What is a good progestin-only pill (POP) for menstruation suppression in endometriosis in Canada?

Progestin-Only Pills for Menstruation Suppression in Endometriosis in Canada

Norethindrone (norethisterone) 0.35 mg daily is the recommended progestin-only pill for menstruation suppression in endometriosis in Canada, though higher doses of norethindrone acetate (5-10 mg daily) are more effective for pain control and menstrual suppression. 1, 2, 3

Recommended Progestin-Only Pills

First-Line: Norethindrone/Norethisterone

• Standard POP dose: Norethindrone 0.35 mg once daily is available as a progestin-only contraceptive pill in Canada 1
• Higher therapeutic dose: Norethindrone acetate 5-10 mg daily is more effective for endometriosis-related pain and menstrual suppression, though this requires off-label use of higher-dose formulations 2, 3
• Norethindrone has been used for over 50 years and reduces or eliminates pain symptoms in approximately 90% of endometriosis patients 3
• It suppresses inflammatory cytokines (IL-6, IL-8, MCP-1) in endometriotic tissue and reduces cell proliferation 4

Alternative: Dienogest

• Dienogest has become one of the most widely used progestins for all endometriosis phenotypes for long-term treatment 2
• However, dienogest is not currently available as a standalone product in Canada (it exists only in combination oral contraceptives)

Other Options

• Medroxyprogesterone acetate (MPA): Available in Canada but depot formulation (DMPA) is not recommended due to thrombogenicity concerns in certain populations 5, 2
• Levonorgestrel IUD: May be more effective than oral progestin-only methods for dysmenorrhea, though this is not a pill formulation 6

Prescribing Instructions for Norethindrone

Dosing

• Start with: Norethindrone 0.35 mg once daily, taken continuously at the same time each day (within 3-hour window) 1
• Timing: Can be initiated anytime if reasonably certain patient is not pregnant 5
• Back-up contraception: If started >5 days after menses began, use barrier methods for 2 days 5
• For better menstrual suppression: Consider higher doses (5-10 mg daily) of norethindrone acetate if available, though this requires different formulations 2, 3

Pharmacokinetics

• Peak plasma concentration occurs approximately 1 hour after administration 1
• Half-life is approximately 8 hours 1
• Bioavailability is approximately 65% due to first-pass metabolism 1
• Strict adherence to timing is critical for effectiveness 6, 1

Expected Outcomes

Pain Relief

• Hormonal treatments including progestins lead to clinically significant pain reduction with mean differences of 13.15-17.6 points on 0-100 visual analog scale compared to placebo 7
• Approximately 90% of patients experience reduction or elimination of pain symptoms 3
• Effects include reduction of dysmenorrhea, non-cyclic pelvic pain, and dyspareunia 7, 8

Menstrual Suppression

• Continuous progestin use effectively suppresses menstruation by altering the endometrium and thickening cervical mucus 1, 2
• Breakthrough bleeding is common initially and should be counseled 6

Important Counseling Points

Common Side Effects

• Irregular bleeding patterns: Most common side effect that affects patient satisfaction 6
• For unscheduled spotting or light bleeding, short-term NSAIDs may be considered 6
• Breakthrough bleeding typically improves with continued use 6

Adherence Requirements

• Critical timing: Must be taken at the same time daily (within 3-hour window) for optimal effectiveness 6, 1
• Failure rate is significantly higher than other hormonal methods due to strict adherence requirements 6

Limitations

• 11-19% of individuals have no pain reduction with hormonal medications 7
• 25-34% experience recurrent pelvic pain within 12 months of discontinuing treatment 7
• Does not protect against sexually transmitted infections; condoms recommended 6

When to Consider Alternatives

If Norethindrone Fails

• Consider surgical removal of lesions if first-line hormonal therapies are ineffective or contraindicated 7
• Second-line options include GnRH agonists/antagonists (e.g., relugolix combination therapy with estradiol and norethindrone acetate) 8
• Levonorgestrel IUD may be more effective for dysmenorrhea 6

Contraindications

• Active thromboembolism or history of VTE (though progestin-only pills have lower risk than combined contraceptives) 5
• Pregnancy 5

Follow-Up

• No routine follow-up visit required, but patients should return if experiencing side effects or problems 6
• Assess satisfaction with method and any changes in health status at follow-up 6
• If bleeding irregularities persist and are unacceptable, counsel on alternative methods 6