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Klinische Bedeutung von gestagenen Partialwirkungen

Clinical significance of partial gestagen effects

  • Arzneimitteltherapie
  • Published:
Gynäkologische Endokrinologie Aims and scope

Zusammenfassung

Die Partialwirkungen der zur Kontrazeption und zur Hormonersatztherapie eingesetzten Gestagene sind nicht dieselben. Sie unterscheiden sich hinsichtlich ihrer Struktur, ihrer Metabolisierung, ihrer Bioverfügbarkeit und ihrer Partialwirkungen. Deshalb ist es unsinnig, die verschiedenen Gestagene mit ihren unterschiedlichen Wirkungsprofilen in eine einheitliche Klasse einzuteilen. Entsprechend ihrer Partialwirkungen werden die Gestagene heute gezielt zur Kontrazeption, zur postmenopausalen Hormontherapie oder als Antiandrogen eingesetzt. Neuere von ihrem Wirkungsprofil her günstige Gestagene sind die Norpregnane, Dienogest und Drospirenon. Diese Übersicht fasst die Einteilung der Gestagene, deren wichtigste Merkmale und Partialwirkungen und deren mögliche Folgen für die Klinik zusammen.

Abstract

The partial effects of progestagens used for contraception and for hormone replacement therapy are not the same. They differ in their structure, metabolization, bioavailability, and partial effects. Thus, it is absurd to classify the various gestagens with their different activity profiles into one uniform category. Nowadays, progestagens are specifically employed for contraception, postmenopausal hormone therapy, or as antiandrogens depending on their partial effects. Newer progestagens that are more beneficial based on their activity profile include norpregnane, dienogest, and drospirenone. This overview summarizes the classification of progestagens, their most important characteristics, and their partial effects as well as possible consequences for clinical practice.

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Literatur

  1. Adams MR, Kaplan JR, Manuck SB et al. (1990) Inhibition of coronary artery atherosclerosis by 17-beta estradiol in ovariectomized monkeys: lack of an effect of added progesterone. Arteriosclerosis 10:1051–1057

    PubMed  Google Scholar 

  2. Al-Azzawi F, Wahab M, Thompson J et al. (2001) Acceptability and patterns of endometrial bleeding in estradiol-based HRT regimens: a comparative study of cyclical sequential combinations of trimegestone or norethisterone acetate, Climacteric 4:343–354

    Google Scholar 

  3. Alexandersen P, Haarbo JH, Zandberg P et al. (2003) Lack of difference among progestins on the antiatherogenic effect of ethinyl estradiol: a rabbit study. Hum Reprod 18:1395–1403

    Article  PubMed  Google Scholar 

  4. Anderson GL, Hutchinson F, Limacher M 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  Google Scholar 

  5. Anthony MS (2001) Effects of hormone replacement therapy on atherosclerosis. Thesis, Wake Forest University, Winston-Salem, NC

  6. Basdevant A, Pelissier C, Conard J et al. (1991) Effects of nomegestrol acetate (5 mg/d) on hormonal, metabolic and hemostatic parameters in premenopausal women. Contraception 44:599–605

    Article  PubMed  Google Scholar 

  7. Beier S, Düsterberg B, El Etreby MF et al. (1983) Toxycology of hormonal fertility-regulating agents. In: Benagiano G, Diczfalusy E (eds) Endocrine mechanisms in fertility regulation. Raven Press, New York, pp 261–346

  8. Björn I, Sundström-Poromaa I, Bixo M et al. (2003) Increase of estrogen dose deteriorates mood during progestin phase in sequential hormonal therapy. J Clin Endocrinol Metab 88:2026–2030

    Article  PubMed  Google Scholar 

  9. Brehme U, Bruck B, Gugel N et al. (1999) Aortic plaque size and endometrial response in cholesterol-fed rabbits treated with estrogen plus continuous or sequential progestin. Arterioscler Thromb Vasc Biol 19:1930–1937

    PubMed  Google Scholar 

  10. Clarkson TB, Appt SE (2003) MPA and postmenopausal coronary artery atherosclerosis revisited. Steroids 68:941–951

    Article  PubMed  Google Scholar 

  11. Cline JM, Soderqvist G, Von Schoultz E et al. (1996) Effects of hormone replacement therapy on the mammary gland of surgically postmenopausal cynomolugs macaques. Am J Obstet Gynecol 174:93–100

