Management of Abnormal Uterine Bleeding

Management of abnormal uterine bleeding - UpToDate 17/06/2018 20)00
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Management of abnormal uterine bleeding
Author: Andrew M Kaunitz, MD

Section Editor: Robert L Barbieri, MD
Deputy Editor: Sandy J Falk, MD, FACOG
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: May 2018. | This topic last updated: Jun 07, 2017.
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 women 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 women will be reviewed here. The general
evaluation of AUB, acute uterine bleeding, bleeding during pregnancy, and postmenopausal bleeding are
discussed separately. (See "Approach to abnormal uterine bleeding in nonpregnant reproductive-age women"
and "Managing an episode of severe or prolonged uterine bleeding" and "Overview of the etiology and
evaluation of vaginal bleeding in pregnant women" and "Postmenopausal uterine bleeding".)
TERMINOLOGY — A revised terminology system for AUB in nongravid reproductive-age women 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 women: Terminology and 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 women 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.
CLINICAL APPROACH — AUB encompasses a heterogeneous group of conditions with diverse etiologies.
Initial management usually consists of progestin-based treatments including combination oral contraceptives,
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the 52 mg levonorgestrel-releasing intrauterine device with an initial release rate of 20 mcg/day for five years
(LNg52/5; Mirena), and high-dose progestin-only oral medications. Surgical treatment plays an important role
in some women with AUB, particularly those who have structural lesions (eg, leiomyomas, endometrial
polyps) and/or have completed childbearing. Prior to initiating management, women with AUB should
undergo evaluation for endometrial hyperplasia or carcinoma, if appropriate (table 1). (See "Approach to
abnormal uterine bleeding in nonpregnant reproductive-age women", section on 'Endometrial sampling'.)
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 women 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 "Approach to abnormal uterine bleeding in
nonpregnant reproductive-age women", 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.
● Ovulatory dysfunction (AUB-O) – AUB-O is irregular, nonovulatory (noncyclic) bleeding. Although

