Prostate cancer: a newly discovered route for testosterone to reach the prostate

Abstract

The prostate, an androgen-regulated exocrine gland, is an integral part of the male reproductive system which has an essential function in sperm survival and motility in its long hostile route to meet and fertilise the egg in the Fallopian tube. Testosterone is known to be the key, obligatory regulator of the prostate that promotes the development and progression of prostate cancer (PCa). Yet, the pathophysiological mechanism of PCa remains unclear and its causal relation to serum testosterone has not been established. Here, we report on the discovery of a previously unrecognized route of flow of free testosterone (FT), at a concentration of 130 times the physiological levels, reaching the prostate via the testicular and prostate venous drainage systems, bypassing the systemic circulation. This condition results from the malfunction of the vertically oriented testicular venous drainage system in humans, a phenomenon with a prevalence that increases rapidly with age, which causes deviation of the testicular venous flow from its normal route. Early results of an interventional radiological procedure, super-selective intraprostatic androgen deprivation therapy are discussed. This treatment has resulted in decrease in prostate volume, and serum PSA, with disappearance of cancerous cells on repeat biopsies in five of six patients. Some of the unresolved biological enigmatic questions associated with PCa are discussed. We conclude that pathological flow of FT from the testes directly to the prostate in an extremely high concentration via the testicular-prostate venous drainage systems was identified may explain the mechanism for the development of PCa. We suggest a time-window for eradication of localised, androgen-sensitive, PCa cells. We anticipate that this treatment may retard, stop or even reverse the development of the disease. A mechanism for the evolution of PCa is discussed.

Childhood height increases the risk of prostate cancer mortality

“…One suggestion is that tall men are at a higher risk of impaired venous drainage (varicocele) of the male reproductive system, resulting in extremely high prostatic testosterone levels thus promoting the development and progression of prostate malignancy. (21) Moreover, child and adult height are correlated(22), thus tracking of height may explain part of the association between childhood height and prostate cancer mortality. However, as we do not have information on adult height, we cannot assess and disentangle these effects.…”

Circulating steroid hormones in prostate carcinogenesis. Part 1 – Androgens

“…A new route for the flow of FT (at very high concentrations), which could reach the prostate via the testicular and prostatic venous drainage systems, bypassing the systemic circulation (73), has very recently been described. This condition results from malfunction of the vertically oriented testicular venous drainage system in humans, a phenomenon with a prevalence that increases rapidly with age and causes a deviation of the testicular venous flow from its normal route.…”

Varicose veins in the male small pelvis (a review of literature)

“…в 2009 г. пред-ложили суперселективную интрапростатическую андро-генную депривацию для лечения рака предстательной железы [36].…”