Testosterone replacement therapy: improved sexual desire and erectile function in men with type 2 diabetes following a 30‐week randomized placebo‐controlled study

Abstract

Although testosterone replacement treatment (TRT) can improve sexual function in many hypogonadal (HG) men with type 2 diabetes (T2DM), some show either no improvement or only in a limited number of domains. Indeed, it is often difficult for the clinician to offer an indication of the likely efficacy of TRT as little data exist on the proportion of TRT-treated men who will demonstrate improvement in domains such as sexual desire (SxD) and erectile function (EF). We describe in men with T2DM: firstly, the likelihood of improved sexual desire (SxD) and erectile function (EF) following TRT at various time points, and secondly, if probability of SxD change predicted likelihood of subsequent EF change. During a 30-week randomized controlled study of testosterone undecanoate (TU), 199 T2DM men with HG (189 men completing) identified from primary care registers (placebo (P): 107, TU: 92) were stratified using baseline total testosterone (TT)/free testosterone (FT) into Mild (TT 8.1-12 nmol/L or FT 0.18-0.25 nmol/L) and Severe HG groups (TT ≤8 nmol/L and FT ≤0.18 nmol/L) and placebo (P)- and TU-treated groups. Associations between TU, SxD and EF were investigated using chi-square and logistic regression analysis. The proportion of men with improved SxD after 6 weeks and EF improvement after 30 weeks was significantly higher following TU treatment compared to P, this particularly evident in Severe HG men. Changes in SxD and EF were significantly associated in all groups. Logistic regression showed that SxD change at 6 weeks predicted of EF change after 30 weeks. Our study confirms TRT leads to changes in SxD and EF at different time points and suggests SxD and EF changes are related. SxD change after 6 weeks predicting EF change at 30 weeks is possibly a useful clinical finding.

Testosterone replacement therapy: Pre‐treatment sex hormone‐binding globulin levels and age may identify clinical subgroups

“…[17][18][19]28 Thus, Hackett et al showed that while 30-week TRT was associated with improvement in different domains of sexual function in men with total testosterone ≤ 8 nmol/L, only sexual desire improved significantly in those with testosterone 8-12nmol/L. 18 Further, in men given TRT only those with testosterone ≤ 8nmol/L showed a significant reduction in SHBG. 14 Age was considered an essential variable as it is linked with many factors that define T2DM and TD.…”

“…10,[12][13][14][15] In men with T2DM and adult-onset TD, testosterone therapy (TRT) can improve sexual health, increase lean mass and reduce body fat, fasting glycaemia, insulin resistance and all-cause mortality though importantly, not all men demonstrate beneficial effects. [15][16][17][18][19][20][21][22] Understanding the role of SHBG in this process is complicated by the finding that in adults, serum SHBG levels increase with age and demonstrate marked interand intra-individual variation. 23 Thus, in 857 men with T2DM, we found concentrations between 7.9 and 185.5 nmol/L.…”

Down‐regulation of steroidogenesis‐related genes and its accompanying fertility decline in streptozotocin‐induced diabetic male rats: ameliorative effect of metformin

“…Both human (Hackett et al ., ) and experimental (Shi et al ., ; Yang et al ., ) studies have reported decreased testosterone level and suppressed sexual function in diabetic state. Testosterone replacement therapy in diabetic males significantly improves sexual appetite and erectile function (Hackett et al ., , ), thus suggesting the importance of testosterone in male fertility. Litter size, gravid uterine weight, fetal weight, and number of implantation sites were significantly lower in DC group compared to NC group.…”

The association of sex hormone‐binding globulin with mortality is mediated by age and testosterone in men with type 2 diabetes

“…HG is characterized by low serum testosterone (TT) and sexual dysfunction (Kapoor et al, 2007;Hackett et al, 2009) with both these factors being independent determinants of mortality (Pye et al, 2014). Importantly, testosterone replacement therapy (TRT) has wide-ranging beneficial effects; for example, Hackett et al (2016aHackett et al ( , 2017a and Corona et al (2017) reported improvement in erectile function, sexual desire, and other sexual parameters. Importantly, testosterone replacement therapy (TRT) has wide-ranging beneficial effects; for example, Hackett et al (2016aHackett et al ( , 2017a and Corona et al (2017) reported improvement in erectile function, sexual desire, and other sexual parameters.…”

“…Recognition of the importance of HG has led to the American Association of Clinical Endocrinologists/American College of Endocrinology guidelines on obesity (https://www.aa ce.com/files/guidelines/ObesityExecutiveSummary.pdf accessed on 04/04/2018) recommending that testosterone deficiency should be excluded in all males with T2DM. Importantly, testosterone replacement therapy (TRT) has wide-ranging beneficial effects; for example, Hackett et al (2016aHackett et al ( , 2017a and Corona et al (2017) reported improvement in erectile function, sexual desire, and other sexual parameters. Further, Corona et al (2016) found significant reduction in body fat and increased lean mass with reduced fasting glycemia and insulin resistance.…”