Phase-Based Management of Heavy Menstrual Bleeding in Women with Bleeding Disorders: From Acute Control to Long-Term Maintenance

Introduction

Heavy menstrual bleeding (HMB) is a common and clinically important manifestation in women with inherited or acquired bleeding disorders (BD). BD comprise a heterogeneous group of conditions affecting primary hemostasis, secondary hemostasis, or both, including thrombocytopenia, platelet function disorders, von Willebrand disease, coagulation factor deficiencies, and acquired disorders related to systemic disease or antithrombotic therapy.^1,2 Because normal menstruation requires coordinated endometrial repair, vasoconstriction, platelet plug formation, coagulation activation, and local fibrinolytic regulation, systemic hemostatic defects can substantially impair menstrual hemostasis and predispose affected women to prolonged or excessive bleeding.^3,4

HMB is defined as excessive menstrual blood loss that interferes with a woman’s physical, emotional, social, or material quality of life.⁵ In women with BD, HMB is often more severe, recurrent, and difficult to manage than in the general population. It may be the first clinical manifestation of an underlying bleeding tendency, especially in adolescents, and is frequently associated with iron-deficiency anemia, emergency visits, transfusion requirements, school or work absence, and impaired quality of life.^6–9 In addition, the increasing use of anticoagulant and antiplatelet therapy in reproductive-aged women has created a growing group of patients in whom clinicians must balance menstrual bleeding control against thrombotic risk.^10,11

Current clinical guidance commonly separates treatment into acute and long-term management.¹² This distinction is useful but incomplete. In real-world practice, many patients remain vulnerable after the initial episode of acute HMB has been controlled. During this interval, anemia may not yet have recovered, the underlying hemostatic defect may still be active, platelet counts or coagulation status may remain unsafe, and definitive maintenance options such as a levonorgestrel-releasing intrauterine system may not yet be feasible. If acute high-dose therapy is stopped abruptly without a transitional plan, recurrent bleeding may occur before long-term suppression is established.^12–14

Several guidelines and studies have addressed important aspects of care, including acute abnormal uterine bleeding, adolescent HMB with suspected bleeding disorders, antifibrinolytic therapy, hormonal suppression, and long-term intrauterine therapy.^8,9,12–17 However, these recommendations are often presented according to treatment modality or clinical population rather than as a continuous pathway from emergency control to stable maintenance. For women with BD, a staged framework may be particularly useful because treatment decisions must account not only for gynecologic bleeding but also for hematologic disease activity, thrombotic risk, anticoagulant use, fertility goals, and patient acceptability.^1,9,16

In this narrative review, we propose a phase-based clinical framework for the management of HMB in women with BD. The framework divides care into three overlapping phases: acute bleeding control, bridging stabilization, and long-term maintenance. We summarize the therapeutic options that may be used in each phase, discuss their strengths and limitations, and emphasize that some therapies may span more than one phase. The goal is to provide a practical, balanced, and multidisciplinary approach that can help clinicians prevent early recurrence while safely transitioning patients toward individualized long-term menstrual suppression.

Review Scope

This article is a narrative review rather than a systematic review. We conducted a targeted literature search of PubMed/MEDLINE, Web of Science, and relevant professional guidelines to identify studies and recommendations on HMB, abnormal uterine bleeding, bleeding disorders, anticoagulant-associated uterine bleeding, and menstrual suppression. Search terms included “heavy menstrual bleeding”, “abnormal uterine bleeding”, “bleeding disorders”, “von Willebrand disease”, “thrombocytopenia”, “platelet function disorders”, “anticoagulation”, “tranexamic acid”, “combined hormonal contraceptives”, “medroxyprogesterone acetate”, “norethindrone acetate”, “mifepristone”, “levonorgestrel-releasing intrauterine system”, and “gonadotropin-releasing hormone analogs”. Priority was given to clinical guidelines, randomized trials, systematic reviews, multicenter cohort studies, and clinically relevant observational studies, including key guidance on acute abnormal uterine bleeding, adolescent HMB with bleeding disorders, inherited bleeding disorders, and hormonal menstrual suppression.^8,9,12–17 Older studies were retained when they provided foundational evidence for acute abnormal uterine bleeding regimens or when more recent evidence was limited.^13,14

Initial Assessment and Phase Allocation

Before selecting a therapeutic regimen, clinicians should first determine the severity of bleeding, hemodynamic status, degree of anemia, underlying hemostatic defect, thrombotic risk, current use of anticoagulant or antiplatelet therapy, fertility intentions, and feasibility of long-term menstrual suppression.^1,9,12,15,16 This initial assessment is particularly important in women with BD because the same menstrual presentation may reflect different combinations of gynecologic bleeding, platelet dysfunction, coagulation factor deficiency, bone marrow suppression, anticoagulant exposure, or systemic disease.^1,2,16

Patients with hemodynamic instability, ongoing heavy active bleeding, severe symptomatic anemia, syncope, hypotension, tachycardia, or suspected hypovolemia should be managed as emergency cases. The immediate priorities are resuscitation, establishment of intravenous access, laboratory evaluation, correction of anemia, targeted hemostatic support, and rapid bleeding control.^9,12 Hospital admission and close collaboration with hematology are usually required in this setting.^1,9

