Carbamazepine protects the endometrium against negative effects of estrogen in rats

ABSTRACT

Carbamazepine (CMZ) increases estrogen metabolism by inducing cytochrome P450 (CYP3A4). We investigated whether CMZ is protective against endometrial hyperplasia (EH). We used 32 female Wistar albino rats divided into four equal groups: the control group received drinking water, the estradiol valerate (EV) group was given EV, the CMZ group was given CMZ, and the EV + CMZ group was given both EV and CMZ. After 30 days the uteri of the rats were removed and serum estrogen and progesterone levels were measured, and endometrial tissue characteristics were evaluated. CYP3A4 expression was assessed using immunohistochemistry. Serum estrogen levels were lowest in the EV group and highest in the CMZ group. Serum progesterone levels were similar among all groups. Glandular density, a proxy measure of EH, was highest in the EV group and lowest in the EV + CMZ group. EH was detected in six of eight rats (75%) in the EV group and two of eight rats (25%) in the EV + CMZ group. Immunohistochemical staining revealed no significant difference in CYP3A4 expression among the four groups. CMZ reduced the negative effect of high dose estrogen that is not balanced by progesterone on the endometrium in rats. The effect likely is probably due to the CYP3A4 enzyme activator effect. CMZ may be protective against EH in high risk women, although confirmation is required.

KEYWORDS:

• Cancer
• carbamazepine
• endometrial hyperplasia
• endometrium
• estrogen
• rat

Acknowledgments

The authors thank Dr. Pınar Kırıcı, Dr. Yağmur Aydın, Dr. Gülnara Ödemiş, Veterinary Surgeon Elif Tosun and Staff Nurhan Tıraşcı for their help with rat care, drug applications and surgery. We also thank Professor Doctor Osman Haldun Develioğlu, who reviewed the article and provided guidance.

Disclosure statement

No potential conflict of interest was reported by the author.