Colorectal tumor prevention by the progestin medroxyprogesterone acetate is critically dependent on postmenopausal status

Bartolomeus J. Meijer, Mattheus C.B. Wielenga, Patricia B. Hoyer, James M. Amos-Landgraf, Theodorus B.M. Hakvoort, Vanesa Muncan, Jarom Heijmans, Gijs R. van den Brink

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

The large randomized placebo controlled trials of the Women's Health Initiative have shown that the combination of estrogen and progestin medroxyprogesterone acetate (MPA) protects from colorectal cancer in postmenopausal women. No effect was observed in women treated with estrogen alone. This suggests that progesterone, or more specifically the progestin MPA may have chemopreventive activity. The effect of MPA on colorectal carcinogenesis has been difficult to study in animal models. Most models are not affected by either depleting female hormones by ovariectomy or treatment with MPA. Importantly, an ovariectomy fails to reproduce one of the hall marks of the postmenopausal state in women with intact ovaries. That is, the continued production of androgens by the atrophic postmenopausal ovaries. Here we show that adenoma incidence is increased in the vinyl cylcohexene diepoxide (VCD) mouse model of the menopause compared to age matched fertile female mice. Treatment with MPA protected VCD treated mice from adenomagenesis, but had no effect on adenoma numbers in age-matched fertile female mice. Our data show that the protective effect of MPA depends on the postmenopausal state and suggest that MPA monotherapy may be studied as a chemopreventive agent in postmenopausal women.

Original languageEnglish (US)
Pages (from-to)30561-30567
Number of pages7
JournalOncotarget
Volume9
Issue number55
DOIs
StatePublished - Jul 17 2018

Keywords

  • Animal models
  • Chemoprevention
  • Colon cancer
  • Hormone replacement
  • Menopause

ASJC Scopus subject areas

  • Oncology

Fingerprint Dive into the research topics of 'Colorectal tumor prevention by the progestin medroxyprogesterone acetate is critically dependent on postmenopausal status'. Together they form a unique fingerprint.

Cite this