Thromboembolic Events in Girls and Young Women Taking Hormonal Contraception

Czech version

Authors: J. Hyánek; V. Maťoška; L. Dubská; H. Pejznochová; S. Vaingátová; F. Pehal; V. Martiníková; J. Privarová
Authors‘ workplace: Lipidová ambulance a Oddělení klinické biochemie, hematologie a imunologie, Nemocnice na Homolce, Praha prim. MUDr. L. Táborský
Published in: Čes-slov Pediat 2010; 65 (6): 369-383.
Category: Original Papers

Overview

The authors describe their 15 years of experience in the changes of total cholesterol levels in plasma of girls with familial hypercholesterolemia (FH) during menarche. In half of them, regardless of the findings of LDL-receptors mutations, cholesterol level decreases to normal values and does not require medication. Moreover, the authors describe the negative effect of combined hormonal contraception on cholesterolemia during medication treatment, since combined hormonal contraception increases cholesterol level by 1.5–2.5 nmol/l in almost half of the girls, whereas the effects of the levels of HDL cholesterol and triacylglycerols are not so significant.

The authors selected fatal or life-threatening case reports of pulmonary embolism, thromboembolism, brain events, thromboses and phlebothromboses, which occurred in connection with the findings of hereditary thromboembolic mutations (Leiden mutation FV, Prothrombin II, MTHFR), combined with hyperhomocysteinemia, deficit of holotranscobalamin, high Lp(a) and other external risk factors from the group of patients (adolescent girls and young women up to 30 years of age) who attended the lipid outpatient over the last 5 years. All of these patients took combined hormonal contraception for a short or long period of time without being sufficiently advised or examined by the physician.

In conclusion, the authors strongly require a carefully taken anamnesis and at least basic laboratory examination of APCR before combined hormonal contraception medication. Moreover, they draw attention to astounding lack of knowledge of possible unfavorable consequences of combined hormonal contraception in the adolescent girls themselves and, especially, in their mothers, influenced by positive advertisements only.

The bad experience of the authors indicates that the diagnosis if FH is not taken into account when the combined hormonal contraception is indicated; in the selected sad case reports, thrombophilic anamnesis has never been examined in the family and the physicians have not offered sufficient information about the unfavorable effects of combined hormonal contraception, nor were absolute or relative contraindications considered there.

Key words:
familial hypercholesterolemia – therapy, menarche, hyperhomocysteinemia, combined hormonal contraception – complications, thromboembolism, thromboembolic disease, cerebrovascular accident, thrombosis, phlebothrombosis in adolescent girls

Sources

1. Nařízení Vlády ČR č. 149/1994 Sb. Zdravotní řád. Věstník MZČR 1994, část 7, par. 4, odst. 2, písm. c.

2. Marek J, Hána V, Kršek M. Jak ovlivňují kortikoidy, růstový hormon a estrogeny lipidy a aterosklerózu. Vnitř. Lék. 2007;; 53: 386–390.

3. Češka R. Cholesterol a ateroskleróza, léčba dyslipidemií. Praha: Triton, 2005.

4. Campos H, Sacks FM, Walsh BW, Schiff I. Differential effects of estrogen on low-density lipoprotein subclasses in healthy menopausa women. Metabolism 1993;; 42: 1153–1158.

5. Giri S, Thompson P-D, Taxel P, et al. Oral estrogen improves serum lipids, homocysteine and fibrinolysis in eldery men. Atherosclerosis 1998;; 137: 359–665.

6. Spenser TA, Chai H, Fu W, et al. Estrogen bloc homocysteine-induced endothelial dysfunction in porcine coronary arteries. J. Surg. Res. 2004;; 118: 83–90.

7. Sack MN, Rader DJ, Cannon RO. Estrogen and inhibition of low-density lipoproteins in postmenopauzal women. Lancet 1994;; 343: 269–270.

