Testosterone Therapy in Prostate Cancer

Is It Still a Controversy?

Alex S. Bart; Alexander Van Hoof; Ryan Badre-Hume; Joshua Selvarajah; Kristian Robillard; David M. Albala

Disclosures

Curr Opin Urol. 2022;32(6):598-606. 

In This Article

Abstract and Introduction

Abstract

Purpose of Review: The benefits of testosterone therapy (TTh) in the hypogonadal male can be dramatic. Historically, TTh has been contraindicated in prostate cancer (PCa). Current evidence has redefined our understanding of the influence serum testosterone has on prostatic androgen activity. Increasing numbers of hypogonadal men with coexisting PCa emphasizes the importance of describing those who may safely receive TTh. This review aims to present literature that evaluates the efficacy and safety of TTh in men with coexisting PCa.

Recent Findings: Our study, a comprehensive review of published literature regarding TTh in men with a history of PCa, consisted of studies conducted from the 1940s to 2022. Our review discusses evidence in accordance with previous studies that TTh has a role in patients with localized PCa as it has not been reported to increase rates of recurrence or progression of PCa.

Summary: The use of TTh in hypongonadal men with a localized PCa has been shown to have positive clinical outcomes without increasing the rate of disease progression or recurrence. Further research, in a randomized controlled setting, is warranted.

Introduction

As the global population has aged, there has been an increase in testosterone prescriptions in men.[1] This has led to an improved understanding of the disease, the breadth of symptoms, and ways to better treat men who suffer from testosterone deficiency (hypogonadism) while also assessing prostate cancer (PCa) risk.[2,3] It is estimated that 10–40% of men experience testosterone deficiency with prevalence increasing with age.[4–7] Twelve percent of men in their 50s and 49% of men in their 80s have biochemical hypogonadism.[8] However, there is no universally agreed upon testosterone calibration standard, so clinicians typically consider testosterone deficiency as serum T (testosterone) levels below a value of 200–400 ng/dl.[9–12] Testosterone therapy (TTh) has been shown to be an effective treatment in alleviating symptoms of testosterone deficiency.[13–15] The symptoms of testosterone deficiency are broad, contributing to decreased energy and fatigue, depression and poor quality of life, insulin resistance, visceral obesity, sexual dysfunction and more.[16] As such the clinical and lifestyle benefits of successful TTh can be dramatic. Despite this, many men with testosterone deficiency are denied exogenous testosterone administration because of their concurrent or previous diagnosis of prostate cancer (PCa), which has been a contraindication to TTh. Recently, TTh use in men with PCa has begun to be re-evaluated because of various studies reporting benefits to exogenous testosterone administration.

The finding that exogenous testosterone administration increased acid phosphatase activity and susceptibility to PCa progression dates back to the 1940s. Urologists Charles Huggins and Clarence V. Hodges were awarded the Nobel Prize for their 'androgen hypothesis', which demonstrated that androgens play a role in the progression of PCa.[17] This established the belief that PCa development and growth was directly associated with androgenic levels in the body. Subsequent studies have supported this hypothesis in which untreated and previously treated PCa patients have suffered adverse effects of TTh.[18,19] Thus, it was concluded that androgens 'activated' PCa, which led to the unchallenged view that increasing serum androgen levels through exogenous testosterone administration would increase disease progression and cancer growth in PCa patients.

Over the past two decades, evidence has emerged that challenges the 'androgen hypothesis'. Studies have shown that testosterone does not initiate PCa growth or result in disease progression following administration.[3,20,21] Additionally, long-acting testosterone injections have not been reported to increase serum prostate-specific antigen (PSA) or result in recurrence.[22] Although it was previously believed that PCa was caused by high levels of serum T, researchers have determined that there is no clear evidence to support this belief.[23,24] Nonetheless, TTh has remained controversial amongst clinicians because of the concern that increased androgen activity may promote PCa progression or recurrence. The purpose of this review is to compile and analyze the literature evaluating the safety of TTh in patients with a history of PCa.

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