Smarter Decisions,
Better Care

UpToDate synthesizes the most recent medical information into evidence-based practical recommendations clinicians trust to make the right point-of-care decisions.

  • Rigorous editorial process: Evidence-based treatment recommendations
  • World-Renowned physician authors: over 5,100 physician authors and editors around the globe
  • Innovative technology: integrates into the workflow; access from EMRs

Choose from the list below to learn more about subscriptions for a:


Subscribers log in here


Related articles

Risks and side effects associated with estrogen-progestin contraceptives

INTRODUCTION

Oral contraceptives (OCs) are a reliable form of contraception with a theoretical failure rate of 0.1 percent and, due to problems with compliance, an actual failure rate of 2 to 3 percent. They also have noncontraceptive benefits, being useful in the treatment of a variety of disorders including hyperandrogenism, dysmenorrhea, and menorrhagia. Currently available preparations are shown in the table (table 1). There are, however, several contraindications to their use. (See "Overview of the use of estrogen-progestin contraceptives".)

Concern about toxicity (such as thromboembolic events and cardiovascular disease) initially limited the long-term use of these drugs. However, the decrease in both estrogen and progestin content since the introduction of the pill in 1960 has led to a reduction in both side effects and cardiovascular complications [1]. As a result, these preparations are a reasonable contraceptive option for most women.

While the US Food and Drug Administration (FDA) had previously set upper age limits for OC use as 35 years for smokers and 40 years for nonsmokers, the age limit was removed in 1989 for healthy, nonsmoking women. Thus, OCs can be given until menopause in such women. Caution is still needed in prescribing OCs for women who smoke and an effort to induce smoking cessation should be made first.

Certain forms of toxicity remain a concern. This topic will review the side effects and major potential risks associated with OC administration. The noncontraceptive benefits of estrogen-progestin contraceptives and other types of contraception are reviewed separately. (See "Overview of the use of estrogen-progestin contraceptives", section on 'Noncontraceptive benefits' and "Overview of contraception".)

SIDE EFFECTS

Early side effects of oral contraceptives (OCs) include bloating, nausea, and breast tenderness [2]. Although they may be bothersome enough to lead to discontinuation of the OC, these side effects usually subside in several months. Abnormal bleeding is a common problem that often resolves. Weight gain is not a consistent finding with low-dose pills. (See 'Weight' below.)

                                                       

Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Sep 2014. | This topic last updated: Jul 28, 2014.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2014 UpToDate, Inc.
References
Top
  1. Petitti DB. Clinical practice. Combination estrogen-progestin oral contraceptives. N Engl J Med 2003; 349:1443.
  2. Rosenberg MJ, Waugh MS, Meehan TE. Use and misuse of oral contraceptives: risk indicators for poor pill taking and discontinuation. Contraception 1995; 51:283.
  3. ESHRE Capri Workshop Group, Collins J, Crosignani PG. Endometrial bleeding. Hum Reprod Update 2007; 13:421.
  4. Endrikat J, Gerlinger C, Plettig K, et al. A meta-analysis on the correlation between ovarian activity and the incidence of intermenstrual bleeding during low-dose oral contraceptive use. Gynecol Endocrinol 2003; 17:107.
  5. Rosenberg MJ, Waugh MS, Stevens CM. Smoking and cycle control among oral contraceptive users. Am J Obstet Gynecol 1996; 174:628.
  6. Lawrie TA, Helmerhorst FM, Maitra NK, et al. Types of progestogens in combined oral contraception: effectiveness and side-effects. Cochrane Database Syst Rev 2011; :CD004861.
  7. Jacobs HS, Knuth UA, Hull MG, Franks S. Post-"pill" amenorrhoea--cause or coincidence? Br Med J 1977; 2:940.
  8. Davis AR, Kroll R, Soltes B, et al. Occurrence of menses or pregnancy after cessation of a continuous oral contraceptive. Fertil Steril 2008; 89:1059.
  9. Chasan-Taber L, Stampfer MJ. Epidemiology of oral contraceptives and cardiovascular disease. Ann Intern Med 1998; 128:467.
  10. Stadel BV. Oral contraceptives and cardiovascular disease (first of two parts). N Engl J Med 1981; 305:612.
  11. Further analyses of mortality in oral contraceptive users. Royal College of General Practitioners' Oral Contraception Study. Lancet 1981; 1:541.
  12. Lidegaard Ø, Løkkegaard E, Jensen A, et al. Thrombotic stroke and myocardial infarction with hormonal contraception. N Engl J Med 2012; 366:2257.
  13. Croft P, Hannaford PC. Risk factors for acute myocardial infarction in women: evidence from the Royal College of General Practitioners' oral contraception study. BMJ 1989; 298:165.
  14. Rosenberg L, Palmer JR, Rao RS, Shapiro S. Low-dose oral contraceptive use and the risk of myocardial infarction. Arch Intern Med 2001; 161:1065.
  15. Petitti DB. Hormonal contraceptives and arterial thrombosis--not risk-free but safe enough. N Engl J Med 2012; 366:2316.
  16. Lewis MA, Spitzer WO, Heinemann LA, et al. Third generation oral contraceptives and risk of myocardial infarction: an international case-control study. Transnational Research Group on Oral Contraceptives and the Health of Young Women. BMJ 1996; 312:88.
  17. Dunn N, Thorogood M, Faragher B, et al. Oral contraceptives and myocardial infarction: results of the MICA case-control study. BMJ 1999; 318:1579.
  18. Tanis BC, van den Bosch MA, Kemmeren JM, et al. Oral contraceptives and the risk of myocardial infarction. N Engl J Med 2001; 345:1787.
  19. Baillargeon JP, McClish DK, Essah PA, Nestler JE. Association between the current use of low-dose oral contraceptives and cardiovascular arterial disease: a meta-analysis. J Clin Endocrinol Metab 2005; 90:3863.
  20. Schiff I, Bell WR, Davis V, et al. Oral contraceptives and smoking, current considerations: recommendations of a consensus panel. Am J Obstet Gynecol 1999; 180:S383.
  21. Stampfer MJ, Willett WC, Colditz GA, et al. A prospective study of past use of oral contraceptive agents and risk of cardiovascular diseases. N Engl J Med 1988; 319:1313.
  22. Merz CN, Johnson BD, Berga S, et al. Past oral contraceptive use and angiographic coronary artery disease in postmenopausal women: data from the National Heart, Lung, and Blood Institute-sponsored Women's Ischemia Syndrome Evaluation. Fertil Steril 2006; 85:1425.
