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Abnormal uterine bleeding in nonpregnant reproductive-age patients: Management

Abnormal uterine bleeding in nonpregnant reproductive-age patients: Management
Author:
Andrew M Kaunitz, MD
Section Editor:
Robert L Barbieri, MD
Deputy Editor:
Alana Chakrabarti, MD
Literature review current through: Apr 2025. | This topic last updated: Oct 22, 2024.

INTRODUCTION — 

Abnormal uterine bleeding (AUB), a term that refers to menstrual bleeding of abnormal quantity, duration, or schedule, is a common gynecologic problem. Heavy or prolonged uterine bleeding can result in anemia, interfere with daily activities, and is the most common presenting symptom in patients with endometrial hyperplasia or carcinoma. It may also be a sign of an underlying bleeding disorder.

Most patients with AUB requiring medical attention can be managed in an outpatient setting. Occasionally, an exacerbation of AUB is severe enough to necessitate emergency medical care.

The management of non-acute AUB in nonpregnant reproductive-age patients will be reviewed here. Other related topics are discussed separately:

●Evaluation and diagnosis of AUB (see "Abnormal uterine bleeding in nonpregnant reproductive-age patients: Terminology, evaluation, and approach to diagnosis")

●Management of acute AUB (see "Managing an episode of acute uterine bleeding")

●Evaluation and management of AUB in adolescents (see "Abnormal uterine bleeding in adolescents: Evaluation and approach to diagnosis" and "Anovulatory uterine bleeding in adolescents: Management")

●Vaginal bleeding during pregnancy (see "Evaluation and differential diagnosis of vaginal bleeding before 20 weeks of gestation")

●Postmenopausal bleeding (see "Approach to the patient with postmenopausal uterine bleeding")

TERMINOLOGY — 

AUB encompasses a heterogeneous group of conditions with diverse etiologies. The International Federation of Gynecology and Obstetrics (FIGO) classification system includes two systems for AUB: FIGO system 1 for the nomenclature and definitions of normal and abnormal uterine bleeding, and FIGO system 2 for the classification of the causes of AUB [1,2]. The latter is referred to by the acronym PALM-COEIN (polyp, adenomyosis, leiomyoma, malignancy and hyperplasia, coagulopathy, ovulatory dysfunction, endometrial, iatrogenic, and not yet classified). These are summarized in the graphics (table 1 and figure 1) and discussed in detail separately. (See "Normal menstrual cycle", section on 'Definitions of normal uterine bleeding (menstruation)' and "Causes of female genital tract bleeding", section on 'Uterine bleeding'.)

MANAGEMENT GOALS AND TREATMENT CONSIDERATIONS

●Management goals – The main goals of AUB management are as follows:

•Correct or treat the underlying primary etiology, if present and feasible.

•Improve quality of life.

•Prevent an episode of acute uterine bleeding requiring urgent evaluation.

•Prevent, or treat, anemia and iron deficiency.

•Establish a regular bleeding pattern (or amenorrhea).

•Prevent, or treat, endometrial hyperplasia/carcinoma.

●Treatment considerations – To help determine which treatment is best for a particular patient, clinicians should consider several patient factors. These include:

•Timing of treatment. The timing of initiating treatment of AUB should be individualized. In patients in whom AUB is not interfering with daily activities, it may be appropriate to delay initiation of treatment until results of diagnostic testing (eg, imaging, endometrial biopsy) are available. (See "Abnormal uterine bleeding in nonpregnant reproductive-age patients: Terminology, evaluation, and approach to diagnosis", section on 'Endometrial sampling: Choice of modality' and "Overview of the evaluation of the endometrium for malignant or premalignant disease", section on 'Premenopausal patients with abnormal bleeding'.)

By contrast, when AUB is interfering with daily activities and/or marked anemia is present, it is appropriate to immediately initiate treatment, as detailed below, while pursuing diagnostic testing. (See 'How to choose' below.)

•Severity of bleeding. Most patients with AUB requiring medical attention can be managed in an outpatient setting. By contrast, patients with an episode of acute uterine bleeding may require urgent evaluation in an emergency department. (See "Managing an episode of acute uterine bleeding".)

•Associated symptoms and issues. AUB is often associated with other symptoms (eg, pelvic pain/pressure, dysmenorrhea) or issues (eg, infertility); the underlying etiology (eg, adenomyosis, uterine fibroid) should be identified to select the optimal treatment approach. Patients with a bleeding disorder may have a history of other bleeding (eg, nose bleeds, bruising, excessive bleeding after a dental procedure) that they may not report to their gynecologist. (See "Abnormal uterine bleeding in nonpregnant reproductive-age patients: Terminology, evaluation, and approach to diagnosis", section on 'History'.)

•Contraceptive needs and plans for future pregnancy. Many treatments for AUB also provide contraception. However, for patients trying to conceive, or those desiring pregnancy in the near future, some treatments (eg, levonorgestrel intrauterine device [LNG IUD], depot medroxyprogesterone acetate [DMPA]) should be avoided. (See 'Patients trying to conceive' below.)

•Medical comorbidities. Some treatments (eg, estrogen-progestin contraceptives) are contraindicated in patients with certain comorbidities (eg, elevated risk of venous thromboembolic disease and/or arterial thrombotic events). (See 'Patients with increased risk of thrombosis' below and 'Patients with other contraindications to estrogen' below.)

•Patient preferences. Patient preferences regarding, as well as access to, medical versus surgical and short-term versus long-term therapy.

•Time to menopause. AUB should resolve when a patient becomes menopausal (which occurs, on average, at the age of 51.5 years). However, there is a wide range of age at onset of menopause, and menopause timing is difficult to predict. (See "Clinical manifestations and diagnosis of menopause", section on 'Menopause'.)

Expectant management may be reasonable for some patients (eg, not anemic, do not desire treatment, approaching menopause). Such patients require close follow-up (eg, ferritin level every 6 to 12 months for patients with heavy menstrual bleeding [HMB], repeat endometrial assessment for patients at risk for hyperplasia/neoplasia).

HOW TO CHOOSE — 

(algorithm 1)

Patients with a known structural, infectious, or endocrine etiology — Treatment of certain underlying conditions may correct the AUB or make further medical treatment of AUB more effective (see 'Medication details' below). These include structural lesions (eg, submucosal fibroids, polyps), endocrine (eg, polycystic ovarian syndrome), and infectious (eg, chronic endometritis) etiologies. Patients with a coagulopathy are discussed separately. (See 'Patients with heavy bleeding' below.)

Structural lesions

●Submucosal fibroids are a common cause of heavy menstrual bleeding (HMB) and can be treated with medical or surgical therapies. (See "Uterine fibroids (leiomyomas): Treatment overview".)

●Endometrial polyps are a common cause of AUB and are typically easily removed with hysteroscopic polypectomy. (See "Endometrial polyps".)

●Adenomyosis is a common cause of HMB and dysmenorrhea; while hysterectomy is the definitive treatment, medical or other surgical therapies may also be effective. (See "Uterine adenomyosis".)

●Cesarean scar defects (CSD; also referred to as isthmocele or niche) is an increasingly common cause of AUB.

CSD can be surgically resected via operative hysteroscopy, vaginal surgery, laparotomy/laparoscopy, or a combined approach (which allows visualization of the defect from two perspectives). In one meta-analysis including randomized trials and observational studies of surgical treatment for CSD, those undergoing a combined approach with laparoscopy and hysteroscopy compared with vaginal surgery or hysteroscopy alone had a greater reduction in the duration of AUB [3].

●Arteriovenous malformations (AVMs) represent a rare cause of AUB. (See "Causes of female genital tract bleeding", section on 'Not otherwise classified (AUB-N)'.)

If bleeding is severe, initial management consists of hemodynamic stabilization with intrauterine tamponade (eg, with a balloon or packing material) followed by uterine artery embolization (UAE). While UAE appears to be safe and effective [4-7], and both restoration of normal menstrual cycles and subsequent successful pregnancies have been reported, patients should be counseled that embolization may result in impaired fertility and the safety of pregnancy after embolization is uncertain [8,9]. Laparoscopic bipolar coagulation of the uterine vessels has also been successful in case reports [10]. (See "Managing an episode of acute uterine bleeding", section on 'Role of uterine artery embolization'.)

