INTRODUCTION — Chronic abnormal uterine bleeding (AUB), a term that refers to menstrual bleeding of abnormal quantity, duration, or schedule, is a common gynecologic problem, occurring in approximately 10 to 35 percent of women [1-3]. Chronic heavy or prolonged uterine bleeding can result in anemia, interfere with daily activities, and raise concerns about uterine cancer. AUB is a common reason for referral to a gynecologist, and 5 percent of women between the ages of 30 and 49 years consult a clinician for evaluation of menorrhagia [4-6]. Iron deficiency anemia develops in 21 to 67 percent of cases [7,8].

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

The management of chronic AUB in nonpregnant premenopausal patients will be reviewed here. The general evaluation of AUB, acute uterine bleeding, bleeding during pregnancy, and postmenopausal bleeding are discussed separately. (See "Abnormal uterine bleeding in nonpregnant reproductive-age patients: Evaluation and approach to diagnosis" and "Managing an episode of acute uterine bleeding" and "Overview of the etiology and evaluation of vaginal bleeding in pregnancy" and "Approach to the patient with postmenopausal uterine bleeding".)

TERMINOLOGY — A revised terminology system for AUB in nongravid reproductive-age patients was introduced in 2011 by the International Federation of Gynecology and Obstetrics (FIGO) [9]. This was the result of an international consensus process with the goal of avoiding poorly defined or confusing terms used previously (eg, menorrhagia, menometrorrhagia, oligomenorrhea). The classification system is referred to by the acronym PALM-COEIN (polyp, adenomyosis, leiomyoma, malignancy and hyperplasia, coagulopathy, ovulatory dysfunction, endometrial, iatrogenic, and not yet classified) (figure 1). (See "Abnormal uterine bleeding in reproductive-age patients: FIGO System 1 terminology and symptoms and System 2 PALM-COEIN etiology classification".)

In the PALM-COEIN system, the term heavy menstrual bleeding (HMB) refers to cyclic (ovulatory) menses that are heavy or prolonged [9]. It does not refer to heavy or prolonged bleeding that occurs in patients with ovulatory dysfunction (AUB-O). The term HMB replaces the term menorrhagia, which was previously used to describe heavy or prolonged uterine bleeding. Menorrhagia is a less precise word because it does not differentiate between volume and duration of bleeding or between cyclic and anovulatory bleeding. The PALM-COEIN classification also does not include the term "dysfunctional uterine bleeding."

CLINICAL APPROACH — AUB encompasses a heterogeneous group of conditions with diverse etiologies. Initial management usually consists of progestin-based treatments including combination oral contraceptives (OCs), the 52 mg levonorgestrel (LNG)-releasing intrauterine device with an initial release rate of 20 mcg/day for five years (LNG 52; Mirena or Liletta), and high-dose progestin-only oral medications. Surgical treatment plays an important role in some patients with AUB, particularly those who have structural lesions (eg, leiomyomas, endometrial or cervical polyps) and/or have completed childbearing. Prior to initiating management, patients with AUB should undergo evaluation for endometrial hyperplasia or carcinoma, if appropriate (table 1). (See "Abnormal uterine bleeding in nonpregnant reproductive-age patients: Evaluation and approach to diagnosis", section on 'Endometrial sampling: Choice of modality'.)

Indications for treatment — Types of chronic AUB and indications for treatment include:

●Heavy menstrual bleeding (HMB) – HMB is ovulatory (cyclic), heavy bleeding. HMB should be treated when it interferes with quality of life or causes anemia. The impact on quality of life in patients with HMB includes the need to change pads or tampons frequently, heavy bleeding that stains clothing or bedding, and avoidance of activities due to bleeding [10]. (See "Abnormal uterine bleeding in nonpregnant reproductive-age patients: Evaluation and approach to diagnosis", section on 'Heavy menstrual bleeding'.)

●Intermenstrual bleeding – Intermenstrual bleeding occurs in between otherwise regular menses. The primary etiology can often be identified and treated (eg, endometrial polyp, chronic endometritis). An evaluation should be performed to identify the etiology and exclude malignancy. If no etiology is found, the goal of treatment is to resolve this bothersome symptom. The volume of blood loss is typically small, and anemia is not generally a concern. (See "Abnormal uterine bleeding in nonpregnant reproductive-age patients: Evaluation and approach to diagnosis", section on 'Intermenstrual bleeding'.)

●Ovulatory dysfunction (AUB-O) – AUB-O is irregular, nonovulatory (noncyclic) bleeding. Although bleeding may be infrequent (oligomenorrhea) in some patients with AUB-O, prolonged or heavy bleeding, even hemorrhage, may occur. The etiology of AUB-O should be identified, since treatment of some etiologies (eg, thyroid disease, hyperprolactinemia) may restore cyclic menses. In many cases, polycystic ovarian syndrome is the etiology. The goals of treatment of AUB-O are to establish a regular bleeding pattern (or amenorrhea), prevent heavy bleeding, and prevent development of endometrial hyperplasia/cancer. In addition, patients with AUB-O often require fertility treatment if they wish to conceive. (See "Treatment of polycystic ovary syndrome in adults" and "Abnormal uterine bleeding in nonpregnant reproductive-age patients: Evaluation and approach to diagnosis", section on 'Irregular bleeding'.)

●Other bleeding patterns – Treatment of oligomenorrhea or amenorrhea are discussed separately. (See "Evaluation and management of primary amenorrhea" and "Evaluation and management of secondary amenorrhea".)

The definition, evaluation, and differential diagnosis of different types of AUB are discussed in detail separately. (See "Abnormal uterine bleeding in nonpregnant reproductive-age patients: Evaluation and approach to diagnosis", section on 'Gynecologic and obstetric history'.)

Choosing a treatment — Management of reproductive-age patients with AUB with a benign etiology is based upon the following factors:

●Etiology

●Severity of bleeding (eg, anemia, interference with daily activities)

●Associated symptoms and issues (eg, pelvic pain, infertility)

●Contraceptive needs and plans for future pregnancy

●Medical comorbidities

●Underlying risk for venous thromboembolic disease and/or arterial thrombotic events

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

Treatment should not be initiated until the etiology of AUB has been evaluated (or evaluation is underway) and premalignant or malignant disease excluded, as appropriate. Empiric treatment without evaluation may miss a primary etiology that may be corrected or mask symptoms of neoplastic disease. Invasive procedures may also be limited by insurance coverage or medical guidelines; for example, the National Health Service (NHS) in the United Kingdom advises against routine performance of dilation and curettage and hysterectomy for HMB [11]. (See "Abnormal uterine bleeding in nonpregnant reproductive-age patients: Evaluation and approach to diagnosis".)

