Chapter 38. Complications of Menstruation & Abnormal Uterine Bleeding

Essentials of Diagnosis

• Symptoms include mood symptoms (irritability, mood swings, depression, anxiety), physical symptoms (bloating, breast tenderness, insomnia, fatigue, hot flushes, appetite changes), and cognitive changes (confusion and poor concentration).
• Symptoms must occur in the second half of the menstrual cycle (luteal phase).
• There must be a symptom-free period of at least 7 days in the first half of the cycle.
• Symptoms must occur in at least 2 consecutive cycles.
• Symptoms must be severe enough to require medical advice or treatment.

General Considerations

Premenstrual syndrome (PMS) has been defined as “the cyclic occurrence of symptoms that are of sufficient severity to interfere with some aspects of life and that appear with consistent and predictable relationship to the menses.” Although the symptoms themselves are not unique, the restriction of the symptoms to the luteal phase of the menstrual cycle is pathognomonic of PMS. It is a psychoneuroendocrine disorder with biologic, psychological, and social parameters that is both difficult to define adequately and quite controversial. One major difficulty in detailing whether PMS is a disease or a description of physiologic changes is its extraordinary prevalence. Up to 75% of women experience some recurrent PMS symptoms; 20–40% are mentally or physically incapacitated to some degree, and 5% experience severe distress. The highest incidence occurs in women in their late 20s to early 30s. PMS is rarely encountered in adolescents and resolves after menopause. Evidence suggests that women who have suffered with PMS and premenstrual dysphoric disorder are more likely to suffer from perimenopausal symptoms.

The symptoms of PMS may include headache, breast tenderness, pelvic pain, bloating, and premenstrual tension. More severe symptoms include irritability, dysphoria, and mood lability. When these symptoms disrupt daily functioning, they are clustered under the name premenstrual dysphoric disorder (PMDD).

Other symptoms commonly included in PMS are abdominal discomfort, clumsiness, lack of energy, sleep changes, and mood swings. Behavioral changes include social withdrawal, altered daily activities, marked change in appetite, increased crying, and changes in sexual desire. In all, more than 150 symptoms have been related to PMS. Thus the symptom complex of PMS has not been clearly defined.

Pathogenesis

The etiology of the symptom complex of PMS is not known, although several theories have been proposed, including estrogen–progesterone imbalance, excess aldosterone, hypoglycemia, hyperprolactinemia, and psychogenic factors. A hormonal imbalance previously was thought to be related to the clinical manifestations of PMS/PMDD, but in the most recent consensus, physiologic ovarian function is believed to be the trigger. This is supported by the efficacy of ovarian cyclicity suppression, either medically or surgically, in eliminating premenstrual complaints.

Further research has shown that serotonin (5-hydroxytryptamine [5-HT]), a neurotransmitter, is important in the pathogenesis of PMS/PMDD. Both estrogen and progesterone have been shown to influence the activity of serotonin and gamma-aminobutyric acid (GABA) centrally. Many of the symptoms of other mood disorders resembling the features of PMS/PMDD have been associated with serotonergic dysfunction. Disturbances in cortical GABA neuronal function and modulation by neuroactive steroids have been implicated as potentially important contributors to the pathogenesis of PMS/PMDD. GABA levels are decreased in women with PMS/PMDD during the late luteal phase compared with normal women.

Diagnosis

No objective screening or diagnostic tests for PMS and PMDD are available; thus special attention must be paid to the patient's medical history. Certain medical conditions (eg, thyroid disease and anemia) with symptoms that can mimic those of PMS/PMDD must be ruled out.

The patient is instructed to chart her symptoms during the month. According to the American College of Obstetricians and Gynecologists criteria, PMS can be diagnosed if the patient reports at least 1 affective symptom (depression, angry outbursts, irritability, anxiety, confusion, or social withdrawal) and somatic symptom (breast tenderness, abdominal bloating, headache, or swelling of extremities) during the 5 days before menses in each of the 3 prior menstrual cycles. These symptoms should be relieved within 4 days of the onset of menses, without recurrence until at least cycle day 13, and should be reproducible during 2 cycles of prospective recording.