Hysterectomy is the definitive treatment option in patients in whom childbearing is complete [11].

The management of enhanced myometrial vascularity (EMV), a diagnostic entity distinct from AVM and occurring in the setting of pregnancy and retained products of conception, is discussed in detail separately. (See "Retained products of conception in the first half of pregnancy", section on 'Management' and "Secondary (late) postpartum hemorrhage", section on 'Management'.)

Infection — AUB in patients with suspected or documented chronic endometritis often resolves following a course of antibiotics. (See "Endometritis unrelated to pregnancy".)

Endocrine abnormalities — Endocrine abnormalities (eg, hypothyroidism, hyperprolactinemia) may cause anovulatory bleeding (AUB-O), and treatment often restores regular ovulatory cycles; treatment of other endocrine abnormalities (eg, polycystic ovarian syndrome) can also help decrease the risk of endometrial hyperplasia or carcinoma [12-15]. (See "Treatment of primary hypothyroidism in adults" and "Management of hyperprolactinemia" and "Treatment of polycystic ovary syndrome in adults".)

Patients without a structural, infectious, or endocrine etiology — For patients without a structural, infectious, or endocrine etiology, initial management may include hormonal therapies (eg, estrogen-progestin contraceptives, 52 mg levonorgestrel-releasing intrauterine device [LNG 52 mg IUD, Mirena or Liletta], progestin-only oral or injectable medications, noncontraceptive estrogen-progestin formulations) and nonhormonal medications (eg, tranexamic acid [TXA], nonsteroidal antiinflammatory drugs [NSAIDs]).

Surgery, either minimally invasive or definitive treatment with hysterectomy, may be an option for some patients but options are limited in patients who desire future childbearing. (See 'Role of surgery' below.)

Most patients (no contraindications to medical therapy)

●First-line management – For most patients with AUB and no known primary etiology, we suggest estrogen-progestin contraceptives or the LNG 52 mg as first-line therapy. Both estrogen-progestin contraceptives and the LNG 52 mg are effective treatments for AUB, provide effective contraception, are well tolerated, and have a low risk of adverse effects. (See 'Estrogen-progestin contraceptives' below and '52 mg levonorgestrel intrauterine device' below.)

The choice is often based on patient preference (table 2). Patients may prefer estrogen-progestin contraceptives if they prefer taking a daily oral medication or are planning to conceive in the near future. Estrogen-progestin contraceptives also typically make bleeding more regular, lighter, and reduce dysmenorrhea. By contrast, patients may prefer the low maintenance of having an IUD or are willing to tolerate the irregular bleeding that initially accompanies placement of an LNG 52 mg given the subsequent light bleeding or amenorrhea that often occurs. (See "Combined estrogen-progestin oral contraceptives: Patient selection, counseling, and use", section on 'Counseling points' and "Intrauterine contraception: Candidates and device selection", section on 'Reasons to choose an LNG IUD'.)

Both estrogen-progestin contraceptives and the LNG 52 mg improve bleeding. In randomized trials including patients with AUB, patients taking estrogen-progestin contraceptives compared with placebo have improved bleeding patterns [16] and reductions in menstrual blood loss ranging from 35 to 69 percent [17]. The LNG 52 mg appears to provide further improvement in bleeding. In systematic reviews and a meta-analysis including randomized trials, the LNG 52 mg reduced menstrual blood loss more than other medical treatments, however, the certainty of this evidence was low [16-20]. In one review including patients with HMB, the LNG 52 mg resulted in a greater reduction in menstrual blood loss (71 to 95 percent reduction) than estrogen-progestin contraceptives (35 to 69 percent reduction) [17].

●Reasonable alternatives – For patients who cannot (eg, active pelvic infection for IUD) or choose not to use an estrogen-progestin contraceptives or the LNG 52 mg, reasonable alternatives include other progestin-therapies (eg, oral progestins, depot medroxyprogesterone acetate [DMPA]), and noncontraceptive doses of estrogen-progestin.

However, oral and injectable progestin-therapies are less well studied than the LNG 52 mg for the treatment of AUB. They may also result in irregular menses, are associated with side effects (eg, dysphoria, bloating, increased appetite) that some patients find bothersome, and reduce menstrual blood loss less than the LNG 52 mg. In the systematic reviews discussed above, oral progestin therapy compared with LNG 52 mg resulted in a smaller reduction of blood loss (87 versus 71 to 95 percent reduction [17]; mean difference [MD] -77 versus -106 mL/cycle [20]). (See 'Progestin-only therapies' below.)

Noncontraceptive estrogen-progestin formulations, marketed for treatment of menopausal vasomotor symptoms, are also less well studied for the treatment of AUB. In our experience, they often result in amenorrhea after several months. Progestin-related side effects appear less common and less severe with this formulation compared with the higher-dose oral progestin regimens. (See 'Noncontraceptive estrogen-progestin formulations' below and "Hormonal contraception for menstrual suppression", section on 'Other'.)

●Other – Other therapeutic options (danazol [18], high-dose oral estrogen, gonadotropin-releasing hormone analogs) are also available for treatment of AUB in selected patients and are discussed in detail separately. (See "Managing an episode of acute uterine bleeding", section on 'Alternative: High-dose intravenous estrogen' and "Uterine fibroids (leiomyomas): Treatment overview", section on 'GnRH analogs'.)

Patients with increased risk of thrombosis — Management options for patients with an increased risk of thrombosis (eg, personal history of a thrombotic event, selected thrombogenic mutations [eg, deficiency of antithrombin, protein C, or protein S]), are more limited.

●Safety of LNG 52 – For such patients, the LNG 52 mg is often a first-line method. While the LNG 52 mg results in a low level of systemic progestin absorption, its use has not been associated with an elevated risk of venous thromboembolism (VTE) in average-risk patients [21]. The LNG 52 mg also does not appear to increase the risk of VTE in patients with elevated risk of thrombosis [22]. In a case-control study including over 128,000 reproductive age patients with and without VTE, current use of LNG 52 mg compared with non-use was associated with similar rates of VTE; results were also similar after controlling for 16 VTE risk factors (including, but not limited to, body mass index [BMI] ≥30 kg/m2, smoking, hypertension, and superficial venous thrombosis) [23]. (See "Contraception: Counseling regarding inherited thrombophilias", section on 'Progestin-only methods'.)

●Treatments that may be contraindicated – The following treatments may be contraindicated in patients with an increased risk of thrombosis; medical consultation is often helpful to help determine the patient’s individual risk (see 'When to refer' below):

•Estrogen-progestin therapies – In general, estrogen-containing therapies are avoided in patients with an increased risk of thrombosis. However, they may be used in carefully counseled patients with a strong medical rationale for their use, especially those with only mild thrombophilias (eg, heterozygous factor V Leiden or prothrombin variant) and no personal or family history of VTE. These issues are discussed in detail separately. (See "Contraception: Counseling regarding inherited thrombophilias", section on 'Estrogen-progestin methods' and "Combined estrogen-progestin oral contraceptives: Patient selection, counseling, and use", section on 'Candidates'.)

•Other progestins – Package labeling for oral and injectable progestins (eg, norethindrone acetate [NETA], medroxyprogesterone acetate [MPA], depot medroxyprogesterone acetate [DMPA]) list a history of VTE as a contraindication to use as they are partially metabolized to ethinyl estradiol [24,25], which may elevate risk of VTE. However, the US Medical Eligibility Criteria for Contraceptive Use classifies progestin-only methods as having "advantages that generally outweigh the theoretical or proven risks" in patients with a history of VTE [26]. Medical consultation may be helpful to determine VTE risk.

