Morphological characteristics of myoma and endometrial tissue in patients with uterine leiomyoma after treatment with ulipristal acetate

Елена Георгиевна Курик, О. О. Литвак, Б. В. Хабрат, Б. М. Лисенко

Abstract


Uterine leiomyoma is a hormone-dependent tumor of the myometrium, one of the most common benign tumors of the female genital organs. For conservative treatment of uterine leiomyoma different progesterone receptor blockers are used. One such drug is ulipristal acetate, a selective modulator of progesterone receptors, which suppress fibroid growth and may lead to its regression.

The aim a selective modulator of progesterone receptors, which suppress fibroid growth and may lead to its regression. The aim of research was to conduct morphological study of myoma and endometrial tissue in patients with uterine leiomyoma after treatment with ulipristal acetate. Histological and immunohistochemical study of leiomyoma and endometrium in 9 patients after three months of ulipristal acetate treatment 5 mg per day (the main group) and 15 patients without hormone therapy (control group) was conducted.

In patients treated with ulipristal acetate in smooth muscle cells of uterine noted a significant decrease of progesterone receptor expression, markers of apoptosis inhibitor Bcl-2 and proliferative activity Ki-67. Thus, in uterine smooth muscle cells under influence ulipristal acetate is a reduction amount of the progesterone receptor, i.e. decreases its action, resulting in the induction of apoptosis and reduced proliferation processes, whereby the uterine involution occurs. In the endometrium under the influence of ulipristal acetate develop reversible changes associated with the use of progesterone receptor modulators. In the study of proliferative activity marker Ki-67 in endometrium in patients receiving ulipristal acetate, we found its expression is very low compared with the group of patients without hormonal treatment of uterine leiomyoma.

The changes in the endometrium under the action of ulipristal acetate must be differentiated from the estrogen-induced changes and endometrial hyperplasias, so the direction of the pathological examination must be necessary indicate that a patient received ulipristal acetate therapy.

In the future, it is necessary to continue to study morphological changes, such as immunohistochemical characteristics of myoma and endometrial tissue in patients after treatment with ulipristal acetate.


Keywords


uterus leiomyoma; ulipristal acetate; progesterone receptors; proliferative activity; apoptosis; endometrium changes

References


Adamyan, L.V., Zairatyants, A.V., Tikhomirov, A.L., et al. “Antiproliferative and proapoptosis action of the selective progesterone receptor modulator ulipristal on uterus leiomyoma in vivo.” Reproduction Problems, 3(2014): 25–28.

Potapov, V.O., Donska, Y.V., Medvedev M.V. “Histological and immunohistochemical assessment of myoma and endometrial tissue in patients with uterus leiomyoma and endometrial hyperplasia.” Morphology, 1(8) (2014): 80–84.

Radzinsky, V.E., Topchiev, G.F. Uterine fibroids: a course on organ saving. Information bulletin. Moscow. The editorial board of the Status Praesens Journal (2014): 24 p.

Tikhomirov, A.L., Zairatyants, V.O. “Clinic and morphological characteristics of uterine fibroids after use of the selective progesterone receptor modulator ulipristal.” Questions of Gynecology, Obstetrics and Perinatology, 1 (Vol. 13) (2014): 67–72.

Tikhomirov, A.L., Kazenashev, V.V., Zairatyants, V.O., Manukhin, I.B. “The first clinical and morphological results of treatment of patients with uterine myoma with ulipristal acetate.” Gynecology, 2(2014): 29–33.

Berger, C., Boggavarapu, N.R., Menezes, J., et al. “Effects of ulipristal acetate on human embryo attachment and endometrial cell gene expression in an in vitro co-culture system.” Hum Reprod, 4 (Vol. 30) (2015): 800–811. DOI: 10.1093/humrep/dev030

Courtoy, G.E., Donnez, J., Marbaix, E., Dolmans, M.M. “In vivo mechanisms of uterine mioma volume reduction with ulipristal acetate treanment.” Fertil Steril, 2 (Vol. 104) (2015): 426–434. DOI: 10.1016/j.fertnstert.2015.04.025

Donnez, J., Vázquez, F., Tomaszewski, J., et al. “PEARL II and PEARL III Extension Study Group Longterm treatment of uterine fibroids with ulipristal acetate.” Fertil Steril, 6 (Vol. 101) (2014): 1565–1573. DOI:10.1016/j.fertnstert.2014.02.008

Engman, M., Granberg, S., Williams, A.R.W., et al. “Mifepristone for treatment of uterine leiomyoma. A prospective randomized placebo controlled trial.” Hum Reprod, 8 (Vol. 24) (2009): 1870–1879.