bleeding may be infrequent (oligomenorrhea) in some women 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, women with ovulatory dysfunction often require fertility treatment if they
wish to conceive. (See "Approach to abnormal uterine bleeding in nonpregnant reproductive-age
women", section on 'Irregular bleeding (ovulatory dysfunction)' and "Treatment of polycystic ovary
syndrome in adults".)
● 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 "Approach to abnormal uterine bleeding in nonpregnant reproductive-age women", section
on 'Menstrual history'.)
Choosing a treatment — Management of reproductive-age women 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. (See "Approach to
abnormal uterine bleeding in nonpregnant reproductive-age women".)
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 women 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 women with chronic AUB is usually pharmacologic treatment. The choice of
medication depends upon the factors listed above. For some women who desire long-acting
contraception, the LNg52/5 is used as first-line therapy.
● Secondary approaches are used for women 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.
Women often choose surgical therapy after long-term medical therapy. A systematic review of eight
randomized trials of women with heavy menstrual bleeding found that 58 percent of women randomly
assigned to medical treatment underwent surgery by two years [11].
As an example, one randomized trial assigned 63 women 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 oral contraceptives (OCs) and a nonsteroidal
antiinflammatory drug (NSAID) (alternative estrogen-progestin regimens were also employed) [12,13]. By 18
months, 53 percent of women 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 $4479 and $6777, respectively [14]. Broken down to resource use
by treatment actually received, the costs for medication only, medicine followed by hysterectomy, and
hysterectomy only were $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 to 21.3) and significantly less likely to cause side
effects (OR 0.2, 95% CI 0.1 to 0.3) [11]. 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 women with chronic AUB-O
prefer definitive therapy and choose hysterectomy.
Some women with AUB will choose the LNg52/5. This provides reversible contraception but can be left in
place for up to five years and over time results in decreasing volume of bleeding until the patient has scant
bleeding or amenorrhea. Other women with AUB may choose minimally invasive surgery or definitive
treatment with hysterectomy.
Women 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 "Overview of
treatment of uterine leiomyomas (fibroids)".)
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.
This includes structural lesions. Submucosal fibroids and endometrial polyps can be resected via operative
hysteroscopy. Arteriovenous malformations can be treated with interventional radiology procedures. (See
"Endometrial polyps" and "Interventional radiology in management of gynecological disorders", section on
'Arteriovenous malformation' and "Laparoscopic myomectomy and other laparoscopic treatments for uterine
leiomyomas (fibroids)", section on 'Myolysis'.)
AUB due to infection in women with suspected or documented chronic endometritis often resolved following a
course of antibiotics. (See "Endometritis unrelated to pregnancy".)
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 [15-
18]. (See "Treatment of primary hypothyroidism in adults" and "Treatment of polycystic ovary syndrome in
adults".)
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 [19]. (See "Treatment of von
Willebrand disease", section on 'Excessive menstrual bleeding'.)
INITIAL APPROACH: MEDICAL THERAPY — Medical therapy is appropriate initial treatment for most
women. If treatment must be continued long-term, some women will prefer a management option that does
not require frequent dosing (eg, levonorgestrel-releasing [20 mcg/day] intrauterine device [LNg52/5 IUD;
Mirena] 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 women with HMB associated with adenomyosis, endometrial ablation may be less effective
than in other conditions.
For most women with HMB, we suggest estrogen-progestin contraceptives or the LNg52/5 as first-line
therapy rather than other medications. Both estrogen-progestin contraceptives and the LNg52/5 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 upon several factors. Estrogen-progestin contraceptives are not an
option in patients with a contraindication to estrogen, (eg, hypertension or an increased risk of thrombosis)
(see 'Elevated venous or arterial thrombosis risk' below). For other patients, the choice depends upon patient
preference. Women may prefer estrogen-progestin contraceptives if they prefer taking a daily oral
medication, while others prefer the low maintenance of having an indwelling device. In addition, some women
prefer the regular bleeding associated with estrogen-progestin contraceptives, while others are willing to
tolerate the initial irregular bleeding that accompanies the LNg52/5 and prefer the eventual light bleeding or
amenorrhea. For women who are planning to conceive in the near future, estrogen-progestin contraceptives
provide a short-term option. (See "Overview of the use of combination oral contraceptives".)
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
antiinflammatory 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 women who are not anemic and do not desire treatment. For
women with HMB who choose expectant management, depending on the volume of bleeding, we check a
hematocrit every 6 to 12 months.
Ovulatory dysfunction — In contrast with hormonal management of HMB, which has been addressed in a
number of randomized trials [20], 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 [21]. In some cases, such as submucosal (intracavitary) uterine fibroids, ovulatory women
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 women with AUB-O.
For women with AUB-O, estrogen-progestin contraceptives, oral progestin therapy, or the LNg52/5 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 women with AUB-O, resulting in moderate, predictable withdrawal
bleeding. Although use of the LNg52/5 does not cause regular withdrawal bleeding, use in patients with AUB
is often appropriate, as most women will eventually become amenorrheic or have only scant bleeding. In
contrast to oral medroxyprogesterone acetate, use of the LNg52/5 also provides effective contraception.
In women with AUB-O who do not desire future pregnancy and are considering surgical management,
endometrial ablation represents a problematic choice for several reasons. Women 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 [22]. (See "An overview of endometrial ablation".)
Treatment options — The comparative efficacy of different therapies for HMB has been evaluated. The
LNg52/5 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 women
with heavy menstrual bleeding, use of tranexamic acid and NSAIDs reduce menstrual blood loss by 26 to 54
percent and 10 to 52 percent, respectively [20,23].
Hormonal treatment
Estrogen-progestin contraceptives — Estrogen-progestin contraceptives (OCs) are first-line

