Search for prognostic markers of the undesirable effects of mifepristone in the treatment of uterine myoma


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Abstract

Objective. To comparatively analyze the data of key molecular pharmacological and biochemical parameters in patients to reveal a potential marker for the risk of endometrial glandular dilatation (EGD) during therapy with mifepristone for its use in the individual choice of therapy for a specific female patient. Subjects and methods. The investigation enrolled 50 late reproductive-aged patients with myoma of the uterus, which corresponded to the size of that of 6-12-week pregnancy and the interstitial and interstitial-subserous sites of myomatous nodules. Peripheral blood mononuclear cells served as a material for molecular genetic tests; the expression of the sex steroid receptor genes in the mononuclear cell fraction was studied by RT-PCR. Results. EGD was detected in 11 (22%) of the 50 patients treated with mifepristone. The androgen receptor (AR) gene expression in the patients with EGD was shown to be 4 times lower than that in the patients without endometrial changes. Conclusion. Comparison of the expression of the AR gene and the presence of EGD in mifepristone-treated patients could reveal a negative correlation between these indicators. ROC analysis has shown the value of mRNA of the AR gene, the excess of which suggests that there is a low risk for mifepristone-induced EGD. A potential marker for the risk of EGD during mifepristone therapy has been revealed.

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About the authors

E. N Kareva

N.I. Pirogov Russian National Research Medical University, Ministry of Health of Russia

Email: elenakareva@mail.ru
Doctor of Medical Science, Professor

L. Kh Bekhbudova

N.I. Pirogov Russian National Research Medical University, Ministry of Health of Russia

Email: lamarabekh@gmail.com
Assistant of Pharmacology Department

O. S Gorenkova

Moscow Regional Research Institute of Obstetrics and Gynecology

Email: olga-gore@mail.ru
PhD, Senior Researcher, Gynecologist-Endocrinologist

T. E Samoilova

N.I. Pirogov National Medical and Surgical Center

Email: tesamoylova@mail.ru
Doctor of Medical Science, Professor of Women Diseases and Reproductive Health Department

