Download PDF
Thromb Haemost 1989; 61(01): 065-069
DOI: 10.1055/s-0038-1646528
Original Article
Schattauer GmbH Stuttgart

A Comparison between Effects of Estradiol Valerate and Low Dose Ethinyl Estradiol on Haemostasis Parameters

U B Lindberg
The Department of Obstetrics and Gynecology and Coagulation Laboratory, Department of Medicine II, Sahlgrenska Hospital, Göteborg, Sweden
,
N Crona
The Department of Obstetrics and Gynecology and Coagulation Laboratory, Department of Medicine II, Sahlgrenska Hospital, Göteborg, Sweden
,
L Stigendal
The Department of Obstetrics and Gynecology and Coagulation Laboratory, Department of Medicine II, Sahlgrenska Hospital, Göteborg, Sweden
,
A C Teger-Nilsson
The Department of Obstetrics and Gynecology and Coagulation Laboratory, Department of Medicine II, Sahlgrenska Hospital, Göteborg, Sweden
,
G Silfverstolpe
The Department of Obstetrics and Gynecology and Coagulation Laboratory, Department of Medicine II, Sahlgrenska Hospital, Göteborg, Sweden
› Author Affiliations
Further Information

Publication History

Received 27 June 1988

Accepted after revision 07 September 1988

Publication Date:
24 July 2018 (online)

  PDF Download  Permissions and Reprints

Summary

Ethinyl estradiol (EE) is still used to some extent as hormonal replacement therapy (HRT) in the climacteric period. As regards oral contraception, it is well known that the induced increase in cardiovascular disease is related to the estrogen component (invariably EE) in a dose-related fashion. Considerably lower doses of EE are needed in HRT compared to oral contraception.

To delineate and compare effects of EE and estradiol valerate (E2V) in doses needed in HRT on haemostasis parameters, 24 postmenopausal women were engaged in a study with an open cross-over design. The doses compared (10 μg EE and 2 mg E2V daily) are the lowest which eliminate climacteric symptoms in a majority of women. Unlike E2V, EE caused increased levels of factor VII: Ag, factor VIII: C and β-thromboglobulin, which may be changes towards hypercoagulability. Both estrogens decreased the AT III activity. Long-term administration (6 + 12 w) of the estrogens induced further changes in haemostatic parameters. 10 μg EE increased factor VII: Ag in contrast to 2 mg E2V. Furthermore both estrogens increased factor VIII :C and factor II-VII-X. A decrease in platelet count was induced by both EE and E2V.

Oral contraception and adjuvant estrogen therapy in men with prostatic carcinoma are known to imply an increased cardiovascular risk. It is noteworthy that the pattern of changes in haemostatic parameters induced by as little as 10 μg of EE is the same as seen after the administration of combined oral contraceptives or the substantially higher doses of EE given as adjuvant therapy to men with prostatic carcinoma.

Key words

Estrogens - Antithrombin III activity - Factor VII: Ag - Factor VIII: C - β-thromboglobulin - Cardiovascular disease
 

