What is the proper usage and dosage of Norethindrone acetate (synthetic progestin)?

Norethindrone Acetate: Proper Usage and Dosage Guidelines

Norethindrone acetate dosage should be tailored based on the specific indication, with 2.5-10 mg daily for menstrual disorders and 5-15 mg daily for endometriosis. 1

Indications and Dosing

Secondary Amenorrhea and Abnormal Uterine Bleeding

• 2.5 to 10 mg daily for 5 to 10 days to produce secretory transformation of the endometrium that has been adequately primed with estrogen 1
• Progestin withdrawal bleeding typically occurs within 3-7 days after discontinuing therapy 1
• Patients with recurrent abnormal uterine bleeding may benefit from planned menstrual cycling with norethindrone acetate 1

Endometriosis

• Initial dosage: 5 mg daily for two weeks 1
• Increase by 2.5 mg daily every two weeks until reaching 15 mg daily 1
• Maintain therapy at 15 mg daily for six to nine months or until breakthrough bleeding requires temporary discontinuation 1

Hormone Replacement Therapy

• When combined with estradiol (0.05 mg/day), norethindrone acetate doses of 0.5-1.0 mg daily for 12 days each month are effective 2
• For continuous combined therapy with estradiol (1 mg), doses as low as 0.1 mg daily effectively prevent endometrial hyperplasia 3

Contraception

• For contraceptive purposes, microdose norethindrone (0.35 mg) is taken daily without interruption 4
• In combined hormonal contraceptives, norethindrone acetate is paired with ethinyl estradiol 5
• The 24-day regimen of norethindrone acetate 1 mg/ethinyl estradiol 20 μg shows better bleeding profile than 21-day regimens 6

Contraindications

Norethindrone acetate is contraindicated in patients with:

• Breast cancer or other estrogen/progestin-sensitive cancers 5
• Active or history of arterial thromboembolic disease (stroke or myocardial infarction) 5
• Deep vein thrombosis, thromboembolic disease, or pulmonary embolism 5
• Undiagnosed genital bleeding 5
• Hepatic adenomas, carcinomas, or active liver disease 5
• Pregnancy (Category X) 5

Adverse Effects

Common adverse effects include:

• Central nervous system: Depression, headache, mood changes, nervousness 5
• Endocrine: Amenorrhea, breakthrough bleeding, breast pain/tenderness, fluid retention 5
• Gastrointestinal: Abdominal cramps, nausea, weight changes, vomiting 5
• Skin: Chloasma, melasma, erythema nodosum 5
• Cardiovascular: Edema, varicose veins aggravation 5

Drug Interactions

Norethindrone acetate effectiveness may be reduced by:

• Certain antibiotics (cephalosporins, macrolides, penicillins, tetracyclines) 5
• Anticonvulsants (barbiturates, carbamazepine, phenytoin, topiramate) 5
• Rifampin or rifabutin therapy 5
• St. John's wort 5
• HIV protease inhibitors 5

Monitoring

• Baseline assessment: Pregnancy status, blood pressure 5
• Ongoing monitoring: Regular assessment of health status and blood pressure 5

Special Considerations

In Fertility Treatment

• Norethindrone acetate (10 mg/day) can be used to program ovarian stimulation in IVF/GIFT cycles 7
• Administration is oral, simple, and inexpensive, with ovarian response to gonadotropin stimulation not affected by norethindrone acetate 7

In Acne Treatment

• Norethindrone acetate combined with ethinyl estradiol is FDA-approved for acne treatment in women who desire oral contraception 5
• The mechanism of action in acne treatment is based on antiandrogenic properties, decreasing androgen production and increasing sex hormone-binding globulin 5

Clinical Pearls

• When used for menstrual disorders, withdrawal bleeding typically occurs 3-7 days after discontinuation 1
• For endometriosis, gradual dose escalation helps minimize side effects while achieving therapeutic benefit 1
• In hormone replacement therapy, continuous low-dose norethindrone acetate (as low as 0.1 mg) with estradiol effectively prevents endometrial hyperplasia 3
• The safety profile of norethindrone acetate in women with premature ovarian insufficiency may be worse in terms of blood pressure and renal function compared to natural micronized progesterone 5
• Extended regimens (24-day active pills vs. 21-day) may reduce breakthrough bleeding and provide better cycle control 6