Usage
Norethisterone, a synthetic progestogen, is prescribed for various gynecological conditions. Its primary uses include:
- Menstrual disorders: Heavy menstrual bleeding (menorrhagia), irregular periods, painful periods (dysmenorrhea), premenstrual syndrome (PMS), endometriosis, and secondary amenorrhea.
- Postponement of menstruation: Delaying the onset of a period for personal convenience or specific events.
- Hormone replacement therapy (HRT): Combined with estrogen to alleviate menopausal symptoms.
- Contraception: Used in some formulations of progestogen-only pills (POPs, or “mini-pills”).
Pharmacological Classification: Progestogen, steroid hormone.
Mechanism of Action: Norethisterone mimics the effects of progesterone, primarily by binding to and activating progesterone receptors. This leads to changes in the endometrium (uterine lining) and alters the hypothalamic-pituitary-ovarian axis, impacting hormone levels and menstrual cycles.
Alternate Names
- Norethindrone
- 17α-ethynyl-19-nortestosterone
Brand Names: Numerous brand names exist globally, such as Norlutin, Primolut N, Noriday, Aygestin, Micronor, and others. Brand names vary significantly by region.
How It Works
Pharmacodynamics: Norethisterone primarily acts on progesterone receptors in the uterus, leading to transformation of the proliferative endometrium into a secretory endometrium. It also inhibits the release of gonadotropin-releasing hormone (GnRH) from the hypothalamus, suppressing ovulation at higher doses. In endometriosis, it induces decidualization of endometrial tissue, resulting in atrophy.
Pharmacokinetics:
- Absorption: Rapidly absorbed after oral administration, reaching peak plasma concentrations within 1-3 hours.
- Metabolism: Extensive hepatic metabolism, primarily by reduction and conjugation reactions. A small amount is metabolized to ethinylestradiol.
- Elimination: Primarily eliminated via urine (as metabolites), with a smaller portion excreted in feces.
- Elimination Half-life: Approximately 8-9 hours.
Mode of Action: Binds to progesterone receptors, affecting gene expression in target tissues. This leads to the described effects on the endometrium and hypothalamic-pituitary-ovarian axis.
Receptor Binding: Progesterone receptor agonist.
Enzyme Inhibition/Neurotransmitter Modulation: Although primarily acting on progesterone receptors, Norethisterone’s impact on the hypothalamic-pituitary-ovarian axis secondarily modulates GnRH, LH, and FSH release.
Elimination Pathways: Predominantly hepatic metabolism followed by renal excretion.
Dosage
Standard Dosage
Adults: Dosage varies according to indication:
- Period delay: 5mg three times daily, starting 3 days before the expected onset of menstruation, for up to 14-17 days.
- Heavy menstrual bleeding: 5mg three times daily for 10 days. For recurrence prevention, 5mg twice daily from days 19 to 26 of the following two cycles.
- Endometriosis: Initial dose of 5mg daily, potentially increasing to 15mg daily over time. Treatment typically continues for 6-9 months.
- Premenstrual syndrome: 5mg daily from days 16 to 25 of the cycle.
Children: Not typically recommended for most indications in children.
Special Cases:
- Elderly Patients: Dosage adjustments may be required due to potential age-related decline in liver and kidney function.
- Patients with Renal Impairment: Limited data available; caution advised.
- Patients with Hepatic Dysfunction: Dosage adjustments are necessary due to impaired metabolism. Close monitoring is recommended.
- Patients with Comorbid Conditions: Consider adjustments based on specific comorbid conditions like cardiovascular disease, diabetes, or epilepsy.
Clinical Use Cases
Norethisterone is not typically used in clinical settings like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations.
Dosage Adjustments: Adjustments may be needed based on patient-specific factors like hepatic or renal impairment, other medical conditions, or concomitant medications.
