Understanding Acute Heavy Menstrual Bleeding: Insights From an Interdisciplinary Panel.

FIGO's definition 1 referred to a single episode and was endorsed by the American College of Obstetricians and Gynecologists. 5 This clinical situation is to be distinguished from chronic AUB , defined as an abnormality in one or a combination of the variables of menstrual frequency, regularity, duration, or perceived volume in the majority of the cycles in the previous 6 months. 1 , 13 These situations can coexist so that individuals compromised by chronic heavy menstrual bleeding are particularly vulnerable to the consequences of rapid and excessive blood loss associated with an acute episode. There are no volumetric criteria for acute heavy menstrual bleeding; the definition rests in the clinician's analysis based on the patient's history, observation of features of bleeding from within the uterus, hemodynamic status, and laboratory findings. Similarly, in clinical practice, no objective measure usually exists for chronic AUB; its definition is based at least in part on the patient's perception of the adverse effect that the bleeding has on her quality of life. 8 , 13 , 14 The incidence of acute heavy menstrual bleeding is challenging to determine, largely because there is no specific International Classification of Diseases, Tenth Revision code that would inform estimations in various populations. Preliminary and anecdotal estimates from different sources suggest that acute heavy menstrual bleeding is relatively common. Dr. O'Brien (pediatric hematology): We reviewed 3 years of data from more than 40 standalone children's hospitals and found more than 1,000 young girls admitted for acute heavy menstrual bleeding. 15 One in 20 of those admitted was placed in the intensive care unit because of how anemic and fragile she was. Dr. Dyne (emergency medicine): I went through our emergency department (ED) logs from 2024 and found 1–3 cases of acute heavy menstrual bleeding per day, approximately 1–3% of all patients with ED. Dr. O'Brien (pediatric hematology): We reviewed 3 years of data from more than 40 standalone children's hospitals and found more than 1,000 young girls admitted for acute heavy menstrual bleeding. 15 One in 20 of those admitted was placed in the intensive care unit because of how anemic and fragile she was. Dr. Dyne (emergency medicine): I went through our emergency department (ED) logs from 2024 and found 1–3 cases of acute heavy menstrual bleeding per day, approximately 1–3% of all patients with ED. Chronic heavy menstrual bleeding appears to be far more common than previously thought; evidence from multiple studies has demonstrated the prevalence to be as high as 50%. 16 – 20 The majority of patients have iron deficiency, 21 and many are anemic. Dr. Dyne: We frequently see people tolerating a hemoglobin of 6 g/dL, but an episode of acute heavy menstrual bleeding can result in serious adverse outcomes. Dr. Dyne: We frequently see people tolerating a hemoglobin of 6 g/dL, but an episode of acute heavy menstrual bleeding can result in serious adverse outcomes. Furthermore, chronic anemia from any source predisposes to reactive thrombocytosis, which can result in an increased risk of venous and arterial thrombosis. 22 This influences the choice of medical therapy; the risk of thrombosis can be further magnified when prothrombotic treatment agents such as estrogen are administered. Dr. Nelson (gynecology): To gauge the severity of the problem, we reviewed the hospital records of women admitted to our hospital for chronic heavy menstrual bleeding with hemoglobin levels below 5 g/dL over 5 years. 23 We identified 148 who were admitted 168 times; the lowest hemoglobin was 1.8 g/dL, and the highest platelet count was 1.8×10 6 /microliters. Dr. Nelson (gynecology): To gauge the severity of the problem, we reviewed the hospital records of women admitted to our hospital for chronic heavy menstrual bleeding with hemoglobin levels below 5 g/dL over 5 years. 23 We identified 148 who were admitted 168 times; the lowest hemoglobin was 1.8 g/dL, and the highest platelet count was 1.8×10 6 /microliters.

