Published Online
on March 4, 2002

A more recent version of this article appeared on March 26, 2002

This Article Full Text (PDF) All Versions of this Article: 105/12/1436    most recent hc1202.105945v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wakatsuki, A. Articles by Fukaya, T. Search for Related Content PubMed Articles by Wakatsuki, A. Articles by Fukaya, T. Related Collections Pathophysiology Acute coronary syndromes

Submitted on November 29, 2001
Revised on January 16, 2002
Accepted on January 18, 2002

Effect of Medroxyprogesterone Acetate on Vascular Inflammatory Markers in Postmenopausal Women Receiving Estrogen

Akihiko Wakatsuki MD^*, Yuji Okatani MD, Nobuo Ikenoue MD, and Takao Fukaya MD

From the Department of Obstetrics and Gynecology, Kochi Medical School, Kochi, Japan.

^* To whom correspondence should be addressed. E-mail: wakatuki{at}kochi-ms.ac.jp.

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.

Methods and 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.

Key words: cell adhesion molecules • hormones • inflammation • lipoproteins • women

This article has been cited by other articles:

				J. R. Meendering, B. N. Torgrimson, N. P. Miller, P. F. Kaplan, and C. T. Minson Estrogen, medroxyprogesterone acetate, endothelial function, and biomarkers of cardiovascular risk in young women Am J Physiol Heart Circ Physiol, April 1, 2008; 294(4): H1630 - H1637. [Abstract] [Full Text] [PDF]

				M. E. Corrigan, J. S. Drouillard, M. F. Spire, D. A. Mosier, J. E. Minton, J. J. Higgins, E. R. Loe, B. E. Depenbusch, and J. T. Fox Effects of melengestrol acetate on the inflammatory response in heifers challenged with Mannheimia haemolytica J Anim Sci, July 1, 2007; 85(7): 1770 - 1779. [Abstract] [Full Text] [PDF]

				J. L. Turgeon, M. C. Carr, P. M. Maki, M. E. Mendelsohn, and P. M. Wise Complex Actions of Sex Steroids in Adipose Tissue, the Cardiovascular System, and Brain: Insights from Basic Science and Clinical Studies Endocr. Rev., October 1, 2006; 27(6): 575 - 605. [Abstract] [Full Text] [PDF]

				K. K. Koh and B.-K. Yoon Controversies regarding hormone therapy: Insights from inflammation and hemostasis Cardiovasc Res, April 1, 2006; 70(1): 22 - 30. [Abstract] [Full Text] [PDF]

				K. K. Koh, S. H. Han, M.-S. Shin, J. Y. Ahn, Y. Lee, and E. K. Shin Significant differential effects of lower doses of hormone therapy or tibolone on markers of cardiovascular disease in post-menopausal women: a randomized, double-blind, crossover study Eur. Heart J., July 2, 2005; 26(14): 1362 - 1368. [Abstract] [Full Text] [PDF]

				R. G. Mishra, R. K. Hermsmeyer, K. Miyagawa, P. Sarrel, B. Uchida, F. Z. Stanczyk, K. A. Burry, D. R. Illingworth, and F. J. Nordt Medroxyprogesterone Acetate and Dihydrotestosterone Induce Coronary Hyperreactivity in Intact Male Rhesus Monkeys J. Clin. Endocrinol. Metab., June 1, 2005; 90(6): 3706 - 3714. [Abstract] [Full Text] [PDF]

				T. C. Register, J. A. Cann, J. R. Kaplan, J. K. Williams, M. R. Adams, T. M. Morgan, M. S. Anthony, R. M. Blair, J. D. Wagner, and T. B. Clarkson Effects of Soy Isoflavones and Conjugated Equine Estrogens on Inflammatory Markers in Atherosclerotic, Ovariectomized Monkeys J. Clin. Endocrinol. Metab., March 1, 2005; 90(3): 1734 - 1740. [Abstract] [Full Text] [PDF]

				A. Ropponen, K. Aittomaki, M. J. Tikkanen, and O. Ylikorkala Levels of Serum C-Reactive Protein during Oral and Transdermal Estradiol in Postmenopausal Women with and without a History of Intrahepatic Cholestasis of Pregnancy J. Clin. Endocrinol. Metab., January 1, 2005; 90(1): 142 - 146. [Abstract] [Full Text] [PDF]

