First clinical-morphological tendencies of the treatment ofpatients with myoma of womb with ulipristal acetate


Cite item

Abstract

The objective. To assess the effectiveness of the selective progesterone receptor modulator ulipristal (Esmya) in presurgicaltherapy of patients with uterine myoma.Patients and methods. The examination included 23 patients with uterine myoma aged 37 to 42 years, 13 patients with uterine myoma aged 21 to 41 years who received Esmya (5 mg/day for 3 months) as a presurgical treatment, 10 patients with uterine myoma aged 33 to 48 years - control group. Removed myoma nodules underwent complex histological examination that included immunohistochemical testing with the use of monoclonal antibodies to estrogen and progesterone receptors; Кi-67; phospho-histone; Вах; Bcl-2; cleaved caspase-3; VEGF.Results. After a 3-month Esmya therapy in 13 patients, the sizes of uterine myoma decreased to correspond to 2-3 wks of gestation, the sizes of the dominant nodule were reduced on the average by 3±0,4 cm in diameter, amenorrhea developed as soon as in the first cycle (complaints of profuse menstrual bleeding stopped). No undesirable effects were noted, the women pointed out to the convenient use of the drug. A morphological examination found large sites of dystrophic changes of leiomyocytes; low-active perivascular growth areas; pseudocapsule sclerosis, single mitotic figures, and marked apoptosis. Analysis of the results of immunohistochemical examination found the following results: phospho-histone and Ki-67 - in single cells; Bax - marked induction; cleaved caspase-3 - distinct expression; VEGF - weak-to-moderate expression; expression of progesterone - 78-87%.Conclusion. As has been demonstrated a decreasing of proliferation and hypertrophy of smooth muscle cells of uterine myoma, under the influence of Esmya; while the surrounding myometrium does not change. The mechanism of the regression effect of Esmya on uterine myoma has been confirmed as a selective tissue-specific «noneffective» receptor protein conformator, inhibiting transcription of progesterone in cells of uterine myoma.

About the authors

A L Tikhomirov

ГБОУ ВПО Московский государственный медико-стоматологический университет им. А.И.Евдокимова Минздрава России

д-р мед. наук, проф., проф. каф. акушерства и гинекологии лечебного фак-та

V V Kazenashev

ГБОУ ВПО Московский государственный медико-стоматологический университет им. А.И.Евдокимова Минздрава России

канд. мед. наук, ассистент каф. акушерства и гинекологии лечебного фак-та

O V Zayratyants

ГБОУ ВПО Московский государственный медико-стоматологический университет им. А.И.Евдокимова Минздрава России

д-р мед. наук, проф., зав. каф. патологической анатомии

I B Manukhin

ГБОУ ВПО Московский государственный медико-стоматологический университет им. А.И.Евдокимова Минздрава России