The clinical problem of acute heavy menstrual bleeding has received relatively little attention from investigators, clinicians, and the life sciences industry despite its adverse effects on reproductive-aged girls and women, as well as the resources used for their care. Existing guidelines have had to rely on consensus because high-quality, adequately powered prospective studies are lacking. The health risks of some pharmacologic therapies can be underappreciated, given the potentially dire consequences of the problem. Assessment of the incidence of acute heavy menstrual bleeding is also challenged by the lack of an International Classification of Diseases, code for this condition. An urgent need exists to increase awareness, not only for clinicians and investigators but also for affected individuals and their families. Too often, affected girls and women have normalized or inadequately treated chronic AUB, and when they experience these acute episodes, they are tipped into a compromised physiologic state. Menstrual cups or Pictorial Blood Loss Assessment charts may help women better quantify their blood losses, and menstrual-tracking applications can help them track the frequency and duration of their bleeding. 52 Management protocols should include interventions that rapidly arrest the acute bleeding episode but also provide more prolonged endometrial suppression to allow the woman to normalize her ferritin levels. These protocols should also assess the frequency of rapid recurrences of acute heavy menstrual bleeding. Iron deficiency, with or without anemia should be diagnosed, evaluated, and appropriately treated as an integral part of the management strategy. A more thorough, robust evaluation of the currently recommended interventions and the development of new, safe, and effective devices and pharmaceutical agents eligible for U.S. Food and Drug Administration approval are critically needed. An array of options are needed to address the problem according to the resources available in different settings. The expertise from several specialties will be required for this work.

No drugs or devices have been approved by the U.S. Food and Drug Administration or other regulatory agencies to treat acute heavy menstrual bleeding. As demonstrated in Table 1 , only a few studies have been published that evaluate the efficacy of medical and procedural interventions for acute heavy menstrual bleeding, and most suffer from limitations that include small numbers, retrospective design, and short-term follow-up. Only two published randomized controlled trials (RCTs) report the effectiveness of treatments for acute heavy menstrual bleeding; the first one, from 1982, evaluated the use of intravenous (IV) conjugated estrogens. 34 Dr. Nelson: The IV estrogen study was a double-blind RCT comprising 34 women with acute heavy menstrual bleeding; 18 received 25 mg IV conjugated equine estrogen (Premarin), and 16 were given IV normal saline as a placebo. All were followed up for at least 5 hours, and bleeding volume was estimated qualitatively and semiobjectively. At 3 hours, the IV estrogen was repeated in those who were still bleeding. At 5 hours, 72% of those in the IV estrogen group had stopped bleeding compared with 38% in the placebo group. Of the eight participants in the placebo group still bleeding at 5 hours, seven received an additional dose of IV estrogen, and all stopped bleeding within 3 hours. Dr. Nelson: The IV estrogen study was a double-blind RCT comprising 34 women with acute heavy menstrual bleeding; 18 received 25 mg IV conjugated equine estrogen (Premarin), and 16 were given IV normal saline as a placebo. All were followed up for at least 5 hours, and bleeding volume was estimated qualitatively and semiobjectively. At 3 hours, the IV estrogen was repeated in those who were still bleeding. At 5 hours, 72% of those in the IV estrogen group had stopped bleeding compared with 38% in the placebo group. Of the eight participants in the placebo group still bleeding at 5 hours, seven received an additional dose of IV estrogen, and all stopped bleeding within 3 hours. Although IV conjugated estrogens arrested the episode of acute heavy menstrual bleeding more effectively than placebo, no follow-up was reported on the duration of the treatment effects. Furthermore, the doses of estrogen used in this study are associated with an increased risk of thromboembolism, particularly in patients with anemia-associated reactive thrombocytosis or when there is a genetic predisposition such as factor V Leiden. The latter is an autosomal dominant trait present in 3–8% of female individuals of European ancestry, 35 many of whom are unaware of their increased risk for thromboembolic sequelae. The second RCT compared combined oral contraceptive–based estrogen–progestin therapy with an oral progestin-only regimen. 