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Clinical study comparing the effects of sequential hormone replacement therapy with oestradiol/dydrogesterone and conjugated equine oestrogen/norgestrel on lipids and symptoms

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Abstract

A clinical study comparing the effects of sequential hormone replacement therapy with oestradiol/dydrogesterone and conjugated equine oestrogen/norgestrel on lipids and symptoms. Objective: The objective of the study was to compare the effects of sequential 17β-oestradiol/dydrogesterone and conjugated equine oestrogens (CEE)/norgestrel on lipid parameters, climacteric symptoms, bleeding patterns and tolerability. Study design: This double-blind study was conducted in 193 peri- and post-menopausal women randomised to receive six, 28-day cycles of oral sequential oestradiol 1 mg/dydrogesterone 10 mg or CEE 0.625 mg/norgestrel 0.15 mg. The change from baseline in serum lipids and hot flushes was analysed using a two-way analysis of variance. Results: After 24 weeks there was a statistically significant increase in high-density lipoprotein (HDL) cholesterol in the oestradiol/dydrogesterone group and a significant reduction in the CEE/norgestrel group. The difference between the groups was significant (P=0.001). The number of hot flushes was reduced by 86% in both groups; this improvement was supported by the Greene Climacteric Symptom Scale score, the patients’ opinion and quality of life assessments. The percentage of women experiencing cyclic bleeding was greater with CEE/norgestrel, as was the mean duration and severity of bleeding. Both treatments were well tolerated. Conclusion: Oestradiol/dydrogesterone and CEE/norgestrel were equally effective in treating climacteric symptoms, but oestradiol/dydrogesterone showed some advantages in terms of lipid profile and incidence of bleeding.

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References

  1. Haas S, Schiff I (1988) Symptoms of oestrogen deficiency. The menopause. Blackwell, Oxford, pp 15–23

    Google Scholar 

  2. Jokinen K, Rautava P, Makinen J, Ojanlatva A, Sundell J, Helenius H (2003) Experience of climacteric symptoms among 42–46 and 52–56-year-old women. Maturitas 46:199–205

    Article  PubMed  CAS  Google Scholar 

  3. Pitkin J, Rees MC, Gray S et al (2003) Managing the menopause—British Menopause Society Council consensus on hormone replacement therapy. J Br Menopause Soc 9:129–131

    Article  PubMed  Google Scholar 

  4. Grady D Rubin SM, Petitti DB et al (1992) Hormone therapy to prevent disease and prolong life in postmenopausal women. Ann Intern Med 117:1016–1037

    Google Scholar 

  5. Beresford S, Weiss N, Voight L, Mckight B (1997) Risk of endometrial cancer in relation to use of oestrogen combined with cyclic progestogen therapy in postmenopausal women. Lancet 349:458–461

    Article  PubMed  CAS  Google Scholar 

  6. Haarbo J, Hassager C, Jensen S Riis BJ, Christiansen C (1991) Serum lipids, lipoproteins and apolipoproteins during postmenopausal estrogen replacement therapy combined with either 19-nortestosterone derivatives or 17-hydroxyprogesterone derivatives. Am J Med 90:584–589

    PubMed  CAS  Google Scholar 

  7. The Writing Group for the PEPI Trial (1995) Effects of estrogen or estrogen/progestin regimens on heart disease risk factors in post-menopausal women. The postmenopausal estrogen/progestin interventions (PEPI) trial. JAMA 273:199–208

    Google Scholar 

  8. van der Mooren MJ, Demacker PNM, Thomas CMG, Borm GF, Rolland R (1993) A 2-year study on the beneficial effects of 17β-oestradiol-dydrogesterone therapy on serum lipoproteins and Lp(a) in postmenopausal women: no additional unfavourable effects of dydrogesterone. Eur J Obstet Gynaecol Reprod Biol 52:117–123

    Article  Google Scholar 

  9. Crook D, Godsland IF, Stevenson JC (1995) The cardiovascular risk profile of hormone replacement therapies containing dydrogesterone: a review. Eur Menopause J 2(Suppl):23–30

    Google Scholar 

  10. van der Mooren MJ, Demacker PNM, Thomas CMG, Rolland R (1992) Beneficial effects on serum lipoproteins by 17β-oestradiol-dydrogesterone therapy in postmenopausal women—a prospective study. Eur J Obstet Gynaecol Reprod Biol 47:153–160

