What are the clinical uses of progesterone?

Clinical Uses of Progesterone

Progesterone is primarily used for prevention of preterm birth in high-risk pregnancies, treatment of menstrual irregularities, and endometrial protection during hormone therapy. 1, 2

Prevention of Preterm Birth

Progesterone plays a crucial role in pregnancy maintenance and preterm birth prevention in specific high-risk populations:

Singleton Pregnancies with Prior Preterm Birth

• 17-alpha-hydroxy-progesterone caproate (17P): 250 mg IM weekly from 16-20 weeks until 36 weeks 1
• This intervention significantly reduces the risk of recurrent preterm birth and perinatal morbidity/mortality

Singleton Pregnancies with Short Cervix (≤20 mm)

• Vaginal progesterone: Either 90-mg gel or 200-mg suppository daily from diagnosis until 36 weeks 1
• Significantly reduces preterm birth rates and improves neonatal outcomes

Gynecological Applications

Treatment of Menstrual Irregularities

• Secondary amenorrhea: 400 mg oral micronized progesterone daily at bedtime for 10 days 3, 4
• Induces withdrawal bleeding in women with amenorrhea or oligomenorrhea due to progesterone deficiency
• Used diagnostically as a challenge test to evaluate primary or secondary amenorrhea 4

Dysfunctional Uterine Bleeding

• Treats abnormal uterine bleeding due to anovulatory cycles, particularly in adolescents and perimenopausal women 5
• Helps regulate menstrual cycles by providing the progesterone needed for normal endometrial function

Hormone Replacement Therapy

Endometrial Protection

• Postmenopausal women with intact uterus: 200 mg oral micronized progesterone daily at bedtime for 12 continuous days per 28-day cycle 3, 2
• Counteracts estrogen-induced endometrial hyperplasia by transforming proliferative endometrium into secretory endometrium 2
• Reduces risk of endometrial cancer in women taking estrogen therapy 5

Other Clinical Applications

• Luteal phase support: Used in assisted reproductive technology procedures to support implantation and early pregnancy 6
• Premenstrual syndrome: May help alleviate symptoms through neurosteroid effects 4
• Polycystic ovary syndrome: Used in management of menstrual irregularities 4

Administration Routes and Formulations

1. Oral micronized progesterone

   • Improved bioavailability compared to non-micronized forms
   • Take at bedtime due to potential drowsiness and dizziness 3
   • Better safety profile than synthetic progestins for cardiovascular and metabolic risks 4

2. Vaginal progesterone

   • Available as gel, suppositories, or tablets
   • Provides direct vagina-to-uterus transport with preferential uterine uptake 7
   • Lower systemic side effects than oral administration

3. Injectable progesterone

   • 17P for preterm birth prevention
   • Higher systemic levels but requires weekly administration

Important Considerations and Cautions

• Side effects: Common side effects include drowsiness, dizziness, and headaches 3

• Contraindications: Should not be used in women with:

  • Current or history of breast cancer
  • Active liver disease
  • Undiagnosed vaginal bleeding
  • History of thromboembolic disorders 3

• Cardiovascular risk: When combined with estrogen, may increase risk of venous thromboembolism 2, 3

• Peanut allergy: Some formulations contain peanut oil and should be avoided in patients with peanut allergies 3

Clinical Pearls

• Administer oral progesterone at bedtime to minimize side effects of drowsiness and dizziness
• Natural micronized progesterone has fewer metabolic side effects than synthetic progestins
• For preterm birth prevention, patient selection is crucial - progesterone is not effective for multiple gestations or women with preterm labor or premature rupture of membranes 1
• Vaginal progesterone may be preferred when systemic side effects are a concern 7