AUB symptoms may persist until menopause. The goal of initial therapy is to control the bleeding, treat anemia (if present), and restore quality of life. Once this has been accomplished, some patients are satisfied with continuing chronic medical therapy, while others desire a treatment that requires less maintenance or is definitive. The approach to treatment is generally stepwise:

●The primary etiology should be treated, if possible. This includes endocrine or infectious disorders that are treated medically (eg, polycystic ovarian syndrome or chronic endometritis) as well as structural lesions that are resectable via hysteroscopy (endometrial polyp, submucosal fibroid).

●The initial approach in patients with chronic AUB is usually pharmacologic treatment. The choice of medication depends upon the factors listed above. For some patients who do not wish to conceive in the next year, the LNG 52 is used as first-line therapy.

●Secondary approaches are used for patients who fail or cannot tolerate medical therapy or who prefer treatment options that do not require frequent dosing. Primary deciding factors are whether the patient is planning future childbearing and the level of invasiveness and risk associated with the procedure.

Patients often choose surgical therapy after long-term medical therapy. A systematic review of eight randomized trials of patients with HMB found that 58 percent of those randomly assigned to medical treatment underwent surgery by two years [12].

As an example, one randomized trial assigned 63 patients with persistent AUB (median duration four years) who were dissatisfied with cyclic oral medroxyprogesterone treatment to undergo hysterectomy (route per provider) or expanded medical therapy, primarily with cyclic OCs and a nonsteroidal anti-inflammatory drug (NSAID; alternative estrogen-progestin regimens were also employed) [13,14]. By 18 months, 53 percent of those in the medical treatment group had asked for and received a hysterectomy (median interval to crossing over was six months). At two years, mean resource use in the medical management and hysterectomy arms were USD $4479 and $6777, respectively [15]. Broken down to resource use by treatment actually received, the costs for medication only, medicine followed by hysterectomy, and hysterectomy only were USD $2595, $6128, and $7024, respectively.

The choice of surgery may be based upon avoidance of medication-related side effects. In the systematic review, at four-month follow-up, endometrial resection was significantly more effective than oral medication in controlling bleeding (odds ratio [OR] 10.6, 95% CI 5.3-21.3) and significantly less likely to cause side effects (OR 0.2, 95% CI 0.1-0.3) [12]. Hysterectomy resulted in significantly greater improvements in mental health at six-month follow-up.

In general, HMB may be treated with either surgical or medical treatment. In contrast, AUB-O is a medical disease and should be treated medically in the majority of cases. However, some patients with chronic AUB-O prefer definitive therapy and choose hysterectomy.

Some patients with AUB will choose the LNG 52. This provides reversible contraception but can be left in place for five or six years, depending on the brand, and over time results in decreasing volume of bleeding until the patient has scant bleeding or amenorrhea. Other patients with AUB may choose minimally invasive surgery or definitive treatment with hysterectomy.

Patients with leiomyomas can also be treated with fibroid-specific minimally invasive procedures (eg, hysteroscopic myomectomy, uterine artery embolization) or major surgery (abdominal myomectomy). These procedures are listed below, but treatment of leiomyomas is discussed in detail separately. (See "Uterine fibroids (leiomyomas): Treatment overview".)

TREATMENT OF THE PRIMARY ETIOLOGY — Treatment of certain underlying conditions before initiating other therapy may correct the bleeding or make further treatment more effective. These include structural lesions or etiologies that can be treated pharmacologically.

●Structural lesions

•Submucosal fibroids and endometrial polyps can be resected via operative hysteroscopy. (See "Endometrial polyps" and "Overview of hysteroscopy", section on 'Indications'.)

•Arteriovenous malformations can be treated with interventional radiology procedures. (See "Differential diagnosis of genital tract bleeding in women", section on 'Arteriovenous malformation'.)

•Cesarean scar defects (ie, isthmocele, niche) can be surgically resected via operative hysteroscopy, vaginal surgery, laparotomy/laparoscopy, or a combined approach. One meta-analysis suggested that a combined approach with laparoscopy and hysteroscopy, which allows visualization of the defect from two perspectives, provided a greater reduction in the duration of AUB when compared with vaginal surgery or hysteroscopy alone [16].

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

●Endocrine abnormalities – Anovulatory bleeding is caused by endocrine abnormalities, and some etiologies (eg, hypothyroidism, hyperprolactinemia) can be treated to restore regular ovulatory cycles, whereas others (eg, polycystic ovarian syndrome) are best treated to regulate or eliminate bleeding episodes and prevent endometrial cancer [17-20]. (See "Treatment of primary hypothyroidism in adults" and "Treatment of polycystic ovary syndrome in adults".)

●Bleeding disorders – When possible, bleeding diatheses should be controlled prior to initiating other therapy. Most bleeding diatheses can be treated medically to reduce menstrual blood loss; options include administration of a hemostatic agent or one of the nonspecific therapies described below [21].

INITIAL APPROACH: MEDICAL THERAPY — Medical therapy is appropriate initial treatment for most patients. If treatment must be continued long-term, some patients will prefer a management option that does not require frequent dosing (eg, levonorgestrel-releasing [20 mcg/day] intrauterine device [LNG 52 IUD; Mirena or Liletta] or surgery).

Heavy menstrual bleeding — The most common etiologies of heavy menstrual bleeding (HMB) are uterine leiomyomas or adenomyosis. Although these conditions may be treated with surgery, medical management represents appropriate initial treatment and indeed, many patients prefer initial medical management. In particular, for patients with HMB associated with adenomyosis, endometrial ablation may be less effective than in other conditions.