In contrast, hemodynamically stable patients with acute excessive uterine bleeding may not require the same emergency pathway, but they still need prompt treatment to stop bleeding and prevent deterioration.¹² For these patients, outpatient or short-stay management may be appropriate when reliable follow-up is available. Treatment options may include high-dose combined oral contraceptives, high-dose oral progestins, tranexamic acid, iron therapy, and correction of the underlying hemostatic disorder when indicated.^12–14

After the initial bleeding episode has been controlled, the treatment goal changes. Many women with bleeding disorders remain at high risk of early recurrence because anemia has not yet recovered, platelet counts or coagulation parameters may remain unstable, and definitive long-term therapy may not yet be feasible.^1,9 This interval should not be regarded as a passive waiting period. Instead, it represents a distinct bridging stabilization phase, during which temporary menstrual suppression or endometrial stabilization may be used to maintain bleeding control until long-term maintenance therapy can be safely introduced.

Therefore, the proposed phase-based framework should be applied flexibly rather than rigidly. Some therapies may span more than one phase: for example, high-dose progestin regimens may provide both acute bleeding control and short-term stabilization, whereas definitive options such as the levonorgestrel-releasing intrauterine system are generally introduced after bleeding has been controlled and hematologic conditions permit safe placement.^13,14,17 The key clinical principle is not the strict classification of each drug into a single phase, but the deliberate planning of treatment continuity from acute control to sustained maintenance.

Phase 1: Acute Bleeding Control

The primary goal of the acute phase is rapid control of active bleeding while simultaneously correcting hemodynamic compromise, anemia, and the underlying hemostatic abnormality. The choice of therapy should be guided by hemodynamic status, severity of anemia, contraindications to estrogen, thrombotic risk, current anticoagulant or antiplatelet therapy, and whether the patient can tolerate oral medication.^9,12,16 In women with BD, acute gynecologic treatment should not be separated from hematologic management; platelet transfusion, factor replacement, desmopressin, or disease-specific therapy may be required according to the underlying disorder.^1,9

Hemodynamically Unstable or Severe Acute Bleeding

Patients with hemodynamic instability, suspected hypovolemia, ongoing torrential bleeding, or inability to tolerate oral medication should be managed in an emergency or inpatient setting. Immediate measures include resuscitation, intravenous access, blood typing and cross-matching, complete blood count, coagulation assessment, pregnancy exclusion, correction of anemia, and targeted hematologic support.^9,12 In selected patients without major thrombotic risk factors, intravenous conjugated estrogen can be considered for rapid endometrial stabilization. Intravenous conjugated equine estrogen is the only therapy specifically approved by the US Food and Drug Administration for acute abnormal uterine bleeding; one randomized trial reported cessation of bleeding in 72% of participants within 8 hours.¹² The labeled regimen is 25 mg intravenously or intramuscularly, with intravenous administration preferred for a more rapid response, and the dose may be repeated in 6–12 hours if necessary.¹⁸ Because unopposed estrogen may promote endometrial proliferation and withdrawal bleeding, transition to a progestin-containing regimen is required after initial control.¹²

Hemodynamically Stable Acute Excessive Bleeding

For hemodynamically stable patients with acute excessive uterine bleeding, high-dose combined oral contraceptives or high-dose oral progestins are commonly used first-line medical options when there are no contraindications.¹² In the randomized trial by Munro et al, a multidose combined oral contraceptive regimen and oral medroxyprogesterone acetate were both effective for acute uterine bleeding, with bleeding cessation in 88% and 76% of patients, respectively, within a median of 3 days¹³ This evidence is clinically important because it demonstrates that high-dose progestin-only therapy can be an effective alternative to estrogen-containing therapy, particularly for patients in whom estrogen exposure is undesirable.

Combined Hormonal Regimens

Combined oral contraceptive regimens for acute bleeding generally use monophasic pills containing 30–35 μg ethinyl estradiol, administered multiple times daily for a short course, followed by dose reduction after bleeding control.^12,13 However, this approach should be used cautiously in women with BD who also have thrombotic risk factors, active malignancy, prolonged immobilization, thrombophilia, migraine with aura, severe hypertension, or current anticoagulant-related complexity. In these patients, the need for rapid endometrial stabilization must be weighed against the potential thrombotic risk of high systemic estrogen exposure.^12,15,16

High-Dose Progestin Regimens

High-dose progestin therapy is particularly relevant for women with BD because it avoids systemic estrogen exposure while providing endometrial stabilization. Medroxyprogesterone acetate deserves specific discussion because prospective evidence supports its use in acute uterine bleeding. In the Munro trial, oral medroxyprogesterone acetate 20 mg three times daily for 7 days, followed by 20 mg daily for 3 weeks, was used as a progestin-only regimen for acute bleeding control.¹³ Ammerman and Nelson also reported an outpatient progestin-only approach using depot medroxyprogesterone acetate combined with short-course oral medroxyprogesterone acetate, suggesting that progestin-based therapy may cover both acute control and early post-acute stabilization.¹⁴ These data directly support the concept that a single regimen may span Phase 1 and Phase 2 rather than belonging exclusively to one phase.

