Ramachandran, S, Strange, RC, Fryer, AA, Saad, F and Hackett, GI (2018) The association of sex hormone binding globulin with mortality is mediated by age and testosterone in men with type 2 diabetes. Andrology. ISSN 2047-2927

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Abstract

BACKGROUND:
Serum sex hormone-binding globulin levels have been associated with mortality in adult men with type 2 diabetes (T2DM).

OBJECTIVES:
To confirm the association of serum sex hormone-binding globulin with mortality and then determine whether this association is mediated by age and total testosterone concentration.

MATERIALS AND METHODS:
We studied 364 men (median age: 66 years) with T2DM over a median follow-up of 4.3 years using the Cox regression to study associations between sex hormone-binding globulin, age, total testosterone, and mortality.

RESULTS:
Mortality was significantly and independently associated with sex hormone-binding globulin, age, and total testosterone. In pairwise combinations of age and sex hormone-binding globulin dichotomized by median values, the association of sex hormone-binding globulin with mortality was age-dependent. Relative to the combination of age >66 years/SHBG >35 nmol/L (mortality 22.5%), the other combinations were associated with significantly less mortality (mortality in men ≤66 years/SHBG ≤ 35 nmol/L was 3.23%). In men >66 years, SHBG ≤ 35 nmol/L was associated with decreased mortality (HR: 0.41, p = 0.037) compared with SHBG > 35 nmol/L. In men ≤66 years, there was no significant difference between those with sex hormone-binding globulin above or below the median (HR: 1.73, p = 0.56, reference: SHBG ≤ 35 nmol/L). TT < 12 nmol/L was associated with increased mortality in both age categories. Men >66 years with the reference combination of SHBG > 35 nmol/L and TT < 12 nmol/L (36.84%) nmol/L had significantly higher mortality than those with SHBG > 35 nmol/L and TT ≥ 12 (18.06%) and those with SHBG ≤ 35 nmol/L and TT < 12 nmol/L (13.79%).

DISCUSSION:
Our data suggest sex hormone-binding globulin and total testosterone have particular impact on mortality in men aged over 66 years. Further, in older men, the combination of high sex hormone-binding globulin levels and low total testosterone is associated with greater risk than either high sex hormone-binding globulin or low total testosterone individually.

CONCLUSIONS:
Our findings are compatible with data suggesting the importance of sex hormone-binding globulin lies in mediating free testosterone levels.

Item Type: Article
Additional Information: This is the accepted author manuscript (AAM). The final published version (version of record) is available online via Wiley at http://dx.doi.org/10.1111/andr.12520 - please refer to any applicable terms of use of the publisher.
Uncontrolled Keywords: age, mortality, sex hormone-binding globulin, statins, testosterone, type 2 diabetes
Subjects: R Medicine > R Medicine (General)
Divisions: Faculty of Medicine and Health Sciences > Institute for Science and Technology in Medicine
Depositing User: Symplectic
Date Deposited: 13 Sep 2018 15:54
Last Modified: 13 Sep 2018 15:54
URI: http://eprints.keele.ac.uk/id/eprint/5309

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