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Menopause Matters

Endometrial Evaluation: Assessing Perimenopausal and Postmenopausal Women

Steven R. Goldstein, MD

In perimenopausal and postmenopausal women, abnormal uterine bleeding (AUB) is defined as excessive and/or erratic bleeding in the presence or absence of uterine pathology. It is different from the normal, irregular uterine bleeding characteristic of the perimenopause transition.

In perimenopausal women, the predominant cause of AUB is less predictable ovulation caused by changes in hypothalamic-pituitary-ovarian function. But it may also be caused by uterine pathologies such as fibroids, endometrial polyps, hyperplasia, or even carcinoma.¹ Accordingly, practice guidelines suggest that perimenopausal women over age 35 years presenting with AUB should be examined for these pathologic conditions.²

In postmenopausal women, the most common cause of uterine bleeding is endometrial atrophy. Women on sequential estrogen-progestogen therapy (EPT) (continuous estrogen with monthly progestogen) will often have an expected withdrawal bleed associated with the progestogen. However, any unexpected postmenopausal uterine bleeding should be considered abnormal. Pathology should also be suspected if uterine bleeding persists longer than 6 months in women using continuous-combined EPT.

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INITIAL EVALUATION

For perimenopausal women who present with AUB, the medical history should include the clinical features of menstrual flow and any restriction of daily activities, intermenstrual uterine bleeding, use of contraceptives or other medications, and systemic diseases.

A pelvic examination is essential for all perimenopausal women with AUB. The following tests should be ordered selectively: pregnancy, complete blood cell count (to determine if anemia is present), thyroid-stimulating hormone, coagulation studies, and serum prolactin.

Charting of uterine bleeding may be helpful in assessing reported menstrual abnormalities. Information should include the days of the bleeding, the amount and color of the flow, the presence of clots, and pain associated with the bleeding. As these are subjective measurements, printed forms often help women to keep more reliable records. A one-page menstrual calendar can be purchased from the consumer education section of the NAMS Web site (www.menopause.org).

In postmenopausal women with uterine bleeding, obtaining a history of estrogen-containing therapy use is crucial. If bleeding is reported with no recent history of estrogen therapy (ET) or EPT use, both a pelvic examination and endometrial evaluation are mandatory.

Because unopposed ET is associated with a high incidence of endometrial hyperplasia, women with a uterus who are using ET should undergo endometrial evaluation at baseline and then annually. If bleeding in postmenopausal women started only after initiation of EPT (which may simply reflect the iatrogenic impact of EPT), is not heavy, and declines in amount over time, no evaluation is needed. If these parameters are not met, or if there is concern regarding the cause of the bleeding, endometrial evaluation is warranted. Women using continuous estrogen and intermittent (eg, every 3 months) progestin therapy have an increased risk of endometrial hyperplasia³ and require regular endometrial evaluation, similar to women with a uterus who use ET.

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ENDOMETRIAL EVALUATION PROCEDURES

The following procedures are used to evaluate the endometrium of peri-menopausal women with AUB as well as postmenopausal women in whom endometrial evaluation is indicated. The woman's preference, the clinician's training and skill, as well as cost and access issues, will determine their use.

Endometrial biopsy provides a convenient, quick, office-based endometrial evaluation with greater than 90% sensitivity in diagnosing endometrial cancer.⁴ During this procedure, a small sample of the endometrium is removed through the cervix for histopathologic evaluation. The narrow-caliber (3 mm outer diameter) biopsy devices, however, may miss some focal benign lesions, including polyps and submucous myomata as well as focal hyperplasias or malignancies.