For most patients with HMB, we suggest estrogen-progestin contraceptives or the LNG 52 as first-line therapy rather than other medications. Both estrogen-progestin contraceptives and the LNG 52 are effective treatments for HMB (see 'Estrogen-progestin contraceptives' below and 'Levonorgestrel intrauterine device' below). Both provide effective contraception. Both are well tolerated and have a low risk of adverse effects. The choice between the two depends on several factors. Estrogen-progestin contraceptives are not an option in patients with a contraindication to contraceptive doses of estrogen (eg, hypertension or an increased risk of thrombosis) (see 'Elevated venous or arterial thrombosis risk' below and "Combined estrogen-progestin oral contraceptives: Patient selection, counseling, and use", section on 'Candidates'). For other patients, the choice depends on patient preference. Patients may prefer estrogen-progestin contraceptives if they prefer taking a daily oral medication, while others prefer the low maintenance of having an IUD. In addition, some patients prefer the regular bleeding associated with estrogen-progestin contraceptives, while others are willing to tolerate the initial irregular bleeding that accompanies the LNG 52 and prefer the eventual light bleeding or amenorrhea. For patients who are planning to conceive in the near future, estrogen-progestin contraceptives provide a short-term option. (See "Combined estrogen-progestin oral contraceptives: Patient selection, counseling, and use".)

High-dose oral or injectable progestin-only medications are also reasonable treatment options. Neither progestin-only contraceptive pills nor the etonogestrel implant are known to be effective in treating HMB. As noted above, continuous progestin-only medications result in irregular menses that some patient find bothersome, and then eventually, in light bleeding or amenorrhea.

While some hormonal treatments are also approved for use as contraceptives, others are not. Nonsteroidal anti-inflammatory drugs (NSAIDs) and tranexamic acid do not provide contraception. Tranexamic acid or NSAIDs are useful for patients with HMB who have contraindications to or would prefer to avoid hormonal agents.

For selected patients with contraindications to contraceptive dose estrogens, ultra-low-dose postmenopausal hormone therapy formulations may be an option. (See 'Noncontraceptive estrogen-progestin formulations' below.)

Expectant management is reasonable for patients who are not anemic and do not desire treatment. For patients with HMB who choose expectant management, depending on the volume of bleeding, we check a hematocrit (often checking a ferritin level as well) every 6 to 12 months.

Ovulatory dysfunction — In contrast with hormonal management of HMB, which has been addressed in a number of randomized trials [22], few studies have addressed the efficacy of hormonal management in treating ovulatory dysfunction (AUB-O), and no randomized trials have compared progestogen-only therapy with estrogen-progestin formulations or with placebo in the management of irregular bleeding associated with oligo/anovulation [23]. In some cases, such as submucosal (intracavitary) uterine fibroids, ovulatory patients may experience prolonged, irregular bleeding. Although the etiologies of prolonged AUB-O and HMB differ, many treatment strategies effective in treating HMB are also effective choices for patients with AUB-O.

For patients with AUB-O, estrogen-progestin contraceptives, oral progestin therapy, or the LNG 52 are first-line treatment options, as these approaches reduce bleeding and decrease the risk of endometrial hyperplasia or cancer.

Estrogen-progestin contraceptives have the advantages of providing contraception and regulating bleeding. Cyclic oral progestin therapy (eg, oral medroxyprogesterone acetate, 10 mg tablets, daily for 10 to 14 days each month) may be effective in some patients with AUB-O, resulting in moderate, predictable withdrawal bleeding. Although use of the LNG 52 does not cause regular withdrawal bleeding, use in patients with AUB is often appropriate, as most patients will eventually become amenorrheic or have only scant bleeding. In contrast to oral medroxyprogesterone acetate, use of the LNG 52 also provides effective contraception.

In patients with AUB-O who do not desire future pregnancy and are considering surgical management, endometrial ablation represents a problematic choice for several reasons. Patients with anovulation are at elevated risk for endometrial neoplasia, but intrauterine scarring caused by ablation may prevent the cardinal symptom of endometrial neoplasia: bleeding. In addition, conventional approaches to evaluating AUB and diagnosing endometrial neoplasia, including biopsy and sonohysterogram, may not be feasible following ablation [24]. (See "Overview of endometrial ablation".)

Treatment options — The comparative efficacy of different therapies for HMB has been evaluated. The LNG 52 represents the most effective medical approach (comparable to the efficacy of endometrial ablation), resulting in 71 to 95 percent reduction in menstrual blood loss. Cyclical oral progestin treatment has been found to reduce bleeding by 87 percent, while estrogen-progestin contraceptive use results in 35 to 69 percent reduction. In systematic reviews that included observational studies and randomized trials of patients with HMB, use of tranexamic acid and NSAIDs reduce menstrual blood loss by 26 to 54 percent and 10 to 52 percent, respectively [22,25].

Hormonal treatment

Estrogen-progestin contraceptives — Estrogen-progestin oral contraceptives (OCs) are first-line management for many patients with AUB. The advantages of estrogen-progestin contraceptives are that they typically make bleeding more regular, lighter, and reduce dysmenorrhea, as well as provide contraception, if needed. In a clinical trial of patients with irregular bleeding, an OC regulated bleeding patterns in significantly more patients than placebo (47 versus 9 percent) [25].

OCs have been extensively studied in patients with HMB, with randomized trials finding reductions in menstrual blood loss ranging from 35 to 69 percent [22]. Other routes of administration include the transdermal contraceptive patch (eg, Xulane, Twirla) and vaginal contraceptive ring (NuvaRing). Although these have not been studied extensively for HMB, it is likely that the efficacy of these in treating AUB is similar, and the choice of delivery system depends on patient preference [26]. (See "Combined estrogen-progestin oral contraceptives: Patient selection, counseling, and use".)

In addition to different routes of administration of OCs, there are many different formulations of OCs that vary by the type, dose, and schedule of estrogen and progestin. It appears that most formulations are effective for treating HMB and for regulating bleeding and providing endometrial protection in AUB-O.

OCs with shorter hormone-free intervals are associated with less withdrawal bleeding than formulations with seven hormone-free days per 28-day pill pack [27]. Although further study is needed to determine which OC formulations are more effective in treating HMB, our preference is to use formulations with four or fewer hormone-free days per pill pack.

