Can Norethisterone Be Added to Manage DMPA-Related Irregular Bleeding?
Yes, norethisterone (5 mg daily) can be added to manage irregular bleeding in DMPA users and has demonstrated significant effectiveness in reducing bleeding frequency and quantity.
Evidence for Norethisterone Use
The most compelling evidence comes from a 2022 prospective study showing that adding 5 mg norethisterone acetate to progesterone-only contraceptives (which share similar bleeding mechanisms with DMPA) significantly reduced bleeding frequency at 2,4, and 6 weeks compared to other management strategies (p-values 0.019,0.002, and 0.002, respectively) 1. Women also reported an overall decrease in combined bleeding quantity and frequency without increased side effects 1.
First-Line Management Approach
Before adding norethisterone, consider these initial steps:
- NSAIDs remain the recommended first-line treatment for breakthrough bleeding with hormonal contraceptives, specifically mefenamic acid 500 mg three times daily or ibuprofen during active bleeding days only 2
- For DMPA users specifically, mefenamic acid 500 mg twice daily for 5 days showed 69.6% bleeding cessation in the first week versus 40% with placebo (p < 0.05), though long-term effectiveness was limited 3
- Counsel patients that irregular bleeding with DMPA typically improves over time and occurs in nearly all patients initially 4
When to Add Norethisterone
Norethisterone addition is appropriate when:
- NSAIDs have failed to adequately control bleeding after a trial period 1
- Bleeding persists beyond 3-6 months and significantly impacts quality of life 2
- The patient requires more sustained bleeding control than NSAIDs provide 1
The recommended regimen is norethisterone acetate 5 mg daily based on the evidence showing superior outcomes compared to doubling the progestin dose or switching formulations 1.
Alternative Treatments from Systematic Review
A 2013 Cochrane review evaluated multiple interventions for progestin-only contraceptive bleeding 5:
- Estrogen treatments reduced bleeding episode duration in DMPA users but frequently caused gastrointestinal upset leading to discontinuation 5
- Tranexamic acid showed promise in terminating bleeding episodes in small studies 5
- Mifepristone (anti-progestin) reduced bleeding days in some progestin implant users but data for DMPA is limited 5
However, the Cochrane review concluded that results do not support routine clinical use of these regimens, particularly for long-term effect 5.
Important Counseling Points
- Reassure patients that irregular bleeding does not indicate reduced contraceptive effectiveness 2
- Emphasize that bleeding irregularities are not harmful 2
- Consistent timing of DMPA injections every 13 weeks (up to 15 weeks maximum) helps minimize bleeding problems 4
- Ensure adequate calcium intake (1300 mg daily) and vitamin D (600 IU) for bone health during DMPA use 4
Evaluation Before Treatment
Rule out other causes of bleeding:
- Pregnancy testing if clinically indicated 6
- Sexually transmitted infections 2
- Medication interactions, particularly enzyme-inducing drugs 2
- New uterine pathology (polyps, fibroids) if bleeding pattern changes abruptly 2, 6
Common Pitfalls to Avoid
- Do not assume all bleeding is solely due to DMPA without excluding other pathology, especially if bleeding pattern changes suddenly 2, 6
- Avoid prescribing estrogen-containing contraceptives to patients with antiphospholipid antibodies, as DMPA itself may carry thrombosis risk in this population 4
- Do not overlook bone health implications with prolonged DMPA use exceeding 2 years 6
Follow-Up Recommendations
- Advise patients to return if bleeding persists beyond 3-6 months or worsens 2
- No routine follow-up is required unless bleeding becomes heavy, prolonged, or unacceptable to the patient 2
- If norethisterone fails after adequate trial, consider switching to alternative long-acting contraceptive methods such as levonorgestrel IUD, which may provide menstrual suppression while avoiding DMPA's bone density effects 4