PDF herunterladen
Thromb Haemost 1994; 72(06): 926-930
DOI: 10.1055/s-0038-1648985
Original Article
Schattauer GmbH Stuttgart

Effect of Oestrogen Dose on Whole Blood Platelet Activation in Women Taking New Low Dose Oral Contraceptives

Lucy A Norris
The Department of Obstetrics and Gynaecology, Trinity College Medical School, St. James’s Hospital, Dublin, Ireland
,
John Bonnar
The Department of Obstetrics and Gynaecology, Trinity College Medical School, St. James’s Hospital, Dublin, Ireland
› Institutsangaben
Weitere Informationen

Publikationsverlauf

Received 28. März 1994

Accepted after resubmission 08. August 1994

Publikationsdatum:
26. Juli 2018 (online)

Auch verfügbar auf
  als PDF herunterladen  Lizenzen und Reprints

Summary

Oral contraceptive use is known to cause changes in the haemostatic system. These changes are thought to be related to oestrogen dose and to provide a possible link between the increased risk of thromboembolic disease known to occur in women taking oestrogen containing oral contraceptives. This study measured whole blood platelet activation, serially, in women taking oral contraceptives containing 20 μg and 30 μg ethinyloestradiol combined with desogestrel. Increased levels of ADP and arachidonic acid induced aggregation were observed in women taking the 30 μg ethinyloestradiol combination. Platelet release of β-thromboglobulin (βTG) was also significantly increased. Increased collagen induced aggregation was observed but this failed to reach statistical significance for the individual treatment groups. In women taking the 20 μg ethinyloestradiol combination, a significant increase was only observed when platelets were stimulated with arachidonic acid. Platelet factor 4 (PF4) levels were unchanged in both groups. Significantly higher levels of βTG were observed in women taking the 30 μg ethinyloestradiol combination compared with women taking the 20 μg ethinyloestradiol combination. These results show that oral contraceptive use is associated with platelet activation. Women taking the 20 μg ethinyloestradiol combination show less changes in platelet activation than women taking the 30 μg ethinyloestradiol combination. This lower dose pill may therefore be particularly suitable for high risk women wishing to use oral contraception.

 

