD) mortality in older men.

PARTICIPANTS:

Participants were community-dwelling men aged 70 to 89 years who were residing in Perth, Western Australia.

MAIN OUTCOME MEASURES:

Plasma total T, DHT, and E2 were assayed using liquid chromatography-tandem mass spectrometry in early morning samples collected in 2001 to 2004 from 3690 men. Deaths to December 2010 were ascertained by data linkage.

RESULTS:

There were 974 deaths (26.4%), including 325 of IHD. Men who died had lower baseline T (12.8±5.1 vs 13.2±4.8 nmol/L [mean±SD], P=.013), DHT (1.4±0.7 vs 1.5±0.7 nmol/L, P=.002), and E2 (71.6±29.3 vs 74.0±29.0 pmol/L, P=.022). After allowance for other risk factors, T and DHT were associated with all-cause mortality (T: quartile [Q] Q2:Q1, adjusted hazard ratio [HR]=0.82, P=.033; Q3:Q1, HR=0.78, P=.010; Q4:Q1, HR=0.86, P>.05; DHT: Q3:Q1, HR=0.76, P=.003; Q4:Q1, HR=0.84, P>.05). Higher DHT was associated with lower IHD mortality (Q3:Q1, HR=0.58, P=.002; Q4:Q1, HR=0.69, P=.026). E2 was not associated with either all-cause or IHD mortality.

CONCLUSIONS:

Optimal androgen levels are a biomarker for survival because older men with midrange levels of T and DHT had the lowest death rates from any cause, whereas those with higher DHT had lower IHD mortality. Further investigations of the biological basis for these associations including randomized trials of T supplementation are needed.

PMID:
24257908
DOI:
10.1210/jc.2013-3272
[Indexed for MEDLINE]
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