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Varicocele Is the Root Cause Of Accepted: 22 January 2018 DOI: 10.1111/and.12992 ORIGINAL ARTICLE Varicocele is the root cause of BPH: Destruction of the valves in the spermatic veins produces elevated pressure which diverts undiluted testosterone directly from the testes to the prostate M. Goren1 | Y. Gat1,2 1Interventional Radiology, Laniado Hospital, Netanya, Israel Summary 2Department of Condensed Matter In varicocele, there is venous flow of free testosterone (FT) directly from the testes Physics, Sub Micron Research Weizmann into the prostate. Intraprostatic FT accelerates prostate cell production and prolongs Institute of Science, Rehovot, Israel cell lifespan, leading to the development of BPH. We show that in a large group of Correspondence patients presenting with BPH, bilateral varicocele is found in all patients. A total of Yigal Gat, Interventional Radiology, Laniado Hospital, Netanya, Israel. 901 patients being treated for BPH were evaluated for varicocele. Three diagnostic Email: [email protected] methods were used as follows: physical examination, colour flow Doppler ultrasound and contact liquid crystal thermography. Bilateral varicocele was found in all 901 patients by at least one of three diagnostic methods. Of those subsequently treated by sclerotherapy, prostate volume was reduced in more than 80%, with prostate symptoms improved. A straightforward pathophysiologic connection exists between bilateral varicocele and BPH. The failure of the one- way valves in the internal sper- matic veins leads to a cascade of phenomena that are unique to humans, a result of upright posture. The prostate is subjected to an anomalous venous supply of undi- luted, bioactive free testosterone. FT, the obligate control hormone of prostate cells, reaches the prostate directly via the venous drainage system in high concentrations, accelerating the rate of cell production and lengthening cell lifespan, resulting in BPH. KEYWORDS benign prostatic hyperplasia, BPH, internal spermatic vein, varicocele 1 | INTRODUCTION in the abdominal cavity as described in an earlier published work (Gat & Gornish, 2006). In the erect human male, there is a mechanism which overcomes the 2. To divide the overall hydrostatic pressure of the vertical blood problem of moving venous blood from the pelvis towards the heart, column within these veins (which is equivalent to a column of against the downward pull of gravity. The vertically oriented internal 35–40 cm of fluid) into 6–8 separate chambers, with the resulting spermatic veins (ISV’s) have 6–8 one-way valves on the left and 6–7 pressure in the lowest of the chambers not exceeding physiologic on the right. levels which range up to about 4 Torr (mmHg). (Gat, Bachar, These valves have several important functions: Zukerman, & Gornish, 2004) 3. To prevent the downward penetration of potentially toxic waste 1. Moving the venous blood upwards against gravity in the ab- products and blood components to the testes, some of which are sence of an active pump. This function is accomplished by vasoactive (such as efflux of catecholamine pre-cursors from the utilising dynamically changing pressure differences which occur left adrenal gland). Andrologia. 2018;e12992. wileyonlinelibrary.com/journal/and © 2018 Blackwell Verlag GmbH | 1 of 5 https://doi.org/10.1111/and.12992 2 of 5 | GOREN AND GAT flow upwards against gravity and prevent downward flow. Their 1.1 | Normal flow pattern of free testosterone destruction starts in the second decade, and an additional 15% to the prostate of men suffer from this disease with each subsequent decade. The blood that drains the testes and flows upward in the ISV’s with (Levinger, Gornish, Gat, & Bachar, 2007) It is our erect posture the assistance of the one- way valves, carries with it free testoster- and the vertical ISVs that exert a hydrostatic pressure overload one. As this blood leaves the testes, its concentration of FT is ex- on the valves leading to their incompetence. tremely high in comparison with the systemic circulation. The ISV Varicocele is not seen in quadruped mammals—the horizontally blood enters the systemic circulation on the left at the renal vein and oriented ISV’s in quadripeds do not have and do not need valves. The on the right (in 93% of patients) at the IVC. It is diluted volumetri- average hydrostatic pressures in their ISV’s systems remain around cally by a factor of nearly 100 (Jarwo, Chen, Trentacoste, & Zirkin, zero Torr. 2001; Walsh, 2002). In addition, protein binding to sex hormone- binding globulin (SHBG) inactivates nearly 99% of the FT (Feldman 1.3.1 | The damage caused by ISV valves’ failure & Feldman, 2001), and the free testosterone, now at physiologic lev- els, will reach the prostate via its arterial supply, having been diluted The elevated hydrostatic pressures produced by failure of the functionally by three orders of magnitude. valves in the ISV and their tributaries are propagated directly to all the venous structures that directly connect to them in compliance with Bernoulli’s principle