  23. Chasan-Taber L, Willett WC, Manson JE, et al. Prospective study of oral contraceptives and hypertension among women in the United States. Circulation 1996; 94:483.
  24. Curtis KM, Chrisman CE, Peterson HB, WHO Programme for Mapping Best Practices in Reproductive Health. Contraception for women in selected circumstances. Obstet Gynecol 2002; 99:1100.
  25. Ischaemic stroke and combined oral contraceptives: results of an international, multicentre, case-control study. WHO Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception. Lancet 1996; 348:498.
  26. Haemorrhagic stroke, overall stroke risk, and combined oral contraceptives: results of an international, multicentre, case-control study. WHO Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception. Lancet 1996; 348:505.
  27. Heinemann LA, Lewis MA, Thorogood M, et al. Case-control study of oral contraceptives and risk of thromboembolic stroke: results from International Study on Oral Contraceptives and Health of Young Women. BMJ 1997; 315:1502.
  28. Petitti DB, Sidney S, Bernstein A, et al. Stroke in users of low-dose oral contraceptives. N Engl J Med 1996; 335:8.
  29. Schwartz SM, Siscovick DS, Longstreth WT Jr, et al. Use of low-dose oral contraceptives and stroke in young women. Ann Intern Med 1997; 127:596.
  30. Siritho S, Thrift AG, McNeil JJ, et al. Risk of ischemic stroke among users of the oral contraceptive pill: The Melbourne Risk Factor Study (MERFS) Group. Stroke 2003; 34:1575.
  31. Oral contraceptives and stroke in young women. Associated risk factors. JAMA 1975; 231:718.
  32. Gillum LA, Mamidipudi SK, Johnston SC. Ischemic stroke risk with oral contraceptives: A meta-analysis. JAMA 2000; 284:72.
  33. Kemmeren JM, Tanis BC, van den Bosch MA, et al. Risk of Arterial Thrombosis in Relation to Oral Contraceptives (RATIO) study: oral contraceptives and the risk of ischemic stroke. Stroke 2002; 33:1202.
  34. Chan WS, Ray J, Wai EK, et al. Risk of stroke in women exposed to low-dose oral contraceptives: a critical evaluation of the evidence. Arch Intern Med 2004; 164:741.
  35. Peragallo Urrutia R, Coeytaux RR, McBroom AJ, et al. Risk of acute thromboembolic events with oral contraceptive use: a systematic review and meta-analysis. Obstet Gynecol 2013; 122:380.
  36. Bushnell C, McCullough LD, Awad IA, et al. Guidelines for the prevention of stroke in women: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2014; 45:1545.
  37. Slooter AJ, Rosendaal FR, Tanis BC, et al. Prothrombotic conditions, oral contraceptives, and the risk of ischemic stroke. J Thromb Haemost 2005; 3:1213.
  38. Urbanus RT, Siegerink B, Roest M, et al. Antiphospholipid antibodies and risk of myocardial infarction and ischaemic stroke in young women in the RATIO study: a case-control study. Lancet Neurol 2009; 8:998.
  39. Porter JB, Hunter JR, Jick H, Stergachis A. Oral contraceptives and nonfatal vascular disease. Obstet Gynecol 1985; 66:1.
  40. Vandenbroucke JP, Rosing J, Bloemenkamp KW, et al. Oral contraceptives and the risk of venous thrombosis. N Engl J Med 2001; 344:1527.
  41. Kujovich JL. Hormones and pregnancy: thromboembolic risks for women. Br J Haematol 2004; 126:443.
  42. Gomes MP, Deitcher SR. Risk of venous thromboembolic disease associated with hormonal contraceptives and hormone replacement therapy: a clinical review. Arch Intern Med 2004; 164:1965.
  43. Douketis JD, Ginsberg JS, Holbrook A, et al. A reevaluation of the risk for venous thromboembolism with the use of oral contraceptives and hormone replacement therapy. Arch Intern Med 1997; 157:1522.
  44. Bloemenkamp KW, Rosendaal FR, Büller HR, et al. Risk of venous thrombosis with use of current low-dose oral contraceptives is not explained by diagnostic suspicion and referral bias. Arch Intern Med 1999; 159:65.