Choice of Progestin: Medroxyprogesterone Acetate versus Norethindrone Acetate

The choice of progestin should be individualized. Medroxyprogesterone acetate has been specifically studied in prospective acute bleeding regimens and has no estrogen component.^13,14 Norethindrone acetate or norethisterone is also widely used for menstrual suppression and abnormal uterine bleeding, but high-dose use requires caution because a small proportion of norethindrone acetate is converted to ethinyl estradiol. ACOG notes that approximately 4 μg of ethinyl estradiol may be produced from 5 mg of norethindrone acetate.¹⁵ Therefore, in patients with high thrombotic risk, high-dose norethindrone acetate should not automatically be assumed to have the same risk profile as low-dose progestin-only contraception.

Antifibrinolytic Therapy

Antifibrinolytic therapy is an important nonhormonal option for women with HMB and BD, especially when excessive endometrial fibrinolysis contributes to bleeding. Tranexamic acid inhibits plasminogen activation and reduces fibrin degradation, thereby supporting clot stability.¹⁹ ACOG states that antifibrinolytic agents such as tranexamic acid or aminocaproic acid, administered orally or intravenously, may be used to stop bleeding in adolescents with HMB and bleeding disorders.⁹ For cyclic HMB, the approved oral tranexamic acid regimen in patients with normal renal function is 1300 mg three times daily for a maximum of 5 days during menstruation.²⁰ In women with thrombotic risk factors, renal impairment, or concurrent anticoagulant therapy, use of tranexamic acid should be individualized in consultation with hematology.

Mechanical Measures

Mechanical interventions should be reserved for severe acute bleeding that is refractory to medical therapy or when immediate temporary control is required. Intrauterine balloon tamponade using a Foley catheter may provide rapid local control while systemic therapy and hematologic correction take effect.¹² This approach may be particularly useful when systemic estrogen is contraindicated or ineffective. However, it should be used selectively because of potential risks, including infection, uterine perforation, pain, and endometrial injury. In women with BD, the decision to use intrauterine tamponade should take into account platelet count, neutropenia, infection risk, sexual history, fertility concerns, and the availability of experienced clinicians.

Transition After Acute Control

Acute bleeding control should not be the end point of care. Once bleeding has slowed or stopped, clinicians should immediately plan the transition to bridging stabilization. Abrupt cessation of high-dose acute therapy may lead to withdrawal bleeding or early recurrence, particularly in women with persistent thrombocytopenia, platelet dysfunction, coagulation factor deficiency, or ongoing anticoagulant exposure. Therefore, acute regimens should usually be followed by a defined short-term suppressive plan, hematologic optimization, iron replacement, and reassessment for definitive long-term maintenance therapy.

Phase 2: Bridging Stabilization

After acute bleeding has been controlled, many women with BD remain vulnerable to early recurrence. This post-acute interval is clinically important because anemia may still be severe, platelet counts or coagulation parameters may remain unstable, antithrombotic therapy may be ongoing, and definitive long-term maintenance therapy may not yet be feasible. Therefore, bridging stabilization should be considered an active treatment phase rather than a passive waiting period.^1,9

Goals of Bridging Stabilization

The goals of bridging stabilization are to maintain endometrial quiescence, prevent withdrawal bleeding or early recurrence, allow hematologic and iron recovery, provide time for multidisciplinary decision-making, and create safer conditions for definitive maintenance therapy. In this phase, treatment should be selected according to the patient’s thrombotic risk, underlying hemostatic defect, prior response to acute therapy, need for contraception, fertility goals, and acceptability of long-term menstrual suppression.^1,15

Progestin-Based Bridging Regimens

Progestin-based regimens are among the most practical bridging options because they avoid systemic estrogen exposure and can be continued after acute bleeding control. When medroxyprogesterone acetate has been used for acute control, the regimen may be tapered or continued as short-term suppression, thereby covering both Phase 1 and Phase 2.^13,14 This point is important because the phase-based framework should not be interpreted as assigning each medication to only one phase; rather, it emphasizes continuity of care across changing clinical goals.

Oral medroxyprogesterone acetate may be particularly useful when estrogen is contraindicated or undesirable, such as in patients with high thrombotic risk, active malignancy, prolonged immobilization, or complex anticoagulant exposure.^1,13 Norethindrone acetate or norethisterone may also be used for short-term menstrual suppression, but high-dose use should be individualized because norethindrone acetate can be partially converted to ethinyl estradiol.¹⁵ Therefore, in women with substantial thrombotic risk, high-dose norethindrone acetate should not automatically be considered equivalent to low-dose progestin-only contraception.

Depot Progestins as Selected Bridging or Suppression Options

Depot medroxyprogesterone acetate may be considered in selected patients who require longer temporary suppression and for whom adherence to daily oral therapy is difficult. The pilot regimen described by Ammerman and Nelson combined depot medroxyprogesterone acetate with short-course oral medroxyprogesterone acetate for outpatient acute abnormal uterine bleeding, illustrating that depot progestin strategies may provide extended post-acute coverage.¹⁴ However, depot medroxyprogesterone acetate is not ideal for every patient because irregular bleeding may occur after initiation, return to fertility may be delayed, and concerns regarding bone mineral density should be considered during prolonged use.¹⁵

Continuous Combined Hormonal Regimens After Acute Control

In patients without major contraindications to estrogen, continuous or extended-cycle combined hormonal regimens may be used after acute bleeding control to avoid hormone-withdrawal bleeding and provide short-term stabilization. These regimens may also transition directly into long-term menstrual suppression if the patient tolerates estrogen and desires contraception.^15,16 However, in women with BD who have concurrent thrombotic risk factors or who are receiving anticoagulant therapy, estrogen-containing regimens should be used only after individualized risk assessment.

