Does Prednisone Decrease the Efficacy of Oral Contraceptive Pills?
No, prednisone does not decrease the efficacy of oral contraceptive pills (OCPs). In fact, the interaction works in the opposite direction: OCPs affect prednisone metabolism, not the other way around.
The Actual Drug Interaction
Estrogens in OCPs increase prednisone/prednisolone levels, not decrease contraceptive efficacy. The FDA drug label for prednisone explicitly states that "estrogens, including oral contraceptives, may decrease the hepatic metabolism of certain corticosteroids, thereby increasing their effect" 1. This is a well-established pharmacokinetic interaction where OCPs enhance corticosteroid activity, potentially requiring dose adjustments of prednisone rather than concerns about contraceptive failure.
Evidence Supporting No Impact on OCP Efficacy
The U.S. Medical Eligibility Criteria for Contraceptive Use (2010) provides comprehensive guidance on drug interactions with contraceptives and does not list corticosteroids or prednisone as medications that reduce OCP effectiveness 2. The guideline specifically identifies drugs that do impair contraceptive efficacy, including:
- Certain anticonvulsants (phenytoin, carbamazepamine, barbiturates, primidone, topiramate, oxcarbazepine) 2
- Rifampin and rifabutin 2
- Some antiretroviral medications (ritonavir-boosted protease inhibitors, certain NNRTIs) 2
Prednisone is notably absent from these lists, indicating no recognized interaction that would compromise contraceptive protection.
Mechanism: OCPs Affect Prednisone, Not Vice Versa
Research demonstrates that women taking OCPs have significantly altered prednisolone pharmacokinetics, with decreased total clearance, increased half-life, and higher drug concentrations compared to non-users 3, 4. Specifically:
- Total prednisolone area under the curve increased more than 2-fold in OCP users (428 vs 188 μg/ml/min) 4
- Unbound prednisolone levels were also significantly elevated (64 vs 41 μg/ml/min) 4
- These changes result from decreased hepatic metabolism and altered protein binding 4
This interaction means prednisone becomes MORE potent in women on OCPs, potentially requiring lower corticosteroid doses to achieve therapeutic effects 1, 4.
Clinical Implications
When prescribing prednisone to women on OCPs:
- No backup contraception is needed - the contraceptive efficacy remains intact 2
- Monitor for increased corticosteroid side effects including hyperglycemia, hypertension, mood changes, and adrenal suppression, as prednisone levels will be elevated 1, 4
- Consider lower prednisone doses in women on OCPs to account for decreased clearance 3, 4
- Counsel patients that this interaction does not compromise their birth control but may enhance steroid effects 1
Common Pitfall to Avoid
Do not confuse this interaction with enzyme-inducing drugs that genuinely reduce OCP efficacy. Prednisone is not a hepatic enzyme inducer in the context of contraceptive metabolism 2. The confusion may arise because glucocorticoids are "moderate inducers of CYP 3A4" for some drug substrates 1, but this does not translate to reduced contraceptive steroid levels or efficacy.