Oxidative stress, vitamin E and progestin breakthrough bleeding.

Endometrial bleeding problems can be the major reason for discontinuing progestin-only contraception. In this study the endometrial angiogenic response in Norplant users was found to be lower than in women with normal menstrual cycles. These disturbances in angiogenic response may be caused by oxidant-antioxidant imbalance in the endometrium. The aims of this study were to investigate the effect of progestin only contraceptives on blood concentrations of lipid peroxide and vitamin E, and the effect of vitamin E supplementation on endometrial angiogenic response in vitro. The subjects for this study were Norplant users, depo-medroxyprogesterone acetate (DMPA) users, and controls. Circulating lipid peroxide and vitamin E concentration was measured by routine methodology. Endometrial angiogenic response was assayed using an endothelial cell migration assay. The results showed that the blood concentrations of lipid peroxide from Norplant users with bleeding problems were significantly higher than normal menstrual controls (P < 0.05) and supplementation of vitamin E (in vitro) increased the endometrial angiogenic score. Blood concentrations of lipid peroxide were significantly increased (P < 0.05), and the blood concentrations of vitamin E were significantly decreased (P < 0.05) after 3 months exposure to Norplant or DMPA. The endometrial angiogenic scores in Norplant and DMPA users were significantly lower than in controls (P < 0.02). It is concluded that in progestin-only contraceptive users, higher lipid peroxide and lower vitamin E concentration may cause endometrial cell damage and decrease the endometrial angiogenic response. It is suggested that vitamin E supplementation may counteract these unwanted side-effects.