What cycle day should a perimenopausal woman with an intact uterus start taking progestin (progestogen) in a 28-day menstrual cycle?

Progestin Initiation Timing in Perimenopausal Women

For a perimenopausal woman with an intact uterus on a 28-day cycle, start progestin on cycle day 15 (or days 15-17) and continue for 12-14 consecutive days, completing the regimen by cycle day 28. This sequential approach provides adequate endometrial protection while allowing predictable withdrawal bleeding. 1

Recommended Regimen Structure

The optimal progestin regimen consists of micronized progesterone 200 mg orally at bedtime for 12-14 days per 28-day cycle, paired with continuous transdermal 17β-estradiol 50-100 μg daily. 1, 2 This combination provides proven endometrial protection with the most favorable cardiovascular and metabolic safety profile compared to synthetic progestins. 1

Specific Cycle Day Protocol

• Start progestin on day 15 of a 28-day cycle (counting from the first day of menstrual bleeding as day 1) 1
• Continue daily dosing through day 28 (completing 12-14 consecutive days of progestin exposure) 1, 2
• Withdrawal bleeding typically occurs 2-3 days after completing the progestin course 1
• Begin the next cycle when menstrual bleeding starts, with estrogen continuing uninterrupted 1

Critical Dosing Principles

The 12-14 day duration is non-negotiable for endometrial safety—shorter durations provide inadequate endometrial protection and increase the risk of endometrial hyperplasia. 1, 3 Sequential progestin regimens with exposure less than 12 days per month are explicitly unsafe and should never be used. 4

Preferred Progestin Selection

• First-line: Micronized progesterone 200 mg orally at bedtime for 12-14 days 1, 2

  • Lowest cardiovascular and thrombotic risk profile 1
  • Can be taken vaginally (200 mg) if oral administration is problematic 1

• Second-line alternatives (if micronized progesterone unavailable): 1

  • Dydrogesterone 10 mg daily for 12-14 days
  • Medroxyprogesterone acetate 10 mg daily for 12-14 days (third-line due to less favorable metabolic effects)

Estrogen Component Pairing

Transdermal 17β-estradiol patches (50-100 μg daily) are explicitly preferred over oral formulations due to significantly lower cardiovascular and thrombotic risk, particularly important given that stroke, venous thromboembolism, and coronary events occur within the first 1-2 years of hormone therapy. 1 The estrogen component is administered continuously without interruption throughout the entire 28-day cycle. 1

Alternative Continuous Combined Regimen

For women who prefer amenorrhea and wish to avoid withdrawal bleeding, a continuous combined regimen can be used instead:

• Micronized progesterone 100 mg orally daily without interruption 1
• Paired with continuous transdermal 17β-estradiol 50-100 μg daily 1
• This eliminates the need to track cycle days but may be associated with irregular spotting initially 5

Common Pitfalls to Avoid

Never prescribe progestin alone without estrogen in perimenopausal women requiring hormone therapy—this may paradoxically increase endometrial cancer risk and fails to address vasomotor symptoms. 1

Do not start progestin earlier than day 12 of the cycle as this provides unnecessary progestin exposure without additional endometrial benefit and may worsen side effects like breast tenderness and mood changes. 1, 5

Avoid using ethinylestradiol or conjugated equine estrogens—17β-estradiol is explicitly preferred for perimenopausal women with superior safety profiles. 1

Monitoring Requirements

• Annual clinical review focusing on compliance, bleeding patterns, and symptom control 1
• No routine laboratory monitoring required unless specific symptoms arise (such as abnormal bleeding, breast concerns, or cardiovascular symptoms) 1
• Adjust dose according to the woman's tolerance and feeling of wellbeing 1

Special Clinical Considerations

If the patient has irregular cycles making day 15 difficult to identify, consider switching to a continuous combined regimen (progestin daily without interruption) to avoid timing confusion and ensure consistent endometrial protection. 1, 6 For women with very irregular bleeding patterns, endometrial assessment may be warranted before initiating therapy. 7

Treatment should continue until the average age of natural menopause (45-55 years) if initiated for premature ovarian insufficiency, with regular reassessment of risks versus benefits. 1