8. Fait T. Antikoncepce. Praha: Jesenius Maxdorf, 2008.

9. Fanta M. Kontraceptiva v gynekologické praxi. Klin. farm. Farmakol. 2008;; 22: 149–151.

10. WHO Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception: Acute myocardial infarction and combined oral contraceptives: Results of an international multicentre case-control study. Lancet 1997;; 349: 102–109.

11. Improving access to quality care in family planning. Medical eligibility criteria for contraceptives. WHO 2000. http://www.who.int/reproduction-health/publications/index.html.

12. Čepický P, Cibula D, Dvořák K, et al. Doporučení k předpisu kombinované hormonální kontracepce. Čs. Gynekol. 2005;; 70: 320–324.

13. Plu-Bureau G, Horellou MH, Gompel A, Conard J. Hormonal contraception and risk of venous thromboembolism: When to ask for an assessment of hemostasis? Which parameters? Gynecol. Obst. Fertilité 2008: 448–454.

14. Van Lunsen RHW, Unzeitig V, Creatsas G. Contraceptive choises and realities. New York, London: The Parthenon Publ. Group, 2000: 79–82.

15. Inman WHW, Vessey MP, Westerholm B. Thromboembolic disease and the steroidal content of oral contraceptives: A report to the Committee on Safety of Drugs. BMJ 1970;;2: 203–289.

16. Meade TW. Risks and mechanisms of cardiovascular events in users of oral contraceptives. Am. J. Obstet. Gynecol. 1988;;158: 1646–1652.

17. Ramakrishnan G, Rana A, Das Ch, Chandra NC. Study of low-density lipoprotein regulation by oral (steroid) contraceptives: desogestrel, levonorgestrel and ethinyl estradiol in JEG-03 cell line and placenta tissue. Contraception 2007;;76: 297–305.

18. Cushman M, Kuller LH, Prentice R, et al. Estrogen plus progestin and risk of venous thrombosis. JAMA 2004;;295: 1573–1580.

19. Mammen EF. Oral contraceptive pills and hormonal replacement therapy and thromboembolic disease. Hematologic Probleme in Obstetrics, Pregnancy, Gynecol. 2000;; 14: 1045–1059.

20. Pernod G, Biron-Aadreani C, Morange PE, et al. Reccommendations on testing for thrombophilia in venous thromboembolic diseases: a French consensus guideline. J. Malad. Vasc. 2009; 34: 156–203.

21. Fruzzetti F, Giannessi D, Ricci C, et al. Platelet-vessel wall interactions with third-generation oral contraceptives: no evidence of detrimental effects. Thromb. Haemost. 1999; 82: 1164–1170.

22. Kvasnička J. Tromboembolie a tromboembolické stavy v klinické praxi. Praha: Grada Avicenum, 2003: 37–65.

23. Roušová E, Hadačová I, Macek M. Hereditární trombofilie – jeden z modelů molekulární medicíny. Klin. Biochem. Metab. 2005; 13: 68–76.

24. Blickstein I. Thrombophilia and women´s health. An overview. Obstet. Gynecol. Clin. N. Am. 2006; 33: 347–356.

25. Khajuria A, Houston DS. Induction of monocyte tissue factor expression by homocysteine: a possible mechanism for thrombosis. Hemostasis, Tromb. Vasc. Biol. 2000; 96: 966–972.

26. Greaves M. Antiphospholipid antibodies and thrombosis. Lancet 1999; 353: 1348–1353.

27. Galajda P, Mokáň M. Nový model homeostázy a problematika aterosklerózy. Ateroskleróza 2001;;5: 143–151.

28. Durand P, Prost M, Blanche D. Folic acid deficienty enhances oral contraceptive-induced platelet hyperacidity. Atheroscler. Thromb. Vasc. Biol. 1997; 17: 1939–1946.