management for many women 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 women with irregular bleeding, an OC regulated bleeding patterns in significantly
more women than placebo (47 versus 9 percent) [23].
OCs have been extensively studied in women with HMB, with randomized trials finding reductions in
menstrual blood loss ranging from 35 to 69 percent [20]. Other routes of administration include the
transdermal contraceptive patch (Xulane) and vaginal contraceptive ring (Nuvaring). These have not been
studied extensively for HMB, but it is likely that the efficacy of these in treating AUB is similar, and the choice
of delivery system depends upon patient preference [24]. (See "Overview of the use of combination oral
contraceptives".)
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 [25]. 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 OCs for treating
HMB, and other short hormone-free interval pills are available (see "Overview of the use of combination oral
contraceptives", section on 'Shorter pill-free interval'). 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 [26]. 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 women 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) [27]. 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
women with HMB (average reduction with OCs is 35 to 69 percent) [20].
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 women, unscheduled
(breakthrough) bleeding is more common with this approach than with 28-day OC formulations, limiting this
strategy’s appeal for some patients [28]. In clinical trials performed in women 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 [29]. (See "Overview of the use of combination oral contraceptives", section on
'Shorter pill-free interval' and "Hormonal contraception for suppression of menstruation".)
OCs are contraindicated in women who are at elevated risk for thrombosis. (See 'Elevated venous or arterial
thrombosis risk' below.)
Noncontraceptive estrogen-progestin formulations — Ultra low estrogen dose formulations

