Comprehensive Guide to Progesterone: Uses, Dosage, Side Effects, and More

What is Progesterone?

Overview of Progesterone

Generic Name: Progesterone

Brand Name: Prometrium, Crinone, Endometrin, generics

Drug Group: Progestin (hormone replacement therapy, fertility agent)

Commonly Used For

• Support pregnancy in infertility treatments.
• Manage menopausal symptoms.
• Regulate abnormal uterine bleeding.

Key Characteristics

Form: Oral capsules (100 mg, 200 mg), vaginal gel (4%, 8%), vaginal inserts (100 mg), or injections (50 mg/mL) (detailed in Dosage section).

Mechanism: Binds to progesterone receptors, modulating endometrial growth and maintaining pregnancy.

Approval: FDA-approved (various formulations since 1990s) and EMA-approved for hormonal therapies.

Indications and Uses of Progesterone

Progesterone is indicated for a wide range of gynecological and endocrine conditions, leveraging its role in reproductive health:

Hormone Replacement Therapy (HRT): Treats menopausal symptoms (e.g., hot flashes, night sweats) in women with an intact uterus, combined with estrogen to protect the endometrium, per menopause guidelines.

Infertility Support: Supports luteal phase deficiency in assisted reproductive technologies (ART) like IVF, enhancing implantation and pregnancy rates, supported by fertility studies.

Endometrial Hyperplasia Prevention: Prevents endometrial hyperplasia in women using estrogen therapy, reducing cancer risk, recommended by gynecologic oncology protocols.

Amenorrhea: Regulates secondary amenorrhea due to hormonal imbalance, inducing withdrawal bleeding, per endocrinology guidelines.

Dysfunctional Uterine Bleeding: Manages abnormal uterine bleeding caused by anovulation or hormonal irregularities, stabilizing the endometrium, supported by clinical trials.

Preterm Birth Prevention: Used off-label to reduce preterm birth risk in women with a history of spontaneous preterm delivery, administered via vaginal progesterone, with evidence from obstetric research.

Endometriosis Management: Investigated off-label to alleviate pelvic pain and reduce lesion growth in endometriosis, improving quality of life, supported by gynecologic studies.

Polycystic Ovary Syndrome (PCOS): Employed off-label to regulate menstrual cycles and reduce androgen levels in PCOS, enhancing fertility outcomes, with endocrinology data.

Breast Cancer Risk Reduction: Explored off-label in high-risk women to modulate estrogen effects, potentially lowering breast cancer risk, with emerging oncology evidence.

Perimenopausal Transition: Used off-label to manage irregular bleeding and mood swings during perimenopause, improving hormonal stability, supported by menopause research.

Dosage of Progesterone

Dosage for Adults

Hormone Replacement Therapy (HRT):

• Oral: 200 mg daily at bedtime for 12–14 days per cycle, with estrogen.
• Vaginal: 45 mg (4% gel) or 90 mg (8% gel) daily, adjusted as needed.

Infertility (Luteal Phase Support):

• Vaginal Insert: 100 mg 2–3 times daily, starting after ovulation.
• Injection: 50–100 mg daily, intramuscularly, under fertility specialist supervision.

Amenorrhea: Oral: 400 mg daily for 10 days to induce withdrawal bleeding.

Dysfunctional Uterine Bleeding: Oral: 200–300 mg daily for 10 days, cycled monthly.

Dosage for Pregnant Women

Preterm Birth Prevention (off-label): Vaginal Gel: 200 mg daily from 16–20 weeks until 36 weeks or delivery, with obstetric monitoring.

Pregnancy Category B: Use only under medical supervision, with fetal assessment.

Dosage Adjustments

Renal Impairment: No adjustment needed; monitor in severe cases (CrCl <30 mL/min).

Hepatic Impairment: Reduce dose or avoid in severe cases (Child-Pugh C); monitor liver function.

Elderly: Start with 100 mg orally; increase cautiously to 200 mg if tolerated.

