Clinical Review

Postmenopausal AUB: Rule out endometrial cancer first

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When a postmenopausal woman presents with abnormal uterine bleeding, endometrial cancer is the biggest concern. But a host of other etiologies also are possible. The author reviews them and outlines a systematic approach to diagnosis.


 

References

KEYPOINTS
  • Uterine bleeding or spotting after the initiation of hormone replacement therapy (HRT) is not unusual.
  • Endometrial evaluation is called for in women not taking HRT who develop uterine bleeding after more than 1 year of amenorrhea. It also is indicated in postmenopausal women on HRT for more than 6 months with persistent uterine bleeding, and previously amenorrheic women on HRT who begin bleeding without apparent cause.
  • Screening asymptomatic women for endometrial cancer through transvaginal ultrasound or endometrial biopsy is not recommended.
  • If endometrial thickness is greater than 4 mm, sonohysterography should be performed.

Approximately 1 of every 8 post-menopausal women who present with abnormal uterine bleeding (AUB) will be diagnosed with endometrial cancer, making this one of the most troubling symptoms clinicians encounter in gynecologic practice. Because a wide variety of pathophysiologic problems can cause AUB in post-menopausal women, these patients require prompt evaluation. At a minimum, this should include a clinical history and physical examination, as well as endometrial sampling or evaluation by ultrasound—especially for women not taking hormone replacement therapy (HRT). This process enables clinicians to detect endometrial cancer at an early stage, before it has spread beyond the uterus. Early detection is associated with an expected survival rate of 90%.1

Over the past decade, the evaluation and treatment of postmenopausal bleeding has evolved significantly, thanks to the availability of office-based transvaginal ultrasound (TVUS) and saline-infusion sonohysterography, as well as the advent of endometrial ablation (TABLE 1). Here, I discuss diagnostic testing and review conditions that can lead to postmenopausal bleeding. Once the etiology is identified, the choice of therapeutic intervention usually is self-evident.

TABLE 1

Tests for evaluating postmenopausal AUB

  • Endometrial biopsy
  • Transvaginal ultrasound
  • Saline-infusion sonohysterography
  • Hysteroscopy and directed endometrial biopsy

Pathophysiology

Our understanding of the pathophysiology of AUB is in its infancy. Here’s what we do know: During a woman’s reproductive years, her endometrium constantly remodels itself under the influence of estrogen, which stimulates cellular growth, and progesterone, which antagonizes the estrogen’s growth effects. When a woman is anovulatory, however, the endometrium can be stimulated by continual estrogen exposure, resulting in endometrial proliferation. This leads to endometrial instability and, in turn, uterine bleeding. Several cellular signaling molecules—such as cytokines, growth factors, and matrix metalloproteinases—are involved. Once menopause occurs, estrogen and progesterone are no longer produced by the ovaries; nor are they produced in any appreciable amounts by the liver and fat. The endometrium regresses to some degree, and no further bleeding should occur. When bleeding does resume, therefore, abnormal pathologies must be investigated.

Endometrial hyperplasia and cancer

Endometrial cancer is the most common gynecologic cancer in the United States, affecting 21 of every 100,000 women, according to the National Cancer Institute’s (NCI) Surveillance, Epidemiology, and End Results (SEER) Program.2 Fortunately, because AUB is an early harbinger of the disease, endometrial cancer generally has a favorable prognosis: When all endometrial cancer cases are considered, the 5-year survival rate is 84%, though the prognosis for individual patients depends on a variety of factors, including the initial stage of the endometrial cancer as well as the cellular differentiation.

Over the past 2 decades, the rate of endometrial cancer has decreased by more than 26%.2 This may be because many women are entering menopause who previously used combination oral contraceptives (OCs) containing progestin, which is associated with a reduced risk of endometrial hyperplasia and cancer. The increased use of progestin in HRT regimens in recent years also likely plays a role.

Risk factors for endometrial cancer are conditions typically associated with chronic elevations of endogenous estrogen levels or increased estrogen action at the level of the endometrium. These include obesity, history of chronic anovulation, diabetes mellitus, estrogen-secreting tumors, exogenous estrogen unopposed by progesterone or progestin, tamoxifen use, and a family history of Lynch type II syndrome (hereditary nonpolyposis colorectal, ovarian, or endometrial cancer). Since endometrial cancer may occur in the absence of risk factors, however, they should not be the sole means of identifying patients.

Since the cost-effectiveness of endometrial biopsy and transvaginal ultrasound are comparable, the choice of modality rests with the physician.

Diagnostic tests. Endometrial evaluation is called for when any menopausal woman not taking HRT develops uterine bleeding after more than 1 year of amenorrhea. It also is indicated in any postmenopausal woman on HRT for 6 months or more with persistent uterine bleeding, and any previously amenorrheic woman on HRT who begins bleeding without apparent cause.

The measurement of endometrial thickness by TVUS is now almost standard in the evaluation of postmenopausal bleeding. However, screening asymptomatic women for endometrial cancer with TVUS is not recommended. Although the test is very specific (the number of false positives is exceedingly small when the endometrial thickness is set at less than 5 mm), it isn’t sensitive. Many women without endometrial cancer will have an endometrial thickness of 5 mm or more.

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