  45. Sidney S, Petitti DB, Soff GA, et al. Venous thromboembolic disease in users of low-estrogen combined estrogen-progestin oral contraceptives. Contraception 2004; 70:3.
  46. Pomp ER, le Cessie S, Rosendaal FR, Doggen CJ. Risk of venous thrombosis: obesity and its joint effect with oral contraceptive use and prothrombotic mutations. Br J Haematol 2007; 139:289.
  47. Abdollahi M, Cushman M, Rosendaal FR. Obesity: risk of venous thrombosis and the interaction with coagulation factor levels and oral contraceptive use. Thromb Haemost 2003; 89:493.
  48. Nightingale AL, Lawrenson RA, Simpson EL, et al. The effects of age, body mass index, smoking and general health on the risk of venous thromboembolism in users of combined oral contraceptives. Eur J Contracept Reprod Health Care 2000; 5:265.
  49. Spitzer WO, Lewis MA, Heinemann LA, et al. Third generation oral contraceptives and risk of venous thromboembolic disorders: an international case-control study. Transnational Research Group on Oral Contraceptives and the Health of Young Women. BMJ 1996; 312:83.
  50. Effect of different progestagens in low oestrogen oral contraceptives on venous thromboembolic disease. World Health Organization Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception. Lancet 1995; 346:1582.
  51. Jick H, Jick SS, Gurewich V, et al. Risk of idiopathic cardiovascular death and nonfatal venous thromboembolism in women using oral contraceptives with differing progestagen components. Lancet 1995; 346:1589.
  52. Lidegaard Ø, Løkkegaard E, Svendsen AL, Agger C. Hormonal contraception and risk of venous thromboembolism: national follow-up study. BMJ 2009; 339:b2890.
  53. Kemmeren JM, Algra A, Grobbee DE. Third generation oral contraceptives and risk of venous thrombosis: meta-analysis. BMJ 2001; 323:131.
  54. Suissa S, Blais L, Spitzer WO, et al. First-time use of newer oral contraceptives and the risk of venous thromboembolism. Contraception 1997; 56:141.
  55. Farmer RD, Lawrenson RA, Thompson CR, et al. Population-based study of risk of venous thromboembolism associated with various oral contraceptives. Lancet 1997; 349:83.
  56. Lidegaard Ø, Nielsen LH, Skovlund CW, et al. Risk of venous thromboembolism from use of oral contraceptives containing different progestogens and oestrogen doses: Danish cohort study, 2001-9. BMJ 2011; 343:d6423.
  57. Rosing J, Tans G, Nicolaes GA, et al. Oral contraceptives and venous thrombosis: different sensitivities to activated protein C in women using second- and third-generation oral contraceptives. Br J Haematol 1997; 97:233.
  58. Rosing J, Middeldorp S, Curvers J, et al. Low-dose oral contraceptives and acquired resistance to activated protein C: a randomised cross-over study. Lancet 1999; 354:2036.
  59. Middeldorp S, Meijers JC, van den Ende AE, et al. Effects on coagulation of levonorgestrel- and desogestrel-containing low dose oral contraceptives: a cross-over study. Thromb Haemost 2000; 84:4.
  60. Kemmeren JM, Algra A, Meijers JC, et al. Effects of second and third generation oral contraceptives and their respective progestagens on the coagulation system in the absence or presence of the factor V Leiden mutation. Thromb Haemost 2002; 87:199.
  61. Kemmeren JM, Algra A, Meijers JC, et al. Effect of second- and third-generation oral contraceptives on the protein C system in the absence or presence of the factor VLeiden mutation: a randomized trial. Blood 2004; 103:927.
  62. Seaman HE, de Vries CS, Farmer RD. The risk of venous thromboembolism in women prescribed cyproterone acetate in combination with ethinyl estradiol: a nested cohort analysis and case-control study. Hum Reprod 2003; 18:522.
  63. Vasilakis-Scaramozza C, Jick H. Risk of venous thromboembolism with cyproterone or levonorgestrel contraceptives. Lancet 2001; 358:1427.
