Evaluation of endometrial steroid receptors and cell mitotic activity in women using copper intrauterine device: Can Cu-T prevent endometrial cancer?

Aims: To study changes in endometrial proliferative indices (i.e. cell mitosis and Ki67), endometrial steroid (estrogen and progesterone) receptors, and serum estradiol and progesterone level in women using copper intrauterine device (IUD) after 6 months of use. Methods: Fifteen healthy women were recruited having no contra indication to IUD or endometrial biopsy. Endometrial biopsies and serum samples were taken on 10/11th day of menstrual cycle at recruitment and after six months. The endometrial samples were subjected to: (i) steroid receptor estimation by immunohistochemistry; (ii) cell mitosis and Ki67 estimation by morphology and proliferative indices. Results: The mean glandular mitotic index was 1.69 +/- (0.39) at first visit and 0.35 +/- (0.15) at second visit after 6 months. Similarly, Ki-67 count in glands was 11.79 +/- (1.59) at first visit and 2.40 +/- (0.54) at second visit. In the stroma, Ki67 decreased from a mean of 0.85 to 0.01 in six months. This suggested statistically significant reduction in proliferation and mitotic activity in endometrial glands and the stroma of women who used Cu-T continuously for a long period.There was a significant reduction of estrogen receptor concentration in glands (from a mean of 51.67 down to 11.67) and the stroma (from a mean of 33.00 to 8.00) over this 6-month period. The observed fall in progesterone receptor counts was less compared to other parameters studied, being marginally significant in stroma (from a mean of 32.00 down to 14.33), but not significant enough in glands (from a mean of 45.00 down to 25.00). No changes were observed in serum hormone levels in these two visits. Conclusion: Continuous use of copper intrauterine device causes significant reduction in endometrial mitotic activity as well as estrogen receptor concentration without affecting serum estradiol or progesterone levels. This finding infers that Cu-T may have a protective role against endometrial cancer.