Testosterone and prostate cancer: an evidence-based review of pathogenesis and oncologic risk

Abstract

Testosterone plays a central role in male development and health. Likewise, androgen deficiency, or hypogonadism, is associated with a variety of symptoms including decreased energy, diminished libido and erectile dysfunction, among others. Male androgen levels steadily decline with age, and, in a subset of symptomatic older men, can result in late-onset hypogonadism (LOH). Over the last decade, increased awareness of hypogonadism among patients and providers has led to a significant rise in the use of testosterone replacement therapy (TRT) for hypogonadism, and especially in LOH. Accompanying the rise in TRT are concerns of potential adverse effects, including cardiovascular risks and the promotion of prostate cancer. The 'androgen hypothesis' asserts that prostate cancer development and progression is driven by androgens, and thus TRT has the theoretical potential to drive prostate cancer development and progression. In this review, we examine existing data surrounding testosterone and prostate cancer. There is significant evidence that androgens promote prostate cancer in experimental systems. However, there is no clear evidence that elevations in endogenous testosterone levels promote the development of prostate cancer in humans. As a result of experimental and historical data on the progression of prostate cancer following TRT, there has been widespread belief that TRT will promote disease progression in prostate cancer patients. Despite these fears, there are a growing number of studies demonstrating no increase in prostate cancer incidence among men on TRT. Furthermore, in studies involving a small number of patients, there has been no discernable increase in disease progression in prostate cancer patients on TRT. While data from large, prospective, randomized, controlled trials are absent, TRT in select prostate cancer patients is likely safe. In the end, the use of TRT in prostate cancer patients is still considered experimental and should only be offered after well-informed shared decision making and with close monitoring.

Association between baseline serum glucose, triglycerides and total cholesterol, and prostate cancer risk categories

“…Nevertheless, in our study, we lacked information on duration of glucose aberrations. Prolonged glucose impairment has been reported to cause destruction of the Leydig cells, thereby, resulting in lower testosterone levels and potentially lowering the risk of worse outcomes [40,[45][46][47][48]. Nonetheless, evidence linking lower testosterone to reduced risk of worse PCa outcomes remains conflicting [46][47][48].…”

Association between Low Serum Testosterone and Prostate Cancer Behaviour

“…In patients with hypogonadal clinical status and with a PSA < 4.0 ng/ml, TRUS guided prostate biopsy has shown cancer in around 15%, with the risk of the tumor increases twice when met with the greater reduction in the serum testosterone levels. 9 The association between serum testosterone and cancer prostate is not yet well established. The possible explanation for the link between low serum testosterone and cancer prostate is due to the negative feedback effect of serum testosterone on hypothalamic-pituitary axis.…”

Az ösztrogénmetabolom biológiai és klinikai jelentősége lokális folyamatokban

“…A prosztata megbetegedéseinek klinikai diagnosztikájá-ban kulcsfontosságú szerep jut az androgén szteroidhormonoknak ("androgénhipotézis") [56]. Az androgén-hormonok, elsősorban a tesztoszteron és az 5α-reduktáz által végzett átalakítása során keletkező DHT vitális paraméterei a prosztatakarcinóma és a jóindulatú prosztata-hyperplasia kialakulásának [56,57].…”

“…Az androgén-hormonok, elsősorban a tesztoszteron és az 5α-reduktáz által végzett átalakítása során keletkező DHT vitális paraméterei a prosztatakarcinóma és a jóindulatú prosztata-hyperplasia kialakulásának [56,57]. A prosztata aromatázenzim-termelése megváltozik malignus folyamatokban, ami az ösztrogénmetabolitok kialakulásának sejtszintű bizonyítéka [58].…”