A review of the endometrial changes in Norplant users.

Abstract

Prolonged exposure to levonorgestrel associated with use of Norplant contraceptive implants leads, in many acceptors, to menstrual irregularities. Endometrial biopsies collected from a group of Norplant acceptors with persistent or prolonged breakthrough bleeding indicated this side effect is associated with proliferative-type endometrium. The number of both proliferative and secretory endometrium was markedly reduced. The stroma showed edema, sloughing, and inflammatory infiltration. Despite chronic levonorgestrel exposure, only 31% of stroma showed poorly developed decidualization. There was no association between endometrial findings and levonorgestrel levels. Hysteroscopy revealed markedly engorged superficial vessels in long-term Norplant users. It is hypothesized that progestin-related bleeding abnormalities may be due to the changes in the vascular system (e.g., damaged vessels) and hemostatic factors. Confirmation of this hypothesis requires detection of the presence of hemostatic plugs in patients with and without abnormal bleeding, study of the perivascular expression of tissue factor, measurement of estrogen and progesterone receptors at bleeding and non-bleeding sites, and identification of factors that increase angiogenesis and the fragility of uterine vessels.