Clinical Review

Can safety and efficacy go hand in hand? Contraception for medically complex patients

OBG Manag. 2008 January;20(1):42-56

References

1. World Health Organization Medical Eligibility Criteria for Contraceptive Use. 3rd ed. Geneva: World Health Organization; 2004. Available at:www.who.int/reproductive-health/publications/mec/index.htm. Accessed Oct. 25, 2007.

2. Hatcher RA, Nelson A. Combined hormonal contraceptive methods. In: Hatcher RA et al, eds. Contraceptive Technology. 18th ed. New York: Ardent Media; 2004;391:460-

3. Faculty of Family Planning and Reproductive Health Care Clinical Effectiveness Unit First Prescription of Combined Oral Contraception. Royal College of Obstetricians and Gynaecologists: 2006.

4. Tanis BC, van den Bosch MA, Kemmeren JM, et al. Oral contraceptives and the risk of myocardial infarction. N Engl J Med. 2001;345:1787-1793.

5. Gillum LA, Mamidipudi SK, Johnston SC. Ischemic stroke risk with oral contraceptives: a meta-analysis. JAMA. 2000;284:72-78.

6. World Health Organization Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception Ischaemic stroke and combined oral contraceptives: results of an international, multicentre, case-control study. Lancet. 1996;348:498-505.

7. Vandenbroucke JP, Rosing J, Bloemenkamp KW, et al. Oral contraceptives and the risk of venous thrombosis. N Engl J Med. 2001;344:1527-1535.

8. Cole JA, Norman H, Doherty M, Walker AM. Venous thromboembolism, myocardial infarction, and stroke among transdermal contraceptive system users. Obstet Gynecol. 2007;109(2 Pt 1):339-346.

9. Schwingl PJ, Ory HW, Visness CM. Estimates of the risk of cardiovascular death attributable to low-dose oral contraceptives in the United States. Am J Obstet Gynecol. 1999;180(1 Pt 1):241-249.

10. Petitti DB, Sidney S, Quesenberry CP. Oral contraceptive use and myocardial infarction. Contraception. 1998;57:143-155.

11. Curtis KM, Mohllajee AP, Peterson HB. Use of combined oral contraceptives among women with migraine and nonmigrainous headaches: a systematic review. Contraception. 2006;73:189-194.

12. 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.-

13. Slooter AJ, Rosendaal FR, Tanis BC, Kemmeren JM, van der Graaf Y, Algra A. Prothrombotic conditions, oral contraceptives, and the risk of ischemic stroke. J Thromb Haemost. 2005;3:1213-1217.

14. Mohllajee AP, Curtis KM, Martins SL, Peterson HB. Does use of hormonal contraceptives among women with thrombogenic mutations increase their risk of thromboembolism? A systematic review. Contraception. 2006;73:166-178.

15. Christiansen SC, Cannegieter SC, Koster T, Vandenbroucke JP, Rosendaal FR. Thrombophilia, clinical factors, and recurrent venous thrombotic events. JAMA. 2005;293:2352-2361.

16. World Health Organization Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception Effect of different progestagens in low oestrogen oral contraceptives on venous thromboembolic disease. Lancet. 1995;346:1582-1588.

17. Sidney S, Petitti DB, Soff GA, Cundiff DL, Tolan KK, Quesenberry CP, Jr. Venous thromboembolic disease in users of low-estrogen combined estrogen-progestin oral contraceptives. Contraception. 2004;70:3-10.

18. Holt VL, Scholes D, Wicklund KG, Cushing-Haugen KL, Daling JR. Body mass index, weight, and oral contraceptive failure risk. Obstet Gynecol. 2005;105:46-52.

19. 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;318:13-18.

20. World Health Organization Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception Cardiovascular disease and use of oral and injectable progestogen-only contraceptives and combined injectable contraceptives Results of an international, multicenter, case-control study. Contraception. 1998;57:315-324.

21. Grimes DA. Intrauterine devices. In: Hatcher RA et al, eds. Contraceptive Technology. 18th ed. New York: Ardent Media; 2004; 495-530.

22. Darney PD. Time to pardon the IUD? N Engl J Med. 2001;345:608-610.

23. Farley TM, Rosenberg MJ, Rowe PJ, Chen JH, Meirik O. Intrauterine devices and pelvic inflammatory disease: an international perspective. Lancet. 1992;339:785-788.

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28. Jamieson DJ, Hillis SD, Duerr A, Marchbanks PA, Costello C, Peterson HB. Complications of interval laparoscopic tubal sterilization: findings from the United States Collaborative Review of Sterilization. Obstet Gynecol. 2000;96:997-1002.

29. Cooper JM, Carignan CS, Cher D, Kerin JF. Selective Tubal Occlusion Procedure Investigators Microinsert nonincisional hysteroscopic sterilization. Obstet Gynecol. 2003;102:59-67.

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Putting the risks of OCs in context

It is very important to interpret these risks in light of the overall rarity of cardiovascular events and the opposing risks of pregnancy. TABLE 2 shows the low incidence of MI, stroke, and VTE among nonpregnant and pregnant women.

