Abnormal uterine bleeding (AUB) is the most common indication for gynecologic consultation. AUB is also believed to be the indication for 80-90% of D&C procedures performed in nonpregnant women in the United States, accounting for about 350,000 procedures annually.185 By some measures AUB is the second most common indication for hysterectomy in the U.S. after uterine leiomyomas, accounting for approximately 20% or 120,000 procedures annually.186,187

AUB may be defined as uterine bleeding occurring at unexpected times or of abnormal duration and may take any of several forms, with the bleeding altered in frequency, duration, and/or amount. AUB always must be differentiated from bleeding originating in the urinary or gastrointestinal tracts. Broadly speaking, AUB can be divided into “organic causes”, which are found in perhaps 25% of cases, and so-called “dysfunctional” (or anovulatory) uterine bleeding (Table 2)

Table 2. Etiology of Abnormal Uterine Bleeding

Organic causes can be divided further into those associated with any of a number of systemic diseases and those associated with disorders of the reproductive tract. DUB may be defined as resulting from a functional abnormality of the hypothalamic-pituitary-ovarian axis and is present in the majority of women with AUB.

The frequency of the various causes of AUB varies with the age of the patient. DUB is more common early and late in the reproductive years. Organic causes, especially neoplasms, increase with advancing age.

Different abnormalities cause AUB during the prepubertal years. Newborn girls sometimes spot for a few days after birth because of placental estrogenic stimulation of the endometrium in utero. Withdrawal of the estrogen at birth leads to sloughing of the endometrium. Accidental trauma to the vulva or vagina is the most common cause of bleeding during childhood. Vaginitis with spotting, most often because of irritation from a foreign body, also may occur. Prolapse of the urethral meatus and tumors of the genital tract also must be considered in the differential diagnosis. When the bleeding is due to the ingestion of estrogen-containing drugs (typically oral contraceptives) by children, there is rarely significant pubertal development. Of course, sexual abuse always must be considered in the young girl presenting with abnormal bleeding. Thus, it is clear that most of the prepubertal causes of bleeding are really not uterine in origin.

Although perhaps as many as half of all menstrual cycles are anovulatory when menses begin, the actual incidence of DUB in adolescents is low. Typically, anovulatory bleeding occurs at intervals longer than normal menstrual cycles, while bleeding due to organic causes tends to occur more frequently than regular menses. In most cases of anovulatory bleeding beginning in adolescence, there is spontaneous resolution. However, it is important to remember that up to 20% of patients with AUB during the teenage years have a primary coagulation disorder.188 It is also important to rule out pregnancy-related bleeding during the reproductive years.

Any woman over the age of 40 with AUB must be evaluated for a malignancy, despite the fact that most causes of such bleeding are benign. Endometrial hyperplasia clearly is a possibility in women who do not ovulate on a regular basis, even at a much earlier age than 40. The finding of endometrial hyperplasia after the menopause always should result in a search for a source of estrogen, either from exogenous therapy or from an endogenous (commonly ovarian) neoplasm.

In the evaluation of the woman with AUB, obtaining a thorough history is of paramount importance. Emphasis should be placed on learning the pattern and quantity of bleeding. Because most women are poor at estimating blood loss and recalling exactly when they bled, all patients should be asked to keep a prospective menstrual calendar in which they record days and severity of bleeding. Menses lasting for more than 8 days or in which more than 80 ml of blood is lost are probably abnormal (i.e., menorrhagia). It has been estimated that up to 20% of women have excessive menstrual blood loss and that the incidence is similar for African-American and white U.S. women.189

Obviously the physical examination also is important. The hemodynamic stability of any patient with abnormal bleeding should be assessed. The pelvic examination will rule out obvious organic causes. Warranted laboratory tests include a complete blood count to assess hematological status, a platelet count and other coagulation studies to rule out a coagulation defect, and thyroid function studies to rule out a thyroid abnormality.

Just which patients should undergo further assessment of the endometrium is problematic, as is the type of evaluation to be undertaken. An endometrial biopsy is indicated in any woman over age 35 with AUB, in any woman with a prolonged history of irregular bleeding, and in most, if not all, women with severe bleeding. Measurement of endometrial thickness by transvaginal ultrasound appears to be of value in postmenopausal women who are not taking exogenous estrogen. Several studies have indicated that there is almost never any significant pathology when the endometrial thickness is less than 5 mm.190 Sonohysterography (SHG), sometimes termed saline infusion sonography (SIS), has become increasingly popular because it can be done in the office at the time of the initial evaluation and appears almost as accurate as hysteroscopy in diagnosing abnormalities within the uterine cavity.191,192 Some clinicians prefer hysteroscopy because it is generally superior to blind biopsy in identifying abnormalities and allows for treatment of many abnormalities at the time of diagnosis. Unfortunately it is also the most expensive of the various procedures; moreover, it is not clear that this procedure is needed to make the diagnosis in most cases. Until definitive data indicate when each of these procedures is warranted, physicians will need to exercise their individual judgment in evaluating women with AUB.

