Weight gain. There is no greater risk of weight gain with OC therapy than with placebo.20 Although there are no specific data regarding ultra-low-dose pills, one would expect the risk of weight gain associated with them to be small.21
Acne. Researchers conducted an RCT using a regimen of 20 μg EE2 and 100 μg levonorgestrel to evaluate the pill’s effect on acne. They placed 350 patients (all of whom were older than 14 years of age) on the OC or placebo for 6 cycles. Inflammatory, noninflammatory, and total lesion counts at cycle 6 were significantly lower with the regimen than with placebo.22
Coexisting medical conditions
Hypertension. OCs increase blood pressure—in general, by an average of 8 mm Hg systolic and 6 mm Hg diastolic, according to reports. In patients with preexisting hypertension, an additional 7-mm Hg increase in both systolic and diastolic blood pressure should be expected.20,23 Hypertension remains a relative contraindication to OC use.
The lipid profile. Most data concern 35- and 50-μg OC preparations. The National Cholesterol Education Program (NCEP) recommends that women with controlled dyslipidemia be placed on OC formulations containing 35 μg estrogen or less. In one study, researchers found that 2 years of OC therapy with 20 μg EE2 and 100 μg levonorgestrel did not cause significant changes from baseline levels of triglycerides, total cholesterol, highdensity lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and apolipoprotein A-1 and B.24 The changes in lipid concentration were less than those associated with higher doses of estrogen. Further, when lipid values were elevated, they returned to baseline after 12 to 24 cycles of OC use. OCs are not recommended in women who have elevated LDL cholesterol (more than 160 mg/dL) or additional risk factors for coronary artery disease, including smoking, diabetes, obesity, hypertension, family history of premature coronary artery disease, HDL cholesterol less than 35 mg/dL, or triglyceride levels exceeding 250 mg/dL.25
Oral contraceptives are not recommended in women who have elevated LDL cholesterol.
Diabetes. In one study involving 43 women with type 1 diabetes mellitus who used OCs for a mean duration of 3.4 years, hemoglobin A1C values did not differ significantly from those of the controls. The authors concluded that 35-μg OC formulations posed no additional risks for these women.26 We lack data on ultra-low-dose OCs and diabetes.
Migraine. In a European multicenter casecontrol trial, women with a history of migraine headaches who used OC formulations containing less than 50 μg estrogen had a 6-fold increased risk of ischemic stroke compared with nonusers with no migraine history, although this difference was not statistically significant.27 Two other studies also found an increased risk of stroke among OC users with a history of migraines.11,28
When smokers with a prior history of migraine were placed on OC therapy, they exhibited a 34-fold increased risk of ischemic stroke in association with the development of migraine headaches compared with nonsmokers who did not use OCs or have a history of migraines.27
A pooled study of patients from Kaiser Permanente in northern and southern California and 3 Washington State counties found that ischemic stroke patients—and, to a lesser extent, hemorrhagic stroke patients—were more likely than controls to report a history of migraines.11 Minimal data exist on migraine headaches and ultra-low-dose pills.
Seizure disorders. The enhanced hepatic enzyme activity associated with the use of phenobarbital, phenytoin, carbamazepine, felbamate, and topiramate can limit the efficacy of OC therapy.29,30 Patients who must remain on 1 or more of these anticonvulsants may require a higher-dosage OC, since there is evidence of increased metabolic clearance of the estrogen and progestin.29 Clinicians also should be aware that progestin-only therapy, such as with depot medroxyprogesterone acetate (DMPA), increases the threshold for seizures.
Sickle cell disease. With its associated hemoglobinopathy, sickle cell disease can produce vaso-occlusive abnormalities. Unfortunately, no well-controlled studies regarding the potential for VTE in OC users with sickle cell disease have been reported. Researchers have found that the use of alternative contraceptives such as DMPA is safe and effective.31,32 Sickle cell anemia remains a relative contraindication to OC use, although the risks of pregnancy in this population also must be considered. The sickle cell trait does not appear to be a contraindication.
Leiomyomata.Research has shown that uterine myomas do not significantly increase in size when a woman takes a low-dose OC.29 While we lack studies involving ultra-low-dose pills, one would expect a similar effect.
Postpartum and lactating women.Combination pills are not the contraceptive of choice for breastfeeding mothers, as there is evidence that even low-dose formulations can decrease milk production.33 There also is controversy over when to initiate OCs in the postpartum period among nonbreastfeeding women to avoid an increased risk of thromboembolism.33 Theoretically, low-er-dose pills would be associated with less risk. The World Health Organization (WHO) recommends that combined pills be initiated no sooner than 6 months after delivery when lactation is planned.34