    Article  Google Scholar 

  11. Mashchak CA, Lobo RA, Dozono-Takano R et al (1982) Comparison of pharmacodynamic properties of various estrogen formulations. Am J Obstet Gynaecol 144:511–518

    CAS  Google Scholar 

  12. Archer DF, Fischer LA, Rich D et al (1992) Estrace® vs Premarin® for treatment of menopausal symptoms: dosage comparison study. Adv Ther 9:21–31

    Google Scholar 

  13. Quigley MET, Martin PL, Burnier NNAM, Brooks P (1987) Estrogen arrests bone loss in elderly women. Am J Obstet Gynecol 156:1516–1523

    PubMed  CAS  Google Scholar 

  14. Greene JG (1998) Construction of a standard climacteric scale. Maturitas 29:25–31

    Article  PubMed  CAS  Google Scholar 

  15. Burch DJ, Spowart KJM, Jesinger DK, Randall S, Smith SK (1995) A dose-ranging study of the use of cyclical dydrogesterone with continuous 17β oestradiol. Br J Obstet Gynaecol 102:243–248

    PubMed  CAS  Google Scholar 

  16. Nelson HD (2004) Commonly used types of postmenopausal estrogen for treatment of hot flashes: scientific review. JAMA 291:1610–1620

    Article  PubMed  CAS  Google Scholar 

  17. Crook D, Godsland IF, Hull J, Stevenson J (1997) Hormone replacement therapy with dydrogesterone and 17β-oestradiol: effects on serum lipoproteins and glucose tolerance during 24 months follow-up. Br J Obstet Gynaecol 104:298–304

    PubMed  CAS  Google Scholar 

  18. Tall AR (1990) Plasma high density lipoproteins: metabolism and relation to atherogenesis. J Clin Invest 86:379–384

    Article  PubMed  CAS  Google Scholar 

  19. Grodstein F, Manson JE, Colditz GA, Willett WC, Speizer FE, Stampfer MJ (2000) A prospective, observational study of postmenopausal hormone therapy and primary prevention of cardiovascular disease. Ann Intern Med 133:933–941

    PubMed  CAS  Google Scholar 

  20. Falkeborn M, Persson I, Adami HO et al (1992) The risk of acute myocardial infarction after oestrogen and oestrogen–progestogen replacement. Br J Obstet Gynaecol 99:821–828

    PubMed  CAS  Google Scholar 

  21. Hulley S, Grady D, Bush T et al (1998) Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. Heart and Estrogen/progestin Replacement Study (HERS) Research Group. JAMA 280:605–613

    Article  PubMed  CAS  Google Scholar 

  22. Grady D, Herrington D, Bittner V et al (2002) Cardiovascular disease outcomes during 6.8 years of hormone therapy: Heart and Estrogen/progestin Replacement Study follow-up (HERS II). JAMA 288:49–57

    Article  PubMed  Google Scholar 

  23. Rossouw JE, Anderson GL, Prentice RL et al (2002) Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women’s Health Initiative randomized controlled trial. JAMA 288:321–333

    Article  PubMed  CAS  Google Scholar 

  24. Anderson GL, Limacher M, Assaf AR et al (2004) Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women’s Health Initiative randomized controlled trial. JAMA 291:1701–1712

    Article  PubMed  CAS  Google Scholar 

  25. Speroff L (1998) The Heart and Estrogen/progestin Replacement Study (HERS). Maturitas 31:9–14

    Article  PubMed  CAS  Google Scholar 

  26. Sitruk-Ware RL (2003) Hormone therapy and the cardiovascular system: the critical role of progestins. Climacteric 6(Suppl 3):21–28

    PubMed  CAS  Google Scholar 

  27. Garbe E, Suissa S (2004) Hormone replacement therapy and acute coronary outcomes: methodological issues between randomized and observational studies. Hum Reprod 19:8–13

    Article  PubMed  CAS  Google Scholar 

  28. Rosano GM, Vitale C, Silvestri A, Fini M (2003) Hormone replacement therapy and cardioprotection: the end of the tale? Ann NY Acad Sci 997:351–357

    Article  PubMed  Google Scholar 

  29. Williams JK, Suparto I (2004) Hormone replacement therapy and cardiovascular disease: lessons from a monkey model of postmenopausal women. ILAR J 45:139–146

