The combined oral contraceptive. Risks and adverse effects in perspective

Abstract

The risks and adverse effects of the low dose, new generation progestogen combined oral contraceptives (COCs) are much lower than original studies involving pills containing 50 micrograms estrogen. The main effects are those on the cardiovascular system, lipid and glucose metabolism and cancer. Any effect of the COC on myocardial infarction is probably minimal if the woman has no other risk factors especially smoking. The third generation progestogen, low dose COCs have very little effect on lipid or glucose metabolism. There may be a slight increase in breast cancer if COCs are used under the age of 25 years and for more than 4 to 8 years, and in the risk of cervical cancer. It is too early to estimate long term cancer effects of the newer COCs. Adverse effects such as nausea and breast tenderness can be managed by changing the estrogen dose or the type of progestogen. Overall, the clinical benefits of the COC probably outweight the risks and adverse effects.

PIP: Recent cohort and case control studies of low-dose combined oral contraceptives (COCs) containing the new generation of progestogens have allowed classification of adverse effects into those which are rare but serious and should be considered risks and those which are more frequent but are less of a threat to health. Low-dose COCs continue to affect coagulation in a complex way, but the risk is less than with the older preparations, and it can be minimized by screening women for a personal or familial history of early or unusual thrombosis and for levels of protein C, S, and antithrombin III. Women with true migraine with focal signs should also avoid using COCs. The relative risk of myocardial infarction (MI) may increase from 4:1 in women with one risk factor (age, smoking, hypertension, hyperlipidemia, and diabetes) to 20:1 with two risk factors and 128:1 with three or more risk factors. In the absence of all risk factors, a recent study indicated that the relative risk of MI with COC use was 1.9 for current and past use. COC use also causes a slight increase in hypertension in most women, especially those who are older or have a family history of hypertension. While the COC can affect carbohydrate and lipid metabolism, the new generation of progestogens has reduced these effects. The COC may accelerate presentation of gallbladder disease in predisposed women. The COC protects against benign breast disease but may increase the risk of breast cancer and cervical cancer slightly. There is a strong link between hepatocellular adenoma and COC use, but the incidence is low. Return to fertility after use has not been a problem. Both estrogenic adverse effects (nausea, dizziness, irritability, weight gain, bloating) and progestogenic adverse effects (vaginal dryness, acne, hirsutism, weight gain, depression, loss of libido) can occur in 50% of women, but these generally disappear after a few months of use. In conclusion, the low-dose, third generation COCs are associated with minimal risks in the absence of other risk factors and have many beneficial effects such as the prevention of ovarian and endometrial cancer; a decrease in pelvic inflammatory disease and ectopic pregnancies; and protection from anemia, primary dysmenorrhea, functional ovarian cysts, and benign breast disease as well as from the morbidity and mortality associated with pregnancy.