Teratogenicity A meta-analysis of 12 prospective studies, including 6,102 women who used OCs and 85,167 women who did not, revealed no increase in overall risk for malformation, congenital heart defects, or limb reduction defects with the use of OCs (201). Progestins were used to prevent miscarriage. A large study compared women showing signs of threatened abortion who were treated with progestins (primarily oral medroxyprogesterone acetate) with women who were not treated. The rate of malformation was the same among the 1,146 exposed infants as among the 1,608 unexposed infants (202). Conversely, estrogens taken in high doses in pregnancy can induce vaginal cancer in female offspring exposed in utero. A recent literature search revealed no recent reports linking teratogenicity to hormonal contraception.
Interaction of Oral Contraceptives with Other Drugs
Some drugs (e.g., rifampin) reduce the effectiveness of oral contraceptives; conversely, OCs can augment or reduce the effectiveness of other drugs (e.g., benzodiazepines) (203,204). Perhaps of greatest clinical significance are six antiepileptic drugs: phenytoin, phenobarbital, carbamazepine, oxcarbazepine, felbamate, and topiramate (205). These drugs and the antibiotic rifampin all induce synthesis of liver cytochrome P450 enzymes and reduce plasma levels of EE in women taking OCs, increasing the likelihood of contraceptive failure. Some antiseizure agents have no effect on the levels of contraceptive steroids in the blood. These include valproic acid, vigabatrin, lamotrigine, gabapentin, tiagabine, levetiracetam, zonisamide, ethosuximide, and the benzodiazepines (205). St. John’s wort induces cytochrome P450 and is reported to increase clearance of EE and norethindrone (206). The antifungal agents griseofulvin, ketoconazole, and itraconazole induce these hepatic enzymes and may reduce OC efficacy (204). Ampicillin and tetracycline were implicated in numerous case reports of OC failure. They kill gut bacteria (primarily clostridia) that are responsible for hydrolysis of steroid glucuronides in the intestine, which allows reabsorption of the steroid through the enterohepatic circulation. It was not possible to demonstrate reduced plasma levels of EE overall or differences in pregnancy rates (207). Some individuals do experience reduced EE plasma levels when on tetracyclines or penicillins; it is best to advise women taking OCs who will be treated with antibiotics to use condoms as well (208). Certain drugs appear to increase plasma levels of contraceptive steroids. Ascorbic acid (vitamin C) and acetaminophen may elevate plasma EE, as do the antiretrovirals efavirenz and atazanavir/ritonavir (7).