Gynecology

Dysfunctional Uterine Bleeding

WHEC Practice Bulletin and Clinical Management Guidelines for healthcare providers. Educational grant provided by Women's Health and Education Center (WHEC).

Dysfunctional uterine bleeding (DUB) is abnormal bleeding from the uterine endometrium that is unrelated to an anatomic lesion of the uterus (ACOG, 1989). It is associated with abnormal ovarian function and anovulation but may occur in ovulatory cycles. Prepubertal or postmenopausal uterine bleeding is a separate entity that warrants a different diagnostic and therapeutic consideration. The wide variation in menstrual patterns often causes difficulty in identifying abnormal bleeding. In practice, any bleeding that is excessive in duration, frequency or amount for a particular patient should be considered abnormal and investigated accordingly.

The purpose of this document is to provide management guidelines for the treatment of patients with menstrual irregularities associated with anovulation based on the best available evidence. Dysfunctional uterine bleeding anovulatory type is the most common form of non-cyclic uterine bleeding and it is a condition for which women frequently seek gynecologic care and accounts for considerable patient anxiety and inconvenience. The choice of treatment for anovulatory bleeding depends on several factors, including the woman's age, the severity of her bleeding, and her desire for fertility. Over the last decade, significant advances have been made in the evaluation and management of women with anovulatory bleeding.

The Normal Menstrual Cycle:

A normal ovulatory cycle is the consequence of endocrine interactions of the hypothalamic-pituitary-ovarian axis. In addition, the event of menstruation occurs as a result of sudden decrease in progesterone and estrogen secretion due to the demise of the corpus luteum. In ovulatory cycles, sequential histological changes of the uterine endometrium from proliferative phase to secretory phase reflect ovarian function, which is characterized by the cyclic pattern of estrogen and progesterone secretion. In anovulatory cycles, these predictable changes in endometrial histology and ovarian steroid hormones are missing.

The normality of menstruation is subjectively determined by the amount and duration of blood flow and by the intervals between menstrual cycles. In the reproductive life, most women experience a consistent cycle interval ranging between 25 and 34 days. The duration of normal menses is 3 to 7 days. Although blood loss cannot be accurately quantitated, blood loss in a normal menstrual period varies from 25 ml to 75 ml. Clinically, however, the number of pads or tampons used often gives some idea as to any changes in menstrual flow, although they are not reliable indicators of actual amount of blood loss.

Causes of Abnormal Uterine Bleeding:

Dysfunctional uterine bleeding: anovulatory bleeding, corpus luteum dysfunction, atrophic endometrium
Intrauterine lesions: submucous fibroids, endometrial polyp, endometritis, intrauterine contraceptive device, endometrial cancer
Leiomyomas of the uterus
Pelvic inflammatory disease
Adenomyosis
Early pregnancy complication: abortion, ectopic pregnancy, hydatidiform mole
Pelvic diseases not detected clinically: uterine lesions, pelvic inflammatory disease, endometriosis, ovarian neoplasm
Various endocrinopathy: hypothalamic/psychogenic, polycystic ovary syndrome, hyperprolactinemia, thyroid dysfunction, adrenal dysfunction.
Systemic diseases: blood dyscrasia, hepatic diseases, renal diseases, and iatrogenic causes.

Patterns of Abnormal Uterine Bleeding:

Polymenorrhea: Frequent menses regularly occurring at intervals of less than 21days.
Hypermenorrhea: Excessive bleeding in amount during normal duration of regular menses.
Hypomenorrhea: Decreased bleeding in amount in regular menstrual cycles.
Menorrhagia: Prolonged bleeding in duration, occurring at regular intervals.
Metrorrhagia: Uterine bleeding occurring at irregular intervals.
Menometrorrhagia: Uterine bleeding, usually excessive and prolonged, occurring at irregular, frequent intervals.

Diagnostic Investigation:

The history should include a detailed menstrual pattern in terms of intervals, duration and amount of the flow; a list of medications; obstetric history; sexual and contraceptive histories; and a general medical history. It should also include recent surgical and gynecologic disorders. Physical examination focuses on general medical conditions that might cause DUB. Examination of the thyroid, breast, liver, and skin is essential. Evaluation of the presence and absence of ecchymotic lesions, obesity, and hirsutism is essential. Pelvic examination of external and internal organs, the source and degree of bleeding, the size and shape of the uterus and any adnexal abnormalities are checked for the diagnosis. A complete blood count, Pap smear, coagulation profile, serum HCG, iron concentration and binding capacity, ovulation detection, thyroid function tests, serum androgens, hepatic function tests, endometrial biopsy, hysteroscopy and hysterogram, pelvic ultrasound, and MRI are usually done depending on the clinical findings and to make an accurate diagnosis.

