Progesterone

BRAND NAMES

1. Prometrium  (for hormone replacement therapy (HRT))

2. Progestasert

3. Utrogestan  (alongside estrogen to manage menopause symptoms)

4. Susten  (female hormone used in the treatment of female infertility.)

5. Dubagest  (at progesterone deficienciesGestofit )

6. Lutigest  (to support the luteal phase)

7. Crinone  (to supplement or replace progesterone in infertile women)

8. Endometrin  a vaginal insert insert containing 100 mg of progesterone

9. Related (synthetic progesterone / progestins)

10. Duphaston (to treat gynecological conditions)

11. Meprate      ( to treat menstrual disorders, including abnormal uterine bleeding)

12. Milprosa

MECHANISM OF ACTION

Progesterone acts by diffusing into target cells and binding to intracellular progesterone receptors (PR-A and PR-B) located in the cytoplasm. This hormone–receptor complex then translocates into the nucleus, where it binds to specific DNA sequences known as progesterone response elements, regulating gene transcription. As a result, it promotes endometrial differentiation, decreases uterine contractility, and prepares the uterus for implantation and maintenance of pregnancy. Progesterone also exerts negative feedback on the hypothalamus and pituitary, suppressing the release of gonadotropins (FSH and LH), thereby inhibiting ovulation.

PHARMACOKINETICS

Absorption

Progesterone is well absorbed through multiple routes of administration, including oral, vaginal, intramuscular, and transdermal forms. Oral progesterone undergoes significant first-pass metabolism in the liver, which reduces its bioavailability; therefore, micronized formulations are used to improve absorption.

Distribution 

After absorption, progesterone is widely distributed throughout the body, particularly to reproductive tissues such as the uterus, ovaries, and breasts. It is highly bound to plasma proteins, mainly albumin and corticosteroid-binding globulin (CBG), with only a small free fraction being biologically active.

Metabolism

Progesterone is extensively metabolized in the liver through reduction and conjugation pathways. It is first converted into inactive pregnanediol and other pregnane derivatives via enzymes such as 5α- and 5β-reductase, followed by conjugation with glucuronic acid.

Elimination

Progesterone and its metabolites are primarily eliminated through the kidneys. After hepatic metabolism, the inactive conjugated metabolites, especially pregnanediol glucuronide, are excreted in urine.

PHARMACODYNAMICS

Progesterone produces its effects by binding to intracellular progesterone receptors (PR-A and PR-B) in target tissues, leading to changes in gene transcription and protein synthesis. In the reproductive system, it transforms the estrogen-primed endometrium into a secretory state, making it suitable for implantation and maintenance of early pregnancy. It also reduces uterine contractility by decreasing the sensitivity of the myometrium to oxytocin and prostaglandins. In the cervix, progesterone increases the viscosity of cervical mucus, forming a barrier to sperm penetration and pathogens.

ADMINISTRATION

Progesterone can be administered through several routes depending on the indication, desired effect, and patient condition. The oral route is commonly used in the form of micronized progesterone capsules, but it has lower bioavailability due to first-pass metabolism. The vaginal route (capsules, gels, or pessaries) is widely used in fertility treatments and pregnancy support because it delivers high local concentrations to the uterus with fewer systemic side effects.

DOSAGE AND STRENGTH

Progesterone is available in several dosage forms and strengths depending on the route of administration. Oral micronized progesterone capsules are commonly available in strengths of 100 mg and 200 mg and are usually given in doses ranging from 100 mg to 200 mg once or twice daily depending on the indication. Vaginal formulations such as capsules or tablets also come in 100 mg and 200 mg strengths and are typically used in doses of 100–400 mg per day, especially for fertility support and luteal phase supplementation.

 DRUG INTERACTIONS

Progesterone may interact with several drugs that affect its metabolism or alter its therapeutic effects. Enzyme inducers such as rifampicin, phenytoin, carbamazepine, and phenobarbital can increase hepatic metabolism of progesterone, thereby reducing its effectiveness.

FOOD INTERACTIONS

Progesterone has minimal clinically significant food interactions, but food can influence its absorption, especially with oral formulations. When taken with food, particularly fatty meals, absorption of oral micronized progesterone may be enhanced, leading to improved bioavailability and more stable blood levels.

CONTRAINDICATIONS

Progesterone is contraindicated in patients with known hypersensitivity to progesterone or any of its formulation components. It should not be used in individuals with undiagnosed vaginal bleeding, as this may indicate serious underlying conditions that need evaluation.

SIDE EFFECTS

• Drowsiness and sedation 

• Dizziness or lightheadedness 

• Headache 

• Fatigue or tiredness 

• Breast tenderness or pain 

• Nausea and vomiting 

• Abdominal bloating or discomfort 

• Irregular vaginal bleeding or spotting 

• Mood changes (irritability, depression in some cases) 

• Weight gain or fluid retention 

• Decreased libido (rare) 

• Injection site pain, swelling, or redness (with IM use) 

• Vaginal irritation or discharge (with vaginal preparations) 

• Rare: allergic reactions and increased risk of blood clots (thromboembolic events)

OVER DOSE

Overdose of progesterone is uncommon and is usually not life-threatening, but excessive intake may intensify its pharmacological effects. Symptoms of overdose may include marked drowsiness, dizziness, confusion, nausea, vomiting, and severe fatigue.

TOXICITY 

Progesterone toxicity is rare because the drug has a relatively wide safety margin, but excessive levels or prolonged high-dose use can lead to enhanced pharmacological and adverse effects. Toxicity mainly affects the central nervous system, causing marked sedation, dizziness, confusion, and impaired coordination.