Open AccessSerum testosterone, testosterone replacement therapy and all‐cause mortality in men with type 2 diabetes: retrospective consideration of the impact of PDE5 inhibitors and statins
Author(s) -
Hackett G.,
Heald A. H.,
Sinclair A.,
Jones P. W.,
Strange R. C.,
Ramachandran S.
Publication year - 2016
Publication title -
international journal of clinical practice
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.756
H-Index - 98
eISSN - 1742-1241
pISSN - 1368-5031
DOI - 10.1111/ijcp.12779
Subject(s) - medicine , testosterone (patch) , type 2 diabetes , statin , proportional hazards model , endocrinology , type 2 diabetes mellitus , diabetes mellitus , cgmp specific phosphodiesterase type 5 , erectile dysfunction
Summary Background Low testosterone levels occur in over 40% of men with type 2 diabetes mellitus (T2 DM ) and have been associated with increased mortality. Testosterone replacement together with statins and phosphodiesterase 5 inhibitors ( PDE 5I) are widely used in men with T2 DM . Purpose To determine the impact of testosterone and testosterone replacement therapy ( TRT ) on mortality and assess the independence of this effect by adjusting statistical models for statin and PDE 5I use. Methods We studied 857 men with T2 DM screened from five primary care practices during April 2007–April 2009. Of the 857 men, 175/637 men with serum total testosterone ≤ 12 nmol/l or free testosterone ( FT ) ≤ 0.25 nmol/l received TU for a mean of 3.8 ± 1.2 ( SD ) years. PDE 5I and statins were prescribed to 175/857 and 662/857 men respectively. All‐cause mortality was the primary end‐point. Cox regression models were used to compare survival in the three testosterone level/treatment groups, the analysis adjusted for age, statin and PDE 5I use, BMI , blood pressure and lipids. Results Compared with the Low T/untreated group, mortality in the Normal T/untreated ( HR : 0.62, CI : 0.41–0.94) or Low T/treated ( HR : 0.38, CI : 0.16–0.90) groups was significantly reduced. PDE 5I use was significantly associated with reduced mortality ( HR : 0.21, CI : 0.066–0.68). After repeating the Cox regression in the 682 men not given a PDE 5I, mortality in the Normal T/untreated and Low T/treated groups was significantly lower than that in the reference Low T/untreated group. Mortality in the PDE 5I/treated was significantly reduced compared with the PDE 5I/untreated group ( OR : 0.06, CI : 0.009–0.47). Conclusions Testosterone replacement therapy is independently associated with reduced mortality in men with T2 DM . PDE 5I use, included as a confounding factor, was associated with decreased mortality in all patients and, those not on TRT , suggesting independence of effect. The impact of PDE 5I treatment on mortality (both HR and OR < 0.25) needs confirmation by independent studies.