How long have you been on Testosterone Replacement Therapy?

I know you may have heard weird and concerning terms like overall prostate cancer risk or favorable risk prostate cancer.

How is it a cancer risk and favorable risk? Is it true that you may have prostate cancer because of TRT?

If you have these concerns in mind, by the end of this article, you are going to be relieved! So stay with us and keep reading…

Key Takeaways

  • TRT does not worsen LUTS and is not contraindicated in men diagnosed with BPH.

  • There is no evidence that TRT may cause prostate cancer. However, administration of TRT for hypogonadal men previously treated for high-risk prostate cancer should be taken with caution.

  • Talk with your doctor about your concerns and make sure to understand the benefits and the possible side effects of TRT before the start of your treatment.

Testosterone – The Male Hormone

Testosterone has many beneficial effects such as:

  • Inducing hematopoiesis. [1]

  • Increasing muscle strength. [1]

  • Increasing bone strength and density. [1]

  • Improving sexual function and libido. [1]

  • Important for epithelial cell differentiation in normal prostate. [7]

The Baltimore Longitudinal Study of Aging reported the incidence of hypogonadism as 20% in men over 60 years, 30% in men over 70 years, and 50% in men over 80 years of age. [2]

Figure 1: There is a clear link between aging and Testosterone decline

With this gradual decline, the beneficial effects of testosterone could be compromised. [1]

Testosterone Replacement Therapy

Testosterone deficiency may lead to an increased risk of bone fracture, low bone mineral density, poor sleep quality, and fatigue. [7]

Testosterone replacement therapy (TRT) is an FDA-approved treatment option for men with low testosterone levels and symptoms of hypogonadism. [1]

A rising trend in the prescription of TRT products worldwide was observed between 2000 and 2010. [7]

This trend was most pronounced in the United States and reached a peak in 2011 [7]

Risks such as worsening prostate cancer, male breast cancer, worsening benign prostatic hyperplasia (BPH), polycythemia, and obstructive sleep apnea (OSA) should be considered before administering TRT to a patient. [1]

TRT can regain the positive effects of testosterone. This, in turn, led to a significant increase in the use of testosterone therapy for men with symptomatic hypogonadism. [1]

A recent randomized trial showed significantly improved sexual activity, sexual desire, and erectile function for hypogonadal men aged> 65 years with testosterone levels, 275 ng/dL who received TRT. [7]

TRT and Benign Prostatic Hyperplasia (BPH)

The effect of TRT on the prostate is concerning for a lot of patients. [1]

In a previous study, Marks et al. showed that TRT for 6 months improves serum androgen levels, but had little effect on the prostate. [3]

Testosterone supplementation has been shown to increase the prostate size by 12%. However, lower urinary tract symptoms (LUTS) and urinary retention do not worsen in men on testosterone therapy. [1]

Similarly, the presence of hypogonadism in 312 men with LUTS was not predictive of worsening International Prostate Symptom Scores (IPSS) or maximal urinary flow rates. [4]

In a randomized controlled trial, 52 men were randomly assigned to receive TRT. At 1 year, the 23 men randomized to 250 mg of testosterone enanthate every 4 weeks reported significant improvements in IPSS and maximal urinary flow rates compared with baseline and controls. [5]

While older men on testosterone therapy do have an increase in overall prostate size, this increase in size does not differ from the increase in prostatic hypertrophy seen in elderly men, not on testosterone therapy. [1]

Taken together, TRT does not appear to grossly worsen LUTS and is not contraindicated in men diagnosed with BPH. [1]

Does TRT Cause Prostate Cancer?

With regard to prostate cancer, previous studies have shown a higher risk of aggressive disease in men with hypogonadism. [7]

In a previous population-based study, the authors found that patients who received TRT did not have an increased risk of overall prostate cancer, a longer duration of adherent TRT was not associated with greater risk, and patients who received TRT had a significantly lower risk of aggressive prostate cancer. [7]

Androgen deprivation therapy is a cornerstone in treatment for men with advanced prostate cancer. Therefore, it is not surprising that TRT is contraindicated in men with prostate cancer, as well as high-risk patients, which includes men with first-degree relatives with prostate cancer and African-Americans who have a prostate-specific antigen (PSA) >3 ng/ml. [1]

Many longitudinal studies investigating the relationship between endogenous testosterone levels and subsequent risk of prostate cancer failed to find any association. [1]

As such, prostate cancer incidence in men on testosterone therapy is similar to men who are not on testosterone therapy. [1]

Similarly, in a 3-year prospective trial, the incidence of prostate cancer was similar among men receiving TRT and controls.[6]

In a large meta-analysis of 18 prospective studies that included over 3500 men, there was no association between serum androgen levels and the risk of prostate cancer development.[8]

For premalignancy, prostatic intraepithelial neoplasia (PIN) appears to be a risk factor for developing prostate cancer, however, this association has been mostly demonstrated for high-grade disease. [1]

There is a lack of long-term data on the use of TRT in men with PINs. In one study, 12 months after TRT, only one patient out of 20 men with the previous PIN developed overt prostate cancer. [1]

For men who have previously undergone definitive treatment for prostate cancer, the usage of TRT is more accepted. [1]

TRT does not appear to increase cancer recurrence in hypogonadal men following radical prostatectomy. [1]

While there have been reports of metastatic prostate cancer in older men who are on testosterone therapy, these are mostly anecdotal. [1]

Because of the potential risk and the controversial data, practitioners are often reluctant to administer testosterone to patients who may be at high risk for prostate cancer. [1]

Men on TRT should have frequent PSA monitoring; any major change in PSA (>1 ng/mL) within the first 3-6 months may reflect the presence of pre-existing cancer and warrants cessation of therapy. [1]

In prostate cells and prostate cancer cells, testosterone stimulates proliferation, but the dependence of prostate cancer cell survival on androgens is more controversial. [7]

Further support of the concept of testosterone as a differentiating agent for prostate cancer comes from the observation that high-dose testosterone treatment of men with castration-resistant prostate cancer transforms cancer cells into a more differentiated phenotype sensitive to further androgen deprivation therapy. [7]

This population-based nested case control in the National Prostate Cancer Register of Sweden showed no evidence of an association between men who received TRT and total prostate cancer risk. [7] The findings suggest that from a prostate cancer perspective, TRT is safe in hypogonadal men. [7]

Male Breast Cancer

The role of testosterone in breast cancer development is yet to be fully understood. However, several studies showed that there is a link between high testosterone levels and the development of breast cancer. [1]

One retrospective review reported an incidence of 11% in 45 men on long-term TRT over 10 years. [1]

Future prospective studies with longer follow-ups will determine if such association between TRT and male breast cancer truly exists.

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