Antifibrinolytic Therapy During Bridging

Tranexamic acid should not be regarded as a continuous menstrual-suppression therapy, but it may be useful during the bridging phase for episodic bleeding or breakthrough bleeding, especially when hormonal escalation is undesirable. In women with BD, its use should be coordinated with hematology, particularly in the presence of renal impairment, previous thrombosis, or concurrent anticoagulant therapy.^9,19,20

Low-Dose Mifepristone as a Selected Bridging Option

Low-dose mifepristone may be considered as a selected bridging option in women with refractory HMB and BD when recurrence prevention and temporary amenorrhea are desired but definitive long-term maintenance therapy is not immediately feasible.²¹ As a selective progesterone receptor modulator, mifepristone may suppress endometrial proliferation and promote endometrial quiescence through both central and peripheral mechanisms.^22–24 These effects may be clinically useful after acute bleeding has been controlled, particularly in patients awaiting hematopoietic stem cell transplantation, recovering from severe anemia, or preparing for delayed placement of definitive long-term therapy.

In a retrospective cohort of women with BD and refractory HMB, low-dose mifepristone was associated with marked reductions in menstrual blood loss, improvement in hemoglobin levels, and acceptable short-term tolerability.²¹ However, this evidence remains observational and should not be interpreted as establishing mifepristone as a universal bridging therapy. Mifepristone is also not appropriate as the sole treatment for torrential or hemodynamically significant acute bleeding because complete bleeding control may not be immediate. It should therefore be positioned as a post-acute stabilization strategy in carefully selected patients rather than as a substitute for emergency bleeding control.

Why Ulipristal Acetate is Not Favored as a Routine Bridging Option

Ulipristal acetate is another selective progesterone receptor modulator and has been used for uterine fibroid-associated bleeding. However, it should not be favored as a routine bridging option for HMB in women with BD. First, its clinical evidence is mainly derived from women with uterine fibroids rather than from women with systemic hemostatic defects. Second, regulatory restrictions have substantially limited its use because of reports of serious liver injury. The European Medicines Agency restricted ulipristal acetate 5 mg to selected premenopausal women with uterine fibroids who cannot undergo surgery or uterine artery embolization, or in whom these procedures have failed.²⁵ Therefore, ulipristal acetate cannot currently be recommended as a general bridging strategy for BD-associated HMB.

Transition from Bridging Stabilization to Long-Term Maintenance

Bridging stabilization should have a defined endpoint. Once bleeding has remained controlled, hemoglobin and iron status have improved, and the hematologic condition permits safer intervention, clinicians should reassess the patient for long-term maintenance therapy. The levonorgestrel-releasing intrauterine system should be regarded primarily as a definitive long-term maintenance option rather than a conventional bridging therapy. In selected patients, its insertion may represent the transition from bridging stabilization to long-term maintenance after active bleeding has subsided and platelet count, infection risk, sexual history, fertility goals, and patient preference have been carefully considered.^1,17

For patients who are not suitable candidates for intrauterine therapy, continued systemic suppression, gonadotropin-releasing hormone analogs, or disease-specific hematologic management may be considered as long-term strategies. The bridging phase should therefore be understood as a structured period of stabilization and planning, not as an indefinite continuation of temporary therapy.

Phase 3: Long-Term Maintenance

Once acute bleeding has been controlled and bridging stabilization has reduced the risk of early recurrence, clinicians should establish a definitive long-term maintenance plan. The goals of long-term maintenance are to reduce menstrual blood loss, prevent recurrent acute bleeding, correct or prevent iron-deficiency anemia, improve quality of life, and align treatment with fertility goals and patient preference.^1,9,15 In women with BD, long-term management should also incorporate hematologic disease control, avoidance of unnecessary thrombotic risk, and close coordination between gynecology and hematology.¹

Levonorgestrel-Releasing Intrauterine System

The 52-mg levonorgestrel-releasing intrauterine system (LNG-IUS) is one of the most effective long-term maintenance options for HMB. It reduces menstrual bleeding primarily through local endometrial suppression, glandular atrophy, decidualization of the stroma, and reduced endometrial responsiveness to circulating estrogen.^26–28 In women without significant cavity-distorting pathology, LNG-IUS is recommended as a first-line long-term treatment for HMB in several clinical guidelines.^1,5

In women with BD, LNG-IUS may provide sustained menstrual control while avoiding systemic estrogen exposure. Studies in adolescents and women with bleeding disorders suggest that LNG-IUS can improve menstrual bleeding and anemia with acceptable continuation and complication profiles.^17,29,30 A multicenter retrospective study of adolescents with HMB found that the 52-mg LNG-IUS was effective in both patients with and without a diagnosed bleeding disorder, supporting its use as a long-term option in this population.¹⁷ ACOG also recognizes the LNG-IUS as an effective treatment for HMB in adolescents with bleeding disorders, although data in this specific population remain more limited than in general HMB cohorts.⁹

However, LNG-IUS placement should be timed carefully. It may be inappropriate during active torrential bleeding, profound thrombocytopenia, severe neutropenia, uncontrolled infection risk, immediate pre-transplant conditioning, or when the patient does not accept intrauterine contraception. Therefore, in high-risk patients, LNG-IUS insertion is often best considered after bridging stabilization, when bleeding has subsided, anemia has improved, and hematologic conditions permit safer placement. In this framework, LNG-IUS represents the transition from bridging stabilization to definitive long-term maintenance rather than a conventional bridging therapy.