marketed for the treatment of menopausal symptoms may be useful in selected women 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 women
[30]. Each pack contains 28 days of hormonally active tablets (continuous therapy). In our experience, use of
this formulation in women with AUB often results in amenorrhea after several months.
Examples of patients in whom these types of formulations may be useful include women 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
Note that both of these patient profiles represent examples of AUB that could be safely and effectively
managed with the LNg52/5 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 LNg52/5. 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 LNg52/5 is a highly effective and easy to use treatment
option for AUB. It may be used as a first-line option for treatment of HMB in women who do not desire
pregnancy. In women with AUB-O, use of this IUD does not result in regular bleeding; however, it decreases
the risk of hemorrhage and provides protection against endometrial hyperplasia and cancer. Most women
using the LNg52/5 develop scant bleeding or amenorrhea. The LNg52/5 is approved by the US FDA for
treatment of HMB.
LNg52/5 is the only progestin IUD that has been evaluated for treatment of AUB. There are other IUDs with
different doses and durations of use, but further study of the role of other device for AUB is needed [31]. (See
"Intrauterine contraception: Background and device types" and "Intrauterine contraception: Candidates and
device selection".)
Although the LNg52/5 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.
LNg52/5 has been found to reduce menstrual blood loss in women with HMB by 71 to 95 percent, an efficacy
higher than for other hormonal and nonhormonal medical treatments and comparable to that of endometrial
ablation [23,32]. In studies of women 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 [33-35]. Serum progestin concentrations produced by
LNg52/5 do not inhibit ovulation in most women. The high local progestin concentration results in a thinning
of the endometrium. A small study of obese women with HMB found that the LNg52/5 was effective in 67
percent of participants, with significant improvements in quality of life indices at 6 and 12 months [36].
In women with HMB, the LNg52/5 has also been found to improve quality of life more than other hormonal or
nonhormonal medical treatments [37].
Several considerations apply to use of the LNg52/5 in treating HMB, including the expulsion rate in women
with uterine fibroids and the frequency of replacing the device,
In general, for contraceptive use, the three-year cumulative expulsion rate is 10 per 100 users [38]. Although
findings from published studies of women with HMB are not consistent regarding this outcome, expulsion
rates also appear to be higher when the LNg52/5 is placed in women with HMB associated with uterine
fibroids compared with other women with HMB [39]. The endometrial cavity is often distorted by the fibroid
tumors. Package labeling for the LNg52/5 lists congenital or acquired distortion of the endometrial cavity (eg,
by fibroids) as a contraindication to placement of this IUD. Nonetheless, in women with HMB who wish to
avoid surgery or in whom the risk of surgical complications is elevated, use of the LNg52/5 may be
appropriate in well-counseled patients. We counsel women with HMB considering placement of the LNg52/5
that expulsion rates are elevated compared with use of this device specifically for contraception.
For women with adenomyosis, one study reported a 25 percent expulsion rate when the LNg52/5. However,
other studies have reported a very low expulsion rates in such patients [32,40].
Women using the LNg52/5 to treat HMB may benefit from more frequent removal and replacement of this
IUD. When used for contraception, the LNg52/5 is replaced every five years. In contrast, when the LNg52/5 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 [32]. The need for more frequent replacement of
the LNg52/5 in this setting may reflect declining intrauterine progestin concentrations during use of this
device. (See "Intrauterine contraception: Background and device types".)
Although the LNg52/5 has been studied considerably less in women with AUB-O, available data as well as
expert opinion, suggests it is effective in treating this condition in younger and older patients [41-44]. (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 women 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 women who are trying to conceive. The contraceptive
effect persists for longer than the three-month dosing interval. (See "Depot medroxyprogesterone acetate for
contraception".)
In women with no complaints of AUB at baseline, approximately one-half of women 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 women with AUB-O or HMB noted that after two months, women using DMPA
experienced a 49 percent reduction in menstrual blood loss [41].
High-dose oral progestins — High-dose oral progestin formulations are generally used to treat AUB
in women who have contraindications to or prefer to avoid estrogen or women 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 [45]. 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 (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 women 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 women 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 [41].
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 women with HMB
[46]. In contrast, high-dose oral progestational therapy (norethindrone acetate 5 mg tablets, one to three
tablets daily) administered for 21 days each month has been found effective in reducing menstrual blood loss
in women with HMB in randomized trials [24,47].
In women 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 women 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 US 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 women 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 [48]. In our practice, we sometimes use this
medication to treat HMB in women for whom use of hormonal therapy is contraindicated (eg, women 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 [49]. (See 'Elevated venous or arterial thrombosis
risk' below and 'Trying to conceive a pregnancy' below.)
US Food and Drug Administration (FDA) labeling for tranexamic acid lists a history of venous
thromboembolism or elevated risk of thrombosis 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 [50,51]. 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 [50]. A British case-control study also
assessed the association between risk of thrombosis and use of tranexamic acid. Use of tranexamic 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, suggesting that anemia associated with HMB represents a prothrombotic
condition regardless of medication use [51].
Studies have found that tranexamic acid reduces menstrual blood loss by 26 to 54 percent in women with
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HMB and in comparative studies was more effective than NSAIDs and less effective than the LNg52/5
[20,52]. In a multicenter randomized trial with 196 women with HMB, women were assigned to tranexamic
acid or placebo [53]. 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 women 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 women 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 antiinflammatory 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 [54,55].
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 women with HMB concluded that NSAIDs were more effective
than placebo at reducing HMB, but less effective than the LNg52/5 and tranexamic acid [56]. 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 women with HMB found that a low-dose monophasic
