What is the appropriate use and dosage of norethindrone (synthetic progestin)?

Appropriate Use and Dosage of Norethindrone (Synthetic Progestin)

Norethindrone is a first-generation progestin that can be used for contraception, menstrual disorders, hormone replacement therapy, and as adjuvant therapy for acne, with dosage varying by indication.

Indications and Dosing

1. Contraception (Progestin-Only Pills)

• Dosage: 0.35 mg taken orally once daily at the same time every day with continuous administration (no breaks between pill packs) 1
• Effectiveness: 93-97% effective when taken correctly 2
• Advantages: No increased stroke risk compared to combined hormonal contraceptives 2

2. Hormone Replacement Therapy (HRT)

• For postpubertal patients with premature ovarian insufficiency:
  • Sequential regimen: 200 mg oral/vaginal norethindrone for 12-14 days every 28 days (when combined with estrogen) 2
  • Continuous regimen: Minimum 1 mg oral norethindrone daily (when combined with estrogen) 2
  • Duration: Should be continued until average age of spontaneous menopause (45-55 years) 2

3. Adjuvant Therapy for Acne

• Dosage: When combined with ethinyl estradiol as norethindrone acetate/ferrous fumarate, taken as 1 pill daily for 21 days followed by 1 week of no tablets 2
• Note: Only FDA-approved for acne in women who also desire contraception 2

Clinical Considerations

Cardiovascular Risk Profile

• Progestin-only pills (norethindrone 0.35 mg) have no increased risk of stroke compared to non-hormonal contraception 2
• Combined oral contraceptives containing norethindrone have a moderate increase in stroke risk compared to progestin-only options 2
• Blood pressure monitoring is required at baseline and during treatment 2

Adverse Effects

• Common: Breakthrough bleeding, irregular menstruation, weight changes, nausea, breast tenderness 2
• Less common: Depression, mood changes, headaches 2
• Rare but serious: Cholestatic jaundice, thromboembolic events (primarily with combined formulations) 2

Contraindications

• Active or history of thromboembolic disorders
• Undiagnosed genital bleeding
• Breast cancer or other hormone-sensitive cancers
• Liver disease or tumors
• Pregnancy 2

Drug Interactions

• Effectiveness may be reduced by:
  • Antibiotics (cephalosporins, macrolides, penicillins, tetracyclines)
  • Anticonvulsants (carbamazepine, phenytoin, topiramate)
  • Rifampin
  • St. John's wort 2

Special Populations

Adolescents

• Not indicated for use before menarche 2
• For adolescents with premature ovarian insufficiency, norethindrone can be used as part of HRT after estrogen-induced puberty 2

Breastfeeding Women

• Norethindrone is compatible with breastfeeding 2

Women with Cardiovascular Risk Factors

• Progestin-only norethindrone (0.35 mg) is preferred over combined hormonal contraceptives in women with cardiovascular risk factors 2

Monitoring Recommendations

• Baseline: Pregnancy status, blood pressure 2
• Ongoing: Blood pressure, assessment of health status changes 2

Clinical Pearl

When choosing between norethindrone formulations, remember that progestin-only pills (0.35 mg) have a significantly better cardiovascular safety profile than combined hormonal contraceptives containing norethindrone. For patients requiring both acne treatment and contraception, the combined formulation may be appropriate if cardiovascular risk factors are absent.