  • References

  • 1 Vessey MP, Villard-Mackintosh L, McPherson K, Yeates D. Mortality among oral contraceptive users: 20 year follow-up study of women in a cohort study. Br Med J 1989; 299: 1487-1491
    CrossrefPubMedGoogle Scholar
  • 2 Thorogood M, Vessey M. An epidemiological survey of cardiovascular disease in women taking oral contraceptives. Am J Obstet Gynecol 1990; 163: 274-291
    CrossrefPubMedGoogle Scholar
  • 3 Hirvonen E, Idanpaan-Heikkila J. Cardiovascular death among women under 40 years of age using low dose oestrogen oral contraceptives and intra-uterine devices in Finland from 1975-1984. Am J Obstet Gynecol 1990; 163: 281-284
    CrossrefPubMedGoogle Scholar
  • 4 Lidegaard O. Oral contraception and risk of a cerebral thromboembolic attack: results of a case-control study. Br Med J 1993; 306: 956-963
    CrossrefPubMedGoogle Scholar
  • 5 Meade TW, Greenberg G, Thomson SG. Progestogens and cardiovascular reactions associated with oral contraceptives and a comparison of the safety of 50 ug and 30 ug oestrogen preparations. Br Med J 1980; 280: 1157-1161
    CrossrefPubMedGoogle Scholar
  • 6 Royal College of General Practitioners Oral Contraceptive Study. Recommendations from the findings of the RCGP oral contraceptive study on the mortality risks of oral contraceptive users. Br Med J 1977; 2: 947-948
    CrossrefPubMedGoogle Scholar
  • 7 Thomson JM, Poller L. Oral contraceptive hormones and blood coagulation. BrMed J 1965; 2: 270-273
    PubMedGoogle Scholar
  • 8 Poller L, Tabiowo A, Thomson JM. Platelet aggregation during oral contraception. Br Med J 1968; 3: 218-219
    CrossrefPubMedGoogle Scholar
  • 9 Sabra A, Bonnar J. Haemostatic changes induced by 50 ug and 30 ug oestrogen/progestogen oral contraceptives. J Rep Med 1983; 28 (01) 85-91
    PubMedGoogle Scholar
  • 10 Kunz F, Pechlaner C, Tabarelli M, Solder E, Zwierzina WD. Influence of oral contraceptives on coagulation tests in native blood and plasma. Am J Obstet Gynecol 1990; 163: 417-420
    CrossrefPubMedGoogle Scholar
  • 11 McGrath KM, Castaldi PA. Changes in coagulation factors and platelet function in response to progestational agents. Haemostasis 1975; 4: 65-72
    PubMedGoogle Scholar
  • 12 Sadurska B, Taccioni MT, di Minno G, Roncaglioni MC, Pangrazzi J, Donati MB, Bizzi A, Silver MJ. Plasma and platelet lipid composition and platelet aggregation by arachidonic acid in women on the pill. Thromb Haemost 1981; 45: 150-153
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 13 Daly L, Bonnar J. Comparative studies of 30 ug ethinyloestradiol combined with gestogene and desogestrel on blood coagulation, fibrinolysis and platelets. Am J Obstet Gynecol 1990; 163: 430-437
    CrossrefPubMedGoogle Scholar
  • 14 Shevde N, Sussman II, Rossner F, Pacholuk V. Oral contraceptives and platelet aggregation. Am J Obstet Gynecol 1978; 132: 303-306
    CrossrefPubMedGoogle Scholar
  • 15 Poller L, Priest CM, Thomson JM, Thomas W, Wray C. Blood clotting and platelet aggregation during oral progestogen contraception: a follow-up study. Br Med J 1971; 1: 705-707
    CrossrefPubMedGoogle Scholar
  • 16 Farag AM, Bottoms SF, Mammen EF, Hosni MA, Ali AA, Moghissi KS. Oral contraceptives and the haemostatic system. Obstet Gynecol 1988; 71: 584-588
    PubMedGoogle Scholar
  • 17 Fox SC, Burgess-Wilson M, Heptinstall S, Mitchell JRA. Platelet aggregation in whole blood determined using the Ultra-Flo-100 platelet counter. Thromb Haemost 1982; 48 (03) 327-329
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 18 Reiss H, Braun G, Brehm G, Hiller G. Critical evaluation of platelet aggregation in whole human blood. Am J Clin Path 1986; 85: 50-56
    CrossrefPubMedGoogle Scholar
  • 19 Lad N, Lunt DO, Tuffin DP. The effect of thromboxane A2 synthetase inhibitors on platelet aggregation in whole blood. Thromb Res 1987; 46: 555-566
    CrossrefPubMedGoogle Scholar
  • 20 Falcon C, Amout J, Vermylen J. Platelet aggregation in whole blood: studies with a particle counting technique-methodological applications and some applications. Thromb Haemost 1989; 61: 423-428
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 21 Norris LA, Bonnar J. The in vitro effect of aspirin on increased whole blood platelet aggregation in oral contraceptive users. Thromb Res 1994; 74 (03) 309-315
    CrossrefPubMedGoogle Scholar
  • 22 Norris LA, Bonnar J. Effect of oestrogen dose on haemostatic changes in oral contraceptive users. Ir J Med Sci 1993; 162 (Suppl. 02) 33
    CrossrefPubMedGoogle Scholar
  • 23 Ludlam CA, Moore S, Bolton AE, Pepper DS, Cash JD. Release of a human platelet specific protein measured by radioimmunoassay\. Thromb Res 1975; 6: 543-548
    CrossrefPubMedGoogle Scholar
  • 24 Kaplan KL, Owen J. Radioimmunoassay of platelet factor 4. Methods in Enzymology 1982; 84 (06) 83-93