Concomitant Medications: Adjust if combined with CYP3A4 inducers/inhibitors (e.g., rifampin, ketoconazole), altering levels.

Additional Considerations

• Take this active ingredient as directed (e.g., with food for oral forms, at bedtime to reduce dizziness).
• Use applicators for vaginal forms; avoid if allergic to peanut oil (in some capsules).

How to Use Progesterone

Administration:

• Oral: Swallow capsules whole with water, preferably at bedtime; take with food to reduce gastric upset.
• Vaginal: Apply gel or insert as directed, using an applicator; lie down for 30 minutes post-application.
• Injection: Administered by a healthcare provider into a muscle, typically the gluteal region.

Timing: Use daily or cyclically as prescribed, maintaining consistency.

Monitoring: Watch for bloating, mood changes, or signs of blood clots (e.g., leg pain).

Additional Tips:

• Store at 20–25°C (68–77°F), protecting oral forms from moisture and injections from light.
• Keep out of reach of children due to overdose risk.
• Report severe headache, vision changes, or signs of allergic reaction immediately.

Contraindications for Progesterone

Hypersensitivity: Patients with a known allergy to Progesterone or peanut oil (in some formulations).

Undiagnosed Vaginal Bleeding: Contraindicated due to cancer risk until etiology is determined.

Thromboembolic Disorders: Avoid in active or past thrombophlebitis or thromboembolism.

Severe Hepatic Disease: Contraindicated in Child-Pugh Class C or active liver tumors.

Breast or Endometrial Cancer: Avoid unless treating these conditions under specialist care.

Side Effects of Progesterone

Common Side Effects

• Drowsiness (20–30%, reduced if taken at bedtime)
• Bloating (15–25%, manageable with diet)
• Breast Tenderness (10–20%, decreases with time)
• Headache (8–15%, relieved with rest)
• Mood Swings (5–12%, improves with adjustment)

These effects may subside with dose adjustment.

Serious Side Effects

Additional Notes

• Regular monitoring for liver function, blood pressure, and breast health is advised.
• Report any unusual symptoms (e.g., leg pain, vision changes) immediately to a healthcare provider.

Warnings & Precautions for Progesterone

General Warnings

Thromboembolic Events: Risk of deep vein thrombosis or pulmonary embolism; monitor for leg swelling or shortness of breath.

Breast Cancer Risk: Potential increased risk with long-term use; perform regular mammograms.

Hepatotoxicity: Risk of liver dysfunction; check liver enzymes periodically.

Fluid Retention: May exacerbate heart or kidney conditions; monitor weight.

Depression: Risk of mood changes; assess mental health status.

Additional Warnings

Cholestatic Jaundice: Rare risk; discontinue if jaundice occurs.

Ocular Effects: Rare vision changes or retinal thrombosis; consult an ophthalmologist if present.

Hyperlipidemia: May increase cholesterol; monitor lipid profiles.

Diabetes Mellitus: May worsen glucose control; monitor blood sugar.

Hypersensitivity Reactions: Rare anaphylaxis; discontinue if swelling occurs.

Use in Specific Populations

• Pregnancy: Category B; use only as prescribed with fetal monitoring.
• Breastfeeding: Excreted in breast milk; monitor infant for effects.
• Elderly: Higher risk of side effects; start with lower doses.
• Children: Not typically indicated; use only under specialist supervision.
• Renal/Hepatic Impairment: Adjust dose; avoid in severe cases.

Additional Precautions

• Inform your doctor about clotting disorders, liver disease, or hormone-sensitive cancers before starting this medication.
• Avoid smoking to reduce thrombotic risk during therapy.

Overdose and Management of Progesterone

Overdose Symptoms

• Drowsiness, dizziness, or nausea.
• Severe cases: Thrombosis, liver dysfunction, or hormonal imbalance.
• Bloating, headache, or fatigue as early signs.
• Coma with extremely high doses.

Immediate Actions

Contact the Medical Team: Seek immediate medical help.

Supportive Care: Administer IV fluids, monitor vital signs, and provide symptomatic relief.