  64. Lidegaard Ø. Absolute and attributable risk of venous thromboembolism in women on combined cyproterone acetate and ethinylestradiol. J Obstet Gynaecol Can 2003; 25:575.
  65. US Food and Drug Administration. Birth Control Pills Containing Drospirenone: Label Change-Products may be associated with a higher risk for blood clots. http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm299605.htm (Accessed on April 17, 2012).
  66. van Hylckama Vlieg A, Helmerhorst FM, Vandenbroucke JP, et al. The venous thrombotic risk of oral contraceptives, effects of oestrogen dose and progestogen type: results of the MEGA case-control study. BMJ 2009; 339:b2921.
  67. Dinger JC, Heinemann LA, Kühl-Habich D. The safety of a drospirenone-containing oral contraceptive: final results from the European Active Surveillance Study on oral contraceptives based on 142,475 women-years of observation. Contraception 2007; 75:344.
  68. Seeger JD, Loughlin J, Eng PM, et al. Risk of thromboembolism in women taking ethinylestradiol/drospirenone and other oral contraceptives. Obstet Gynecol 2007; 110:587.
  69. Parkin L, Sharples K, Hernandez RK, Jick SS. Risk of venous thromboembolism in users of oral contraceptives containing drospirenone or levonorgestrel: nested case-control study based on UK General Practice Research Database. BMJ 2011; 342:d2139.
  70. Jick SS, Hernandez RK. Risk of non-fatal venous thromboembolism in women using oral contraceptives containing drospirenone compared with women using oral contraceptives containing levonorgestrel: case-control study using United States claims data. BMJ 2011; 342:d2151.
  71. FDA Office of Surveillance and Epidemiology. Combined Hormonal Contraceptives (CHCs) and the Risk of Cardiovascular Disease Endpoints. http://www.fda.gov/downloads/Drugs/DrugSafety/UCM277384.pdf (Accessed on February 03, 2012).
  72. European Medicines Agency. PhVWP Monthly report on safety concerns, guidelines and general matters, January 2012 - Issue number: 1201. http://www.ema.europa.eu/docs/en_GB/document_library/Report/2012/01/WC500121387.pdf (Accessed on April 17, 2012).
  73. Vandenbroucke JP, Koster T, Briët E, et al. Increased risk of venous thrombosis in oral-contraceptive users who are carriers of factor V Leiden mutation. Lancet 1994; 344:1453.
  74. van Vlijmen EF, Brouwer JL, Veeger NJ, et al. Oral contraceptives and the absolute risk of venous thromboembolism in women with single or multiple thrombophilic defects: results from a retrospective family cohort study. Arch Intern Med 2007; 167:282.
  75. Vandenbroucke JP, van der Meer FJ, Helmerhorst FM, Rosendaal FR. Factor V Leiden: should we screen oral contraceptive users and pregnant women? BMJ 1996; 313:1127.
  76. de Bruijn SF, Stam J, Koopman MM, Vandenbroucke JP. Case-control study of risk of cerebral sinus thrombosis in oral contraceptive users and in [correction of who are] carriers of hereditary prothrombotic conditions. The Cerebral Venous Sinus Thrombosis Study Group. BMJ 1998; 316:589.
  77. Martinelli I, Sacchi E, Landi G, et al. High risk of cerebral-vein thrombosis in carriers of a prothrombin-gene mutation and in users of oral contraceptives. N Engl J Med 1998; 338:1793.
  78. Martinelli I, Battaglioli T, Pedotti P, et al. Hyperhomocysteinemia in cerebral vein thrombosis. Blood 2003; 102:1363.
  79. Mohllajee AP, Curtis KM, Martins SL, Peterson HB. Does use of hormonal contraceptives among women with thrombogenic mutations increase their risk of venous thromboembolism? A systematic review. Contraception 2006; 73:166.
  80. Leblanc ES, Laws A. Benefits and risks of third-generation oral contraceptives. J Gen Intern Med 1999; 14:625.
  81. Johannisson E. Safety of modern oral contraceptives. The International Committee for Research in Reproduction. Lancet 1996; 347:258.
