TY - JOUR
T1 - Colorectal tumor prevention by the progestin medroxyprogesterone acetate is critically dependent on postmenopausal status
AU - Meijer, Bartolomeus J.
AU - Wielenga, Mattheus C. B.
AU - Hoyer, Patricia B.
AU - Amos-Landgraf, James M.
AU - Hakvoort, Theodorus B. M.
AU - Muncan, Vanesa
AU - Heijmans, Jarom
AU - van den Brink, Gijs R.
PY - 2018
Y1 - 2018
N2 - 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.
AB - 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.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85050083250&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/30093969
U2 - https://doi.org/10.18632/oncotarget.25703
DO - https://doi.org/10.18632/oncotarget.25703
M3 - Article
C2 - 30093969
SN - 1949-2553
VL - 9
SP - 30561
EP - 30567
JO - Oncotarget
JF - Oncotarget
IS - 55
ER -