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Arteriosclerosis, thrombosis, and vascular biology1997; 17(1); 217-221; doi: 10.1161/01.atv.17.1.217

Medroxyprogesterone acetate antagonizes inhibitory effects of conjugated equine estrogens on coronary artery atherosclerosis.

Abstract: Although estrogen replacement therapy is associated with reduced risk of coronary heart disease and reduced extent of coronary artery atherosclerosis, the effects of combined (estrogen plus progestin) hormone-replacement therapy are uncertain. Some observational data indicate that users of combined hormone replacement consisting of continuously administered oral conjugated equine estrogens (CEE) and oral sequentially administered (7 to 14 days per month) medroxyprogesterone acetate (MPA) experience a reduction in risk similar to that of users of CEE alone. However, the effects of combined, continuously administered CEE plus MPA (a prescribing pattern that has gained favor) on the risk of coronary heart disease or atherosclerosis are not known. We studied the effects of CEE (monkey equivalent of 0.625 mg/d) and MPA (monkey equivalent of 2.5 mg/d), administered separately or in combination, on the extent of coronary artery atherosclerosis (average plaque size) in surgically postmenopausal cynomolgus monkeys fed atherogenic diets and treated with these hormones for 30 months. Treatment with CEE alone resulted in atherosclerosis extent that was reduced 72% relative to untreated (estrogen-deficient) controls (P < .004). Atherosclerosis extent in animals treated with CEE plus MPA or MPA alone did not differ from that of untreated controls. Although treatment had marked effects on plasma lipoprotein patterns, statistical adjustment for variation in plasma lipoproteins did not alter the between-group relationships in atherosclerotic plaque size, suggesting that these factors do not explain substantially the atheroprotective effect of estrogen or the MPA-associated antagonism. Although the mechanism(s) remains unclear, we conclude that oral CEE inhibits the initiation and progression of coronary artery atherosclerosis and that continuously administered oral MPA antagonizes this atheroprotective effect.
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Publication Date: 1997-01-01 PubMed ID: 9012659DOI: 10.1161/01.atv.17.1.217Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • U.S. Gov't
  • P.H.S.

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research examines the effects of combined hormone replacement therapy (HRT), specifically conjugated equine estrogens (CEE) and medroxyprogesterone acetate (MPA), on coronary artery atherosclerosis, using postmenopausal monkeys as subjects. The results indicate that while CEE alone significantly reduces atherosclerosis, MPA seems to counter this beneficial effect when used in combination with CEE.

Objective and Approach

  • The primary objective of the study was to investigate the effects of combined hormone replacement therapy (HRT) involving conjugated equine estrogens (CEE) and medroxyprogesterone acetate (MPA) on the development and progression of coronary artery atherosclerosis.
  • To achieve this, the research team utilized postmenopausal cynomolgus monkeys fed atherogenic diets as the study subjects.
  • Over 30 months, the monkeys were treated with CEE and MPA either separately or in combination, mimicking the doses used in humans.
  • The primary measure of interest was the average plaque size in the monkeys’ coronary arteries, indicating the extent of atherosclerosis.

Findings

  • Treatment with just CEE showed a significant reduction in atherosclerosis by 72% when compared with untreated control subjects.
  • In contrast, animals treated with a combination of CEE and MPA or MPA alone did not show a significant difference in atherosclerosis extent compared to untreated controls.
  • The researchers observed a marked effect on plasma lipoprotein patterns due to the treatment. However, statistical adjustment for variations in plasma lipoproteins did not significantly alter the relationships between treatment regimens and plaque size.
  • This finding implies that the variation in plasma lipoproteins does not contribute materially to the atheroprotective effect of estrogen or the MPA-associated inhibition.

Conclusion

  • The research concluded that orally administered CEE can significantly inhibit the initiation and progression of coronary artery atherosclerosis.
  • However, when continuously administered oral MPA is added to the CEE treatment, it seems to antagonize, or counteract, this beneficial effect.
  • While the exact mechanisms through which this occurs remain uncertain, the findings have important implications for hormone replacement therapy in postmenopausal women and the potential risk for coronary heart disease or atherosclerosis.

Cite This Article

APA
Adams MR, Register TC, Golden DL, Wagner JD, Williams JK. (1997). Medroxyprogesterone acetate antagonizes inhibitory effects of conjugated equine estrogens on coronary artery atherosclerosis. Arterioscler Thromb Vasc Biol, 17(1), 217-221. https://doi.org/10.1161/01.atv.17.1.217

Publication

Arteriosclerosis, thrombosis, and vascular biology
ISSN: 1079-5642
NlmUniqueID: 9505803
Country: United States
Language: English
Volume: 17
Issue: 1
Pages: 217-221

Researcher Affiliations

Adams, M R
  • Comparative Medicine Clinical Research Center, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, NC 27157-1040, USA. madams@cpm.bgsm.edu
Register, T C
    Golden, D L
      Wagner, J D
        Williams, J K

          MeSH Terms

          • Administration, Oral
          • Animals
          • Coronary Artery Disease / chemically induced
          • Drug Antagonism
          • Drug Therapy, Combination
          • Estrogen Replacement Therapy / adverse effects
          • Estrogens / administration & dosage
          • Female
          • Macaca fascicularis
          • Medroxyprogesterone Acetate / administration & dosage
          • Ovariectomy
          • Progesterone Congeners / administration & dosage

          Grant Funding

          • HL-P0145666 / NHLBI NIH HHS

          Citations

          This article has been cited 54 times.
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