Substantiation of testosterone replacement therapy between courses of androgen blockade in patients with prostate cancer

40^th World Cancer Conference

August 25-26, 2021 WEBINAR

Pechersky A.V

North-Western State Medical University named after I.I. Mechnikov, St. Petersburg, Russia

Scientific Tracks Abstracts: J Cancer Sci Ther

Abstract :

Androgen blockade leads not only to the death of malignant prostate cells, but also to a violation of the division and differentiation of androgen-dependent cells (needing testosterone, formed in a physiological pulse mode). In response to a decrease in testosterone production, compensatory and adaptive reactions develop, aimed at increasing mitogenic stimulation, and their severity is proportional to the degree of decrease in testosterone production. Low-grade basal progenitor cells of the prostate epithelium are formed from stem cells that migrate from the intercellular space through the basement membrane. In the process of differentiation into the main cells, they have androgen receptors. With androgen blockade in patients with prostate cancer, low-differentiated basal progenitor cells of the prostate epithelium (normal and tumor) are deprived of the opportunity to transform into differentiated androgen-dependent main cells. This is accompanied by an additional increase in mitogenic stimulation. As a result, with androgen blockade, despite the death of cells of the primary highly differentiated androgen-dependent malignant tumor of the prostate gland, a new lowdifferentiated androgen-independent malignant tumor is formed, consisting of low-differentiated cancer cells of the primary tumor (which were previously a minority) and from malignantly transformed low-differentiated basal cells (which were previously normal). If malignant cells retain the ability to differentiate into androgendependent differentiated cells, then the administration of testosterone at a dose corresponding to its age-related decrease (with the preservation of testosterone production by Leydig's own cells in a physiological pulse mode) will lead to the restoration of androgen sensitivity of the tumor. In this case, repeated courses of androgen blockade will be more effective. Also, during adequate testosterone replacement therapy, compensatorily elevated levels of cellular growth factors, 5α-dihydrotestosterone, 17β-estradiol, insulin and other mitogenic factors that stimulate proliferation are reduced, the levels of LH, FSH, total and free testosterone are normalized. Thus, between relatively short courses of androgen blockade (up to 6 months), it is necessary to conduct adequate testosterone replacement therapy. It is necessary to abandon high doses of testosterone preparations (recommended by the authors of bipolar therapy), which lead to an excessive increase in factors that stimulate cell division (testosterone, 5α-dihydrotestosterone, 17β-estradiol, and others). The appointment of adequate testosterone replacement therapy between courses of androgen blockade can significantly improve the results of treatment of patients with prostate cancer.
Recent Publications:
1. Pechersky AV, Pechersky VI, Aseev MV, Droblenkov AV, Semiglazov VF. Several aspects of the regeneration process carried out by means of pluripotent stem cells. Tsitologiya 2008; 50(6): 511-520 (submitted July 06, 2007).
2. Pechersky AV, Pechersky VI, Smolyaninov AB, Vilyaninov VN, Adylov ShF, Shmelev AYu, Pecherskaya OV, Semiglazov VF. Regeneration and Carcinogenesis. Journal of Stem Cells 2015; 10(4): 255-270.
3. Pechersky AV, Pechersky VI, Aseev MV, Droblenkov AV, Semiglazov VF. Immune system and regeneration. Journal of Stem Cells 2016; 11 (2): 69-87.
4. Pechersky AV. Revisiting Terminology and Characteristics of Stem Cells. Journal of Stem Cells 2016; 11 (2): 63-67.
5. Pechersky AV, Pechersky VI, Shpilenya ES, Gaziev AH, Semiglazov VF. Regeneration and Cicatrization. Journal of Stem Cells 2016; 11(2): 89-97.
6. Pechersky AV, Pechersky VI, Vilyaninov VN, Pecherskaya OV, Semiglazov VF. Regeneration’s role in the development of desensitization and immunological tolerance. Journal of Stem Cells 2019; 14(2): 75-102 (submitted July 19, 2019).
7. Pechersky AV, Pechersky VI, Pecherskaya OV, Semiglazov VF. Features of the Immune Response to One’s Own Antigens and Foreign Antigens. Journal of Stem Cells 2020; 14(4): 187-202.
8. Pechersky AV. Role of partial androgen deficiency of aging men in development of the metabolic syndrome. American Research Journal of Urology 2016; 1: 1-13.
9. Pechersky AV. The influence of partial androgen deficiency in aging men (PADAM) on the development of benign prostatic hyperplasia and prostate cancer. American Research Journal of Urology 2019; 3(1): 1-16.
10. Pechersky AV. Features of diagnostics and treatment of partial androgen deficiency of aging men. Central European Journal of Urology 2010; 67 (4): 397-404.
11. Pechersky AV. Influence of violation of regeneration in people over 35-40 years old on decrease in production of sexual hormones. Journal of Stem Cells 2016; 11 (2): 99-109.

Biography :

Pechersky, Alexander is an Associate Professor at North-Western State Medical University named after I.I. Mechnikov, St. Petersburg, Russia. His achievements include the original articles devoted to the influence of partial androgen dеficiency among aging men (PADAM) on the development of benign prostatic hyperplasia, prostate cancer and metabolic syndrome, diagnostics and treatment of partial androgen deficiency of aging men, regeneration, immune system, carcinogenesis, cicatrization, desensitization, immunological tolerance and antitumor immunotherapy.