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Long-term testosterone therapy in type 2 diabetes is associated with reduced mortality without improvement in conventional cardiovascular risk factors

Hackett, Geoffrey; Cole, Nigel; Mulay, Akhilesh; Strange, Richard C.; Ramachandran, Sudarshan

Authors

Geoffrey Hackett

Nigel Cole

Akhilesh Mulay

Richard C. Strange

Sudarshan Ramachandran



Abstract

Objective
To further characterise the beneficial impact of testosterone replacement therapy (TRT) on the association between mortality and hypogonadism (HG) in men with type 2 diabetes (T2DM). We aimed to determine firstly, if changes in cardiovascular disease (CVD) risk factors following TRT play a role, secondly whether the reduction in mortality is lost following TRT discontinuation and finally, the presence of subgroups where benefit may be greater.

Materials and Methods
We studied 857 men with T2DM, screened for the BLAST RCT, over 3.8 years follow-up. The men were stratified by testosterone levels; Group 1: total testosterone (TT) >12nmol/l and free testosterone (FT) >0.25nmol/l, Group 2: TT =12nmol/l or FT =0.25nmol/l and by TRT (Group 2 further stratified into those not on TRT (Group 2a) and on TRT (Group 2b). Group 2b was further stratified by whether TRT was discontinued (Group 2b1) or not (Group 2b2). The principal outcome, mortality, was studied using Cox regression.

Results
TRT was not associated with improvements in the CVD risk factors. The CVD risk factors (baseline and changes during follow-up) were not associated with mortality. Men in Group 1 and Group 2b demonstrated lower mortality (reference: Group 2a) even with CVD risk factors included in regression models. Mortality was lower in the Group 2b1 (6.2%) and Group 2b2 men (0%) compared to Group 2a men (16.9%). The lower mortality associated with Group 1 and Group 2b was primarily in older (>64.6 years) and less overweight (=93.8Kg) men.

Conclusions
The benefits associated with normal testosterone levels and TRT (even after discontinuation) do not appear to be related to improvements in the CVD risk factors studied. In view of TRT having greater impact in men of lower weight, better outcomes may be achieved with concurrent TRT and weight reduction programmes.

Citation

Hackett, G., Cole, N., Mulay, A., Strange, R. C., & Ramachandran, S. (2019). Long-term testosterone therapy in type 2 diabetes is associated with reduced mortality without improvement in conventional cardiovascular risk factors. BJU International, 123(3), 519-529. https://doi.org/10.1111/bju.14536

Journal Article Type Article
Acceptance Date Sep 10, 2018
Online Publication Date Sep 14, 2018
Publication Date 2019-03
Publicly Available Date May 26, 2023
Journal BJU International
Print ISSN 1464-4096
Publisher Wiley
Peer Reviewed Peer Reviewed
Volume 123
Issue 3
Pages 519-529
DOI https://doi.org/10.1111/bju.14536
Keywords type 2 diabetes; all-cause mortality; testosterone therapy; Hypogonadism; Testosterone; Andrology
Public URL https://keele-repository.worktribe.com/output/411796
Publisher URL http://doi.org/10.1111/bju.14536