Clinical Findings

A careful history and physical examination are most important to exclude organic causes of PMS localized to the reproductive, urinary, or gastrointestinal tracts. Most patients readily describe their symptoms, but careful questioning may be needed with some patients who may be reluctant to do so. Although it is important not to lead a patient to exaggerate her concerns, it is equally important not to minimize them.

Symptoms of PMS may be specific, well localized, and recurrent. They may be exacerbated by emotional stress. Migraine-like headaches may occur, often preceded by visual scotomas and vomiting. Symptomatology varies among patients but often is consistent in the same patient.

One of the most common symptoms of PMS is mastodynia, or mastalgia (pain, and usually swelling, of the breasts caused by edema and engorgement of the vascular and ductal systems). A positive correlation between degree of ductal dilatation and degree of breast pain has been documented. Mastodynia specifically refers to a cyclical occurrence of severe breast pain, usually in the luteal phase of the menstrual cycle, and it may be the primary symptom of this syndrome in some. It has been shown to be related to high gonadotropin levels. Estrogen stimulates the ductal elements, whereas progesterone stimulates the stroma. An augmented response to prolactin has also been suggested. Examination is always necessary to rule out neoplasm, although most malignant tumors are painless. The presence of solitary or multiple cystic areas suggests fibrocystic change. The diagnosis usually can be confirmed by aspiration, but excisional biopsy occasionally is necessary. Serial mammograms or ultrasound examinations can be used to help monitor these patients (see Chapter 5).

A psychiatric history should be obtained, with special attention paid to a personal history of psychiatric problems or a family history of affective disorders. A mental status evaluation of affect, thinking, and behavior should be performed and recorded. A prospective diary correlating symptoms, daily activities, and menstrual flow can be useful to document changes and to encourage patient participation in her care.

If underlying psychiatric illness is suspected, a psychiatric evaluation is indicated. The most common associated psychiatric illness is depression, which generally responds to antidepressant drugs and psychotherapy. Recall that psychiatric illnesses have premenstrual exacerbations, so medications should be altered accordingly.

Treatment

Treatment of PMS/PMDD depends on the severity of the symptoms. For some women, changes in eating habits—limiting caffeine, alcohol, tobacco, and chocolate intake, and eating small, frequent meals high in complex carbohydrates—may be sufficient. Decreasing sodium intake may alleviate edema. Stress management, cognitive behavioral therapy, and aerobic exercise have all been shown to improve symptoms.

Low-risk pharmacologic interventions that may be effective include calcium carbonate (1000–1200 mg/d) for bloating, food cravings, and pain; magnesium (200–360 mg/d) for water retention; vitamin B6 (note that prolonged use of 200 mg/d may cause peripheral neurotoxicity) and vitamin E; nonsteroidal anti-inflammatory drugs (NSAIDs); spironolactone for cyclic edema; and bromocriptine for mastalgia. Traditional Chinese herbal medicines are frequently used to treat PMS in China. A recent well-designed study has reported on the effectiveness of Jingqianping in the treatment of PMS. However, currently there is insufficient evidence to support the use of Chinese herbal medicine for PMS.

For symptoms of severe PMS and PMDD, further pharmacologic intervention may be necessary. Large, well-designed, randomized, placebo-controlled trials of fluoxetine and sertraline and smaller trials of several other serotonin reuptake inhibitors have shown clear benefit compared with placebo for women diagnosed with PMDD, with at least moderately beneficial response rates in 50–60% of women taking active drug. This is not a generic antidepressant effect, because agents with different mechanisms are not effective. Treatment should be given 14 days prior to the onset of menstruation and continued through the end of the cycle. Anxiolytics such as alprazolam and buspirone also have been shown to be efficacious, but their side effects and potential for dependence must be seriously considered.

Hormonal interventions have been shown to be effective. Use of selected oral contraceptives and transdermal estradiol patch has been suggested because they suppress ovulation. Recently, the US Food and Drug Administration approved the use of a pill containing drospirenone, which is a progestin derived from spironolactone rather than 19-nortestosterone, for treating PMDD. This approval permits the manufacturer to make claims about the drug's effectiveness in treating PMDD. However, the product label notes that effectiveness after 3 cycles is unknown.

