Estradiol × Phenobarbital

Phenobarbital is a strong CYP3A4 inducer; it lowers oestradiol levels by 40–60%. On menopausal hormone therapy, menopausal symptoms may return. On combined oral contraceptives, unplanned pregnancy risk arises.

Return of vasomotor symptoms: hot flushes, night sweats, sleep disturbance. On oral contraceptives: breakthrough bleeding, conception risk.

On menopausal hormone therapy, raise the oestradiol dose or switch to transdermal forms. For contraception on phenobarbital, combined oral contraceptives are unsuitable — choose a levonorgestrel IUS, copper IUD, or depot medroxyprogesterone acetate. In young women with epilepsy, consider switching phenobarbital to levetiracetam or lamotrigine (no CYP3A4 induction).