Fiscella, J., Bonfiglio, T., Winters, P., et al. “Distinguishing features of endometrial pathology after exposure to the progesterone receptor modulator mifepristone.” Hum Pathol, 42(2011): 947–953.

Ноrnе, F.M., Blithe, D.L. “Progesterone receptor modulators and the endometrium: changes and consequences.” Hum Reprod Update, 13(2007): 567–580.

Melis, G.B., Piras, B., Marotto, M.F., et al. “Pharmacokinetic evaluation of ulipristal acetate for uterine leiomyoma treatment.” Expert Opin Drug Metab Toxicol, 8(2012): 901–908.

Murdoch, М., Roberts, M. “Selective progesterone receptor modulators and their use within gynaecology.” Obstet Gynaecol, 1 (Vol. 16) (2014): 46–50. DOI: 10.1111/tog.12072

Mutter, G.L., Bergeron, С., Deligdisch, L., et al. “The spectrum of endometrial pathology induced bу progesterone receptor modulators.” Mod Pathol, 21(2008): 591–598.

Nisolle, M., Gillerot, S., Casanas-Roux, F., et al. “Immunohistochemical study of the proliferation index, oestrogen receptors and progesterone receptors A and B in leiomyomata and normal myometrium during the menstrual cycle and under gonadotrophin-releasing hormone agonist therapy.” Hum Reprod, 11 (Vol. 14) (1999): 2844–2850.

Talaulikar, V.S., Manyonda, I.T. “Progesterone and progesterone receptor modulators in the management of symptomatic uterine fibroids.” Eur J Obstet Gynecol Reprod Biol, 2 (Vol. 165) (2012): 135–140. DOI: 10.1016/j.ejogrb.2012.07.023

Talaulikar, V.S., Manyonda, I.T. “Ulipristal acetate: a novel option for the medical management of symptomatic uterine fibroids.” Adv Ther, 8 (Vol. 29) (2012): 655–663. DOI: 10.1007/s12325-012-0042-8

Williams, A.R.W., Bergeron, C., Barlow, D.H., Ferenczy, A. “Endometrial morphology after treatment of uterine fibroids with the selective progesterone receptor modulator, Ulipristal Acetate.” Int J Gynecol Pathol, 6 (Vol. 31) (2012): 556–569.

Yoshida, S., Ohara, N., Xu, Q., et al. “Cell-type specific actions of progesterone receptor modulators in the regulation of uterine leiomyoma growth.” Semin Reprod Med, 28(2010): 260–273. DOI: 10.1055/s-0030-1251483


GOST Style Citations


1. Адамян, Л.В. Антипролиферативное и проапоптотическое действие селективного модулятора рецепторов прогестерона улипристала на лейомиому матки in vivo / Л.В. Адамян, О.В. Зайратьянц, А.Л. Тихомиров и др. // Проблемы репродукции. — 2014. — № 3. — С. 25–28.

2. Потапов, В.О. Гістологічна та імуногістохімічна оцінка стану міоматозної тканини та ендометрія у хворих на лейоміому матки та гіперплазію ендометрія / В.О. Потапов, Ю.В. Донська, М.В. Медвєдєв // Морфологія. — 2014. — № 1 (8). — C. 80–84.

3. Радзинский, В.Е. Миома матки: курс на органосохранение. Информационный бюлетень / В.Е. Радзинский, Г.Ф. Топчиев // М.: Редакция журнала Status Praesens. — 2014. — 24 с.

4. Тихомиров, А.Л. Клинико-морфологическая характеристика миомы матки после применения селективного модулятора рецепторов прогестерона улипристала / А.Л. Тихомиров, В.О. Зайратьянц // Вопросы гинекологии, акушерства и перинатологии. — 2014. — Т. 13, № 1. — С. 67–72 .

