What dose of progesterone (Progesterone) should be started for a patient with low progesterone levels?

Progesterone Dosing for Low Progesterone Levels

For women with low progesterone requiring hormone replacement therapy, start with micronized progesterone (MP) 200 mg orally or vaginally for 12-14 days every 28 days when used sequentially with estrogen, or 100-200 mg daily for continuous regimens. 1

Sequential Regimen (First-Line Recommendation)

Micronized progesterone is the preferred progestogen due to its superior cardiovascular and thromboembolism safety profile compared to synthetic progestins. 1

• Oral or vaginal micronized progesterone: 200 mg daily for 12-14 days every 28 days when combined with continuous estrogen therapy 1
• Alternative dosing: 100 mg daily for 12-14 days per month is acceptable for lower-dose estrogen regimens 1
• Vaginal administration achieves physiologic endometrial effects despite lower systemic levels due to direct uterine uptake 2, 3

Alternative Progestins (Second-Line)

If micronized progesterone is contraindicated or poorly tolerated:

• Medroxyprogesterone acetate (MPA): 10 mg daily for 12-14 days per month 1
• Dydrogesterone: 10 mg daily for 12-14 days per month 1
• Norethisterone: 5 mg daily for 12-14 days per month 1

Continuous Combined Regimens

For patients who wish to avoid withdrawal bleeding:

• Micronized progesterone: minimum 100 mg daily continuously 4
• MPA: 2.5 mg daily continuously 1
• Dydrogesterone: 5 mg daily continuously 1
• Norethisterone: 1 mg daily continuously 1

Route-Specific Considerations

Vaginal administration offers advantages over oral dosing:

• 400 mg vaginal progesterone twice daily achieves optimal secretory transformation (90% rate) compared to lower doses 5
• 200 mg vaginal suppositories every 12 hours maintain stable physiologic levels (mean 46.4 nmol/L) with minimal fluctuation 2
• Peak plasma concentrations occur at 2-6 hours with vaginal administration, lasting 24 hours 6, 7
• Vaginal route bypasses first-pass hepatic metabolism, reducing drowsiness and dizziness common with oral dosing 3

Oral micronized progesterone:

• 300-400 mg daily for 10 days induces withdrawal bleeding in 73-77% of women with secondary amenorrhea 4
• 400 mg daily for 10 days produces complete secretory transformation in 45% of estrogen-primed women 4
• Food increases bioavailability; should be taken consistently with or without food 4

Critical Timing Considerations

Progestin should only be added after 2-3 years of estrogen-only therapy in pubertal induction, or when breakthrough bleeding occurs. 1

• Confirm adequate endometrial thickness via ultrasound before initiating progestin 1
• In post-pubertal women with established cycles, begin progestin immediately with estrogen therapy 1

Important Caveats

Avoid progestins with anti-androgenic effects in women with low testosterone or sexual dysfunction, as they may worsen hypoandrogenism 1

Do not confuse different progesterone formulations:

• Injectable 17-alpha-hydroxyprogesterone caproate (17P) 250 mg IM weekly is specifically for preterm birth prevention, not for general progesterone replacement 8
• Vaginal gel 90 mg daily or suppositories 200 mg daily are alternatives for early pregnancy bleeding with prior miscarriage history 8

Pharmacokinetic considerations:

• Progesterone exhibits dose-dependent but not dose-proportional absorption 5, 7
• The ratio of AUC for 200 mg versus 100 mg vaginal dose is only 1.37, not 2.0 7
• Ketoconazole and other CYP3A4 inhibitors may increase progesterone bioavailability 4

Monitoring and Duration

• Continue hormone replacement therapy until the average age of natural menopause (45-55 years) 1
• No specific laboratory monitoring is required beyond standard gynecologic care 8
• Adjust dosing based on symptom control and tolerance rather than serum levels 1