References

  1. Rein M.S., Barbieri R.L., Friedman A.J. Progesterone: a critical role in the pathogenesis of uterine myomas. Am. J. Obstet. Gynecol. 1995; 172(1, Pt 1): 14-8.
  2. Andersen J. Growth factors and cytokines in uterine leiomyomas. Semin. Reprod. Endocrinol. 1996; 14(3): 269-82.
  3. Maruo T., Matsuo H., Samoto T., Shimomura Y., Kurachi O., Gao Z. et al. Effects of progesterone on uterine leiomyoma growth and apoptosis. Steroids. 2000; 65(10-11): 585-92.
  4. Волков В.Г., Гусева Н.В., Горшкова И.А. Оптимизация консервативного лечения миомы матки антипрогестеронами и оценка влияния проводимой терапии на качество жизни женщин. Вестник новых медицинских технологий. 2011; 18(1): 92-3. [Volkov V.G., Guseva N.V., Gorshkova I.A. Optimization of conservative treatment of uterine fibroids by antiprogesterone and evaluation of the impact of therapy on quality of life of women. Vestnik novyih meditsinskih tehnologiy. 2011; 18(1): 92-3. (in Russian)]
  5. Wilkens J., Chwalisz K., Han C., Walker J., Cameron I.T., Ingamells S. et al. Effects of the selective progesterone receptor modulator asoprisnil on uterine artery blood flow, ovarian activity, and clinical symptoms in patients with uterine leiomyomata scheduled for hysterectomy. J. Clin. Endocrinol. Metab. 2008; 93(12): 4664-71.
  6. Rabe T., Ahrendt H.J., Albring C., Bitzer J., Bouchard P. Cirkel U. et al. Ulipristal acetate for symptomatic uterine fibroids and myoma-related hypermenorrhea joint statement by the German Society for Gynecological Endocrinology and Reproductive Medicine (DGGEF) and the German Professional Association of Gynecologists (BVF). J. Reprod. Endokrinol. 2013; 10(Sonderheft 1): 82-101.
  7. Chabbert-Buffet N., Meduri G., Bouchard P., Spitz I.M. Selective progesterone receptor modulators and progesterone antagonists: mechanisms of action and clinical applications. Hum. Reprod. Update. 2005; 11(3): 293-307.
  8. Ноте F.M., Blithe D.L. Progesterone receptor modulators and the endometrium: changes and consequences. Hum. Reprod. Update. 2007; 13(6): 567-80.
  9. Mutter G.L., Bergeron C., Deligdisch L., Ferenczy A., Giant M., Merino M. et al. The spectrum of endometrial pathology induced by progesterone receptor modulators. Mod. Pathol. 2008; 21(5): 591-8.
  10. Fiscella J., Bonfiglio T., Winters P., Eisinger S.H., Fiscella K. Distinguishing features of endometrial pathology after exposure to the progesterone receptor modulator mifepristone. Hum. Pathol. 2011; 42(7): 947-53.
  11. Патент № 2312354, Российская Федерация. Способ диагностики эстроген- и прогестеронзависимой патологии гениталий. Гаспарян Н.Д., Карева Е.Н., Горенкова О. С., Маняхина А.Е. Заявка 7 декабря 2006, опубликовано 10 декабря 2007. [Patent number 2312354, the Russian Federation. A method for diagnosing estrogen and progesterone-dependent pathologies of the genitals. Gasparyan N.D., Kareva E.N., Gorenkova O.S., Manyahina A.E. Application December 7, 2006, published on 10 December 2007. (in Russian)]
  12. Klein S.L., Roberts C.W., eds. Sex hormones and immunity to infection. Berlin, Heidelberg: Springer-Verlag; 2010. 319p.
  13. Карева Е.Н., Ганковская Л.В., Шимановский Н.Л. Половые стероиды и иммунитет. Российский иммунологический журнал. 2012; 6(1): 3-13. [Kareva E.N., Gankovskaya V.L., Shimanovskiy N.L. Sex steroids and the immune system. Rossiyskiy immunologicheskiy zhurnal. 2012; 6(1): 3-13. (in Russian)]
  14. Schmittgen T.D., Livak K.J. Analyzing real-time PCR data by the comparative C(T) method. Nat. Protoc. 2008; 3(6): 1101-8.
  15. Esteve J.L., Acosta R., Pérez Y., Rodriguez B., Seigler I., Sanchez C., Tomasi G. Mifepristone versus placebo to treat uterine myoma: a double blind, randomized clinical trial. Int. J. Womens Health. 2013; 5: 361-9.
  16. Eisinger S.H., Meldrum S., Fiscella K., le Roux H.D., Guzick D.S. Low-dose mifepristone for uterine leiomyomata. Obstet. Gynecol. 2003; 101(2): 243-50.
  17. Bagaria M., Suneja A., Vaid N.B., Guleria K., Mishra K. Low-dose mifepristone in treatment of uterine leiomyoma: a randomised double-blind placebo-controlled clinical trial. Aust. N. Z. J. Obstet. Gynaecol. 2009; 49(1): 77-83.
  18. Engman M., Granberg S., Williams A.R., Meng C.X., Lalitkumar P.G., Gemzell-Danielsson K. Mifepristone for treatment of uterine leiomyoma. A prospective randomized placebo controlled trial. Hum. Reprod. 2009; 24(8): 1870-9.
  19. Kulshrestha V., Kriplani A., Agarwal N., Sareen N., Garg P., Hari S., Thulkar J. Low dose mifepristone in medical management of uterine leiomyoma. Indian J. Med. Res. 2013; 137(6): 1154-62.
  20. Carbonell J.L., Acosta R., Pérez Y., Marrero A.G., Trellez E., Sánchez C., Tomasi G. Safety and effectiveness of different dosage of mifepristone for the treatment of uterine fibroids: a double blind randomized clinical trial. Int. J. Womens Health. 2013; 5: 115-24.
  21. Seth S., Goel N., Singh E., Mathur A.S., Gupta G. Effect of mifepristone (25 mg) in treatment of uterine myoma in perimenopausal woman. J. Midlife Health. 2013; 4(1): 22-6.
  22. Ellis T.M., Moser M.T., Le P.T., Flanigan R.C., Kwon E.D. Alterations in peripheral B cells and B cell progenitors following androgen ablation in mice. Int. Immunol. 2001; 13(4): 553-8.
  23. Lai K.P., Lai J.J., Chang P., Altuwaijri S., Hsu J.W., Chuang K.H. et al. Targeting thymic epithelia AR enhances T-cell reconstitution and bone marrow transplant grafting efficacy. Mol. Endocrinol.2013; 27(1): 25-37.
  24. Schneider C.P., Schwacha M.G., Samy T.S., Bland K.I., Chaudry I.H. Androgen-mediated modulation of macrophage function after trauma-hemorrhage: central role of 5-alfa-dihydrotestosterone. J. Appl. Physiol. 20003; 95(1): 104-12.
  25. Chao T.C., Van Alten P.J., Walter R.J. Steroid sex hormones and macrophage function: modulation of reactive oxygen intermediates and nitrite release. Am. J. Reprod. Immunol. 1994; 32(1): 43-52.

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