In the case-control study discussed above, use of NETA or MPA was associated with higher rates of VTE compared with non-use (adjusted odds ratio [aOR] 3, 95% CI 2.17-4.15 and 1.98, 95% CI 1.53-2.58, respectively) [23].

Some data also suggest an increased risk of thrombosis with DMPA [23,27,28]. (See 'Depot medroxyprogesterone acetate' below.)

•TXA (a treatment option for patients with HMB) is contraindicated in some patients with increased risk of thrombosis. This is discussed in detail below. (See 'Patients with heavy bleeding' below.)

Patients with other contraindications to estrogen — In addition to increased risk of thrombosis, other contraindications to estrogen include the following [29,30]:

•Age ≥35 years who are smoking ≥15 cigarettes per day.

•Multiple risk factors for arterial cardiovascular disease (such as older age, smoking, diabetes, and hypertension). Because age and obesity represent independent risk factors for VTE [31,32], in our practice, we also avoid estrogen-progestin contraceptives in patients ≥40 years of age with obesity.

•Hypertension. Blood pressure parameters are detailed separately. (See "Combined estrogen-progestin contraception: Side effects and health concerns", section on 'Contraindications'.)

•Known ischemic heart disease.

•History of stroke.

•Complicated valvular heart disease (pulmonary hypertension, risk for atrial fibrillation, history of subacute bacterial endocarditis).

•Selected patients with systemic lupus erythematosus (eg, patients with positive or unknown antiphospholipid antibodies). (See "Approach to contraception in women with systemic lupus erythematosus", section on 'Choosing a method of contraception'.)

•Migraine with aura at any age.

For such patients, the LNG 52 mg is often a first-line method. Other options, including oral and injectable progestin-only therapies, noncontraceptive estrogen-progestin formulations, and surgery may be reasonable alternatives for such patients. (See 'Progestin-only therapies' below and 'Noncontraceptive estrogen-progestin formulations' below and 'Role of surgery' below.)

Patients with heavy bleeding — In addition to other medical (eg, estrogen-progestin contraceptives, LNG 52 mg) and surgical therapies (see 'Estrogen-containing therapies' below and 'Progestin-only therapies' below and 'Role of surgery' below), TXA or NSAIDs are also options for selected patients with HMB. The choice of therapy depends on a number of factors, which are detailed in the table (table 2).

Both TXA and NSAIDs appear to reduce menstrual blood loss less than estrogen-progestin contraceptives or the LNG 52 mg. In one systematic review of randomized trials, the percent reduction of menstrual blood loss by treatment method was as follows: LNG 52 mg: 71 to 95 percent reduction; estrogen-progestin contraceptives: 35 to 69 percent reduction; TXA: 26 to 54 percent reduction; and NSAIDs: 10 to 52 percent reduction [17]. Similarly, a subsequent systematic review showed the largest reduction of menstrual blood loss with the LNG 52 mg (mean difference [MD] -106 mL/cycle) compared with antifibrinolytic (MD -80 mL/cycle) and NSAID (MD -41 mL/cycle) therapy [20].

●TXA – TXA is an antifibrinolytic agent approved by the FDA for the treatment of HMB (see 'Tranexamic acid' below). In our practice, we sometimes use this medication in patients with any of the following:

•Suspected bleeding disorder; HMB is a common finding in such patients. This is discussed in detail separately. (See "Causes of female genital tract bleeding", section on 'Coagulopathy (AUB-C)' and "von Willebrand disease (VWD): Gynecologic and obstetric considerations", section on 'Interventions for HMB' and "Bleeding disorder of unknown cause (BDUC)", section on 'Heavy menstrual bleeding'.)

•Certain contraindications to hormonal therapy (eg, personal history of breast cancer).

•Did not respond to, or prefers to avoid, another first-line agent (ie, estrogen-progestin contraceptive, LNG 52). (See 'Most patients (no contraindications to medical therapy)' above.)

The role of TXA in patients with an increased risk of thrombosis is controversial [33,34]. Venous and arterial thrombosis or thromboembolism has been reported in patients treated with TXA [35], and US Food and Drug Administration (FDA) labeling lists active thrombosis, history of thrombosis, or concomitant use of combined hormonal contraception as contraindications to use [36]. Some experts, however, consider concomitant use of TXA and combined hormonal contraception to be reasonable in patients with a bleeding disorder (eg, von Willebrand disease) [37], or those in whom additional thrombosis risk factors (eg, obesity, immobility) are not present [38].

Representative studies include the following:

•In a case-control study from Sweden, TXA was not associated with an increased risk of venous thrombosis [33].

•In a British case-control study, TXA was associated with an increased trend of thrombosis, but this did not reach statistical significance. Additionally, anemia associated with HMB itself was found to be associated with an elevated risk of thrombosis, likely a result of reactive thrombocytosis [39]. While this suggests that anemia associated with HMB represents a prothrombotic condition regardless of medication use [34], the anemia should be treated.

●NSAIDs – NSAIDs used to treat HMB include ibuprofen, naproxen, and mefenamic acid (see 'Nonsteroidal antiinflammatory drugs' below); they reduce the volume of menstrual blood loss by causing a decline in the rate of prostaglandin (PGE2 and PGF2 alpha) synthesis in the endometrium, leading to vasoconstriction and reduced bleeding [40,41].

NSAIDs are generally avoided in individuals receiving an anticoagulant or with concern for a bleeding disorder, as they may worsening bleeding in such patients (see "Risks and prevention of bleeding with oral anticoagulants", section on 'Concomitant medications'). They are also not typically used to treat patients with anovulatory AUB (AUB-O).

NSAIDs are often prescribed concurrently with combined estrogen-progestin contraceptives or LNG 52 mg.

●Other – Other medical therapies (eg, epsilon aminocaproic acid [EACA], desmopressin [DDAVP], von Willebrand factor concentrate) may also be appropriate for patients with bleeding disorders [42,43]. The choice of therapy depends on the specific bleeding disorder and is typically managed by the patient’s hematologist. This is discussed in detail separately. (See "von Willebrand disease (VWD): Gynecologic and obstetric considerations", section on 'Interventions for HMB' and "Bleeding disorder of unknown cause (BDUC)", section on 'Heavy menstrual bleeding'.)

MEDICATION DETAILS

Estrogen-containing therapies

Estrogen-progestin contraceptives — There are many formulations of estrogen-progestin contraceptives that vary by the type, dose, route, and schedule (table 3); most formulations are effective for treating heavy menstrual bleeding (HMB), and for regulating bleeding and providing endometrial protection in patients with anovulatory bleeding (AUB -O).

●Oral – The only oral estrogen-progestin contraceptive approved by the US Food and Drug Administration (FDA) for treatment of HMB is estradiol-dienogest (Natazia; includes 2 to 3 mg of estradiol valerate [dose varies and is equivalent to 1.5 to 2.25 mg of micronized oral estradiol or <20 mcg of ethinyl estradiol [44]]), which has 26 hormonally active tablets per each 28-day pill pack. In a randomized placebo-controlled trial including 190 patients with AUB (more than three-quarters of whom had documented HMB; the remainder had prolonged or frequent bleeding), estradiol-dienogest compared with placebo reduced menstrual blood loss in more patients (64 versus 8 percent) [45]. It is uncertain whether estradiol-dienogest has greater efficacy than other estrogen-progestin contraceptives in reducing menstrual blood loss in patients with HMB, as there have been no studies that directly compare them.

Oral estrogen-progestin contraceptives with shorter hormone-free intervals are associated with less withdrawal bleeding than formulations with seven hormone-free days per 28-day pill pack [46]. Although further study is needed to determine which formulations are more effective in treating HMB, our preference is to use formulations with four or fewer hormone-free days per pill pack.

●Other routes – Other routes of administration include the transdermal contraceptive patch (eg, Xulane, Twirla) and vaginal contraceptive ring (eg, NuvaRing, Annovera). Although these have not been studied extensively for HMB, it is likely that the efficacy of these in treating AUB is similar to oral estrogen-progestin contraceptives, and the choice of delivery system depends on patient preference [47]. (See "Combined estrogen-progestin oral contraceptives: Patient selection, counseling, and use".)

