Comparative analysis of the uterine and mammary gland effects of progesterone and medroxyprogesterone acetate.
OBJECTIVE
In combined hormone replacement therapy (HRT) progestins are used to inhibit estradiol-activated uterine epithelial cell proliferation. In comparison to estradiol-only therapy, combined HRT leads to enhanced proliferation of mammary epithelial cells. In a quantitative mouse model, we assessed the balance between uterine and undesired mammary gland effects for two progestins that are widely used in HRT, progesterone and medroxyprogesterone acetate.


METHODS
Mice were ovariectomized and after 14 days they were treated subcutaneously with either vehicle, estradiol (100 ng) or estradiol plus increasing doses of progesterone or medroxyprogesterone acetate for three weeks.


METHODS
Measures for progestogenic mammary gland activity were stimulation of side-branching and stimulation of epithelial cell proliferation. Progestogenic activity in the uterus was assessed by measuring inhibition of estradiol-activated uterine epithelial cell proliferation. ED(50) and ID(50) values for the distinct readouts were obtained and dissociation factors for uterine versus mammary gland activity were calculated.


RESULTS
MPA demonstrated uterine activity and mitogenic activity in the mammary gland at the same doses. In contrast, progesterone showed uterine activity at doses lower than those leading to significant stimulation of epithelial cell proliferation in the mammary gland.


CONCLUSIONS
Progestins do not behave the same. Use of the natural hormone progesterone, but not MPA, in combined hormone therapy might offer a safety window between uterine effects and undesired proliferative activity in the mammary gland.
Otto
Christiane
C
TRG Women's Healthcare, Bayer Schering Pharma AG, Muellerstrasse 178, 13342 Berlin, Germany. christiane.otto@bayerhealthcare.com
Fuchs
Iris
I
Vonk
Richardus
R
Fritzemeier
Karl-Heinrich
KH
D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects*; D004347:Drug Interactions; D004958:Estradiol / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D008321:Mammary Glands, Animal / Q000187:drug effects*; D017258:Medroxyprogesterone Acetate / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D014599:Uterus / Q000187:drug effects*
D018931:Antineoplastic Agents, Hormonal; D004967:Estrogens; D004958:Estradiol; D017258:Medroxyprogesterone Acetate