Norethisterone Pharmacology and Clinical Use

Active Pharmaceutical Ingredient

• Norethisterone (norethindrone) is the sole active component, classified as a normethyltestosterone derivative progestin with mild androgenic activity 1, 2
• The standard formulation contains 5 mg norethisterone per tablet, though 10 mg formulations also exist for specific indications 1, 2

Pharmacological Classification

• Norethisterone is a synthetic progestogen with potent antigonadotropic properties when used at doses of 5-10 mg daily 1, 2
• At therapeutic doses (5-15 mg daily), it functions as a potent antigonadotropic agent with mild androgenic activity, distinguishing it from pure progestational molecules 1

Clinical Dosing Context

• For menstrual regulation and hormonal imbalances, norethisterone is typically prescribed at 5 mg daily for 10-14 days per cycle 1, 2
• For hormone replacement therapy, norethisterone acetate 1 mg daily provides adequate endometrial protection with a superior cardiovascular profile compared to higher doses 3, 4

Important Pharmacological Distinctions

• Norethisterone differs fundamentally from natural micronized progesterone, which has a more favorable cardiovascular and metabolic safety profile 3, 4
• The androgenic properties of norethisterone can cause adverse effects on lipid profiles, vasomotion, and blood pressure, particularly when combined with ethinyl estradiol rather than natural estradiol 3, 1

Clinical Effects and Therapeutic Use of Norethisterone (Synthetic Progestogen)

Pharmacological Profile

• Norethisterone is a first‑generation synthetic progestin derived from testosterone that acts as a potent antigonadotropic agent while retaining mild androgenic activity at typical doses (≈10 mg once daily). 5

Metabolic and Cardiovascular Impact

• The drug’s off‑target activation of androgen and glucocorticoid receptors can provoke acne and lower high‑density lipoprotein cholesterol, indicating adverse metabolic and vascular effects. 6

Contraceptive Applications

• Progestin‑only pills (POPs) formulated with norethisterone are effective for contraception but are associated with irregular uterine bleeding; strict adherence to the same daily dosing time is required to maintain efficacy. 7