Glossary · Pharmacology

Route of administration

Definition: Route of administration is how a drug is delivered to the body — oral, transdermal, vaginal, intramuscular, subcutaneous, sublingual, or intrauterine. For HRT, route choice profoundly affects pharmacokinetics, side effects, and safety. Transdermal estradiol vs. oral estradiol is the most consequential route choice in modern HRT.

Detailed definition

Route of administration determines a drug's pharmacokinetics: absorption rate and extent, first-pass metabolism, distribution, and elimination. For estrogens, the relevant routes in HRT are: oral (tablets — extensive first-pass hepatic metabolism, raising VTE risk and SHBG), transdermal (patches, gels, sprays — bypass first-pass, neutral on VTE), vaginal (creams, tablets, inserts, rings — local effect with minimal systemic absorption at low doses, or systemic at higher-dose rings like Femring), intramuscular (depot injectables, less common in modern HRT), and subcutaneous (pellets — not recommended). For progestogens, oral micronized progesterone produces sleep-promoting allopregnanolone via first-pass metabolism (a benefit), while vaginal progesterone produces less allopregnanolone but adequate endometrial protection. The 52-mg LNG-IUD is an intrauterine route option for endometrial protection.

Why it matters in menopause

Route choice is one of the most consequential decisions in HRT. ClearedRx defaults to transdermal estradiol plus oral micronized progesterone for most women, with vaginal estrogen for GSM and the LNG-IUD as alternatives.

Sources

External references: Wikipedia.

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