●By schedule – Estrogen-progestin contraceptives may be prescribed in a cyclic (with a monthly withdrawal bleed), extended (eg, with a withdrawal bleeding every three months), or continuous (no withdrawal bleed) regimen. Although extended or continuous contraceptive use may more effectively suppress menstrual blood loss, unscheduled (breakthrough) bleeding is more common with this approach than with cyclic dosing, limiting this strategy's appeal for some patients. In clinical trials performed in patients with normal menses, extended-cycle formulations that replace hormonally inactive tablets with low-dose ethinyl estradiol, a formulation which also modifies the ethinyl estradiol dose during each three-month pill pack, appear to reduce unscheduled bleeding [48,49]. (See "Combined estrogen-progestin oral contraceptives: Patient selection, counseling, and use", section on 'Hormone components' and "Hormonal contraception for menstrual suppression".)

Estrogen-progestin contraceptives are contraindicated in some patients. (See 'Patients with increased risk of thrombosis' above and 'Patients with other contraindications to estrogen' above.)

Noncontraceptive estrogen-progestin formulations — Ultra-low estrogen dose formulations marketed for treatment of menopausal vasomotor symptoms (eg, ethinyl estradiol 5 mcg with 1 mg of norethindrone acetate [Jinteli 1/5 and other generics]) may be used off-label to treat AUB [50]. (See 'Most patients (no contraindications to medical therapy)' above.)

Such formulations contain 28 days of hormonally active tablets (continuous therapy) with estrogen doses lower than the typical oral estrogen-progestin contraceptive dose (20 to 35 mcg ethinyl estradiol). Because of its low estrogen dose, some clinicians may consider using this formulation when lower estrogen doses are preferred (eg, females >35 years who smoke cigarettes, or those with migraines without aura). Such use requires careful assessment, patient counseling, and possible medical consultation regarding risk. (See 'When to refer' below.)

This formulation is also not proven to provide effective contraception. Thus, patients should be counseled to use concomitant back-up (eg, barrier) contraception if needed.

Progestin-only therapies — Progestin-therapies used to treat AUB include the 52 mg levonorgestrel-releasing intrauterine device (LNG 52 mg IUD, Mirena or Liletta), oral (norethindrone acetate [NETA], medroxyprogesterone acetate [MPA]), and injectable medications (depot medroxyprogesterone acetate [DMPA]).

Neither progestin-only contraceptive pills (eg, norethindrone 0.35 mg, drospirenone) nor the etonogestrel implant are known to be effective in treating AUB [51-53]. Further study is needed to determine the efficacy of other progestin IUDs (eg, 19.5 mg and 13.5 mg LNG devices) in treating HMB [54].

52 mg levonorgestrel intrauterine device — The LNG 52 mg IUD is approved by the US FDA for treatment of HMB [55,56]. (See "Intrauterine contraception: Background and device types" and "Intrauterine contraception: Candidates and device selection".)

Factors specific to treatment of HMB with the LNG 52 mg include:

●Reduction of bleeding – Most patients using the LNG 52 mg develop scant bleeding or amenorrhea, and some studies suggest this treatment, compared with other hormonal or nonhormonal treatments, is associated with an improved quality of life [19,20,57-60]. In studies of patients with HMB, within three months of IUD placement, most patients experience spotting [61-63]. At six months, menstrual suppression is substantially greater, with most patients experiencing amenorrhea or infrequent bleeding; median hemoglobin and ferritin levels also increased from baseline (7.5 and 68.8 percent, respectively). In one retrospective study including 89 patients with HMB in whom follow-up data were available, treatment with the LNG 52 resulted in a median decrease in blood loss of 93 and 98 percent at three and six months, respectively [59]. Results were similar for patients with body mass index (BMI) <30 compared with ≥30 kg/m2 and for nulliparous compared with parous patients.

Furthermore, users of the LNG 52 mg require fewer subsequent additional interventions. In one large observational study, increasing use of the LNG 52 mg (a 14-fold increase over 22 years) was accompanied by a decrease in use of oral tranexamic acid (TXA), oral progestogen, and hysterectomy [64]. These observations underscore the efficacy of the LNG 52 mg in preventing and/or treating AUB.

●Risk of expulsion – Expulsion rates are higher in patients using the LNG 52 mg for treatment of HMB compared with those using the device specifically for contraception (up to 20 versus 10 percent, respectively) [65,66]. For patients with adenomyosis, one study reported a 25 percent expulsion rate with the LNG 52 mg [67]. Package labeling for the LNG 52 mg lists congenital or acquired distortion of the endometrial cavity (eg, by fibroids) as a contraindication to placement of this IUD. Nonetheless, in patients with HMB who wish to avoid surgery or in whom the risk of surgical complications is elevated, use of the LNG 52 mg may be appropriate in well-counseled patients. When placing the LNG 52 mg in patients with a distorted endometrial cavity, some clinicians use abdominal ultrasound guidance to ensure optimal placement.

●Frequency of replacing the device – When the LNG 52 mg is used to treat HMB, it is approved by the FDA for five years [55,56]. By contrast, when the LNG 52 mg is used for contraception, it is approved for eight years. Thus, menstrual suppression may attenuate before it needs to be removed for contraception, and patients using the LNG 52 mg for treatment of HMB may benefit from more frequent removal and replacement of the device [68]. The need for more frequent replacement may reflect declining intrauterine progestin concentrations during use of this device. (See "Intrauterine contraception: Background and device types".)

LNG 52 mg is contraindicated in some patients (eg, anatomic abnormalities that severely distort the uterine cavity; active pelvic infection). This is discussed in detail separately. (See "Intrauterine contraception: Candidates and device selection", section on 'Contraindications'.)

Oral progestins — Oral progestin formulations include NETA and MPA. The contraceptive efficacy of these regimens has not been evaluated, and a back-up method (eg, barrier contraceptives) is recommended if needed.

●Dose – The dose of oral progestins varies and includes NETA 5 mg (one tablet) orally daily (dose range 2.5 mg [one half tablet] to 15 mg [three tablets] daily) and MPA 5 to 30 mg orally daily. In our practice, we typically start with NETA 5 mg once daily; higher doses within these ranges are typically used in patients with obesity. If bleeding does not resolve, the dose is increased (eg, NETA: by 5 mg increments every one to three months to a maximum dose of 15 mg/day; MPA: by 5 to 10 mg increments every one to three months to a maximum dose of 30 mg/day), and other therapies (eg, LNG 52 mg, combined estrogen-progestin) should be more strongly considered (see '52 mg levonorgestrel intrauterine device' above and 'Estrogen-progestin contraceptives' above).

In patients in whom bleeding resolves, the dose may be slowly tapered down (eg, NETA: by 2.5 mg increments every month as tolerated; MPA: by 5 mg increments every month as tolerated) to reduce side effects and risk of VTE. Similarly, if cost or side-effect considerations in a specific patient preclude use of one agent, the other agent may be used.

Most data about use of oral progestins for HMB have evaluated NETA, and compared with MPA, it is substantially more potent in promoting endometrial suppression [69]. In one study, the potency of NETA was ten times that of MPA [70].

●Schedule – While there are no high-quality data comparing cyclic and continuous progestin therapy for treatment of AUB, we can extrapolate from the LNG 52 mg and DMPA that continuous progestin regimens effectively reduce uterine bleeding. In our experience, we find that continuous rather than cyclical progestin therapy is more effective at reducing blood loss and easier for patients to comply with. Cyclic regimens may be used in select patients (eg, cannot tolerate a continuous regimen, trying to conceive). (See 'Patients trying to conceive' below.)

In a mixed population of older reproductive-age patients with AUB-O or HMB, one study found that oral MPA 5 mg tablets administered continuously for two months reduced menstrual blood loss by 33 percent [71]. By contrast, a systematic review including six randomized trials evaluating oral progestins administered cyclically for 7 to 11 days each month did not find this regimen to be effective in ovulatory patients with HMB [72]. However, longer cyclic therapy (eg, 21 days each month) may be effective [47,73] and result in moderate, predictable withdrawal bleeding.

