Oral Contraceptives Interactions

St. John's Wort induces CYP3A4 and P-glycoprotein, which accelerates the metabolism of ethinyl estradiol and progestins in combined oral contraceptives. Clinical trials have documented breakthrough bleeding and reduced contraceptive hormone exposure when the two are combined, raising the risk of ovulation and unintended pregnancy.

Smoking while using estrogen-containing oral contraceptives synergistically increases the risk of serious cardiovascular events including myocardial infarction, stroke, and venous thromboembolism. The risk is especially pronounced in women over 35 and increases with the number of cigarettes smoked.

Combined oral contraceptives lower pyridoxal 5'-phosphate (the active form of vitamin B6) by altering tryptophan metabolism and increasing B6 turnover. Long-term pill users have lower B6 status than non-users, which may contribute to mood symptoms in some women.

Several studies have shown that combined oral contraceptive use is associated with lower serum magnesium levels, possibly through estrogen-related shifts in intracellular and extracellular distribution. Low magnesium can contribute to fatigue, premenstrual symptoms, and may modestly elevate venous thromboembolism risk in pill users.

Oral contraceptive use is associated with lower plasma and red blood cell folate levels, likely through increased turnover and urinary excretion. Because pregnancies can occur shortly after stopping the pill, low folate stores increase the risk of neural tube defects in any unplanned conception.

Ethinyl estradiol in oral contraceptives inhibits CYP1A2, the enzyme that metabolizes caffeine. This roughly doubles caffeine's area-under-the-curve and prolongs its half-life, intensifying jitteriness, insomnia and palpitations.