Abnormal uterine bleeding includes abnormal menstrual bleeding and bleeding due to other causes such as pregnancy, systemic disease, or cancer. The diagnosis and management of abnormal uterine bleeding present some of the most difficult problems in gynecology. Patients may not be able to localize the source of the bleeding from the vagina, urethra, or rectum. In childbearing women, a complication of pregnancy must always be considered, and one must always remember that more than 1 entity may be present, such as uterine myomas and cervical cancer.
Patterns of Abnormal Uterine Bleeding
The standard classification for patterns of abnormal bleeding recognizes 7 different patterns.
Menorrhagia (hypermenorrhea) is heavy or prolonged menstrual flow. The presence of clots may not be abnormal but may signify excessive bleeding. “Gushing” or “open-faucet” bleeding is always abnormal. Submucous myomas, complications of pregnancy, adenomyosis, IUDs, endometrial hyperplasias, malignant tumors, and dysfunctional bleeding are causes of menorrhagia.
Hypomenorrhea (cryptomenorrhea) is unusually light menstrual flow, sometimes only spotting. An obstruction such as hymenal or cervical stenosis may be the cause. Uterine synechiae (Asherman's syndrome) can be causative and are diagnosed by a hysterogram or hysteroscopy. Patients receiving oral contraceptives occasionally complain of light flow and can be reassured that this is not significant.
Metrorrhagia (intermenstrual bleeding) is bleeding that occurs at any time between menstrual periods. Ovulatory bleeding occurs midcycle as spotting and can be documented with basal body temperatures. Endometrial polyps and endometrial and cervical carcinomas are pathologic causes. In recent years, exogenous estrogen administration has become a common cause of this type of bleeding.
Polymenorrhea describes periods that occur too frequently. This usually is associated with anovulation and rarely with a shortened luteal phase in the menstrual cycle.
Menometrorrhagia is bleeding that occurs at irregular intervals. The amount and duration of bleeding also vary. Any condition that causes intermenstrual bleeding can eventually lead to menometrorrhagia. Sudden onset of irregular bleeding episodes may be an indication of malignant tumors or complications of pregnancy.
Oligomenorrhea describes menstrual periods that occur more than 35 days apart. Amenorrhea is diagnosed if no menstrual period occurs for more than 6 months. Bleeding usually is decreased in amount and associated with anovulation, either from endocrine causes (eg, pregnancy, pituitary-hypothalamic causes, menopause) or systemic causes (eg, excessive weight loss). Estrogen-secreting tumors produce oligomenorrhea prior to other patterns of abnormal bleeding.
Contact bleeding (postcoital bleeding) is self-explanatory but must be considered a sign of cervical cancer until proved otherwise. Other causes of contact bleeding are much more common, including cervical eversion, cervical polyps, cervical or vaginal infection (eg, Trichomonas), or atrophic vaginitis. A negative cytologic smear does not rule out invasive cervical cancer, and colposcopy, biopsy, or both may be necessary.
Evaluation of Abnormal Uterine Bleeding
Detailed history, physical examination, cytologic examination, pelvic ultrasound, and blood tests are the first steps in the evaluation of abnormal uterine bleeding. The main aim of the blood tests is to exclude a systemic disease, pregnancy, or a trophoblastic disease. The blood tests usually include complete blood count, assay of the β subunit of human chorionic gonadotropin (hCG), and thyroid-stimulating hormone (TSH).
Many causes of bleeding are strongly suggested by the history alone. Note the amount of menstrual flow, the length of the menstrual cycle and menstrual period, the length and amount of episodes of intermenstrual bleeding, and any episodes of contact bleeding. Note also the last menstrual period, the last normal menstrual period, age at menarche and menopause, and any changes in general health. The patient must keep a record of bleeding patterns to determine whether bleeding is abnormal or only a variation of normal. However, most women have an occasional menstrual cycle that is not in their usual pattern. Depending on the patient's age and the pattern of the bleeding, observation may be all that is necessary.
Abdominal masses and an enlarged, irregular uterus suggest myoma. A symmetrically enlarged uterus is more typical of adenomyosis or endometrial carcinoma. Atrophic and inflammatory vulvar and vaginal lesions can be visualized, and cervical polyps and invasive lesions of cervical carcinoma can be seen. Rectovaginal examination is especially important to identify lateral and posterior spread or the presence of a barrel-shaped cervix. In pregnancy, a decidual reaction of the cervix may be the source of bleeding. The appearance is a velvety, friable erythematous lesion on the ectocervix.