Oral progestins are contraindicated in some patients. (See 'Patients with increased risk of thrombosis' above.)

Depot medroxyprogesterone acetate — DMPA results in a reduction in bleeding in most patients. In patients with no complaints of AUB at baseline and using DMPA for contraception, approximately one-half become amenorrheic after four injections (one year), and approximately three-quarters of users will become amenorrheic after eight injections (two years). In patients using DMPA for treatment of AUB-O or HMB, one short-term study noted a 49 percent reduction in menstrual blood loss after two months [71].

DMPA is not an option for patients who are trying to conceive or interested in conceiving in the next one to two years as the contraceptive effect persists for longer than the three-month dosing interval. (See 'Patients trying to conceive' below.)

Some data suggest an increased risk of thrombosis with DMPA [23,27,28]. This is discussed in more detail separately. (See "Depot medroxyprogesterone acetate (DMPA): Efficacy, side effects, metabolic impact, and benefits", section on 'Cardiovascular and thromboembolic risk' and "Depot medroxyprogesterone acetate (DMPA): Formulations, patient selection and drug administration".)

Nonhormonal therapies

Tranexamic acid — Tranexamic acid (TXA) is an antifibrinolytic agent that competitively blocks the conversion of plasminogen to plasmin, thereby reducing fibrinolysis. (See "von Willebrand disease (VWD): Gynecologic and obstetric considerations", section on 'Interventions for HMB'.)

●Dose and duration – When used for treatment of HMB, TXA is taken only during menses. For patients with normal kidney function, the recommended dose is 1300 mg (two 650 mg tablets) three times daily for as long as five days during menstruation. The dose should be adjusted downwards for patients with impaired kidney function.

●Evidence for efficacy – In a multicenter randomized trial including almost 200 patients with HMB, individuals assigned to TXA compared with placebo had a greater decrease in menstrual blood loss (40 versus 8 percent reduction) [74].

●Adverse effects – TXA is generally well tolerated. In the multicenter randomized trial discussed above, the most common reported adverse effects were menstrual cramps, headache, back pain, and nausea, but the frequency of these events was similar to those treated with placebo [74].

●Contraindications – TXA is typically contraindicated in those with active thrombosis, history of thrombosis, or concomitant use of combined hormonal contraception. This is discussed in detail above. (See 'Patients with heavy bleeding' above.)

Nonsteroidal antiinflammatory drugs

●Dose and duration – When used for treatment of HMB, NSAIDs are prescribed to start on the first day of bleeding and should be continued for two to three days or until menstruation ceases. Example regimens include:

•Ibuprofen 600 mg two [75] to four times daily.

•Naproxen 500 mg at onset and three to five hours later, then 250 to 500 mg twice a day [76-78].

•Mefenamic acid 500 mg three times per day [79,80] or 500 mg followed by 250 mg every six hours (similar to the dosing used for primary dysmenorrhea) [81].

●Evidence for efficacy – In systematic reviews of randomized trials including patients with HMB, NSAIDs were more effective than placebo at reducing HMB [18,20]. In this study, the efficacy of naproxen and mefenamic acid in treating HMB were similar.

●Contraindications – NSAIDs are generally avoided in individuals receiving an anticoagulant or with concern for a bleeding disorder, as they may worsening bleeding in such patients. (See 'Patients with heavy bleeding' above.)

ROLE OF SURGERY — 

For patients with AUB and a known structural etiology (eg, submucosal fibroid, endometrial polyp), surgery (eg, hysteroscopic myomectomy, hysteroscopic polypectomy) may correct the AUB or make further medical treatment of AUB more effective. (See 'Structural lesions' above.)

For patients with AUB but without a structural etiology, surgical therapy (eg, endometrial ablation, hysterectomy) may also be an option; this includes patients who have completed childbearing and who prefer to avoid medical therapy, in whom medical therapy was ineffective or resulted in bothersome side effects, or who desire definitive therapy (hysterectomy). One cost-effective approach is to start with the LNG 52 mg and, if unsuccessful, follow with endometrial ablation or hysterectomy [82,83].

The choice between endometrial ablation and hysterectomy is discussed here and, in more detail, separately. (See "Overview of endometrial ablation", section on 'Ablation versus other treatments'.)

●Endometrial ablation – Endometrial ablation is a minimally invasive treatment option for patients who have completed childbearing and have heavy or prolonged uterine bleeding despite medical therapy or do not want to use chronic medical therapy [84]. (See "Overview of endometrial ablation".)

Both endometrial ablation (performed with resectoscopic or nonresectoscopic techniques) and LNG 52 mg are effective in reducing menstrual blood loss [20]. The decision to use endometrial ablation or LNG 52 mg depends on a patient's preferences regarding treatment factors, such as plans for fertility and contraception, convenience, and risks of anesthesia. Advantages of the LNG 52 mg are that it provides reversible contraceptive, is placed in an office setting and requires no or local anesthesia; one disadvantage is the LNG 52 mg needs to be replaced at regular intervals (see '52 mg levonorgestrel intrauterine device' above). By contrast, pregnancy is contraindicated after endometrial ablation, but the procedure does not prevent pregnancy; thus, patients will need to continue to use contraception following ablation. In addition, while endometrial ablation can be performed in an office, it is often performed in an operating room under general anesthesia; but if successful, is performed once and often does not require repeating.

In a meta-analysis and systematic reviews of randomized trials, the LNG 52 mg and endometrial ablation had similar reductions of menstrual blood loss as well as similar improvements in quality of life [16,19]. However, patients treated with the LNG 52 mg appear to require more reinterventions. In a randomized trial of 270 patients with heavy menstrual bleeding (HMB), patients treated with the LNG 52 mg compared with endometrial ablation underwent more than twice as many surgical reinterventions (27 versus 10 percent, relative risk 2.64, 95% CI 1.49-4.68), which included endometrial ablation and hysterectomy, within two years [85]. The surgical reintervention rate remained elevated (RR 1.84, 95% CI 1.11-3.1) when the patients were followed through 7.5 years [86]. In an earlier systematic review of eight randomized trials including patients with HMB, over half of those assigned to medical treatment underwent surgery by two years [87]. At four-month follow-up, endometrial resection was more effective than oral medication in controlling bleeding (odds ratio [OR] 10.6, 95% CI 5.3-21.3) and less likely to cause side effects (OR 0.2, 95% CI 0.1-0.3).

Details regarding endometrial ablation in patients with bleeding disorders or on anticoagulation therapy are presented separately. (See "Overview of endometrial ablation", section on 'Patients with bleeding disorders or anticoagulation therapy'.)

●Hysterectomy – Hysterectomy is the definitive treatment for uterine bleeding. This procedure has a high rate of patient satisfaction because it is curative, is frequently performed after medical management has failed, is not associated with drug-related side effects, and does not require repeated procedures or prolonged follow-up. Hysterectomy also has the advantage of eliminating future risk of uterine and cervical cancer and, in patients who also undergo complete salpingectomy, reduces the risk of developing epithelial ovarian carcinomas. However, hysterectomy has a risk of perioperative complications and, depending on the operative approach, a prolonged recovery. (See "Hysterectomy (benign indications): Selection of surgical route" and "Opportunistic salpingectomy for ovarian, fallopian tube, and peritoneal carcinoma risk reduction", section on 'Ovarian cancer risk reduction'.)

While hysterectomy is curative, treatment with the LNG 52 mg has several potential short- and long-term advantages, in addition to absence of surgical morbidity and reversibility if patients decide they want to try to conceive.

In a 2013 study of 236 patients with HMB that followed patients for 10 years after they were randomized to placement of a LNG 52 mg or hysterectomy, 46 percent of those initially randomized to IUD placement ultimately underwent hysterectomy [88]. Overall, costs were lower among patients initially randomized to the IUD, while health-related quality of life and psychosocial well-being were similar in the two groups. In the same trial, 10-year follow-up reported that patients in the IUD group had lower rates of stress urinary incontinence (34 versus 48 percent) and usage of medications for urinary incontinence (1 versus 12 percent) [89]. In the systematic review of randomized trials evaluating patients with HMB discussed above, hysterectomy compared with medical treatment resulted in greater improvements in mental health at six-month follow-up [87].

