Hormonal pathology of the endometrium

The endometrial tissue is a sensitive target for steroid sex hormones and is able to modify its structural characteristics with promptness and versatility. This article discusses briefly endogenous hormonal effects (cyclic changes, luteal phase defect, unopposed estrogen effect) and describes the histologic patterns encountered in the most commonly used hormone therapies: oral contraceptives, ovulation stimulation, hormone replacement therapy, and antitumoral hormone therapy. Oral contraceptives exert a predominant progestational effect on the endometrium, inducing an arrest of glandular proliferation, pseudosecretion, and stromal edema followed by decidualized stroma with granulocytes and thin sinusoidal blood vessels. Prolonged use results in progressive endometrial atrophy. Ovulation induction therapy accelerates the maturation of the stroma and is often associated with a discrepancy between early secretory glands and an edematous or decidualized stroma with spiral arterioles. Hormone replacement therapy with estrogen alone may result in continuous endometrial proliferation, hyperplasia, and neoplasia. The use of both estrogen and progesterone elicits a wide range of histologic patterns, seen in various combinations: proliferative and secretory changes, often mixed in the same tissue sample; glandular hyperplasia (in polyps or diffuse) ranging from simple to complex atypical; stromal hyperplasia and/or decidual transformation; epithelial metaplasia (eosinophilic, ciliated, mucinous); and inactive and atrophic endometrium. Progesterone therapy for endometrial hyperplasia and neoplasia induces glandular secretory changes, decidual reaction, and spiral arterioles. Glandular proliferation is usually arrested, but neoplastic changes may persist and coexist with secretory changes. Lupron therapy produces a shrinking of uterine leiomyomas by accelerating their hyaline degeneration, similar to that in postmenopausal involution. It generally produces endometrial atrophy. Tamoxifen for breast carcinoma has an estrogen agonist effect on the uterus in approximately 20% of patients, who develop endometrial polyps, glandular hyperplasia, adenomyosis, and/or leiomyomata. Both endometrioid and nonendometrioid carcinomas are seen, often in polyps. Their causal relationship to tamoxifen therapy is debatable.