Although most useful in diagnosing asymptomatic intraepithelial lesions of the cervix, cytologic smears can help screen for invasive cervical (particularly endocervical) lesions. Although cytology is not reliable for the diagnosis of endometrial abnormalities, the presence of endometrial cells in a postmenopausal woman is abnormal unless she is receiving exogenous estrogens. Likewise, women in the secretory phase of the menstrual cycle should not shed endometrial cells. Of course, a cytologic examination that is positive or suspicious for endometrial cancer demands further evaluation.
Tubal or ovarian cancer can be suspected based on a cervical smear. The technique of obtaining a smear is important, because a tumor may be present only in the endocervical canal and may not shed cells to the ectocervix or vagina. Laboratories should report the presence or absence of endocervical cells. The current use of a spatula and endocervical brush has significantly increased the adequacy of cytologic smears from the cervix. Any abnormal smear requires further evaluation (see Chapter 48).
Pelvic ultrasonography has become an integral part of the gynecologic pelvic examination. The scan can be performed either transvaginally or transabdominally. The transvaginal examination is performed with an empty bladder and enables a closer look with greater details at the pelvic organs. The transabdominal examination is performed with a full bladder and enables a wider, but less discriminative, examination of the pelvis. The ultrasound scan can add many details to the physical examination, such as a description of the uterine lining and its width and regularity (Fig. 38–1) and the presence of intramural or submucous fibroids (Fig.38–1), intrauterine polyps, and adnexal masses. Persistent thick and irregular endometrium is one of the preoperative predictors of endometrial pathology and demands further evaluation and tissue biopsy.
Typical ultrasound scan of a uterine fibroid (A) and normal endometrial lining (B).
Sonohysterography is a modification of the pelvic ultrasound scan. The ultrasound is performed following injection of saline by a thin catheter into the uterus. This technique increases significantly the sensitivity of transvaginal ultrasonography and has been used to evaluate the endometrial cavity for polyps, fibroids, and other abnormalities.
Methods of endometrial biopsy include use of the Novak suction curette, the Duncan curette, the Kevorkian curette, or the Pipelle. Cervical dilatation is not necessary with these instruments. Small areas of the endometrial lining are sampled.
If bleeding persists and no cause of bleeding can be found or if the tissue obtained is inadequate for diagnosis, hysteroscopy and, in some cases, formal dilatation and curettage (D&C) must be performed.
Placing an endoscopic camera through the cervix into the endometrial cavity allows direct visualization of the cavity (Fig. 38–2). Because of its higher diagnostic accuracy and suitability for outpatient investigation, hysteroscopy is increasingly replacing D&C for the evaluation of abnormal uterine bleeding. Hysteroscopy currently is regarded as the gold standard evaluation of pathology in the uterine cavity. Resection attachments allow immediate capability to remove or biopsy lesions.
Hysteroscopic view of the uterine cavity.
For many years, D&C has been regarded as the gold standard for the diagnosis of abnormal uterine bleeding. It can be performed with the patient under local or general anesthesia, almost always in an outpatient or ambulatory setting. With general anesthesia, relaxation of the abdominal musculature is greater, allowing for a more thorough pelvic examination, more precise evaluation of pelvic masses, and more complete curettage. Nevertheless, D&C is a blind procedure, and its accuracy, particularly when the cause of the abnormal uterine bleeding is a focal lesion such as a polyp, is debatable.
General Principles of Management (Fig. 38–3)
General principles of management of abnormal uterine bleeding. IUS-LNG, intrauterine system-levonorgestrel releasing.
In making the diagnosis, it is important not to assume the obvious. A careful history and pelvic examination are vital. The possibility of pregnancy must be considered, as well as use of oral contraceptives, IUDs, and hormones.
Another important evaluation during the workup of abnormal uterine bleeding is to decide whether the bleeding is associated with ovulatory or anovulatory cycles. In ovulatory cycles, the bleeding might be due to a persistent corpus luteum cyst or short luteal phase. In anovulatory cycles, the endometrium outgrows its blood supply, partially breaks down, and is sloughed in an irregular manner. In these cases, an organic cause of anovulation must be excluded (eg, thyroid or adrenal abnormalities). Conversion from proliferative to secretory endometrium (by combined oral contraceptive pills or progesterone in the luteal phase) corrects most acute and chronic bleeding problems.
