What is the recommended dosing regimen for progesterone (a progestin) in postmenopausal women?

From the Guidelines

The recommended dosing regimen for progesterone in postmenopausal women is typically 100-200 mg daily, taken orally at bedtime. For women with an intact uterus who are using estrogen therapy, progesterone is added to prevent endometrial hyperplasia and reduce the risk of endometrial cancer. Micronized progesterone is generally preferred over synthetic progestins due to its more favorable side effect profile and cardiovascular risk profile, as noted in a study published in 2021 1. The progesterone should be taken continuously if estrogen is used continuously, or for 12-14 days per month if using a cyclic estrogen regimen. Vaginal progesterone preparations are also available at doses of 45-100 mg daily or every other day, which may cause fewer systemic side effects while still providing endometrial protection. Progesterone therapy may cause side effects including drowsiness (hence the bedtime dosing recommendation), dizziness, breast tenderness, and mood changes. Women should be monitored periodically with endometrial assessment if abnormal bleeding occurs. The duration of therapy should be individualized based on menopausal symptoms, risk factors, and treatment goals, with regular reassessment of the benefits and risks.

Some key points to consider when prescribing progesterone therapy include:

• The use of the lowest effective dose for the shortest possible time, as recommended by other expert groups 1
• The potential benefits and harms of hormone therapy, including the increased risk of stroke, deep vein thrombosis, and breast cancer, as well as the potential benefits of reducing the risk of fractures and colorectal cancer 1
• The importance of individualizing therapy based on a woman's clinical situation, preferences, and values, as well as her risk factors and treatment goals 1
• The need for regular monitoring and reassessment of the benefits and risks of therapy, including periodic endometrial assessment if abnormal bleeding occurs 1
• The potential benefits of using micronized progesterone, which has a more favorable side effect profile and cardiovascular risk profile compared to synthetic progestins 1
• The importance of considering alternative approaches to prevention, such as weight-bearing exercise, bisphosphonates, and calcitonin for osteoporosis, and tamoxifen or raloxifene for breast cancer prevention 1

From the FDA Drug Label

Prevention of Endometrial Hyperplasia: A postmenopausal woman with a uterus who is taking estrogens should take a single daily dose of 200 mg progesterone capsules at bedtime for 12 continuous days per 28-day cycle. Progesterone capsules should be given as a single daily dose at bedtime, 200 mg orally for 12 days sequentially per 28-day cycle, to a postmenopausal woman with a uterus who is receiving daily conjugated estrogens tablets.

The recommended dosing regimen for progesterone in postmenopausal women is 200 mg orally at bedtime for 12 days per 28-day cycle to prevent endometrial hyperplasia when taken with estrogens 2 2.

From the Research

Progesterone Dosing Regimens

The recommended dosing regimen for progesterone in postmenopausal women varies depending on the specific formulation and the individual's needs. Some key points to consider include:

• Oral micronized progesterone can be taken at a dose of 200 mg/day for 12-14 days/month to provide endometrial protection 3
• Vaginal micronized progesterone may be used at a dose of 4% (45 mg/day) or 100 mg/day every other day for at least 10 days/month to provide endometrial protection 3
• Continuous daily oral micronized estradiol and progesterone can be taken at a dose of 0.7-1.05 mg and 200-300 mg, respectively, to alleviate menopausal symptoms and provide endometrial protection 4
• Oral micronized progesterone can be taken at a dose of 300 mg at bedtime to treat hot flushes and night sweats, improve sleep, and prevent breast cancer in estrogen-treated women 5

Factors to Consider

When determining the appropriate progesterone dosing regimen for postmenopausal women, several factors should be considered, including:

• The individual's medical history and current health status
• The specific formulation of progesterone being used (e.g. oral, vaginal, transdermal)
• The presence of any contraindications or potential interactions with other medications
• The individual's response to treatment and any potential side effects

Potential Side Effects

Some potential side effects of progesterone therapy in postmenopausal women include:

• Mild and transient drowsiness, which can be minimized by taking the medication at bedtime 6
• Changes in bleeding patterns, including amenorrhea or withdrawal bleeding 6, 4
• Potential effects on lipid profiles and cardiovascular health, although these effects may be beneficial in some cases 4, 5