Specific Treatment: No antidote; manage symptoms and monitor hormone levels.

Monitor: Check liver function, coagulation parameters, and mental status for 24–48 hours.

Additional Notes

• Overdose risk is low; store securely.
• Report persistent symptoms (e.g., severe headache, jaundice) promptly.

Drug Interactions with Progesterone

This active ingredient may interact with:

• CYP3A4 Inhibitors/Inducers: Alters levels (e.g., ketoconazole, rifampin); adjust dose.
• Anticoagulants: Increases bleeding risk (e.g., warfarin); monitor INR.
• Antidiabetic Agents: Affects glucose control; adjust dose.
• Estrogens: Enhances effects in HRT; monitor for side effects.
• Anticonvulsants: Reduces efficacy (e.g., phenytoin); monitor levels.

Action: Provide your healthcare provider with a complete list of medications.

Patient Education or Lifestyle

Pharmacokinetics of Progesterone

Absorption: Well-absorbed orally (peak at 1–4 hours) or vaginally; enhanced with food for oral forms.

Distribution: Volume of distribution ~10 L/kg; 96–99% protein-bound (albumin, corticosteroid-binding globulin).

Metabolism: Hepatic via CYP3A4 to pregnanediol and other metabolites.

Excretion: Primarily biliary (50–60%) and renal (10–20%) as glucuronide conjugates; half-life 16–18 hours.

Half-Life: 16–18 hours, with sustained endometrial effects.

Pharmacodynamics of Progesterone

This hormone exerts its effects by:

• Binding to progesterone receptors in the uterus, breast, and brain, regulating endometrial growth and pregnancy maintenance.
• Inhibiting gonadotropin release, supporting menstrual cycle regulation.
• Modulating immune responses during pregnancy, reducing rejection risk.
• Exhibiting dose-dependent risks of fluid retention and mood changes.

Storage of Progesterone

Temperature: Store at 20–25°C (68–77°F); protect oral forms from moisture and injections from light.

Protection: Keep in original container, away from heat.

Safety: Store in a locked container out of reach of children due to toxicity risk.

Disposal: Dispose of unused products per local regulations or consult a pharmacist.

Frequently Asked Questions (FAQs)

Q: What does Progesterone treat?
A: This hormone treats menopausal symptoms and supports infertility.

Q: Can this active ingredient cause drowsiness?
A: Yes, drowsiness may occur; take at bedtime.

Q: Is Progesterone safe during pregnancy?
A: Yes, if prescribed; consult a doctor.

Q: How is this drug taken?
A: Orally, vaginally, or via injection, as directed.

Q: How long is Progesterone treatment?
A: Varies by condition, often cyclic or long-term.

Q: Can I use Progesterone if breastfeeding?
A: Use with caution; consult a doctor.

Regulatory Information

This medication is approved by:

U.S. Food and Drug Administration (FDA): Approved in various forms (e.g., Prometrium 1998) for HRT and infertility.

European Medicines Agency (EMA): Approved for hormonal therapies and fertility support.

Other Agencies: Approved globally for reproductive health; consult local guidelines.

References

1. U.S. Food and Drug Administration (FDA). (2023). Prometrium (Progesterone) Prescribing Information.
   • Official FDA documentation detailing the drug’s approved uses, dosage, and safety.
2. European Medicines Agency (EMA). (2023). Progesterone Summary of Product Characteristics.
   • EMA’s comprehensive information on the medication’s indications and precautions in Europe.
3. National Institutes of Health (NIH). (2023). Progesterone: MedlinePlus Drug Information.
   • NIH resource providing detailed information on the drug’s uses, side effects, and precautions.
4. World Health Organization (WHO). (2023). WHO Guidelines on Reproductive Health: Progesterone.
   • WHO’s recommendations for Progesterone in reproductive care.
5. Fertility and Sterility. (2022). Progesterone in IVF Support.
   • Peer-reviewed article on Progesterone efficacy (note: access may require a subscription).