Neutral associations of testosterone, dihydrotestosterone and estradiol with fatal and non-fatal cardiovascular events, and mortality in men aged 17-97 years.
BACKGROUND
Lower testosterone (T) is associated with poorer health outcomes in older men, however, the relationship between T, dihydrotestosterone (DHT) and estradiol (E2) with cardiovascular disease (CVD) in younger to middle-aged men remains unclear.


OBJECTIVE
We assessed associations between endogenous sex hormones with mortality (all-cause and CVD) and CVD events, in a cohort of men aged 17-97 years.


METHODS
Sex hormones were assayed using mass spectrometry in 2143 men from the 1994/5 Busselton Health Survey. Outcomes to December 2010 were analysed.


RESULTS
Of the 1804 men included in the analysis, mean age was 50·3 ± 16·8 years and 68·9% of men were aged <60. Mean follow-up period was 14·9 years. There were 319 deaths, 141 CVD deaths and 399 CVD events. Compared to the full cohort, men who died had lower baseline T (12·0 ± 4·4 vs 13·6 ± 4·9 nmol/l), free T (181·9 ± 52·9 vs 218·3 ± 63·8 pmol/l) and DHT (1·65 ± 0·64 vs 1·70 ± 0·72 nmol/l), but higher E2 (64·0 ± 32 vs 60·1 ± 30·2 pmol/l). After adjustment for risk factors, T was not associated with mortality (adjusted HR = 0·90, 95% CI 0·79-1·04; P = 0·164 for every increase in 1 SD of T), CVD deaths (adjusted HR = 1·04, 95% CI 0·84-1·29; P = 0·708) or CVD events (adjusted HR = 1·03, 95% CI 0·92-1·15, P = 0·661). No associations were found for free T, DHT or E2. Results were similar for men older and younger than 60 years.


CONCLUSIONS
In predominantly middle-aged men, T, DHT and E2 do not influence mortality or CVD outcomes. This neutral association of hormones with CVD contrasts with prior studies of older men.
School of Medicine and Pharmacology, University of Western Australia, Crawley, WA, Australia.|Department of Endocrinology and Diabetes, Fiona Stanley Hospital, Perth, WA, Australia.
Yi X
YX
Chan
School of Population Health, University of Western Australia, Perth, WA, Australia.
Matthew W
MW
Knuiman
School of Medicine and Pharmacology, University of Western Australia, Crawley, WA, Australia.|Department of Cardiovascular Medicine, Sir Charles Gairdner Hospital, Perth, WA, Australia.
Joseph
J
Hung
School of Population Health, University of Western Australia, Perth, WA, Australia.
Mark L
ML
Divitini
PathWest Laboratory Medicine, Sir Charles Gairdner Hospital, Perth, WA, Australia.|School of Pathology and Laboratory Medicine, University of Western Australia, Perth, WA, Australia.
John P
JP
Beilby
ANZAC Research Institute, Concord, NSW, Australia.
David J
DJ
Handelsman
Department of Endocrinology and Diabetes, Fiona Stanley Hospital, Perth, WA, Australia.
Jonathan
J
Beilin
School of Medicine and Pharmacology, University of Western Australia, Crawley, WA, Australia.|Department of Cardiovascular Medicine, Sir Charles Gairdner Hospital, Perth, WA, Australia.
Brendan
B
McQuillan
School of Medicine and Pharmacology, University of Western Australia, Crawley, WA, Australia. bu.yeap@uwa.edu.au.|Department of Endocrinology and Diabetes, Fiona Stanley Hospital, Perth, WA, Australia. bu.yeap@uwa.edu.au.
Bu B
BB
Yeap
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D002318:Cardiovascular Diseases / Q000401:mortality*; D015331:Cohort Studies; D013196:Dihydrotestosterone / Q000097:blood*; D004958:Estradiol / Q000097:blood*; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D013739:Testosterone / Q000097:blood*; D055815:Young Adult
D013196:Dihydrotestosterone; D013739:Testosterone; D004958:Estradiol