Cyclic Progesterone Dosing
For women with an intact uterus receiving estrogen therapy, administer progesterone for 12-14 days every 28 days, using either 200 mg oral micronized progesterone daily, 10 mg medroxyprogesterone acetate daily, or 10 mg dydrogesterone daily. 1
Standard Dosing Regimens
Sequential (Cyclic) Therapy - First Choice
When estrogen is given continuously, add progestin cyclically to protect the endometrium:
- Micronized progesterone (MP): 200 mg orally or vaginally for 12-14 days every 28 days 1
- Medroxyprogesterone acetate (MPA): 10 mg orally for 12-14 days per month 1
- Dydrogesterone: 10 mg orally for 12-14 days per month 1
Micronized progesterone is the preferred first-line progestin because it demonstrates lower cardiovascular and venous thromboembolism risk compared to synthetic progestins while providing adequate endometrial protection 1. This is particularly important for women at elevated cardiovascular risk.
Continuous Combined Therapy - Alternative Option
For women who wish to avoid withdrawal bleeding:
However, continuous progestin exposure has raised concerns about increased breast cancer risk with certain synthetic progestins 2, making sequential therapy generally preferable when withdrawal bleeding is acceptable.
Long-Cycle Alternative
Long-cycle therapy using progestin for 14 days every 3 months has been proposed to reduce breast exposure to progestins 2. While not as well-validated for endometrial protection, this approach may be considered in select patients, though it requires careful endometrial monitoring 2.
Route-Specific Considerations
Oral Administration
The standard and most studied route. Oral micronized progesterone at 200 mg daily for 12-14 days per month provides proven endometrial protection for up to 5 years 3.
Vaginal Administration
Vaginal micronized progesterone 200 mg daily for 12-14 days every 28 days is equally effective as oral administration 1. Vaginal progesterone at 4% gel (45 mg/day) or 100 mg every other day for at least 10 days per month may provide endometrial protection for 3-5 years, though this is off-label use 3.
Transdermal Administration
Transdermal progesterone does NOT provide adequate endometrial protection and should not be used for this purpose 3.
Critical Monitoring Points
Any unexpected or breakthrough bleeding requires immediate endometrial evaluation with ultrasound and endometrial biopsy, regardless of the bleeding pattern 2. There are no specific bleeding patterns reliably associated with normal versus abnormal endometrial histology.
Common Pitfalls to Avoid
Insufficient duration: Progestin must be given for at least 10-14 days per cycle—shorter durations do not provide adequate endometrial protection 2, 4, 2
Wrong route: Never rely on transdermal progesterone alone for endometrial protection 3
Unopposed estrogen: In women with an intact uterus, estrogen without progestin dramatically increases endometrial cancer risk and is contraindicated 2, 4
Ignoring breakthrough bleeding: Any unscheduled bleeding warrants endometrial assessment regardless of the regimen used 2
Practical Implementation
Start progesterone on day 14-15 of a 28-day cycle (or after 14 days of continuous estrogen) and continue through day 27-28. This produces predictable withdrawal bleeding in most women, typically beginning 2-3 days after stopping progesterone 1, 2.
The dose should remain consistent throughout the treatment period—do not taper or adjust mid-cycle. Adjust the overall regimen based on bleeding patterns, side effects, and patient tolerance, but maintain adequate dosing for endometrial protection.