Continuous or Extended-Cycle Combined Hormonal Regimens

Continuous or extended-cycle combined hormonal regimens, including combined oral contraceptives, transdermal patches, and vaginal rings, may be useful for long-term menstrual suppression in patients who can safely use estrogen.^15,16 By reducing or eliminating hormone-free intervals, these regimens may decrease withdrawal bleeding and improve cycle control. They may be particularly useful for patients who desire contraception, prefer nonintrauterine methods, and have no major contraindications to estrogen.

Estrogen-containing regimens require careful risk assessment in women with BD because bleeding disorders do not necessarily protect patients from thrombosis. Patients with thrombophilia, previous venous thromboembolism, migraine with aura, severe hypertension, active malignancy, prolonged immobilization, or complex anticoagulant indications may not be appropriate candidates.^15,16 The 2024 U.S. Medical Eligibility Criteria for Contraceptive Use provides updated recommendations for safe use of contraceptive methods in patients with specific medical conditions and should be consulted when selecting long-term combined hormonal therapy.¹⁶

Progestin-Only Maintenance Options

Progestin-only therapies are important long-term options for patients in whom estrogen is contraindicated or undesirable. Available options include oral progestins, depot medroxyprogesterone acetate, etonogestrel implants, and other progestin-only contraceptive methods.^15,16 These therapies may reduce menstrual bleeding through endometrial suppression, but bleeding patterns vary substantially among methods and individuals.

Oral norethindrone acetate can be effective for menstrual suppression, but it is not approved as a contraceptive and high-dose use should be distinguished from low-dose progestin-only contraception because of partial conversion to ethinyl estradiol.¹⁵ Depot medroxyprogesterone acetate may induce amenorrhea in many users over time and can be useful when adherence to daily medication is difficult, but irregular bleeding during initiation, delayed return to fertility, weight change, and bone mineral density concerns should be discussed.¹⁵ Etonogestrel implants and low-dose progestin-only pills may be acceptable for contraception but may be less predictable for complete menstrual suppression, especially in patients in whom breakthrough bleeding could be clinically consequential.

For women with BD, progestin-only strategies should be selected according to the severity of previous bleeding, need for contraception, acceptability of irregular bleeding, bone health, fertility plans, and thrombotic risk. When breakthrough bleeding occurs, short courses of adjunctive therapy, such as tranexamic acid during bleeding days or temporary adjustment of hormonal suppression, may be considered with hematology input.^1,9,20

Gonadotropin-Releasing Hormone Agonists and Antagonists

Gonadotropin-releasing hormone (GnRH) agonists and antagonists may be considered when other long-term options are ineffective, contraindicated, or not feasible. GnRH agonists suppress ovarian steroid production after an initial flare effect, whereas GnRH antagonists suppress gonadotropin secretion without a flare.^31,32 Both approaches can reduce menstrual bleeding by inducing hypoestrogenism and endometrial atrophy, but their use in women with BD specifically remains limited.

GnRH agonists are generally not ideal for immediate acute bleeding control because the initial flare may transiently worsen bleeding and endometrial atrophy usually requires several weeks to develop.^31,33 In contrast, oral GnRH antagonists may offer faster suppression and avoid the flare effect, but evidence in BD-associated HMB is sparse, cost and availability may limit use, and long-term treatment requires attention to hypoestrogenic symptoms and bone health.³² Add-back therapy may be needed during prolonged treatment, but the choice of add-back regimen should be individualized in patients with thrombotic risk or contraindications to estrogen.^15,16

Anticoagulant-Associated HMB

Anticoagulant-associated HMB deserves separate consideration because treatment must balance menstrual bleeding control against prevention of thrombosis. Women receiving oral anticoagulants may experience new or worsened abnormal uterine bleeding, and interruption or inappropriate dose reduction of anticoagulation may increase thrombotic risk.^10,11,34 Therefore, management should be coordinated with the clinician responsible for anticoagulation rather than handled solely as a gynecologic problem.

Long-term strategies may include LNG-IUS after bleeding stabilization, progestin-only suppression, selected continuous combined hormonal therapy when not contraindicated, treatment of iron deficiency, and reassessment of the anticoagulant regimen when clinically appropriate.^1,10,34 Tranexamic acid should be used cautiously and only after individualized assessment in patients receiving anticoagulants because evidence in this setting is limited and thrombotic risk must be considered.^9,20,34

Hematologic Disease-Directed Maintenance

Long-term menstrual control in women with BD cannot rely solely on gynecologic suppression. Optimization of the underlying hematologic condition is often essential. Depending on the diagnosis, this may include von Willebrand factor concentrate, factor replacement, desmopressin, platelet support, treatment of bone marrow failure or hematologic malignancy, modification of antithrombotic therapy when safe, and correction of iron deficiency.^1,9 Regular monitoring of hemoglobin, ferritin, platelet count, coagulation parameters when relevant, treatment adherence, adverse effects, and patient-reported bleeding burden should be incorporated into follow-up.