The only OC approved by the US Food and Drug Administration (FDA) for treatment of HMB has a short hormone-free interval. However, there is no evidence that this pill is more effective than other OC formulations for treating HMB, and other short hormone-free interval pills are available. The FDA-approved OC (Natazia) includes estradiol valerate (dose varies from 2 to 3 mg); this dose is equivalent to 1.5 to 2.25 mg of micronized oral estradiol, which is equivalent to <20 mcg of ethinyl estradiol [28]. The progestin component is dienogest (dose varies from 2 to 3 mg). The estradiol valerate/dienogest OC formulation has 26 hormonally active tablets per each 28-day pill pack. The estradiol valerate/dienogest OC was evaluated in a randomized trial of patients with AUB (more than three-quarters of the study population had documented HMB; the remainder had prolonged or frequent bleeding) that found significantly reduced menstrual blood loss compared with placebo (reduced by 64 versus 8 percent) [29]. Because this OC has not been directly compared with other OC formulations, it is uncertain if this formulation's efficacy is greater than that of other OCs in reducing menstrual blood loss in patients with HMB (average reduction with OCs is 35 to 69 percent) [22].

OCs may be prescribed in a cyclic (with a monthly withdrawal bleed), extended (for instance, with a withdrawal bleeding every three months), or continuous (no withdrawal bleed) regimen. Although extended or continuous OC use may more effectively suppress menstrual blood loss in many patients, unscheduled (breakthrough) bleeding is more common with this approach than with traditional 28-day OC formulations, limiting this strategy's appeal for some patients [30]. In clinical trials performed in patients with normal menses, extended-cycle OC 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 [31]. (See "Combined estrogen-progestin oral contraceptives: Patient selection, counseling, and use", section on 'Hormone components' and "Hormonal contraception for suppression of menstruation".)

OCs are contraindicated in patients who are at elevated risk for thrombosis. (See 'Elevated venous or arterial thrombosis risk' below.)

Noncontraceptive estrogen-progestin formulations — Off-label use of ultra-low estrogen dose formulations marketed for the treatment of menopausal symptoms may be useful in selected patients with AUB who have relative contraindications to contraceptive doses of estrogen (eg, older patients who are obese, hypertensive, diabetic, or smokers). Such use requires careful assessment, patient counseling, and possible medical consultation regarding thrombotic risk. (See 'Elevated venous or arterial thrombosis risk' below.)

Postmenopausal hormone therapy preparations have doses lower than the typical OC dose (20 to 35 mcg ethinyl estradiol). These are not proven as effective contraceptives, and contraception is required if needed (eg, barrier contraceptives). As an example, a formulation combining ethinyl estradiol 5 mcg with 1 mg of norethindrone acetate (Jinteli 1/5) is approved for treatment of vasomotor symptoms in menopausal patients [32]. Each pack contains 28 days of hormonally active tablets (continuous therapy). In our experience, use of this formulation in patients with AUB often results in amenorrhea after several months.

Examples of patients in whom these types of formulations may be useful include those in their late 30s or 40s with:

●AUB-O as well as obesity and/or hypertension

●HMB and uterine leiomyomas as well as obesity and/or hypertension

●AUB-O or HMB who smoke cigarettes

Note that both of these patient profiles represent examples of AUB that could be safely and effectively managed with the LNG 52 or high-dose oral progestin therapy (eg, norethindrone acetate 5 mg tablets, one to three daily). In our practice, we offer treatment with the ethinyl estradiol 5 mcg/norethindrone acetate 1 mg pill for patients who have relative contraindications to contraceptive dose estrogen and who prefer not to use or do not have financial access to the LNG 52. Likewise, in our experience, progestin-related side effects are less common and severe with the ethinyl estradiol 5 mcg/norethindrone acetate 1 mg formulation than with the higher-dose oral progestin regimens. (See 'High-dose oral progestins' below.)

Levonorgestrel intrauterine device — The LNG 52 is a highly effective and easy-to-use treatment option for AUB and is approved by the FDA for treatment of HMB. Further study is needed to determine if other progestin IUDs (eg, 19.5 mg and 13.5 mg LNG devices) can also be used for treatment of HMB [33]. (See "Intrauterine contraception: Background and device types" and "Intrauterine contraception: Candidates and device selection".)

For treatment of heavy menstrual bleeding — The LNG 52 is a first-line option for treatment of HMB in patients who do not desire pregnancy [34]; factors specific to HMB include:

●Reduction of bleeding – Most patients using the LNG 52 develop scant bleeding or amenorrhea, and studies suggest this treatment, compared with other hormonal or nonhormonal treatments, is associated with an improved quality of life [35,36]. In studies of patients with HMB, three months after IUD placement, the most common bleeding pattern is spotting. At six months, menstrual suppression is substantially greater, with the majority of patients experiencing amenorrhea or infrequent bleeding, and median hemoglobin and ferritin levels increase 7.5 and 68.8 percent from baseline, respectively [37-39].

In a meta-analysis of randomized trials, the LNG 52 reduced menstrual blood loss more than other medical treatments and was comparable to endometrial ablation; however, the certainty of this evidence was low [40]. Furthermore, users of the LNG 52 require fewer subsequent additional interventions. In one large observational study, increasing use of the LNG 52 (a 14-fold increase over 22 years) was accompanied by a decrease in use of oral tranexamic acid, oral progestogen, and hysterectomy [41]. These observations underscore the efficacy of the LNG 52 in preventing and/or treating AUB.

●Risk of expulsion – Expulsion rates are higher in patients using the LNG 52 for treatment of HMB compared with those using the device specifically for contraception (up to 20 versus 10 percent, respectively) [42,43]. For patients with adenomyosis, one study reported a 25 percent expulsion rate with the LNG 52 [44]. Package labeling for the LNG 52 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 may be appropriate in well-counseled patients. When placing the LNG 52 in patients with a distorted endometrial cavity, a relative contraindication for IUD use, some clinicians use abdominal ultrasound guidance to ensure optimal placement.

●Frequency of replacing the device – When the LNG 52 is used to treat HMB, menstrual suppression may attenuate prior to five years of use, and patients may benefit from more frequent removal and replacement of the device [34]. The need for more frequent replacement may reflect declining intrauterine progestin concentrations during use of this device. (See "Intrauterine contraception: Background and device types".)

Although the LNG 52 is highly effective in treating HMB, insurance and/or financial issues may make this device unavailable for the indication of HMB if contraception is not needed.

For treatment of ovulatory dysfunction — In patients with AUB-O, the LNG 52 does not result in regular bleeding; however, it decreases the risk of hemorrhage and provides protection against endometrial hyperplasia and cancer [45-48]. Although the LNG 52 has been studied considerably less in patients with AUB-O, available data as well as expert opinion suggest it is an effective treatment for this indication [45-48]. (See "Treatment of polycystic ovary syndrome in adults" and "Intrauterine contraception: Background and device types", section on 'Levonorgestrel IUD'.)

