Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Medroxyprogesterone interferes with ovarian steroid protection against coronary vasospasm

Nature Medicine volume 3, pages 324–327 (1997)Cite this article

Abstract

Cardiovascular disease, the major cause of death in post-menopausal women, can be reduced by re-placement of ovarian steroid hormones. To compare medroxyprogesterone with progesterone as the progestin in hormone replacement therapy from the standpoint of coronary artery vasospasm, we treated ovariectomized rhesus monkeys with physiological levels of estradiol-17β in combination with medroxyprogesterone or progesterone for four weeks. Coronary vasospasm in response to pathophysiological stimulation without injury showed that progesterone plus estradiol protected but medroxyprogesterone plus estradiol failed to protect, allowing vasospasm. We conclude that medroxyprogesterone in contrast to progesterone increases the risk of coronary vasospasm.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Gorodeski, G.I. & Utian, W.H. Epidemiology and risk factors of cardiovascular disease in postmenopausal women, in Treatment of the PostmenopausalWoman: Basic and Clinical Aspects (ed. Lobo, R.A.) 199–221 (Raven, New York, 1994).

  2. Wenger, N.K., Speroff, L. & Packard, B. Cardiovascular health and disease in women. New Engl. J. Med. 329, 247–256 (1993).

    Article  CAS  Google Scholar 

  3. The writing Group for the PEPI Trial. Effects of estrogen or estrogen/progestin regimens on heart disease risk factors in postmenopausal women, the Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial. JAMA 273, 199–208 (1995).

    Article  Google Scholar 

  4. Lobo, R.A., Pickar, J.H., Wild, R.A., Walsh, B. & Hirvonen, E. Metabolic impact of adding medroxyprogesterone acetate to conjugated estrogen therapy in postmenopausal women. Obstet. Cynecol. 84, 987–995 (1994).

    CAS  Google Scholar 

  5. Poulter, N.R. Venous thromboembolic disease and combined oral contraceptives: Results of international multicentre case-control study. Lancet 346, 1575–1582 (1995).

    Article  Google Scholar 

  6. Meirik, O. Effect of different progestagens in low oestrogen oral contraceptives on venous thromboembolic disease. Lancet 346, 1582–1588 (1995).

    Article  CAS  Google Scholar 

  7. Jick, H., Jick, S.S., Gurewich, V., Myers, M.W. & Vasilakis, C. Risk of idiopathic cardiovascular death and nonfatal venous thromboembolism in women using oral contraceptives with differing progestagen components. Lancet 346, 1589–1593 (1995).

    Article  CAS  Google Scholar 

  8. Bloemenkamp, W.M., Rosendaal, F.R., Helmerhorst, P.M., Buller, H.R. & Vandenbrouke, J.P. Enhancement by factor V Leiden mutation of risk of deep-vein thrombosis associated with oral contraceptives containing a third-generation progestagen. Lancet 346, 1593–1596 (1995).

    Article  CAS  Google Scholar 

  9. Gilmore, J.P. Neural control of extraCellular volume in the human and nonhuman primate. in Handbook of Physiology. Section 2: The Cardiovascular System, Vol. Ill, Part 2 (eds. Shepherd, J.T. & Abboud, F.M.) 885–915 (American Physiological Society, Baltimore, Maryland, 1983).

    Google Scholar 

  10. Adams, M.R., Washburn, S.A., Wagner, J.D., Williams, J.K. & Clarkson, T.B. Arterial changes: Estrogen deficiency and effects of hormone replacement, in Treatment of the Postmenopausal Woman: Basic and Clinical Aspects (ed. Lobo, R. A.) 243–250 (Raven, New York, 1994).

    Google Scholar 

  11. Hermsmeyer, K. et al. Reactivity-based coronary vasospasm independent of atherosclerosis in rhesus monkeys. J. Am. Coll. Cardiol. (in the press).