  82. Barbieri RL, Speroff L, Walker AM, McPherson K. Therapeutic controversy: The safety of third-generation oral contraceptives. J Clin Endocrinol Metab 1999; 84:1822.
  83. Vandenbroucke JP, Rosendaal FR. End of the line for "third-generation-pill" controversy? Lancet 1997; 349:1113.
  84. Julkunen HA. Oral contraceptives in systemic lupus erythematosus: side-effects and influence on the activity of SLE. Scand J Rheumatol 1991; 20:427.
  85. Julkunen HA, Kaaja R, Friman C. Contraceptive practice in women with systemic lupus erythematosus. Br J Rheumatol 1993; 32:227.
  86. Contraceptive Technology Update June 2004; 25:61.
  87. Høibraaten E, Qvigstad E, Arnesen H, et al. Increased risk of recurrent venous thromboembolism during hormone replacement therapy--results of the randomized, double-blind, placebo-controlled estrogen in venous thromboembolism trial (EVTET). Thromb Haemost 2000; 84:961.
  88. Hannaford PC, Selvaraj S, Elliott AM, et al. Cancer risk among users of oral contraceptives: cohort data from the Royal College of General Practitioner's oral contraception study. BMJ 2007; 335:651.
  89. Long-term oral contraceptive use and the risk of breast cancer. The centers for Disease Control Cancer and Steroid Hormone Study. JAMA 1983; 249:1591.
  90. Oral-contraceptive use and the risk of breast cancer. The Cancer and Steroid Hormone Study of the Centers for Disease Control and the National Institute of Child Health and Human Development. N Engl J Med 1986; 315:405.
  91. Hankinson SE, Colditz GA, Manson JE, et al. A prospective study of oral contraceptive use and risk of breast cancer (Nurses' Health Study, United States). Cancer Causes Control 1997; 8:65.
  92. Marchbanks PA, McDonald JA, Wilson HG, et al. Oral contraceptives and the risk of breast cancer. N Engl J Med 2002; 346:2025.
  93. Davidson NE, Helzlsouer KJ. Good news about oral contraceptives. N Engl J Med 2002; 346:2078.
  94. Vessey M, Painter R. Oral contraceptive use and cancer. Findings in a large cohort study, 1968-2004. Br J Cancer 2006; 95:385.
  95. Vessey M, Yeates D. Oral contraceptive use and cancer: final report from the Oxford-Family Planning Association contraceptive study. Contraception 2013; 88:678.
  96. Moorman PG, Havrilesky LJ, Gierisch JM, et al. Oral contraceptives and risk of ovarian cancer and breast cancer among high-risk women: a systematic review and meta-analysis. J Clin Oncol 2013; 31:4188.
  97. Grabrick DM, Hartmann LC, Cerhan JR, et al. Risk of breast cancer with oral contraceptive use in women with a family history of breast cancer. JAMA 2000; 284:1791.
  98. Ursin G, Peters RK, Henderson BE, et al. Oral contraceptive use and adenocarcinoma of cervix. Lancet 1994; 344:1390.
  99. Thomas DB, Ray RM. Oral contraceptives and invasive adenocarcinomas and adenosquamous carcinomas of the uterine cervix. The World Health Organization Collaborative Study of Neoplasia and Steroid Contraceptives. Am J Epidemiol 1996; 144:281.
  100. Moreno V, Bosch FX, Muñoz N, et al. Effect of oral contraceptives on risk of cervical cancer in women with human papillomavirus infection: the IARC multicentric case-control study. Lancet 2002; 359:1085.
  101. Smith JS, Green J, Berrington de Gonzalez A, et al. Cervical cancer and use of hormonal contraceptives: a systematic review. Lancet 2003; 361:1159.
  102. International Collaboration of Epidemiological Studies of Cervical Cancer, Appleby P, Beral V, et al. Cervical cancer and hormonal contraceptives: collaborative reanalysis of individual data for 16,573 women with cervical cancer and 35,509 women without cervical cancer from 24 epidemiological studies. Lancet 2007; 370:1609.
  103. de Villiers EM. Relationship between steroid hormone contraceptives and HPV, cervical intraepithelial neoplasia and cervical carcinoma. Int J Cancer 2003; 103:705.
