Abnormal bleeding affects up to 30% of women at some time during their lives. Evaluating vaginal bleeding involves an examination of the patient’s menstrual cycle. The normal menstrual cycle is generally 21-35 days in length with a menstrual flow lasting 2-7 days and a total menstrual blood loss of 20-60 mL. During the normal menstrual cycle the endometrium is exposed initially to estrogen, followed by ovulation and production of progesterone as well as estrogen, and finally the withdrawal of estrogen and progesterone causing menstruation. Different diseases are associated with certain patterns of vaginal bleeding, although there is a wide variation in presentation within each. Common terminology used to discuss vaginal bleeding includes menorrhagia, metrorrhagia, menometrorrhagia, hypermenorrhea, polymenorrhea, and oligomenorrhea. The bleeding patterns associated with each term are listed in Table 33-1.

Throughout their lifetimes there are normal changes in most women’s menstrual patterns. Just as anovulation is common during the years following menarche, the perimenopausal patient usually experiences changes in her menstrual cycle related to decreasing, irregular anovulation. Although age plays an important role in constructing a differential diagnosis in a patient presenting with vaginal bleeding, many of the causes can occur in any adult woman.

Symptoms and Signs

History

Taking a history of a patient presenting with vaginal bleeding should begin with an exploration of the patient’s usual bleeding pattern. The physician should try to establish whether the patient’s pattern is cyclic or anovulatory. If the patient menstruates every 21-35 days her cycle is consistent with an ovulatory pattern of bleeding. To confirm ovulation patients can check their basal body temperature, cervical mucus, and luteinizing hormone (LH) levels. Basal body temperature can be checked using a basal body temperature thermometer, which allows for a precise measurement of the patient’s temperature within a narrower range than a standard thermometer. The patient takes her temperature orally as soon as she awakens in the morning and records it on a chart. After ovulation the ovary secretes an increased amount of progesterone, causing an increase in temperature of approximately 0.5°F over the baseline temperature in the follicular phase. The luteal phase is often accompanied by an elevation of temperature that lasts 10 days. In addition, patients can be taught to check the consistency of their cervical mucus, watching for a change from the sticky, whitish cervical mucus of the follicular phase to the clear, stretching mucus of ovulation. Finally, the patient can use an enzyme-linked immunosorbent assay (ELISA) available as a home testing kit to check for the elevation of LH over baseline that occurs with ovulation.

The patient should then be asked by the physician to describe the current vaginal bleeding in terms of onset, frequency, duration, and severity. This history will help the physician to focus the differential diagnosis. For example, if the patient reports a long-standing history of anovulatory bleeding the workup can focus on causes for chronic hyperandrogenicity such as polycystic ovarian syndrome and congenital adrenal hyperplasia. Age, parity, sexual history, previous gynecological disease, and obstetrical history will further assist the physician in focusing the evaluation of the women with vaginal bleeding. These questions will help in evaluating the likelihood of pregnancy-related causes of vaginal bleeding, infectious disease, and cancer.

The physician should ask about medications, including contraceptives, prescription medications, and over-the-counter medications and supplements. Contraception is a common cause of vaginal bleeding in women. The patient should be directly asked about any over-the-counter preparations she may be taking. Patients may not be aware that herbal preparations may contribute to vaginal bleeding. Ginseng, which has estrogenic properties, can cause vaginal bleeding and St John’s Wort can interact with oral contraceptives to cause breakthrough bleeding. A review of symptoms should include questions regarding fever, fatigue, abdominal pain, hirsutism, galactorrhea, changes in bowel movements, and heat/cold intolerance. A careful family history will aid in identifying patients with a predisposition to polycystic ovarian syndrome, congenital adrenal hyperplasia, thyroid disease, premature ovarian failure, fibroids, and cancer. Physicians should also keep in mind that women usually present complaining of vaginal bleeding when symptoms deviate from the patient’s normal bleeding pattern. Patients with chronic anovulatory bleeding patterns or lifelong heavy menses secondary to von Willebrand disease may not perceive their underlying menses pattern as abnormal. Therefore, the physician should avoid asking the patient if her periods has been “normal” and instead should ask for specific details regarding the patient’s bleeding pattern.