As many of the randomized trials comparing treatment modalities for AUB in patients who have completed childbearing are over 10 years old and may have evaluated only open abdominal hysterectomy, further studies are needed to compare laparoscopic hysterectomy with other treatments for AUB.

It is important to note that surgical procedures may be limited by insurance coverage and/or medical guidelines; for example, the National Health Service in the United Kingdom advises against routine performance of dilation and curettage and hysterectomy for HMB [90]. Surgical procedures are also costly. In one trial, 63 patients with persistent AUB (median duration four years) who were dissatisfied with cyclic oral progestin therapy were randomized to undergo either hysterectomy or expanded medical therapy (eg, estrogen-progestin contraceptives, nonsteroidal antiinflammatory drugs (NSAIDs), low-dose estrogen-progestin regimens) [91,92]. By 18 months, over 50 percent of those randomized to medical treatment had asked for and received a hysterectomy (median interval to crossing over was six months). At 24 months, mean resource use was higher in the surgical versus medical management arms [93]. However, an undefined cost/benefit is elimination of future risk of endometrial carcinoma in patients undergoing hysterectomy; this should not be overlooked as patients with AUB often have characteristics associated with increased rates of endometrial carcinoma.

SPECIAL POPULATIONS

Patients trying to conceive — When counseling a patient regarding treatment of AUB, it is important to ask whether the patient is planning on trying to conceive a pregnancy in the near future. Treatment of AUB is particularly challenging for such patients, but options include estrogen-progestin contraceptives or oral cyclic progestin therapy (eg, norethindrone acetate [NETA] or medroxyprogesterone acetate [MPA] administered on days 5 to 26 of the menstrual cycle); tranexamic acid (TXA) and nonsteroidal antiinflammatory drugs (NSAIDs) are also options for patients with heavy menstrual bleeding (HMB) (see 'Estrogen-progestin contraceptives' above and 'Oral progestins' above and 'Tranexamic acid' above and 'Nonsteroidal antiinflammatory drugs' above). It is important to note that estrogen-progestin contraceptives may delay time to conception by several months after discontinuation; the effect of TXA and NSAIDs on ovulation are less clear [94-97]. These medications should be stopped upon conception.

By contrast, medroxyprogesterone acetate (DMPA) does not represent an appropriate option for treating patients with AUB who may wish to conceive in the next one to two years as its contraceptive effect persists for long periods of time. Similarly, placement of a LNG 52 mg may not be desirable or cost-effective for patients who are planning to conceive a pregnancy within the upcoming year.

For patients with infertility, AUB should be treated before proceeding with infertility treatments; treatments to induce ovulation will also often correct symptoms of AUB in patients in whom infertility is the result of anovulation. (See "Overview of ovulation induction".)

Patients on anticoagulant therapy — Approximately two-thirds of patients using oral anticoagulant treatment experience AUB [98]. In such patients, anticoagulant therapy is often not the primary etiology of AUB, but rather exacerbates the underlying issue. The presence of AUB is dose dependent. In our experience, AUB occurs more frequently during warfarin treatment if the International Normalized Ratio (INR) is >3; adjusting the warfarin dose to achieve an INR range of 2 to 3 (if clinically appropriate) often resolves the AUB. AUB also appears to occur more frequently with rivaroxaban than with enoxaparin or vitamin K antagonists [99,100].

Patients who are on anticoagulant medications who have heavy, prolonged, or irregular uterine bleeding should be evaluated for the etiology and treated as appropriate. Structural lesions (eg, endometrial polyps, uterine fibroids) may be removed with appropriate perioperative consultation with the clinician prescribing anticoagulation therapy. (See 'Structural lesions' above and "Perioperative management of patients receiving anticoagulants".)

For patients on anticoagulant therapy without structural lesions, we typically prefer progestin-only therapies, specifically the LNG 52 mg, for treatment of AUB as well as for contraception [98]. However, in anticoagulated patients, neither estrogen-progestin combination contraceptives nor progestin-only methods appears to increase risk of recurrent venous thrombosis [99]. Thus, if an estrogen-progestin contraceptive is used, it is important to discontinue the contraceptive prior to stopping anticoagulation as the procoagulant effects of combination contraceptives may persist for up to six weeks after stopping them [101]. There is limited published evidence addressing medical management of AUB in patients with a history of VTE using low molecular weight heparin or direct oral anticoagulants and further study is needed.

Patients with iron deficiency — Iron deficiency is common in individuals with HMB; testing for iron deficiency and/or iron deficiency anemia is discussed separately. (See "Diagnosis of iron deficiency and iron deficiency anemia in adults".)

In addition to treating AUB, patients with iron deficiency (with or without anemia) should have their iron deficiency corrected and undergo appropriate monitoring. This is described in detail elsewhere. (See "Treatment of iron deficiency anemia in adults".)

However, it is important not to attribute all iron deficiency to menstrual bleeding; individuals with new onset iron deficiency or iron deficiency in an adult >50 years (sometimes younger) should prompt evaluation for other causes, which may include upper gastrointestinal disorders (eg, celiac disease, autoimmune gastritis) or colorectal disorders, including cancer. (See "Determining the cause of iron deficiency in adolescents and adults", section on 'Evaluation for the cause'.)

Patients with dysmenorrhea or pelvic pain/pressure — Patients with AUB and dysmenorrhea or pelvic pain/pressure often will be diagnosed with a primary etiology (eg, adenomyosis, uterine fibroid). The optimal approach in these patients is to address both issues with one type of treatment. (See "Uterine adenomyosis", section on 'Management of symptomatic patients' and "Uterine fibroids (leiomyomas): Treatment overview".)

WHEN TO REFER — 

AUB is a common reason for referral to a gynecologist, and 5 percent of female patients between the ages of 30 and 49 years consult a clinician for evaluation of heavy menstrual bleeding (HMB) [102-104]. Referral to a gynecologist is appropriate for patients with heavy bleeding, persistent bleeding despite treatment, if there is suspicion of malignancy, or if surgery is required. Referral is also appropriate if the patient's primary clinician is not comfortable performing endometrial sampling or placing an intrauterine device.

Referral to a bleeding disorders expert is often appropriate for patients who report other types of excess bleeding or those with an increased risk of thrombosis. The likelihood of a bleeding disorder can be assessed using an easy-to-administer (by the clinician or the patient) bleeding assessment tool. Similarly, assessment regarding the risk of thrombosis can help determine if certain medical therapies (eg, estrogen-progestin contraceptives, oral progestins, depot medroxyprogesterone acetate, tranexamic acid) should be avoided. (See "Approach to the adult with a suspected bleeding disorder", section on 'Bleeding history' and "Approach to the adult with a suspected bleeding disorder", section on 'Bleeding score' and 'Patients with increased risk of thrombosis' above.)

Patients with severe anemia, acute heavy bleeding, or hemodynamic instability should be sent to the emergency department. (See "Approach to the adult with vaginal bleeding in the emergency department" and "Managing an episode of acute uterine bleeding".)

PATIENT PERSPECTIVE TOPIC — 

Patient perspectives are provided for selected disorders to help clinicians better understand the patient experience and patient concerns. These narratives may offer insights into patient values and preferences not included in other UpToDate topics. (See "Patient perspective: von Willebrand disease".)

SOCIETY GUIDELINE LINKS — 

Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Abnormal uterine bleeding".)

