What is the proper usage and dosage of Norethindrone (a progestin) for contraceptive purposes or menopausal symptoms?

Norethindrone: Clinical Usage and Dosing

Contraceptive Use

For contraceptive purposes, norethindrone (progestin-only pill) must be taken as one tablet daily at the same time every day, with continuous administration and no interruption between pill packs. 1

Key Administration Points for Contraception:

• Timing is critical: Pills must be taken at the same time daily to maintain contraceptive effectiveness 1
• Backup contraception required: Use condoms and spermicides for 48 hours if a pill is taken 3 or more hours late 1
• Contraceptive effectiveness: Progestin-only pills (norethindrone or drospirenone) have <90% effectiveness and carry no increased stroke risk, unlike combined oral contraceptives 2
• Rapid return to fertility: Normal ovulation and fertility return quickly after discontinuation 1

Important Contraceptive Considerations:

• Pregnancy is an absolute contraindication (Category X) 3, 1
• Baseline monitoring: Check pregnancy status and blood pressure before initiation 3
• Ongoing monitoring: Blood pressure at each visit and annual clinical review for stable patients 3
• Drug interactions: Effectiveness may be reduced by rifampin, anticonvulsants (phenytoin, carbamazepine), St. John's Wort, and certain anti-HIV protease inhibitors 1

Hormone Replacement Therapy (Endometrial Protection)

For endometrial protection when combined with estrogen replacement therapy, the minimum effective dose is norethindrone 1 mg daily taken continuously without interruption. 4

Dosing Regimens for HRT:

• Continuous combined regimen: 1 mg norethindrone daily with transdermal or oral estradiol provides adequate endometrial protection while avoiding withdrawal bleeding 4
• Sequential regimen: 10 mg daily for 12-14 days every 28 days when combined with continuous estrogen (allows withdrawal bleeding) 4
• Important distinction: Do not confuse norethindrone with norethindrone acetate—norethindrone acetate requires lower doses due to higher potency 4

Clinical Positioning for HRT:

• Second-line progestin: Norethindrone is listed as a second-choice progestin after micronized progesterone for hormone replacement therapy due to higher cardiovascular and thrombotic risk compared to micronized progesterone 4
• Monitoring for HRT: Annual clinical review for stable patients, with liver function tests monitored periodically, especially at doses ≥10 mg daily (consider every 3-6 months initially, then annually if stable) 4, 3

Acne Treatment (Combined Oral Contraceptive)

For acne treatment in women who also desire contraception, norethindrone acetate combined with ethinyl estradiol is FDA-approved and should be taken as 1 pill daily at the same time for 21 days followed by 1 week without tablets. 2, 3

Acne Treatment Details:

• Indication: For teens >15 years and adults with acne who desire oral contraception 3
• Mechanism: Combined oral contraceptives provide anti-androgenic effects through decreased ovarian androgen production, increased sex hormone-binding globulin, and reduced free testosterone 2
• Monitoring: Baseline pregnancy status and blood pressure; ongoing blood pressure and health status monitoring 3

Special Populations and Precautions

Cardiovascular Risk Considerations:

• Stroke risk: Progestin-only pills (including norethindrone) carry no increased stroke risk, unlike combined hormonal contraceptives containing estrogen 2
• Post-GDM women: In Latino breastfeeding women with prior gestational diabetes, progestin-only oral contraceptives (0.35 mg/day norethindrone) were associated with a two- to threefold increase in diabetes risk—use with caution during breastfeeding 2

Contraindications and Warnings:

• Absolute contraindications: Pregnancy (Category X), history of breast cancer 3, 1
• Headache warning: Discontinue if recurrent, persistent, or severe headache or worsening migraine with new pattern develops 1
• Gastrointestinal effects: Diarrhea and/or vomiting may reduce hormone absorption and decrease contraceptive effectiveness 1

Breastfeeding:

• Compatible but monitor: Small amounts pass into breast milk (1-6% of maternal plasma levels), with isolated cases of decreased milk production reported 1
• Pediatric use: Safety and efficacy established for postpubertal adolescents; use before menarche is not indicated 1