The anorectic agent, lorcaserin, disturbs estrous cyclicity and produces endometrial hyperplasia without affecting ovarian population in female rats

Life Sci. 2017 Aug 15:183:69-77. doi: 10.1016/j.lfs.2017.06.006. Epub 2017 Jun 6.

Abstract

Aims: The present study aims to investigate the effect of the new anorectic agent, lorcaserin, on estrous cyclicity, reproductive hormones and folliculogenesis in female mature rats.

Materials and methods: Rats were divided into four groups; Group i: control group. Group ii-iv: rats treated with lorcaserin (5, 10 or 30mg/kg/day, p.o.), respectively. The treatment continued for 28days.

Key findings: Lorcaserin (5 or 10mg/kg) caused estrous cycle disturbance in 40% of treated rats while the high dose (30mg/kg) produced disturbances in 100% of the treated rats. Lorcaserin (5-30mg/kg) altered some of female hormones where it enhanced estradiol but reduced luteinizing hormone. Minimal edema with congested vessels was observed in the medulla of ovarian sections. Further, epithelial and uterine sections showed hyperplasia.

Significance: Taken together, the present results demonstrated that lorcaserin affected some reproductive hormones, disturbed estrous cyclicity and induced histopathological changes in the ovaries and uteri without affecting the ovarian populations. Therefore, lorcaserin should be used with caution in women of child bearing potential until adequate clinical safety data are available.

Keywords: Estrous cyclicity; Female reproductive hormones; Lorcaserin; Ovaries; Rat; Uterus.

MeSH terms

  • Animals
  • Appetite Depressants / administration & dosage
  • Appetite Depressants / pharmacology*
  • Benzazepines / administration & dosage
  • Benzazepines / pharmacology*
  • Dose-Response Relationship, Drug
  • Endometrial Hyperplasia / chemically induced*
  • Estradiol / metabolism
  • Estrous Cycle / drug effects*
  • Female
  • Luteinizing Hormone / metabolism
  • Ovarian Follicle / drug effects
  • Ovary / drug effects*
  • Ovary / pathology
  • Rats
  • Rats, Wistar
  • Uterus / drug effects
  • Uterus / pathology

Substances

  • Appetite Depressants
  • Benzazepines
  • Estradiol
  • lorcaserin
  • Luteinizing Hormone