Follow-up should also reassess fertility intentions, contraception needs, acceptability of amenorrhea, adverse effects, and patient preferences. A treatment that is effective biologically may fail clinically if it is unacceptable, inaccessible, or inconsistent with reproductive goals. Therefore, shared decision-making is central to long-term maintenance, especially in adolescents, patients planning pregnancy, and patients with chronic hematologic disease.^1,9,15

Special Clinical Scenarios

Although the three-phase framework provides a general structure, management should be adapted to specific clinical contexts. Women with BD are not a homogeneous population, and treatment decisions may differ substantially according to age, underlying hematologic disease, platelet count, anticoagulant exposure, transplant status, fertility goals, and acceptability of hormonal or intrauterine therapy.^1,9,15

Adolescents with Heavy Menstrual Bleeding and Bleeding Disorders

Adolescents require particular attention because HMB may be the first presentation of an underlying BD. Evaluation should include assessment of anemia and iron deficiency, screening for bleeding symptoms, exclusion of pregnancy when appropriate, and consideration of endocrine or structural causes of abnormal uterine bleeding.^8,9 In this group, the treatment goal is not only to stop bleeding but also to prevent recurrence, restore iron stores, maintain school and social functioning, and provide developmentally appropriate counseling.

Acute treatment may include high-dose combined hormonal therapy, high-dose progestins, and antifibrinolytic therapy, depending on contraindications and bleeding severity.⁹ Long-term suppression can be achieved with continuous combined hormonal regimens, progestin-only therapy, or LNG-IUS in selected adolescents who accept intrauterine therapy.^9,15,17 Counseling should address expected bleeding patterns, adherence, privacy, contraception, parental involvement when appropriate, and the need for hematology follow-up.

Thrombocytopenia, Bone Marrow Failure, and Hematologic Malignancy

Women with thrombocytopenia, bone marrow failure, or hematologic malignancy often have more complex and unstable bleeding risks than patients with isolated inherited BD. Menstrual bleeding may worsen during periods of severe thrombocytopenia, chemotherapy-induced marrow suppression, infection, or transfusion dependence. In these patients, acute gynecologic treatment should be combined with platelet support, correction of anemia, and disease-specific hematologic therapy when indicated.^1,9

Estrogen-containing regimens may be effective for endometrial stabilization, but they should be used cautiously in patients with active malignancy, prolonged immobilization, central venous catheters, infection, or other thrombotic risk factors.^15,16 Progestin-based regimens may be preferable in many high-risk patients because they avoid systemic estrogen exposure. However, breakthrough bleeding can still occur when platelet counts remain extremely low, and hematologic optimization remains essential.

Intrauterine procedures, including LNG-IUS insertion or balloon tamponade, should be considered carefully in patients with profound thrombocytopenia, neutropenia, active infection, or severe immunosuppression. For some patients, temporary medical suppression during periods of marrow recovery may be more appropriate than immediate intrauterine intervention.

Hematopoietic Stem Cell Transplantation and Chemotherapy

Patients preparing for chemotherapy or hematopoietic stem cell transplantation may benefit from anticipatory menstrual suppression because conditioning regimens can induce profound thrombocytopenia and mucosal bleeding risk. Ideally, menstrual suppression should be planned before the expected nadir in blood counts rather than initiated only after severe bleeding occurs.¹ The choice of regimen should consider urgency of treatment, hepatic function, thrombotic risk, drug interactions, expected duration of cytopenia, and future ovarian function.

Short-term progestin-based suppression, continuous combined hormonal therapy in appropriate candidates, GnRH analogs, or selected use of low-dose mifepristone may be considered depending on the clinical situation.^1,15,21 LNG-IUS insertion is generally not ideal during active severe bleeding, profound thrombocytopenia, or periods of high infection risk. If LNG-IUS is desired as long-term maintenance, insertion is usually safer after bleeding stabilization and hematologic recovery.

Patients Receiving Anticoagulant or Antiplatelet Therapy

Women receiving anticoagulant or antiplatelet therapy require individualized management because the cause of bleeding cannot be addressed simply by stopping antithrombotic treatment. Interruption or inappropriate dose reduction of anticoagulation may increase thrombotic risk, particularly in patients treated for venous thromboembolism, mechanical heart valves, atrial fibrillation, or other high-risk conditions.^10,11,34 Therefore, decisions regarding anticoagulant adjustment should be made jointly with hematology, cardiology, or the prescribing specialist.

Menstrual management options may include LNG-IUS after bleeding stabilization, progestin-only suppression, selected continuous combined hormonal therapy when not contraindicated, treatment of iron deficiency, and careful use of antifibrinolytic therapy when appropriate.^1,9,15,34 In this group, the phase-based framework is particularly useful because it separates immediate bleeding control from the longer-term goal of maintaining menstrual suppression without compromising antithrombotic protection.

