Additional effects of medroxyprogesterone acetate on mammary tumors in oophorectomized, estrogenized, DMBA-treated rats

Anticancer Res. Nov-Dec 1997;17(6D):4583-7.

Abstract

Although hormone replacement therapy not only relieves vasomotor symptoms but also reduces cardiovascular disease and osteoporosis, long-term estrogen therapy increases the risk of endometrial and/or mammary cancer. We investigated the effects of conjugated estrogens with or without medroxyprogesterone acetate in oophorectomized, 7,12-dimethylbenz(a)anthracene-treated rats. Chemically induced mammary carcinogenesis was completely suppressed by the simultaneous oophorectomy, but conjugated estrogens replacement with or without medroxyprogesterone acetate markedly stimulated mammary carcinogenesis in the ovariectomized rats. The chronic administration of conjugated estrogens and medroxyprogesterone acetate markedly reduced the activities of thymidylate synthetase and thymidine kinase and bromodeoxyuridine-immunoreactive (S-phase) cells in mammary tumors. These results indicate that the treatment using conjugated estrogens with or without medroxyprogesterone acetate may promote the mammary carcinogenesis in postmenopausal women but the chronic administration of medroxyprogesterone acetate may alter the development of established mammary cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 9,10-Dimethyl-1,2-benzanthracene
  • Animals
  • Bone Density / drug effects
  • Bone Density / physiology
  • Estradiol / blood*
  • Estrogen Replacement Therapy
  • Female
  • Humans
  • Mammary Neoplasms, Experimental / blood
  • Mammary Neoplasms, Experimental / chemically induced
  • Mammary Neoplasms, Experimental / enzymology
  • Mammary Neoplasms, Experimental / pathology*
  • Medroxyprogesterone Acetate / pharmacology*
  • Ovariectomy*
  • Postmenopause
  • Progesterone / blood*
  • Prolactin / blood
  • Rats
  • Rats, Sprague-Dawley
  • Thymidine Kinase / metabolism
  • Thymidylate Synthase / metabolism

Substances

  • Progesterone
  • Estradiol
  • 9,10-Dimethyl-1,2-benzanthracene
  • Prolactin
  • Medroxyprogesterone Acetate
  • Thymidylate Synthase
  • Thymidine Kinase