  104. Auborn KJ, Woodworth C, DiPaolo JA, Bradlow HL. The interaction between HPV infection and estrogen metabolism in cervical carcinogenesis. Int J Cancer 1991; 49:867.
  105. Newfield L, Bradlow HL, Sepkovic DW, Auborn K. Estrogen metabolism and the malignant potential of human papillomavirus immortalized keratinocytes. Proc Soc Exp Biol Med 1998; 217:322.
  106. Collaborative Group on Epidemiological Studies of Ovarian Cancer, Beral V, Doll R, et al. Ovarian cancer and oral contraceptives: collaborative reanalysis of data from 45 epidemiological studies including 23,257 women with ovarian cancer and 87,303 controls. Lancet 2008; 371:303.
  107. Combination oral contraceptive use and the risk of endometrial cancer. The Cancer and Steroid Hormone Study of the Centers for Disease Control and the National Institute of Child Health and Human Development. JAMA 1987; 257:796.
  108. Feskanich D, Hunter DJ, Willett WC, et al. Oral contraceptive use and risk of melanoma in premenopausal women. Br J Cancer 1999; 81:918.
  109. Pfahlberg A, Hassan K, Wille L, et al. Systematic review of case-control studies: oral contraceptives show no effect on melanoma risk. Public Health Rev 1997; 25:309.
  110. Vessey M, Painter R, Yeates D. Mortality in relation to oral contraceptive use and cigarette smoking. Lancet 2003; 362:185.
  111. Colditz GA. Oral contraceptive use and mortality during 12 years of follow-up: the Nurses' Health Study. Ann Intern Med 1994; 120:821.
  112. Hannaford PC, Iversen L, Macfarlane TV, et al. Mortality among contraceptive pill users: cohort evidence from Royal College of General Practitioners' Oral Contraception Study. BMJ 2010; 340:c927.
  113. Krauss RM, Burkman RT Jr. The metabolic impact of oral contraceptives. Am J Obstet Gynecol 1992; 167:1177.
  114. Kjos SL, Peters RK, Xiang A, et al. Contraception and the risk of type 2 diabetes mellitus in Latina women with prior gestational diabetes mellitus. JAMA 1998; 280:533.
  115. Lobo RA, Skinner JB, Lippman JS, Cirillo SJ. Plasma lipids and desogestrel and ethinyl estradiol: a meta-analysis. Fertil Steril 1996; 65:1100.
  116. LaRosa JC. Effects of oral contraceptives on circulating lipids and lipoproteins: maximizing benefit, minimizing risk. Int J Fertil 1989; 34 Suppl:71.
  117. Greenlund KJ, Webber LS, Srinivasan S, et al. Associations of oral contraceptive use with serum lipids and lipoproteins in young women: the Bogalusa Heart Study. Ann Epidemiol 1997; 7:561.
  118. Foulon T, Payen N, Laporte F, et al. Effects of two low-dose oral contraceptives containing ethinylestradiol and either desogestrel or levonorgestrel on serum lipids and lipoproteins with particular regard to LDL size. Contraception 2001; 64:11.
  119. Kiriwat O, Petyim S. The effects of transdermal contraception on lipid profiles, carbohydrate metabolism and coagulogram in Thai women. Gynecol Endocrinol 2010; 26:361.
  120. Li DK, Daling JR, Mueller BA, et al. Oral contraceptive use after conception in relation to the risk of congenital urinary tract anomalies. Teratology 1995; 51:30.
  121. Bagwell MA, Thompson SJ, Addy CL, et al. Primary infertility and oral contraceptive steroid use. Fertil Steril 1995; 63:1161.
  122. Dickerson J, Bressler R, Christian CD. Liver function tests and low-dose estrogen oral contraceptives. Contraception 1980; 22:597.
  123. Paseka J, Unzeitig V, Cibula D, Chroust K. [Liver function tests during administration of triphasic contraceptives containing Norgestimate]. Ceska Gynekol 2000; 65:420.
  124. Szlendak-Sauer K, Radowicki S, Skórzewska K. [The impact of a new low dose oral contraceptive containing drospirenone on lipid profile, carbohydrate metabolism and hepatic function]. Ginekol Pol 2009; 80:99.