Transvaginal ultrasonography is playing an increasing role in the evaluation of women with AUB. A probe inserted into the vagina produces images to measure the thickness of the endometrium and evaluates the uterine and adnexal anatomy. For a postmenopausal woman experiencing uterine bleeding, transvaginal ultrasonography can be used to exclude malignancy, provided that the entire endo-metrium can be visualized and the endometrial-myometrial interface is distinct. An endometrial lining thinner than 4 to 5 mm has a 99% negative predictive value.⁵ If the endometrium is not thin, further evaluation should be conducted. Sonohysteroscopy or hysteroscopy can be used to distinguish global lesions that can be biopsied blindly as opposed to focal lesions (polyps, focal thickening) that should be biopsied under direct vision.⁶

Sonohysterography utilizes transvaginal ultrasound, with saline infused transcervically to distend and, thus, better visualize the endometrial cavity and identify focal lesions such as endometrial polyps and submucous fibroids. Technologic advances have led to increased use of this procedure to evaluate perimenopausal AUB. Such evaluation should be performed as soon as possible after bleeding ends, when the endo-metrium is expected to be at its thinnest. Sonohysterography can also be useful in evaluating uterine bleeding in postmenopausal women, especially if unenhanced transvaginal ultrasound is not diagnostic (eg, axial uterus, coexisting fibroids, obesity).

Hysteroscopy is a procedure in which a small flexible or rigid endoscope is inserted into the vagina and through the cervix to view the uterine lining directly. Hysteroscopy may be useful in identifying and taking biopsies of (or removing) endometrial polyps and submucous fibroids. Although diagnostic hysteroscopy is sometimes performed in the physician's office, operative hysteroscopy to resect intracavity tissue is most commonly performed in an operating room with sufficient anesthesia.

Dilation and curettage is a surgical procedure in which the cervix is dilated and the uterine lining is blindly sampled by scraping or by suction and scraping. This procedure is performed less frequently than endometrial biopsy because it usually requires anesthesia. Dilation and curettage should be done in conjunction with hysteroscopy and may be appropriate when an endometrial biopsy cannot be performed because of cervical stenosis.

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Recommendations for evaluation

The following strategies are prudent approaches for the endometrial evaluation of the perimenopausal woman presenting with AUB, as well as the postmenopausal woman requiring endometrial evaluation for uterine bleeding.

Begin with endometrial biopsy or transvaginal sonography (with fluid enhancement when indicated). If the histology demonstrates benign endometrium, including hyperplasia without atypia, proceed with medical or expectant management. Likewise, if unenhanced transvaginal sonography is reassuring, proceed with medical management.

If such management does not result in a satisfactory bleeding pattern, or if sonohysterography was not initially used, proceed with sonohysteroscopy or hysteroscopy as early as possible in a bleeding cycle.

Given the absence of large, randomized, controlled trials comparing different evaluation strategies in the evaluation of AUB in perimenopausal women and postmenopausal uterine bleeding, clinicians—guided by patient preference—should use the techniques with which they are most technically comfortable and which are most accessible and cost-effective in their practices.

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Steven R. Goldstein, MD, is professor of obstetrics and gynecology, New York University School of Medicine, New York. He is chair of the 2004/2005 Professional Education Committee of The North American Menopause Society.

References

1. Kaunitz AM. Gynecologic problems of the perimenopause: evaluation and treatment. Obstet Gynecol Clin North Am. 2002;29(3):455-473.
2. American College of Obstetricians and Gynecologists. Management of Anovulatory Bleeding. Washington, DC: American College of Obstetricians and Gynecologists; March 2000. ACOG Practice Bulletin No. 14.
3. Williams DB, Voight BJ, Fu YS, Schoenfeld MJ, Judd HL. Assessment of less than monthly progestin therapy in postmenopausal women given estrogen replacement. Obstet Gynecol. 1994;84(5):787-793.
4. Goldstein RB, Bree RL, Benson CB, et al. Evaluation of the woman with postmenopausal bleeding: Society of Radiologists in Ultrasound-Sponsored Con- sensus Conference statement. J Ultrasound Med. 2001;20(10):1025-1036.
5. Langer RD, Pierce JJ, O'Hanlan KA, et al. Transvaginal ultrasonography compared with endometrial biopsy for the detection of endometrial disease. Postmenopausal Estrogen/Progestin Interventions Trial. N Engl J Med. 1997; 337(25):1792-1798.
6. Goldstein SR, Monteagudo A, Popiolek D, Mayberry P, Timor-Tritsch I. Evaluation of endometrial polyps. Am J Obstet Gynecol. 2002;186(4):669-674. 2002;288(3):321-333.

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