36 Dr. Munro (gynecology): We performed this randomized trial as a pilot study with a relatively small sample size comparing oral medroxyprogesterone acetate 20 mg three times a day for a week and then 20 mg daily for a total of 4 weeks with a monophasic combined oral contraceptive containing 1 mg norethindrone and 35 micrograms of ethinyl estradiol administered three times daily for a week and then once daily for 3 weeks. Both interventions were well tolerated and prevented procedural interventions with a median time to cessation of bleeding of 3 days. We demonstrated that estrogen may be unnecessary in an oral regimen for acute heavy menstrual bleeding, thereby reducing the risk of venous thromboembolism. Dr. Munro (gynecology): We performed this randomized trial as a pilot study with a relatively small sample size comparing oral medroxyprogesterone acetate 20 mg three times a day for a week and then 20 mg daily for a total of 4 weeks with a monophasic combined oral contraceptive containing 1 mg norethindrone and 35 micrograms of ethinyl estradiol administered three times daily for a week and then once daily for 3 weeks. Both interventions were well tolerated and prevented procedural interventions with a median time to cessation of bleeding of 3 days. We demonstrated that estrogen may be unnecessary in an oral regimen for acute heavy menstrual bleeding, thereby reducing the risk of venous thromboembolism. The selection of medroxyprogesterone acetate was not random. Because up to 1% of norethindrone and norethindrone acetate is metabolized in the liver to ethinyl estradiol, a daily dose of 10–20 mg norethindrone acetate (eg, Aygestin) equates to 20–30 micrograms of ethinyl estradiol, an amount similar to that contained in most combined oral contraceptives. 37 No such conversion occurs with C-21 progestins such as medroxyprogesterone acetate or megestrol acetate. Dr. Nelson: The early use of combined oral contraceptives to treat acute heavy menstrual bleeding called for 4 tablets of Ovral (50 micrograms ethinyl estradiol and 500 micrograms of norgestrel) four times a day for 5 days. 38 This dose was reduced to two times a day without evidence of efficacy when reports of pulmonary embolism surfaced. The “taper” used today by many clinicians often prematurely reduces the dose, causing bleeding to resume. To provide longer-term endometrial suppression, we conducted a single-arm prospective study in hematologically stable patients with hemoglobin above 8 g/dL, combining medroxyprogesterone acetate 20 mg orally three times a day for 3 days with an intramuscular injection of 150 mg depot medroxyprogesterone acetate. This suppressed bleeding rapidly and provided most with 3 months of light or no bleeding, allowing replenishment of their iron stores and time to perform appropriate diagnostic evaluation. 23 Dr. Nelson: The early use of combined oral contraceptives to treat acute heavy menstrual bleeding called for 4 tablets of Ovral (50 micrograms ethinyl estradiol and 500 micrograms of norgestrel) four times a day for 5 days. 38 This dose was reduced to two times a day without evidence of efficacy when reports of pulmonary embolism surfaced. The “taper” used today by many clinicians often prematurely reduces the dose, causing bleeding to resume. To provide longer-term endometrial suppression, we conducted a single-arm prospective study in hematologically stable patients with hemoglobin above 8 g/dL, combining medroxyprogesterone acetate 20 mg orally three times a day for 3 days with an intramuscular injection of 150 mg depot medroxyprogesterone acetate. This suppressed bleeding rapidly and provided most with 3 months of light or no bleeding, allowing replenishment of their iron stores and time to perform appropriate diagnostic evaluation. 23 Tranexamic acid is another pharmacologic agent successfully administered orally or intravenously in gynecologic surgery for the treatment of some causes of chronic heavy menstrual bleeding. This has led to its use anecdotally in acute heavy menstrual bleeding, absent any published evidence evaluating efficacy in this setting. 39 – 42 Although not available in the United States, one case report found that ulipristal acetate arrested acute bleeding that did not respond to other treatments for severe acute heavy menstrual bleeding. 43 Regardless of the pharmacologic approach, successful endometrial suppression should be continued to allow the repletion of iron stores and time for the return of results from investigations designed to determine the cause of the episode, including for any chronic AUB state. For some, it may be appropriate to consider the use of longer-term suppression with progestins or gonadotropin-releasing hormone antagonists or agonists, remembering that for agonists, suppression with progestins or aromatase inhibitors should be maintained until the “flare” has subsided, generally by 3 weeks. 44 Dr. Munro: Despite the obvious need for more effective therapies, enrollment in clinical trials has been challenging, especially in settings where these patients present. Reliance on traditional, short-term therapies has persisted. In our study of medroxyprogesterone acetate, we could enroll only 40 participants over 2 years from all the EDs in a large health maintenance organization in Southern California. 