Prevalence of Hypogonadism in Low-Risk Prostate Cancer Survivors

Recent studies have shown that there may be a more complex relationship between serum T and PCa risk than was previously established. ³⁷ Although PCa cells have been shown to become androgen-independent as they progress into the castrate-resistant phase, ⁹ several studies have indicated that low-serum T is associated with greater PCa risk and more worrisome features of PCa. ^38,39 Hence, a saturation model has been proposed: Changes in serum T concentrations below the point of maximal androgen-androgen receptor (AR) binding will elicit substantial changes in PCa growth, as seen with castration or with serum T administration to castrated men. ⁴⁰ However, once maximal androgen-AR binding is reached, the presence of additional androgen produces little further effect, suggesting that there is a limit to the ability of androgens to stimulate growth of PCa. ⁴⁰

A meta-analysis of 45 articles studying the relationship between serum T and PCa risk has reported conflicting results. ⁴ Eugonadal testosterone levels, whether physiologically or pharmacologically replaced, do not seem to promote PCa growth. It is unclear whether the timing of sex hormone exposure affects PCa or whether the cancer may influence blood levels of sex hormones. Since 2004, there have been case series totaling almost 150 men treated with prostatectomy, brachytherapy, or external beam radiation who have been safely treated with TRT. ^6-9 These case studies suggest that after a thorough discussion of risks and benefits, TRT may be safer than previously thought for men who have been successfully treated for PCa, are deemed low risk for recurrence, and are monitored closely. However, no randomized controlled trials are available, and published guidelines recommend against starting TRT in patients with a history of breast or PCa. ¹

Limitations

This study has limitations. The sample size is small and, therefore, it may not have had enough power to show differences in prevalence by subgroups. In addition, the population may not be representative of all male veterans who seek care in the VA or of men in other health care settings, because this was a convenience sample of VA patients who received most of their care in the VA. However, the prevalence of hypogonadism, in this outpatient population is very similar to that found among men seen in primary care clinics. ¹⁴ Finally, because pretreatment serum T levels were lacking, the authors were unable to assess whether hypogonadism was present before surgery or radiation therapy, and unable to determine whether treatment had any effect on serum T levels.

The study has several strengths. First, to the authors’ knowledge, this is the first study to assess the prevalence of hypogonadism after patients with low-risk PCa have received treatment with curative intent. Second, the authors assessed hypogonadism in every patient by measuring serum T levels in the early morning when levels are known to be at their highest. Third, differentiating primary and secondary hypogonadism helped provide insight into the possible etiology of the low serum T levels. Fourth, this study was performed at a single institution that uses electronic medical records, with almost complete data on patient demographics, PCa treatment, and receipt of TRT or androgen deprivation therapy. Fifth, because this study had the participation of endocrinologists and urologists, the study design helped answer questions pertinent to both medical and surgical specialties.