Norethisterone Dosing for Menstrual Cycle Management
For menstrual cycle management, norethisterone acetate dosing is 2.5-10 mg daily for 5-10 days to induce withdrawal bleeding, or 5 mg three times daily for menstrual delay, with continuous regimens requiring a minimum of 1 mg daily for endometrial protection when combined with estrogen. 1
Dosing by Clinical Indication
For Abnormal Uterine Bleeding and Secondary Amenorrhea
- Standard dose: 2.5-10 mg norethisterone acetate daily for 5-10 days 1
- Produces secretory transformation of adequately primed endometrium
- Withdrawal bleeding typically occurs 3-7 days after discontinuation
- For recurrent episodes, planned menstrual cycling can be implemented 1
For Menstrual Delay
- Acute delay: 5 mg norethisterone three times daily (15 mg total daily) 2
- Must be started on or before cycle day 12 for optimal efficacy
- Superior to combined oral contraceptives when started late in cycle, with only 8% experiencing breakthrough bleeding vs 43% with OCPs 2
- Patients report higher satisfaction (80% willing to repeat) despite transient weight gain 2
For Continuous Hormonal Replacement (with Estrogen)
Sequential regimens (for withdrawal bleeding):
- 5 mg norethisterone daily for 12-14 days every 28 days when combined with transdermal estradiol 3
- Alternative: 10 mg norethisterone for 12-14 days per month 3
Continuous regimens (to avoid withdrawal bleeding):
- Minimum dose: 1 mg norethisterone daily 3
- This is the lowest effective dose for continuous endometrial protection when combined with estrogen 3
For Endometriosis
- Initial dose: 5 mg daily for 2 weeks 1
- Dose escalation: Increase by 2.5 mg every 2 weeks until reaching 15 mg daily
- Maintain at 15 mg daily for 6-9 months or until breakthrough bleeding occurs 1
Important Clinical Considerations
Norethisterone vs Norethisterone Acetate
The evidence uses these terms somewhat interchangeably, but norethisterone acetate is the more commonly prescribed formulation. The FDA label specifically addresses norethisterone acetate dosing 1.
Conversion to Ethinyl Estradiol
Critical caveat: Norethisterone partially converts to ethinyl estradiol—10-20 mg norethisterone corresponds to 20-30 μg ethinyl estradiol 4. This has significant implications:
- Contraindicated in migraine with aura at therapeutic doses due to stroke risk
- Increased VTE risk at therapeutic doses (though contraceptive doses carry no increased risk) 4
- Consider alternative progestins (micronized progesterone, dydrogesterone) in high-risk patients 3
Efficacy Considerations
For heavy menstrual bleeding: Norethisterone 5 mg twice daily (days 19-26) is not effective for ovulatory menorrhagia, increasing blood loss by 20% rather than reducing it 5. Only 9.5% of patients achieved normal menstrual loss with this regimen 5. Consider tranexamic acid or levonorgestrel IUD instead for this indication.
For adolescents: Younger age, obesity, and heavy baseline bleeding predict failure of menstrual suppression with norethisterone 0.35 mg 6. These patients may require norethisterone acetate at higher doses for adequate suppression 6.
Dosing for Specific Populations
Adolescents with premature ovarian insufficiency: When inducing puberty, start with lower doses and escalate over 24 months. After 2-3 years, add norethisterone 5 mg daily for 12-14 days every 28 days for endometrial protection 3.
Etonogestrel implant users with prolonged bleeding: 10 mg norethisterone acetate daily until 2 consecutive bleeding-free days (maximum 30 days) effectively stops bleeding in 86.7% within 7 days, though recurrence is common (median 5 days) 7.
Ranking Among Progestins
When used for hormone replacement therapy, norethisterone is considered a second-choice progestin after micronized progesterone 3. Micronized progesterone is preferred due to lower cardiovascular and thrombotic risk 3. However, norethisterone's pronounced endometrial effects make it particularly effective for abnormal uterine bleeding and endometriosis 4.