The purpose of the Nebido® publications portal (NPP) is to present testosterone related research, in an easily searchable and navigable interface, to health professionals who search for scientific information on hypogonadism, testosterone replacement therapy and testosterone related health issues.
1. Testosterone deficiency is a well-established, significant medical condition. 2. Testosterone deficiency has well-established symptoms. 3. Testosterone therapy for men with testosterone deficiency is effective, rational and evidence based. 4. There is no scientific basis for withholding testosterone therapy from men on the basis of age. 5. Testosterone deficiency is associated with increased cardiovascular and all-cause mortality. 6. The evidence does not support an increased cardiovascular risk associated with testosterone therapy. 7. There is no evidence that supports any increase in the risk of cancer of the prostate with testosterone replacement therapy. 8. A major research initiative to explore the benefits of testosterone therapy in cardiometabolic disease is overdue.
This is the first study to demonstrate a beneficial effect of TRT on BMD among hypogonadal men with osteopenia.
The prevalence of osteopenia/osteoporosis among men with testosterone deficiency is double that of those with normal testosterone levels. This study supports the utility of testosterone therapy for prevention and management of osteoporosis in hypogonadal men.
This study shows a concentration-dependent relationship between blood levels of sex steroids and body composition changes in men. A wide range of serum T, E2 and DHT levels was achieved by suppressing endogenous sex steroid production and administering incremental doses of exogenous T. Serum T and E2 concentrations ranged from below normal to the high-normal range for healthy young men.
Results showed a significant effect of T dose on change in lean mass. Increased lean mass strongly and positively correlated with serum concentrations of all three sex steroids, as these rise in a colinear fashion with the dose of administered T.
Testosterone has a clear direct effect on bone health. Testosterone signaling stimulates osteoblasts to form trabecular bone and helps osteocytes prevent trabecular bone loss. This is why hypogonadism leads to decreased BMD and increased fracture risk.
Testosterone also has indirect effects on bone through its aromatization to estrogen via aromatase. Data suggests that testosterone therapy in hypogonadal men likely reduces fracture risk and may potentially contribute to BMD and bone health via both its direct and indirect actions.
This meta-analysis confirms that TTh provides several important sexual benefits, and by extension, strongly indicates that sexual dysfunctions are a hallmark of TD. Although it has been proposed by the US Food and Drug Administration that hypogonadism should only be treated in men with a limited list of underlying conditions (Klinefelter’s syndrome, pituitary injury, or toxic damage to the testicles), which has been called ‘‘classic hypogonadism’’, nearly all studies included in this meta-analysis were comprised of populations of men without classic hypogonadism.
The positive results reported here thus indicate that symptomatic testosterone-deficient men benefit from TTh regardless of the underlying etiology. These results provide scientific evidence that directly contradicts the recommendation to limit the use of TTh only to men with classic hypogonadism. Although the positive effects of TTh on hypogonadal men with ED were more apparent in lean subjects, it is possible that the positive effect of TTh on body composition can eventually result in an improvement of ED even in hypogonadal obese patients, after longer-term therapy.
CV safety concerns related to TTh are based on a limited number of observational and randomized controlled trials that had important methodological flaws, which invalidates the reported findings. Prostate safety remains one of the most important controversial issues of TTh in large part because prostate cancer is commonly treated with androgen deprivation therapy. However, this belief ignores the modern scientific evidence showing that androgen stimulation of the prostate only occurs at very low hypogonadal blood testosterone levels.
When hypogonadism is properly diagnosed and TTh correctly performed, no CV nor prostate risk has been documented.
In this analysis of absolute serum testosterone levels (one-time measure and 5-year average) and age-related annual changes in serum total testosterone, higher age-related annual reductions, rather than absolute testosterone levels, was associated with increased prostate cancer risk.
This indicates a role for testosterone reduction in prostate cancer and suggest that slowing age-related testosterone decline may be relevant to prostate cancer prevention
There is no credible evidence that testosterone therapy increases cardiovascular risk. In contrast there is substantial evidence that testosterone therapy
Many studies have indicated that low serum T levels are associated with increased cardiovascular risk and mortality and that testosterone replacement therapy may have clinically relevant cardiovascular benefits.
Studies have reported reduced CV risk with higher endogenous testosterone levels, improvement of known CV risk factors with T therapy, and reduced mortality in testosterone-deficient men who underwent testosterone replacement therapy versus untreated men.
Testosterone replacement therapy has been shown to:
improve myocardial ischemia in men with CAD
improve exercise capacity in men with CHF
improve serum glucose levels, HbA1c, and insulin resistance in men with diabetes and prediabetes