Expression of sex steroid receptors and Ki-67 in the endometria of menorrhagic women: effects of intrauterine levonorgestrel

The levonorgestrel-releasing intrauterine system (LNG-IUS) has proven to be the most effective medical treatment in reducing the amount of menstrual b lood loss. However, the molecular mechanisms underlying menorrhagia and/or accounting for the therapeutic effect of the LNG-IUS are still obscure. In this study, we used immunohistochemistry to compare the distribution of sex steroid receptors and the proliferation marker Ki-67 in the endometria of women with and without menorrhagia before and after 6 and 12 months of trea tment with an LNG-IUS. The study sample included 67 women (aged 35-49 years ) who had spontaneous ovulatory cycles. In women with menorrhagia, secretor y phase endometrium exhibited more proliferative activity than in women wit hout menorrhagia. Mo significant differences were found in the immunoreacti vity of the oestrogen or progesterone receptors in women either with or wit hout menorrhagia suggesting that, in addition to endocrine hormones, other factors are involved in the regulation of endometrial proliferation and men strual blood loss. A total of 35 women were treated with LNG-IUS. After 6 m onths use of an LNG-IUS, the immunoreactivity of both epithelial and stroma l progesterone receptors, as well as those of epithelial Ki-67 declined, an d no differences were detectable between the women in the menorrhagia and c ontrol groups. Breakthrough bleeding remained a problem for nine; (26%) LNG -IUS users, with no association with the pre-treatment amount of bleeding. No significant differences were found in the parameters studied between the women with and without breakthrough bleeding 6 months after insertion of a n LNG-IUS.