Effect of medroxyprogesterone acetate on vascular inflammatory markers in postmenopausal women receiving estrogen.
BACKGROUND
Estrogen increases C-reactive protein (CRP) in postmenopausal women. Estrogen also decreases cell adhesion molecules, whereas elevated CRP stimulates the expression of cell adhesion molecules. Because androgens have antiinflammatory effects, androgenic progestins such as medroxyprogesterone acetate (MPA) may inhibit proinflammatory effects of estrogen. We investigated the effects of MPA on estrogen-induced changes in acute inflammatory proteins and cell adhesion molecules in postmenopausal women.


RESULTS
Postmenopausal women were treated daily with conjugated equine estrogen (CEE, 0.625 mg), CEE plus MPA 2.5 mg, or CEE plus MPA 5.0 mg for 3 months. CEE significantly increased CRP concentrations by 320.1+/-210.2% (P<0.05). The addition of MPA to CEE, however, inhibited the increase in CRP in a concentration-dependent manner (MPA 2.5 mg, 169.8+/-66.9%, P<0.05; MPA 5 mg, 55.0+/-30.4%, not significant). Similarly, CEE increased amyloid A protein concentrations, whereas MPA reversed this effect. Interleukin-6 concentration did not change significantly in any treatment group. CEE alone significantly decreased the concentration of E-selectin, but the concentrations of intercellular adhesion molecule and vascular cellular adhesion molecule did not change significantly. The addition of MPA tended to decrease the levels of cell adhesion molecules, and use of 5.0 mg MPA showed significant decreases in all cell-adhesion molecule concentrations.


CONCLUSIONS
Concurrent MPA administration may attenuate estrogen's proinflammatory effect. Because MPA in combination with CEE decreased cell adhesion molecule concentrations, the anti-inflammatory effect of MPA may actually be responsible for the favorable effect of estrogen-progestogen combinations on cell adhesion molecules in postmenopausal women.
Wakatsuki
Akihiko
A
Department of Obstetrics and Gynecology, Kochi Medical School, Kochi, Japan. wakatuki@kochi-ms.ac.jp
Okatani
Yuji
Y
Ikenoue
Nobuo
N
Fukaya
Takao
T
D000328:Adult; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D019040:E-Selectin / Q000097:blood; D004717:Endometrium / Q000166:cytology / Q000187:drug effects; D004967:Estrogens / Q000097:blood; D004966:Estrogens, Conjugated (USP) / Q000494:pharmacology*; D005260:Female; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D007564:Japan; D008055:Lipids / Q000097:blood; D017258:Medroxyprogesterone Acetate / Q000494:pharmacology*; D008875:Middle Aged; D017698:Postmenopause; D011374:Progesterone / Q000097:blood; D012307:Risk Factors; D000685:Serum Amyloid A Protein / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood
D015415:Biomarkers; D015815:Cell Adhesion Molecules; D008078:Cholesterol, LDL; D019040:E-Selectin; D004967:Estrogens; D004966:Estrogens, Conjugated (USP); D015850:Interleukin-6; D008055:Lipids; D000685:Serum Amyloid A Protein; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D011374:Progesterone; D002097:C-Reactive Protein; D017258:Medroxyprogesterone Acetate