Drugs for Heavy Menstrual Bleeding

Heavy menstrual bleeding (HMB) is excess menstrual blood loss that disrupts life, and it is a common cause of iron deficiency anaemia. After excluding pregnancy, structural disease, bleeding disorders and thyroid disease, drug treatment is first-line. Options include the levonorgestrel intrauterine system, tranexamic acid, NSAIDs, combined hormonal contraception and progestogens, with surgery for failure.

Classification. Antifibrinolytics (tranexamic acid); NSAIDs (mefenamic acid, naproxen, ibuprofen); hormonal drugs (levonorgestrel intrauterine system, combined pill, progestogens, GnRH analogues); iron and desmopressin where indicated.

Mechanism. Tranexamic acid blocks plasminogen activation and reduces endometrial fibrinolysis. NSAIDs lower prostaglandins and uterine blood flow. Hormones thin the endometrium and suppress ovulation.

Acute heavy bleeding.

• Tranexamic acid 1 g intravenously or orally three times daily.
• Norethisterone 5 mg three times daily for 10 days, then reduce.
• Combined pill three times daily for 7 days (if no contraindication), then once daily.
• Admit if unstable; consider uterine tamponade, procedure or surgery.

Iron. Treat iron deficiency anaemia: ferrous sulphate 200 mg once daily or on alternate days, and intravenous iron for intolerance or severe loss.

Bleeding disorders. Desmopressin 0.3 micrograms/kg with tranexamic acid is used in von Willebrand disease with a proven response.

• First-line. Levonorgestrel intrauterine system when contraception or long-term treatment is wanted; tranexamic acid or an NSAID for women who want no hormones or no contraception; the combined pill for women wanting contraception.
• Alternative. Cyclic norethisterone; DMPA or implant; switching between options after 3 cycles.
• Specialist. GnRH analogues or antagonists before surgery or for fibroids; endometrial ablation, myomectomy, uterine artery embolisation and hysterectomy; investigation for bleeding disorders.
• Emergency. Acute heavy bleeding with instability.

Selection. Offer treatment that fits the woman’s wish for contraception or pregnancy. Tranexamic acid and NSAIDs are taken only during bleeding and can be combined. Review after 3 months.

Contraindications. Pregnancy; undiagnosed bleeding between periods or after sex; suspected cancer (investigate first). Tranexamic acid: active thromboembolism, history of seizures (relative), severe renal impairment. NSAIDs: peptic ulcer, severe asthma triggered by NSAIDs, renal disease. Combined pill: thrombosis and cardiovascular contraindications. Levonorgestrel system: pelvic infection, uterine anomaly.

Serious adverse effects.

• Tranexamic acid: nausea, diarrhoea, headache; rare thrombosis and visual disturbance.
• NSAIDs: gastrointestinal upset and bleeding, renal injury.
• Combined pill: thrombosis, hypertension, breast tenderness, mood change.
• Progestogens: irregular bleeding, bloating, weight gain, bone loss (DMPA).
• Levonorgestrel system: irregular spotting for 3 to 6 months, expulsion, perforation (rare).

Major interactions. Tranexamic acid with combined hormonal contraception (thrombosis risk); NSAIDs with anticoagulants and ACE inhibitors; enzyme inducers lower hormonal levels; warfarin with tranexamic acid and NSAIDs.

Common prescribing errors.

• Starting treatment without excluding structural disease and bleeding disorders.
• Giving tranexamic acid with combined contraception without weighing thrombosis risk.
• Not treating iron deficiency.
• Using NSAIDs in women with ulcers or kidney disease.
• Not reviewing the response at 3 months.

Special groups.

• Pregnancy: not applicable; exclude pregnancy first.
• Breastfeeding: progestogen-only methods and tranexamic acid are acceptable.
• Adolescents: investigate for bleeding disorders; use tranexamic acid, NSAIDs or hormones.
• Older adults: investigate for endometrial cancer in perimenopausal bleeding.
• Kidney: reduce tranexamic acid and avoid NSAIDs in impairment.
• Liver: avoid combined pills in severe disease.
• East Africa: anaemia from heavy bleeding is common and adds to malaria and hookworm anaemia, so test haemoglobin and treat; tranexamic acid and mefenamic acid are affordable, while the levonorgestrel system may be costly or unavailable; fibroids are frequent and need ultrasound.

Monitoring. Bleeding score or pad count, haemoglobin and ferritin, blood pressure, side effects at 3 months, and endometrial assessment for persistent bleeding.

Referral and escalation. Bleeding between periods or after sex; no response after 3 months of treatment; haemoglobin under 100 g/L; suspected fibroids over 12 weeks size or bleeding disorder; adolescents with severe bleeding.

Comparison with alternative classes. The levonorgestrel intrauterine system is the most effective drug treatment and often avoids surgery. Tranexamic acid and NSAIDs offer non-hormonal options but are less effective, and surgery is reserved for failure of drug treatment.