Depot medroxyprogesterone acetate — Depot medroxyprogesterone acetate (DMPA) is typically used for patients with AUB who have contraindications to or prefer to avoid estrogen and/or if they prefer this method of contraception. DMPA is not an option for patients who are trying to conceive or interested in conceiving in the next one to two years. The contraceptive effect persists for longer than the three-month dosing interval. (See "Depot medroxyprogesterone acetate (DMPA): Formulations, patient selection and drug administration".)

In patients with no complaints of AUB at baseline, approximately one-half of those using DMPA for contraception become amenorrheic after four injections (one year), and some three-quarters of users will become amenorrheic after eight injections (two years).

One short-term study in patients with AUB-O or HMB noted that after two months, those using DMPA experienced a 49 percent reduction in menstrual blood loss [45].

High-dose oral progestins — High-dose oral progestin formulations are generally used to treat AUB in patients who have contraindications to or prefer to avoid estrogen or patients who are trying to conceive a pregnancy.

Examples of oral progestin regimens used to treat AUB include:

●Norethindrone acetate 5 mg tablets one to three tablets daily

●Medroxyprogesterone acetate 5 to 30 mg daily

The contraceptive efficacy of these regimens has not been evaluated, and contraception is required if needed (eg, barrier contraceptives).

High-dose progestin formulations (eg, norethindrone 5 mg) may cause progestin-related side effects, including dysphoria, bloating, and an increased appetite. In some patients in whom AUB has responded well to higher doses of norethindrone acetate (eg, one to three 5 mg tablets daily), we slowly taper the dose down to, if possible, as low as 2.5 mg (one-half of a 5 mg tablet) daily.

In promoting endometrial suppression, norethindrone acetate is substantially more potent than medroxyprogesterone acetate; there are no data regarding use of megestrol, another potent progestin, for HMB [49]. In addition, the majority of the data about use of high-dose oral progestins for HMB have evaluated norethindrone acetate. Accordingly, if cost or side-effect considerations in a specific patient preclude use of norethindrone acetate, we sometimes find it useful to prescribe 20 to 30 mg of medroxyprogesterone acetate daily when treating AUB, particularly in obese patients.

The progestin-only pill (norethindrone 0.35 mg) is a low-dose formulation that has not been studied in the treatment of AUB. Likewise, the 4 mg drospirenone progestin-only pill has not been studied in the treatment of AUB. (See "Progestin-only pills (POPs) for contraception".)

In terms of regimen, there are no high-quality data comparing cyclic and continuous progestin therapy for AUB. When treating patients with HMB, in our experience, we find that continuous rather than cyclical progestin therapy is more effective and easier for patients to comply with. In a mixed population of older reproductive-age patients with AUB-O or HMB, one study found that oral medroxyprogesterone acetate 5 mg tablets administered continuously for two months reduced menstrual blood loss by 33 percent [45].

The data regarding cyclic regimens are mixed and suggest that a longer duration of therapy per cycle is more effective. A systematic review that included six randomized trials that evaluated oral progestins administered cyclically for 7 to 11 days each month did not find this regimen to be effective in ovulatory patients with HMB [50]. By contrast, randomized trials have found that high-dose oral progestational therapy (norethindrone acetate 5 mg tablets, one to three tablets daily) administered for 21 days each month is effective in reducing menstrual blood loss in patients with HMB [26,51].

In patients with AUB-O, some clinicians prescribe cyclic oral progestational therapy (eg, medroxyprogesterone acetate 5 or 10 mg tablets, 10 to 14 days each month). This typically results in moderate, predictable withdrawal bleeding.

Tranexamic acid — Tranexamic acid represents an option for treatment of patients with HMB who do not desire or should not use hormonal treatment. The best patient population for tranexamic acid is not well defined.

Tranexamic acid is an antifibrinolytic agent that competitively blocks the conversion of plasminogen to plasmin, thereby reducing fibrinolysis. Tranexamic acid was approved by the FDA for the treatment of HMB in 2009; it had already been used widely in other countries to treat HMB, including Canada and Europe.

Advantages of this antifibrinolytic medication are that it may be used while trying to conceive and is taken only during menses, rather than daily. However, the role of this medication in patients with an increased risk of thrombosis is controversial, and thus, it is generally not used for this patient population. In addition, the preference for tranexamic acid depends upon the cost, which varies from very expensive in the United States to quite inexpensive and available over-the-counter in Sweden [52]. Generic formulations of tranexamic acid are now available, which may result in this medication becoming less expensive in the United States. In our practice, we sometimes use this medication to treat HMB in patients for whom use of hormonal therapy is contraindicated (eg, patients with a personal history of breast cancer). We reserve tranexamic acid for short-term therapy because there have been cases of thrombosis associated with long-term use [53]. (See 'Elevated venous or arterial thrombosis risk' below and 'Trying to conceive a pregnancy' below.)

FDA labeling for tranexamic acid lists a history of venous thromboembolism or elevated risk of thrombosis (including current use of combination hormonal contraceptives) as a contraindication to use of this antifibrinolytic agent. However, in contrast to the FDA labeling, studies do not confirm that use of tranexamic acid is associated with a significantly elevated risk of thrombosis [54,55]. Tranexamic acid has been used in Sweden for treatment of HMB since the 1960s. A case-control study conducted in that country did not identify an association between use of tranexamic acid and venous thrombosis [54]. A British case-control study also assessed the association between risk of thrombosis and use of tranexamic acid. Use of tranexamic acid was associated with an elevated risk of thrombosis, which did not achieve statistical significance. Of note, however, the presence of anemia associated with HMB itself was also found to be associated with an elevated risk of thrombosis, likely a result of reactive thrombocytosis [56], suggesting that anemia associated with HMB represents a prothrombotic condition regardless of medication use [55]. Some experts think that short-term use of tranexamic acid is appropriate in patients currently using combined hormonal contraceptives, provided additional thrombosis risk factors (eg, obesity, immobility, coagulopathy) are not present [57].

Studies have found that tranexamic acid reduces menstrual blood loss by 26 to 54 percent in patients with HMB and in comparative studies was more effective than NSAIDs and less effective than the LNG 52 [22,58]. In a multicenter randomized trial with 196 patients with HMB, participants were assigned to tranexamic acid or placebo [59]. The tranexamic acid group had a significantly greater decrease in menstrual blood loss (40 versus 8 percent). The most common reported adverse effects were menstrual cramps, headache, back pain, and nausea. The occurrence of these adverse effects was similar in the tranexamic acid and placebo groups.