Physical Examination

The physical examination for women complaining of vaginal bleeding should begin with an evaluation of the patient’s vital signs. Does the patient present with a fever (indicating possible infection), increased pulse, low blood pressure, or significant orthostatic changes in her blood pressure (indicating significant acute blood loss)? Has she had a significant weight change and an enlarged or tender thyroid gland indicating thyroid disease? The physician should also evaluate the patient’s weight for obesity and hair distribution for hirsutism. These can indicate possible chronic anovulation syndromes. The pelvic examination will aid in identifying other causes of bleeding including anatomic abnormalities such as cervical polyps; signs of infections such as cervical discharge, cervical motion tenderness, and uterine or adnexal tenderness; signs of pregnancy such as changes in the cervix and a symmetrically enlarged uterus; and signs of fibroids such as an enlarged but irregular uterus.

Evaluation

The evaluation of patients presenting with vaginal bleeding includes a combination of laboratory testing, imaging studies, and sampling techniques. The evaluation is directed both by patient presentation and a risk evaluation for endometrial cancer. For example, a patient who presents with a history and physical examination consistent with pelvic inflammatory disease will obviously be tested for gonorrhea and chlamydia. If the physician feels an enlarged uterus on physical examination the initial evaluation will include a pregnancy test followed by a pelvic ultrasound. If the results are inconclusive a sonohysterogram can aid in detecting a focal versus a diffuse lesion. This in turn can lead to a hysteroscopy for further evaluation of a focal lesion or an endometrial biopsy for a diffuse lesion.

The choice of evaluation is also based on the risk of endometrial cancer. For a patient who is at risk, an endometrial biopsy should be included in the evaluation. Patients having prolonged exposure to unopposed estrogen (either iatrogenically or because of chronic anovulation) for more than a year, regardless of age, should also have an endometrial biopsy. In addition, because the incidence of endometrial cancer begins to increase after the age of 35, any patient older than this should also have an endometrial biopsy during an evaluation for unexplained vaginal bleeding.

Laboratory Studies

Most patients presenting with vaginal bleeding should be evaluated with a complete blood count. In addition, every woman of reproductive age should have a urine or serum pregnancy test. A thyroid-stimulating hormone (TSH) should be drawn on women presenting with symptoms consistent with hypo- or hyperthyroidism or in women presenting with a change from a normal menstrual pattern.

Adolescents presenting with menorrhagia at menarche should have an evaluation for coagulopathies including a prothrombin time (PT), partial thromboplastin time (PTT), and bleeding time.

There is no general agreement on the diagnostic criteria for polycystic ovarian syndrome (PCOS). In patients with symptoms suggestive of PCOS it is reasonable to check for elevated LH, testosterone, and androstenedione. These may be elevated in patients with PCOS, but due to the large variation among individual women these tests are not definitive. Therefore, the physician needs to interpret test results in conjunction with the clinical picture to make a diagnosis of PCOS.

Overall, the incidence of adult-onset congential adrenal hyperplasia (CAH) is about 2% in women with hyperandrogenic symptoms. The incidence is higher in individuals of Italian, Ashkenazi, and Yugoslav heritage. Deciding on screening for adult-onset CAH should be based on both the patient’s clinical presentation and the patient’s ethnic background. A basal 17-hydroxyprogesterone (17-HP) should be drawn in the early morning to screen for adult-onset CAH. Patients with an abnormal result can have another 17-HP level drawn after receiving a dose of adrenocorticotropic hormone (ACTH).

