Effects of Testosterone Therapy in Men With Prostate Cancer

Introduction

Testosterone deficiency (TD), also known as hypogonadism (when the sex glands generate little or no hormones), and prostate cancer are both common in older men and can have a negative impact on general health and quality of life. TD affects up to 25 percent of elderly males. Testosterone therapy is a popular and successful treatment for clinically severe testosterone deprivation. Testosterone replacement therapy has been demonstrated to be beneficial in relieving the symptoms of testosterone insufficiency.

Despite overwhelming evidence of effectiveness, external testosterone treatment is typically rejected by a considerable proportion of men with TD (those with concurrent or previous prostate cancer). It was considered axiomatic that testosterone therapy was contraindicated in men with prostate. This was based on historical tradition and circumstantial evidence. The overwhelming body of evidence indicating the health and quality of life benefits of testosterone therapy has prompted a rethinking of traditional ideas about the effect of exogenous androgens on the prostate, particularly in men with prostate cancer.

What Is the History of Prostate Cancer and Testosterone Therapy?

The correlation between testosterone and prostate cancer has a lengthy history, tracing back to the early 1900s. The first observation was that men with advanced prostate cancer often had low testosterone levels, leading to the hypothesis that testosterone played a role in the growth and progression of prostate cancer. A key study on this association is the 1941 Huggins and Hodges study, which found that men with advanced prostate cancer who were given androgen deprivation therapy (ADT), which lowers testosterone levels, had a significant reduction in PSA (prostate specific antigen) levels and improvement in symptoms.

However, the relationship between testosterone and prostate cancer remains controversial, with studies in the 1960s and 1970s suggesting men with high levels of testosterone had an increased risk of prostate cancer, while other studies found no association. Current research indicates that males with reduced testosterone levels might have an increased likelihood of acquiring prostate cancer, yet further investigations are required to completely comprehend the link between testosterone and prostate cancer.

What Are the Effects of Testosterone Deficiency?

The use of exogenous testosterone was previously limited, but recent advancements in understanding testosterone deficiency and its adverse effects, as well as the benefits of testosterone therapy, have led to a re-evaluation of the potential risks of testosterone therapy, including its relationship to prostate cancer. TD is a medical condition that is characterized by a combination of these symptoms such as decreased sexual desire, infertility, increased body fat, reduced muscle mass and strength, decreased bone density, breast enlargement, anemia, hair loss, lack of energy, decreased motivation or self-confidence, feelings of sadness or depression, difficulty concentrating or remembering things, libido, erectile dysfunction, reduced morning erections, and fatigue.

Is Testosterone Therapy Effective in Males for Prostate Cancer?

The use of testosterone therapy in males treated for prostate cancer has drawn attention in the medical field. In the early 2000s, clinical evidence showed that testosterone was not a direct cause of prostate cancer growth. Instead, alternative hypotheses were proposed, such as the "saturation model," which suggested that testosterone could only promote the growth of cancer cells up to a certain point. The alteration in perception, together with the increasing recognition of the adverse health consequences and reduced quality of life among males with low testosterone levels (TD), resulted in a shift in the method of managing men with TD who had previously received prostate cancer treatment.

Case series studies from the mid-2000s provided safety data for testosterone therapy in men with prostate cancer. According to a study conducted by Kaufman and Graydon in 2004, seven males with low-risk prostate cancer who underwent radical prostatectomy and testosterone therapy did not experience any recurrences, with follow-up periods ranging from 24 months to 12 years. Another study from 2005 by Agarwal and Oefelein reported undetectable PSA levels in ten men with mostly intermediate-risk prostate cancer treated with radical prostatectomy and testosterone therapy, with a median follow-up of 19 months. A 2009 study by Khera et al. reported no recurrences in 57 men with primarily low- and intermediate-risk disease treated with testosterone therapy for an average of 36 months after radical prostatectomy, with a median follow-up of 13 months.

A 2013 study by Pastuszak et al. reported on 103 hypogonadal men previously treated with radical prostatectomy who underwent testosterone treatment. Unfortunately, 25 percent of these men had high-risk diseases, and the cohort was compared with a control group of 49 men who did not receive testosterone. PSA levels increased in the treatment group during the 27.5-month follow-up period, but there were more true prostate cancer recurrences in the control group.

Overall, studies have reported no recurrences in men with low-risk prostate cancer treated with testosterone therapy after surgery or radiation therapy, with follow-up times ranging from a few months to 12 years. The most significant radiation therapy series to date, from Pastuszak et al. in 2015, reported a slight increase in mean PSA from 0.08 ng/mL to 0.09 ng/mL in 98 men treated with testosterone after radiation therapy, with 6 (6.1 percent) men meeting criteria for biochemical recurrence during the study period.

In a 2014 review, Khera et al. discussed criteria to consider before initiating testosterone therapy in men with a history of prostate cancer. They recommend that clinicians:

1. Confirm that the clinical history is consistent with a testosterone deficiency laboratory diagnosis.

2. Disclose that limited data are confirming the safety of testosterone therapy and that the actual risks are unknown.

3. Obtain informed consent.

4. Confirm that there are no medical contraindications, such as erythrocytosis.

5. Ensure that PSA levels are either undetectable or stable.

6. Be prepared for a possible prostate cancer recurrence, which may or may not be related to the testosterone therapy.

7. Use testosterone therapy with considerable caution in men at high risk of prostate cancer recurrence or progression.

8. Not recommended concomitant use of testosterone with Androgen Deprivation Therapy (ADT).

Conclusion

Testosterone therapy for men treated for prostate cancer has been debated in the medical community. Historically, testosterone therapy was believed to promote prostate cancer growth. However, recent studies have shown that testosterone therapy can be safely administered to men with prostate cancer and may improve the quality of life for those with testosterone deficiency (TD). Despite this, the relationship between testosterone and prostate cancer remains controversial, and more research is needed to understand the relationship entirely. In general, testosterone therapy is a popular and effective treatment for clinically severe TD and can relieve the symptoms of testosterone insufficiency.