Use of gonadotropin-releasing hormone (GnRH) agonists leads to a temporary “medical menopause” and an improvement in symptoms. Their limitations lie in a hypoestrogenic state and a risk for osteoporosis, although “add-back” therapy with estrogen and progesterone may obviate these problems. There is no conclusive evidence that progesterone can help women with PMS. Danazol may improve mastalgia. Finally, bilateral oophorectomy is a definitive surgical treatment option; again, estrogen replacement would be recommended.

Dysmenorrhea, or painful menstruation, is one of the most common complaints of gynecologic patients. Many women experience mild discomfort during menstruation, but the term dysmenorrhea is reserved for women whose pain prevents normal activity and requires medication, whether an over-the-counter or a prescription drug.

There are 3 types of dysmenorrhea: (1) primary (no organic cause), (2) secondary (pathologic cause), and (3) membranous (cast of endometrial cavity shed as a single entity). This discussion focuses mainly on primary dysmenorrhea. Secondary dysmenorrhea is discussed elsewhere in this book in association with specific diseases and disorders (eg, endometriosis, adenomyosis, pelvic inflammatory disease, cervical stenosis, fibroids, and endometrial polyps). Membranous dysmenorrhea is rare; it causes intense cramping pain due to passage of a cast of the endometrium through an undilated cervix. Another cause of dysmenorrhea that should be considered is cramping due to the presence of an intrauterine device (IUD).

Pathogenesis

Pain during menstruation has long been known to be associated with ovulatory cycles. The mechanism of pain has been attributed to prostaglandin activity. Advances in the last 3 decades and current understanding suggest that in primary dysmenorrheal there is abnormal and increased prostanoid and possibly eicosanoid secretion, which in turn induces abnormal uterine contractions. The contractions reduce uterine blood flow, leading to uterine hypoxia.

Other studies have confirmed increased leukotriene levels as a contributing factor. Vasopressin was thought to be an aggravating agent, but atosiban, a vasopressin antagonist, has shown no effect on menstrual pain.

Psychological factors may be involved, including attitudes passed from mother to daughter. Girls should receive accurate information about menstruation before menarche; this can be provided by parents, teachers, physicians, or counselors. Emotional anxiety due to academic or social demands may be a cofactor.

Clinical Findings

Reactions to pain are subjective, and questioning by the physician should not lead the patient to exaggerate or minimize her discomfort. History taking is most important and should include the following questions: When does the pain occur? What does the patient do about the pain? Are there other symptoms? Do oral contraceptives relieve or intensify the pain? Does the pain become more severe over time?

Because dysmenorrhea almost always is associated with ovulatory cycles, it does not usually occur at menarche but rather later in adolescence. As many as 14–26% of adolescents miss school or work as a result of pain. Typically, pain occurs on the first day of the menses, usually about the time the flow begins, but it may not be present until the second day. Nausea and vomiting, diarrhea, and headache may occur. The specific symptoms associated with endometriosis are not present.

The physical examination does not reveal any significant pelvic disease. When the patient is symptomatic, she has generalized pelvic tenderness, perhaps more so in the area of the uterus than in the adnexa. Occasionally, ultrasonography or laparoscopy is necessary to rule out pelvic abnormalities such as endometriosis, pelvic inflammatory disease, or an accident in an ovarian cyst.

Differential Diagnosis

The most common misdiagnosis of primary dysmenorrhea is secondary dysmenorrhea due to endometriosis. With endometriosis, the pain usually begins 1–2 weeks before the menses, reaches a peak 1–2 days before, and is relieved at the onset of flow or shortly thereafter. Severe pain during sexual intercourse or findings of adnexal tenderness or mass or cul-de-sac nodularity, particularly in the premenstrual interval, help to confirm the diagnosis (see Chapter 56). A similar pain pattern occurs with adenomyosis, although in an older age group and in the absence of extrauterine clinical findings.

Treatment

NSAIDs or acetaminophen may relieve mild discomfort. Addition of continuous heat to the abdomen in addition to NSAIDs decreases pain significantly. For severe pain, codeine or other stronger analgesics may be needed, and bed rest may be desirable. Occasionally, emergency treatment with parenteral medication is necessary. Analgesics may cause drowsiness at the dosages required.