5. Тихомиров, А.Л. Первые клинико-морфологические результаты лечения больных миомой матки с использованием улипристала ацетата / А.Л. Тихомиров, В.В. Казенашев, В.О. Зайратьянц, И.Б. Манухин // Гинекология. — 2014. — № 2. — С. 29–33.

6. Berger, C., Boggavarapu, N.R., Menezes, J., et al. “Effects of ulipristal acetate on human embryo attachment and endometrial cell gene expression in an in vitro co-culture system.” Hum Reprod, 4 (Vol. 30) (2015): 800–811. DOI: 10.1093/humrep/dev030

7. Courtoy, G.E., Donnez, J., Marbaix, E., Dolmans, M.M. “In vivo mechanisms of uterine mioma volume reduction with ulipristal acetate treanment.” Fertil Steril, 2 (Vol. 104) (2015): 426–434. DOI: 10.1016/j.fertnstert.2015.04.025

8. Donnez, J., Vázquez, F., Tomaszewski, J., et al. “PEARL II and PEARL III Extension Study Group Longterm treatment of uterine fibroids with ulipristal acetate.” Fertil Steril, 6 (Vol. 101) (2014): 1565–1573. DOI:10.1016/j.fertnstert.2014.02.008

9. Engman, M., Granberg, S., Williams, A.R.W., et al. “Mifepristone for treatment of uterine leiomyoma. A prospective randomized placebo controlled trial.” Hum Reprod, 8 (Vol. 24) (2009): 1870–1879.

10. Fiscella, J., Bonfiglio, T., Winters, P., et al. “Distinguishing features of endometrial pathology after exposure to the progesterone receptor modulator mifepristone.” Hum Pathol, 42(2011): 947–953.

11. Ноrnе, F.M., Blithe, D.L. “Progesterone receptor modulators and the endometrium: changes and consequences.” Hum Reprod Update, 13(2007): 567–580.

12. Melis, G.B., Piras, B., Marotto, M.F., et al. “Pharmacokinetic evaluation of ulipristal acetate for uterine leiomyoma treatment.” Expert Opin Drug Metab Toxicol, 8(2012): 901–908.

13. Murdoch, М., Roberts, M. “Selective progesterone receptor modulators and their use within gynaecology.” Obstet Gynaecol, 1 (Vol. 16) (2014): 46–50. DOI: 10.1111/tog.12072

14. Mutter, G.L., Bergeron, С., Deligdisch, L., et al. “The spectrum of endometrial pathology induced bу progesterone receptor modulators.” Mod Pathol, 21(2008): 591–598.

15. Nisolle, M., Gillerot, S., Casanas-Roux, F., et al. “Immunohistochemical study of the proliferation index, oestrogen receptors and progesterone receptors A and B in leiomyomata and normal myometrium during the menstrual cycle and under gonadotrophin-releasing hormone agonist therapy.” Hum Reprod, 11 (Vol. 14) (1999): 2844–2850.

16. Talaulikar, V.S., Manyonda, I.T. “Progesterone and progesterone receptor modulators in the management of symptomatic uterine fibroids.” Eur J Obstet Gynecol Reprod Biol, 2 (Vol. 165) (2012): 135–140. DOI: 10.1016/j.ejogrb.2012.07.023

17. Talaulikar, V.S., Manyonda, I.T. “Ulipristal acetate: a novel option for the medical management of symptomatic uterine fibroids.” Adv Ther, 8 (Vol. 29) (2012): 655–663. DOI: 10.1007/s12325-012-0042-8

18. Williams, A.R.W., Bergeron, C., Barlow, D.H., Ferenczy, A. “Endometrial morphology after treatment of uterine fibroids with the selective progesterone receptor modulator, Ulipristal Acetate.” Int J Gynecol Pathol, 6 (Vol. 31) (2012): 556–569.

19. Yoshida, S., Ohara, N., Xu, Q., et al. “Cell-type specific actions of progesterone receptor modulators in the regulation of uterine leiomyoma growth.” Semin Reprod Med, 28(2010): 260–273. DOI: 10.1055/s-0030-1251483





DOI: http://dx.doi.org/10.18370/2309-4117.2015.26.36-40

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