д-р мед. наук, проф., зав. каф. акушерства и гинекологии лечебного фак-та

References

  1. Тихомиров А.Л. Миома, патогенетическое обоснование органосохраняющего лечения. М., 2013.
  2. Morrison J, Mac Kenzie I.Z. Uterine fibroids. M.Rees, S.Hope, V.Ravnikar (eds). The Abnormal Menstrual Cycle. Abingdon: Taylor and Francis, 2005; p. 79-93.
  3. Dixon D, Parrott E.C, Segars J.H et al. The second National Institutes of Health International Congress on advances in uterine leiomyoma research: conference summary and future recommendations. Fertil Steril 2006; 86: 800-6.
  4. Levy B.S. Management of uterine fibroids. Acta Obstet Gynecol Scand 2008; 87 (8): 812-23.
  5. Somigliana E, Vercellini P, Daguati R et al. Fibroids and female reproduction: a critical analysis of the evidence. Hum Reprod Update 2007; 13: 465-76.
  6. Practice Committee of American Society for Reproductive Medicine in collaboration with Society of Reproductive Sur geons. Myomas and reproductive function. Fertil Steril 2008; 90 (Suppl. 5): S125-S130.
  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: 293-307.
  8. Attardi B.J, Burgenson J, Hild S.A, Reel J.R. In vitro antiprogestational/ antiglucocorticoid activity and progestin and glucocorticoid receptor binding of the putative metabolites and synthetic derivatives of CDB-2914, CDB-4124, and mifepristone. J Steroid Biochem Mol Biol 2004; 88: 277-88.
  9. Attardi B.J, Burgenson J, Hild S.A et al. CDB-4124 and its putative mon - odemethylated metabolite, CDB-4453, are potent antiprogestins with reduced antiglucocorticoid activity: in vitro comparison to mifepristone and CDB-2914. Mol Cell Endocrinol 2002; 188: 111-23.
  10. Gainer E.E, Ulmann A. Pharmacologic properties of CDB(VA)-2914. Steroids 2003; 68: 1005-11.
  11. Yoshida S, Ohara N, Xu Q et al. Celltype specific actions of progesterone receptor modulators in the regulation of uterine leiomyoma growth. Semin Reprod Med 2010; 28: 260-73.
  12. Chabbert-Buffet N et al. Effects of the progesteron receptor modulator VA2914 in continuous low dose on the hypothalamic - pituitary - ovarian axis and endometrium in normal women: a prospective, randomized, placebo - controlled trial. J Clin Endocrinol Metab 2007; 92 (9): 3582-9.
  13. Mutter G.L, Bergeron C, Deligdisch L et al. The spectrum of endometrial pathology induced by progesterone receptor modulators. Mod Pathol 2008; 21: 591-8.
  14. Spitz I.M. Clinical utility of progesterone receptor modulators and their effect on the endometrium. Curr Opin Obstet Gynecol 2009; 21: 318-24.
  15. Ioffe O.B, Zaino R.J, Mutter G.L. Endometrial changes from short - term therapy with CDB-4124, a selective progesterone receptor modulator. Mod Pathol 2009; 22: 450-9.
  16. Home F.M, Blithe D.L. Progesterone receptor modulators and the endometrium: changes and consequences. Hum Reprod Update 2007; 13: 567-80.
  17. Зайратьянц О.В. PAEC (Progesterone receptor modulator Associated Endometrial Changes). Изменения эндометрия, ассоциированные с модулятором РП. Новый вид обратимых морфологических изменений эндометрия при терапии лейомиом матки препаратом Эсмия® (улипристала ацетат, фармацевтическая компания «Гедеон Рихтер»). Руководство для врачей - патологоанатомов и акушеров - гинекологов.М.,2013.
  18. Williams А, Glant М. PRM-Associated Endometrial Changes (PAEC). ESMYA® (ulipristal acetate). Pathologist’s guide. Medical Information Service Preglem S.A. Geneva, Switzerland, 2012.
  19. Maruo T, Ohara N, Yoshida S et al. Translational research with progesterone receptor modulator motivated by the use of levonorgestrel - releasing intrauterine system. Contraception 2010; 82 (5): 435-41.
  20. Kinsel L.B, Szabo E, Greene G.L et al. Immunocytochemical analysis of estrogen receptors as a predictor of prognosis in breast cancer patients: comparison with quantitative biochemical methods. Cancer Res 1989; 49 (4): 1052-6.
  21. Jacques Donnez et al. Ulipristal Acetate versus Placebo for Fibroid Treatment before Surgery. N Engl J Med 2012; 366: 409-20.
  22. Jacques Donnez et al. Ulipristal acetate versus leuprolide acetate for uterine fibroids. N Engl J Med 2012; 366 (5): 421-32.
  23. Rabe T, Ahrendt H.J, Albring C, Bitzer J et al. Ulipristal Acetate for Symptomatic Uterine Fibroidsand 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 Reproduktionsmed Endokrinol 2013; 10 (Sonderheft 1): 82-101.
  24. Kurman R.J, Ellenson L.H, Ronnett B.M. Blaustein`s Pathology of the Female Genital Tract. 6th Edition, Springer, N.-Y. et al., 2011; p. 453-528.

Supplementary files

Supplementary Files
Action
1. JATS XML

Copyright (c) 2014 Consilium Medicum

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.

Согласие на обработку персональных данных

 

Используя сайт https://journals.rcsi.science, я (далее – «Пользователь» или «Субъект персональных данных») даю согласие на обработку персональных данных на этом сайте (текст Согласия) и на обработку персональных данных с помощью сервиса «Яндекс.Метрика» (текст Согласия).