    PubMedGoogle Scholar
  • 25 Notelovitz M, Kitchens CS, Khan FY. Changes in coagulation and anticoagulation in women taking low dose triphasic oral contraceptives: A controlled comparative 12-month clinical trial. Am J Obstet Gynecol 1992; 167: 1255-1261
    CrossrefPubMedGoogle Scholar
  • 26 Cohen H, Mackie IJ, Walshe K, Gillmer MDG, Machin SJ. A comparison of the effects of two triphasic oral contraceptives on haemostasis. Br J Haematol 1988; 69: 259-263
    CrossrefPubMedGoogle Scholar
  • 27 Meade TW. Oral contraceptives, clotting factors and thrombosis. Am J Obstet Gynecol 1982; 142: 758-761
    CrossrefPubMedGoogle Scholar
  • 28 Gevers LeuvenJA, Kluft C, Bertina RM, Hessel LW. Effects of two low-dose oral contraceptives on circulating components of the coagulation and fibrinolytic systems. J Lab Clin Med 1987; 109: 631-636
    PubMedGoogle Scholar
  • 29 Inauen W, Baumgartner HR, Haeberli H, Straub PW. Excessive deposition of fibrin, platelets and platelet thrombi on vascular subendothelium during contraceptive drug treatment. Thromb Haemost 1987; 57 (03) 306-309
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 30 Bolton CH, Hampton JR, Mitchell JRA. Effect of oral contraceptive agents on platelets and plasma phospholipids. Lancet 1968; i: 1336-1340
    PubMedGoogle Scholar
  • 31 Eckles RS, Hampton JR, Mitchell JRA. Effect of oestrogen on human platelet behavioure. Lancete 1968; ii: 315-318
    PubMedGoogle Scholar
  • 32 Poller L, Priest CM, Thomson JM. Platelet aggregation during oral contraceptione. Br Med J 1969; 4: 273-274
    CrossrefPubMedGoogle Scholar
  • 33 Davies T, Fieldhouse G, McNicol GP. The effects of therapy with oestriol succinate and ethinyl oestradiol on the haemostatic mechanism in post menopausal women. Thromb Haemost 1976; 35: 403-414
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 34 Nordoy A, Svensson B, Haycraft D, Hoak JC, Wiebe D. The influence of age, sex and the use of oral contraceptives on the inhibitory effects of endothelial cells and prostacyclin on platelet function. Scan J Haematol 1978; 21: 177-187
    PubMedGoogle Scholar
  • 35 Ylikorkala O, Kuusi T, Tikkanen MJ, Viinika L. Desogestrel and levonor-gestrel containing oral contraceptives have different effects on urinary excretion of prostacyclin metabolites and serum high density lipoproteins. J Clin Endocrinol Metab 1987; 65: 1238-1242
    CrossrefPubMedGoogle Scholar
  • 36 Schorer AE, Gerrard JM, White JG, Krivit W. Oral contraceptive use alters the balance of platelet prostaglandins and thromboxane A2 synthesis. Prostaglandins and Medicine 1978; 1: 5-11
    CrossrefPubMedGoogle Scholar
  • 37 Elam MB, Lipscomb GE, Chesney CM, Terragno TA. Effect of synthetic oestrogen on platelet aggregation and vascular release of prostacyclin-like material in the rabbit. Prostaglandins 1980; 20: 1039-1051
    CrossrefPubMedGoogle Scholar
  • 38 Ylikorkala O, Poulakka J, Viinikka L. The effect of oral contraceptives on anti-aggregatory prostacyclin and thromboxane A4 in humans. Am J Obstet Gynecol 1982; 142: 573-576
    CrossrefPubMedGoogle Scholar
  • 39 Sinzinger H, Klein K, Kaliman J, Silberbauer K, Feigl W. Enhanced prostacyclin formation in veins of women under chronic treatment with oral contraceptive drugs. Pharmacol Res Commun 1980; 12: 515-521
    CrossrefPubMedGoogle Scholar
  • 40 Pan J-QI, Hall ER, Wu KK. Alteration of platelet responses to metabolites of arachidonic acid by oral contraceptives. Br J Haem 1984; 58: 317-323
    CrossrefPubMedGoogle Scholar
  • 41 Aranda M, Saez M, Abril V, Carrach J, Castells E, Castellanos JM. β-thromboglobulin and oral contraception. Lancet 1979; ii: 308-309
    PubMedGoogle Scholar
  • 42 Huch KM, Elam MB, Chesney CM. Oral contraceptive steroid induced platelet coagulant hyperactivity: dissociation of in vivo and in vitro events. Thromb Res 1987; 48: 41-50
    CrossrefPubMedGoogle Scholar
  • 43 Needleman SW, Stump DC, Cohen DP. Catecholoestrogens and thrombosis lack of direct effect of 2-hydroxy-estradiol on platelets. Contraception 1982; 25: 185-189
    CrossrefPubMedGoogle Scholar
  • 44 Poller L, Thomson JM, Thomas PW. Effects of progestogen oral contraception with norethisterone on blood clotting and platelets. Br Med J 1972; 4: 391-393
    CrossrefPubMedGoogle Scholar
  • 45 Melis GB, Frussetti F, Nicoletti N, Ricci C, Lammers P, Atsma WJ, Fioretti P. A comparative study of the effects of a monophasic pill containing desogestrel plus 20 ug ethinyloestradiol, a triphasic combination containing gestodene on coagulatory factors. Contraception 1991; 43 (01) 23-31
    CrossrefPubMedGoogle Scholar
  • 46 Stadel BV. Oral contraceptives and cardiovascular diseasee. N Engl J Med 1981; 305: 672-677
    CrossrefPubMedGoogle Scholar