combined oral contraceptive appeared more effective than mefenamic acid or naproxen in reducing
menstrual blood loss, but these differences did not achieve statistical significance [57].
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 [58,59]
● Naproxen 500 mg at onset and three to five hours later, then 250 to 500 mg twice a day [57,60,61]
● Ibuprofen 600 mg once per day [62]
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
[56]. The short-term use of intravenous estrogen may be helpful in treating women with acute AUB (see
"Managing an episode of severe or prolonged uterine bleeding"). Gonadotropin-releasing hormone agonists
may be useful in preventing AUB in women who will undergo chemotherapy. (See "Heavy or irregular uterine
bleeding 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, women 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 upon the patient’s characteristics and therapeutic goals. For patients
considering surgery, the risks and benefits should be compared with the levonorgestrel-releasing (20
mcg/day) intrauterine device (LNg52/5 IUD; Mirena), which has many of the advantages of surgery with a low
risk of complications and no recovery time.
The choice of whether to proceed with surgery and the type of procedure depends upon plans for fertility. For
women who desire future childbearing, surgical options are limited. Myomectomy for women with fibroids is
the only fertility-preserving surgical option. For women with intracavitary fibroids, a myomectomy may reduce
bleeding and also improve fertility.
For women who do not desire to preserve fertility, a minimally invasive option may be appropriate.
Procedures include endometrial ablation or uterine artery embolization. Hysterectomy is appropriate for
women who have failed other surgical treatments and/or who desire definitive treatment.
Levonorgestrel IUD versus surgical treatments — A systematic review of six randomized trials and a
subsequent randomized trial found that women with menorrhagia who were treated with either the LNg52/5 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 [23,63].
In a study of 236 patients with HMB which followed women for 10 years after they were randomized to
placement of a LNg52/5 or hysterectomy, 46 percent of women initially randomized to IUD placement
ultimately underwent hysterectomy. Overall, costs were lower among women randomized to the IUD while
health-related quality of life and psychosocial well-being were similar in the two groups [64]. In the same trial,
10-year follow-up reported that women in the IUD group had significantly lower rates of stress urinary
incontinence (34 versus 48 percent) and usage of medications for urinary incontinence (1 versus 12 percent)
[65].
The decision to use the LNg52/5 or endometrial ablation depends upon a patient's preferences regarding
treatment factors such as plans for fertility and contraception, convenience, and risks of anesthesia. The
LNg52/5 is a reversible contraceptive. Pregnancy is contraindicated after endometrial ablation, but the
procedure may not prevent pregnancy; thus, women will need to continue to use contraception following
ablation. The LNg52/5 is placed in an office setting and requires no or local anesthesia. Endometrial ablation
can also be done in an office by surgeons who are appropriately equipped but is often performed in an
operating room under general anesthesia. If successful, endometrial ablation is performed once, while the
LNg52/5 needs to be replaced regularly.
Women who desire fertility
Myomectomy — Myomectomy is an option for women with uterine leiomyomas. If one or two intracavitary
myomas are present, a hysteroscopic myomectomy is minimally invasive and may resolve AUB symptoms.
(See "Hysteroscopic myomectomy".)
Women 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 her fertility. Patients considering myomectomy should be counseled that this surgery may commit
them to cesarean delivery for subsequent pregnancies. (See "Laparoscopic myomectomy and other
laparoscopic treatments for uterine leiomyomas (fibroids)" and "Abdominal myomectomy".)
Women finished with childbearing
Endometrial ablation — Endometrial ablation is a minimally invasive option for treatment of heavy or
prolonged uterine bleeding when medical therapy fails or in women who do not want to use chronic medical
therapy [66]. Pregnancy is contraindicated after endometrial ablation, but contraception is still required. As
described above, endometrial ablation and the LNg52/5 have equivalent efficacy in reducing menstrual blood
flow in women with HMB. (See 'Levonorgestrel IUD versus surgical treatments' above and "An overview of
endometrial ablation".)
Uterine artery embolization — Uterine artery embolization is an option for women with uterine
leiomyomas. The safety of pregnancy after this procedure has not been established; therefore, it is usually
reserved for women who are not contemplating future childbearing. (See "Uterine leiomyomas (fibroids):
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 "Choosing a route of hysterectomy for
benign uterine disease".)
SPECIAL CONSIDERATIONS
Dysmenorrhea or pelvic pain — Women 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-releasing (20 mcg/day) intrauterine device (LNg52/5 IUD; Mirena) has been found to reduce
pain and AUB in women with adenomyosis [32,67]. Nonsteroidal antiinflammatory drugs (NSAIDs) are
another useful option. (See "Uterine adenomyosis".)
Women 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 "Overview of treatment of uterine leiomyomas (fibroids)".)
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 women with symptomatic
uterine fibroids noted that with six months of therapy with DMPA, all women experienced an improvement in
AUB (with 30 percent of women experiencing amenorrhea), with overall and fibroid volume declining by 48
and 33 percent, respectively [68]. Our clinical experience supports these findings. (See "Depot
medroxyprogesterone acetate for contraception".)
Trying to conceive a pregnancy — When counseling a woman regarding treatment of AUB, it is important
to ask whether she 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 [69,70].
For women with HMB, NSAIDs may be used but should be stopped upon conception, since they are
associated with miscarriage and congenital anomalies [71]. There is insufficient evidence about the safety of
tranexamic acid in pregnancy. Also, animal studies suggest that tranexamic acid interferes with ovulation
[72,73]. For women with infertility, AUB should be treated before proceeding with infertility treatments.
For women with ovulatory dysfunction (AUB-O), 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
women with AUB who may wish to conceive in the next one to two years (see "Depot medroxyprogesterone
acetate for contraception"). In addition, use of the LNg52/5 may not be cost-effective in women who are
planning to conceive a pregnancy within the upcoming year.
Elevated venous or arterial thrombosis risk — Treatment with estrogens (ie, estrogen-progestin
contraceptives) is contraindicated in women with an increased risk of venous or arterial thrombosis. In
general, use of estrogen-progestin contraceptives should be avoided in women with the following
characteristics [74,75]:
● 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
● 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 venous thromboembolism (VTE) [76,77], in
our practice, we also avoid treating with estrogens (ie, estrogen-progestin contraceptives) in obese women
40 years and older. As noted above, for selected women with relative contraindications to contraceptive dose
estrogen, ultra low-dose estrogen formulations may be appropriate. (See 'Noncontraceptive estrogen-
progestin formulations' above.)
Contraindications to estrogen-progestin contraceptives are discussed in detail separately. (See