The management of AUB also requires judgment, but a few principles serve the clinician well. First, rule out an organic cause for the bleeding. Then remember that hormonal therapy can almost always stop anovulatory bleeding, but both the patient and the physician must recognize that bleeding will recur at a later (hopefully controlled and planned) time. In general, medical management is always preferred for the treatment of DUB, especially if the patient is interested in future childbearing or if menopause will occur shortly. The actual management of DUB depends on the severity of the problem, the age of the patient, and her desires regarding future fertility.

In young women, typically teenagers, with DUB, only reassurance and prospective charting may be necessary in those with mild irregular bleeding, especially because most adolescents will begin or resume regular ovulatory cycles within several months.188 In teens in whom the bleeding has been more prolonged and erratic such that there is some anemia (but the patient is hemodynamically stable), therapy must be individualized. If the young woman is sexually active (but not pregnant), a progestin-dominant oral contraceptive should control the bleeding and simultaneously provide contraception. Alternatively, a progestin such as medroxyprogesterone acetate (5-10 mg daily for 10-14 days) may be given every 30 to 60 days to induce intermittent “chemical curettage” and prevent chronic unopposed stimulation of the endometrium. However, it often takes several months before intermittent progestins can control irregular uterine bleeding. Oral iron therapy should always be provided as well. In general, the hormonal therapy can be discontinued, if desired, in 6 to 12 months. Most women will have regular menses when therapy is stopped, but thorough evaluation is warranted if irregular bleeding recurs.

In acute severe menorrhagia (with signs of acute blood loss such that the patient is hemodynamically unstable), blood transfusion may be required to restore hemodynamic stability. Once more hormonal therapy is almost always effective in controlling the bleeding. Any of several regimens may be utilized, but in general large doses of estrogen must be given initially and progestin must be added to stabilize the endometrium. For example, an oral contraceptive agent containing 35 micrograms of ethinyl estradiol may be given every 6 hours until the bleeding stops (generally within 48 hours). The dosage then may be tapered by reducing by one pill every other day. Withdrawal bleeding may be permitted after the dosage has been reduced to one tablet each day or may be deferred for several days by continuing to administer one tablet daily. The patient then should be maintained on oral contraceptives given in the usual cyclic fashion for 6 to 12 months. If hormonal therapy cannot control the bleeding, the diagnosis of DUB should be questioned, and evaluation and biopsy of the endometrium are warranted.

Treatment of the woman over age 35 with AUB is more problematic. Organic causes of uterine bleeding are more common and mandate at least visualization if not sampling of the endometrium. Hormonal therapy with a progestin alone or with estrogen and a progestin can be used to control bleeding; combination therapy may be more effective. It is clear that low-dose combination oral contraceptive agents are effective in the majority of women with DUB.193 Hysterectomy is more commonly employed in this age group, particularly if the patient no longer desires childbearing.

A number of medications have proven effective in the treatment of menorrhagia associated with ovulatory menstrual cycles. Non-steroidal anti-inflammatory agents (NSAIDs) are clearly of benefit in some, but not all, women with increased menstrual blood loss. Five of seven randomized trials concluded that mean menstrual blood loss was less with NSAIDs than placebo, while two showed no significant difference.194 This therapy can be used for long-term treatment because side effects, mainly gastrointestinal, are mild with intermittent therapy administered only when the patient is bleeding. They can be given in combination with oral contraceptives or progestins to achieve more effective reduction in menstrual blood loss. Although not approved by the FDA for this purpose, studies from Europe indicate that progestin-containing IUDs may be the most effective therapy for menorrhagia, effecting a reduction in blood loss of as much as 90% in some women.195 The androgenic steroid danazol is also effective in reducing blood loss, even at relatively low doses of 200-400 mg per day, but side effects are common and more severe than with other medical therapies. Epsilon-aminocaproic acid (EACA), tranexamic acid (AMCA), and para-aminomethylbenzoic acid (PAMBA) are potent inhibitors of fibrinolysis and have been used effectively, particularly in Europe, to reduce menstrual blood loss, but side effects limit their utility and they have not been approved for this purpose by the FDA.196,197 Although extensive data are lacking, it is likely that GnRH analogs, perhaps with “add back” therapy to prevent bone loss, are very effective in reducing blood loss,198 but their expense mitigates using them except in those women who fail to respond to other methods of medical management and who wish to retain their childbearing capacity.

A few other comments are warranted. For women of reproductive age who desire childbearing, induction of ovulation is an effective means of controlling anovulatory bleeding. More than half of functional ovarian cysts, most commonly follicular and corpora lutea cysts, induce some form of menstrual irregularity, ranging from amenorrhea to menorrhagia, and most resolve spontaneously. Clearly abnormal bleeding is also a common complaint of women using hormonal and other forms of contraception. It is also important to remember that thyroid dysfunction may cause any disorder of bleeding ranging from amenorrhea to menorrhagia.

Lastly there is little if any role for the use of depot medroxyprogesterone acetate in the management of AUB. This is particularly true for the treatment of acute bleeding and for individuals in whom the cause of the bleeding has not been established with certainty. Although DMPA may be effective in some women, the drug is also known to cause irregular bleeding and may merely compound the problem. Other, more easily reversible forms of contraception are equally or more effective and should be used.