  12. Williams, C.L. & Stancel, G.M. Estrogens and Progestins. in Goodman and Gilman's The Pharmacological Basis of Therapeutics (eds. Hardman, J.G., Limbird, L.E., Molinoff, P.B., Ruddon, R.W., & Gilman, A.G.,) 1411–1440 (McGraw-Hill, New York, 1995).

    Google Scholar 

  13. Stanczyk, F.Z. Structure-function relationships, potency, and pharmacokinetics of progestogens. in Treatment of the Postmenopausal Woman: Basic and Clinical Aspects (ed. Lobo, R.A.) 69–89 (Raven, New York, 1994).

    Google Scholar 

  14. Resko, J.A., Ploem, J.G. & Stadelman, H.L. Estrogens in fetal and maternal plasma of the rhesus monkey. Endocrinology 98, 425–430 (1975).

    Article  Google Scholar 

  15. Mishra, S.K. & Hermsmeyer, K. Inhibition of signal Ca2+ in dog coronary arterial vascular muscle Cells by Ro 40–5967. J. Cardiovasc. Pharmacol. 24, 1–7 (1994).

    Article  CAS  Google Scholar 

  16. Maseri, A., Davies, G., Hackett, D. & Kaski, J.C. Coronary artery spasm and vasoconstriction. Circulation 81, 1983–1990 (1990).

    Article  CAS  Google Scholar 

  17. Miller, V.M. & Vanhoutte, P.M. Progesterone and modulation of endothelium-dependent responses in canine coronaiy arteries. Am. J. Physiol. 261, R1022–R1027 (1991).

    CAS  PubMed  Google Scholar 

  18. Slayden, O.D., Hirst, J.J. & Brenner, R.M. Estrogen action in the reproductive tract of rhesus monkeys during antiprogestin treatment. Endocrinology 132, 1845–1856 (1993).

    Article  CAS  Google Scholar 

  19. Hiroi, M. et al. Radioimmunoassay of serum medroxyprogesterone acetate (Provera) in women following oral and intravaginal administration. Steroids 26, 373–386 (1975.)

    Article  CAS  Google Scholar 

  20. Resko, J.A., Norman, R.L., Niswender, G.D. & Spies, H.G. The relationship between progesterone and gonadotropins during the late luteal phase of the menstrual cycle in rhesus monkeys. Endocrinology 94, 128–135 (1974).

    Article  CAS  Google Scholar 

  21. Jiang, C.W., Sarrel, P.M., Lindsay, D.C., Poole-Wilson, P.A. & Collins, P. Progesterone induces endothelium-independent relaxation of rabbit coronary artery in vitro. Eur. J. Pharmacol. 211, 163–167 (1992).

    Article  CAS  Google Scholar 

  22. Healy, B. PEPI in Perspective, good answers spawn pressing questions. JAMA 273, 240–241 (1995).

    Article  CAS  Google Scholar 

  23. Belchetz, P.E. Hormonal treatment of postmenopausal women. New Engl. J. Med. 330, 1062–1071 (1994).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Oregon Regional Primate Research Center and Departments of Medicine and Cell and Developmental Biology, Oregon Health Sciences University, Beaverton, Oregon, 97006, USA

    Koichi Miyagawa, Frank Stanczyk & Kent Hermsmeyer

  2. The Charles Dotter Institute for Interventional Radiology, Oregon Health Sciences University, Portland, Oregon, 97201, USA

    Josef Rösch

  3. University of Southern California, School of Medicine, Women's and Children's Hospital, 1240 N Mission Road, Los Angeles, California, 90033, USA

    Frank Stanczyk

Authors
  1. Koichi Miyagawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Josef Rösch
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Frank Stanczyk
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kent Hermsmeyer
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Miyagawa, K., Rösch, J., Stanczyk, F. et al. Medroxyprogesterone interferes with ovarian steroid protection against coronary vasospasm. Nat Med 3, 324–327 (1997). https://doi.org/10.1038/nm0397-324

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nm0397-324

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing