What is the typical usage and dosage of Norethindrone (progestin) 5mg for conditions like endometriosis?

Norethindrone 5mg: Clinical Usage and Dosing

Norethindrone 5mg daily is primarily used for endometrial protection in hormone replacement therapy and as add-back therapy with GnRH agonists for endometriosis, administered continuously for 12-14 days per 28-day cycle in HRT or daily when combined with GnRH agonists. 1

Primary Indications and Dosing

Hormone Replacement Therapy (Endometrial Protection)

• Norethindrone 5mg daily for 12-14 days every 28 days is the standard alternative when micronized progesterone (100-200mg) is contraindicated or poorly tolerated in post-pubertal patients with premature ovarian insufficiency 1
• This sequential regimen provides endometrial protection and induces regular withdrawal bleeding 1
• Medroxyprogesterone acetate (MPA) 5-10mg daily represents another equivalent alternative with the same dosing schedule 1

Endometriosis Management with GnRH Agonist Add-Back Therapy

• Norethindrone 5-10mg daily continuously when combined with GnRH agonists effectively treats symptomatic endometriosis while preventing hypoestrogenic side effects 2, 3
• The regimen typically starts at 5mg daily, then increases to 10mg daily as tolerated 2
• This combination maintains therapeutic efficacy for endometriosis while:
  • Eliminating vasomotor symptoms (hot flashes) 2
  • Preventing bone mineral density loss 2, 3
  • Reducing vaginal dryness 2

Endometriosis Monotherapy (Post-Surgical)

• Norethindrone acetate 5-15mg daily continuously as single-agent therapy effectively suppresses post-operative endometriosis symptoms 4
• Median pain scores decreased from 5 to 0 (p=0.0001) and bleeding scores from 2 to 0 (p=0.001) across all disease stages 4
• Lower dose norethindrone acetate 2.5mg daily has also demonstrated efficacy for symptomatic rectovaginal endometriosis with 73% patient satisfaction at 12 months 5

Key Clinical Considerations

Monitoring Requirements

• Baseline assessment: Pregnancy status (Category X contraindication), blood pressure, and breast cancer history 6
• Ongoing monitoring: Annual clinical review for stable patients, with more frequent monitoring during initial therapy 6
• Liver function tests: Monitor periodically, especially at doses ≥10mg daily—consider every 3-6 months initially, then annually if stable 6

Metabolic Effects

• Reversible decrease in HDL-cholesterol and increase in LDL:HDL ratio occurs with norethindrone add-back therapy 2
• Mean BMI increase of 1.2 ± 1.6 kg/m² at 12 months when used as monotherapy, though 55.2% of patients report no side effects 4
• Weight gain is the most common adverse effect (16.1% of patients) 4

Advantages Over Alternatives

• Preferred over other progestins (except micronized progesterone and dydrogesterone) due to less negative effects on lipid metabolism and fewer androgenic effects 1
• More cost-effective than repeat surgery for symptomatic endometriosis in patients not seeking conception 5
• Allows prolonged GnRH agonist therapy (up to 48 weeks) without significant bone loss when combined with cyclic bisphosphonates 3

Dosing Algorithm by Clinical Scenario

For HRT in POI:

• Start estrogen replacement first
• Add norethindrone 5mg daily for 12-14 days/month after 2-3 years of estrogen or when breakthrough bleeding occurs 1

For endometriosis with GnRH agonist:

• Initiate GnRH agonist (e.g., leuprolide 3.75mg IM monthly)
• Add norethindrone 5mg daily, increase to 10mg daily as needed 2
• Continue for 24-48 weeks with appropriate monitoring 3

For post-surgical endometriosis suppression:

• Start norethindrone acetate 5mg daily, titrate up to 15mg based on symptom control 4
• Alternative: Low-dose 2.5mg daily for milder symptoms or rectovaginal disease 5

Common Pitfalls to Avoid

• Do not use norethindrone in pregnancy (Category X) 6
• Do not prescribe without assessing breast cancer history (absolute contraindication) 6
• Do not add progestin too early in pubertal induction—wait at least 2 years of estrogen therapy 1
• Do not overlook lipid monitoring when using higher doses or combination therapy 2