Patients Desiring Fertility or Declining Intrauterine Therapy

Fertility goals should be discussed early. Some patients may need temporary bleeding control without contraception, whereas others may desire reliable contraception in addition to menstrual suppression. The LNG-IUS may be highly effective for long-term HMB control, but it may not be acceptable to patients who decline intrauterine therapy, have no history of sexual activity, desire near-term pregnancy, or have clinical conditions that make insertion unsafe.^1,9,15

For patients who desire future pregnancy, temporary medical suppression should be selected with attention to reversibility, expected time to return of ovulation, anemia correction, and optimization of the underlying hematologic condition before conception. Depot medroxyprogesterone acetate may not be ideal when near-term fertility is desired because return to fertility can be delayed.¹⁵ Shared decision-making is therefore essential when balancing bleeding control, contraceptive effects, fertility timing, and patient preferences.

Refractory or Recurrent Bleeding Despite Phase-Based Management

Some patients may continue to experience recurrent or refractory bleeding despite appropriate phase-based medical management. In such cases, clinicians should reassess the diagnosis, treatment adherence, structural uterine pathology, medication interactions, severity of the underlying hemostatic defect, and adequacy of hematologic support.^1,9,12 Escalation may include modification of hormonal suppression, addition of antifibrinolytic therapy during bleeding episodes, optimization of hematologic therapy, delayed LNG-IUS placement when feasible, or selected procedural intervention.

Procedural options should be individualized and are generally reserved for patients who have completed childbearing or have life-threatening bleeding unresponsive to medical therapy. In women with BD, any invasive procedure requires careful planning around platelet count, coagulation status, transfusion support, infection risk, and fertility implications.¹

Clinical Application of the Phase-Based Framework

The proposed phase-based framework is intended to support clinical decision-making rather than to replace individualized judgment. In practice, treatment should begin with assessment of hemodynamic status, bleeding severity, anemia, the underlying hemostatic disorder, thrombotic risk, anticoagulant or antiplatelet exposure, fertility goals, and patient preference.^1,9,12,15,16 Based on this assessment, patients can be allocated to acute bleeding control, bridging stabilization, or long-term maintenance, while recognizing that these phases may overlap and that some therapies may serve more than one purpose.

Step 1: Identify Emergency versus Non-Emergency Presentation

The first decision point is whether the patient has hemodynamic instability or severe active bleeding. Patients with hypotension, syncope, tachycardia, suspected hypovolemia, severe symptomatic anemia, or ongoing torrential bleeding require emergency management, including resuscitation, intravenous access, blood preparation, correction of anemia, targeted hematologic support, and rapid bleeding control.^9,12 In contrast, hemodynamically stable patients with acute excessive bleeding may be managed with urgent medical therapy and close follow-up when reliable reassessment is available.

Step 2: Select Acute Bleeding-Control Therapy

In the acute phase, therapy should be selected according to the severity of bleeding and contraindications. Options may include intravenous estrogen in carefully selected patients without major thrombotic risk, multidose combined oral contraceptives, high-dose oral progestins such as medroxyprogesterone acetate, tranexamic acid, and intrauterine balloon tamponade in refractory or severe cases.^12–14,20 In women with BD, acute gynecologic therapy should be accompanied by hematologic correction when indicated, such as platelet support, factor replacement, desmopressin, or disease-specific treatment.^1,9

Step 3: Do Not Stop After Acute Control

Once bleeding has slowed or stopped, clinicians should avoid treating acute control as the endpoint. This is the point at which many women with BD remain vulnerable to recurrence because anemia, thrombocytopenia, coagulation abnormalities, or anticoagulant exposure may persist. Therefore, a bridging stabilization plan should be established before acute high-dose therapy is discontinued or tapered.

Step 4: Choose Bridging Stabilization According to Risk Profile

Bridging stabilization may include short-term continuation or tapering of progestin-based therapy, continuous combined hormonal regimens in patients without estrogen contraindications, selected depot progestin strategies, tranexamic acid for breakthrough bleeding episodes, or selected low-dose mifepristone when temporary amenorrhea is desired and definitive maintenance therapy is not immediately feasible.^{13–15,20,21} The choice should be individualized according to thrombotic risk, need for contraception, acceptability of amenorrhea, expected duration of hematologic instability, and the feasibility of long-term maintenance.

Step 5: Transition to Definitive Long-Term Maintenance

Bridging stabilization should have a defined endpoint. Once bleeding control is sustained and hematologic conditions permit, patients should transition to long-term maintenance. The 52-mg LNG-IUS is best regarded as a definitive long-term maintenance option rather than a conventional bridging therapy. Other long-term options include continuous or extended-cycle combined hormonal regimens, progestin-only therapies, depot medroxyprogesterone acetate, GnRH agonists or antagonists, and disease-specific hematologic management.^{1,9,15–17,34}

Step 6: Reassess and Adjust

Follow-up should reassess menstrual bleeding, hemoglobin and ferritin levels, platelet count or coagulation parameters when relevant, treatment adherence, adverse effects, thrombotic events, patient satisfaction, fertility goals, and need for ongoing contraception. Failure to achieve adequate control should prompt reassessment of structural uterine disease, treatment adherence, medication interactions, severity of the hemostatic defect, and adequacy of hematologic support.^1,9,12,15

Table 1 summarizes phase-specific treatment goals, therapeutic options, and practical considerations. Figure 1 presents a proposed clinical decision-support algorithm for applying the phase-based framework in women with HMB and BD.