36 No recent work has been done prospectively in inpatient settings, even in children’s hospitals where this is frequently seen. Dr. Munro: Despite the obvious need for more effective therapies, enrollment in clinical trials has been challenging, especially in settings where these patients present. Reliance on traditional, short-term therapies has persisted. In our study of medroxyprogesterone acetate, we could enroll only 40 participants over 2 years from all the EDs in a large health maintenance organization in Southern California. 36 No recent work has been done prospectively in inpatient settings, even in children’s hospitals where this is frequently seen. Intrauterine tamponade for acute heavy menstrual bleeding has received relatively little attention despite a series published more than 40 years ago by Dr. Milton Goldrath 45 from Michigan. A single case report of a 10-year-old was published relatively recently by the Mayo Clinic describing the successful use of a 30-mL Foley balloon inserted transcervically. 46 Another case report from 2010 also supported this option. 47 One of the potential advantages of tamponade is that bleeding may be immediately stopped, a circumstance quite different from pharmacologic interventions in which blood loss continues until the drug or technique becomes effective. In an office or urgent care setting, tamponade may facilitate safe patient transport to an institutional environment or specialty care. 48 Dr. Munro: We have used a transcervical Foley balloon that often stops the bleeding immediately. For adult women, it may be important to use the 30-mL balloon, especially in larger cavities, because their capacity is known to safely accommodate 60–80 mL, allowing inflation until a satisfactory response is seen. Dr. Munro: We have used a transcervical Foley balloon that often stops the bleeding immediately. For adult women, it may be important to use the 30-mL balloon, especially in larger cavities, because their capacity is known to safely accommodate 60–80 mL, allowing inflation until a satisfactory response is seen. Although there is no evidence-based guidance for the duration of the tamponade, the balloon is usually left inflated for several hours up to a day, depending on the clinical situation. 46 Tamponade should be coupled with a pharmacologic approach such as the medroxyprogesterone acetate regimen described above. Other procedural approaches deserve mention for more serious cases requiring hospitalization and those refractory to medical management. Dilation and curettage, perhaps with hysteroscopy, may have a limited role in selected individuals if there is suspicion of retained products of conception or when medical therapy fails. Uterine artery occlusion with gel foam may have the advantage of providing hemostasis without the use of embolic agents that remain indefinitely in the uterus but with unclear effects on future fertility and pregnancy. Endometrial ablation and hysterectomy have been described and may be necessary in highly selected, usually life-threatening situations. Hysterectomy is a treatment of last resort.

Once the acute episode is controlled, the clinician or team should determine the appropriate next steps. Most therapies described in existing guidelines target only the acute bleeding episode and do not provide the intermediate respite needed for women to recover. 5 A few specify more complete treatments. 6 , 10 , 23 In addition, studies rarely report the incidence of rapid recurrences of acute heavy menstrual bleeding. An isolated episode of acute heavy menstrual bleeding may not require additional care. However, in many, if not most, cases, the acute episode occurs in the context of ongoing chronic AUB. Consequently, as discussed, maintenance of suppression will often be necessary. Patients who are stabilized but moderately to severely anemic should be considered for IV iron instead of blood transfusion. 49 For patients with mild to moderate anemia, even orally ingested iron can be effective and well tolerated when appropriately administered, not two or three times a day but once daily or on alternate days to optimize absorption and minimize gastrointestinal side effects. 50 , 51 Such women should be followed up to ensure an appropriate response that should be apparent by 4 weeks; treatment should continue until iron stores are replete, not just until hemoglobin is normalized. In the follow-up period, patients with chronic AUB need appropriate investigation, preferably following the framework provided by the two FIGO AUB systems. 13 Such girls and women can then be managed in a targeted fashion that is appropriate for the presumed cause or causes of the chronic AUB and in keeping with their immediate and future desires regarding pregnancy. Lack of health insurance, reproductive health deserts, and other socioeconomic factors and social determinants of health can profoundly affect the health of individuals who face these challenges and are made vulnerable to serious recurrences.

