Norethindrone

• Birth Control
• Endometriosis
• Abnormal Uterine Bleeding
• Secondary Amenorrhea

Norethindrone is a synthetic progestin used in various hormonal preparations for contraception, menstrual disorders, and hormone therapy. It is one of the oldest and most widely used progestins, available in different formulations with distinct clinical applications.

Mechanism of Action

Norethindrone exerts multiple mechanisms depending on its use:

Contraception:

• Suppresses ovulation by inhibiting LH surge
• Thickens cervical mucus, impeding sperm penetration
• Creates an unfavorable endometrial environment for implantation
• Reduces fallopian tube motility

Menstrual Disorders:

• Converts proliferative endometrium to secretory phase
• Stabilizes endometrium in anovulatory bleeding
• Reduces endometrial growth

Available Formulations

Progestin-Only Pills (POP):

• Norethindrone 0.35 mg tablets

Combined with Estrogen (various brands):

• Multiple combinations with ethinyl estradiol

Higher Dose for Therapeutic Uses:

• Norethindrone acetate 5 mg tablets (for amenorrhea, endometriosis)

With Conjugated Estrogens (HRT):

• Various combinations for menopausal hormone therapy

Medical Uses

FDA-Approved Indications:

• Contraception (progestin-only or combined)
• Secondary amenorrhea
• Abnormal uterine bleeding due to hormonal imbalance
• Endometriosis (norethindrone acetate)

The progestin-only pill is an option for women who cannot take estrogen.

Dosing Guidelines

Progestin-Only Contraception:

• 0.35 mg daily continuously without breaks
• Must be taken at the same time each day (within 3-hour window)
• No placebo pills

Abnormal Uterine Bleeding:

• Norethindrone acetate: 2.5-10 mg daily for 5-10 days
• Cycling regimen may be used

Endometriosis:

• Norethindrone acetate: 5 mg daily
• May increase by 2.5 mg every 2 weeks up to 15 mg if needed
• Continue for 6-9 months

Important Safety Information

Black Box Warning (Estrogen-Progestin Combinations):

• Cigarette smoking increases risk of serious cardiovascular events
• Risk increases with age and heavy smoking (≥15 cigarettes/day)
• Women over 35 who smoke should not use combined hormonal contraceptives

Contraindications:

• Known or suspected pregnancy
• Breast cancer (current or history)
• Undiagnosed abnormal genital bleeding
• Liver tumors or active liver disease
• Known or suspected progestin-dependent neoplasia

Warnings and Precautions:

• Thromboembolic disorders (lower risk with POP than combined pills)
• Depression: Monitor patients with history
• Glucose intolerance
• Lipid changes

Drug Interactions

• CYP3A4 inducers (rifampin, phenytoin, carbamazepine): Decrease norethindrone levels
• Antiretrovirals: Various interactions; check specific drug
• St. John's Wort: May reduce effectiveness
• Antibiotics: Generally do not affect efficacy (except rifampin)

Special Populations

• Lactation: Progestin-only pills are preferred during breastfeeding (no effect on milk production)
• Adolescents: Safe for use after menarche
• Hepatic Impairment: Contraindicated in severe liver disease
• Cardiovascular Disease: Use with caution; lower risk with POP

Missed Pill Instructions (POP)

• If >3 hours late: Take immediately, use backup contraception for 48 hours
• If vomiting within 2 hours: Take another pill
• Efficacy depends on consistent daily use