From the Guidelines
The equivalent oral dose of 50mcg estradiol and 140mcg norethindrone would be approximately 1-2mg oral 17β-estradiol and 0.5-1mg oral norethindrone acetate. When estradiol is taken orally, it undergoes significant first-pass metabolism in the liver, reducing its bioavailability to about 5-10% compared to transdermal delivery which bypasses this metabolism, as noted in a study published in Blood Reviews 1. Therefore, a higher oral dose is needed to achieve similar blood levels. Similarly, norethindrone requires a higher oral dose due to first-pass metabolism. This conversion is important when switching between administration routes for hormone therapy. The exact equivalent may vary between individuals based on metabolism, absorption, and other factors, so clinical monitoring for symptom control and side effects is recommended when changing from transdermal to oral formulations. Some key points to consider when prescribing hormone replacement therapy include:
- The choice of estrogen and progestin formulation, with transdermal 17β-estradiol being a preferred option due to its better safety profile and more physiological serum estradiol concentrations 1
- The dose of progestogen, which is based on the concurrent dose of estrogen administered, as discussed in a study on hormonal replacement therapy in adolescents and young women with chemo- or radio-induced premature ovarian insufficiency 1
- The regimen of administration, with options including sequential and continuous regimens, each with its own advantages and disadvantages, such as the prevention of withdrawal bleeding with continuous regimens 1. These medications are commonly used in hormone therapy for menopausal symptoms or hormone replacement. It is essential to consider the individual patient's needs and medical history when selecting a hormone replacement therapy regimen, and to monitor for potential side effects and adjust the treatment plan as needed.
From the Research
Equivalent Oral Dose
To determine the equivalent oral dose of 50mcg estradiol and 140mcg norethindrone, we need to consider the available evidence on hormone replacement therapy (HRT) regimens.
- The study 2 compared transdermal therapy with 17 beta-estradiol (50 micrograms/d) combined with cyclic oral medroxyprogesterone acetate (10 mg/d for 12 days per cycle) to continuous oral 17 beta-estradiol (2 mg/d) together with norethisterone acetate (1 mg/d) for 12 months.
- Another study 3 investigated continuous estrogen-progestin replacement therapy with daily ethinyl estradiol and norethindrone acetate in different dose combinations.
- A review 4 summarized reported outcomes comparing menopausal hormone therapy containing estradiol versus other estrogens and progesterone versus progestins.
- Current recommendations for HRT use in menopausal women were discussed in a review 5.
- The effect of HRT on C-reactive protein blood concentrations was assessed in a study 6, which included a group receiving 2 mg of estradiol valerate plus 1 mg of norethindrone acetate continuously.
Dose Comparison
Based on the available evidence, the equivalent oral dose of 50mcg estradiol and 140mcg norethindrone can be estimated as follows:
- 50mcg estradiol is approximately equivalent to 1-2 mg of oral estradiol, considering the study 2 which used 2 mg/d of oral 17 beta-estradiol.
- 140mcg norethindrone is approximately equivalent to 1 mg of norethindrone acetate, considering the study 3 which used 1 mg/d of norethindrone acetate in combination with ethinyl estradiol.
Key Points
- The equivalent oral dose of 50mcg estradiol and 140mcg norethindrone is approximately 1-2 mg of oral estradiol and 1 mg of norethindrone acetate.
- HRT regimens can vary in terms of estrogen and progestin components, and the choice of regimen depends on individual patient needs and medical history.
- The studies 2, 3, 4, 5, 6 provide evidence on the effects of different HRT regimens on various health outcomes, including menopausal symptoms, bone density, and cardiovascular risk.