What does progesterone do?

What Progesterone Does

Progesterone is a steroid hormone essential for pregnancy maintenance that works through multiple mechanisms including maintaining uterine quiescence, modulating maternal immune response, and supporting endometrial development.

Core Physiological Functions

Reproductive Role

• Progesterone prepares the endometrium for embryo implantation by inducing secretory transformation of the endometrial lining after ovulation 1, 2
• Maintains pregnancy by suppressing uterine contractility and preventing premature labor through counteracting prostaglandin and oxytocin stimulatory activity 2
• Modulates maternal immune response to prevent rejection of the embryo/fetus, with progesterone-progesterone receptor interactions at the decidua playing a major role in maternal defense strategy 2
• Promotes trophoblast invasion into the decidua by inhibiting apoptosis of extravillous trophoblasts, improving utero-placental circulation 2

Mechanism of Action

Progesterone works through several pathways 3:

• Anti-inflammatory effects: Decreases prostaglandin synthesis and infection-mediated cytokine production by fetal membranes and placenta 3
• Myometrial quiescence: Changes progesterone receptor expression (decreased PR-A/PR-B ratio keeps uterus quiescent) 3
• Cervical protection: Reduces cervical stromal degradation and provides barrier to ascending infection 3, 4

Clinical Therapeutic Applications

Prevention of Preterm Birth

For singleton pregnancies with prior spontaneous preterm birth (20-36 6/7 weeks): 17-alpha-hydroxy-progesterone caproate (17P) 250 mg intramuscularly weekly from 16-20 weeks until 36 weeks is recommended 3, 4

For singleton pregnancies without prior preterm birth but with short cervical length (≤20 mm) at 18-24 weeks: vaginal progesterone (90-mg gel or 200-mg suppository) daily from diagnosis until 36 weeks is recommended 3, 4

Important Limitations

• Progesterone is NOT effective in multiple gestations (twins, triplets) for preterm birth prevention 3, 4
• Progesterone is NOT effective for active preterm labor in the current pregnancy 3, 4
• Progesterone is NOT effective for preterm premature rupture of membranes 3, 4

Menstrual Disorders

• Treats secondary amenorrhea (absence of menstrual periods) when progesterone deficiency is the cause 5
• Progesterone 300-400 mg daily for 10 days induces withdrawal bleeding in 73-80% of women with secondary amenorrhea 5

Endometrial Protection

• Protects the endometrium from hyperplasia in postmenopausal women taking estrogen by opposing estrogen's proliferative effects 5
• Progesterone 200 mg daily for 12 continuous days per 28-day cycle reduces hyperplasia risk from 64% (estrogen alone) to 6% (estrogen plus progesterone) 5

Hormone Replacement Therapy

• Natural micronized progesterone is preferred for premature ovarian insufficiency as part of hormone replacement therapy due to favorable cardiovascular and thrombotic risk profile 4

Safety Profile

• No long-term adverse effects have been identified in children exposed to progesterone in utero, even with first trimester exposure 3, 4
• Follow-up at mean 4 years of children exposed to 17P showed no differences in physical examination, health status, or developmental performance compared to placebo 3

Clinical Pitfalls

• Serum progesterone levels are NOT routinely used to guide progesterone supplementation decisions - treatment is based on clinical risk factors (prior preterm birth, short cervix), not hormone measurements 6
• Progesterone capsules contain peanut oil and should not be used in patients with peanut allergy 5
• Some women experience drowsiness, dizziness, blurred vision, or difficulty walking after taking oral progesterone - these should be taken at bedtime 5