Morphological Changes Induced by Exogenous Gestagens in Normal Human Endometrium

Abstract

The synthetic gestagens used clinically differ both chemically and metabolically from natural progesterone. Most are derivatives of 17α-hydroxy progesterone or 19-nor-testosterone. Although their gestogenic potencies vary considerably, most are more potent than natural progesterone. Norgestrel, which in its d-form is the most active gestogen known at present, is fifty times more active than progesterone.

The administration of progesterone alone during the proliferative phase depresses the maturation of Graafian follicles, arrests endometrial proliferation, and prevents ovulation. Even if given only for short periods, progesterone prolongs the menstrual cycle. When progesterone is discontinued a withdrawal bleeding occurs within a few days; when continued at low doses a breakthrough bleeding develops during therapy. If doses of 5–6mg are given daily for 4 weeks or longer, then the secretory change is abolished and the endometrium remains in a state of “arrested proliferation.” With treatment beyond 6 weeks the arrested proliferation gives way to progressive atrophy of the glands and decidualization of the stroma. After three months of therapy, amounting to a total dose of about 500 mg progesterone, a typical appearing decidualized stroma develops with extreme or complete atrophy of the glands: “arrested secretion.” If treatment is continued it may eventually lead to an irreversible atrophy with hyalinization of the stroma. The various synthetic gestagens differ both quantitatively and qualitatively in their action. The dosage required to produce a transformation of the endometrium varies from preparation to preparation. Moreover, some gestagens may affect mostly the stroma, others primarily the glands. Following therapy with derivatives of 19-nor-testosterone decidualization is more pronounced and the subsequent atrophy more extreme than with derivatives of progesterone. Since the glandular epithelial cells are more sensitive to progesterone and react to it earlier than the stromal cells do, the epithelium usually becomes refractory sooner to abnormal stimulation by gestogens, whereas the stroma begins to atrophy only after a prolonged decidualization.

Intrauterine contraceptive devices impregnated with progesterone promote focal decidualization sharply limited to the upper functionalis adjacent to the device. The striking histologic picture of a localized arrested secretion overlying a normally proliferating or secretory endometrium is characteristic.

In the endocervix gestagens induce adenomatous hyperplasia and reserve cell hyperplasia.