Late‐onset hypogonadism: Prostate safety

Abstract

Background There have always been concerns regarding testosterone replacement therapy and prostate safety because of the central role of testosterone in prostate tissue. Even though there is a body of evidence supporting that the benefits of testosterone replacement therapy outbalance the risks of prostate disease, this matter is still debatable and represents a common concern among testosterone prescribers. Objectives The aim of this article was to review the influence of testosterone on prostate pathophysiology and discuss the potential impact of testosterone replacement therapy on the most common prostate pathologies, including benign prostatic hyperplasia and prostate cancer. Materials and Methods We have performed an extensive PubMed review of the literature examining the effects of testosterone replacement therapy on the prostate and its most common affections, especially in terms of safety. Results Testosterone replacement therapy has been shown to improve components of metabolic syndrome and decrease prostate inflammation, which is related to the worsening of lower urinary tract symptoms (LUTS) in patients with benign prostatic hyperplasia. Studies evaluating the link between testosterone replacement therapy and benign prostatic hyperplasia/LUTS have mostly demonstrated no change in symptom scores and even some benefits. There are a significant number of studies demonstrating the safety of testosterone replacement therapy in individuals with late‐onset hypogonadism and a history of prostate cancer. The most recently published guidelines have already acknowledged this fact and do not recommend against T treatment in this population, particularly in non–high‐risk disease. Conclusion Testosterone replacement therapy could be considered for most men with late‐onset hypogonadism regardless of their history of prostate disease. However, a discussion about the risks and benefits of testosterone replacement therapy is always advised, especially in men with prostate cancer. Appropriate monitoring is mandatory.

Burden of Male Hypogonadism and Major Comorbidities, and the Clinical, Economic, and Humanistic Benefits of Testosterone Therapy: A Narrative Review

“…Its benefits include significantly improving glycemia and preventing progression from prediabetes to T2DM, significantly improving body composition and waist circumference, and conferring improvements in patient-reported symptoms that persist into the long-term. Limitations include the monitoring of prostate parameters that may be necessary during treatment, 47 and the potential negative effect on male fertility. 48 As the prevalence of male hypogonadism is likely to increase globally, and this condition may be currently underdiagnosed, cost-effective and cost-saving testosterone therapies should be increasingly considered for use in order to manage this condition.…”

Endocrinology of the Aging Prostate: Current Concepts

“…LUTS and BPH have long been considered a relative contraindication to testosterone replacement therapy (TRT). However, recent studies have contradicted the classic idea that androgens inevitably stimulate prostate growth ( 17 ). According to the saturation model, the prostate is sensitive to changes in androgen levels when they occur in a severe low range, but this sensitivity is lost for T levels corresponding to mild hypogonadism or eugonadal.…”

“…Indeed, prostate ARs become saturated at relatively low T levels and thus, the gland becomes unresponsive to further increases in T levels ( 18 ). Experimental and clinical studies suggest that the saturation point for human prostate tissue probably occurs in the very low range of T levels, but a precise cutoff value has not been established; it could vary among men ( 17 ). According to this model, the association between T and prostate-specific antigen (PSA) is represented by a sigmoid curve.…”

“…T levels of 8 nmol/L corresponds to the plateau value below which small changes in T levels cause greater variations in PSA ( 19 ). As reported in recent reviews ( 12 , 17 ), studies evaluating the link between TRT and BPH/LUTS have mostly shown that TRT does not have any effect on BPH symptoms [measured by the International Prostate Symptom Score (IPSS)] and occasionally the IPSS score may decrease ( 20 – 22 ). A recent meta-analysis did not show a worsening of LUTS severity in hypogonadal patients treated with T vs. placebo ( 23 ).…”

Late‐onset hypogonadism a challenging task for the andrology field

“…10 Prostate safety has been considered among the most risky side effects related to TRT. 14 Substantial clinical and experimental data have clarified that androgens are not only involved in the stimulation of prostate cell proliferation but also contribute to the regulation of prostate cell differentiation. In line with the latter findings, no increased risks of prostate cancer or prostate-related events during TRT have been documented so far.…”