29. Guba SC, Fonseca V, Fink LM. Hyperhomocysteinemia and thrombosis. Semin. Thromb. Hemost. 1999; 25: 291–310.

30. Dulíček P, Kalousek P, Malý J. Hormonální antikoncepce a trombofilická nemoc – jak je to ve skutečnosti? Intern. Med. 2002; 4: 4–8.

31. Dardik R, Varon D, Tamarin A, et al. Homocysteine and oxidized LDL lipoproteid enhance platelet adhesion to endothelial cells under flow conditions: distinct mechanisms of thrombogenic modulation. Thromb. Hemost. 2000; 83: 338–344.

32. Caplice NM, Panetta C, Peterson T, et al. Lipoprotein(a) binds and inactivates tissue factor pathway inhibitor: a novel link between lipoproteins and thrombosis. Blood 1989; 98: 2980–2987.

33. Chapman JM, Huly T, Migon JE, et al. Lipoprotein(a): implication in atherosclerosis. Atherosclerosis 1994; 110: 69–75.

34. Blickstein D. Screening for thrombophilia. Obstet. Gynecol. Clin. N. Am. 2006; 33: 389–395.

35. Hyánek J, Martiníková V, Matoška V, et al. Desetileté zkušenosti s medikamentózní léčbou familiární hypercholesterolémie u dětí a adolescentů. Čes.-slov. Pediat. 2002; 57: 404–412.

36. McCrindle BW, Urbina EM, Dennison BA, et al. Drug therapy of high-risk lipid abnormalities in children and adolescents: A scientific statement from the AHA atherosclerosis, hypertension, and obesity in youth committee, council of cardiovacular disease in the young, with the council on cardiovascular nursing. Circulation 2007; 115: 1948–1967.

37. Baass A, Dubrec G, Tremblay M, et al. Plasma PCSK9 is associated with age, sex and multiple metabolic markers in a population based sample of children and adolescents. Clin. Chem. 2009; 55: 1637–1645.

38. Odlind V, Misoma I, Persson I, et al. Can change in sex hormones binding globulin predict the risk of venous thromboembolism with combined oral contraception pills? Acta Obstet. Gynecol. Scand. 2002; 81: 482–490

39. Rozendal FR. Oral contraceptives and screening for Factor V Leiden. Thromb. Haemost. 1996; 75: 524–525.

40. Creinin M-D, Lisman R, Strickler RC. Screening for factor V Leiden mutation before prescribing combination oral contraceptives. Fertil. Steril. 1996; 72: 646–651.

41. Dietrich JE, Yee DL. Thrombophilic conditions in the adolescent: the gynecologic impact. Obstet. Gynecol. Clin. N. Am. 2009; 36: 163–175.

42. Chroustová D, Krátká K, Palyzová D, Patr R. Výskyt plicní embolizace u mladých dívek ve věku 15–25 let z hlediska používání hormonální perorální antikoncepce. Výsledky 5leté studie. Prakt. Lék. 2009; 89: 439–443.

43. Hadačová I. Žilní trombóza a hormonální antikoncepce. Čes.-slov. Pediat. 2008; 63: 383.

44. Šmirová S, Chochola M, Vařejka P, Ascherman M. Tromboembolické komplikace užívání orální estrogen-gestagenní antikoncepce. Vnitř. Lék. 2001; 47: 460–464.

45. Wu O, et al. Screening for thrombophilia in high risk situations: a metaanalysis and cost effectiveness. Br. J. Haematol. 2005; 131: 82–90.

Labels

Neonatology Paediatrics General practitioner for children and adolescents

Hydroa vacciniforme

Risk of Hormonal Contraceptives in Adolescent Girls

Inherited Thrombophilic Tendencies and Oral Contraceptive Pills

Rapidly Progressive Complications of the Influenza A Type in Children

Methotrexate in Children with Juvenile Idiopathic Arthritis

Body Temperature and Thermoregulation in the Newborn

Article was published in

Czech-Slovak Pediatrics

2010 Issue 6