  • References

  • 1 Inman WH W, Vessey MP, Westerholm B, Engelund A. Thromboembolic disease and the steroidal content of oral contraceptives. A report to the committee on safety of drugs Br Med J 1970; 2: 203-209
    CrossrefPubMedGoogle Scholar
  • 2 Meade TW, Greenberg G, Thompson SG. Progestogens and cardiovascular reactions associated with oral contraceptives and a comparison of the safety of 50- and 30-μg oestrogen preparations. Br Med J 1980; 280: 1157-1161
    CrossrefPubMedGoogle Scholar
  • 3 Böttiger LE, Boman G, Eklund G, Westerholm B. Oral contraceptives and thromboembolic disease: effects of lowering oestrogen content. Lancet 1980; 1: 1097-1101
    PubMedGoogle Scholar
  • 4 Stamler J. The coronary drug project - findings with regard to estrogen, dextrothyroxine, clofibrate and niacin. Acta Exp Med Biol 1977; 82: 52-75
    PubMedGoogle Scholar
  • 5 McDowell F, Louis S, McDevitt E. A clinical trial of Premarin in cerebrovascular disease. J Chron Dis 1967; 20: 679-684
    CrossrefPubMedGoogle Scholar
  • 6 Ross RK, Paganini-Hill A, Mack TM, Arthur M, Henderson BE. Menopausal oestrogen therapy and protection from death from ischaemic heart disease. Lancet 1981; 1: 858-860
    PubMedGoogle Scholar
  • 7 Colditz GA, Willett WC, Stampfer MJ, Rosner B, Speizer FE, Hennekens CH. Menopause and the risk of coronary heart disease in women. N Engl J Med 1987; 316: 1105-1110
    CrossrefPubMedGoogle Scholar
  • 8 Hardisty RM, Macpherson JC. A one-stage factor VIII (anti- haemophilic globulin) assay and its use on venous and capillary plasma. Thromb Diath Haemorrh 1962; 7: 215-229
    PubMedGoogle Scholar
  • 9 Laurell C-B. Electroimmunoassay. Scand J Clin Lab Invest 1972; 29 suppl (Suppl. 124) 21-37
    CrossrefPubMedGoogle Scholar
  • 10 Amiral J, Adalbert B, Adam M. Application of enzyme immunoassays to coagulation testing. Clin Chem 1984; 30: 1512-1516
    PubMedGoogle Scholar
  • 11 Korsan-Bengtsen K. Comparison between various methods to control dicumarol therapy. Acta Med Scand 1970; 188: 327-335
    PubMedGoogle Scholar
  • 12 Ludlam CA, Moore S, Bolton AE, Pepper DS, Cash JD. The release of a human platelet specific protein measured by a radioimmunoassay. Thromb Res 1975; 6: 543-548
    CrossrefPubMedGoogle Scholar
  • 13 Handin RI, McDonough M, Lesch M. Elevation of platelet factor four in acute myocardial infarction: measurement by radioimmunoassay. J Lab Clin Med 1978; 91: 340-349
    PubMedGoogle Scholar
  • 14 Nilsson IM, Olow B. Determination of fibrinogen and fibrinogenoly- tic activity. Thromb Diath Haemorrh 1962; 8: 297-310
    PubMedGoogle Scholar
  • 15 Abildgaard U, Lie M, Ödegård OR. Antithrombin (heparin cofactor) assay with “new” chromogenic substrates (S-2238 and chromozym TH). Thromb Res 1977; 11: 549-553
    CrossrefPubMedGoogle Scholar
  • 16 Kaplan KL, Owen J. Plasma levels of β-thromboglobulin and platelet factor 4 as indices of platelet activation in vivo. Blood 1981; 57: 199-202
    PubMedGoogle Scholar
  • 17 Boyer C, Wolf M, Rothschild C, Migaud M, Amiral J, Mannucci PM, Meyer D, Larrieu MJ. An enzyme immunoassay (ELISA) for the quantitation of human factor VII. Thromb Haemostas 1986; 56: 250-255
    PubMedGoogle Scholar
  • 18 Bonnar J, Sabra AM. Oral contraceptives and blood coagulation. J Reprod Med 1986; 31: 551-556
    PubMedGoogle Scholar
  • 19 OmsjÖ JH, öian P, österud B. Thromboplastin activity in blood monocytes from oral contraceptive users. Gynecol Obstet Invest 1986; 22: 194-197
