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Dysfunctional uterine bleeding is abnormal uterine bleeding that, after examination and ultrasonography, cannot be attributed to the usual causes (structural gynecologic abnormalities, cancer, inflammation, systemic disorders, pregnancy, complications of pregnancy, use of oral contraceptives or certain drugs). Treatment is usually with hormonal therapy, such as oral contraceptives.
Dysfunctional uterine bleeding (DUB), the most common cause of abnormal uterine bleeding, occurs most often in women > 45 (> 50% of cases) and in adolescents (20% of cases).
About 90% of cases are anovulatory; 10% are ovulatory.
Pathophysiology
During an anovulatory cycle, the corpus luteum does not form. Thus, the normal cyclical secretion of progesterone does not occur, and estrogen stimulates the endometrium unopposed. Without progesterone, the endometrium continues to proliferate, eventually outgrowing its blood supply; it then sloughs and bleeds incompletely, irregularly, and sometimes profusely or for a long time. When this abnormal process occurs repeatedly, the endometrium can become hyperplastic, sometimes with atypical or cancerous cells.
In ovulatory DUB, progesterone secretion is prolonged; irregular shedding of the endometrium results, probably because estrogen levels remain low, near the threshold for bleeding (as occurs during menses). In obese women, ovulatory DUB can occur if estrogen levels are high, resulting in amenorrhea alternating with irregular or prolonged bleeding.
Complications:
Chronic bleeding may cause iron deficiency anemia. If DUB is due to chronic anovulation, infertility may also be present.
Etiology
Anovulatory DUB can result from any disorder or condition that causes anovulation (see Table 1: Menstrual Abnormalities: Some Causes of Anovulatory Amenorrhea ). Anovulation is most often secondary to polycystic ovary syndrome or is idiopathic (sometimes occurring when gonadotropin levels are normal); sometimes anovulation results from hypothyroidism. During perimenopause, DUB may be an early sign of ovarian failure; follicles are still developing but, despite increasing levels of follicle-stimulating hormone (FSH), do not produce enough estrogen to trigger ovulation. About 20% of women with endometriosis (see Endometriosis) have anovulatory DUB due to unknown mechanisms.
Ovulatory DUB may occur in polycystic ovary syndrome (because progesterone secretion is prolonged) or in endometriosis, which does not affect ovulation. Other causes are a short follicular phase and luteal phase dysfunction (due to inadequate progesterone stimulation of the endometrium); a rapid decrease in estrogen before ovulation can cause spotting.
Symptoms and Signs
Compared with typical menses, bleeding may occur more frequently (< 21 days apart—polymenorrhea), last longer or involve more blood loss (> 7 days or > 80 mL—menorrhagia, or hypermenorrhea), or occur frequently and irregularly between menses (metrorrhagia).
Ovulatory DUB tends to cause excessive bleeding during regular menstrual cycles. Women may have other symptoms of ovulation, such as premenstrual symptoms, breast tenderness, midcycle cramping pain (mittelschmerz), a change in basal body temperature with ovulation (see Infertility: Ovulatory Dysfunction), and sometimes dysmenorrhea. Anovulatory DUB occurs at unpredictable times and in unpredictable patterns and is not accompanied by cyclic changes in basal body temperature.
Diagnosis
Women should be evaluated for DUB when the amount or timing of vaginal bleeding is inconsistent with normal menses. DUB is a diagnosis of exclusion; other conditions that can cause similar bleeding must be excluded (see Symptoms of Gynecologic Disorders: Vaginal Bleeding).Pregnancy should be excluded, even in young adolescents and perimenopausal women. Coagulation disorders should be considered, particularly in adolescents who have anemia or require hospitalization for bleeding. Regular cycles with prolonged or excessive bleeding (possible ovulatory DUB) suggest structural abnormalities.
Laboratory testing:
Several tests are typically done:
All women of reproductive age should have a pregnancy test. CBC is routinely done. However, Hct may be normal in women who report heavy bleeding, or anemia may be severe in women who regularly have heavy periods.