  125. Maheshwari S, Sarraj A, Kramer J, El-Serag HB. Oral contraception and the risk of hepatocellular carcinoma. J Hepatol 2007; 47:506.
  126. Goldenberg NM, Wang P, Glueck CJ. An observational study of severe hypertriglyceridemia, hypertriglyceridemic acute pancreatitis, and failure of triglyceride-lowering therapy when estrogens are given to women with and without familial hypertriglyceridemia. Clin Chim Acta 2003; 332:11.
  127. Reubinoff BE, Grubstein A, Meirow D, et al. Effects of low-dose estrogen oral contraceptives on weight, body composition, and fat distribution in young women. Fertil Steril 1995; 63:516.
  128. Gallo MF, Lopez LM, Grimes DA, et al. Combination contraceptives: effects on weight. Cochrane Database Syst Rev 2014; 1:CD003987.
  129. Rosenberg MJ, Waugh MS. Oral contraceptive discontinuation: a prospective evaluation of frequency and reasons. Am J Obstet Gynecol 1998; 179:577.
  130. Loder EW, Buse DC, Golub JR. Headache as a side effect of combination estrogen-progestin oral contraceptives: a systematic review. Am J Obstet Gynecol 2005; 193:636.
  131. Walsh J, Smith C. The clinical enquiry service; benign intracranial hypertension. Br J Fam Plann 2000; 26:169.
  132. Granella F, Sances G, Zanferrari C, et al. Migraine without aura and reproductive life events: a clinical epidemiological study in 1300 women. Headache 1993; 33:385.
  133. Couturier EG, Bomhof MA, Neven AK, van Duijn NP. Menstrual migraine in a representative Dutch population sample: prevalence, disability and treatment. Cephalalgia 2003; 23:302.
  134. Rasmussen BK. Migraine and tension-type headache in a general population: precipitating factors, female hormones, sleep pattern and relation to lifestyle. Pain 1993; 53:65.
  135. Aegidius K, Zwart JA, Hagen K, et al. Oral contraceptives and increased headache prevalence: the Head-HUNT Study. Neurology 2006; 66:349.
  136. Sulak P, Willis S, Kuehl T, et al. Headaches and oral contraceptives: impact of eliminating the standard 7-day placebo interval. Headache 2007; 47:27.
  137. De Leo V, Scolaro V, Musacchio MC, et al. Combined oral contraceptives in women with menstrual migraine without aura. Fertil Steril 2011; 96:917.
  138. Etminan M, Takkouche B, Isorna FC, Samii A. Risk of ischaemic stroke in people with migraine: systematic review and meta-analysis of observational studies. BMJ 2005; 330:63.
  139. MacClellan LR, Giles W, Cole J, et al. Probable migraine with visual aura and risk of ischemic stroke: the stroke prevention in young women study. Stroke 2007; 38:2438.
  140. Chang CL, Donaghy M, Poulter N. Migraine and stroke in young women: case-control study. The World Health Organisation Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception. BMJ 1999; 318:13.
  141. Lidegaard O. Oral contraceptives, pregnancy and the risk of cerebral thromboembolism: the influence of diabetes, hypertension, migraine and previous thrombotic disease. Br J Obstet Gynaecol 1995; 102:153.
  142. Bousser MG, Conard J, Kittner S, et al. Recommendations on the risk of ischaemic stroke associated with use of combined oral contraceptives and hormone replacement therapy in women with migraine. The International Headache Society Task Force on Combined Oral Contraceptives & Hormone Replacement Therapy. Cephalalgia 2000; 20:155.
  143. Loder EW, Buse DC, Golub JR. Headache and combination estrogen-progestin oral contraceptives: integrating evidence, guidelines, and clinical practice. Headache 2005; 45:224.
  144. Lashner BA, Kane SV, Hanauer SB. Lack of association between oral contraceptive use and ulcerative colitis. Gastroenterology 1990; 99:1032.
  145. Bork K, Fischer B, Dewald G. Recurrent episodes of skin angioedema and severe attacks of abdominal pain induced by oral contraceptives or hormone replacement therapy. Am J Med 2003; 114:294.