    CrossrefPubMedGoogle Scholar
  • 20 Meade TW. Factor VII and ischaemic heart disease: Epidemiological evidence. Haemostasis 1983; 13: 178-185
    PubMedGoogle Scholar
  • 21 Balleisen L, Bailey J, Epping P-H, Schulte H, van de Loo J. Epidemiological study on factor VII, factor VIII and fibrinogen in an industrial population: 1. Baseline data on the relation to age, gender, body-weight, smoking, alcohol, pill-using and menopause. Thromb Haemostas 1985; 54: 475-479
    PubMedGoogle Scholar
  • 22 Poller L, Path FR. Oral contraceptives, blood clotting and thrombosis. Br Med Bull 1978; 34: 151-156
    CrossrefPubMedGoogle Scholar
  • 23 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 Haemostas 1976; 35: 403-414
    PubMedGoogle Scholar
  • 24 Christe M, Delley A, Marbet GA, Biland L, Duckert F. Fibrinogen, factor VIII related antigen, antithrombin III and α2-antiplasmin in peripheral arterial disease. Thromb Haemostas 1984; 52: 240-242
    PubMedGoogle Scholar
  • 25 Sabra A, Bonnar J. Hemostatic system changes induced by 50 μg and 30 μg estrogen/progestogen oral contraceptives. Modification of estrogen effects by levonorgestrel J Reprod Med 1983; 28: 85-91
    PubMedGoogle Scholar
  • 26 Connard J, Cazenave B, Samama M, Horellou MH, Zorn JR, Neau C. AT III content and antithrombin activity in oestrogen-progestogen and progestogen - only treated women. Thromb Res 1980; 18: 675-681
    CrossrefPubMedGoogle Scholar
  • 27 Blombäck M, Hall K, Ritzén M. Estrogen treatment of tall girls: risk of thrombosis?. Pediatrics 1983; 72: 416-419
    PubMedGoogle Scholar
  • 28 Weenink GH, Cate JW, Kahle LH, Lamping RJ, Treffers PE. “Morning-after pill” and antithrombin III. Acta Obstet Gynecol Scand 1983; 62: 359-363
    PubMedGoogle Scholar
  • 29 Barrowcliffe TW, Johnson EA, Thomas D. Antithrombin III and heparin. Br Med Bull 1978; 34: 143-150
    CrossrefPubMedGoogle Scholar
  • 30 Kutti J, Wadenvik H, Johansson S, Vilén L, Vedin A, Wilhelmsson C. The relation between platelet reactivity and coronary angiographic findings in young female survivors of acute myocardial infarction. Thromb Haemostas 1986; 56: 207-210
    PubMedGoogle Scholar
  • 31 Nichols AB, Owen J, Kaplan KL, Sciacca RR, Canaon PJ, Nossel HL. Fibrinopeptide A, platelet factor 4 and β-thromboglobulin levels in coronary heart disease. Blood 1982; 60: 650-654
    PubMedGoogle Scholar
  • 32 Mammen EF. Oral contraceptives and blood coagulation: A critical review. Am J Obstet Gynecol 1982; 142: 781-790
    CrossrefPubMedGoogle Scholar
  • 33 Bush TL, Barret-Connor E, Cowan LD, Criqui MH, Wallace RB, Suchiudran CM, Tyroler HA, Rifkind BM. Cardiovascular mortality and noncontraceptive use of estrogen in women: results from the Lipid Research Clinics Program Follow-up Study. Circulation 1987; 75: 1102-1109
    CrossrefPubMedGoogle Scholar
  • 34 Wilson PW F, Garrison RJ, Castelli PW. Postmenopausal estrogen use, cigarette smoking, and cardiovascular morbidity in women over 50. N Engl J Med 1985; 313: 1038-1043
    CrossrefPubMedGoogle Scholar
  • 35 Lindberg U-B, Crona N, Enk L, Silfverstolpe G. A comparison of the effects of ethinyl estradiol and estradiol valerate on serum and lipoprotein lipids. Maturitas 1988; 10: 343-352
    CrossrefPubMedGoogle Scholar
  • 36 Horseman A, Jones M, Francis R, Nordin C. The effect of estrogen dose on postmenopausal bone loss. N Engl J Med 1983; 309: 1405-1407
    CrossrefPubMedGoogle Scholar