Improved diagnostic techniques and treatment have resulted in decreased use of hysterectomy to treat abnormal bleeding patterns. If pathologic causes (eg, submucous myomas, adenomyosis) can be excluded, if there is no significant risk for cancer development (as from atypical endometrial hyperplasia), and if there is no acute life-threatening hemorrhage, most patients can be treated with hormone preparations or minimally invasive procedures, which are considered as alternatives to hysterectomy. Myomectomy (hysteroscopic, laparoscopic, or conservative) can be suggested for treatment of myoma if the patient wishes to retain her childbearing potential. Endometrial ablation and endometrial resection may offer successful outpatient and in-office alternatives.
For menorrhagia, antifibrinolytic therapy has been shown to significantly decrease blood loss during menses, as have prostaglandin synthetase inhibitors. Long-acting intramuscular progestin administration (Depo-Provera) can be given but may result in erratic bleeding or even amenorrhea. Finally, levonorgestrel-releasing IUDs are as effective as endometrial resection in decreasing blood loss.
Abnormal Bleeding Due to Nongynecologic Diseases & Disorders
In the differential diagnosis of abnormal bleeding, nongynecologic causes of bleeding (eg, rectal or urologic disorders) must be ruled out, because patients may have difficulty differentiating the source of bleeding. Gynecologic and nongynecologic causes of bleeding may coexist. Systemic disease may cause abnormal uterine bleeding. For example, myxedema usually causes amenorrhea, but less severe hypothyroidism is associated with increased uterine bleeding. Liver disease interferes with estrogen metabolism and may cause variable degrees of bleeding. Both of these conditions are usually clinically apparent before gynecologic symptoms appear. Blood dyscrasias and coagulation abnormalities can also produce gynecologic bleeding. Patients receiving anticoagulants or adrenal steroids may expect abnormalities. Extreme weight loss due to eating disorders, exercise, or dieting may be associated with anovulation and amenorrhea.
Dysfunctional Uterine Bleeding
Exclusion of all possible pathologic causes of abnormal bleeding establishes the diagnosis of dysfunctional uterine bleeding (nearly 60% of cases). Dysfunctional bleeding occurs most commonly at the extremes of reproductive age (20% of cases occur in adolescents and 40% in patients over age 40 years). Management depends on the age of the patient (adolescent, young woman, or premenopausal woman).
Because the first menstrual cycles frequently are anovulatory, the menses not unusually are irregular, and explanation of the reason is all the treatment that is necessary. Heavy bleeding—even hemorrhage—may occur. Invasive diagnostic procedures usually are not necessary in young patients, but physical (pelvic or rectal if possible) examination, pelvic ultrasonography, and basic blood tests must be performed to exclude pregnancy or pathologic conditions. Estrogens given orally should be adequate for all patients except extremely rare cases requiring curettage to control hemorrhage. Numerous regimens are available, including estrogens followed by progesterone, progesterone alone, or combination oral contraceptives. For acute hemorrhage, high-dose estrogen given intravenously (25 mg conjugated estrogen every 4 hours) gives rapid response. In hemodynamically stable patients, the oral dose of conjugated estrogens is 2.5 mg every 4–6 hours for 14–21 days. Once bleeding has stopped, medroxyprogesterone acetate 5 mg once or twice per day should be given for 7–10 days.
Oral contraceptives, 3–4 times the usual dose, are just as effective and may be simpler to use than sequential hormones. Again, the dose is lowered after a few days, and the lower dose is continued for the next few cycles, particularly to raise the hemoglobin levels in an anemic patient. Medroxyprogesterone acetate 10 mg/d for 10 days can be given to patients who have proliferative endometrium on biopsy. In patients receiving cyclic therapy, 3–6 monthly courses are usually administered, after which treatment is discontinued and further evaluation performed if necessary. In adolescents in whom the bleeding is not severe, oral contraceptives can be used as normally prescribed.
In patients 20–30 years old, pathologic causes are similarly not very common, and the appropriate diagnostic procedures should be considered after the initial evaluation by history, physical and cytologic examination, and pelvic ultrasound. Hormonal management is the same as for adolescents.
In the later reproductive years, even more care must be given to excluding pathologic causes because of the possibility of endometrial cancer. The initial evaluation should be complemented by hysteroscopy and endometrial biopsy and should clearly establish anovulatory or dyssynchronous cycles as the cause before hormonal therapy is started. Recurrences of abnormal bleeding demand further evaluation.
