Testosterone Replacement in Prostate Carcinoma: A Systematic Review of an Emerging Paradigm and Therapeutic Potential.

Prostate carcinoma is one of the most prevalent cancers among men. It is a dreaded outcome in the elderly male population and most commonly affects those 65 years of age and older. The etiologic nature of this common urological cancer is multifactorial and has an environmental, racial, and genetic interplay. One of the important factors believed to be involved in the causation of prostate carcinoma are androgens and prostatic sensitivity. Conventional treatment for this neoplasm ranges from radical surgery (prostatectomy), external beam radiation, brachytherapy, and androgen deprivation therapy (ADT) to radiopharmaceutical techniques. The conventional consensus is that external testosterone replacement therapy (TRT) is contraindicated in patients with prostate carcinoma or who are at risk thereof. The latest data and studies are challenging this notion and relationship. It is paramount that these misconceptions and older conventions are definitively and clearly corrected so as to ensure the best and most suitable treatment is made available to patients. This systematic review aims to find the relation between testosterone replacement therapy and prostate carcinoma. An extensive review of literature was done on the following databases: Google Scholar, Trip Database, EMBASE, PubMed, and PubMed Central to collate the latest data available on testosterone replacement therapy and prostate carcinoma for a systematic review. A combination of keywords was used for data extraction: "Hormone Replacement Therapy" OR "Prostate" OR "Prostatic Neoplasms" OR "Testosterone" OR "Urology." A triad of findings were noted: (1) exogenous testosterone replacement therapy is not contraindicated in men who have undergone definite treatment for their prostatic carcinoma (prostatectomy, external beam radiation, and/or chemotherapy), (2) exogenous testosterone replacement therapy does not alter intraprostatic dehydroepiandrosterone (DHEA) levels and thus does not attenuate or catalyze any change in the prostatic milieu, and (3) castration-resistant prostatic carcinoma does not undergo disease progression when treated using high-dose testosterone replacement therapy. No correlation between testosterone replacement therapy and prostate carcinoma exists, and TRT is not contraindicated in men post-definitive treatment for their primary neoplastic prostatic lesion. TRT is indicated in hypogonadal men post-primary treatment for its myriad of benefits and ultimate improvement of quality of life. The role of TRT in men prior to the diagnosis of prostatic carcinoma is unclear; thus, patients should give their informed consent before receiving the testosterone therapy. The role of TRT in prostate cancer is evolving, even in cases of advanced prostate cancer. One area of interest is bipolar androgen therapy (BAT), which has been studied in various clinical trials focused on castrate-resistant prostate cancer. Prostate cancer cells adapt to chronic low testosterone levels by increasing androgen receptor activity, resulting in a 30- to 90-fold rise in androgen receptor levels. Although this significant upregulation of androgen receptors can lead to castration resistance, it also creates a therapeutic vulnerability to treatment with high doses of testosterone, which can result in growth arrest or cell death. The term "bipolar" in BAT refers to the rapid switching between two extremes: from high testosterone levels (supraphysiologic) to near-castrate serum testosterone levels.