What are the considerations for choosing cyclic versus daily progesterone (progestogen) in Hormone Replacement Therapy (HRT)?

From the Guidelines

When choosing between cyclic and daily progestogen in hormone replacement therapy (HRT), cyclic progestogen (typically 12-14 days per month) is generally recommended for women with premature ovarian insufficiency (POI), as it allows for an earlier recognition of a pregnancy and may have a more favorable safety profile 1.

Key Considerations

• The choice between cyclic and daily progestogen regimens should consider the woman's menopausal status, bleeding preferences, and side effect profile.
• Women with an intact uterus must take progestogen with estrogen to prevent endometrial hyperplasia.
• Micronized progesterone (MP) is considered a first-choice progestin due to its favorable safety profile, with a lower risk of cardiovascular disease and venous thromboembolism when taken with cyclical administration 1.

Progestogen Options

• For cyclic therapy, common options include micronized progesterone (200mg for 12-14 days/month), medroxyprogesterone acetate (5-10mg for 12-14 days/month), or norethindrone acetate (1-2mg for 12-14 days/month) 1.
• For continuous combined therapy, common options include micronized progesterone (100mg daily), medroxyprogesterone acetate (2.5-5mg daily), or norethindrone acetate (0.5-1mg daily) 1.

Important Factors

• The dose of progestogen is based on the concurrent dose of estrogen administered.
• Women with POI may spontaneously ovulate, and cyclic administration allows for an earlier recognition of a pregnancy.
• The European Society for Human Reproduction and Embryology (ESHRE) recommends MP among the progestogens in HRT in adult women with ovarian insufficiency 1.

From the FDA Drug Label

When estrogen is prescribed for a postmenopausal woman with a uterus, a progestin should also be initiated to reduce the risk of endometrial cancer. Administration should be cyclic (e.g., 3 weeks on and 1 week off).

The choice between cyclic and daily progestogen HRT should be based on the individual woman's needs and treatment goals.

• For women with a uterus, cyclic administration (e.g., 3 weeks on and 1 week off) is recommended to reduce the risk of endometrial cancer 2.
• The decision to use cyclic or daily progestogen HRT should be made under the guidance of a healthcare provider, taking into account the lowest effective dose and shortest duration consistent with treatment goals and risks for the individual woman.

From the Research

Cyclic vs Daily Progesterone HRT

• The choice between cyclic and daily progesterone hormone replacement therapy (HRT) depends on various factors, including the individual's menopausal symptoms, medical history, and personal preferences 3.
• Cyclic progesterone HRT involves taking progesterone for a certain number of days each month, usually 12-14 days, to mimic the natural menstrual cycle 3.
• Daily progesterone HRT, on the other hand, involves taking a combination of estrogen and progesterone every day to minimize bleeding and maximize symptom relief 4, 3.

Benefits of Cyclic Progesterone HRT

• Cyclic progesterone HRT has been shown to have several benefits, including minimal progestin exposure, low rate of withdrawal bleeding, and lowered side effects 3.
• This type of HRT is often used with low-dose estrogen, which can help minimize the risk of endometrial hyperplasia and other side effects 5, 3.
• Cyclic progesterone HRT can also provide a higher comfort level for some women, as it allows for a more natural hormonal cycle 3.

Benefits of Daily Progesterone HRT

• Daily progesterone HRT has been shown to be effective in relieving menopausal symptoms, including hot flashes and night sweats 4, 3.
• This type of HRT can also help minimize bleeding, as the continuous combination of estrogen and progesterone can help thin the uterine lining 4, 3.
• Daily progesterone HRT is often simpler and easier to use than cyclic progesterone HRT, as it involves taking a single pill or patch every day 3.

Endometrial Safety

• Both cyclic and daily progesterone HRT have been shown to be effective in providing endometrial protection, although the risk of endometrial hyperplasia may vary depending on the specific regimen and individual factors 6, 7.
• A systematic review of 84 RCTs found that most progestogens used in combined MHT were effective in providing endometrial protection, although study quality varied 6.
• Another study found that a triphasic sequential hormone replacement estradiol valerate/medroxyprogesterone acetate therapy regimen was well tolerated and produced endometrial effects similar to those of two comparator treatments 7.