What are the uses and dosages of norethindrone acetate?

Norethindrone Acetate: Uses and Dosages

Norethindrone acetate is FDA-approved for the treatment of secondary amenorrhea, endometriosis, and abnormal uterine bleeding due to hormonal imbalance in the absence of organic pathology. 1

FDA-Approved Indications and Dosages

• Secondary amenorrhea: Norethindrone acetate is administered at doses of 2.5-10 mg daily for 5-10 days to induce withdrawal bleeding 1
• Endometriosis: Initial dose of 5 mg daily for 2 weeks, increased in increments of 2.5 mg per day every 2 weeks until 15 mg daily is reached 1, 2
• Abnormal uterine bleeding: 2.5-10 mg daily for 5-21 days, starting on day 5-21 of the menstrual cycle 1

Contraceptive Uses

• When used for contraception as part of progestin-only pills, norethindrone acetate is typically administered at a dose of 10 mg daily as a potent antigonadotropic agent 3
• Norethindrone derivatives (including norethindrone acetate) have mild androgenic activity and can display metabolic and vascular side effects related to their androgenic potencies 3

Other Therapeutic Applications

• Add-back therapy with GnRH agonists: Norethindrone acetate at doses of 5 mg daily can be used as add-back therapy with GnRH agonists for endometriosis to alleviate hypoestrogenic symptoms while preserving therapeutic efficacy 2
• Hormone replacement therapy: When combined with estradiol, norethindrone acetate doses as low as 0.1 mg can effectively negate the risk of endometrial hyperplasia associated with unopposed estradiol 4
• Acne treatment: Norethindrone acetate combined with ethinyl estradiol is FDA-approved for acne treatment in women who also desire contraception 5

Special Considerations

Contraindications

• Pregnancy: Norethindrone acetate is contraindicated during pregnancy as it may cause fetal harm, including increased risk of minor birth defects if taken during the first 4 months of pregnancy 1
• History of thromboembolism: Should not be used in patients with history of blood clots in the legs, lungs, eyes, brain, or elsewhere 1
• Liver impairment or disease 1
• Known or suspected cancer of the breast 1
• Undiagnosed vaginal bleeding 1
• Hypersensitivity to norethindrone acetate 1

Side Effects and Monitoring

• Thromboembolism risk: Norethindrone acetate has been associated with changes in the blood-clotting system that may allow clots to form more easily 1
• Visual disturbances: Discontinue immediately and seek medical attention for sudden partial or complete loss of vision, blurred vision, or sudden onset of bulging eyes, double vision, or migraine 1
• Monitoring requirements:
  • Baseline assessment of pregnancy status and blood pressure 5
  • Periodic monitoring of liver function tests, especially for patients on higher doses (≥10 mg daily) 5
  • Annual clinical review for stable patients, with more frequent monitoring during initial therapy 5

Comparison with Other Progestins

• Norethindrone acetate is a first-generation progestin with mild androgenic activity, whereas newer progestins like dienogest may have better tolerability profiles 6, 7
• In a comparative study, 71% of women were satisfied with norethindrone acetate treatment for endometriosis compared to 72% with dienogest, but dienogest was better tolerated (80% vs 58%) 7
• For women with hereditary angioedema, progestin-only pills containing norethindrone are well-tolerated in about two-thirds of patients 6

Practical Considerations

• Norethindrone acetate should not be used in postmenopausal women for endometrial protection when used with concomitant estrogen therapy 1
• For patients with thrombotic risk factors who require contraception, norethindrone acetate may be preferred over combined estrogen-containing contraceptives 3, 6
• When considering cost-effectiveness, norethindrone acetate may be preferred as first-line therapy for endometriosis over newer progestins like dienogest, with dienogest reserved for those who don't tolerate norethindrone acetate 7