What is the dose of progesterone for Hormone Replacement Therapy (HRT)?

From the Guidelines

The typical dose of progesterone for hormone replacement therapy (HRT) is 100-200 mg daily, taken orally at bedtime, as recommended by the most recent guidelines 1. For women with an intact uterus who are using estrogen therapy, progesterone is essential to protect the uterine lining from excessive growth. Micronized progesterone (Prometrium) is the preferred form as it's identical to the body's natural progesterone and has fewer side effects than synthetic progestins, with a safer pharmacological profile 1. The medication should be taken continuously for women on continuous estrogen therapy, or for 12-14 days per month for those on cyclical estrogen therapy. Some key points to consider when prescribing progesterone for HRT include:

• The dose of progestogen is based on the concurrent dose of estrogen administered 1
• Micronized progesterone has a neutral or beneficial effect on blood pressure and one of the best safety profiles in terms of thrombotic risk 1
• Progesterone therapy should be individualized based on symptoms, medical history, and risk factors 1
• Women should have regular follow-ups to assess effectiveness and adjust dosing as needed 1
• Progesterone works by stabilizing the endometrial lining and preventing estrogen-induced hyperplasia, which could increase the risk of endometrial cancer 1. Common side effects include drowsiness (hence bedtime dosing), dizziness, and breast tenderness. Vaginal progesterone preparations are also available (45-100 mg daily) and may cause fewer systemic side effects. It's worth noting that other progestins, such as medroxyprogesterone acetate (MPA) and dydrogesterone, can be used as alternatives, but micronized progesterone is generally preferred due to its safer profile 1.

From the FDA Drug Label

The treatment groups were: Progesterone capsules at the dose of 200 mg per day for 12 days per 28-day cycle in combination with conjugated estrogens 0.625 mg per day Progesterone capsules administered orally for 10 days at 400 mg per day Progesterone capsules, 300 mg per day or 400 mg per day, for 10 days of each treatment cycle

The dose of progesterone for hormone replacement is 200 mg per day for 12 days per 28-day cycle in combination with conjugated estrogens, or 300-400 mg per day for 10 days. 2

From the Research

Dose of Progesterone for Hormone Replacement

• The dose of progesterone for hormone replacement therapy (HRT) can vary depending on the specific regimen and the individual woman's needs 3.
• A study published in 1999 found that a cyclic combined regimen comprising estrogen and 100 mg micronized progesterone administered on days 1-25 provided endometrial safety, absence of bleeding, and a high rate of tolerability 3.
• Another study published in 2012 found that the addition of a minimum of 1 mg norethisterone acetate (NETA) or 1.5 mg medroxyprogesterone acetate (MPA) to estrogen therapy decreased the risk of endometrial hyperplasia 4.
• A review published in 2000 found that the addition of progestogens, either in continuous combined or sequential regimens, helped to prevent the development of endometrial hyperplasia and improved adherence to therapy 5.
• A review published in 2004 found that continuous therapy was more effective than sequential therapy in reducing the risk of endometrial hyperplasia at longer durations of treatment 6.
• A systematic review published in 2024 found that most progestogens were only available as oral formulations and that the most frequently studied progestogens were assessed in continuously as well as in sequentially combined MHT regimens 7.

Progesterone Dosing Regimens

• Cyclic combined regimen: estrogen and 100 mg micronized progesterone administered on days 1-25 3.
• Continuous combined regimen: estrogen and a minimum of 1 mg norethisterone acetate (NETA) or 1.5 mg medroxyprogesterone acetate (MPA) 4.
• Sequential regimen: estrogen and progestogen administered in a sequential manner, with progestogen given every month or every three months 5, 6.

Key Findings

• The addition of progestogens to estrogen therapy decreases the risk of endometrial hyperplasia 3, 4, 5, 6.
• Continuous therapy is more effective than sequential therapy in reducing the risk of endometrial hyperplasia at longer durations of treatment 6.
• The choice of progestogen and dosing regimen should be individualized based on the woman's specific needs and medical history 7.