Testosterone therapy in hypogonadal men: a systematic review and network meta-analysis

Abstract

ObjectiveTo assess the relative effects of individual testosterone products among hypogonadal men.DesignSystematic review and network meta-analysis.MethodsWe searched MEDLINE, Embase, Cochrane CENTRAL, and grey literature (25 May 2017) for randomised-controlled trials (RCTs) and non-randomised studies (NRS) that involved hypogonadal men given testosterone replacement therapy (TRT) for ≥3 months. Comparators were placebo, another TRT, or the same product at a different dose. Outcomes were quality of life, depression, libido, erectile function, activities of daily living and testosterone levels, as well as cardiovascular death, myocardial infarction, stroke, prostate cancer, heart disease, diabetes, serious adverse events, withdrawals due to adverse events and erythrocytosis. RCT data were pooled via meta-analysis and network meta-analysis. Risk of bias was assessed using Cochrane’s risk of bias tool (RCTs) andScottish Intercollegiate Guidelines Network (SIGN)50 (NRS).ResultsEighty-seven RCTs and 51 NRS were included. Most were at high or unclear risk of bias, with short treatment duration and follow-up. When compared as a class against placebo, TRT improved quality of life (standardised mean difference (SMD) −0.26, 95% CI −0.41 to –0.11), libido (SMD 0.33, 95% CI 0.16 to 0.50), depression (SMD −0.23, 95% CI −0.44 to –0.01) and erectile function (SMD 0.25, 95% CI 0.10 to 0.41). Most individual TRTs were significantly better than placebo at improving libido (6/10). Only one TRT was better than placebo at improving quality of life, and no individual TRTs improved depression or erectile function. There was no increased risk of adverse events, with the exception of withdrawals due to adverse events with the use of some TRTs.ConclusionDespite a class effect of improving quality of life, depression, erectile function and libido, major improvements were not observed with the use of any individual product. We observed no statistically significant increase in the risk of adverse events; however, longer-term high-quality trials are needed to fully assess the risk of harm.PROSPERO registration numberCRD42014009963.

Impact of Men with Undescended Testis on Fertility and Hormonal Function Promoting Hypogonadism

“…Hypogonadism is also related to low testosterone levels. 25 Men with bilateral and unilateral UDT had lower testosterone levels than men without UDT, even though they were all within the normal range. Hypogonadism results from abnormal amounts of physiological concentrations of testosterone due to the pathological functioning of the testes, which produce testosterone which has an essential role in male reproductive and sexual function, metabolism, and body composition.…”

The association of hypogonadism with depression and its treatments

“…In a setting where only patients with hypogonadism were considered, Elliott and coll. evaluated the effect of TRT on many outcomes, including quality of life, depression, sexual function, metabolic and adverse events ( 128 ). As far as depressive symptoms are concerned, the analysis of 12 RCTs (852 patients) showed that, compared with placebo, treatment with any TRT improved depression.…”

Major adverse cardiovascular events associated with testosterone treatment: a pharmacovigilance study of the FAERS database

“…Testosterone is essential for the maintenance of muscle mass, sex drive, bone density, and fertility of men. Testosterone deficiency (TD) could be caused by various conditions, and testosterone is widely used for testosterone replacement therapy (TRT), to restore the testosterone level of men with hypogonadism or with low testosterone levels (low-T), which is considered as a safe and effective hormone supplement ( Elliott et al, 2017 ; Bhasin et al, 2018 ) and treatment for certain types of cancers, such as hormone therapy for prostate cancer ( Bhasin et al, 2018 ).…”

“…In 2022, Bhasin et al (2022 ) excised a study including 6,000 subjects and determined that TT in middle-aged and older men with hypogonadism was with or at increased risk of CV diseases. On the contrary, there were other publications that pointed out that TT has no effect on MACEs or that it even presented some beneficial effects ( Wang et al, 2011 ; Baillargeon et al, 2015 ; Cheetham et al, 2017 ), including statements that TT is associated with a decrease in atherosclerosis, hypertension, intima–media thickness of carotid arteries, insulin resistance, and mortality in men due to all causes ( Morgentaler et al, 2015 ) and no short-term increased risk of adverse events (AEs) is observed among subjects with hypogonadism ( Elliott et al, 2017 ).…”