What are the typical doses of progesterone and estrogen (hormone replacement therapy, HRT) used for hormone replacement?

From the Guidelines

The recommended dose of progesterone and estrogen for hormone replacement therapy is oral conjugated equine estrogen 0.625 mg/d and medroxyprogesterone acetate 2.5 mg/d, as this combination has been shown to have a moderate benefit in reducing the risk for fractures in postmenopausal women 1.

Key Considerations

• The dose of estrogen and progesterone should be individualized based on the patient's age, time since menopause, symptom severity, and personal risk factors for cardiovascular disease, breast cancer, and venous thromboembolism.
• Treatment should start at the lowest effective dose and be adjusted based on symptom control.
• Regular follow-up appointments are essential to monitor effectiveness and potential side effects, with annual reassessment of the risk-benefit profile to determine if continued therapy is appropriate.

Alternative Options

• Transdermal options, such as estradiol patches (0.025-0.1 mg/day) changed twice weekly, may be considered for patients who cannot tolerate oral medications or have certain medical conditions.
• Micronized progesterone (Prometrium) 100-200 mg daily may be used as an alternative to medroxyprogesterone acetate (Provera) for patients who experience side effects or have certain medical conditions.

Important Safety Information

• Estrogen and progesterone therapy has been associated with an increased risk of stroke, dementia, gallbladder disease, and urinary incontinence, as well as a small increase in the risk for invasive breast cancer and breast cancer deaths 1.
• Patients should be closely monitored for these potential side effects and the risk-benefit profile should be regularly reassessed to determine if continued therapy is appropriate.

From the Research

Dose of Progesterone and Estrogen for Hormone Replacement

• The dose of progesterone and estrogen for hormone replacement therapy (HRT) can vary depending on the regimen and the individual woman's needs 2, 3, 4, 5, 6.
• Low doses of estrogens, such as estradiol 1 mg and conjugated equine estrogens 0.3 mg orally per day, or transdermally applied estradiol 25 mug per 24 hours, have been shown to be effective for the treatment of vasomotor symptoms and for prevention of bone loss 4, 5, 6.
• Low doses of progestogen, especially if given on a continuous basis, have been shown to protect the endometrium from hyperplasia 4.
• Emerging trends suggest that lower doses of estrogen (i.e. ethinylestradiol 5 microg/day, estradiol 0.25 mg/day or conjugated estrogens [CEE] 0.3 mg/day) continuously combined with lower doses of medroxyprogesterone (MPA) are equally effective at relieving vasomotor symptoms as the most commonly prescribed regimen in the US (CEE 0.625mg/MPA 2.5mg daily), with fewer adverse events 5.
• The lowest doses of estrogen currently approved by the FDA for prevention of osteoporosis include 0.3 mg esterified estrogens, 0.025 microg transdermal estradiol patch, and 0.5 mg micronized estradiol 6.

Regimens for HRT

• Continuous combined HRT using 2.5 mg of medroxyprogesterone was designed to increase patient compliance by eliminating withdrawal bleeding while at the same time retaining the beneficial effects of HRT 3.
• Cyclic estrogen regimens with higher doses have been in use longer, but they often necessitate more frequent progestin treatment and may result in cyclic bleeding or breast tenderness 6.
• Continuous combined regimens are simple and easy-to-use, and are designed to minimize bleeding 6.

Considerations for Dosing

• The protective effect of progestogens against hyperplasia and endometrial cancer does not appear to differ with different progestogens (micronized progesterone or progestogens), but appears to be affected by the regimen and thus the dose, with continuous combined treatment conferring better protection 2.
• The possible increased risk of endometrial cancer associated with continuous combined HRT may be related to inadequate progestin dose, prior use of unopposed estrogen, poor patient compliance, use of less effective progestins, less efficient reversal of hyperplasia, and the use of progestin continuously 3.