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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. 2014

Bu B Yeap, and Helman Alfonso, and S A Paul Chubb, and David J Handelsman, and Graeme J Hankey, and Osvaldo P Almeida, and Jonathan Golledge, and Paul E Norman, and Leon Flicker
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.

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

UI MeSH Term Description Entries
D008297 Male Males
D011379 Prognosis A prediction of the probable outcome of a disease based on a individual's condition and the usual course of the disease as seen in similar situations. Prognostic Factor,Prognostic Factors,Factor, Prognostic,Factors, Prognostic,Prognoses
D012015 Reference Standards A basis of value established for the measure of quantity, weight, extent or quality, e.g. weight standards, standard solutions, methods, techniques, and procedures used in diagnosis and therapy. Standard Preparations,Standards, Reference,Preparations, Standard,Standardization,Standards,Preparation, Standard,Reference Standard,Standard Preparation,Standard, Reference
D002423 Cause of Death Factors which produce cessation of all vital bodily functions. They can be analyzed from an epidemiologic viewpoint. Causes of Death,Death Cause,Death Causes
D003940 Diagnostic Techniques, Endocrine Methods and procedures for the diagnosis of diseases or dysfunction of the endocrine glands or demonstration of their physiological processes. Diagnostic Technic, Endocrine,Diagnostic Technics, Endocrine,Diagnostic Technique, Endocrine,Endocrine Diagnostic Technic,Endocrine Diagnostic Technics,Endocrine Diagnostic Technique,Endocrine Diagnostic Techniques,Technic, Endocrine Diagnostic,Technics, Endocrine Diagnostic,Technique, Endocrine Diagnostic,Techniques, Endocrine Diagnostic
D004958 Estradiol The 17-beta-isomer of estradiol, an aromatized C18 steroid with hydroxyl group at 3-beta- and 17-beta-position. Estradiol-17-beta is the most potent form of mammalian estrogenic steroids. 17 beta-Estradiol,Estradiol-17 beta,Oestradiol,17 beta-Oestradiol,Aerodiol,Delestrogen,Estrace,Estraderm TTS,Estradiol Anhydrous,Estradiol Hemihydrate,Estradiol Hemihydrate, (17 alpha)-Isomer,Estradiol Monohydrate,Estradiol Valerate,Estradiol Valeriante,Estradiol, (+-)-Isomer,Estradiol, (-)-Isomer,Estradiol, (16 alpha,17 alpha)-Isomer,Estradiol, (16 alpha,17 beta)-Isomer,Estradiol, (17-alpha)-Isomer,Estradiol, (8 alpha,17 beta)-(+-)-Isomer,Estradiol, (8 alpha,17 beta)-Isomer,Estradiol, (9 beta,17 alpha)-Isomer,Estradiol, (9 beta,17 beta)-Isomer,Estradiol, Monosodium Salt,Estradiol, Sodium Salt,Estradiol-17 alpha,Estradiol-17beta,Ovocyclin,Progynon-Depot,Progynova,Vivelle,17 beta Estradiol,17 beta Oestradiol,Estradiol 17 alpha,Estradiol 17 beta,Estradiol 17beta,Progynon Depot
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000368 Aged A person 65 years of age or older. For a person older than 79 years, AGED, 80 AND OVER is available. Elderly
D000369 Aged, 80 and over Persons 80 years of age and older. Oldest Old
D012738 Sex Hormone-Binding Globulin A glycoprotein migrating as a beta-globulin. Its molecular weight, 52,000 or 95,000-115,000, indicates that it exists as a dimer. The protein binds testosterone, dihydrotestosterone, and estradiol in the plasma. Sex hormone-binding protein has the same amino acid sequence as ANDROGEN-BINDING PROTEIN. They differ by their sites of synthesis and post-translational oligosaccharide modifications. Sex Steroid-Binding Protein,Testosterone-Estradiol Binding Globulin,Binding Globulin, Testosterone-Estradiol,Globulin, Sex Hormone-Binding,Globulin, Testosterone-Estradiol Binding,Hormone-Binding Globulin, Sex,Sex Hormone Binding Globulin,Sex Steroid Binding Protein,Steroid-Binding Protein, Sex,Testosterone Estradiol Binding Globulin

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