Treatment:

It is individualized according to the patient's age, her desire for contraception or fertility, and the severity and chronicity of the bleeding. The goals of treatment are to arrest the acute episode of bleeding, to prevent recurrences, and to induce ovulation in the patient desiring to conceive. If the pelvic examination shows a normal uterus and no systemic diseases are suspected, hormonal therapy is usually effective in managing DUB.

Acute, Profuse Bleeding: When a patient presents with acute, profuse, and uncontrollable hemorrhage, the usual steps taken for any other serious hemorrhage must be instituted immediately. High-dose estrogen therapy or injectable progesterone is sometimes helpful to control the bleeding. Emergency dilatation and curettage or hysterectomy might be needed in some occasions to control the bleeding and save the patient's life.

Chronic, Recurrent Bleeding: Treatment is based on the patient's complaint, age, and desire for fertility. Observation only is a reasonable approach for adolescent girls without any evidence of anemia. However, if the patient is sexually active, combination oral contraceptives is offered.

Surgical Therapy: Although most of the patients with DUB can be managed by hormonal therapy, a D & C can be effective both diagnostically and therapeutically. For those older than age 35, histology evaluation of the endometrium is essential either by an endometrial biopsy or a D & C to rule out endometrial hyperplasia and endometrial cancer. Endometrial ablation either by thermal balloon or by Nd: YAG laser or electrocoagulations through the hysteroscope are surgical options. Hysterectomy is regarded as the definitive treatment. Please discuss with your healthcare provider to decide what the right treatment for you is.

Clinical Considerations and Suggested Approach:

Adolescents (13-18 Years): Anovulatory bleeding is a normal physiologic process in the perimenarchal years of the reproductive cycle. Ovulatory menstrual cycles may not be established until a year or more after menarche. This phenomenon is attributed to immaturity or hypothalamic-pituitary-gonadal axis. Occasionally, adolescents with blood dyscrasias, including Von Willebrand's disease and prothrombin deficiency, have heavy vaginal bleeding at menarche. Disorders such as leukemia, idiopathic thrombocytopenic purpura, and hypersplenism can all produce platelet dysfunction and cause excessive bleeding. These conditions require specific treatments, and routine screening for coagulation disorders is suggested in adolescents.

For chronic anovulation, treatment with low-dose oral contraceptives is the treatment of choice. Oral contraceptives suppress both ovarian and adrenal androgen production and increase sex hormone binding globulins.

Women of Reproductive Age (19-39): Although anovulation may be considered physiologic in adolescents, adult women of reproductive age who have menorrhagia, metrorrhagia, or amenorrhoea require evaluation for the specific cause. The laboratory tests should include a pregnancy test, thyroid stimulating hormone (TSH) level, and prolactin level. Chronic anovulation that results from hypothalamic dysfunction, as diagnosed by a low follicular stimulating hormone (FSH) level, may be the result of excessive psychologic stress, exercise, or weight loss. A history of rapidly progressing hirsutism accompanied by virilization suggests a tumor. In most cases, tumors can be ruled out by testing testosterone and dehydroepinandrostetrone sulfate levels in serum. The incidence of endometrial carcinoma increases with age. Therefore, based on age alone, endometrial assessment to exclude cancer is indicated in any woman older than 35 years who is suspected of having anovulatory uterine bleeding. Adult women of reproductive age with anovulatory uterine bleeding can be treated safely with either a cyclic progestrogen or oral contraceptives. If pregnancy is desired, induction of ovulation with clomiphene citrate is the initial treatment of choice.

Women of Later Reproductive Age (40 Years to Menopause): The incidence of anovulatory uterine bleeding increases as women approach the end of their reproductive years. In perimenopausal women, the onset of anovulatory cycles represents a continuation of declining ovarian function. These patients need to be educated regarding the specific health risks associated with menopause so that an early proactive approach toward the prevention of menopause associated conditions such as osteoporosis can be initiated. In addition to the use of hormone replacement therapy for cycle control, important lifestyle changes include exercise, dietary modification, and smoking cessation. The incidence of endometrial carcinoma in women ages 40-49 years was 36.2 per 100,000 in 1995. Therefore, all women older than 40 years who present with suspected anovulatory uterine bleeding should be evaluated with endometrial assessment (after pregnancy has been excluded). Women who have failed medical therapy and no longer desire future childbearing are candidates for endometrial ablation, which appears to be an efficient and cost-effective treatment to hysterectomy for anovulatory uterine bleeding. However, endometrial ablation may not be definite therapy.

