NEW POSSIBILITIES FOR THE TREATMENT OF ENDOMETRIAL HYPERPLASIA WITH NATURAL MICRONIZED PROGESTERONE


Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract

Objective. To determine the efficiency of different cyclic micronized progesterone (MP) treatment regimens for simple endometrial hyperplasia (SHE) and the possible mechanisms of their therapeutic action. Subject and methods. Clinical and laboratory examinations were made in 64 patients (mean age 40.8±7.02 years; mean BMI 27.3±2.1) with SHE treated with 14- and 21-day MP 400 mg/day treatment regimens (Groups 1 and 2 consisted of 31 and 33 patients, respectively). Endometrial biopsy and morphological and immunohistochemical examinations were performed before and 6 months after hormone therapy. The expression of estrogen receptor-α (ERα) progesterone receptor (PgR), proliferation (Ki-67) and apoptosis (BIRC5) regulators was estimated. Endometrial tissue samples collected in the proliferation (n=8) and secretory (n = 7) phases were examined as a control. Results. In Groups 1 and 2, 6-month MP treatment regimen-induced SHE regression was 75 and 84.6%, respectively (p>0.05); secretory endometrial transformation was in 47.2 and 38.5% of cases, and a deciduous reaction was in 46.1 and 27.8%. Whatever its regimen, MP treatment caused a reduction in the expression of ER-α, PgR, the proliferation marker Ki-67, and the apoptosis inhibitor BIRC5. The changes in the above indicators were 2—4 times more marked during the deciduous reaction of the endometrium than during its secretory transformation. Conclusion. The 14- and 21-day MP 400 mg treatment regimens were comparable in their effectiveness in treating SHE. Considerably reduced expression of sex steroid hormones, decreased proliferative activity, and activated apoptosis are presumably regarded as the pathophysiological mechanisms of action of MP. There was an association with the magnitude of an endometrial response to hormone therapy (secretory transformation or deciduous reaction).

