Objective To describe differences in the age of onset of menopause and in the prevalence of climacteric symptoms in different geographical areas. Design Systematic review of published data on onset of menopause and symptoms in Europe, North America, Latin America and Asia. Methods We identified publications by searching electronic databases, including MEDLINE (1966–October 2009) and EMBASE (1975–October 2009). Primary search criteria were age of menopause and climacteric symptoms. A sensitive analysis that excluded papers without full data was performed. Results The median age at menopause in Europe ranges from 50.1 to 52.8 years, in North America from 50.5 to 51.4 years, in Latin America from 43.8 to 53 years, and in Asia from 42.1 to 49.5 years. The frequency of vasomotor symptoms varies widely depending on the geographical region, selection of criteria, and method of symptom identification. The prevalence of such symptoms ranges from 74% of women in Europe, 36–50% in North America, 45–69% in Latin America and 22–63% in Asia, as reported in different, large, epidemiological studies. Conclusion There are wide geographical differences in the prevalence of menopausal symptomatology and some differences in the age of onset of menopause. Both in Asia and Latin America, women of poorer socioeconomic status have significantly earlier onset of menopause. Within a geographical region, there are ethnic differences in menopause symptoms. Given differences in study methodologies, firm conclusions are not possible. However, regional differences in age at menopause and in climacteric symptoms are important to acknowledge and lay the foundation for an informed approach to the management of menopause and an understanding of its impact on women's health in the different regions of the world.

To investigate the efficacy and safety of ulipristal acetate (UPA) for long-term treatment of symptomatic uterine fibroids. Repeated intermittent open-label UPA courses, each followed by randomized double-blind norethisterone acetate (NETA) or placebo. European clinical gynecology centers. Two hundred and nine women with symptomatic fibroids including heavy menstrual bleeding. Patients received up to four 3-month courses of UPA 10 mg daily, immediately followed by 10-day double-blind treatment with NETA (10 mg daily) or placebo. Amenorrhea, fibroid volume, endometrial histology. After the first UPA course, amenorrhea occurred in 79% of women, with median onset (from treatment start) of 4 days (interquartile range, 2-6 days). Median fibroid volume change was -45% (interquartile range, -66%; -25%). Amenorrhea rates were 89%, 88%, and 90% for the 131, 119, and 107 women who received treatment courses 2, 3, and 4, respectively. Median times to amenorrhea were 2, 3, and 3 days for treatment courses 2, 3, and 4, respectively. Median fibroid volume changes from baseline were -63%, -67%, and -72% after treatment courses 2, 3, and 4, respectively. All endometrial biopsies showed benign histology without hyperplasia; NETA did not affect fibroid volume or endometrial histology. Repeated 3-month UPA courses effectively control bleeding and shrink fibroids in patients with symptomatic fibroids. ClinicalTrials.gov (www.clinicaltrials.gov) registration numbers NCT01156857 (PEARL III) and NCT01252069 (PEARL III extension).

A systematic review was conducted to analyze the tolerability of several oral iron supplements based on data obtained in available publications and to report the incidence of adverse effects (AEs) for each supplement both overall and gastrointestinal. Electronic databases – Medline, the Cochrane Library, and Embase were searched for studies published up to January 2009. Clinical or observational studies reporting data on the tolerability of oral iron supplements were included. Results were described statistically and a quasi-binomial logistic regression model was developed to evaluate and compare the tolerability of the supplements studied. For this review 111 studies were included, with data on 10,695 patients. Ferrous sulfate with mucoproteose had the lowest incidence of AEs (4.1% for overall AEs, 3.7% for gastrointestinal AEs [GAEs]) and was used as the reference supplement in the regression model. Incidence rates of overall AEs for the other supplements were 7.3% for iron protein succinylate [GAEs: 7%; OR for AE compared to the reference supplement, 1.96], 23.5% for ferrous glycine sulfate [GAEs: 18.5%; OR: 5.90], 30.9% for ferrous gluconate [GAEs: 29.9%; OR: 11.06], 32.3% for ferrous sulfate without mucoproteose [GAEs: 30.2%; OR: 11.21], and 47.0% for ferrous fumarate [GAEs: 43.4%; OR: 19.87]. The differences in incidence of AEs between extended-release ferrous sulfate with mucoproteose and all other supplements except iron protein succinylate were statistically significant at p < 0.001. These findings are subject to some limitations as the designs and methodologies of the studies included show heterogeneity among them that has partially been counteracted by the large sample size provided by the substantial number of trials, which is considered a strength in tolerability studies. Extended-release ferrous sulfate with mucoproteose appears to be the best tolerated of the different oral iron supplements evaluated.

Several 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). A 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. Several 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. In 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.

Vulvovaginal atrophy (VVA) or atrophic vaginitis is a medical challenge because it is under-reported by women, under-recognized by health-care providers and, therefore, under-treated. More or less 50% of postmenopausal women experience vaginal discomfort attributable to VVA. Very recent surveys suggest health-care providers should be proactive in order to help their patients to disclose the symptoms related to VVA and to seek adequate treatment when vaginal discomfort is clinically relevant. Women are poorly aware that VVA is a chronic condition with a significant impact on sexual health and quality of life and that effective and safe treatments may be available. Indeed, female sexual dysfunction and genitourinary conditions are more prevalent in women with VVA. That being so, it is very important to include VVA in the menopause agenda, by encouraging an open and sensible conversation on the topic of intimacy and performing a gynecological pelvic examination, if indicated. According to very recent guidelines for the appropriate management of VVA in clinical practice, it is essential to overcome the vaginal 'taboo' in order to optimize elderly women's health care.

Objectives The aim of the European REVIVE survey was to achieve a better understanding of vulvovaginal atrophy (VVA), a chronic and progressive condition after menopause. We investigated perceptions, experiences and needs in terms of sexual and vaginal health in a sample of European postmenopausal women. Methods An online internet based survey was conducted in Italy, Germany, Spain and the UK with a total surveyed sample of 3768 postmenopausal women (age: 45–75 years). Results The most common VVA symptom was vaginal dryness (70%). VVA has a significant impact on the ability to be intimate (62%), to enjoy sexual intercourse (72%) and to feel sexual spontaneity (66%). Postmenopausal women with VVA are sexually active (51%), but their sexual drive is reduced. Health-care professionals (HCPs) have discussed VVA with postmenopausal women (62%), but they initiated the conversation only in 10% of the cases. The most common treatments for VVA are over-the-counter, non-hormonal, local vaginal products. Thirty-two per cent of postmenopausal women were naïve to any kind of treatment, whereas discussion with the HCP was relevant to be on current treatment (60% of postmenopausal women that discussed VVA with a HCP vs. 23% who did not). The top reasons for poor compliance with vaginal treatments were: not bothersome enough symptoms (18%); vaginal changes not therapeutically reversed (18%); relief from VVA symptoms (17%). Approximately 45% were satisfied with treatment. The most frequent disliked aspects of treatment were the route of administration or the messiness. The fear of hormones was common in postmenopausal women using vaginal prescription products. Conclusions The European REVIVE survey confirmed that VVA symptoms are frequent in postmenopausal women and demonstrates a significant impact on quality of life and sexual life. However, the condition is still under-diagnosed and under-treated, with a high rate of dissatisfaction for actual available treatments in the four European countries surveyed. The discussion of symptoms with HCPs seems the most critical factor for diagnosis and treatment of VVA.