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A recently published paper by Clarke and colleagues is a meta-analysis of 129 studies of over 34,000 patients with postmenopausal bleeding (PMB) that yielded 6358 cases of endometrial (EM) cancer [1]. This is a huge undertaking and there are several points worthy of re-emphasizing. Why is this issue of PMB and EM cancer so important? It is the most common gynecologic malignancy (although, fortunately, not the most lethal). It is also said that one in ten women will experience PMB in their lifetime [2].

In this analysis, 9% of women with PMB had an endometrial cancer. In 2010, I wrote an Invited Expert Series manuscript for Obstetrics and Gynecology entitled ‘Modern Evaluation of the Endometrium’ [3]. I reported that, of all the series that I reviewed, they had a range of endometrial cancer with PMB from 1 to 14%, with most studies being in the 3–7% range. Regardless of any exact incidence, our undergraduate medical students are emphatically taught that any PMB is ‘EM cancer until proven otherwise’, in spite of the fact that the overwhelming majority will not harbor a malignancy. So there is a bit of a disconnect. It is essential to be sure that all postmenopausal patients know that any bleeding, even spotting, staining, or brown discharge, should be reported and evaluated promptly but, once that happens, they should be counseled that, although thorough and prompt evaluation is mandatory, the likelihood that they have cancer is low, less than one in ten.

I would be remiss if I did not use this opportunity (now that I have your attention) to reiterate the potential foibles of blind biopsy. When cancer occupies less than 50% of the surface area of the endometrium, blind endometrial biopsy can miss it [4]. In fact, in the paper by Guido et al. [5], in patients with known endometrial cancer, a Pipelle suction piston biopsy in the operating room prior to their hysterectomy missed 16% of these known cancers! However, every one of those cases was less than 50% of the uterine cavity surface area. Thus, although clinicians may start their evaluation with a blind biopsy, they should be aware that a negative finding is not a stopping point, especially in cases of persistent or recurrent bleeding. Sonohysterography, also referred to as saline infusion sonohysterography, or hysteroscopy, preferably in an office setting, will distinguish global from focal processes.

Another interesting point that comes from Clarke et al.’s paper is the difference in the finding of endometrial cancer in women with PMB by geographic region [1]. In North America, it was as low as 5%, Northern Europe, 7%, and Western Europe, 13%. This cannot be explained by obesity as the rates in North America are considerably higher than Europe. This report does not include the hyperplasias (newer terminology: endometrial interepithelial neoplasia or EIN). Are some rates of endometrial cancer different because it is being identified at the stage of EIN? Does this have more to do with access to care, fear of liability, or even education and cultural perceptions about bleeding into the menopause by the patients?

Certainly, we as health-care providers with a specific interest in menopause are hopefully already aware of and attuned to the information reiterated in this update and will remain vigilant in our education of and evaluation of our patients before and after any report of postmenopausal bleeding.


  • Steve Goldstein
    Department of Obstetrics & Gynecology, New York University School of Medicine, New York, USA


  1. Clarke MA, Long BJ, Del Mar Morillo A, et al. Association of endometrial cancer risk with postmenopausal bleeding in women: A systematic review and meta-analysis. JAMA Intern Med 2018 Aug 6. Epub ahead of print
  2. Matteson KS, Robison K, Jacoby VL. Opportunities for early detection of endometrial cancer in women with postmenopausal bleeding. JAMA Intern Med 2018 Aug 6. Epub ahead of print
  3. Goldstein SR. Modern evaluation of the endometrium. Obstet Gynecol 2010;116:168-76
  4. ACOG Committee on Practice Bulletins-Gynecology. ACOG practice bulletin. No. 128. Diagnosis of abnormal uterine bleeding in reproductive-aged women. Obstet Gynecol 2012;120:197-206
  5. Guido RS, Kanbour-Shakir, Rulin MC, Christopherson WA. Pipelle endometrial sampling. Sensitivity in the detection of endometrial cancer. J Reprod Med 1995;40:553-5
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