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Benefits and Risks of OCPs Beyond Contraception



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Am Fam Physician. 2004 May 1;69(9):2233-2236.

Using a clinical vignette of a healthy, non-smoking 35-year-old woman who wants information about oral contraceptive pills (OCPs), Petitti reviews the risks and benefits that figure into each decision about the use of these agents.

The noncontraceptive benefits reviewed by the author include decreasing the risk for ovarian cancer by one half. This reduction is apparent after five years of use and persists for 10 to 20 years after OCPs are discontinued. Risk of endometrial cancer also is reduced within five years of use, and the protection persists over the long term. The occurrence of acne is decreased by all combination OCPs, but only a few formulations have been allowed to make this specific claim. Menstrual blood flow is reduced, which is associated with lower rates of anemia and reduced severity of dysfunctional uterine bleeding.

Guidelines for the Use of Combination Estrogen-Progestin Oral Contraceptives in Women with Characteristics That Might Increase the Risk of Adverse Effects*

Variable ACOG guidelines WHO guidelines

Smoker, > 35 years of age

< 15 cigarettes per day

Risk unacceptable

Risk usually outweighs benefit

15 cigarettes per day

Risk unacceptable

Risk unacceptable

Hypertension

Blood pressure controlled

Risk acceptable; no definition of blood-pressure control

Risk usually outweighs benefit if systolic blood pressure is 140 to 159 mm Hg and diastolic blood pressure is 90 to 99 mm Hg

Blood pressure uncontrolled

Risk unacceptable; no definition of uncontrolled blood pressure

Risk unacceptable if systolic blood pressure is 160 mm Hg or diastolic blood pressure is 100 mm Hg

History of stroke, ischemic heart disease, or venous thromboembolism

Risk unacceptable

Risk unacceptable

Diabetes

Risk acceptable if no other cardiovascular risk factors and no end-organ damage

Benefit outweighs risk if no end-organ damage and diabetes is of 20 years’ duration

Hypercholesterolemia

Risk acceptable if LDL cholesterol < 160 mg per dL (4.14 mmol per L) and no other cardiovascular risk factors

Benefit-risk ratio is dependent on the presence or absence of other cardiovascular risk factors

Multiple cardiovascular risk factors

Not addressed

Risk usually outweighs benefit or risk unacceptable, depending on risk factors

Migraine headache

Age 35 years

Risk usually outweighs benefit

Risk usually outweighs benefit

Focal symptoms

Risk unacceptable

Risk unacceptable

Breast cancer

Current disease

Risk unacceptable

Risk unacceptable

Past disease, no active disease for five years

Risk unacceptable

Risk usually outweighs benefit

Family history of breast or ovarian cancer

Risk acceptable

Risk acceptable


ACOG = American College of Obstetricians and Gynecologists; WHO = World Health Organization; LDL = low-density lipoprotein.

*—The ACOG guidelines recommend the use of formulations containing less than 50 mcg of ethinyl estradiol with the “lowest progestin dose,” without mention of the type of progestin. The WHO guidelines pertain explicitly to formulations containing 35 mcg or less of ethinyl estradiol and do not mention the dose or type of progestin.

Adapted with permission from Petitti DB. Combination estrogen-progestin oral contraceptives. N Engl J Med 2003;349:1448.

Guidelines for the Use of Combination Estrogen-Progestin Oral Contraceptives in Women with Characteristics That Might Increase the Risk of Adverse Effects*

View Table

Guidelines for the Use of Combination Estrogen-Progestin Oral Contraceptives in Women with Characteristics That Might Increase the Risk of Adverse Effects*

Variable ACOG guidelines WHO guidelines

Smoker, > 35 years of age

< 15 cigarettes per day

Risk unacceptable

Risk usually outweighs benefit

15 cigarettes per day

Risk unacceptable

Risk unacceptable

Hypertension

Blood pressure controlled

Risk acceptable; no definition of blood-pressure control

Risk usually outweighs benefit if systolic blood pressure is 140 to 159 mm Hg and diastolic blood pressure is 90 to 99 mm Hg

Blood pressure uncontrolled

Risk unacceptable; no definition of uncontrolled blood pressure

Risk unacceptable if systolic blood pressure is 160 mm Hg or diastolic blood pressure is 100 mm Hg

History of stroke, ischemic heart disease, or venous thromboembolism

Risk unacceptable

Risk unacceptable

Diabetes

Risk acceptable if no other cardiovascular risk factors and no end-organ damage

Benefit outweighs risk if no end-organ damage and diabetes is of 20 years’ duration

Hypercholesterolemia

Risk acceptable if LDL cholesterol < 160 mg per dL (4.14 mmol per L) and no other cardiovascular risk factors

Benefit-risk ratio is dependent on the presence or absence of other cardiovascular risk factors

Multiple cardiovascular risk factors

Not addressed

Risk usually outweighs benefit or risk unacceptable, depending on risk factors

Migraine headache

Age 35 years

Risk usually outweighs benefit

Risk usually outweighs benefit

Focal symptoms

Risk unacceptable

Risk unacceptable

Breast cancer

Current disease

Risk unacceptable

Risk unacceptable

Past disease, no active disease for five years

Risk unacceptable

Risk usually outweighs benefit

Family history of breast or ovarian cancer

Risk acceptable

Risk acceptable


ACOG = American College of Obstetricians and Gynecologists; WHO = World Health Organization; LDL = low-density lipoprotein.

*—The ACOG guidelines recommend the use of formulations containing less than 50 mcg of ethinyl estradiol with the “lowest progestin dose,” without mention of the type of progestin. The WHO guidelines pertain explicitly to formulations containing 35 mcg or less of ethinyl estradiol and do not mention the dose or type of progestin.

Adapted with permission from Petitti DB. Combination estrogen-progestin oral contraceptives. N Engl J Med 2003;349:1448.

Making a decision about using OCPs also requires consideration of the known risks (see accompanying table). Older contraceptives with higher estrogen doses were associated with increased risks of myocardial infarction and ischemic stroke. Interpretation of older studies was complicated by the higher prevalence of smoking and undiagnosed hypertension in women in that era. More recent studies of lower-estrogen OCPs have not shown consistent or statistically significant increases in ischemic events. The type of progestin used did not alter the risk of heart attack or stroke in patients using lower-estrogen pills.

The risk of venous thromboembolism is increased threefold to fourfold, and patients taking pills containing so-called third-generation progestins (desogestrel or gestodene) have an even higher risk of blood clot. The risk for clot formation is highest in the first year of pill use. The author notes that screening for thrombophilia (i.e., factor V Leiden, prothrombin gene mutations, and protein C or S deficiency) has been suggested, but it is not recommended routinely and has not been demonstrated to be cost-effective.

Uncontrolled hypertension, diabetes, and hyperlipidemia are associated with increased risk for ischemic events in patients using OCPs, but whether any elevated risk remains when these conditions are controlled is not clear. The degree of any association between OCPs and breast cancer also remains unclear, despite more than 60 epidemiologic studies. The most recent and largest studies have shown no increased risk or a slight increase in risk (relative risk of 1.24).

The author notes that several estrogen-progestin combinations are available, but no particular formulation has been shown to be superior in contraceptive effectiveness, cycle control, bleeding pattern, or prevalence of minor side effects, such as weight gain.

Petitti DB. Combination estrogen-progestin oral contraceptives. N Engl J Med. October 9, 2003;349:1443–50.



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