Serum testosterone, testosterone replacement therapy and all‐cause mortality in men with type 2 diabetes: retrospective consideration of the impact of PDE5 inhibitors and statins. Issue 3 (24th February 2016)

• Record Type: Journal Article
• Authors: Hackett, G.; Heald, A. H.; Sinclair, A.; Jones, P. W.; Strange, R. C.; Ramachandran, S.
• Is Part Of: International journal of clinical practice. Volume 70:Issue 3(2016)
• Page Start: 244
• Page End: 253
• Publication Date: 2016-02-24
• Subjects: Clinical medicine -- Periodicals; Medicine -- Periodicals; 610.5
• DOI: 10.1111/ijcp.12779
• Languages: English
• ISSNs: 1368-5031

Abstract

Summary: Background: Low testosterone levels occur in over 40% of men with type 2 diabetes mellitus (T2DM) and have been associated with increased mortality. Testosterone replacement together with statins and phosphodiesterase 5 inhibitors (PDE5I) are widely used in men with T2DM. 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 PDE5I use. Methods: We studied 857 men with T2DM 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. PDE5I 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 PDE5I 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. PDE5I 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 PDE5I, 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 PDE5I/treated was significantly reduced compared with the PDE5I/untreated group (OR: 0.06, CI: 0.009–0.47). Conclusions: Testosterone replacement therapy is independently associated with reduced mortality in men with T2DM. PDE5I 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 PDE5I treatment on mortality (both HR and OR < 0.25) needs confirmation by independent studies.