Testosterone Replacement Therapy with Long‒Acting Testosterone Undecanoate Improves Sexual Function and Quality‒of‒Life Parameters vs. Placebo in a Population of Men with Type 2 Diabetes

Abstract

Introduction Sexual dysfunction, particularly erectile dysfunction (ED), is common in men with type 2 diabetes, occurring in up to 75% of cases. The prevalence of hypogonadism is also high in men with diabetes and low testosterone is associated with both sexual dysfunction and a reduced response to oral therapy for ED. Aim This study aimed to determine the effect of testosterone replacement with long‒acting Testosterone Undecanoate (TU) on sexual function, mood and quality of life vs. placebo over a treatment period of 30 weeks followed by 52 weeks of open‒label medication. The study was conducted in a primary care population of men with type 2 diabetes attending their primary care physician for routine visits. Methods The male diabetic populations of seven general practices were screened at routine diabetes visits to detect symptomatic men with total testosterone levels of 12 nmol/L or less or with free testosterones of 250 pmol/L or less. Two hundred eleven men were screened. A double‒blind placebo‒controlled study was conducted in 199 men with type 2 diabetes and hypogonadism treated for 30 weeks with either 1,000 mg of TU or matching placebo followed by 52‒week open‒label follow on. Main Outcome Measures The primary outcome measure, International Index of Erectile Function (IIEF), was used to evaluate sexual dysfunction, and the Ageing Male Symptom (AMS), Hospital Anxiety and Depression Scale, and Global Efficacy Question were used as secondary outcome measures to assess mood and self‒reported quality of life. Results Testosterone replacement therapy with long‒acting TU improved all domains of sexual function at 30 weeks (erectile function [EF], P = 0.005; intercourse satisfaction, P = 0.015; sexual desire, P = 0.001; overall satisfaction, P = 0.05; and orgasm, P = 0.04), with benefit as early as 6 weeks. Improvements in AMS score were significant in men without depression (P = 0.02) and the presence of depression at baseline was associated with marked reduction in response to both sexual function and psychological scores. All responses in sexual function continued to improve significantly up to 18 months with an improvement in EF score of 4.31 from baseline. In a small cohort of 35 men taking phosphodiesterase type 5 inhibitors, there was no change during the double‒blind phase but a nine‒point improvement in EF domain during 52‒week open‒label treatment. After 30 weeks, 46% vs. 17% of patients on active therapy vs. placebo felt that the treatment had improved their health, reaching 70% after open‒label therapy. Less obese and older patients responded better to testosterone therapy. There were no significant adverse events. Conclusion TU significantly improved all domains of the IIEF and patient reported quality of life at 30 weeks and more significantly after 52‒week open‒label extension. Improvement was most marked in less obese patient and those without coexisting depression. In men with type 2 diabetes, trials of therapy may need to be given for much longer than 3–6 months suggested in current guidelines.

Clinical significance and expression of microRNA in diabetic patients with erectile dysfunction

“…In conclusion, the results of the current study demonstrated that the HbA1c level was a risk factor for diabetic ED, while the TT level was a protective factor, which was the same as a previous result; however, the BMI, FPG, TC and TG did not show a correlation with diabetic ED (4,21,22,(29)(30)(31). These results may have been caused by the small sample size.…”

“…Changes in the androgenic level are also an important factor in diabetic ED (29,30). Diabetes affects the secretion of androgen, which plays a key role in maintaining sexual desire; therefore, low androgenic levels caused by diabetes reduces sexual desire, which leads to the incidence of ED.…”

Erectile dysfunction, diabetes and cardiovascular risk

“…This suggests that treatment may need to be given for a prolonged time. 31 In view of the association between hypogonadism and diabetes, researchers have postulated whether TRT can also improve metabolic parameters in diabetes. Studies have shown an association between TRT and reductions in HbA1c, 32 improvement in insulin resistance 33 and a reduction in body mass index.…”

Erectile dysfunction – the old and the new

“…Free testosterone levels and bioavailable testosterone levels were found to be inversely correlated with ED while the correlation with total testosterone seems to be clouded by the rise in sex hormone-binding globulin with age [10]. Also several studies have shown the high prevalence of hypogonadotropic hypogonadism in type 2 diabetes [11]. All these factors indicate the importance of assessing for features of testosterone deficiency in patients with ED.…”

“…For example, addition of testosterone therapy to 5PDEI treatment in patients with low testosterone levels did not improve the erectile function compared to placebo [20]. However testosterone replacement with long-acting testosterone undecanoate in diabetic patients with low testosterone showed improvements in all domains of the IIEF at 30 weeks and further improvement after a 52-week open-label extension [11]. The Endocrine Society clinical practice guidelines suggest testosterone therapy to those with ED and low testosterone levels following assessment of underlying causes and consideration of other conventional therapies [21].…”