Women’s Health · Clinical trials
Heavy Menstrual Bleeding Clinical Trials
Approved therapies, the pivotal-trial endpoints they were judged on, the magnitude of benefit — and the drugs that failed their endpoints, and why.
Indication overview
About heavy menstrual bleeding — and why its trials are hard
Heavy menstrual bleeding (HMB, formerly menorrhagia) is excessive menstrual blood loss - clinically defined as more than 80 mL per cycle or bleeding that impairs quality of life - and is a leading cause of iron-deficiency anaemia in reproductive-age women. Causes span structural lesions (fibroids, polyps, adenomyosis) and non-structural factors (ovulatory dysfunction, coagulopathy, endometrial and iatrogenic causes). Management is tailored to cause and fertility goals. Non-hormonal tranexamic acid (Lysteda) reduces bleeding during menses, while the levonorgestrel-releasing intrauterine system (Mirena) markedly reduces blood loss and is often first-line for those desiring contraception. For fibroid-associated HMB, oral GnRH antagonist combinations (relugolix/Myfembree, elagolix/Oriahnn) achieve large, objectively measured reductions in menstrual blood loss. Combined and progestin-only hormonal contraceptives, and surgical options such as endometrial ablation and hysterectomy, complete the ladder. The unifying efficacy standard is objective reduction of menstrual blood loss below 80 mL, and unmet needs include non-hormonal, fertility-preserving therapies for non-structural HMB.
Approved therapies & pivotal evidence
What's been approved — and by how much it moved the endpoint
| Drug (brand) | Approved | Setting | Pivotal trial | Primary endpoint | Magnitude of benefit |
|---|---|---|---|---|---|
| Tranexamic acid (Lysteda) | 2009 | Cyclic heavy menstrual bleeding (non-hormonal antifibrinolytic) | Phase 3 randomized placebo-controlled trials (Lukes et al., Obstet Gynecol 2010) | Reduction in menstrual blood loss measured by the alkaline hematin method | Approximately 40% reduction in mean menstrual blood loss vs placebo (roughly -69 mL vs -13 mL), P<0.001 |
| Levonorgestrel-releasing intrauterine system (Mirena) | 2009 | Heavy menstrual bleeding in women choosing intrauterine contraception | Randomized trials vs oral therapy and placebo (e.g., ECLIPSE, Gupta et al., NEJM 2013) | Reduction in menstrual blood loss / improvement in bleeding-related quality of life | Reduces menstrual blood loss by approximately 70-95% and outperformed usual medical treatment on quality-of-life measures |
| Relugolix + estradiol + norethindrone acetate (Myfembree) | 2021 | Heavy menstrual bleeding associated with uterine fibroids | LIBERTY 1 and LIBERTY 2 (NEJM 2021) | Menstrual blood loss <80 mL AND >=50% reduction from baseline | 71.7% responders vs 15.7% placebo at week 24 (P<0.0001) |
Where trials have failed
Drugs that missed their endpoint — and what contributed
The most instructive lessons in heavy menstrual bleeding development come from programmes that failed the endpoint that mattered.
| Drug / trial | Endpoint outcome | What contributed |
|---|---|---|
| Ulipristal acetate (selective progesterone receptor modulator) — PEARL programme (fibroid-associated HMB) | Effective on bleeding but not approved in the US and restricted in Europe | Rare serious hepatotoxicity including liver failure requiring transplantation led to regulatory restriction and precluded US approval |
| Oral desmopressin (for HMB in bleeding disorders) — Randomized crossover trials in women with menorrhagia (including von Willebrand disease) | No robust reduction in objective menstrual blood loss as monotherapy | Effect on menstrual blood loss was inconsistent/modest and did not support broad approval for HMB as a standalone therapy |
Choosing the right endpoint
Primary endpoints that matter in heavy menstrual bleeding trials
- Menstrual blood loss <80 mL — The objective clinical threshold defining normal menses; the primary efficacy target across HMB trials, measured by alkaline hematin
- >=50% reduction in blood loss — Relative-change criterion often combined with the <80 mL threshold to define a responder
- Haemoglobin / ferritin — Correction of iron-deficiency anaemia is a clinically meaningful secondary endpoint
- Pictorial Blood loss Assessment Chart (PBAC) — Semi-quantitative patient-reported measure used when direct volumetric measurement is impractical
- Bleeding-related quality of life — Instruments capturing impact on daily activities, a key patient-centred outcome (e.g., in the ECLIPSE trial)
How iNGENū runs heavy menstrual bleeding trials
Physician-led design, built for FDA submission
Endpoint & biomarker strategy
Board-certified specialists design endpoints and patient selection aligned to current FDA guidance for this indication.
FDA-ready data
Built to ICH-GCP and 21 CFR 312.120, with direct FDA submission — data accepted by the FDA, EMA and MHRA.
Faster, lower-cost delivery
~4-week ethics via the TGA CTN scheme, up to 43.5% R&D rebate, and 80–90% below US CRO cost.
Request a fixed-milestone proposal and a tailored endpoint & feasibility summary for this indication.
Frequently asked questions
Heavy Menstrual Bleeding clinical trials — FAQs
What counts as heavy menstrual bleeding?
Is tranexamic acid a hormonal treatment?
Which option reduces bleeding the most?
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