Joseph C. Gambone
Dysfunctional uterine bleeding (DUB) is defined as abnormal uterine bleeding (AUB) in women between menarche and menopause that cannot be attributed to medications, blood dyscrasias, systemic diseases, trauma, uterine neoplasms, or pregnancy. This form of AUB is almost always caused by aberrations in the hypothalamic-pituitary-ovarian hormonal axis resulting in anovulation. The diagnosis of DUB is made by excluding other treatable causes of AUB.
The bleeding is generally from a proliferative, or discordant (mixed), endometrium. In most cases, it is associated with anovulatory or oligo-ovulatory ovarian cycles (e.g., polycystic ovary syndrome), and estrogen levels are frequently unopposed by progesterone. On occasion, it occurs with apparently normal ovulatory cycles. It is one of the most common problems dealt with in the gynecologic clinic or private office.
Abnormal bleeding patterns are defined in Box 33-1. Taken together, these abnormal patterns are sometimes designated as menometrorrhagia.
BOX 33-1 Common Abnormal Bleeding Patterns
• Polymenorrhea: abnormally frequent menses at intervals of <24 days
• Menorrhagia (hypermenorrhea): excessive and/or prolonged menses (>80 mL and >7 days) occurring at normal intervals
• Metrorrhagia: irregular episodes of uterine bleeding
• Menometrorrhagia: heavy and irregular uterine bleeding
• Intermenstrual bleeding: scant bleeding at ovulation for 1 or 2 days
Most DUB occurs during the years around the menarche (11 to 14 years of age) or menopause (45 to 50 years of age). During the perimenopausal years, the anovulatory bleeding is mainly caused by the declining functional capacity of the ovary. In adolescence, the anovulatory bleeding may be caused by a failure of the hypothalamic-pituitary system to respond to the positive feedback effect of estrogen.
Abnormalities of menstrual bleeding are thought to be associated with alterations in endometrial vascular homeostasis. A normally efficient menstrual cycle is discussed in detail in Chapter 4, and the normal events are briefly summarized as follows.
First, gradually increasing estrogen levels support and maintain the growth of endometrium during the proliferative phase of the cycle. The proliferative phase is variable in length, but it generally lasts 13 days from the onset of menses to the luteinizing hormone surge. The increasing level of estrogen supports growth, prevents breakthrough bleeding, and stimulates an increase in endometrial progesterone receptors.
Second, about 24 hours after the luteinizing hormone surge, ovulation occurs, and the corpus luteum forms. It produces estrogen and progesterone in increasing amounts and lasts for about 14 days unless an intervening pregnancy prolongs it by secretion of human chorionic gonadotropin (hCG). With the demise of the corpus luteum, the levels of estrogen and progesterone fall precipitously, and the decidual portion of the endometrium desquamates.
Third, during the luteal phase of the endometrial cycle, there is a marked increase in tissue levels of prostaglandin F2α, which is a powerful vasoconstrictor, and this eventually leads to endometrial ischemia. The process allows for a complete sloughing of the outer two thirds of the endometrium and avoids prolonged menstruation. During anovulatory cycles, the resulting nonsecretory endometrium contains less prostaglandin and is less apt to initiate an efficient menstrual period of short duration. The unopposed estrogenic effect is likely to result in cycles of irregular duration and prolonged menses. With repeated cycles of unopposed estrogen, endometrial hyperplasia or even cancer may develop.
The diagnosis of DUB is usually made by excluding other causes of AUB. A possible unexpected pregnancy should always be ruled out initially. Box 33-2 lists possible causes of AUB to be considered. A pelvic examinationmust be performed to verify that the source of bleeding is uterine and not the result of a cervical, rectal, vaginal, vulvar, or urethral lesion. Iatrogenic causes such as oral contraceptive–induced breakthrough bleeding or bleeding associated with an intrauterine device should be considered. Dyscrasias of the blood such as von Willebrand’s disease should be ruled out. Systemic diseases such as liver, renal, or thyroid conditions may represent treatable causes of AUB. Trauma, although unusual, is an occasional cause of vaginal and even uterine bleeding and should be considered at the time of the pelvic examination. Organic causes of AUB include tumors, infections, and complications of pregnancy. Benign tumors and growths include endocervical and endometrial polyps, leiomyomas (uterine fibroids), adenomyosis, and endometrial hyperplasia. Malignant neoplastic conditions include cervical and uterine cancers. Infections that may cause AUB include cervicitis, endometritis, and pelvic inflammatory disease.
BOX 33-2 Nondysfunctional Causes of Abnormal Uterine Bleeding
Exogenous estrogen (e.g., oral contraceptives)
Heparin, sodium warfarin (Coumadin)
Von Willebrand’s disease
Hepatic disease (impaired metabolism of estrogens)
Renal disease (hyperprolactinemia)
Complications of pregnancy
Malignancies of cervix or corpus
Two investigations are most useful for confirming DUB: a pelvic ultrasound and an endometrial biopsy. If they are both normal and show nothing more than a nonsecretory endometrium, a presumptive diagnosis of DUB is highly likely. Other tests and procedures that may be useful to exclude other causes of AUB are listed in Box 33-3.
