Study: Long-term Testosterone Replacement in Men with Type 2 Diabetes Improves Survival

It’s known that low testosterone levels in men are associated with increased mortality.  It’s also known that men with type 2 diabetes have a high prevalence of testosterone deficiency.  Previously, it’s been shown that there is an increased mortality in men with type 2 diabetes and low testosterone, but there hasn’t been any long-term data published on the effect of testosterone replacement (TRT) in men with type 2 diabetes and hypogonadism.

Therefore, a group of researchers from the United Kingdom wanted to examine the effect of TRT in hypogonadal men with type 2 diabetes on all-cause mortality.  They presented their results at the 2011 Endocrine Society Annual Meeting in a study called “Long-Term Testosterone Replacement Improves Survival in Men with Type 2 Diabetes and Hypogonadism.”

This was a 6-year follow-up study.  There were 585 patients (mean age: 59.45, SD 10.8) with type 2 diabetes, and they had testosterone levels tested between 2002 and 2005.  They were followed-up for a mean period of 5.8 years (SD 1.3).

Patients were analyzed in 3 groups (after excluding for death in the first 6 months, n=4).  The three groups were:

• Total testosterone (TT) >10.4 nmol/L (300 ng/dL)
• TT <10.4 nmol/L without TRT
• TT <10.4 nmol/L with physiological TRT of >12 months duration (testosterone gel, or i.m. testosterone undeconoate)

Out of the 581 patients who were analyzed, 343 (59% had TT levels of >10.4 nmol/L and 238 (41%) had low TT.

The mean duration of TRT was 41.6 months (SD+20.7).  There were 60 patients who received TRT for >12 months; 51 of those had TRT for >2 years.

Compared to the normal TT group, those in the low TT group were more likely to have poor diabetes control (A1c 7.5±1.3 for the low TT group; A1c 7.1±1.4 for the normal TT group, p=0.002).  The low TT group was also more likely to have a higher weight (102±21.5 vs. 95.3±18.4, p<0.0001) than the normal TT group.

The low TT groups (treated and non-treated) were equally matched for age, weight, A1c, smoking status, pre-existing cardiovascular disease, statin, and ACEi/ARB use. 

There were 72 deaths (12.4%), and the mortality rate was the highest in the low TT group without treatment.  For that group, 33 out of 182 patients died (19.2%).  This is compared to the normal TT group:  31 out of 343 patients died in that group (9%).  The death rate was lowest in the TRT group:  5 out of 60 patients (8.3%).

The survival rate was significantly decreased for patients in the low TT group without treatment (p=0.001 log rank) when compared to the normal TT group.

A Cox Regression model was used, and with it, the multivariate adjusted hazard ratio was 2.2 (CI 95%; 1.3-3.7, p=0.001) for the low TT group without treatment.

The low TT group with treatment had an improved mean survival of 86.2 months (SE 1.6); this is compared to the mean survival in the low TT group without treatment—83.8 months (SE 1.8, p=0.048 log rank).

This study showed that long-term TRT in hypogonadal men with type 2 diabetes improves survival.