Detailed definition
Oral HRT formulations include estradiol tablets (Estrace, generic), conjugated equine estrogens (Premarin), oral micronized progesterone (Prometrium), medroxyprogesterone acetate (Provera), and combination tablets (Activella, Prempro). Oral estradiol is absorbed from the small intestine, undergoes substantial first-pass conversion to estrone in the liver and gut, and reaches systemic circulation at a fraction of the dose. The first-pass effect on hepatic protein synthesis raises sex hormone-binding globulin (SHBG), thyroid-binding globulin, certain clotting factors, and triglycerides. This translates to a small but measurable increase in VTE risk relative to transdermal estradiol, generally around a doubling of relative risk in observational studies (still a low absolute risk in healthy women under 60). Oral progesterone, by contrast, undergoes first-pass conversion to allopregnanolone — the basis for its sleep-promoting effect when dosed at bedtime.
Why it matters in menopause
For estrogen, transdermal is generally preferred over oral when feasible. For progesterone, oral is often preferred for women who want the sleep benefit. ClearedRx commonly prescribes a transdermal estradiol patch or gel paired with bedtime oral micronized progesterone for women with an intact uterus.
Related terms
Sources
External references: Wikipedia.