Safety of testosterone therapy in men with prostate cancer

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Safety of testosterone therapy in men with prostate cancer

Abraham Morgentaler & Monica Caliber








Abstract

Introduction: The use of testosterone therapy (TTh) in men with prostate cancer (PCa) is relatively new, and controversial, due to the longstanding maxim that TTh is contraindicated in men with PCa. Scientific advances have prompted a reevaluation of the potential role for TTh in men with PCa, particularly as TTh has been shown to provide important symptomatic and general health benefits to men with testosterone deficiency (TD), including many men with PCa who may expect to live 30-50 years after diagnosis.


Areas covered: This review outlines the historical underpinnings of the historical belief that TTh “fuels” PCa and the experimental and clinical studies that have radically altered this view, including description of the saturation model. The authors review studies of TTh in men with PCa following radical prostatectomy and radiation therapy, in men on active surveillance, and in men with advanced or metastatic PCa.


Expert opinion: TTh provides important symptomatic and overall health benefits for men with PCa who have TD. Although more safety studies are needed, TTh is a reasonable therapeutic option for men with low-risk PCa after surgery or radiation. Data in men on active surveillance are limited, but initial reports are reassuring.
 

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Article highlights

Many men with a history of prostate cancer suffer from testosterone deficiency.

Testosterone therapy in these men improves symptoms and confers significant health benefits, including improved sexual function, increased energy and sense of wellbeing, loss of fat mass and gain in lean mass, resolution of anemia, and increased bone mineral density.

Although no large, long-term, controlled studies have yet been performed to provide definitive evidence regarding the safety of testosterone therapy in men with prostate cancer, the available data is reassuring.

Testosterone therapy may be reasonably offered to symptomatic men with testosterone deficiency who have low-risk disease after treatment for localized prostate cancer with surgery or radiation.

Testosterone therapy in men on active surveillance is less well established, however, several initial reports have shown progression rates comparable to those seen in men who did not receive testosterone therapy.

New clinical trial data suggests there may even be a therapeutic role for testosterone therapy in men with advanced prostate cancer
 
Figure 1: The saturation model. Increasing T levels result in PSA elevation and/or prostate tissue growth until the saturation point is reached, beyond which T does not further stimulate the prostate.
Screenshot (566).webp

----------------------------Serum Testosterone Concentrations ------------------------
 
Table 2: Expert recommendations for managing TD in men with active or treated PCa.


Prior to initiating testosterone therapy

Candidates for TTh should have a diagnosis of testosterone deficiency based on clinical history and laboratory diagnosis.

Patients must be made aware that safety data are limited and the degree of risk of PCa progression or recurrence is unknown.

Confirm there are no medical contraindications (eg, erythrocytosis) to testosterone therapy.

PSA should be undetectable or <0.1 ng/mL following radical prostatectomy, or stable following radiation treatment.

The most suitable candidates are those with low-risk disease with apparent cure at least one year following PCa treatment.

Men with moderate- or high-risk disease, or those on active surveillance should be advised that they are at risk for cancer recurrence or progression, even without TTh. Should recurrence or progression occur, it is unknown to what extent TTh may have contributed to this outcome.

The clinician should use shared decision-making and obtain informed consent.

Patients should be advised that PSA may rise with TTh, particularly if baseline serum T is below the saturation point, ie, 250ng/dL. A new PSA plateau will be achieved at 3-6 months. If PSA continues to rise after 6 months, this may indicate disease progression and appropriate investigative steps should be taken.




Suitable options for testosterone therapy

Short-acting formulations are preferred for initial treatment. Longer-acting formulations such as intramuscular testosterone undecanoate or subcutaneous pellets may be considered once PSA is stable.





Following initiation of testosterone therapy

Measure hematocrit and/or hemoglobin 2–4 times in the 1st year, then at least 1-2 times annually.

Measure PSA every 3–4 month in the 1st year after initiating testosterone and at least twice a year thereafter.

Perform DRE 1–2 times within 1st year, then annually.

Men on active surveillance should undergo prostate biopsy annually for the first two years, and if no progression is noted, may then follow standard AS protocols.



 
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I had a successful Radical Prostatectomy 7 months ago with clear margins. I have had 3 PSA tests showing undetectable. My T has recently dropped rapidly from 385 to 284 to 174. I have no erectile function since the surgery and have been using Prostaglandin E1. My Urologist says no TTh until 1 year PSA undetectable. Contrary to what the above-quoted studies show I have found several studies on PubMed that show no biochemical reoccurance with TTh in hypogonadal men after successful prostatectomy. You thoughts, please.
 
 

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Scientific Reference

Lakshman KM, Kaplan B, Travison TG, Basaria S, Knapp PE, Singh AB, LaValley MP, Mazer NA, Bhasin S. The effects of injected testosterone dose and age on the conversion of testosterone to estradiol and dihydrotestosterone in young and older men. J Clin Endocrinol Metab. 2010 Aug;95(8):3955-64.

DOI: 10.1210/jc.2010-0102 | PMID: 20534765 | PMCID: PMC2913038

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