For every 100,000 woman-years, combined OCs are estimated to contribute three additional cases of MI, four additional cases of stroke, and 10 to 20 additional cases of VTE.^3,5,9 For these severe conditions, the baseline incidence plus additional cases attributed to use of combination OCs still does not approach the risk of pregnancy itself. One study showed that women face a higher risk of cardiovascular death in pregnancy than when taking combined OCs, with the exception of smokers over the age of 35 years.⁹

For most women, combined OCs pose no greater cardiovascular risk than pregnancy does—but baseline cardiovascular risk factors augment that risk. Women who have hypertension, those who smoke, and those over age 35 face higher risks of MI and stroke while taking combined OCs.^4,10 Diabetes and hypercholesterolemia further elevate the risk of MI,⁴ and migraine headache and thrombophilia raise the risk of stroke.^6,11-13 Women with thrombophilia, a history of a clotting disorder, elevated body mass index (BMI), and, possibly, those who smoke face a higher risk of VTE when using a combined hormonal contraceptive.^14-17

Because of these risks, the WHO classifies significant cardiovascular risk factors as category 4 (contraindicated) in regard to combined OCs (TABLE 3).

These risk factors include:

known vascular disease
ischemic heart disease
history of stroke
known thrombotic mutation
complicated valvular disease.

When systolic blood pressure exceeds 160 mm Hg or diastolic blood pressure surpasses 100 mm Hg, combined OCs are again contraindicated. Use of combined OCs in women who have milder blood pressure elevations and adequately controlled hypertension is classified as category 3—theoretical or proven risks usually outweigh the advantages of using the method. Individual risk factors such as hyperlipidemia or uncomplicated diabetes are classified as category 3 in regard to combined OCs—unless multiple factors coexist, in which case they fall into category 4.

TABLE 2

Incidence of major cardiovascular events per 100,000 woman-years

GROUP	MYOCARDIAL INFARCTION	STROKE	VENOUS THROMBOEMBOLISM³
Nonpregnant	0.2–5³⁰	4–14³⁰	5
Additional cases attributed to oral contraceptive use	0.6–3⁹	4.1⁵	10–20
Pregnant	2.7³¹ –6.2³²	20³³	60

TABLE 3

Risk states in which combined hormonal contraceptives are contraindicated

CARDIOVASCULAR RISK
Multiple cardiovascular risk factors age smoking abnormal lipid profile strong family history obesity hypertension diabetes
Systolic blood pressure >160 mm Hg
Diastolic blood pressure >100 mm Hg
Current vascular disease
History of ischemic heart disease
Advanced diabetes nephropathy, retinopathy, or neuropathy macrovascular disease disease for more than 20 years
CLOTTING RISK
History of deep venous thrombosis or pulmonary embolism
Major surgery with prolonged immobilization
Known thrombophilia
Complicated valvular heart disease
STROKE RISK
History of stroke
Migraine over age 35
Migraine with aura
GASTROINTESTINAL ILLNESS
Active viral hepatitis
Decompensated cirrhosis
Liver tumor
CANCER RISK
Current breast cancer
SOURCE: World Health Organization

Obese women may benefit from OCs—but efficacy may decline

Although obesity increases the risk of VTE¹⁷ and possibly MI⁴ during use of combined OCs, the WHO classifies it as category 2 in regard to this contraceptive method—advantages generally outweigh the theoretical or proven risks. This rating is based on the low number of major adverse events associated with use of low-dose combined OCs in obese women.¹

However, combined OCs appear to be less effective in obese women than in their normal-weight peers. A recent case-control study showed diminished efficacy for women with a BMI over 27, and an even higher rate of contraceptive failure for those with a BMI over 32.¹⁸ Nevertheless, it is important for clinicians and patients to recognize the benefits likely to accrue from this method—probably at a higher rate than is seen with most barrier methods.

Obese women who suffer from oligoovulation may also benefit from the progestin in combined OCs, which can mitigate the effects of unopposed estrogen.

Nevertheless, it may be wise, when counseling these women, to consider a more effective method that carries less risk, such as a progestin-releasing intrauterine contraceptive.

Stroke risk in migraine sufferers may render OC option unwise

Patients who experience migraine have a higher risk of stroke than their migraine-free peers. The risk is even higher when the migraine is preceded by an aura (a 5- to 10-minute episode of moving lights in a visual field, speech disturbance, paresthesias, or weakness that precedes the headache).^12,19 Risk is especially elevated when women who suffer migraines use a combined OC, with an odds ratio for stroke ranging from 6.6 to 8.7.

Because of these heightened risks, the WHO classifies migraine with aura as category 4 (contraindicated) for combined OCs. When no aura is present, the advisability of OC use depends on the woman’s age and whether her symptoms predate hormone use. Migraine without aura falls into category 4 for women over age 35 whose symptoms develop while on the contraceptive. It falls into category 2 if the woman is under age 35 and her symptoms predate contraceptive use. In other situations, migraine without aura falls into category 3.