INFORMATION FOR PATIENTS — 

UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topics (see "Patient education: Heavy periods (The Basics)")

●Beyond the Basics topics (see "Patient education: Abnormal uterine bleeding (Beyond the Basics)" and "Patient education: Heavy periods (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Management goals and treatment considerations (see 'Management goals and treatment considerations' above)

•Goals of abnormal uterine bleeding (AUB) management are to correct the underlying etiology (if present and feasible), improve quality of life, prevent an episode of acute uterine bleeding requiring urgent evaluation, prevent (or treat) anemia, establish a regular bleeding pattern, and prevent (or treat) endometrial hyperplasia/carcinoma.

•To help determine which therapy is best for a particular patient, clinicians should consider several patient factors including etiology; severity of bleeding; associated symptoms (eg, dysmenorrhea/pelvic pain, infertility); contraceptive needs and plans for future pregnancy; medical comorbidities; patient preferences.

•Expectant management may be reasonable for some patients (eg, not anemic, do not desire treatment, approaching menopause).

●Patients with a known structural, infectious, or endocrine etiology – For patients with AUB and a known structural lesion, endocrine abnormality, or infectious etiology, treating the underlying condition (if feasible) before initiating other therapy may correct the AUB or make other treatment more effective (algorithm 1). (See 'Patients with a known structural, infectious, or endocrine etiology' above.)

●Patients without a structural, infectious, or endocrine etiology (algorithm 1)

•Most patients – For most patients with AUB in whom no etiology was found on evaluation, we suggest estrogen-progestin contraceptives or the 52 mg levonorgestrel-releasing intrauterine device (LNG 52 mg IUD) rather than other medical therapies or surgery (Grade 2C). Both estrogen-progestin contraceptives and the LNG 52 mg are effective treatments for AUB, provide effective contraception, are well tolerated, and have a low risk of adverse effects. (See 'Most patients (no contraindications to medical therapy)' above.)

For patients who cannot or choose not to use one of the above methods, reasonable alternatives include treatment with other progestin-only therapies (eg, oral progestins, depot medroxyprogesterone acetate [DMPA]) or noncontraceptive estrogen-progestin formulations; surgery also may be an option for selected patients. (See 'Most patients (no contraindications to medical therapy)' above and 'Role of surgery' above.)

•Patients with increased risk of thrombosis or other contraindications to estrogen – For most patients with AUB who are at an increased risk of thrombosis (eg, history of thrombosis, selected thrombogenic mutations) or with other contraindications to estrogen, we suggest treatment with the LNG 52 mg rather than other medical therapies or surgery (Grade 2C). Medical consultation with a hematologist is often helpful to determine the patient’s individual risk of thrombosis and to determine if other medical therapies (eg, oral progestins, DMPA, noncontraceptive estrogen-progestin formulations) are an option. (See 'Patients with increased risk of thrombosis' above and 'Patients with other contraindications to estrogen' above.)

•Additional options for patients with heavy bleeding – In addition to other medical and surgical therapies, tranexamic acid (TXA) and nonsteroidal antiinflammatory drugs (NSAIDs) are also options for selected patients with heavy menstrual bleeding (HMB). The choice of therapy depends on a number of factors, which are detailed in the table (table 2). Epsilon aminocaproic acid (EACA), desmopressin (DDAVP), and von Willebrand factor concentrate may also be appropriate for patients with certain bleeding disorders; the choice of therapy depends on the specific bleeding disorder and is typically managed by the patient’s hematologist. (See 'Patients with heavy bleeding' above.)

●Patients trying to conceive – For patients with AUB who are trying to conceive or planning a pregnancy in the near future, treatment is challenging but options include estrogen-progestin contraceptives, oral cyclic progestin therapy, TXA, or NSAIDs. Estrogen-progestin contraceptives may delay time to conception by several months after discontinuation. DMPA and the LNG 52 mg are usually not options for such patients because of more prolonged time to conception after discontinuation. The effects of TXA and NSAIDs on ovulation are less clear. (See 'Patients trying to conceive' above.)

●Role of surgery – For patients with AUB and a known structural etiology, surgery (eg, hysteroscopic myomectomy, hysteroscopic polypectomy) may correct the AUB or make further medical treatment of AUB more effective. (See 'Structural lesions' above.)

For patients without a structural etiology, surgical therapies (eg, endometrial ablation, hysterectomy) may also be an option for some patients (eg, completed childbearing and who prefer to avoid medical therapy, in whom medical therapy was ineffective or resulted in bothersome side effects, or desire definitive therapy [hysterectomy]). In our practice, we often start with medical therapy (eg, LNG 52 mg) and, if unsuccessful, follow with endometrial ablation or hysterectomy. The choice between endometrial ablation and hysterectomy is also discussed separately. (See 'Role of surgery' above and "Overview of endometrial ablation", section on 'Ablation versus other treatments'.).

ACKNOWLEDGMENT — 

The UpToDate editorial staff acknowledges Howard Zacur, MD, who contributed to earlier versions of this topic review.

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Topic 5476 Version 74.0

References

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2 : Corrigendum to "The two FIGO systems for normal and abnormal uterine bleeding symptoms and classification of causes of abnormal uterine bleeding in the reproductive years: 2018 revisions" [Int J Gynecol Obstet 143(2018) 393-408.].

3 : Four Surgical Strategies for the Treatment of Cesarean Scar Defect: A Systematic Review and Network Meta-analysis.

4 : Uterine artery embolization: the role in obstetrics and gynecology.

5 : Conservative treatment of uterine arteriovenous fistula.

6 : Embolization of bleeding residual uterine vascular malformations in patients with treated gestational trophoblastic tumors.

7 : Obstetric iatrogenic arterial injuries of the uterus: diagnosis with US and treatment with transcatheter arterial embolization.

8 : Pregnancy following successful embolisation of a uterine vascular malformation.

9 : Selective transcatheter embolization of a uterine arteriovenous malformation with preservation of the reproductive capacity.

10 : Successful treatment of symptomatic arteriovenous malformation of the uterus using laparoscopic bipolar coagulation of uterine vessels.

11 : Hysterectomy for Uterine Arteriovenous Malformation: Laparoscopic View.

12 : Management of abnormal uterine bleeding.

13 : Menorrhagia management options.

14 : Is medical management of menorrhagia obsolete?

15 : Randomised controlled trial of educational package on management of menorrhagia in primary care: the Anglia menorrhagia education study.

16 : Levonorgestrel-releasing intrauterine system and endometrial ablation in heavy menstrual bleeding: a systematic review and meta-analysis.

17 : Nonsurgical management of heavy menstrual bleeding: a systematic review.

18 : Non-steroidal anti-inflammatory drugs for heavy menstrual bleeding.

19 : Progestogen-releasing intrauterine systems for heavy menstrual bleeding.

20 : Interventions for heavy menstrual bleeding; overview of Cochrane reviews and network meta-analysis.

21 : Venous thrombosis in users of non-oral hormonal contraception: follow-up study, Denmark 2001-10.

22 : Use of the levonorgestrel-releasing intrauterine system in women with hemostatic disorders.

23 : Association of Progestogens and Venous Thromboembolism Among Women of Reproductive Age.

24 : Formation of ethinyl estradiol in women during treatment with norethindrone acetate.

25 : Formation of ethinyl estradiol in women during treatment with norethindrone acetate.

26 : U.S. Medical Eligibility Criteria for Contraceptive Use, 2024.

27 : Association of venous thromboembolism with hormonal contraception and thrombophilic genotypes.

28 : Assessing the risk of venous thromboembolic events in women taking progestin-only contraception: a meta-analysis.

29 : Assessing the risk of venous thromboembolic events in women taking progestin-only contraception: a meta-analysis.

30 : Assessing the risk of venous thromboembolic events in women taking progestin-only contraception: a meta-analysis.

31 : Risk of venous thrombosis: obesity and its joint effect with oral contraceptive use and prothrombotic mutations.

32 : The effects of age, body mass index, smoking and general health on the risk of venous thromboembolism in users of combined oral contraceptives.

33 : No increased risk of venous thrombosis in women taking tranexamic acid.

34 : The risk of venous thromboembolism associated with the use of tranexamic acid and other drugs used to treat menorrhagia: a case-control study using the General Practice Research Database.

