When is it typical to increase the dose of progesterone (a progestin hormone) after starting therapy with 100 milligrams?

When to Increase Progesterone Dose After Starting at 100 mg

For patients on progesterone therapy who started at 100 mg, the typical time to increase the dose is after 6 months if the current dose is not achieving the desired clinical effect, as demonstrated by endometrial protection and symptom control. 1

Dosing Guidelines Based on Clinical Context

For Hormone Replacement Therapy in Premature Ovarian Insufficiency:

• In post-pubertal patients with premature ovarian insufficiency, progesterone dosing depends on the estrogen dose and administration pattern:

  • For sequential regimens: 200 mg of oral/vaginal micronized progesterone (MP) for 12-14 days every 28 days 2
  • For continuous regimens: Lower doses (100 mg daily) may be sufficient for endometrial protection 2, 1

• Dose adjustments should be guided by:

  • Patient tolerance and feeling of wellbeing 2
  • Presence of breakthrough bleeding (may indicate need for dose increase) 2
  • Endometrial thickness on ultrasound (if available) 1

Pharmacokinetic Considerations:

• Oral micronized progesterone shows dose-proportional increases in serum concentration across the 100-300 mg range:

  • 100 mg: Cmax 17.3 ng/mL
  • 200 mg: Cmax 38.1 ng/mL
  • 300 mg: Cmax 60.6 ng/mL 3

• Maximum serum concentrations are typically reached within 1.5-2.3 hours after oral administration 3

Evidence-Based Dosing Protocols

For Endometrial Protection in Postmenopausal Women:

• A multicenter study demonstrated that 100 mg/day of micronized progesterone for 25 days per month effectively protected the endometrium and induced amenorrhea in 91.6% of women after 6 months 1

• Higher doses (200-300 mg) are typically used for shorter durations (10-14 days per month) in women who prefer cyclic withdrawal bleeding 4

• For continuous regimens aiming for amenorrhea: 100 mg daily for 25 days per month is effective 1, 4

Common Pitfalls and Considerations:

• Oral progesterone undergoes extensive first-pass metabolism (>90%), resulting in lower bioavailability compared to other routes 5

• Taking progesterone with food increases bioavailability 3

• Drowsiness is a common side effect of oral progesterone, so bedtime administration is recommended 4

• Drug interactions: Ketoconazole and other CYP3A4 inhibitors may increase progesterone bioavailability 3

• Monitoring for endometrial protection should be considered before increasing dose beyond 6 months of therapy 1

Conclusion for Clinical Practice

For most patients starting on 100 mg progesterone, clinicians should:

1. Evaluate clinical response after 3 months
2. If inadequate symptom control or breakthrough bleeding occurs, consider increasing to 200 mg
3. For long-term therapy, reassess at 6 months with consideration of endometrial thickness if available 1, 4

The optimal dose should balance efficacy (endometrial protection, symptom control) with tolerability (minimizing side effects like drowsiness) 4.