    PubMed  CAS  Google Scholar 

  30. Koh KK, Sakuma I (2004) Should progestins be blamed for the failure of hormone replacement therapy to reduce cardiovascular events in randomized controlled trials? Arterioscler Thromb Vasc Biol 24:1171–1179

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

We would like to thank the following for their participation in this study: Dr W.R.C. Aitchison, Dr G. McLaren, Dr M. Scott, Dr D. McKeith, Dr F. Doig, Dr A.G. McHattie, Dr G. Hosie, Dr A. Dawson, Dr J. Vernon, Dr A. Fuat, Dr B. Penney, Dr R.S. Charlton, Dr D. Russell, Dr I.G. Smith, Dr S. Young, Dr E. Greene, Dr R.E. Liddle, Dr B.D. Silvert, Dr J. Turley, Dr F. Lossock, Dr R. Brownlie, Dr D. Birrell, Dr G. Crawford, Dr I. Mason, Dr W. Carr, Dr J.G. Duggie, Dr D.I. Ballantine, Dr D.I. Selfridge, Dr E. Williamson, Dr J. Ross, Dr C. MacKinnon, Dr D. Huggan, Dr M. Haughney, Dr B. Kilgallon, Dr A. Wall, Dr P. Shearer.

Author information

Authors and Affiliations

  1. Solvay Pharmaceuticals BV, Weesp, The Netherlands

    Diana Cieraad

  2. Solvay Pharmaceuticals GmbH, Hannover, Germany

    Christian Conradt

  3. Solvay Healthcare Ltd, Mansbridge Road, West End, SO183JD, Southampton, UK

    Diana Jesinger & Marie Bakowski

Authors
  1. Diana Cieraad
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  2. Christian Conradt
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  3. Diana Jesinger
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  4. Marie Bakowski
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Corresponding author

Correspondence to Marie Bakowski.

Additional information

Condensation : Sequential oestradiol/dydrogesterone and conjugated equine oestrogen/norgestrel are equally effective in treating climacteric symptoms, but oestradiol/dydrogesterone shows advantages in terms of lipid profile and bleeding.

Appendix: Participating investigators

Appendix: Participating investigators

Dr W.R.C. Aitchison, Dr G. McLaren, Bridge of Weir, Renfrewshire, UK

Dr M. Scott, Glasgow, UK

Dr D. McKeith, Dr. F. Doig, Irvine, Ayrshire, UK

Dr A.G. McHattie, Troone, Ayrshire, UK

Dr G. Hosie, Knightswood, Glasgow, UK

Dr A Dawson, Dr J. Vernon, Hawkhill, Dundee, UK

Dr A. Fuat, Dr B. Penney, Darlington, Co. Durham, UK

Dr R.S. Charlton, Dr D. Russel, Darlington, Co. Durham, UK

Dr I.G. Smith, Dr S. Young, Coppull, Chorley, Lancashire, UK

Dr E. Greene, Neilston, Renfrewshire, UK

Dr R.E. Liddle, Edinburgh, UK

Dr B.D. Silvert, Farnworth, Bolton, Lancashire, UK

Dr J. Turley, Newcastle-Upon-Tyne, UK

Dr F. Lossock, Edinburgh, UK

Dr R. Brownlie, Highvalleyfield, Dunfermline, UK

Dr D. Birrell, Dundee, UK

Dr G. Crawford, Clydebank, Glasgow, UK

Dr I. Mason, Dunfermline, UK

Dr W. Carr, Leslie, Glenrothes, Fife, UK

Dr J.G. Duggie, Dr D.I. Ballantine, Dr D.I. Selfridge, Grangemouth, UK

Dr E. Williamson, South Queensferry, UK

Dr J. Ross, Glasgow, UK

Dr C. MacKinnon, Glasgow, UK

Dr D. Huggan, Kilwinning, UK

Dr M. Haughney, Glasgow, UK

Dr B. Kilgallon, Dundee, UK

Dr A. Wall, Woking, Surrey, UK

Dr P. Shearer, Ayr, UK

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Cieraad, D., Conradt, C., Jesinger, D. et al. Clinical study comparing the effects of sequential hormone replacement therapy with oestradiol/dydrogesterone and conjugated equine oestrogen/norgestrel on lipids and symptoms. Arch Gynecol Obstet 274, 74–80 (2006). https://doi.org/10.1007/s00404-006-0132-4

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  • DOI: https://doi.org/10.1007/s00404-006-0132-4

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