What is the function of a progesterone pill?

What is the Work of a Progesterone Pill?

Progesterone pills serve multiple critical functions: protecting the uterine lining when taking estrogen, treating menstrual irregularities, preventing preterm birth in high-risk pregnancies, and supporting early pregnancy in assisted reproduction.

Primary Functions

Endometrial Protection

• Progesterone prevents endometrial hyperplasia (overgrowth of the uterine lining) in postmenopausal women taking estrogen therapy 1
• When estrogen is taken alone, it increases the risk of uterine cancer; adding progesterone counteracts this dangerous effect 1
• The standard dose is 200 mg daily at bedtime for 12 continuous days per 28-day cycle when combined with estrogen 1
• Progesterone induces secretory transformation of the endometrium, creating a protective effect against abnormal cell growth 2

Treatment of Menstrual Irregularities

• Progesterone treats secondary amenorrhea (absence of periods in women who previously menstruated) 1
• The typical dose is 400 mg at bedtime for 10 days to induce withdrawal bleeding 1
• It works by providing the progesterone your body fails to produce naturally, allowing normal menstrual cycling to resume 1

Prevention of Preterm Birth

• In women with prior spontaneous preterm birth (20-36 6/7 weeks), 17-alpha-hydroxyprogesterone caproate (17P) 250 mg intramuscularly weekly from 16-20 weeks until 36 weeks reduces recurrent preterm birth risk 3
• Vaginal progesterone (90 mg gel or 200 mg suppository) prevents preterm birth in women with short cervical length (≤20 mm) at 24 weeks 3
• Progesterone works through anti-inflammatory effects that counteract inflammatory processes leading to preterm labor 2, 3
• It maintains uterine quiescence (keeps the uterus relaxed) and reduces cervical degradation 2, 3

Support in Assisted Reproduction

• Progesterone is standard luteal phase support in assisted reproductive technology (IVF/IUI) 4
• It prepares the endometrium for embryo implantation and maintains early pregnancy 4, 5
• Vaginal progesterone allows secretory transformation of the endometrium despite low systemic levels due to direct vagina-to-uterus transport 6

Mechanisms of Action

Hormonal Effects

• Progesterone binds to specific progesterone receptors to induce progestational effects 7
• It exhibits anti-estrogenic activity on the endometrium, preventing excessive proliferation 7, 8
• It has anti-androgenic and anti-mineralocorticoid properties 7

Pregnancy Maintenance

• Progesterone modulates the maternal immune system to prevent rejection of the embryo 5
• It maintains the gestational sac in the uterus during early pregnancy 5
• It alters the cervical barrier to ascending infection 3

Neurological Effects

• When taken orally, progesterone acts as a neurosteroid, alleviating anxiety, depression, and sleep problems 8
• This explains why oral progesterone causes drowsiness and must be taken at bedtime 1

Formulations and Routes

Oral Micronized Progesterone

• Natural progesterone in micronized form for better absorption 2, 7
• Micronized progesterone (MP) is preferred over synthetic progestins due to superior cardiovascular and thrombotic safety profile 2, 3
• Causes drowsiness, dizziness, and sometimes blurred vision—must be taken at bedtime 1

Vaginal Progesterone

• Provides direct uterine delivery with lower systemic side effects 6
• Available as gel or suppositories for luteal phase support and preterm birth prevention 3, 6

Intramuscular Injection

• 17-alpha-hydroxyprogesterone caproate (17P) given weekly for preterm birth prevention 2, 3

Important Safety Considerations

Contraindications

• Do not use if allergic to peanuts—progesterone capsules contain peanut oil 1
• Avoid in women with unusual vaginal bleeding, current or past cancers (especially breast or uterine), stroke, heart attack, blood clots, or liver problems 1
• Not for use if pregnant (except for specific indications like preterm birth prevention) 1

Side Effects

• Drowsiness, dizziness, blurred vision, difficulty speaking or walking when taken orally 1
• These symptoms require immediate discussion with healthcare provider 1
• Fewer side effects compared to synthetic progestins, particularly regarding lipid profile, blood pressure, and coagulation factors 7

When Progesterone Does NOT Work

• Progesterone is ineffective for preventing preterm birth in multiple gestations (twins, triplets) 3
• It does not prevent preterm birth in women with active preterm labor in the current pregnancy 3
• It does not prevent preterm birth in women with preterm premature rupture of membranes 3

Clinical Pitfalls

• Synthetic progestins (like medroxyprogesterone acetate) have different effects and risks compared to natural progesterone—they are not interchangeable 2, 7
• When used with estrogen in postmenopausal women, progestins may increase risk of heart attacks, strokes, breast cancer, and blood clots 1
• Natural micronized progesterone has a more favorable safety profile than synthetic progestins for cardiovascular and thrombotic risks 2, 8
• Long-term safety data shows no adverse effects in children exposed to progesterone in utero 2, 3