What are the indications and dosages for progesterone (a steroid hormone)?

Indications and Dosages for Progesterone

Progesterone is indicated primarily for prevention of endometrial hyperplasia in postmenopausal women receiving estrogen therapy, treatment of secondary amenorrhea, and prevention of preterm birth in specific high-risk populations. 1, 2

FDA-Approved Indications and Dosages

Prevention of Endometrial Hyperplasia

• Oral progesterone 200 mg daily at bedtime for 12 days sequentially per 28-day cycle in postmenopausal women with intact uterus who are receiving daily conjugated estrogens 1
• Clinical studies show this regimen significantly reduces the incidence of endometrial hyperplasia (6% with progesterone plus estrogen vs. 64% with estrogen alone) 1

Treatment of Secondary Amenorrhea

• Oral progesterone 400 mg daily at bedtime for 10 days 1
• Administration results in approximately 80% of women experiencing withdrawal bleeding within 7 days of the last dose 1

Preterm Birth Prevention

Singleton Pregnancy with Prior Spontaneous Preterm Birth (SPTB)

• 17-alpha-hydroxyprogesterone caproate (17P) 250 mg IM weekly starting at 16-20 weeks until 36 weeks is the recommended treatment 2
• This regimen reduces the incidence of recurrent preterm birth at <37 weeks (RR 0.66; 95% CI 0.54-0.81) and reduces neonatal complications 2

Singleton Pregnancy with Short Cervical Length (CL)

• Vaginal progesterone 90 mg gel or 200 mg suppository daily from diagnosis of short cervical length (≤20 mm at ≤24 weeks) until 36 weeks 2
• This is recommended for women without prior preterm birth but with short cervical length identified on transvaginal ultrasound 2

Important Clinical Considerations

Multiple Gestations

• Progesterone therapy (either 17P or vaginal progesterone) is not effective for prevention of preterm birth in multiple gestations 2
• Multiple clinical trials have shown no significant reduction in preterm birth rates or perinatal morbidity/mortality in twin or triplet pregnancies 2

Threatened Preterm Labor

• Insufficient evidence to recommend progesterone for primary, adjunctive, or maintenance tocolysis 2
• Some studies show reduced contraction frequency with oral progesterone 400 mg, but without significant impact on preterm birth outcomes 2

Preterm Premature Rupture of Membranes (PPROM)

• Insufficient evidence to recommend progesterone therapy in women with PPROM 2
• In women already receiving 17P for prior spontaneous preterm birth, it is reasonable to continue after membrane rupture 2

Threatened Abortion/Early Pregnancy Bleeding

• Evidence for progesterone use in threatened abortion is inconsistent 3, 4
• Recent large RCT (PRISM) found progesterone did not significantly increase live birth rates overall, but showed benefit in the subgroup of women with early pregnancy bleeding and history of previous miscarriage(s) 5

Route of Administration Considerations

• Oral progesterone: Effective for endometrial protection and secondary amenorrhea; may cause mild drowsiness (take at bedtime) 1, 6
• Vaginal progesterone: Preferred for preterm birth prevention in women with short cervical length; may provide endometrial protection at 45 mg/day for at least 10 days/month 2, 7
• Intramuscular progesterone (17P): Preferred for preterm birth prevention in women with prior spontaneous preterm birth 2
• Transdermal progesterone: Does not provide adequate endometrial protection 7

Common Pitfalls and Caveats

• Progesterone should not be used in multiple gestations as it shows no benefit 2
• Cervical length screening and progesterone treatment should follow strict guidelines with proper technique and quality control 2
• For preterm birth prevention, different progesterone preparations are not interchangeable; use 17P for prior preterm birth and vaginal progesterone for short cervical length 2
• Oral progesterone should be taken with water while standing to avoid swallowing difficulties 1