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Reversal of BPH by Super-selective Intraprostatic Androgen Deprivation Therapy
Physical Deterioration of the One-way Valves in the Table 1: Prostate Volume, Prostate-specific Antigen and
Internal Spermatic Vein
Nocturia Before and After Treatment of 28 Patients with
Normally, lacking an active pump in the testicular venous drainage
Benign Prostate Hyperplasia
system, the OWVs function as a unique hydraulic system that raises
the venous blood upwards, stepwise, against gravity while preventing
Parameters Before After Change p-value
Treatment Treatment
downward flow. The valves do not open and close in a synchronous
Prostate 56 37 55% (compared <0.0001
way (as they do in the lower limbs), but are activated by intermittent
volume (cc) with normal
pressure fluctuations produced by the action of nearby muscles and
prostate volume)
abdominal structures. Under these conditions, some of the valves are PSA (ng/ml) 3.5 3.2 None 0.1117
closed while others above them are open. Hence, there is a high Nocturia 3.5 1 70% <0.0001
probability that the average hydrostatic pressure exerted on lower PSA = prostate-specific antigen.
valves is higher than the average calculated physiological hydrostatic
pressure exerted on each valve, which is ~4–6mmHg (see above and It is clear that under these conditions the supply of FT to the prostate
Figures 1 and 2). This is also the approximate hydrostatic pressure at that arrives physiologically via the prostate artery is negligible
the testicular and the prostate venous drainage systems under compared with the FT flow via the prostate venous drainage system
normal conditions. This pressure can be calculated via the equation (back door). This blood is carries undiluted FT and is unbound to SHBG
for calculation the hydrostatic pressure (a derivative of Pascal and with extremely high concentrations, which bypasses the systemic
Newton's principles): circulation. These levels of FT are not detected in the peripheral blood;
therefore, the information on testosterone levels we receive from
P = ρxh (1) blood tests are entirely dissociated from intraprostatic testosterone
levels. Hence, serum testosterone is not relevant as a source of
where ρ is the density of the liquid and h the vertical height of the blood information about the intraprostatic androgen microenvironment.
column (cm). Moreover, P is independent of the shape or size of the
liquid column and of any motion in the liquid. For a normal It should be noted that in contrast to the erect posture of humans, the
compartment size of 6–8mm (see Figures 1 and 2), the physiological horizontal posture of quadruped animals does not exert a downward
average pressure on a valve is ~4–6 mmHg. This pressure is also the gravitational force on the venous drainage of the reproductive system
approximate hydrostatic pressure at the testicular and the prostate and, therefore, OWVs are not necessary (and do not exist).
venous drainage systems under normal conditions.
Two parallel effects then occur in the prostate: a rapid mechanical
Since each valve opens and closes at least 100,000 times a year effect – hypertrophy – and a slower, biological process – hyperplasia.
(~2–3% of the number of heart beats), the valves are exposed Hypertrophy occurs due to the elevated venous back-pressure causing
repeatedly to an excessive load exerted on their elastic collagen congestion and enlargement of the gland. It can be appreciated by
tissue, leading to their progressive physical deterioration culminating studying its effect on the lower segment of the ISVs and the PP, which
eventually in their complete destruction. The vertical height of the dilate until they can be easily palpated (variocele). The volume of the
blood column in the right ISV is ~35cm and in the left ISV ~40cm. ISVs and, in particular, that of the PP can increase by three- to nine-fold
When all of the valves in each of the ISVs are incompetent, the under the elevated pressure.
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The prostate, exposed to that elevated
hydrostatic pressure at the drainage system relative to the pressure and composed of elastic tissue, enlarges in response to the
corresponding insertion of the ISV is more than 30mmHg on the left increasing pressure in a similar manner, leading to hypertrophy of
side and 27mmHg on the right side. Recent studies have shown that the prostate.
the incidence of this phenomenon increases with age,
7
reaching >75%
in those 70 years of age.
8
Hyperplasia, the biological process, can be explained as follows: under
normal conditions FT reaches the prostate gland via the prostatic artery
Effect of Elevated Pressure in the Testicular Venous after travelling through the general circulation system. Over this long
Drainage System on the Entire Reproductive System route the testosterone dilutes by 70–100-fold
19,20
and binds to SHBG. Only
When the valves are destroyed, venous blood in the ISVs cannot flow a small fraction of the testosterone (less than 2%) remains free.
3
upward against gravity; ISVs on both sides cease to function as normal However, when the valves are destroyed, the blood that arrives directly
physiological testicular venous drainage systems. The venous drainage from the testes to the prostate via the back door travels only 10–15cm,
from the testes is thus diverted into three other alternative channels in which FT, undiluted and not yet bound to SHBG, is in concentrations
(shunts) with elevated pressure. One of these, the DV, which drains the approximately 130 times above physiological levels, arrives from its
testes, creates a hydraulic connection with the PVP (Santorini's production site within the testes directly to the prostate, promoting
plexus), which partially drains the prostate via the VV. The VV, being the accelerated prostatic cell proliferation. The result is a change in the
connecting vessel between the two systems, is a common space normal proliferation/ apoptosis balance of prostatic cells,
2
leading to
shared by the testicular and prostate drainage systems. However, on hyperplasia of the prostate. Of course, this process of accelerated
the side of the prostatic drainage system there is physiological proliferation of prostate cells would not be expected to stop with
pressure; on the side of the testicular drainage systems the pressure hyperplasia and could, we suggest, progress with time to neoplasia.
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is substantially higher. Venous blood from the testicular side will flow
retrograde into the prostate venous drainage (via the VV and the PVP), Reversal of Benign Prostate Hyperplasia
reaching the prostate at elevated hydrostatic pressure with an After Treatment (Gat–Goren Technique)
elevated concentration of FT (approximately 130-fold above We can consider this treatment as super-selective intra-prostatic
physiologicallevels ) (see Figure 2). androgen deprivation (SPAD) therapy. When restoration of normal
EUROPEAN UROLOGICAL REVIEW 13