"Contraceptive counseling for women with inherited thrombophilias", section on 'Estrogen-progestin
methods'.)
Progestins may be appropriate for some women with such risk factors, but medical consultation may be
required.
In terms of the choice of progestin-only method, the LNg52/5 results in a low level of systemic progestin
absorption and use has not been associated with an elevated risk of VTE in average-risk women [78].
However, there are few data regarding use of the LNg52/5 in women with elevated risk of thrombosis [79].
(See "Contraceptive counseling for women with inherited thrombophilias", section on 'Progestin-only
methods'.)
Some data suggest an increased risk of thrombosis with DMPA [80,81]. (See "Depot medroxyprogesterone
acetate for contraception", section on 'Cardiovascular and thromboembolic risk' and "Contraceptive
counseling for women with inherited thrombophilias", section on 'Progestin-only methods'.)
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 [82]. 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. In addition, package labeling
for norethindrone acetate 5 mg tablets lists a history of VTE as a contraindication to use.
Based upon the available data regarding progestin-only treatments for AUB, for women at an increased risk
of venous or arterial thrombosis treated with progestins, we suggest the LNg52/5 rather than DMPA or high-
dose oral progestins.
Surgical options should also be considered for women with risk factors for venous or arterial thrombosis. The
advantage of surgery is that it may be an option for women 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 women using oral anticoagulant treatment experience
AUB [83]. In some women treated with anticoagulants, this treatment is not the primary etiology of AUB, but
may exacerbate it.
The presence of AUB is dose-dependent. In women 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 [84].
Women 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 women, neither estrogen-progestin combination contraceptives nor progestin-only methods