In patients who have normal renal function, the recommended dose of tranexamic acid for treatment of HMB is 1300 mg (two 650 mg tablets) three times daily (a total of 3900 mg) for as long as five days during menstruation. In patients who have impaired renal function, the dose should be adjusted according to the package insert.

There is no known contraindication to concurrent use of NSAIDs and tranexamic acid.

Nonsteroidal anti-inflammatory drugs — NSAIDs are a nonhormonal, noncontraceptive option for treatment of HMB. NSAIDs used to treat HMB include ibuprofen, naproxen, and mefenamic acid. These drugs are not typically used to treat AUB-O.

NSAIDs 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 [60,61].

Advantages of NSAIDs include:

●Do not increase risk of thrombosis

●Low risk of adverse effects

●Reduction of dysmenorrhea

●Low cost and often available over the counter

●Unlike most hormonal therapies, they do not need to be taken daily

A systematic review of randomized trials of patients with HMB concluded that NSAIDs were more effective than placebo at reducing HMB, but less effective than the LNG 52 and tranexamic acid [62]. This review also noted that the efficacy of naproxen and mefenamic acid in treating HMB were similar. In comparison with OCs, a small randomized trial (n = 26) conducted in patients with HMB found that a low-dose monophasic combined OC appeared more effective than mefenamic acid or naproxen in reducing menstrual blood loss, but these differences did not achieve statistical significance [63].

NSAIDs used for treatment of HMB are prescribed to start on the first day of bleeding and should be continued for four or five days or until menstruation ceases. Reported regimens include:

●Mefenamic acid 500 mg three times per day [64,65].

●Naproxen 500 mg at onset and three to five hours later, then 250 to 500 mg twice a day [63,66,67].

●Ibuprofen 600 mg once per day [68].

Other medical treatments — Although other therapeutic options are available, these are either less effective or have more adverse effects than other treatments.

The side effects associated with danazol make this agent less acceptable than other drugs for long-term use [62]. The short-term use of intravenous estrogen may be helpful in treating patients with acute AUB (see "Managing an episode of acute uterine bleeding"). Gonadotropin-releasing hormone agonists may be useful in preventing AUB in patients who will undergo chemotherapy. (See "Management of menorrhagia during chemotherapy".)

SECONDARY APPROACH: SURGICAL TREATMENTS — Medical therapy may not be effective in all patients, or patients may desire a procedure that has long-term efficacy or is definitive therapy (hysterectomy). In addition, patients may desire surgery to and avoid continued frequent dosing or adverse effects associated with medication.

Heavy menstrual bleeding (HMB) due to structural lesions (leiomyomas, adenomyosis) is typically the main indication for surgery. The etiologies of ovulatory dysfunction (AUB-O) are medical and are generally treated pharmacologically. The exception to this is patients with AUB-O who desire hysterectomy as definitive treatment.

The choice of surgical therapy depends on the patient's characteristics, therapeutic goals, and plans for fertility. For patients who desire future childbearing, surgical options are limited. Myomectomy for patients with fibroids is the only fertility-preserving surgical option. For patients with intracavitary fibroids, a myomectomy may reduce bleeding and also improve fertility.

For patients who do not desire to preserve fertility, a minimally invasive option may be appropriate (eg, endometrial ablation or uterine artery embolization). Hysterectomy is appropriate for patients who have failed other surgical treatments and/or who desire definitive treatment.

Levonorgestrel intrauterine device versus surgical treatments — For patients considering surgery, the risks and benefits should be compared with the levonorgestrel-releasing (20 mcg/day) intrauterine device (LNG 52 IUD; Mirena or Liletta), which has many of the advantages of surgery but with a low risk of complications and no recovery time. In the United States, one cost-effective approach is to start with the LNG 52 and, if unsuccessful, follow with endometrial ablation and, lastly, hysterectomy.

●Compared with endometrial ablation – Both the LNG 52 IUD and endometrial ablation are effective in reducing menstrual blood loss. The decision to use the LNG 52 or endometrial ablation depends on a patient's preferences regarding treatment factors, such as plans for fertility and contraception, convenience, and risks of anesthesia. The LNG 52 is a reversible contraceptive. Pregnancy is contraindicated after endometrial ablation, but the procedure may not prevent pregnancy; thus, patients will need to continue to use contraception following ablation. The LNG 52 is placed in an office setting and requires no or local anesthesia. Endometrial ablation can also be done in an office but is often performed in an operating room under general anesthesia. If successful, endometrial ablation is performed once, while the LNG 52 needs to be replaced at regular intervals (every five [Mirena] to six [Liletta] years).

A systematic review of six randomized trials and a subsequent randomized trial found that patients with menorrhagia who were treated with either the LNG 52 or endometrial ablation had similar reductions in menstrual blood loss at 6, 12, and 24 months, as well as similar improvements in quality of life [25,69].

However, patients treated with the LNG 52 appear to require more reinterventions. In a randomized trial of 270 patients with HMB, patients treated with the LNG 52 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 [70].

●Compared with hysterectomy – While hysterectomy is the definitive treatment option for HMB, treatment with the LNG 52 IUD 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 study of 236 patients with HMB that followed patients for 10 years after they were randomized to placement of an LNG 52 or hysterectomy, 46 percent of those initially randomized to IUD placement ultimately underwent hysterectomy [71]. Overall, costs were lower among patients 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) [72].

Patients who desire fertility

Myomectomy — Myomectomy is an option for patients with uterine leiomyomas. If one or two intracavitary myomas are present, a hysteroscopic myomectomy is minimally invasive and may resolve AUB symptoms. (See "Uterine fibroids (leiomyomas): Hysteroscopic myomectomy".)

Patients with fibroids at other sites that result in AUB may be initially treated with medical therapy. However, laparoscopic or open myomectomy is required if medical management fails and if the patient desires to preserve fertility. Patients considering myomectomy should be counseled that this surgery may commit them to cesarean delivery for subsequent pregnancies. (See "Uterine fibroids (leiomyomas): Laparoscopic myomectomy and other laparoscopic treatments" and "Uterine fibroids (leiomyomas): Open abdominal myomectomy".)

