Endometrial surveillance in tamoxifen users: role, timing and accuracy of hysteroscopic investigation: observational longitudinal cohort study.

To determine the role, timing and indications for endometrial hysteroscopic investigation in relation to the clinical, ultrasound and histological features of the endometrium during tamoxifen (TAM) use. We performed an observational longitudinal cohort study (years 2007-2012) that investigated the endometria of 151 TAM users with hysteroscopy and histology. For all patients, gynaecological history, years of adjuvant treatment, ultrasound endometrial thickness measurement and indications for hysteroscopy were recorded. Hysteroscopic findings showed that 100% of patients referred for simple follow-up had no evidence of endometrial disease. We found a strong correlation between previous history of abnormal uterine bleeding (with or without endometrial thickening) and hysteroscopic suspicion of endometrial atypia that was confirmed by histology. Hysteroscopy had 83.3% sensitivity, 99% specificity, 83.3% positive predictive value (PPV) and 99% negative predictive value (NPV) in detecting endometrial atypia. No significant correlation was found between endometrial thickening to >5 mm without bleeding and histological atypia. Similarly, the duration of treatment was not related to endometrial thickening and histological atypia. Endometrial stromal hyperplasia was detected by histology in 70.5% of patients with endometrial thickness measurements ranging from 5 to 10 mm. In contrast, no atypia was detected when endometrial thickness was <5 mm. Ultrasound performed using a 5-mm cut-off threshold for endometrial thickness resulted in 100% sensitivity, 15% specificity, 4% PPV and 100% NPV in detecting endometrial atypia, while a 10-mm cut-off threshold resulted in 84% sensitivity, 69% specificity, 10% PPV and 99% NPV. Low-risk TAM users do not require different endometrial surveillance than the general population. Hysteroscopy could play a fundamental role in determining the endometrial status of patients before the initiation of TAM treatment and in assessing the endometrial status of patients when bleeding occurs.

Update on raloxifene: mechanism of action, clinical efficacy, adverse effects, and contraindications.

Raloxifene is the only selective estrogen receptor modulator approved for long-term treatment in the prevention of osteoporotic fractures and for the reduction of invasive breast cancer risk in post-menopausal women. The demonstrated beneficial effects on bone and mammalian tissue led clinical and molecular research to focus mainly on these organs, giving less attention to all other systemic effects. The aim of this review was to evaluate all described systemic effects of raloxifene, investigating its molecular and tissutal mechanism of action. A literature research was carried out in electronic databases MEDLINE, EMBASE, ScienceDirect, and the Cochrane Library in interval time between 2000 and 2012. Outcomes were considered in relation to positive/adverse effects concerning bone metabolism, lipid metabolism, coagulation pattern, menopausal symptoms, breast cancer onset, and endometrial cancer onset. Raloxifene acts as an estrogen agonist or antagonist depending on the tissue. This feature is related to specific actions on at least 2 distinct estrogen receptors, whose proportions vary according to tissue type. Raloxifene is a drug for the treatment of osteoporosis and for the prevention of estrogen receptor-positive breast cancer because it guarantees a safety profile on the endometrium. Raloxifene is furthermore an effective therapy in women with increased levels of plasma cholesterol. Raloxifene treatment shifts the coagulation pattern toward prothrombosis, and the patients should be exhaustively informed about the risks associated with therapy. Raloxifene does not show to affect memory and cognition. Finally, it is noteworthy that quality-of-life studies demonstrated some favorable effects of raloxifene.