35 : The risk of venous thromboembolism associated with the use of tranexamic acid and other drugs used to treat menorrhagia: a case-control study using the General Practice Research Database.

36 : The risk of venous thromboembolism associated with the use of tranexamic acid and other drugs used to treat menorrhagia: a case-control study using the General Practice Research Database.

37 : Review of interventions and effectiveness for heavy menstrual bleeding in women with moderate and severe von Willebrand disease.

38 : Heavy menstrual bleeding: is tranexamic acid a safe adjunct to combined hormonal contraception?

39 : Severe anemia from heavy menstrual bleeding requires heightened attention.

40 : Leukotriene release by endometrium and myometrium throughout the menstrual cycle in dysmenorrhoea and menorrhagia.

41 : Prostaglandin synthesis in the endometrium of women with ovular dysfunctional uterine bleeding.

42 : Gynaecological and obstetric management of women with inherited bleeding disorders.

43 : Gynecologic and obstetric management of women with von Willebrand disease: summary of 3 systematic reviews of the literature.

44 : Bioequivalence assessment of three different estradiol formulations in postmenopausal women in an open, randomized, single-dose, 3-way cross-over study.

45 : Effective treatment of heavy menstrual bleeding with estradiol valerate and dienogest: a randomized controlled trial.

46 : Efficacy and safety of a new 24-day oral contraceptive regimen of norethindrone acetate 1 mg/ethinyl estradiol 20 micro g (Loestrin 24 Fe).

47 : Contraceptive vaginal ring treatment of heavy menstrual bleeding: a randomized controlled trial with norethisterone.

48 : A multicenter, randomized study of an extended cycle oral contraceptive.

49 : Efficacy and safety of an ascending-dose, extended-regimen levonorgestrel/ethinyl estradiol combined oral contraceptive.

50 : Reduced vaginal bleeding in postmenopausal women who receive combined norethindrone acetate and low-dose ethinyl estradiol therapy versus combined conjugated equine estrogens and medroxyprogesterone acetate therapy.

51 : Effects of Etonogestrel implants on pelvic pain and menstrual flow in women suffering from adenomyosis or endometriosis: Results from a prospective, observational study.

52 : A clinical observational study on the efficacy of subcutaneous etonogestrel implants for adenomyosis in 20 patients.

53 : Efficacy of etonogestrel subcutaneous implants versus the levonorgestrel-releasing intrauterine system in the conservative treatment of adenomyosis.

54 : Two low-dose levonorgestrel intrauterine contraceptive systems: a randomized controlled trial.

55 : Two low-dose levonorgestrel intrauterine contraceptive systems: a randomized controlled trial.

56 : Two low-dose levonorgestrel intrauterine contraceptive systems: a randomized controlled trial.

57 : The effectiveness of the levonorgestrel intrauterine system in obese women with heavy menstrual bleeding.

58 : Levonorgestrel intrauterine system versus medical therapy for menorrhagia.

59 : Heavy Menstrual Bleeding Treatment With a Levonorgestrel 52-mg Intrauterine Device.

60 : LNG-IUS vs. medical treatments for women with heavy menstrual bleeding: A systematic review and meta-analysis.

61 : Therapeutic use of levonorgestrel-releasing intrauterine system in women with menorrhagia: a pilot study(1).

62 : Levonorgestrel-releasing intrauterine system or medroxyprogesterone for heavy menstrual bleeding: a randomized controlled trial.

63 : Levonorgestrel-releasing intrauterine system for heavy menstrual bleeding improves hemoglobin and ferritin levels.

64 : Decline in Danish use of oral tranexamic acid with increasing use of the levonorgestrel-releasing intrauterine system: a nationwide drug utilization study.

65 : Association of age and parity with intrauterine device expulsion.

66 : Intrauterine device use among women with uterine fibroids: A systematic review.

67 : Insertion of the Mirena intrauterine system for treatment of adenomyosis-associated menorrhagia: a novel method.

68 : The levonorgestrel-releasing intrauterine system in heavy menstrual bleeding: a benefit-risk review.

69 : A randomized, double-blind, placebo-controlled, multicenter study that assessed the endometrial effects of norethindrone acetate plus ethinyl estradiol versus ethinyl estradiol alone.

70 : Assessment of the potency of orally administered progestins in women.

71 : Continuous oral or intramuscular medroxyprogesterone acetate versus the levonorgestrel releasing intrauterine system in the treatment of perimenopausal menorrhagia: a randomized, prospective, controlled clinical trial in female smokers.

72 : Cyclical progestogens for heavy menstrual bleeding.

73 : Randomised comparative trial of the levonorgestrel intrauterine system and norethisterone for treatment of idiopathic menorrhagia.

74 : Tranexamic acid treatment for heavy menstrual bleeding: a randomized controlled trial.

75 : Primary and myoma-associated menorrhagia: role of prostaglandins and effects of ibuprofen.

76 : Randomized trial of 2 hormonal and 2 prostaglandin-inhibiting agents in women with a complaint of menorrhagia.

77 : Naproxen reduces idiopathic but not fibromyoma-induced menorrhagia.

78 : Naproxen in menorrhagia.

79 : Randomised comparative trial of the levonorgestrel intrauterine system and mefenamic acid for the treatment of idiopathic menorrhagia: a multiple analysis using total menstrual fluid loss, menstrual blood loss and pictorial blood loss assessment charts.

80 : Effects of mefenamic acid on menstrual hemostasis in essential menorrhagia.

81 : Effects of mefenamic acid on menstrual hemostasis in essential menorrhagia.

82 : The levonorgestrel intrauterine system versus endometrial ablation for heavy menstrual bleeding: a cost-effectiveness analysis.

83 : Cost-effectiveness of hysterectomy, first- and second-generation endometrial ablation, and levonorgestrel-releasing device for treatment of heavy menstrual bleeding: a systematic review.

84 : Endometrial resection and ablation techniques for heavy menstrual bleeding.

85 : Levonorgestrel-releasing intrauterine system versus endometrial ablation for heavy menstrual bleeding.

86 : A 52-mg levonorgestrel-releasing intrauterine system vs bipolar radiofrequency nonresectoscopic endometrial ablation in women with heavy menstrual bleeding: long-term follow-up of a multicenter randomized controlled trial.

87 : Surgery versus medical therapy for heavy menstrual bleeding.

88 : Quality of life and costs of levonorgestrel-releasing intrauterine system or hysterectomy in the treatment of menorrhagia: a 10-year randomized controlled trial.

89 : The effect of hysterectomy or levonorgestrel-releasing intrauterine system on lower urinary tract symptoms: a 10-year follow-up study of a randomised trial.

90 : NHS proposes to stop funding 17 "unnecessary" procedures.

91 : Effect of hysterectomy vs medical treatment on health-related quality of life and sexual functioning: the medicine or surgery (Ms) randomized trial.

92 : Hysterectomy versus expanded medical treatment for abnormal uterine bleeding: clinical outcomes in the medicine or surgery trial.

93 : Randomized trial of medical treatment versus hysterectomy for abnormal uterine bleeding: resource use in the Medicine or Surgery (Ms) trial.

94 : The effects of proteolytic enzymes on in vitro ovulation in the rabbit.

95 : The role of protein kinase-C in gonadotropin-induced ovulation in the in vitro perfused rabbit ovary.

96 : Fertility and infertility in rheumatoid arthritis.

97 : Novel contraceptive targets to inhibit ovulation: the prostaglandin E2 pathway.

98 : Menstrual problems and contraception in women of reproductive age receiving oral anticoagulation.

99 : Recurrent venous thromboembolism and abnormal uterine bleeding with anticoagulant and hormone therapy use.

100 : Heavy menstrual bleeding in women on oral anticoagulants.

101 : Less menorrhagia for women with VTE.

102 : Referral for menstrual problems: cross sectional survey of symptoms, reasons for referral, and management.

103 : The epidemiology of hysterectomy: findings in a large cohort study.

104 : von Willebrand disease and other inherited bleeding disorders in women with diagnosed menorrhagia.