BOX 33-3 Evaluation of a Patient Who May Have Dysfunctional Uterine Bleeding
Complete blood count
Serum iron and iron-binding globulin
Coagulation studies (prothrombin time and partial thromboplastin time)
Urinary human chorionic gonadotropin assay
Thyroid function studies
Liver function studies
Serum follicle-stimulating hormone levels
Cervical cytology (Papanicolaou smear)
Pipelle (flexible syringe suction curette)
Office curette (Novak, Randall type)
Vacuum (Vabra) curette
Pelvic ultrasonic imaging
Hysteroscopy, hysterosonogram, and/or dilation and curettage
∗ Used selectively based on history and physical examination.
The management of DUB becomes relatively clear once other, more serious causes of bleeding have been excluded, particularly endometrial or cervical cancer. For less significant bleeding, observation and expectant management may be reasonable. Box 33-4 lists the appropriate hormonal management of significant DUB.
BOX 33-4 Hormonal Management of Dysfunctional Uterine Bleeding
Massive Intractable Bleeding
Administer 25 mg IV of conjugated estrogens.
Continued Management after Massive Bleeding Has Abated
Administer conjugated estrogens, 2.5 mg orally daily for 25 days.∗ May double the dose if bleeding recurs or increases.
Add 10 mg of medroxyprogesterone acetate (MPA)† for the last 10 days of treatment.
Allow 5 to 7 days for withdrawal bleeding.
Administer the Mirena intrauterine system, which releases levonorgestrel through an intrauterine device.
Management of Moderate Menometrorrhagia
Administer conjugated estrogen,∗ 1.25 mg orally each day for 25 days with 10 mg MPA† orally for the last 10 days of the estrogen treatment.
Administer oral contraceptive (e.g., Brevicon)‡ for 21 days, with a 7-day withdrawal.
Administer MPA†, 10 mg orally each day for 10 to 15 days each month, usually for a 3-month trial; a 5- to 7-day period of menstrual withdrawal should follow cessation of the MPA each month.
Mirena Intrauterine System with Levonorgestrel-Releasing Intrauterine Device
∗ May substitute other oral estrogen (e.g., ethinyl estradiol, 0.02 mg).
† May substitute other progestin (e.g., Megace, 5 mg).
‡ May substitute other combined oral contraceptives and may increase dose up to 4 tablets daily for heavier bleeding.
Heavy endometrial hemorrhage from menarche through the perimenopause may require high-dose estrogens (sometimes given intravenously) to support the endometrium and diminish bleeding. If the bleeding substantially abates, lower-dose oral estrogen followed by, or in combination with, a progestin can then be initiated. If the bleeding is unremitting, dilation and curettage may be necessary.
The more common and less urgent type of DUB is best managed by cyclic estrogens with a progestin added in the latter 10 to 15 days of the 25-day estrogen cycle (see Box 33-4). A 5- to 7-day withdrawal bleed is expected each month as the medications are withdrawn on the 21st or 25th day. The cycle is repeated each month for 3 to 6 months, after which a normal pattern may be spontaneously established. Oral contraceptives should not be used for women in their 40s who are smokers, because of the high content of estrogens and their association with thrombophlebitis and myocardial infarction. Cyclic progestins alone may be used for younger patients who are likely to have sufficient endogenous estrogens to prime the endometrial progesterone receptors. The Mirena intrauterine system, which releases levonorgestrel, has been reported to be useful for treating DUB. It has a 55% 5-year continuation rate and a 30% early discontinuation rate in women being treated for DUB. These drugs are unlikely to be effective after prolonged bleeding. Only when these measures are ineffective should a dilation and curettage or hysteroscopy and biopsy be performed.
For older patients who do not respond to medical therapy and who do not anticipate later pregnancies, more radical and potentially permanent therapeutic measures may be considered. Endometrial ablation at the time of hysteroscopy provides an amenorrhea rate of up to 75% and relief of excessive bleeding in most of the remainder. However, about 10% continue to have bleeding problems. Vaginal hysterectomy may be appropriate for women who have associated problems such as pelvic relaxation or severe dysmenorrhea or for patients who are refractory to endometrial ablation.
Although DUB is annoying or even distressing, it is seldom life-threatening. Conservative treatment, after a thorough evaluation, is generally successful, although it may extend over several months, and the problem may recur.
It is important rule out unsuspected pregnancies and genital tract cancers, reserving hysterectomy for those patients with significant precancerous lesions or refractory problems.
Association of Professors of Gynecology and Obstetrics. Clinical Management of Abnormal Uterine Bleeding, Educational Series on Women’s Health Issues. Boston: Jespersen and Associates; 2002.
Hillard P.J.A. Benign diseases of the female reproductive tract. In: Berek J.S., editor. Berek and Novak’s Gynecology. 14th ed. Philadelphia: Lippincott Williams & Wilkins; 2007:461-467.
Mukherjee K., Jones K. The treatment of DUB with Mirena IUS: A survival analysis. Gynecol Surg. 2005;2:251-254.