    Article  PubMed  Google Scholar 

  12. Duc I, Botella J, Bonnet P et al. (1995) Anti-androgenic properties of nomegestrol acetate. Arzneim Forsch Drug Res 45:70–74

    Google Scholar 

  13. Dusterberg B, Humpel M, Speck U (1981) Terminal half-lives in plasma and bioavailability of norethisterone, levonorgestrel, cyproterone acetate and gestodene in rats, beagles and rhesus monkeys. Contraception 24:673–651

    Article  PubMed  Google Scholar 

  14. Ezan E, Benech H, Bucourt R et al. (1993) Enzyme immunoassay for nomegestrol acetate in human plasma. J Steroid Biochem Mol Biol 46:507–514

    Article  PubMed  Google Scholar 

  15. Farmer RDT, Lawrenson RA, Thompson CR et al. (1997) Population-based study of risk of venous thromboembolism associated with various oral contraceptives. Lancet 349:83–88

    Article  PubMed  Google Scholar 

  16. Foidart JM, Wuttke W, Bouw GM et al. (2000) A comparative investigation of contraceptive reliability. Eur J Contracept Reprod Health Care 5:124–134

    PubMed  Google Scholar 

  17. Foster RH (1998) Dienogest. Drugs 56:825–833

    Article  PubMed  Google Scholar 

  18. Fuhmann U, Krattenmacher R, Slater EP, Fritzemeier KH (1996) The novel progestin drospirenone and its natural counterpart progesterone: biochemical profile and anti-androgenic potential. Contraception 54:243–251

    Article  PubMed  Google Scholar 

  19. Grodstein F, Starnpfer MJ, Manson JE et al. (1996) Postmenopausal estrogen and progestin use and the risk of cardiovascular disease. N Engl J Med 335:453–461

    Article  PubMed  Google Scholar 

  20. Grodstein F, Stampfer MS, Colditz GA et al. (1997) Postmenopausal hormone therapy and mortality. N Engl J Med 336:1769–1775

    Article  PubMed  Google Scholar 

  21. Grodstein F, Manson JE, Colditz GA et al. (2000) A prospective, observational study of postmenopausal hormone therapy and primary prevention of cardiovascular disease. Ann Intern Med 133:933–941

    PubMed  Google Scholar 

  22. Hellmann L, Yoshida K, Zumoff B et al. (1976) The effect of medroxyprogesterone acetate on the pituitary-adrenal axis. J Clin Endocrinol Metab 42:912–917

    PubMed  Google Scholar 

  23. Henzl MR, Edwards JA (2000) Pharmacology of progestins: 17α-hydroxyprogesterone derivatives and progestins of the first and second generation. In: Sitruk-Ware R, Mishell Jr DR (eds) Progestins and antiprogestins in clinical practice. Marcel Dekker, New York, pp 101–132

  24. Herkert O, Kuhl H, Sandow J et al. (2001) Sex steroids used in hormonal treatment increase vascular procoagulant activity by inducing thrombin receptor. Circulation 104:2826–2831

    PubMed  Google Scholar 

  25. Huber J, Foidart JM, Wuttke W et al. (2000) Efficacy and tolerability of a monophasic oral contraceptive containing ethinylestradiol and drospirenone. Eur J Contracept Reprod health Care 5:25–34

    Google Scholar 

  26. Hulley S, Grady D, Bush T et al. (1998) Randomized trial for estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. JAMA 280:605–613

    Article  PubMed  Google Scholar 

  27. Jonas HA, Kronmal RA, Psaty BM et al. (1996) Current estrogen-progestin and estrogen replacement therapy in elderly women: association with carotid atherosclerosis. CHS Collaborative Research Group. Cardiovascular Health Study. Ann Epidemiol 6:314–323

    Article  PubMed  Google Scholar 

  28. Kemmeren JM, Algra A, Meijers JCM et al. (2002) Effects of second and third generation oral contraceptives and their respective progestagens on the coagulation system in the absence or presence of factor V leaden mutation. Thromb Haemost 65:187–196