For patients whose bleeding cannot be controlled with hormones, who are symptomatically anemic, and whose lifestyle is compromised by persistence of irregular bleeding, D&C may temporarily stop bleeding. If bleeding persists, levonorgestrel-releasing IUDs or a minimally invasive procedure such as endometrial ablation may be offered. Studies have shown that approximately 80% of patients scheduled for hysterectomy changed their minds following endometrial ablation. However, if these minimally invasive procedures fail or if the patient prefers a definitive solution, hysterectomy may be necessary. Definitive surgery may also be needed for coexistent endometriosis, myoma, and disorders of pelvic relaxation.
Postmenopausal bleeding may be defined as bleeding that occurs after 12 months of amenorrhea in a middle-aged woman. When amenorrhea occurs in a younger person for 1 year and premature ovarian failure or menopause has been diagnosed, episodes of bleeding may be classified as postmenopausal, although resumption of ovulatory cycles can occur. Follicle-stimulating hormone (FSH) levels are particularly helpful in the differential diagnosis of menopausal versus hypothalamic amenorrhea. An FSH level greater than 30 mIU/mL is highly suggestive of menopause.
Postmenopausal bleeding is more likely to be caused by pathologic disease than is bleeding in younger women and must always be investigated. Nongynecologic causes must be excluded; these causes are more likely to result from pathologic disease in older women, and patients may be unable to determine the site of bleeding. The source of bleeding should not be assumed to be nongynecologic unless there is good evidence or proper evaluation has excluded gynecologic causes.
Neither normal (“functional”) bleeding nor dysfunctional bleeding should occur after menopause. Although pathologic disorders are more likely, other causes may also occur. Atrophic or proliferative endometrium is not unusual. Secretory patterns should not occur unless the patient has resumed ovulation or has received progesterone therapy. After nongynecologic causes of bleeding are excluded, gynecologic causes must be considered.
The most common cause of postmenopausal uterine bleeding is the use of exogenous hormones. In the past, face creams and cosmetics contained homeopathic amounts of estrogens, but today, this cause is highly unlikely. Careful history taking becomes vital, because patients may not follow specific instructions on the use of estrogen and progesterone therapy.
In light of the new caution placed on postmenopausal hormone replacement therapy (HRT) because of cardiovascular risks, long-term estrogen/progesterone administration for prevention of osteoporosis is no longer recommended. Women continue HRT for menopausal symptoms to improve their quality of life. Regular menstrual bleeding may resume if they take HRT agents cyclically. Not uncommonly, these patients present with vaginal bleeding as many as 6–12 months after initiation of HRT. If bleeding is still occurring by that time, further investigation is warranted to determine its etiology. If endometrial hyperplasia is found, specific attention must be paid to the presence of atypia and treatment started by increasing the progesterone component or by hysterectomy.
Vaginal Atrophy & Vaginal & Vulvar Lesions
Bleeding from the lower reproductive tract almost always is related to vaginal atrophy, with or without trauma. Examination reveals thin tissue with ecchymosis. Rarely, a tear at the introitus or deep in the vagina requires suturing. With vulvar dystrophies, a white area and cracking of the skin of the vulva may be present. Cytologic study of material obtained from the cervix and vagina will reveal immature epithelial cells with or without inflammation. After coexisting upper tract lesions are excluded, treatment can include local or systemic estrogen therapy for vaginal lesions. Vulvar lesions require further diagnostic evaluation to determine the proper treatment.
Tumors of the Reproductive Tract
The differential diagnosis of organic causes of postmenopausal uterine bleeding includes endometrial hyperplasias (simple, complex, and atypical), endometrial polyps, endometrial carcinoma or other more rare tumors such as cervical or endocervical carcinoma, uterine sarcomas (including mixed mesodermal and carcinosarcomas), and, even more rarely, uterine tube and ovarian cancer. Estrogen-secreting ovarian tumors also should be considered.
Uterine sampling must be done and tissue obtained. Endocervical curettage should be performed, along with any endometrial sampling technique. If a diagnosis cannot be established or is questionable with office procedures, D&C is necessary. Hysteroscopy performed in the office or operating room may prove helpful in locating endometrial polyps or fibroids that could be missed even by fractional curettage. Pelvic ultrasonography may be extremely helpful in the diagnosis of ovarian tumors and in evaluation of the thickness of the endometrium, as well as in discerning between uterine myomas and adnexal tumors. Recurring episodes of postmenopausal bleeding may rarely require hysterectomy, even when a diagnosis cannot be established by endometrial sampling.
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