What are the indications and usage for Norethisterone (progestin) 5mg?

Indications and Usage for Norethisterone 5mg

Norethisterone 5mg is primarily indicated for the treatment of dysfunctional uterine bleeding, endometrial protection in hormone replacement therapy, and management of bleeding associated with progesterone-only contraceptives. 1, 2, 3

Primary Indications

• Dysfunctional Uterine Bleeding (DUB)

  • Effective for both ovulatory and anovulatory DUB
  • Dosage: 5-10mg three times daily
  • Administration: Days 5-25 of cycle for ovulatory DUB; Days 12-25 for anovulatory DUB 2
  • Significantly reduces menstrual blood loss and duration of bleeding

• Endometrial Protection in Hormone Replacement Therapy (HRT)

  • Used as the progestin component in HRT regimens
  • Continuous regimens: Minimum 1mg daily 4
  • Sequential regimens: Higher doses (5mg) for 12-14 days per month
  • Prevents endometrial hyperplasia in women receiving estrogen therapy

• Management of Bleeding with Progesterone-Only Contraceptives

  • Add-on therapy (5mg) to reduce breakthrough bleeding/spotting with progesterone-only pills
  • Significantly decreases bleeding frequency and quantity 3

Secondary Indications

• Contraception

  • Component in some progestin-only oral contraceptives
  • First-year perfect use failure rate: 0.3%
  • Typical use failure rate: approximately 9% 1

• Premature Ovarian Insufficiency (POI)

  • Used in continuous combined HRT regimens (1mg daily) 4
  • Alternative to micronized progesterone in sequential regimens

• Hereditary Angioedema

  • May reduce symptoms in some patients with hereditary angioedema caused by C1 inhibitor deficiency 4

Important Clinical Considerations

1. Dosage Forms and Administration

   • Oral tablets: 5mg
   • Dosing varies by indication (5-10mg daily or three times daily)
   • Can be used in continuous or cyclical regimens

2. Mechanism of Action

   • Potent progestogenic effects on the endometrium
   • Partial conversion to ethinylestradiol (10-20mg NET corresponds to 20-30μg EE) 5
   • This conversion is clinically significant for risk assessment

3. Risk Profile

   • Thromboembolism: Moderate dose-dependent risk due to partial conversion to ethinylestradiol
     • Contraceptive doses carry minimal risk
     • Therapeutic doses (5mg and above) may increase risk 5
   • Cardiovascular: Generally neutral to positive effects
   • Bone Health: Beneficial effects on bone mineral density
   • Breast Cancer: Slightly increased risk with long-term use 5

4. Contraindications

   • Active thromboembolic disorders
   • History of arterial thrombotic disease
   • Undiagnosed vaginal bleeding
   • Liver problems
   • History of breast cancer 6

Clinical Pearls

• When using norethisterone for endometrial protection, ensure adequate dosing (minimum 1mg daily for continuous regimens, higher doses for sequential regimens) to prevent endometrial hyperplasia 4, 7

• For dysfunctional uterine bleeding, higher doses (5-10mg three times daily) are more effective than lower doses 2

• Consider the partial conversion to ethinylestradiol when prescribing to patients with risk factors for thromboembolism or with migraine with aura 5

• Norethisterone at 5mg is highly effective as an add-on therapy for managing breakthrough bleeding with progesterone-only contraceptives 3

• In patients with hereditary angioedema, norethisterone may be better tolerated than combined hormonal contraceptives 4