What are the uses and dosages of progesterone in medical treatment?

Progesterone: Clinical Uses and Dosing

Progesterone is primarily used in obstetrics for preterm birth prevention and in gynecology for endometrial protection during hormone replacement therapy, with specific dosing regimens that depend on the clinical indication and patient characteristics.

Preterm Birth Prevention

Singleton Pregnancies with Prior Spontaneous Preterm Birth

For women with a history of spontaneous preterm birth, 17-alpha-hydroxyprogesterone caproate (17P) 250 mg intramuscularly weekly from 16-20 weeks until 36 weeks is the standard of care. 1

• This regimen significantly reduces preterm birth rates and improves neonatal outcomes 1
• Treatment should begin between 16-20 weeks gestation and continue through 36 weeks 1
• If cervical length shortens to ≤25 mm by transvaginal ultrasound at ≥24 weeks despite 17P therapy, continue 17P as there is insufficient evidence to switch formulations 1

Singleton Pregnancies with Short Cervix (No Prior Preterm Birth)

For women without prior spontaneous preterm birth but with cervical length ≤20 mm at 24 weeks, vaginal progesterone 90-mg gel or 200-mg suppository daily from diagnosis until 36 weeks is recommended. 1

• This reduces preterm birth <33 weeks (RR 0.54) and composite neonatal morbidity/mortality (RR 0.41) 1
• Vaginal progesterone 100-mg suppositories between 24-34 weeks reduced preterm birth <37 weeks (24% vs 50%) and <34 weeks (5.4% vs 26.5%) 1
• Progesterone appears most efficacious for moderately short cervical length, while cerclage may be superior for cervical length <15 mm 1

Populations Where Progesterone is NOT Effective

Progesterone should NOT be used in multiple gestations, active preterm labor, or preterm premature rupture of membranes as there is no evidence of benefit. 1

• Multiple trials in twin and triplet gestations showed no reduction in preterm birth or neonatal morbidity with either 17P or vaginal progesterone 1
• No evidence supports progesterone use for acute tocolysis in symptomatic preterm labor 1

Hormone Replacement Therapy

Endometrial Protection in Postmenopausal Women

For postmenopausal women with an intact uterus receiving estrogen therapy, progesterone 200 mg orally at bedtime for 12 days per 28-day cycle is FDA-approved to prevent endometrial hyperplasia. 2, 3, 2

• This regimen reduced endometrial hyperplasia from 64% (estrogen alone) to 6% (estrogen plus progesterone) over 36 months 2
• The medication should be taken as a single daily dose at bedtime with a glass of water while standing 3, 2
• Sequential regimens involve 12-14 days of progesterone per 28-day cycle for patients who accept withdrawal bleeding 4

Alternative Dosing Regimens

Continuous combined regimens are appropriate for patients who prefer to avoid withdrawal bleeding, using lower daily doses of progesterone without interruption. 4

• Micronized progesterone is the first-choice progestin due to lower cardiovascular and thromboembolism risk 4
• Continuous regimens may use minimum doses of 100 mg micronized progesterone daily (though specific FDA approval is for sequential dosing) 4
• Common initial side effects (mood changes, breast tenderness, bloating) typically resolve within 3 months 4

Secondary Amenorrhea

For treatment of secondary amenorrhea, progesterone 400 mg orally at bedtime for 10 days induces withdrawal bleeding in approximately 80% of women. 2, 3, 2

• This single daily dose for 10 days resulted in 73.8-76.8% of women experiencing withdrawal bleeding across treatment cycles 2
• The 400 mg dose induced complete secretory transformation in 45% of estrogen-primed postmenopausal women 2

Assisted Reproductive Technology

Progesterone is critical for luteal phase support following in-vitro fertilization, typically administered via intramuscular or vaginal routes. 5, 6

• Vaginal and intramuscular formulations are effective for luteal support in ART cycles 6
• Non-oral formulations appear more effective than oral routes in this setting 5

Important Clinical Considerations

Formulation Selection

• Micronized progesterone has superior safety profile regarding cardiovascular disease, venous thromboembolism, and breast cancer risk compared to synthetic progestins 4, 7
• Avoid progestins with anti-androgenic effects in patients with diminished libido 4

Monitoring and Adjustment

• Clinical review should occur after 3 months to assess symptom improvement and side effects 4
• If significant side effects persist beyond 6 months, consider alternative formulations 4
• No routine laboratory monitoring is required unless prompted by specific symptoms 4

Common Pitfalls

• Do not use progesterone for acute tocolysis in active preterm labor—it is ineffective 1
• Do not prescribe progesterone for multiple gestations to prevent preterm birth—multiple large trials show no benefit 1
• Ensure adequate duration (12-14 days) when using sequential regimens for endometrial protection—shorter durations may be inadequate 1, 4, 2