Most existing guidelines agree that evaluating vital signs, including blood pressure and pulse, is critical to identifying patients requiring resuscitative care. In every case, the initial objective is to arrest the bleeding. The source of the bleeding should be confirmed by history and especially physical examination to ensure that the bleeding is coming from the uterus and not the vulva, perianal areas, or the urinary tract. The clinician must also evaluate for pregnancy, because the diagnostic and therapeutic pathways for pregnancy-related AUB are vastly different from those for nonpregnant gynecologic patients in their reproductive years. Dr. Dyne: If the vital signs are normal, essential questions include a query for fatigue, dizziness, exertional dyspnea, chest pain, and palpitations, all symptoms associated with iron-deficiency anemia. It is also crucially important to identify comorbidities such as preexisting heart disease, diabetes, hypertension, and kidney disease that may make the patient especially susceptible to the consequences of acute heavy menstrual bleeding. Dr. Dyne: If the vital signs are normal, essential questions include a query for fatigue, dizziness, exertional dyspnea, chest pain, and palpitations, all symptoms associated with iron-deficiency anemia. It is also crucially important to identify comorbidities such as preexisting heart disease, diabetes, hypertension, and kidney disease that may make the patient especially susceptible to the consequences of acute heavy menstrual bleeding. There is controversy among some clinicians about the need for a pelvic examination, but the speculum examination is essential to assess the source of the bleeding. The bimanual examination may identify masses but may miss structural abnormalities of the endometrial cavity such as polyps and leiomyomas (which can be properly assessed only by imaging) and endometrial neoplasia by endometrial sampling and histopathologic examination. The patient's risk factors may guide in determining the role of biopsy and imaging. Dr. Dyne: An ultrasound is routine in our ED setting because we see so much acute and chronic heavy menstrual bleeding, and it helps our gynecologic colleagues carry the ball forward more efficiently afterward. Dr. O'Brien: Because anatomic reasons are less common in the pediatric population, ultrasound is often not part of the initial evaluation, so we typically defer imaging in the emergency setting. Imaging may be deemed necessary if follow-up evaluation fails to reveal a cause or other reasons suggest a structural or neoplastic cause of the bleeding. Dr. Dyne: An ultrasound is routine in our ED setting because we see so much acute and chronic heavy menstrual bleeding, and it helps our gynecologic colleagues carry the ball forward more efficiently afterward. Dr. O'Brien: Because anatomic reasons are less common in the pediatric population, ultrasound is often not part of the initial evaluation, so we typically defer imaging in the emergency setting. Imaging may be deemed necessary if follow-up evaluation fails to reveal a cause or other reasons suggest a structural or neoplastic cause of the bleeding. A complete blood count provides valuable information on anemia, thrombocytopenia, or even thrombocytosis that may discourage the use of estrogen. Most patients with acute heavy menstrual bleeding will be found to be iron deficient, and many will be anemic, particularly if the acute bleeding is superimposed on chronic heavy menstrual bleeding. Evaluation of iron status is an essential part of the workup. The most commonly used measure of iron stores is serum ferritin. Although there has been controversy about the lower limit of normal, it is now generally accepted that the level should be at least 30 ng/mL. However, ferritin may be falsely elevated in chronic inflammatory states, a circumstance that does not affect transferrin saturation, which should be at least 20%. 29 , 30 Some women presenting with acute heavy menstrual bleeding may harbor endometrial neoplasia, including endometrial cancer. Existing guidelines recommend endometrial biopsy for patients with chronic unopposed estrogen exposure and those older than age 45 years. 5 However, patients in their 40s with diabetes or obesity are also at risk of having serious endometrial pathology and long-term chronic ovulatory dysfunction, and obesity can manifest with endometrial cancer even in the third decade of life. 31 Whether the sensitivity of endometrial sampling is compromised in the setting of an episode of acute heavy menstrual bleeding is not clear, but if an abnormality is detected, it can guide therapy. When testing for disorders of hemostasis, it is important to consider that although testing for von Willebrand disease (the most common inherited bleeding disorder) will detect most affected individuals, both acute bleeding and anemia lead to elevated levels of von Willebrand factor. 32 Delaying testing or repeating testing once active bleeding and anemia have resolved will provide a more accurate evaluation for inherited bleeding disorders. Acquired platelet aggregation disorders are also common, but to improve diagnostic accuracy, the investigation should be deferred until the hemoglobin is at least 10 g/dL and should be performed in conjunction with a hematologist. 33

