title: Evaluation of adverse effects in tamoxifen exposed healthy female dogs.
abstract: BACKGROUND
  Mammary tumors are among the most frequent neoplasms in female dogs, but the strategies employed in animal treatment are limited. In human medicine, hormone manipulation is used in cancer therapy. Tamoxifen citrate is a selective inhibitor of oestrogen receptors and exerts a potent anti-oestrogen effect on the mammary gland. The aim of this study was to evaluate the adverse effects when exposing healthy female dogs to tamoxifen.
  
  
  METHODS
  Tamoxifen was administered for 120 days at a dose of 0.5 or 0.8 mg/kg/day to either intact or spayed female dogs. The effects were assessed through clinical examination, haematology, serum biochemistry, ophthalmology and bone marrow aspirate examination. Ovariohysterectomy was performed and the uterus examined by histopathology.
  
  
  RESULTS
  Vulva oedema and purulent vaginal discharge developed with 10 days of tamoxifen exposure in all groups. Pyometra was diagnosed after around 90 days of exposure in intact females with frequencies increasing during the following 30 days of exposure. Up to 50% of dogs within the groups developed retinitis but none of the dogs had signs of reduced visual acuity. The prevalence of retinitis in each group was similar after 120 days of exposure. Haematological, biochemical and bone marrow changes were not observed. Due to the high risk of developing pyometra after prolonged exposure to tamoxifen, only spayed animals should be given this medication.
  
  
  CONCLUSIONS
  A dose of 0.8 mg tamoxifen/kg body weight/day is recommended when treating tamoxifen-responsive canine mammary tumors. Due to the high risk of developing pyometra, ovariohysterectomy is recommended.
authors.affiliation: Department of General Pathology, Institute of Biological Sciences, Federal University of Minas Gerais, Brazil.
authors.forename: Wanessa L F
authors.initials: WL
authors.lastname: Tavares
authors.forename: Gleidice E
authors.initials: GE
authors.lastname: Lavalle
authors.forename: Mariana S
authors.initials: MS
authors.lastname: Figueiredo
authors.forename: Aline G
authors.initials: AG
authors.lastname: Souza
authors.forename: Angelica C
authors.initials: AC
authors.lastname: Bertagnolli
authors.forename: Fernando A B
authors.initials: FA
authors.lastname: Viana
authors.forename: Paulo R O
authors.initials: PR
authors.lastname: Paes
authors.forename: Rubens A
authors.initials: RA
authors.lastname: Carneiro
authors.forename: Guilherme A O
authors.initials: GA
authors.lastname: Cavalcanti
authors.forename: Marilia M
authors.initials: MM
authors.lastname: Melo
authors.forename: Geovanni D
authors.initials: GD
authors.lastname: Cassali
mesh_terms: D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000009:adverse effects*; D004283:Dog Diseases / Q000139:chemically induced*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000139:chemically induced / Q000662:veterinary; D005260:Female; D007044:Hysterectomy / Q000662:veterinary; D055112:Pyometra / Q000139:chemically induced / Q000662:veterinary; D012173:Retinitis / Q000139:chemically induced / Q000662:veterinary; D013629:Tamoxifen / Q000008:administration & dosage / Q000009:adverse effects*; D014845:Vulvar Diseases / Q000139:chemically induced / Q000662:veterinary
chemical_list: D018931:Antineoplastic Agents, Hormonal; D013629:Tamoxifen