Therapeutic options for management of endometrial hyperplasia

Abstract

Endometrial hyperplasia (EH) comprises a spectrum of changes in the endometrium ranging from a slightly disordered pattern that exaggerates the alterations seen in the late proliferative phase of the menstrual cycle to irregular, hyperchromatic lesions that are similar to endometrioid adenocarcinoma. Generally, EH is caused by continuous exposure of estrogen unopposed by progesterone, polycystic ovary syndrome, tamoxifen, or hormone replacement therapy. Since it can progress, or often occur coincidentally with endometrial carcinoma, EH is of clinical importance, and the reversion of hyperplasia to normal endometrium represents the key conservative treatment for prevention of the development of adenocarcinoma. Presently, cyclic progestin or hysterectomy constitutes the major treatment option for EH without or with atypia, respectively. However, clinical trials of hormonal therapies and definitive standard treatments remain to be established for the management of EH. Moreover, therapeutic options for EH patients who wish to preserve fertility are challenging and require nonsurgical management. Therefore, future studies should focus on evaluation of new treatment strategies and novel compounds that could simultaneously target pathways involved in the pathogenesis of estradiol-induced EH. Novel therapeutic agents precisely targeting the inhibition of estrogen receptor, growth factor receptors, and signal transduction pathways are likely to constitute an optimal approach for treatment of EH.

Keywords: Endometrial Hyperplasia; Progestins; Receptors, Estrogen; Therapy.

Fig. 1

Overview of endometrial hyperplasia, risk factors, classification and treatment options. (A) The cross-sectional view of uterus showing endometrium. (B) H&E staining of endometrium at proliferative and secretory phase of endometrium. Adapted from Horne et al. [3], with permission from Oxford University Press. (C) Risk factors associated with endometrial hyperplasia. (D) The cross-sectional view of uterus showing proliferative endometrium and the H&E staining of endometrium hyperplasia showing abnormal increase of endometrial glands. (E) H&E stained section of endometrial: (a) proliferative endometrium; (b) simple hyperplasia; (c) complex hyperplasia; and (d) complex atypical hyperplasia. Adapted from Palmer et al. [15], with permission from John Wiley and Sons. (F) Different therapeutic options of endometrial hyperplasia. MPA, medroxy-progesterone acetate.

Fig. 2

The investigations and management schemes for endometrial hyperplasia. CCHRT, continuous-combined hormone replacement therapy.