appears to increase risk of recurrent venous thrombosis [84]. 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 [85]. Accordingly, in women with a history of VTE on
warfarin anticoagulation, we prefer progestin-only therapies, specifically LNg52/5 or DMPA, for treatment of
AUB as well as for contraception [83]. Given the limited published evidence addressing medical management
of AUB in women 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.).
REFERRAL TO A GYNECOLOGIST — If the woman'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 women who have
persistent bleeding despite treatment or require surgery.
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 or prolonged menstrual bleeding (menorrhagia) (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
● 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
women 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 women 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-releasing intrauterine device with an initial release rate
of 20 mcg/day used for five years (LNg52/5; Mirena) LNg52/5is 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.)
● Tranexamic acid or nonsteroidal antiinflammatory drugs are useful for patients with HMB who have
contraindications to or would prefer to avoid hormonal agents. Expectant management is reasonable for
women who are not anemic and do not desire treatment. (See 'Heavy menstrual bleeding' above.)
● For women with AUB-O, estrogen-progestin formulations, oral progestin therapy, or the LNg52/5 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 LNg52/5 rather than endometrial ablation (Grade 2C). Endometrial ablation is a
reasonable choice in women who do not desire future pregnancy and wish to avoid using or changing an
intrauterine device. Hysterectomy is a reasonable option in women who do not desire future pregnancy,
who desire definitive therapy, and who are aware of the risk of perioperative complications. (See
'Hysterectomy' above and 'Levonorgestrel intrauterine device' above.)
● Estrogen-progestins contraceptives are contraindicated in women 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 women with such risk factors, but
medical consultation may be required. For women at an increased risk of venous or arterial thrombosis
treated for AUB with progestins, we suggest the LNg52/5 rather than depot medroxyprogesterone
acetate (DMPA) or high-dose oral progestins (Grade 2C). (See 'Elevated venous or arterial thrombosis
risk' above.)
ACKNOWLEDGMENT — The editorial staff at UpToDate would like to acknowledge Howard Zacur, MD, who
contributed to an earlier version of this topic review.
Use of UpToDate is subject to the Subscription and License Agreement.
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Topic 5476 Version 33.0
GRAPHICS
PALM-COEIN classification system for abnormal uterine bleeding