Patients finished with childbearing — Patients who no longer desire fertility have several additional treatment options.

Endometrial ablation — Endometrial ablation is a minimally invasive option for treatment of heavy or prolonged uterine bleeding when medical therapy fails or in patients who do not want to use chronic medical therapy [73]. Pregnancy is contraindicated after endometrial ablation, but contraception is still required. As described above, endometrial ablation and the LNG 52 have equivalent efficacy in reducing menstrual blood flow in patients with HMB. (See 'Levonorgestrel intrauterine device versus surgical treatments' above and "Overview of endometrial ablation".)

Uterine artery embolization — Uterine artery embolization is an option for patients with uterine leiomyomas. The safety of pregnancy after this procedure has not been established; therefore, it is usually reserved for patients who are not contemplating future childbearing. (See "Uterine fibroids (leiomyomas): Treatment with uterine artery embolization".)

Hysterectomy — Hysterectomy represents 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. On the other hand, hysterectomy has a risk of perioperative complications and, depending on the operative approach, a prolonged recovery. (See "Hysterectomy: Selection of surgical route (benign indications)".)

A comparison of endometrial ablation is hysterectomy is presented elsewhere. (See "Overview of endometrial ablation", section on 'Endometrial ablation versus other treatments'.)

SPECIAL CONSIDERATIONS

Management of patients with iron deficiency — Patients with iron deficiency with or without anemia should be monitored and treated as indicated. This is described in detail elsewhere. (See "Treatment of iron deficiency anemia in adults".)

Dysmenorrhea or pelvic pain — Patients with adenomyosis or uterine leiomyomas may present with AUB and dysmenorrhea and pelvic pain/pressure. The optimal approach in these patients is to address both issues with one type of treatment.

Progestin-based treatments have the potential to address both AUB and dysmenorrhea. Use of the levonorgestrel (LNG)-releasing (20 mcg/day) intrauterine device (LNG 52; Mirena or Liletta) has been found to reduce pain and AUB in patients with adenomyosis [34,74]. Nonsteroidal anti-inflammatory drugs (NSAIDs) are another useful option. (See "Uterine adenomyosis".)

Patients with fibroids may experience symptoms due to pressure on surrounding viscera, including abdominal or pelvic discomfort, urinary frequency, or constipation. Only treatments that remove or reduce the size of the leiomyomas can simultaneously treat both the pressure and bleeding symptoms. These treatments include gonadotropin-releasing hormone agonists, uterine fibroid embolization, myomectomy, and hysterectomy. (See "Uterine fibroids (leiomyomas): Treatment overview".)

Some data suggest that use of depot medroxyprogesterone acetate (DMPA) reduces fibroid size, likely due to a decrease in endogenous estradiol levels. A case series of 20 premenopausal patients with symptomatic uterine fibroids noted that with six months of therapy with DMPA, all patients experienced an improvement in AUB (with 30 percent of patients experiencing amenorrhea), with overall and fibroid volume declining by 48 and 33 percent, respectively [75]. Our clinical experience supports these findings. (See "Depot medroxyprogesterone acetate (DMPA): Formulations, patient selection and drug administration".)

Trying to conceive a pregnancy — 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 challenging in this setting. Experts advise that the best option is oral progestin therapy [76,77].

For patients with heavy menstrual bleeding, NSAIDs may be used but should be stopped upon conception, since they are associated with miscarriage and congenital anomalies [78]. There is insufficient evidence about the safety of tranexamic acid in pregnancy. Also, animal studies suggest that tranexamic acid interferes with ovulation [79,80]. For patients with infertility, AUB should be treated before proceeding with infertility treatments.

For patients with ovulatory dysfunction, treatments to induce ovulation will also correct their AUB symptoms.

Because of its prolonged duration of action, DMPA does not represent an appropriate option for treating patients with AUB who may wish to conceive in the next one to two years (see "Depot medroxyprogesterone acetate (DMPA): Formulations, patient selection and drug administration"). In addition, use of the LNG 52 may not be cost-effective in patients who are planning to conceive a pregnancy within the upcoming year.

Elevated venous or arterial thrombosis risk — Treatment with contraceptive doses of estrogens (ie, estrogen-progestin contraceptives) is contraindicated in patients with an increased risk of venous or arterial thrombosis. In general, use of estrogen-progestin contraceptives should be avoided in patients with the following characteristics [81,82]:

●Age ≥35 years and smoking ≥15 cigarettes per day

●Multiple risk factors for arterial cardiovascular disease (such as older age, smoking, diabetes, and hypertension)

●Hypertension

●Venous thromboembolism (VTE)

●Known thrombogenic mutations

●Known ischemic heart disease

●History of stroke

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

●Systemic lupus erythematosus (positive or unknown antiphospholipid antibodies)

●Migraine with aura at any age

Because age and obesity represent independent risk factors for VTE [83,84], in our practice, we also avoid estrogen-progestin contraceptives in obese patients 40 years and older. As noted above, for selected patients with relative contraindications to contraceptive-dose estrogen, ultra-low-dose estrogen-progestin formulations marketed for treatment of menopausal symptoms may be appropriate. (See 'Noncontraceptive estrogen-progestin formulations' above.)

Contraindications to estrogen-progestin contraceptives are discussed in detail separately. (See "Contraception: Counseling for women with inherited thrombophilias", section on 'Estrogen-progestin methods'.)

In contrast with combination estrogen-progestin contraceptives, progestins may be appropriate for some patients with such risk factors, but medical consultation may be required.

In terms of the choice of progestin-only method, the LNG 52 results in a low level of systemic progestin absorption and use has not been associated with an elevated risk of VTE in average-risk patients [85]. However, there are few data regarding use of the LNG 52 in patients with elevated risk of thrombosis [86]. (See "Contraception: Counseling for women with inherited thrombophilias", section on 'Progestin-only methods'.)

Some data suggest an increased risk of thrombosis with DMPA [87,88]. (See "Contraception: Counseling for women with inherited thrombophilias", section on 'Progestin-only methods' and "Depot medroxyprogesterone acetate (DMPA): Efficacy, side effects, metabolic impact, and benefits", section on 'Cardiovascular and thromboembolic risk'.)

