Is Norethisterone a Synthetic Progestogen?
Yes, norethisterone (norethindrone) is definitively a synthetic progestogen—specifically a normethyltestosterone derivative with mild androgenic activity. 1
Pharmacological Classification
Norethisterone is classified as a synthetic progestin derived from testosterone (19-nortestosterone derivative, estrane group), fundamentally distinguishing it from natural progesterone. 2, 3
At therapeutic doses (5-15 mg daily), norethisterone functions as a potent antigonadotropic agent with mild androgenic activity, which distinguishes it from pure progestational molecules. 1
As a first-generation progestin, norethisterone was originally used in high doses and has potent off-target effects on androgen and glucocorticoid receptors, contributing to acne and adverse metabolic effects such as lower high-density lipoprotein levels. 4
Key Distinguishing Features from Natural Progesterone
Norethisterone differs fundamentally from natural micronized progesterone, which has a more favorable cardiovascular and metabolic safety profile. 1
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. 1
Natural micronized progesterone has demonstrated a favorable safety profile compared to synthetic progestogens like norethisterone, particularly regarding cardiovascular risks and thrombotic risk. 5, 6
All comparative studies conclude that the side effects of synthetic progestins like norethisterone can be minimized or eliminated through the use of natural progesterone, which is identical to the steroid produced by the corpus luteum. 6
Clinical Context
Norethisterone is one of several normethyltestosterone derivatives used in contraception and hormone therapy, including norethisterone acetate, lynestrenol, and ethynodiol diacetate. 4
These compounds are usually administered in a single daily dose of 10 mg and at this dosage level, they are potent antigonadotropic agents with mild androgenic activity. 4
Progestin-only pills (POPs) containing norethindrone (first generation) are available for contraceptive purposes but are associated with irregular bleeding and need to be taken at the same time each day. 4
Important Clinical Caveat
Norethisterone has a unique characteristic: it partially converts to ethinylestradiol (EE)—10-20 mg NET corresponds to 20-30 µg EE—which is clinically important when considering contraindications such as migraine with aura or thrombotic risk. 7