Long-term treatment with bromocriptine inhibits endometrial adenocarcinoma development in rats

The effects of long-term blockade of prolactin (PRL) action by bromocriptine (BRC) treatment on uterine carcinogenesis and on related ovarian physiology were investigated using a rat uterine cancer model. Ten-week-old cycling female Donryu rats, a high yield strain for uterine corpus tumors (endometrial adenocarcinomas), were treated with N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG), as a tumor initiator, and injected with 1 mg/kg body weight BRC subcutaneously 4 times per week until 14.5 months of age to block the proestrus PRL surge. The study was terminated at 15 months of age, and the results showed that long-term BRC treatment significantly inhibited endometrial adenocarcinoma development in terms of both incidence (34.6% to 13.0% with significant difference at 5%) and multiplicity (0.35 to 0.18 with significant difference at 5%), which indicates the number of adenocarcinomas per animals. While BRC did not affect estrous cyclicity in the treated animals, a significant decline was evident in the serum 17 beta-estradiol (E2) to progesterone (P) ratio (E: P ratio), and the serum E2 level showed a decreased tendency at 15 months of age. While the precise pathway to the inhibitory effect could not be determined; the pathway by which ovarian hormonal imbalance decreases the serum E: P ratio most likely plays a crucial role.