Side Effects
Common Side Effects:
- Breakthrough bleeding or spotting
- Breast tenderness
- Headache
- Nausea
- Mood changes
- Acne
- Fluid retention
Rare but Serious Side Effects:
- Blood clots (thrombosis)
- Allergic reactions
- Liver dysfunction
- Jaundice
- Stroke
- Heart attack
Contraindications
- Pregnancy
- Current or history of venous thromboembolism
- Arterial thromboembolic disease (e.g., stroke, myocardial infarction)
- Severe liver disease
- Undiagnosed vaginal bleeding
- Breast cancer (known or suspected)
- Endometrial cancer (known or suspected)
- Porphyria
- Hypersensitivity to norethisterone
Drug Interactions
Norethisterone interacts with numerous medications, including:
- Enzyme-inducing drugs: Rifampicin, phenytoin, carbamazepine (reduce norethisterone’s efficacy)
- Enzyme-inhibiting drugs: Azole antifungals (ketoconazole, itraconazole), some HIV protease inhibitors (increase norethisterone levels)
- St. John’s wort: Reduces norethisterone efficacy
- Grapefruit juice: May increase norethisterone levels
Pregnancy and Breastfeeding
- Pregnancy Safety Category: X (contraindicated)
- Fetal Risks: Norethisterone is contraindicated during pregnancy due to potential teratogenic effects.
- Breastfeeding: Small amounts are excreted in breast milk. While generally considered safe, discuss potential risks and benefits with a physician. Alternatives may be preferred.
Drug Profile Summary
- Mechanism of Action: Progesterone receptor agonist, impacting endometrium and HPO axis.
- Side Effects: Breakthrough bleeding, breast tenderness, headache, nausea, mood changes, acne, fluid retention. Serious side effects: blood clots, allergic reactions, liver dysfunction.
- Contraindications: Pregnancy, thromboembolic disease, liver disease, undiagnosed vaginal bleeding, breast/endometrial cancer, porphyria.
- Drug Interactions: Numerous drug interactions, including with enzyme inducers/inhibitors, St. John’s wort, and grapefruit juice.
- Pregnancy & Breastfeeding: Contraindicated in pregnancy. Generally safe during breastfeeding, but alternatives might be preferred.
- Dosage: Varies by indication; see detailed dosage section.
- Monitoring Parameters: Liver function tests, blood pressure, signs of thrombosis, menstrual patterns.
Popular Combinations
Norethisterone is often combined with estrogen in HRT and some contraceptive pills. This combination aims to balance hormonal effects and reduce the risk of endometrial hyperplasia associated with unopposed estrogen.
Precautions
- General Precautions: Evaluate for contraindications and potential drug interactions. Monitor for side effects, especially thromboembolic events and liver dysfunction.
- Specific Populations: Caution is advised in patients with renal or hepatic impairment, diabetes, cardiovascular disease, epilepsy, or migraine.
- Pregnant Women: Contraindicated.
- Breastfeeding Mothers: Discuss risks and benefits with physician.
- Children & Elderly: Use with caution in these populations, with dose adjustments as necessary.
- Menstruating Individuals: Monitor for changes in menstrual bleeding patterns.
- Lifestyle Considerations: No specific lifestyle restrictions, but advise patients to avoid smoking due to increased thrombotic risk, especially when combined with estrogen.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Norethisterone?
A: Dosage varies by indication. See detailed dosage section above.
Q2: Can Norethisterone be used as a contraceptive?
A: While found in some progestogen-only pills (POPs), Norethisterone 5mg tablets are not primarily intended for contraception. Use appropriate contraceptive methods while taking Norethisterone for other indications.
Q3: What are the common side effects of Norethisterone?
A: Common side effects include breakthrough bleeding, breast tenderness, headache, nausea, and mood changes.
Q4: Is Norethisterone safe during pregnancy?
A: No, Norethisterone is contraindicated during pregnancy due to potential harm to the fetus.
Q5: How does Norethisterone work to delay periods?
A: By mimicking progesterone, it prevents the shedding of the uterine lining, thus delaying the onset of menstruation.
Q6: What should I do if I miss a dose of Norethisterone?
A: Take the missed dose as soon as you remember, unless it is close to the time for your next dose. Do not double the dose.
Q7: Can Norethisterone be used to treat endometriosis?
A: Yes, it is commonly used to treat endometriosis by suppressing endometrial tissue growth.
Q8: What are the warning signs of a serious side effect while taking Norethisterone?
A: Seek immediate medical attention if you experience symptoms such as severe allergic reactions, signs of blood clots (chest pain, shortness of breath, leg pain/swelling), jaundice, or severe headache.
Q9: How long does it take for Norethisterone to stop bleeding?
A: Bleeding typically stops within 1-3 days when used to treat heavy menstrual bleeding.
Q10: Does Norethisterone interact with other medications?
A: Yes, Norethisterone has several drug interactions. Consult the drug interaction section above or a pharmacist for detailed information. Always inform your doctor about all medications you are currently taking, including over-the-counter drugs and herbal supplements.