There are several approaches to the surgical treatment of abnormal uterine bleeding. The appropriate procedure depends on the individual circumstances.

Dilatation and curettage (D&C) is indicated for diagnostic purposes in those women in whom endometrial sampling is warranted but in whom endometrial biopsy in the office is not feasible or has been nondiagnostic. Although D&C has been found empirically to be effective in the management of acute uterine bleeding unresponsive to medical therapy, the therapeutic effect of the procedure is usually limited to the current bleeding episode. When D&C is performed for acute bleeding, it should be followed immediately by administration of cyclic exogenous estrogen and progestin in order to optimize long-term cycle control.

It has been estimated that the blind technique of D&C misses the diagnosis of intrauterine lesions in 10 to 25% of patients. Several studies have indicated that hysteroscopy with directed biopsy is at least as accurate as D&C in detecting endometrial abnormalities. Difficulties with hysteroscopy include its cost, the skill required to perform the procedure and evaluate what is seen, and the fact that it is not useful as a simple screening procedure. Hysteroscopy is probably most useful in individuals with AUB in whom no lesion is detected by other methods but in whom the abnormal bleeding persists.

Surgery that attempts to destroy the endometrium selectively, called endometrial ablation, has been reported for decades. Early approaches utilized thermocoagulation and irradiation. Hysteroscopic endometrial ablation can be conducted in several ways: using laser or electrical or thermal energy to coagulate or vaporize the tissue or resecting the endometrium with a loop electrode deployed via a modified urological resectoscope. Non-hysteroscopic endometrial ablation, involving blind destruction of the endometrium using computer-assisted energy delivery systems, is becoming increasingly popular because newly available approaches and those under development are less expensive than surgical approaches, require less training, and some can be performed in an office setting. Thermal balloon ablation systems are now available in the United States. Although trials comparing the various approaches are relatively uncommon, it appears that all the approved methods of endometrial ablation are equally effective.199-201 The reported incidence of complications with endometrial ablation is relatively low.200 A comprehensive survey of 87 Dutch hospitals indicates half of all complications are related to entry into the endometrial cavity (i.e., uterine perforation and cervical trauma).202 Other complications include those related to anesthesia, failed access, hemorrhage, and the systemic absorption of distension media. Complications are more commonly encountered early in the experience of a given surgeon.

Data from several reported series suggest that endometrial ablation will result in initial amenorrhea in 50-75% of patients, acceptable reduction in blood loss in another 20-30%, and no significant reduction in blood loss in approximately 10%.199,201 Repeating the procedure a second time appears to be successful in over half the patients initially experiencing a treatment failure.

There is class I evidence from a Cochrane review that use of GnRH agonists prior to endometrial ablation results in shorter procedures, greater ease of surgery, a lower rate of post-operative dysmenorrhea, and a higher rate of post-surgical amenorrhea.203 Several randomized trials allowed a meta-analysis which documented that women undergoing hysteroscopic endometrial ablation had shorter hospital stays, fewer post-operative complications, and resumed activities earlier than those undergoing hysterectomy for increased menstrual bleeding.204 However, there was a significant advantage in favor of hysterectomy in the improvement in heavy menstrual bleeding and satisfaction rates up to 4 years after surgery compared with endometrial ablation. Moreover, rates of re-operation in women undergoing endometrial ablation increase steadily over time after the initial surgery, up to about 40% at 4 years.205 The direct costs of endometrial ablation may well be greater than hysterectomy if patients are followed long enough after their initial procedure.205 Thus, currently endometrial ablation may be an appropriate alternative to hysterectomy for the rare case of DUB or menorrhagia that is unresponsive to conservative management in a woman who is not desirous of future childbearing. Ablation may be very useful in women who are sufficiently ill such that they are poor candidates for hysterectomy.

The most common indication for myomectomy is menorrhagia, followed by pelvic pain or pressure and infertility. The reported effectiveness of myomectomy for menorrhagia is about 80%, but it is not clear what percentage of these patients have failed medical therapy. Although recurrence of myomas following myomectomy is observed in up to 50% of cases, reportedly only 10-15% of women undergoing myomectomy require subsequent surgery such as hysterectomy.

The effectiveness of hysterectomy for AUB (virtually 100%) has contributed to its popularity as a primary treatment modality for this disorder. Unfortunately, the inefficiency of hysterectomy, due to its greater morbidity, mortality, and cost, makes it an inappropriate choice for management of the great majority of patients presenting with AUB. Current data would suggest that only 1-2% of women presenting with abnormal bleeding will ultimately require hysterectomy when given an appropriate trial of nonsurgical management. Hysterectomy usually should be reserved for the patient with other indications, such as leiomyomas or uterine prolapse. Hysterectomy should be used to treat persistent AUB after all other medical therapy has failed and the amount of menstrual blood loss has been documented to be excessive by some direct measurement (such as a fall in hematocrit).