Hormonal regulation of endometriosis and clinical significance

ABSTRACT

Worldwide almost 10% of reproductive-aged women are affected by endometriosis and suffer from dysmenorrhea, dyspareunia, chronic pelvic pain, and infertility. Endometriosis is a gynecological condition in which endometrial cells are deposited outside the uterine cavity and eventually develop into functional endometrial glands and stroma. It is an estrogen-dependent disease and is critically modulated by other hormones of the reproductive system. Estrogen promotes the cell survival and pro-inflammatory roles for both endometrial epithelial and stromal cells. Overexpression of ER-β promotes invasion of endometriotic lesions as well as epithelial-mesenchymal transition. Moreover, estrogen stimulates the production of prostaglandin E2 (PGE2), which supports angiogenesis in the ectopic lesions. Progesterone counteracts estrogen and inhibits the growth of the endometrial glandular cells. Progesterone resistant endometrial cells confer apoptotic-resistance and aggravate disease condition. Oxytocin stimulates the contraction of uterine muscles by upregulating PGF2α secretion via calcium-mediated pathways leading to dysmenorrhea in endometriosis. On the contrary, gonadotropin and its receptor produce amenorrhea by inducing mitochondrial apoptosis and reducing angiogenesis. Scientists are now exploring these hormone-dependent pathologies of endometriosis to develop anti-endometriotic drugs, which mostly include androgen-based drugs and/or potential estrogen inhibitors. This review highlights the role of some important hormones e.g. estrogen, progesterone, prostaglandin, oxytocin, gonadotropin and melatonin in endometriosis progression and their pharmaceutical potentials.