Table 1 Phase-Specific Management of Heavy Menstrual Bleeding in Women with Bleeding Disorders

Figure 1 Proposed phase-based clinical decision-support algorithm for heavy menstrual bleeding in women with bleeding disorders. The algorithm begins with assessment of hemodynamic status, bleeding severity, anemia, the underlying hemostatic disorder, thrombotic risk, anticoagulant or antiplatelet use, fertility goals, and patient preference. Patients with hemodynamic instability or severe active bleeding require emergency resuscitation, hematologic support, and rapid bleeding control. Hemodynamically stable patients with acute excessive bleeding may be managed with urgent medical therapy and close follow-up when appropriate. After acute bleeding control, bridging stabilization should be used to prevent early recurrence, support hematologic recovery, and create a safer window for transition to definitive long-term maintenance. The LNG-IUS is positioned as a long-term maintenance option introduced after bleeding stabilization rather than as conventional bridging therapy. Abbreviations: BD, bleeding disorders; GnRH, gonadotropin-releasing hormone; HMB, heavy menstrual bleeding; LNG-IUS, levonorgestrel-releasing intrauterine system; TXA, tranexamic acid.

Limitations and Future Perspectives

This review has several limitations. First, it is a narrative review rather than a systematic review or evidence-graded clinical guideline. Although we prioritized guidelines, randomized trials, systematic reviews, multicenter studies, and clinically relevant observational studies, the proposed phase-based framework remains a practical clinical model rather than a formally validated treatment algorithm.

Second, the evidence base for HMB management in women with BD remains limited and heterogeneous. Many recommendations are extrapolated from studies of acute abnormal uterine bleeding in the general population, adolescent HMB, fibroid-associated bleeding, anticoagulant-associated bleeding, or general menstrual suppression.^{8,9,12–17,32,34} Direct comparative studies specifically focused on women with inherited or acquired BD are scarce. In addition, BD include diverse conditions such as thrombocytopenia, platelet function disorders, von Willebrand disease, coagulation factor deficiencies, bone marrow failure, hematologic malignancy, and antithrombotic therapy-related bleeding. Therefore, no single regimen can be considered universally appropriate for all patients.

Third, the concept of bridging stabilization is clinically intuitive but not yet supported by high-quality comparative evidence. Existing studies support several potential components of bridging care, including high-dose progestins, depot progestin strategies, continuous hormonal suppression, antifibrinolytic therapy, and selected low-dose mifepristone.^{13–15,20,21} However, the optimal regimen, duration, patient selection criteria, and safety monitoring strategy for bridging stabilization remain uncertain. Future studies should specifically evaluate whether structured bridging therapy reduces early recurrence, transfusion requirements, emergency visits, treatment discontinuation, and progression to invasive procedures.

Fourth, although low-dose mifepristone may be useful in selected post-acute or refractory cases, the available evidence remains observational.²¹ It should therefore be interpreted cautiously and should not be regarded as a universal bridging therapy or as a replacement for acute emergency bleeding control. Further prospective studies are needed to clarify its efficacy, optimal dose, duration, safety profile, endometrial effects, hepatic safety, and appropriate patient population in BD-associated HMB.

Fifth, long-term maintenance outcomes are insufficiently standardized across studies. Future research should evaluate not only short-term bleeding cessation but also recurrent HMB, hemoglobin and ferritin recovery, transfusion requirements, emergency visits, hospital admission, quality of life, treatment continuation, fertility outcomes, thrombotic events, hepatic safety, endometrial safety, bone health, and patient acceptability. Patient-reported outcomes are particularly important because the clinical success of menstrual suppression depends not only on bleeding reduction but also on tolerability, convenience, reproductive goals, and patient preference.

Future studies should aim to develop prospective, multicenter, phase-based care pathways for women with BD and HMB. Such studies should clearly define acute bleeding control, bridging stabilization, and long-term maintenance; stratify patients by bleeding disorder type, platelet count, anticoagulant exposure, thrombotic risk, age, fertility goals, and prior treatment response; and compare different bridging and maintenance strategies using standardized outcomes. Research is also needed to determine the safest timing for LNG-IUS insertion after acute bleeding, the role of systemic suppression in patients who decline intrauterine therapy, and optimal management of anticoagulant-associated HMB without compromising thrombosis prevention.

Conclusion

Heavy menstrual bleeding in women with inherited or acquired bleeding disorders requires a continuous and individualized management pathway rather than isolated acute bleeding control. The proposed phase-based framework organizes care into acute bleeding control, bridging stabilization, and definitive long-term maintenance, thereby addressing the vulnerable interval during which recurrent bleeding may occur before durable menstrual suppression is established. Acute management should prioritize hemodynamic stabilization, rapid bleeding control, correction of anemia, and targeted hematologic support. Bridging stabilization may include progestin-based regimens, continuous combined hormonal regimens in appropriate patients, depot progestins, episodic antifibrinolytic therapy, or selected low-dose mifepristone, while long-term maintenance should be tailored to bleeding phenotype, thrombotic risk, anticoagulant exposure, fertility goals, and patient preference. The levonorgestrel-releasing intrauterine system should be regarded primarily as a definitive long-term maintenance option rather than a conventional bridging therapy. This framework may support multidisciplinary decision-making, but prospective multicenter studies are needed to compare strategies, define optimal transition pathways, and evaluate standardized clinical and patient-reported outcomes.