				A. F. Kernohan, A. Spiers, N. Sattar, C. Hillier, S. J Cleland, M. Small, M.-A. Lumsden, J. M. Connell, and J. R Petrie Effects of low-dose continuous combined HRT on vascular function in women with type 2 diabetes Diabetes and Vascular Disease Research, October 1, 2004; 1(2): 82 - 88. [Abstract] [PDF]

				K. K. Koh and I. Sakuma Should Progestins Be Blamed for the Failure of Hormone Replacement Therapy to Reduce Cardiovascular Events in Randomized Controlled Trials? Arterioscler Thromb Vasc Biol, July 1, 2004; 24(7): 1171 - 1179. [Abstract] [Full Text] [PDF]

				R. K. Hermsmeyer, R. G. Mishra, D. Pavcnik, B. Uchida, M. K. Axthelm, F. Z. Stanczyk, K. A. Burry, D. R. Illingworth, J. C. Kaski, and F. J. Nordt Prevention of Coronary Hyperreactivity in Preatherogenic Menopausal Rhesus Monkeys by Transdermal Progesterone Arterioscler Thromb Vasc Biol, May 1, 2004; 24(5): 955 - 961. [Abstract] [Full Text]

				A. Wakatsuki, N. Ikenoue, K. Shinohara, K. Watanabe, and T. Fukaya Effect of Lower Dosage of Oral Conjugated Equine Estrogen on Inflammatory Markers and Endothelial Function in Healthy Postmenopausal Women Arterioscler Thromb Vasc Biol, March 1, 2004; 24(3): 571 - 576. [Abstract] [Full Text]

				B. L. Stauffer, G. L. Hoetzer, D. T. Smith, and C. A. DeSouza Plasma C-reactive protein is not elevated in physically active postmenopausal women taking hormone replacement therapy J Appl Physiol, January 1, 2004; 96(1): 143 - 148. [Abstract] [Full Text] [PDF]

				K. K. Koh, J. Y. Ahn, D. K. Jin, B.-K. Yoon, H. S. Kim, D. S. Kim, W. C. Kang, S. H. Han, I. S. Choi, and E. K. Shin Significant Differential Effects of Hormone Therapy or Tibolone on Markers of Cardiovascular Disease in Postmenopausal Women: A Randomized, Double-Blind, Placebo-Controlled, Crossover Study Arterioscler Thromb Vasc Biol, October 1, 2003; 23(10): 1889 - 1894. [Abstract] [Full Text] [PDF]

				A. P. Miller, Y.-F. Chen, D. Xing, W. Feng, and S. Oparil Hormone Replacement Therapy and Inflammation: Interactions in Cardiovascular Disease Hypertension, October 1, 2003; 42(4): 657 - 663. [Abstract] [Full Text] [PDF]

				S. Davison and S. R. Davis New Markers for Cardiovascular Disease Risk in Women: Impact of Endogenous Estrogen Status and Exogenous Postmenopausal Hormone Therapy J. Clin. Endocrinol. Metab., June 1, 2003; 88(6): 2470 - 2478. [Abstract] [Full Text] [PDF]

				W. Vongpatanasin, M. Tuncel, Z. Wang, D. Arbique, B. Mehrad, and I. Jialal Differential effects of oral versus transdermal estrogen replacement therapy on C-reactive protein in postmenopausal women J. Am. Coll. Cardiol., April 16, 2003; 41(8): 1358 - 1363. [Abstract] [Full Text] [PDF]

				A. Wakatsuki, Y. Okatani, T. Fukaya, K. K. Koh, W. H. Schenke, R. O. Cannon III, M. A. Waclawiw, and G. Csako Statin Attenuates Increase in C-Reactive Protein During Estrogen Replacement Therapy in Postmenopausal Women * Response Circulation, December 10, 2002; 106 (24): e198 - e199. [Full Text] [PDF]

				D. Rachon, A. Wakatsuki, Y. Okatani, N. Ikenoue, and T. Fukaya The Antiinflammatory Properties of Medroxyprogesterone Acetate * Response Circulation, November 26, 2002; 106 (22): e185 - e185. [Full Text] [PDF]

				P. Garnero, C. Jamin, C.-L. Benhamou, C. Pelissier, and C. Roux Effects of tibolone and combined 17{beta}-estradiol and norethisterone acetate on serum C-reactive protein in healthy post-menopausal women: a randomized trial Hum. Reprod., October 1, 2002; 17(10): 2748 - 2753. [Abstract] [Full Text] [PDF]