in nongravid reproductive-age women
Basic classification system. The basic system comprises four categories that are
defined by visually objective structural criteria (PALM: polyp, adenomyosis,
leiomyoma, and malignancy and hyperplasia), four that are unrelated to structural
anomalies (COEI: coagulopathy, ovulatory dysfunction, endometrial, iatrogenic), and
one reserved for entities that are not yet classified (N). The leiomyoma category (L)
is subdivided into patients with at least one submucosal myoma (LSM) and those
with myomas that do not impact the endometrial cavity (LO).
Reproduced from: Munro MG, Critchley HO, Broder MS, Fraser IS, FIGO Working Group on
Menstrual Disorders. FIGO classification system (PALM-COEIN) for causes of abnormal
uterine bleeding in nongravid women of reproductive age. Int J Gynaecol Obstet 2011;
113:3. Illustration used with the permission of Elsevier Inc. All rights reserved.
Graphic 90483 Version 2.0
Women who should undergo evaluation for endometrial hyperplasia or

endometrial cancer
Abnormal uterine bleeding
Postmenopausal women – Any uterine bleeding, regardless of volume (including spotting or staining).
Pelvic ultrasound to evaluate endometrial thickness is an alternative to endometrial sampling in
appropriately selected women. A thickened endometrium should be further evaluated with endometrial
sampling.
Age 45 years to menopause – In any woman, bleeding that is frequent (interval between the onset of
bleeding episodes is <21 days), heavy, or prolonged (>5 days). In women who are ovulatory, this
includes intermenstrual bleeding.
Younger than 45 years – Any abnormal uterine bleeding in obese women (BMI ≥30). In non-obese
women, abnormal uterine bleeding that is persistent and occurs in the setting of one of the following:
chronic ovulatory dysfunction, other exposure to estrogen unopposed by progesterone, failed medical
management of the bleeding, or women at high risk of endometrial cancer (eg, Lynch syndrome, Cowden
syndrome).
In addition, endometrial neoplasia should be suspected in premenopausal women who are anovulatory
and have prolonged periods of amenorrhea (six or more months).
Cervical cytology results
Presence of AGC-endometrial.
Presence of AGC-all subcategories other than endometrial – If ≥35 years of age OR at risk for
endometrial cancer (risk factors or symptoms).
Presence of benign-appearing endometrial cells in women ≥40 years of age who also have abnormal
uterine bleeding or risk factors for endometrial cancer.
Other indications
Monitoring of women with endometrial pathology (eg, endometrial hyperplasia).
Screening in women at high risk of endometrial cancer (eg, Lynch syndrome).
These recommendations are based on an average age of menopause of 51 years. Evaluation of women
who undergo menopause earlier should be individualized based upon gynecologic history and risk of
endometrial neoplasia.
BMI: body mass index; AGC: atypical glandular cells.
Graphic 58600 Version 11.0
Contributor Disclosures
Andrew M Kaunitz, MD Grant/Research/Clinical Trial Support: Bayer [Investigational treatment for uterine
fibroids (Contraceptives, menopausal hormone therapy)]; Agile [Contraception (Investigational contraceptive
patch)]; Radius [Treatment of menopausal vasomotor symptoms (Investigational SERM)]; TherapeuticsMD
[Menopause (Investigational treatments)]; Mithra [Contraception (Investigational contraceptive)]; Allergan
[Contraception, menopause]; Endoceutics [Vaginal DHEA for genital atrophy]; Evafem [Investigational
spermicide]. Consultant/Advisory Boards: Allergan [Contraception, menopause]; AMAG [Genital atrophy
(Vaginal DHEA for genital atrophy)]; Bayer [Contraception, menopause]; Merck [Contraception
(Contraceptive vaginal ring, contraceptive implant)]; Medicines 360 [Intrauterine contraception (LNg IUD)];
Mithra [Contraception (Investigational contraceptive)]; Shionogi [Genital atrophy (Ospemifene for genital
atrophy)]. Other Financial Interest: Femasys Safety Monitoring Board [Investigational transcervical
sterilization]. Robert L Barbieri, MD Nothing to disclose Sandy J Falk, MD, FACOG Nothing to disclose
Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are
addressed by vetting through a multi-level review process, and through requirements for references to be
provided to support the content. Appropriately referenced content is required of all authors and must
conform to UpToDate standards of evidence.
Conflict of interest policy

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Management of abnormal uterine bleeding - UpToDate 17/06/2018 20)00

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Author: Andrew M Kaunitz, MD

● Ovulatory dysfunction (AUB-O) – AUB-O is irregular, nonovulatory (noncyclic) bleeding. Although

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

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

● Contraceptive needs and plans for future pregnancy

mental health at six-month follow-up.

than in other conditions.

Estrogen-progestin contraceptives — Estrogen-progestin contraceptives (OCs) are first-line

Noncontraceptive estrogen-progestin formulations — Ultra low estrogen dose formulations

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

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

Depot medroxyprogesterone acetate — Depot medroxyprogesterone acetate (DMPA) is typically

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

In promoting endometrial suppression, norethindrone acetate is substantially more potent than

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

Nonsteroidal antiinflammatory drugs — NSAIDs are a nonhormonal, noncontraceptive option for

Advantages of NSAIDs include:

● Do not increase risk of thrombosis

● Low risk of adverse effects

● Low cost and often available over the counter

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

● Mefenamic acid 500 mg three times per day [58,59]

● Ibuprofen 600 mg once per day [62]

Women who desire fertility

Women finished with childbearing

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

● Known thrombogenic mutations

● Known ischemic heart disease

● Systemic lupus erythematosus (positive or unknown antiphospholipid antibodies)

● Migraine with aura at any age

Contraindications to estrogen-progestin contraceptives are discussed in detail separately. (See

In anticoagulated women, neither estrogen-progestin combination contraceptives nor progestin-only methods

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

SUMMARY AND RECOMMENDATIONS

Use of UpToDate is subject to the Subscription and License Agreement.

inherited bleeding disorders. Int J Gynaecol Obstet 2006; 95:75.

Cochrane Database Syst Rev 2013; :CD000400.

Topic 5476 Version 33.0

PALM-COEIN classification system for abnormal uterine bleeding

Graphic 90483 Version 2.0

Women who should undergo evaluation for endometrial hyperplasia or

Abnormal uterine bleeding

Cervical cytology results

Monitoring of women with endometrial pathology (eg, endometrial hyperplasia).

Screening in women at high risk of endometrial cancer (eg, Lynch syndrome).

BMI: body mass index; AGC: atypical glandular cells.

Graphic 58600 Version 11.0

Conflict of interest policy

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