of communicating vessels. Because there 1.2 | The control functions of FT in the prostate cell are no venous valves in the subinguinal testicular venous struc- FT is the obligate controller of prostatic cells. It regulates prolifera- tures or in the pelvic venous plexus, this entire venous pool is sub- tion, differentiation, cell maintenance, cell survival and apoptosis jected to the elevated hydrostatic pressures that occur in the ISVs (Isaacs, 1984). Under physiologic conditions in which FT supply to in varicocele. Normally, the pressures in the prostatic veins are the prostate is solely via the prostatic arteries, a “steady state” is low (around 4 Torr), but slightly higher than the pressures in the established between the rates of cell proliferation and cell death, pelvic venous plexus, so the direction of flow is out of the pros- and the gland’s volume remains normal. Elevated intraprostatic tate and towards the internal iliac veins and IVC. Under the condi- levels of FT increase the rate of cell proliferation and prolong cell tions created by varicocele, the pressure in the deferential vein survival, increasing the cell population and thus enlarging the gland. (DV) is some eight times above that in the prostatic venous plexus. (Chatterjee, 2003; Feldman & Feldman, 2001) Therefore, the direction of venous flow from the deferential vein divides into two flows. One, as usual, flows towards the IVC by way of the iliac veins. The second is diverted towards the prostate 1.2.1 | Varicocele gland where the extant venous pressure is lower (Gat, Gornish, Varicocele occurs when the valves in the vertically oriented ISV’s Heiblum & Joshua,2008; Gat, Joshua, Gornish, 2009). The pres- deteriorate, then malfunction and disappear as a result of incremen- sure gradient between the DV (which is at a higher venous pres- tal damage. Gravitational force produces elevated hydrostatic pres- sure) to the lower pressure prostatic venous system drives free sure in the vertically oriented ISVs. Elevated hydraulic stress on the testosterone- rich blood from the testes via the DV and Santorini delicate valve leaflets over time exceeds their elastic strength. (Gat venous plexus into the prostate. This, in essence, creates a highly & Gornish, 2006). Damage occurs to the one way valves of the ISVs abnormal flow phenomenon, unique in humans, in which an organ progressively from about the end of puberty until about the age of receives blood supply anomalously via its venous system. Under 75 years. This progressive valve failure begins at the lowest valve, the conditions which obtain in varicocele, the prostate gland is which is intermittently exposed to the highest hydrostatic pressure supplied with testosterone from two sources: and proceeds upwards, with the upper valves being the last to be affected. As the valves deteriorate and eventually resorb, a vertical 1. The physiologic supply from the prostatic artery. This is vol- column of blood (up to 35 cm on the right and 45 cm on the left) is umetrically diluted testosterone which is also bound to sex established in the ISV and its tributaries. That hydrostatic pressure hormone-binding globulin (SBHG), and reaches the prostate is propagated within the entire ISV system, down to the testes and in the appropriate, normal concentration. into the pelvic fossa venous plexus (Santorini), according to the law 2. The pathologic supply from the prostate venous system of free of communicating vessels (Bernoulli’s Principle). It can reach 27 Torr testosterone in very high uncontrolled concentration directly (mmHg) on the right and 33 Torr on the left, that is, 6- 8 times normal. from the testes via the DV, via the Santorini plexus, the peripros- tatic plexus and directly into the prostate gland. 1.3 | A unique phenomenon It should be noted here that the above observations of patho- It should be pointed out here that varicocele is a unique phenom- logical backflow from the testes directly to the prostate are not enon which only occurs in bipedal human males. The function of hypothetical. This pathologic backflow can be and is observed the one- way valves in the ISV’s is to enable and assist venous directly during venographic examinations of the ISV’s which are GOREN AND GAT | 3 of 5 performed during treatment. After effective occlusion of the ISVs at open surgery, as they are so small and are collapsed. Initially, these and all associated vertically oriented bypasses, the control veno- tiny veins provide assistance to the failing ISV system by capillary grams demonstrate that this pathologic backflow towards the flow upwards according to Laplace’s principle of “capillary force.” prostate gland ceases since the pressure gradient between the (Streeter, 1971a,b) At some point, as these vessels dilate under the testicular-prostatic drainage systems that exists in varicocele is persisting elevated pressures, the widened vessels lose their “capil- eliminated. The prostate then receives the testosterone its cells lary force” and can no longer support flow against gravity.
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