    Article  Google Scholar 

  29. Kuhl H (1996) Comparative pharmacology of newer progestogens. Drugs 51:188–215

    PubMed  Google Scholar 

  30. Kuhl H (2001) Pharmacology of progestogens. Basic aspects — progesterone derivatives. Menopause Rev 6:9–1619

    Google Scholar 

  31. Kuhl H (2005) Pharmacology of estrogens and progestogens: influence of different routes of administration. Climacteric 8 [Suppl 1]:3–63

    Google Scholar 

  32. Kuhnz W, Heuner A, Hümpel M et al. (1997) In vino conversion of norethisterone and norethisterone acetate to ethinyl estradiol in postmenopausal women. Contraception 56:379–385

    Article  PubMed  Google Scholar 

  33. Kumar N, Koide SS, Tsong YY, Sundaram K (2003) Nestorone®: a progestin with a unique pharmacological profile. Steroids 65:629–636

    Article  Google Scholar 

  34. Liang YL, Teede H, Shiel LM et al. (1997) Effects of estrogen and progesterone on age-related changes in arteries of postrnenopausal women. Clin Exp Pharmacol Physiol 24:457–459

    PubMed  Google Scholar 

  35. Lidegaard Ø, Edström B, Kreiner S (2002) Oral contraceptives and venous thromboembolism: a five-year national case-control study. Contraception 65:187–196

    Article  PubMed  Google Scholar 

  36. Manson JE, Hsia J, Johnson KC et al. (2003) Estrogen plus progestin and the risk of coronary heart disease. N Engl J Med 349:523–534

    Article  PubMed  Google Scholar 

  37. Meuwissen JHJM, Beijers-De Bie L, Vihtamaki T et al. (2001) A 1-year comparison of the efficacy and clinical tolerance in postmenopausal women of two hormone replacement therapies containing estradiol in combination with either norgestrel or trimegestone. Gynecol Endocrinol 15:349–358

    PubMed  Google Scholar 

  38. Mikkola TS, Clarkson TB (2002) Estrogen replacement therapy, atherosclerosis, and vascular function. Cardiovasc Res 15:605–619

    Article  Google Scholar 

  39. Noé G, Salvatierra A, Heikinheimo O et al. (1993) Pharmacokinetics and bioavilability of STI1435 administered by different routes. Contraception 48:548–556

    Article  PubMed  Google Scholar 

  40. Oelkers W, Berger V, Bolik A et al. (1991) Dihydrospirorenone, a new progestogen with antimineralocorticoid activity : effects on ovulation, electrolyte excretion, and the reninaldosterone system in normal women. J Clin Endocrinol Metab 73:837–842

    PubMed  Google Scholar 

  41. Oelkers W, Foidart JM, Dombovicz N et al. (1995) Effects of the new oral contraceptive containing an antimineralocorticoid progestogen, drospirenone, on the reninaldosterone system, body weight, blood pressure, glucose tolerance and lipid metabolism. J Clin Endocrinol Metab 80:1816–1821

    Article  PubMed  Google Scholar 

  42. Oettel M. Holz C (2000) Hybrid progestins: the example of dienogest. In: Sitruk-Ware R, Mishell Jr DR (eds) Progestins and anti-progestins in clinical practice. Marcel Dekker, New York, pp 163–178

  43. Paris J, Thevenot R, Bonnet P et al. (1983) The pharmacological profile of TX066 (17ą-acteoxy-6-methyl-19-nor-4,6-pregna-diene-3,20-dione), a new oral progestative. Drug Res 33:710–715

    Google Scholar 

  44. Philibert D, Bouchoux F, Degryse M et al. (1999) The pharmacological profile of a novel norpregnana progestin (trimegestone). Gynecol Endocrinol 13:316–326

    PubMed  Google Scholar 

  45. Pollow K, Jucham N, Elger W et al. (1991) Dihydrospirorenone (ZK30595), a new progestogen with anti-mineralocorticoid activity: effects on ovulation, electrolyte excretion, and the rennin-aldosterone system in normal women. J Clin Endocrinol Metab 73:873–842

