Objective The aim of this article is to summarize the recommended updates to the 2001 Stages of Reproductive Aging Workshop (STRAW) criteria. The 2011 STRAW + 10 reviewed advances in understanding of the critical changes in hypothalamic-pituitary-ovarian function that occur before and after the final menstrual period. Methods Scientists from five countries and multiple disciplines evaluated data from cohort studies of midlife women and in the context of chronic illness and endocrine disorders on change in menstrual, endocrine, and ovarian markers of reproductive aging including antimüllerian hormone, inhibin-B, follicle-stimulating hormone, and antral follicle count. Modifications were adopted by consensus. Results STRAW + 10 simplified bleeding criteria for the early and late menopausal transition, recommended modifications to criteria for the late reproductive stage (Stage –3) and the early postmenopause stage (Stage +1), provided information on the duration of the late transition (Stage–1) and early postmenopause (Stage +1), and recommended application regardless of women's age, ethnicity, body size, or lifestyle characteristics. Conclusions STRAW + 10 provides a more comprehensive basis for assessing reproductive aging in research and clinical contexts. Application of the STRAW + 10 staging system should improve comparability of studies of midlife women and facilitate clinical decision making. Nonetheless, important knowledge gaps persist, and seven research priorities are identified.

BackgroundSeveral guidelines have been reported for bone-directed treatment in women with early breast cancer (EBC) for averting fractures, particularly during aromatase inhibitor (AI) therapy. Recently, a number of studies on additional fracture related risk factors, new treatment options as well as real world studies demonstrating a much higher fracture rate than suggested by randomized clinical controlled trials (RCTs). Therefore, this updated algorithm was developed to better assess fracture risk and direct treatment as a position statement of several interdisciplinary cancer and bone societies involved in the management of AI-associated bone loss (AIBL).Patients and methodsA systematic literature review identified recent advances in the management of AIBL. Results with individual agents were assessed based on trial design, size, follow-up, and safety.ResultsSeveral fracture related risk factors in patients with EBC were identified. Although, the FRAX algorithm includes fracture risk factors (RF) in addition to BMD, it does not seem to adequately address the effects of AIBL. Several antiresorptive agents can prevent and treat AIBL. However, concerns regarding compliance and long-term safety remain. Overall, the evidence for fracture prevention is strongest for denosumab 60 mg s.c. every 6 months. Additionally, recent studies as well as an individual patient data meta-analysis of all available randomized trial data support additional anticancer benefits from adjuvant bisphosphonate treatment in postmenopausal women with a 34% relative risk reduction in bone metastasis and 17% relative risk decrease in breast cancer mortality that needs to be taken into account when advising on management of AIBL.ConclusionsIn all patients initiating AI treatment, fracture risk should be assessed and recommendation with regard to exercise and calcium/vitamin D supplementation given. Bone-directed therapy should be given to all patients with a T-score<−2.0 or with a T-score of <–1.5 SD with one additional RF, or with ≥2 risk factors (without BMD) for the duration of AI treatment. Patients with T-score>−1.5 SD and no risk factors should be managed based on BMD loss during the first year and the local guidelines for postmenopausal osteoporosis. Compliance should be regularly assessed as well as BMD on treatment after 12 - 24 months. Furthermore, because of the decreased incidence of bone recurrence and breast cancer specific mortality, adjuvant bisphosphonates are recommended for all postmenopausal women at significant risk of disease recurrence.

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Participants in the Euralox 1 Study Group are listed on pages 165 -166Objective To compare the uterine effects of 60 mg of raloxifene with a continuous combined hormone replacement therapy, a preparation of 2 mg 17h-oestradiol (E 2 ) and 1 mg norethisterone acetate for a duration of 12 months. Design A randomised, double-blind trial.Setting Multicentre: Europe, Israel, South Africa.Population Asymptomatic postmenopausal women with risk factors for osteoporosis or cardiovascular disease who had an endometrial thickness of less than 5 mm. One thousand and eight women were randomised for the six month core; of these 420 were invited to continue into a six month extension period. Methods Randomisation to either raloxifene or continuous combined hormone replacement therapy. Patients, recruiters and assessors were blinded to the treatment used. Main outcome measures The frequency of vaginal spotting/bleeding as recorded in a diary, endometrial thickness and uterine volume as measured by transvaginal ultrasonography at baseline and after 6 and 12 months. Results After six months of therapy with raloxifene, the rate of women on raloxifene reporting vaginal bleeding and spotting (6.8%) was similar to the rate in the lead-in phase (8.3%) but increased from 7.0% to 55.1% in the continuous combined hormone replacement therapy group. Raloxifene treatment was not associated with a significant change from baseline to endpoint in mean endometrial thickness ( P ¼ 0.11), whereas continuous combined hormone replacement therapy treatment was associated with an increase in this value of mean (SD) of 1.2 (2.2) mm ( P < 0.001). Compared with raloxifene, mean endometrial thickness for women on continuous combined hormone replacement therapy was significantly increased at endpoint [4.6 (2.1) mm vs 3.5 (1.7) mm; change from baseline P < 0.001]. In the raloxifene group, there was a trend towards a decrease from baseline in uterine volume [from 31.4 (20.3) to 30.3 (16.2) mm; P ¼ 0.37]; in the continuous combined hormone replacement therapy group, there was a significant increase in uterine volume [from 31.3 (16.3) to 54.0 (36.1) mm; P < 0.001], and the difference in the effect of both compounds on change in uterine volume at endpoint reached statistical significance ( P < 0.001). Statistically significant differences between the treatment groups were sustained for all parameters during the extension period. Early discontinuation rates, both overall and due to adverse events, were significantly lower ( P < 0.001) in the raloxifene group after 6 and 12 months. Conclusion Compared with continuous combined hormone replacement therapy, 6 and 12 months of raloxifene treatment do not lead to vaginal bleeding/spotting, are not associated with increased endometrial thickness or uterine volume and result in a significantly lower rate of early treatment discontinuations in asymptomatic women receiving treatment to prevent long term postmenopausal health risks.