Glossary · Pharmacology

Cytochrome P450 (CYP450)

Also called: Cytochrome P450, CYP.

Definition: Cytochrome P450 enzymes are a large family of liver enzymes that metabolize most prescription drugs and steroid hormones. CYP3A4 is the most clinically important for HRT; inhibitors and inducers of CYP3A4 can alter circulating estrogen levels. CYP2D6 affects tamoxifen metabolism, with implications for hot-flash drug choice in tamoxifen patients.

Detailed definition

The cytochrome P450 (CYP) superfamily contains roughly 50 functional enzymes in humans, predominantly localized to liver and gut. The major drug-metabolizing isoforms are CYP3A4 (most abundant; metabolizes ~50% of marketed drugs), CYP2D6, CYP2C9, CYP2C19, and CYP1A2. Estradiol metabolism involves CYP3A4 and CYP1A2 primarily. Genetic polymorphisms in CYP enzymes produce variation in drug metabolism between individuals (poor metabolizers, extensive metabolizers, ultrarapid metabolizers). For HRT-relevant interactions: CYP3A4 inducers (rifampin, carbamazepine, phenytoin, St. John's wort) can lower estradiol levels; strong CYP3A4 inhibitors (ketoconazole, ritonavir) can raise them. CYP2D6 metabolizes tamoxifen to its active metabolite endoxifen; strong CYP2D6 inhibitors (paroxetine, fluoxetine, bupropion) reduce tamoxifen efficacy and should be avoided in tamoxifen patients.

Why it matters in menopause

For most HRT prescribing, CYP-mediated drug interactions are a small consideration. The notable exception is choosing hot-flash treatment in tamoxifen patients: avoid paroxetine and fluoxetine, prefer venlafaxine, gabapentin, or fezolinetant.

Sources

External references: Wikipedia.

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