    Google Scholar 

  46. Raudaskoski T, Tapanainen J, Tomas E et al. (2002) Intrauterine 10 µg and 20 µg levonorgestrel systems in postmenopausal women receicing oral oestrogen replacement therapy: xlinical, endometrial and metabolic response. Br J Obstet Gynaecol 109:136–144

    Google Scholar 

  47. 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. J Am Med Assoc 288:321–333

    Article  Google Scholar 

  48. Rübig A (2003) Drospirenon: a new cardiovascular-active progestin with antialdosterone and antiandrogenic properties. Climacteric 6 [Suppl 3]:49–54

    Google Scholar 

  49. Schindler AE, Campagnoli A, Druckmann R et al. (2003) Classification and pharmacology of progestins. Maturitas 46 [Suppl 1]:S7–S16

  50. Sitruk-Ware R (2002) Progestogens in hormonal replacement therapy: new molecules, risks, and benefits. Menopause 9:6–15

    Article  PubMed  Google Scholar 

  51. Sitruk-Ware R, Sundaram K (2000) Pharmacology of new progestogens: the 19-norprogesterone derivatives. In: Sitruk-Waer R, Mishell DR (eds) Progestins and antiprogestins in clinical practice. Marcel Dekker, New York, 7:153–161

  52. Stadberg E, Westlund P, Landgren BM et al. (1999) Biovailability of norethisterone acetate alone and in combination with estradiol administered in single or multiple oral doses to postmenopausal women. Maturitas 33:59–69

    Article  PubMed  Google Scholar 

  53. Stampfer MJ, Colditz GA, Willett WC et al. (1991) Postmenopausal estrogen therapy and cardiovascular disease. Ten-year follow-up from the nurses‘ health study. N Engl J Med 325:756–762

    PubMed  Google Scholar 

  54. Tikkanen MJ, Kuusi T, Nikkilä EA et al. (1986) Postmenopausal hormone replacement therapy: effects of progestogens on serum lipids and lipoproteins. A review. Maturitas 8:7–17

    Article  PubMed  Google Scholar 

  55. Tuba Z, Bardin CW, Cancri A et al. (2000) Synthesis and biological activity of a new progestogen, 16-methylene-17a-hydroxy-18-methyl-10-norpregn-4ene-3, 20-dione acetate. Steroids 65:266–274

    Article  PubMed  Google Scholar 

  56. Wahab M, Al-Azzawi F (2001) Trimegestone expanding Therapeutic choices for the treatment of the menopause. Expert Opin Invest Drugs 10:1737–1744

    Article  Google Scholar 

  57. Wiegratz I, Lee JH, Kutschera E et al. (2002) Effect of dienogest-containing oral contraceptives on lipid metabolism. Contraception 65:223–229

    Article  PubMed  Google Scholar 

  58. Williams AK, Honore EK, Washburn SA, Clarkson TB (1994) Effects of hormone replacement therapy on reactivity of atherosclerotic coronary arteries in cynomoglus monkeys. J Am Coll Cardiol 24:1757–1761

    PubMed  Google Scholar 

  59. Williams JK, Cline JM, Honoré EK et al. (1998) Coadministration of nomegestrol acetate does not diminish the beneficial effects of estradiol on coronary artery dilator responses in non human primates. Am J Obstet Gynecol 179:1288–1294

    Article  PubMed  Google Scholar 

  60. Wiseman LR, McTavish D (1994) Transdermal estradiol/norethisterone. A rewiew of its pharmacological properties and clinical use in postmenopausal women. Drugs Aging 4:238–256

    PubMed  Google Scholar 

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  1. Universitäts-Frauenklinik, Inselspital, Bern

    M. Birkhäuser

  2. Abteilung für Gynäkologische Endokrinologie und Reproduktionsmedizin, Universitäts-Frauenklinik, Inselspital, Effingerstrasse 102, 3010, Bern, Schweiz

    M. Birkhäuser

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Birkhäuser, M. Klinische Bedeutung von gestagenen Partialwirkungen. Gynäkologische Endokrinologie 4, 52–64 (2006). https://doi.org/10.1007/s10304-006-0139-8

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