Thyroid-stimulating hormone levels are usually measured, and prolactin levels are measured, even when galactorrhea is absent, because thyroid disorders and hyperprolactinemia are common causes of abnormal bleeding. To determine whether bleeding is anovulatory or ovulatory, some clinicians measure serum progesterone levels during the luteal phase (after day 14 of a normal menstrual cycle or after basal body temperature increases, as occurs during this phase). A level of ≥ 3 ng/mL (≥ 9.75 nmol/L) suggests that ovulation has occurred.
Other tests are done depending on results of the history and physical examination and include the following:
If all clinically indicated tests are normal, the diagnosis is DUB.
Additional testing:
Transvaginal ultrasonography is done if women have any of the following:
These criteria include almost all women with DUB.
Transvaginal ultrasonography can detect structural abnormalities, including most masses and focal thickening of the endometrium. If focal thickening is detected, hysteroscopy or saline-infusion sonohysterography may be needed to identify smaller intrauterine masses (eg, endometrial polyps, submucous myomas).
Endometrial sampling is usually recommended to rule out hyperplasia or cancer in women with any of the following:
Directed biopsy (with hysteroscopy) may be done to visualize the endometrial cavity directly and target the abnormal tissue.
Treatment
Bleeding:
Patients with very heavy bleeding (which is uncommon) are stabilized hemodynamically with IV crystalloid fluid, blood products, and other measures as needed. If bleeding persists, a bladder catheter is inserted into the uterus and inflated with 30 mL of water to tamponade the bleeding. Once patients are stable, hormonal therapy is used to control bleeding.
For anovulatory DUB with very heavy bleeding, conjugated estrogens 25 mg IV q 4 to 6 h for a total of 4 doses may be used. Immediately afterward, women are given a combination (estrogen/progestin) oral contraceptive, which may be continued until bleeding abates. Otherwise, anovulatory DUB is usually treated with combination oral contraceptives (see Family Planning: Oral Contraceptives). Depending on the severity of bleeding, an oral contraceptive can be given bid or tid for 5 to 6 days, then once/day. After acute bleeding is controlled, a combination oral contraceptive is given continually for about 3 mo to prevent recurrence.
Other options include a levonorgestrel-releasing intrauterine device (IUD), depot medroxyprogesterone acetate injections, and cyclic use of a progestin (eg, medroxyprogesterone acetate 5 to 10 mg po once/day, norethindrone 5 mg po once/day for 10 to 14 days/mo). These treatments may be indicated when estrogen is contraindicated or when spontaneous cyclic menses do not resume after 3 mo of oral contraceptive therapy.
If pregnancy is desired and bleeding is not heavy, ovulation induction with clomiphene (50 mg po on days 5 through 9 of the menstrual cycle) can be tried.
Endometrial ablation (eg, using freezing or burning) may help control bleeding (in 60 to 80%). If this treatment does not control bleeding, bleeding is usually caused by adenomyosis and thus is not DUB.
Hysteroscopy with D & C may be therapeutic as well as diagnostic; it may be the treatment of choice when anovulatory bleeding is severe or when hormone therapy is ineffective. Structural causes such as polyps or fibroids may be identified or removed during hysteroscopy. This procedure may decrease bleeding but, in some women, causes amenorrhea due to endometrial scarring (Asherman's syndrome).
For ovulatory DUB, oral contraceptives are usually effective. Other options include NSAIDs given during menses, ovarian suppression with depot leuprolide, depot medroxyprogesterone acetate, and a levonorgestrel-releasing IUD.
Endometrial hyperplasia:
In postmenopausal women, atypical adenomatous endometrial hyperplasia is usually treated with hysterectomy. In premenopausal women, it is treated with medroxyprogesterone acetate 20 to 40 mg po once/day for 3 to 6 mo.
If repeat endometrial sampling indicates resolution of hyperplasia, women may be given cyclic medroxyprogesterone acetate (5 to 10 mg po once/day for 10 to 14 days each month) or, if pregnancy is desired, clomiphene. If sampling shows persistent or progressive atypical hyperplasia, hysterectomy is necessary.
More benign cystic or adenomatous hyperplasia can usually be treated with high-dose cyclic progesterone therapy (eg, cyclic medroxyprogesterone acetate); sampling is repeated after about 3 mo.
Last full review/revision January 2010 by JoAnn V. Pinkerton, MD
Content last modified January 2010
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