Antiprostaglandins

Antiprostaglandins are now used for treatment of dysmenorrhea. The newer, stronger, faster-acting drugs appear to be more useful than aspirin. Ibuprofen and naproxen, NSAIDs that are available over the counter, have been extremely effective in reducing menstrual prostaglandin and relieving dysmenorrhea. More specific cyclooxygenase-2 (COX-2) inhibitors are now available, but concerns about their adverse effects have recently attracted attention. Rofecoxib, valdecoxib, and lumiracoxib are effective for treating primary dysmenorrhea. Thus far, COX-2 inhibitors are equally effective but not better than naproxen. Given the above considerations, concerns about safety of COX-2 inhibitors, the short duration of therapy for relieving primary dysmenorrhea, and the low costs of NSAIDs, it is prudent to recommend established NSAIDs with track records of long-term safety as the preferred pharmacologic agent. The drug must be used at the earliest onset of symptoms, usually at the onset of, and sometimes 1–2 days prior to, bleeding or cramping.

Antiprostaglandins work by blocking prostaglandin synthesis and metabolism. Once the pain has been established, antiprostaglandins are not nearly as effective as with early use.

Oral Contraceptives

Cyclic administration of oral contraceptives, usually in the lowest dosage but occasionally with increased estrogen, prevents pain in most patients who do not obtain relief from antiprostaglandins or cannot tolerate them. The mechanism of pain relief may be related to absence of ovulation or to altered endometrium resulting in decreased prostaglandin production. In women who do not require contraception, oral contraceptives are given for 6–12 months. Many women continue to be free of pain after treatment has been discontinued. NSAIDs act synergistically with oral contraceptive pills to improve dysmenorrhea.

Surgical Treatment

In a few women, no medication controls dysmenorrhea. Cervical dilatation is of little use. Laparoscopic uterosacral ligament division and presacral neurectomy are infrequently performed, although some physicians consider these procedures to be important adjuncts to conservative operation for endometriosis.

Adenomyosis, endometriosis, or residual pelvic infection unresponsive to medical therapy or conservative surgical therapy eventually may require hysterectomy with or without ovarian removal in extreme cases. Rarely, a patient with no organic source of pain eventually requires hysterectomy to relieve symptoms.

Adjuvant Treatments

Continuous low-level topical heat therapy has been shown to be as effective as ibuprofen in treating dysmenorrhea, although its practicality in daily life may be questionable. Many studies have indicated that exercise decreases the prevalence and/or improves the symptomatology of dysmenorrhea, although solid evidence is lacking.

A recent Cochrane review analyzed 7 randomized controlled trials of transcutaneous electrical nerve stimulation (TENS) compared with placebo or no treatment. Overall, high-frequency TENS is more effective for pain relief in primary dysmenorrhea than placebo TENS.

Currently, there is insufficient evidence to recommend the use of herbal and dietary therapies for dysmenorrhea.

Essentials of Diagnosis

• Abnormal uterine bleeding includes abnormal menstrual bleeding and bleeding due to other causes such as pregnancy, systemic disease, or cancer.
• In childbearing women, a complication of pregnancy must always be considered.
• Exclusion of all possible pathologic causes of abnormal bleeding establishes the diagnosis of dysfunctional uterine bleeding (nearly 60% of cases).

General Considerations

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.

1. 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.

2. 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.

3. 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.

4. Polymenorrhea describes periods that occur too frequently. This usually is associated with anovulation and rarely with a shortened luteal phase in the menstrual cycle.

5. 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.

6. 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.

7. 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).

History

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.

Physical Examination

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.

Cytologic Examination

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 Ultrasound Scan

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.

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.

Endometrial Biopsy

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.

Hysteroscopy

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.

Dilatation & Curettage

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)

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 Uterine Bleeding during Pregnancy

See Chapter 18.

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).

Treatment

Adolescents

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.

Young Women

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.

Premenopausal Women

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.

Surgical Measures

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

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.

Exogenous Hormones

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.