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The aims of this study were: (1) to review the rate of concurrent endometrial cancer in patients with a preoperative diagnosis of atypical endometrial hyperplasia (AEH); and (2) to determine the features of concurrent endometrial carcinoma and their impact on the subsequent management of AEH. We reviewed a retrospective series of 219 AEHs diagnosed locally in routine practice, over 24 years, and followed by a repeat biopsy or hysterectomy. Another series of 65 cases with a malignant diagnosis on preoperative sampling was included as a control group. Clinicopathologic parameters were obtained. In addition, published data on the risk of malignancy and features of malignant tumors after a diagnosis of AEH were collected and analyzed. This study reported on 2571 patients diagnosed in 31 published studies in addition to the current one. This showed a wide variation in the positive predictive value (PPV) of AEH in detecting endometrial cancer (6% to 63%) with an overall PPV of 37%. This variation is not only based on the differences among studies but also on the degree of atypia [mild/moderate (PPV 13%) or severe (PPV 50%)], the type of subsequent intervention (biopsy vs. hysterectomy), and more importantly the time period of diagnosis (around 20% in studies published before 1990s and up to 40% to 48% in recently published cases). Of the benign outcome cases, nearly 40% to 50% showed AEH with a potential risk of progressing to invasive carcinoma in 25% of cases. Malignant tumors after AEH diagnosis are associated with features of good prognosis with endometrioid morphology, lower grade, and early stage. Although the overall PPV of AEH is 37%, a figure of 40% to 48% is expected in the cases currently diagnosed in routine practice. Providing qualifying criteria for AEH will help identify its different associated risks and therefore should be included in routine pathology reports whenever possible. Unless there is a clinical contraindication, hysterectomy should be performed to treat concurrent carcinoma and to reduce the risk of subsequent carcinoma in nonmalignant cases with residual AEH.

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The lipoxygenase products (leukotrienes) have been demonstrated in many mammalian tissues including humans. They are widely distributed in the lungs, gut, uterus, kidneys, skin, heart and the liver. Their roles as mediators of inflammation have made them therapeutic targets. Significant amounts of leukotrienes have been demonstrated in the endometrium of women with primary dysmenorrhoea who do not respond to treatment with anti-prostaglandins. Also, in endometriosis, cytokines, which can initiate the cascade for the biosynthesis of leukotrienes, have been shown to be elevated. It is estimated that 10-30% of patients with painful periods fail to respond to prostaglandin (PG) synthetase inhibitors. Of adult females approximately 40% have painful menstruation and 10% of these are incapacitated for 1-3 days per month, and approximately 10% of women aged between 15-45 years suffer from endometriosis, which is a significant cause of infertility. Leukotriene receptor antagonists have recently been licensed for the treatment of asthma in the UK. In this review, we present the case for the potential use of these products in the management of primary dysmenorrhoea (especially in patients who are not responding to the traditional treatment using PG synthetase inhibitors) and possibly also in cases of endometriosis.