MONTREAL — Contrary to its effect with other progesterone-only contraceptives, mifepristone increases breakthrough bleeding in patients using the levonorgestrel intrauterine system, according to a new study.
“Mifespristone cannot be recommended as a therapy for breakthrough bleeding in new users of the LNG-IUS [levonorgestrel intrauterine system],” reported Dr. Megan Econimidis of the Keck School of Medicine at the University of Southern California in Los Angeles.
Mifepristone, an antiprogesterone, has been shown to decrease irregular bleeding in users of progesterone-only implants and injectables. It has been suggested that this effect may be due to mifepristone's functional inhibition of progesterone, which leads to the upregulation of endometrial estrogen receptors, she said at the joint annual meeting of the American Society for Reproductive Medicine and the Canadian Fertility and Andrology Society.
But Dr. Econimidis' study found that, when given to 20 regularly menstruating women who were new starters of the LNG-IUS, mifepristone actually had the opposite effect. “The local effect of the levonorgestrel on the endometrium may be triggering bleeding … [and] may not be allowing the mifepristone to act on the endometrium,” she said in an interview. “In women who are on a progesterone-only implant or injectable, that mechanism, in terms of concentration of levonorgestrel on the endometrium, is less.”
The women in the study, 18-45 years old, were randomized to mifepristone 50 mg or placebo every 2 weeks for six cycles. Treatment was started 2 weeks after LNG-IUS insertion. Subjects recorded their bleeding events in a diary and returned to the clinic for 14 visits during the study period. Endometrial biopsies were taken on day 21 of the menstrual cycle before LNG-IUS insertion, 14 days after insertion, and 7 days after the first dose of mifepristone or placebo.
Over the six cycles, the median number of days of breakthrough bleeding was 57 in the mifepristone group, compared with 26 in the placebo group; this difference was statistically significant. In addition, when all the subjects' cycles were combined, there were 22 (42%) mifepristone cycles with more than 8 days of breakthrough bleeding, compared with 16 (27%) placebo cycles. This difference was not statistically significant.
Endometrial biopsy results showed a decrease in endometrial estrogen receptors after mifepristone treatment, in contrast to other studies of progesterone implants and injectables, which have shown an increase in estrogen receptors after mifepristone, she said.