1. Clinical Overview
Progesterone 400mg is a high-dose formulation of the natural female sex hormone, progesterone. It is primarily used in the management of infertility, luteal phase support in Assisted Reproductive Technology (ART) cycles, and secondary amenorrhea. In the Indian context, it is a critical component of hormonal support therapy, available as a sustained-release vaginal or oral formulation. It acts by transforming the proliferative endometrium into a secretory one, making it receptive for embryo implantation and maintaining pregnancy.
| Onset | Duration | Bioavailability |
|---|---|---|
| Oral: 1-2 hours for peak plasma concentration. Vaginal: Systemic absorption is slower, with local endometrial effects occurring more directly. | Oral: Approximately 24 hours, requiring once or twice-daily dosing. Vaginal (sustained-release): Provides continuous release over 24-48 hours. | Oral: <10% due to extensive first-pass metabolism. Vaginal: Variable, but local uterine tissue concentrations are significantly higher than plasma levels ('first uterine pass effect'). |
2. Mechanism of Action
Progesterone is the natural ligand for the intracellular progesterone receptor (PR). Upon binding, the receptor-hormone complex translocates to the nucleus, binds to specific progesterone response elements (PREs) on DNA, and modulates gene transcription. This leads to the transformation of the estrogen-primed endometrium from a proliferative to a secretory state, essential for embryo implantation and maintenance of pregnancy. It also suppresses gonadotropin (LH, FSH) secretion, inhibits uterine contractility, and promotes mammary gland development.
3. Indications & Uses
- Luteal Phase Support in Assisted Reproductive Technology (ART) cycles like IVF/ICSI
- Secondary Amenorrhea (to induce secretory transformation of endometrium after estrogen priming)
- Infertility due to luteal phase deficiency
4. Dosage & Administration
Adult Dosage: Luteal Phase Support (ART): 400mg vaginally twice daily, starting from the day of oocyte retrieval/embryo transfer and continuing for up to 10-12 weeks of pregnancy. Secondary Amenorrhea: 400mg orally daily for 10-12 days, following adequate estrogen priming.
Administration: Vaginal Tablet/Insert: Insert deeply into the vagina using the applicator or finger. Preferably at the same times each day (e.g., morning and evening). Can be used in any position. Oral Capsule: Take with food to improve absorption and reduce dizziness/drowsiness. Swallow whole; do not crush or chew.
5. Side Effects
Common side effects may include:
- Drowsiness, somnolence (more common with oral route)
- Headache
- Breast tenderness
- Abdominal bloating/cramping
- Nausea
- Vaginal discharge (with vaginal use)
- Mood swings, irritability
6. Drug Interactions
| Drug | Effect | Severity |
|---|---|---|
| Ketoconazole, Itraconazole, Ritonavir | Strong CYP3A4 inhibitors increase progesterone levels, increasing risk of side effects. | Major |
| Rifampicin, Carbamazepine, Phenytoin, St. John's Wort | Strong CYP3A4 inducers decrease progesterone levels, potentially reducing efficacy. | Major |
| Other CNS Depressants (Alcohol, Benzodiazepines, Opioids) | Additive sedative effect; increased drowsiness and dizziness. | Moderate |
| Enzyme-inducing Antiepileptics (e.g., Phenobarbital) | May increase metabolism of progesterone, reducing effect. | Moderate |
7. Patient Counselling
- DO take/insert the medication at the same time(s) each day as prescribed.
- DO use the vaginal applicator correctly and maintain hygiene.
- DO inform your doctor if you become pregnant or plan to become pregnant.
- DO report any severe headache, chest pain, leg swelling, or shortness of breath immediately.
- DONT stop the medication abruptly without consulting your doctor, especially during ART cycles.
- DONT drink alcohol while on this medication.
- DONT take other medicines (including OTC, herbal) without informing your doctor.
8. Toxicology & Storage
Overdose: Symptoms are an extension of side effects: Severe drowsiness, dizziness, nausea, vomiting. No specific life-threatening acute overdose syndrome reported at therapeutic doses.
Storage: Store below 25°C, in a cool, dry place. Protect from light and moisture. Keep out of reach of children. Do not freeze. For vaginal inserts, store in the original blister pack until use.