An acute episode of excess “menstrual” blood loss can have a wide range of causes, which can be categorized with the FIGO AUB System 2, the PALM-COEIN system. Although leiomyomas are notoriously common and are a frequent cause of chronic heavy menstrual bleeding, it is generally perceived that acquired and especially inherited bleeding disorders and ovulatory dysfunction are the most common causes of acute heavy menstrual bleeding. Progesterone is a key element in the production of endometrial molecular expressions that contribute to local endometrial hemostasis, 24 and without ovulation, there is no progesterone. Therefore, ovulatory dysfunction creates a circumstance that places the individual at risk of an episode of acute heavy menstrual bleeding. Dr. Nelson: A meta-analysis determined that von Willebrand disease can be identified in 13% of girls and women with chronic heavy menstrual bleeding. 25 However, even more common are acquired platelet aggregation defects for which testing is rarely performed. 26 , 27 These functional platelet disorders can develop at any age. An episode of acute heavy menstrual bleeding may be the first clinical manifestation that the patient can no longer clot her blood promptly, which would be essential to know if she were to require surgery or be injured. In addition, ovulatory disorders are frequently seen at the extremes of reproductive life, but even in otherwise normally ovulating individuals, a single episode of anovulation can occur at any age and manifest with an episode of acute heavy menstrual bleeding. The increasing prevalence of obesity and metabolic syndrome, both of which often result in ovulatory dysfunction, is contributing to increases in the prevalence of AUB-O. Dr. Munro: Although most clinicians recognize that anticoagulant medications can result in iatrogenic heavy menstrual bleeding (AUB-I), the effect of other drugs is less well anticipated. For example, gonadotropin-releasing hormone agonists, typically leuprolide acetate, which may be used for women with heavy menstrual bleeding and leiomyomas (AUB-L), result in an estradiol “flare” after the initial injection that can cause a heavy bleed, leading to an episode of iatrogenic acute heavy menstrual bleeding. Dr. O'Brien: For the pediatric and adolescent age group, anovulatory bleeding is probably the number 1 cause of acute bleeding. As Dr. Nelson states, bleeding disorders are also common and may first manifest with acute heavy menstrual bleeding. One prospective study of patients referred to hematology for evaluation of heavy menstrual bleeding showed that one-third turned out to have an underlying bleeding disorder. 28 Dr. Nelson: A meta-analysis determined that von Willebrand disease can be identified in 13% of girls and women with chronic heavy menstrual bleeding. 25 However, even more common are acquired platelet aggregation defects for which testing is rarely performed. 26 , 27 These functional platelet disorders can develop at any age. An episode of acute heavy menstrual bleeding may be the first clinical manifestation that the patient can no longer clot her blood promptly, which would be essential to know if she were to require surgery or be injured. In addition, ovulatory disorders are frequently seen at the extremes of reproductive life, but even in otherwise normally ovulating individuals, a single episode of anovulation can occur at any age and manifest with an episode of acute heavy menstrual bleeding. The increasing prevalence of obesity and metabolic syndrome, both of which often result in ovulatory dysfunction, is contributing to increases in the prevalence of AUB-O. Dr. Munro: Although most clinicians recognize that anticoagulant medications can result in iatrogenic heavy menstrual bleeding (AUB-I), the effect of other drugs is less well anticipated. For example, gonadotropin-releasing hormone agonists, typically leuprolide acetate, which may be used for women with heavy menstrual bleeding and leiomyomas (AUB-L), result in an estradiol “flare” after the initial injection that can cause a heavy bleed, leading to an episode of iatrogenic acute heavy menstrual bleeding. Dr. O'Brien: For the pediatric and adolescent age group, anovulatory bleeding is probably the number 1 cause of acute bleeding. As Dr. Nelson states, bleeding disorders are also common and may first manifest with acute heavy menstrual bleeding. One prospective study of patients referred to hematology for evaluation of heavy menstrual bleeding showed that one-third turned out to have an underlying bleeding disorder. 28