Imaging Studies

Pelvic Ultrasound

A pelvic ultrasound can be used to evaluate the ovaries, uterus, and endometrial lining for abnormalities. An evaluation of the ovaries can assist in the diagnosis of PCOS as many women with PCOS will have enlarged ovaries with multiple, small follicles. As with the laboratory testing, this study will not provide a definitive diagnosis.

A pelvic ultrasound is also useful for evaluating an enlarged uterus for the presence of fibroids. Fibroids will appear as hypoechoic, solid masses seen within the borders of the uterus. Subserosal fibroids can be pedunculated and therefore can be seen outside the borders of the uterus.

An endovaginal ultrasound can be used to evaluate the thickness of the endometrial stripe. The results need to be interpreted based on the whether a patient is pre- or postmenopausal. For all women the thicker the endometrial stripe, the more likely the patient has an endometrial abnormality.

An endovaginal ultrasound is a sensitive test for patients with postmenopausal bleeding whether or not they are using hormone replacement therapy. Therefore, postmenopausal patients with an endometrial stripe thicker than 4-5 mm should have a histological biopsy. Hormone replacement therapy can cause proliferation of a patient’s endometrium, making an endovaginal evaluation less specific.

An endovaginal ultrasound is also useful in evaluating the endometrial stripe in premenopausal or perimenopausal patients. Whereas the normal endometrial stripe is thicker in the premenopausal patient than in the postmenopausal patient, the median thickness of an abnormal endometrium is similar for both. The endovaginal ultrasound examination is less likely to detect myomas and polyps.

Sonohysterography

In a patient who has an endometrial strip thicker than 5 mm, a saline infusion sonohysterography (SIS) may be helpful in delineating the cause. SIS involves performing a transvaginal ultrasound following installation of saline into the uterus. Done after an abnormal vaginal ultrasound, the study is most useful in differentiating focal from diffuse endometrial abnormalities. Detection of a focal abnormality indicates evaluation by hysteroscopy and detection of an endometrial abnormality indicates the need to perform an endometrial biopsy or dilatation and curettage. This can be considered as a study of first choice in premenopausal women with abnormal uterine bleeding.

Magnetic Resonance Imaging

Magnetic resonance imaging (MRI) can be used to evaluate the uterine structure. The endometrium can be evaluated with an MRI, but the endometrial area seen on MRI does not correspond exactly to the endometrial stripe measured with ultrasound. In most situations, a transvaginal ultrasound is the preferred imaging modality, but if the patient cannot tolerate the procedure MRI does provide an option for evaluation. MRI is better than ultrasound in distinguishing adenomyosis from fibroids, so if the history and examination suggests adenomyosis, an MRI may be the best first choice. MRI is also sometimes used to evaluate fibroids prior to uterine artery embolization or to map multiple myomas.

Endometrial Sampling

The workup for endometrial cancer should be pursued most aggressively with patients at greatest risk for the disease, such as postmenopausal patients who present with vaginal bleeding. In patients younger than 40 years, endometrial cancer is usually seen in obese patients and/or patients who are chronically anovulatory. Therefore, a patient who presents with an anovulatory pattern of bleeding for greater than a year should be evaluated for hyperplasia and neoplasm with an endometrial sample. In addition, the evaluation of women older than 35-40 years presenting with a new onset of menorrhagia should include endometrial sampling since the incidence of endometrial cancer increases after the age of 35.

Findings from the initial workup and response to treatment will determine the need for additional studies including sonohysterography, diagnostic hysterography, and MRI.

Dilatation and Curretage

Dilatation and curretage (D&C) provides a blind sampling of the endometrium. The D&C generally will provide sampling of less than half of the uterine cavity. Because an endometrial biopsy can be completed in the office setting, it has generally replaced the D&C as the initial method of obtaining an endometrial sample. The D&C is useful in patients with cervical stenosis or other anatomic factors that prevent an adequate endometrial biopsy. The D&C is not effective as the sole treatment for menorrhagia.

Endometrial Biopsy