1. Clinical Overview
Progesterone (Natural Micronized) 400mg is a high-dose oral formulation of bioidentical progesterone, derived from plant sources (typically diosgenin from yams or soy). The micronization process reduces particle size, significantly enhancing its oral bioavailability without the need for chemical modification. It acts as a crucial female sex hormone, primarily preparing and maintaining the endometrium for pregnancy. In the Indian context, it is a cornerstone of Luteal Phase Support (LPS) in Assisted Reproductive Technology (ART) and is widely used in Hormone Replacement Therapy (HRT) for menopausal women with an intact uterus.
| Onset | Duration | Bioavailability |
|---|---|---|
| Oral: Initial hormonal effects can be observed within 1-2 hours, but full therapeutic effect for endometrial transformation or symptom relief may take several days of consistent dosing. | Approximately 24 hours, necessitating once or twice-daily dosing to maintain stable serum levels. | Micronization increases absolute oral bioavailability to approximately 10-15% (compared to <5% for non-micronized). Bioavailability can be highly variable between individuals and is significantly increased when taken with food. |
2. Mechanism of Action
Progesterone is the natural ligand for the intracellular progesterone receptor (PR). Upon binding, the receptor-ligand complex undergoes dimerization, translocates to the nucleus, and binds to specific progesterone response elements (PREs) on DNA, regulating the transcription of target genes. This leads to the secretory transformation of the estrogen-primed endometrium, inhibition of gonadotropin secretion, and maintenance of myometrial quiescence.
3. Indications & Uses
- Luteal Phase Support in Assisted Reproductive Technology (ART/IVF cycles)
- Secondary Amenorrhea
- Hormone Replacement Therapy (HRT) in combination with estrogen for women with an intact uterus to prevent endometrial hyperplasia
4. Dosage & Administration
Adult Dosage: **Secondary Amenorrhea:** 400mg daily in the evening for 10 days. **HRT (Sequential combined therapy with estrogen):** 400mg daily for the last 12-14 days of each estrogen cycle. **Luteal Phase Support in ART:** 400mg to 600mg daily in divided doses (e.g., 200mg twice daily), starting after oocyte retrieval/embryo transfer and continuing for up to 10-12 weeks of pregnancy if successful.
Administration: **MUST be taken with food, preferably a meal containing fats, to significantly increase bioavailability and reduce CNS side effects.** Capsules should be swallowed whole with a full glass of water. For ART, doses are often split (e.g., morning and evening) to maintain stable levels. The evening dose can help mitigate daytime drowsiness.
5. Side Effects
Common side effects may include:
- Drowsiness, somnolence, dizziness
- Breast tenderness or pain
- Headache
- Mild abdominal bloating or cramping
- Mood swings, irritability
- Breakthrough bleeding or spotting
6. Drug Interactions
| Drug | Effect | Severity |
|---|---|---|
| Ketoconazole, Itraconazole, Clarithromycin | Strong CYP3A4 inhibitors; increase progesterone levels, risk of toxicity/sedation. | Major |
| Rifampicin, Carbamazepine, Phenytoin, St. John's Wort | Strong CYP3A4 inducers; decrease progesterone levels, reducing efficacy. | Major |
| Other CNS Depressants (Alcohol, Benzodiazepines, Opioids) | Additive sedative effects; increased risk of dizziness and drowsiness. | Moderate |
| Enzyme-inducing Antiepileptics (Phenobarbital, Primidone) | Decrease progesterone levels. | Moderate |
| Drugs affecting liver metabolism (Griseofulvin) | May alter progesterone levels. | Moderate |
7. Patient Counselling
- DO take this medication exactly as prescribed, at the same time(s) each day.
- DO take the capsule with food, preferably your largest meal containing some fat.
- DO swallow the capsule whole with a full glass of water; do not crush or chew.
- DONT drive or operate heavy machinery if you feel drowsy or dizzy.
- DONT drink alcohol while on this medication.
- DONT stop taking the medication abruptly if used for HRT or ART support; consult your doctor.
- DO inform all your healthcare providers (including dentists) that you are taking progesterone.
8. Toxicology & Storage
Overdose: Symptoms are an extension of its pharmacological effects: Severe drowsiness, dizziness, lethargy, ataxia, nausea. No specific life-threatening acute overdose syndrome has been reported at typical doses.
Storage: Store at room temperature (15-25°C), protected from light and moisture. Keep the container tightly closed. Keep out of reach of children. Do not use after the expiry date printed on the pack.