What are the reasons for giving progesterone (a steroid hormone)?

Reasons for Giving Progesterone

Progesterone is primarily indicated for prevention of preterm birth in high-risk pregnancies, treatment of menstrual irregularities, hormone replacement therapy, and prevention of pregnancy loss in specific populations. 1, 2

Prevention of Preterm Birth

• In singleton pregnancies with prior spontaneous preterm birth (20-36 6/7 weeks), 17-alpha-hydroxy-progesterone caproate (17P) 250 mg intramuscularly weekly, preferably starting at 16-20 weeks until 36 weeks, is recommended to reduce the risk of recurrent preterm birth 1

• In singleton pregnancies without prior preterm birth but with short cervical length (≤20 mm) at 24 weeks, vaginal progesterone (either 90-mg gel or 200-mg suppository) is effective in reducing preterm birth and perinatal morbidity and mortality 1

• Progesterone works through multiple mechanisms to prevent preterm birth:

  • Anti-inflammatory effects that counteract inflammatory processes leading to preterm birth 1
  • Local increase in progesterone in gestational tissues that counteracts functional progesterone decrease 1
  • Reduction of uterine contractility by counteracting prostaglandin stimulatory activity and oxytocin 3
  • Alteration of cervical stromal degradation and barrier to ascending infection in the cervix 1

Menstrual Disorders

• Treatment of secondary amenorrhea (absence of menstrual periods in women who previously had periods) due to decreased progesterone production 2

  • Typically administered as a single daily dose of 400 mg at bedtime for 10 days 2

• Management of abnormal uterine bleeding due to disordered ovulation 4

• Treatment of luteal phase deficiency, which can contribute to infertility and early pregnancy loss 4

Hormone Replacement Therapy

• Protection of the endometrium (uterine lining) in postmenopausal women with a uterus who are taking estrogen 2

  • Prevents estrogen-induced endometrial hyperplasia that may lead to endometrial cancer 2
  • Typically administered as 200 mg daily at bedtime for 12 continuous days per 28-day cycle 2

• Management of premature ovarian insufficiency (POI) as part of hormone replacement therapy 1

  • Natural micronized progesterone (MP) is preferred due to favorable cardiovascular and thrombotic risk profile 1

Prevention of Pregnancy Loss

• Treatment for women with history of recurrent miscarriage, particularly when combined with current pregnancy bleeding 5

  • Vaginal micronized progesterone 400 mg twice daily has shown benefit in this population 5
  • Greatest benefit observed in women with three or more previous miscarriages and current pregnancy bleeding (15% increase in live birth rate) 5

• Maintenance of early pregnancy by:

  • Modulating maternal immune response and suppressing inflammatory response 3
  • Promoting invasion of extravillous trophoblasts to the decidua by inhibiting apoptosis 3
  • Improving utero-placental circulation 3

Administration Routes and Considerations

• Progesterone can be administered through multiple routes:

  • Vaginal (gel, suppository, tablet) - preferred for pregnancy maintenance and assisted reproduction 6
  • Oral micronized - improved bioavailability but more systemic effects 4
  • Intramuscular - commonly used for preterm birth prevention (17P) 1

• Important safety considerations:

  • Progesterone capsules contain peanut oil and should not be used in patients with peanut allergies 2
  • Common side effects include drowsiness and dizziness, particularly with oral administration 2, 4
  • No long-term adverse effects have been identified in children exposed to progesterone in utero 1

Clinical Pitfalls and Caveats

• Progesterone is not effective for prevention of preterm birth in:

  • Multiple gestations (twins, triplets, etc.) 1
  • Women with preterm labor in current pregnancy 1
  • Women with preterm premature rupture of membranes 1

• When using progesterone for menstrual disorders or hormone replacement, it's important to rule out abnormal vaginal bleeding due to cancer or other pathology 2

• For optimal absorption and to minimize side effects, oral progesterone should be taken at bedtime 2, 4