Medical versus Surgical Management:

Women who experience acute, profuse anovulatory bleeding are candidates for estrogen therapy. In approximately 90% of cases, acute bleeding does not require surgical intervention, but it can be treated with medical therapy. Conjugated equine estrogen therapy can be administered intravenously (25 mg every 4 hours for 24 hours). However, oral conjugated estrogen therapy at 10-20 mg per day in four divided doses can be substituted for intravenous estrogen administration. Patients who do not respond to 1-2 doses of estrogen with a significant decline in blood loss or are not hemodynamically stable should undergo dilatation and curettage. Furthermore, high dose estrogen therapy is commonly associated with nausea, concomitant medical therapy with antiemetics should be considered. After the acute episode of bleeding has been controlled, amenorrhea should be maintained for several weeks to allow for resolution of anemia. The best method of therapy is a combination oral contraceptive. To extend the interval before next menses, continuous oral contraceptives (without the use of placebo pills) can be given for several months; however, over time the patient will be susceptible again to breakthrough bleeding. Once patient's anemia has resolved, cyclic oral contraceptives can be prescribed. All anemic patients should be given iron therapy.

Currently, there are few randomized trials comparing medical versus surgical therapy for anovulatory uterine bleeding. Few randomized trial that compared endometrial resection with medical management for women with menorrhagia found that women who underwent medical therapy were less likely to be satisfied with their therapy. However, because of its reduced cost and risks, medical therapy should be offered before surgical intervention unless it is otherwise contraindicated. Surgical therapy is indicated for women with excessive anovulatory bleeding in whom medical management has failed and who have completed their childbearing. Avoidance of anemia, reduction of excessively heavy bleeding, and increased, though imperfect, predictability of bleeding are appropriate goals to attempt to achieve with medical therapy. Success or failure of medical therapy should be defined in partnership with the patient, to better achieve the therapeutic goal.

Efficacy among Surgical Techniques:

The surgical options include hysterectomy and endometrial ablation. Recent studies have reported morbidity rates of 7% and 15% for women undergoing hysterectomy for various indications. The overall mortality rate for hysterectomy is 12 deaths per 10,000 procedures, for all surgical indications. A surgical alternative to hysterectomy is endometrial ablation. Endometrial ablation can be performed with or without the assistance of hysteroscopy. Hysteroscopic-assisted endometrial ablation can be performed with the resectoscope. Using the resectoscope, the endometrium can be removed or resected with an electrocautery loop or ablated with the roller-ball. Endometrial ablation also can be accomplished with the YAG laser. The most frequently reported complications of hysteroscopy are uterine perforation, which occurs in approximately 14 per 1,000 procedures and fluid overload, which occurs in approximately 2 per 1,000 cases. Women with anovulatory uterine bleeding are candidates for endometrial ablation if they have failed medical therapy and have completed their childbearing. The proportion of women who are amenorrheic after undergoing and endometrial ablation is approximately 45% and the percentage of women at 12 months postoperatively who are satisfied with their therapy approaches 90%. This high degree of satisfaction indicates that reduction of flow is adequate symptom control for most women, and achievement of amenorrhea is not as important.

Numerous studies have compared costs and surgical outcomes between endometrial resection or ablation and hysterectomy. The evidence suggests that hysteroscopic endometrial ablation results in less morbidity and shorter recovery periods and is more cost effective than hysterectomy. However, if as many as one third of women who undergo endometrial ablation undergo hysterectomy within the following 5 years that would have a significant impact on these cost analysis. The long-term satisfaction of women who have undergone endometrial ablation has been questioned. In a 3-year follow-up study, 8.5% of women who had undergone endometrial ablation later underwent repeat ablation, and an additional 8.5% had undergone hysterectomy. In a 5-year follow-up study, 34% of women who had undergone hysteroscopic ablation subsequently had a hysterectomy. Because women who undergo endometrial ablation can have residual active endometrium, these women should receive progestogen if they are prescribed estrogen replacement therapy.

Summary:

The treatment of choice for anovulatory uterine bleeding is medical therapy with oral contraceptives. Cyclic progestins also are effective. Women who have failed medical therapy and no longer desire future childbearing are candidates for endometrial ablation, which appears to be an efficient and cost-effective alternative treatment to hysterectomy for anovulatory uterine bleeding. However, endometrial ablation may not be definitive therapy. An underlying coagulopathy, such as von Willebrand's disease, should be considered in all patients (particularly adolescents) with abnormal bleeding, especially when bleeding is not otherwise easily explained or does not respond to medical therapy. Although there is limited evidence evaluating the efficacy of conjugated equine estrogen therapy in anovulatory bleeding, it is effective in controlling abnormal uterine bleeding.

Resources:

National Institutes of Health - Dysfunctional Uterine Bleeding