High-dose oral progestins are not used for contraception and thus are less well studied. Their thrombosis risk is uncertain. Norethindrone acetate is partially metabolized to ethinyl estradiol [89]. Although this conversion rate is low, use of 5 mg tablets can result in clinically meaningful amounts of ethinyl estradiol, raising concerns that use of this relatively high dose might elevate risk of VTE. It is not known if oral medroxyprogesterone acetate impacts risk of VTE. However, limited data suggest DMPA may increase VTE risk (see 'Depot medroxyprogesterone acetate' above). Package labeling for norethindrone acetate 5 mg tablets as well as oral medroxyprogesterone acetate lists a history of VTE as a contraindication to use.

Based on the available data regarding progestin-only treatments for AUB, for patients at an increased risk of venous or arterial thrombosis treated with progestins, we suggest the LNG 52 rather than DMPA or high-dose oral progestins.

Surgical options should also be considered for patients with risk factors for venous or arterial thrombosis. The advantage of surgery is that it may be an option for patients with absolute or relative contraindications to hormonal medications. On the other hand, surgery itself is thrombogenic and requires careful management of thromboprophylaxis in this patient population. (See "Prevention of venous thromboembolic disease in adult nonorthopedic surgical patients", section on 'Assess risk for thrombosis'.)

Anticoagulant therapy — Approximately two-thirds of patients using oral anticoagulant treatment experience AUB [90]. In some patients treated with anticoagulants, this treatment is not the primary etiology of AUB, but may exacerbate it.

The presence of AUB is dose-dependent. In patients chronically taking warfarin therapy titrated to a target International Normalized Ratio (INR) range of 2 to 3, and not reporting excess menstrual flow, in our experience, AUB is most likely to occur when this target range is exceeded. AUB appears to occur more frequently with rivaroxaban than with enoxaparin or vitamin K antagonists [91].

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 "Perioperative management of patients receiving anticoagulants".)

In anticoagulated patients, neither estrogen-progestin combination contraceptives nor progestin-only methods appears to increase risk of recurrent venous thrombosis [91]. However, because the procoagulant effects of combination contraceptives may persist for up to six weeks after stopping them, it is important to discontinue the contraceptive prior to stopping anticoagulation [92]. Accordingly, in patients with a history of VTE on warfarin anticoagulation, we prefer progestin-only therapies, specifically LNG 52 or DMPA, for treatment of AUB as well as for contraception [90]. Given the limited published evidence addressing medical management of AUB in patients with a history of VTE using low molecular weight heparin or other newer anticoagulants, our approach is the same as discussed in the previous section. (See 'Elevated venous or arterial thrombosis risk' above.)

WHEN TO REFER — If the patient's primary care clinician is not comfortable performing endometrial sampling or placing an intrauterine device, the patient should be referred to a gynecologist should these services be appropriate. Referral to a gynecologist is also appropriate for patients with heavy bleeding, persistent bleeding despite treatment, if there is suspicion of malignancy, or if surgery is required. Patients with severe anemia, acute heavy bleeding, or hemodynamic instability should be sent to the emergency department.

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 5^th to 6^th 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 10^th to 12^th 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 or prolonged menstrual bleeding (menorrhagia) (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Abnormal uterine bleeding (AUB) is a common gynecologic problem and may cause anemia and impair quality of life. Prolonged bleeding that is not cyclical is often caused by ovulatory dysfunction (AUB-O). In contrast, heavy menstrual bleeding (HMB) is cyclical and often associated with structural uterine disorders. (See 'Terminology' above.)

●AUB treatment choices should take the following factors into consideration: etiology; severity of bleeding (eg, anemia, interference with daily activities); associated symptoms and issues (eg, dysmenorrhea/pelvic pain, infertility); contraceptive needs and plans for future pregnancy; medical comorbidities; risk of venous or arterial thrombosis; and patient preferences regarding, as well as access to, medical versus surgical and short-term versus long-term therapy. (See 'Clinical approach' above.)

●The goal of initial therapy is to control the bleeding, treat anemia (if present), and restore quality of life. Initial therapy is typically pharmacologic. Once the initial treatment goals have been accomplished, some patients are satisfied with continuing chronic medical therapy, while others desire a treatment that requires less maintenance or is definitive. (See 'Clinical approach' above.)

●For most patients with HMB, we suggest estrogen-progestin contraceptives rather than other medications as first-line therapy (Grade 2C). Oral or injectable progestin-only medications are also reasonable as first-line management. The 52 mg levonorgestrel (LNG)-releasing intrauterine device (IUD) with an initial release rate of 20 mcg/day used for five years (LNG 52; Mirena) LNG 52 is the most effective medical treatment of HMB. However, due to logistical/financial issues, it is often appropriate to begin therapy with estrogen-progestin regimens or oral/injectable progestin therapy. (See 'Heavy menstrual bleeding' above.)

●Although not as effective as hormonal management, tranexamic acid or nonsteroidal anti-inflammatory drugs are useful for patients with HMB who have contraindications to or would prefer to avoid hormonal agents. Expectant management is reasonable for patients who are not anemic and do not desire treatment. (See 'Heavy menstrual bleeding' above.)

●For patients with AUB-O, estrogen-progestin formulations, oral progestin therapy, or the LNG 52 are first-line treatment options, as these approaches reduce bleeding and decrease the risk of endometrial hyperplasia or cancer. (See 'Ovulatory dysfunction' above.)

●We suggest the LNG 52 rather than endometrial ablation (Grade 2C). Endometrial ablation is a reasonable choice in patients who do not desire future pregnancy and wish to avoid using or changing an IUD. Hysterectomy is a reasonable option in patients who do not desire future pregnancy, who desire definitive therapy, and who are aware of the risk of anesthesia and perioperative complications. (See 'Hysterectomy' above and 'Levonorgestrel intrauterine device' above.)

●Estrogen-progestins contraceptives are contraindicated in patients with risk factors for venous or arterial thrombosis (eg, history of venous thromboembolism, known thrombogenic mutations, ≥35 years-old and smoking ≥15 cigarettes/day). Progestins may be appropriate for some patients with such risk factors, but medical consultation may be required. For patients at an increased risk of venous or arterial thrombosis treated for AUB with progestins, we suggest the LNG 52 rather than depot medroxyprogesterone acetate or high-dose oral progestins (Grade 2C). (See 'Elevated venous or arterial thrombosis risk' above.)

ACKNOWLEDGMENT — The editorial staff at UpToDate acknowledge Howard Zacur, MD, who contributed to an earlier version of this topic review.