Full Text

Restricted Access

About the authors

G. E CHERNUKHA

Academician V.I. Kulakov Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia

Email: g_chernukha@oparina4.ru
Moscow

M. R DUMANOVSKAYA

Academician V.I. Kulakov Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia

Email: m_dumanovskaya@oparina4.ru
Moscow

E. A KOGAN

Academician V.I. Kulakov Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia

Email: e_kogan@oparina4.ru
Moscow

A. V ASATUROVA

Academician V.I. Kulakov Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia

Email: a_asaturova@oparina4.ru
Moscow

N. M FAIZULLINA

Academician V.I. Kulakov Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia

Email: n_faizullina@oparina4.ru
Moscow

References

  1. Jabbour H.N., Kelly R.W., Fraser H.M., Critchley H.O. Endocrine regulation of menstruation. Endocr. Rev. 2006; 27: 17—46.
  2. Mills A.M., Longacre T.A. Endometrial hyperplasia. Semin. Diagn. Pathol. 2010; 27(4): 199—214.
  3. Iram S., Musonda P., Ewies A.A. Premenopausal bleeding: When should the endometrium be investigated?—A retrospective non-comparative study of 3006 women. Eur. J. Obstet. Gynecol. Reprod. Biol. 2010; 148: 86—9.
  4. Armstrong A. J., Hurd W. W., Elguero S., Barker N. M., Zanotti K. M. Diagnosis and management of endometrial hyperplasia. J. Minim. Invasive Gynecol. 2012; 19(5): 562—71.
  5. Gallos I.D., Krishan P., Shehmar M., Ganesan R., Gupta J.K. LNG-IUS (Mirena(R)) versus oral progestogen treatment for endometrial hyperplasia: a long-term comparative cohort study. Hum. Reprod. 2013; 28(11): 2966—71.
  6. Ørbo A., Arnes M., Hancke C., Vereide A.B., Pettersen I., Larsen K. Treatment results of endometrial hyperplasia after prospective D-score classification: a follow-up study compar ing effect of LNG- IUD and oral progestins versus observation only. Gynecol. Oncol. 2008; 111(1): 68—73.
  7. Vereide A.B., Arnes M., Straume B., Maltau J.M., Ørbo A. Nuclear morphometric changes and therapy monitoring in patients with endometrial hyperplasia: a study comparing effects of intrauterine levonorgestrel and systemic medroxyprogesterone. Gynecol. Oncol. 2003; 91(3): 526—33.
  8. Sitruk-Ware R., Bricaire C., De Lignieres B., Yaneva H., Mauvais-Jarvis P. Oral micronized progesterone. Bioavailability pharmacokinetics, pharmacological and therapeutic implications — a review. Contraception. 1987; 36(4): 373—402.
  9. Agorastos T., Vaitsi V., Paschopoulos M., Vakiani A., Zournatzi-Koiou V., Saravelos H. et al. Prolonged use of gonadotropin-releasing hormone agonist and tibolone as add-back therapy for the treatment of endometrial hyperplasia. Maturitas. 2004; 48(2): 125—32.
  10. Agorastos T., Vaitsi V., Pantazis K., Efstathiadi E., Vavilis D., Bontis J.N. Aromatase inhibitor anastrozole for treating endometrial hyperplasia in obese postmenopausal women. Eur. J. Obstet. Gynecol. Reprod. Biol. 2005; 118(2): 239—40.
  11. Wentz W.B. Treatment of persistent endometrial hyperplasia with progestins. Am. J. Obstet. Gynecol. 1966; 96(7): 999— 1004.
  12. Guillebaud J. The levonorgestrel intrauterine system: a clinical perspective from the UK. Ann. N. Y. Acad. Sci. 2003; 997: 185—93.
  13. Magalhaes J., Aldrighi J.M., de Lima G.R. Uterine volume and menstrual patterns in users of the levonorgestrel-releasing intrauterine system with idiopathic menorrhagia or menorrhagia due to leiomyomas. Contraception. 2007; 75(3): 193—8.
  14. Gallos I.D., Shehmar M., Thangaratinam S., Papapostolou T.K., Coomarasamy A., Gupta J.K. Oral progestogens vs levonorg-estrel-releasing intrauterine system for endometrial hyperplasia: a systematic review and meta-analysis. Am. J. Obstet. Gynecol. 2010; 203: 547; e1—10.
  15. Signorelli M., Caspani G., Bonazzi C., Chiappa V., Perego P., Mangioni C. Fertility-sparing treatment in young women with endometrial cancer or atypical complex hyperplasia: a prospective single-institution experience of 21 cases. Br. J. Obstet. Gynaecol. 2009; 116: 114—8.
  16. Simon J.A. Secondary amenorrhea: Uses of progesterone for induction of bleeding. Supplement to OBG Management. February 2007: 6—8.
  17. De Lignieres B., Dennerstein L., Backstrom T. Influence of route of administration on progesterone metabolism. Maturitas. 1995; 21: 251—7.
  18. Nahoul K., Dehennin L., Jondet M., Roger M. Profiles of plasma estrogens, progesterone and their metabolites after oral or vaginal administration of estradiol or progesterone. Maturitas. 1993; 16: 185—202.
  19. Jarvela I.Y., Santala M. Treatment of nonatypic endometrial hyperplasia using thermal balloon endometrial ablation therapy. Gynecol. Obstet. Invest. 2005; 59: 202—6.
  20. Yener C., Okan E., Mutluay S., Sengun Y. Comparison of two therapies in simple endometrial hyperplasia: oral medroxyprogesterone acetate versus depot GNRH agonist. Jinekoloji. Obstet. Dergisi. 1997; 11: 143—6.
  21. Amalinei C., Cianga C., Balan R., Cianga P., Giusca S., Caruntu I. Immunohistochemical analysis of steroid receptors, proliferation markers, apoptosis related molecules, and gelatinases in non-neoplastic and neoplastic endometrium. Ann. Anat. 2011; 193(1): 43—55.
  22. Pieczynska B., Wojtylak S., Zawrocki A., Biernat W. Analysis of PTEN, estrogen receptor a and progesterone receptor expression in endometrial hyperplasia using tissue microarray. Pol. J. Pathol. 2011; 62(3): 133—8.
  23. Ørbo A., Arnes M., Pettersen I., Larsen K., Hanssen K., Moe B. Down-regulated progesterone receptor A and B coinciding with successful treatment of endometrial hyperplasia by the levonorgestrel impregnated intrauterine system. Acta Obstet. Gynecol. Scand. 2010; 89 (11): 1438—46.
  24. Vereide A.B., Kaino T., Sager G., Arnes M., Ørbo A. Effect of levonorgestrel IUD and oral medroxyprogesterone acetate on glandular and stromal progesterone receptors (PRA and PRB), and estrogen receptors (ER-a and ER-ß) in human endometrial hyperplasia. Gynecol. Oncol. 2006; 101: 214—23.
  25. Gallos I.D., Devey J., Ganesan R., Gupta J.K. Predictive ability of estrogen (ER), progesterone (PR), COX-2, Mlh1, and Bcl-2 expression for regression and relapse of endometrial hyperplasia treated with LNG-IUS: A prospective cohort study. Gynecol. Oncol. 2013; 130(1): 58—63.
  26. Risberg B., Karlsson K., Abeler V., Lagrelius A., Davidson B., Karlsson M.G. Dissociated expression of Bcl-2 and Ki-67 in endometrial lesions: diagnostic and histogenetic implications. Int. J. Gynecol. Pathol. 2002; 21(2): 155—60.
  27. Ambros R.A. Simple hyperplasia of the endometrium: an evaluation of proliferative activity by Ki-67 immunostaining. Int. J. Gynecol. Pathol. 2000; 19 (3): 206—11.
  28. Uchikawa J., Shiozawa T., Shih H.C., Miyamoto T., Feng Y.Z., Kashima H. et al. Expression of steroid receptor coactivators and corepressors in human endometrial hyperplasia and carcinoma with relevance to steroid receptors and Ki-67 expression. Cancer. 2003; 98(10): 2207—13.
  29. Scully R.E. The need for uniform terminology. Hum. Pathol. 1973; 4: 602—3.
  30. Fox H., Langley F.A. Tumours of the ovary. London: William Heinemann Medical Books Limited; 1976.
  31. Sivridis E., Giatromanolaki A. The endometrial hyperplasias revisited. Virchows Arch. 2008; 453(3): 223—31.

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies