EMAS position statement: Testosterone replacement therapy in older men.

INTRODUCTION: Late-onset hypogonadism is the clinical entity characterised by low testosterone concentrations associated with clinical symptoms in the absence of organic disease in ageing men. It has been associated with metabolic syndrome, reduced bone mineral density, and increased cardiovascular morbidity and mortality risk. Although testosterone replacement therapy (TRT) reverses most of these conditions in young hypogonadal men, the risk/benefit ratio of TRT in older men is debatable. AIM: To update the 2015 EMAS statement on TRT in older men with new research on late-onset hypogonadism and TRT. MATERIALS AND METHODS: Literature review and consensus of expert opinion. SUMMARY RECOMMENDATIONS: TRT should be offered only to symptomatic older men with confirmed low testosterone concentrations after explaining the uncertainties regarding the long-term safety of this treatment. TRT may be offered to men with severe hypogonadism and erectile dysfunction to improve sexual desire, erectile, and orgasmic function. It should also be considered in hypogonadal men with severe insulin resistance or pre-diabetes mellitus. TRT may also be considered, in combination with proven treatment strategies, for osteoporosis, or for selected patients with persistent mild depressive symptoms and/or low self-perceived quality of life, combined with standard medical care for each condition. TRT is contraindicated in hypogonadal men actively seeking fertility treatment. Due to a lack of data, TRT should not be routinely used in older men to improve exercise capacity/physical function, improve cognitive function, or prevent cognitive decline. TRT must be avoided in older, frail men with known breast cancer or untreated prostate cancer and all men who have had myocardial infarction or stroke within the last four months, and those with severe or decompensated heart failure. The quality of evidence regarding patients with previous prostate cancer or cardiovascular disease is too low to draw definitive conclusions. Any limits on duration of use are arbitrary, and treatment should continue for as long as the man feels the benefits outweigh the risks for him, and decisions must be made on an individual basis. Withdrawal should be considered when hypogonadism is reversed after the resolution of underlying disorder. Short-acting transdermal preparations should be preferred for TRT initiation in older men, but injectable forms may be considered subsequently. Older men on TRT should be monitored at 3, 6, and 12 months after initiation and at least yearly thereafter, or earlier and more frequently if indicated. Evaluation should include assessment of the clinical response, and measurement of total testosterone, haematocrit, and prostate-specific antigen (PSA) concentrations. Bone density and/or quality should also be assessed. Obese and overweight patients should be encouraged to undergo lifestyle modifications, including exercise and weight loss, to increase endogenous testosterone.

Vitamin D, Menopausal Health and COVID-19: Critical Appraisal of Current Data.

Inconsistency exists across studies conducted in postmenopausal women regarding the effect of vitamin D deficiency (VDD) and supplementation on several aspects of menopausal health, such as fractures, vasomotor symptomatology, cardiovascular disease (CVD), cancer and infections, including coronavirus disease 2019 (COVID-19). The aim of this review is to critically summarize the evidence provided by observational studies and randomized controlled trials (RCTs) of vitamin D supplementation in postmenopausal women with VDD. Observational studies have found that VDD is associated with an increased risk of falls and fractures after the menopause. VDD also has a negative effect on menopausal symptomatology. VDD, especially its severe form, is associated with an increased risk of CVD risk factors and CVD events. VDD is associated with increased risk and mortality from several cancer types and risk of infections. The evidence from RCTs regarding the effect of vitamin D supplementation on falls, fractures, menopausal symptoms, cardiovascular disease, cancer and infections is not robust. Thus, skeletal health may benefit only when vitamin D is co-administered with calcium, especially in those ≥70 years old and with severe VDD. There is no evidence of a favorable effect on menopausal symptoms or risk of CVD or cancer, except for a modest reduction in cancer-related mortality. Inconsistency still exists regarding its effect on infection risk, disease severity and mortality due to COVID-19.

EMAS position statement: Vitamin D and menopausal health.

INTRODUCTION: There is increasing evidence that vitamin D has widespread tissue effects. In addition to osteoporosis, vitamin D deficiency has been associated with cardiovascular disease, diabetes, cancer, infections and neurodegenerative disease. However, the effect of vitamin D supplementation on non-skeletal outcomes requires clarification, especially in postmenopausal women. AIM: This position statement provides an evidence-based overview of the role of vitamin D in the health of postmenopausal women based on observational and interventional studies. MATERIALS AND METHODS: Literature review and consensus of expert opinion. RESULTS AND CONCLUSIONS: Vitamin D status is determined by measuring serum 25-hydroxyvitamin D levels. Concentrations <20 ng/ml (<50 nmol/l) and <10 ng/ml (<25 nmol/l) are considered to constitute vitamin D deficiency and severe deficiency, respectively. Observational data suggest an association between vitamin D deficiency and adverse health outcomes in postmenopausal women, although they cannot establish causality. The evidence from randomized controlled trials concerning vitamin D supplementation is not robust, since many studies did not consider whether people were deficient at baseline. Moreover, high heterogeneity exists in terms of the population studied, vitamin D dosage, calcium co-administration and duration of intervention. Concerning skeletal health, vitamin D deficiency is associated with low bone mass and an increased risk of fractures. Vitamin D supplementation at maintenance doses of 800-2000 IU/day (20-50 µg/day), after repletion of vitamin D status with higher weekly or daily doses, may be of benefit only when co-administered with calcium (1000-1200 mg/day), especially in the elderly populations and those with severe vitamin D deficiency. Concerning cardiovascular disease, vitamin D deficiency is associated with an increased prevalence of cardiovascular risk factors, mainly metabolic syndrome, type 2 diabetes mellitus and dyslipidemia. Vitamin D deficiency, especially its severe form, is associated with an increased risk of cardiovascular events (coronary heart disease, stroke, mortality), independently of traditional risk factors. Vitamin D supplementation may have a modestly beneficial effect on lipid profile and glucose homeostasis, especially in obese individuals or those ≥60 years old and at doses of ≥2000 IU/day (≥50 µg/day). However, it has no effect on the incidence of cardiovascular events. Concerning cancer, vitamin D deficiency is associated with increased incidence of and mortality from several types of cancer, such as colorectal, lung and breast cancer. However, the data on other types of gynecological cancer are inconsistent. Vitamin D supplementation has no effect on cancer incidence, although a modest reduction in cancer-related mortality has been observed. Concerning infections, vitamin D deficiency has been associated with acute respiratory tract infections, including coronavirus disease 2019 (COVID-19). Vitamin D supplementation may decrease the risk of acute respiratory tract infections and the severity of COVID-19 (not the risk of infection). Concerning menopausal symptomatology, vitamin D deficiency may have a negative impact on some aspects, such as sleep disturbances, depression, sexual function and joint pains. However, vitamin D supplementation has no effect on these, except for vulvovaginal atrophy, at relatively high doses, i.e., 40,000-60,000 IU/week (1000-1500 IU/week) orally or 1000 IU/day (25 µg/day) as a vaginal suppository.

Menopause, wellbeing and health: A care pathway from the European Menopause and Andropause Society.

This care pathway from the European Menopause and Andropause Society (EMAS) provides an updated pathway for monitoring and guidance of women at midlife, focusing on those approaching the end of the reproductive life-cycle, going through the menopausal transition and beyond. The care pathway is written by professionals involved in women's health and provides a stepwise individualized approach, stratified according to needs, symptoms and reproductive stage. Furthermore, the pathway provides details on screening for chronic diseases related to menopause and ageing. Treatment options for climacteric symptoms range from menopausal hormone therapy to non-hormonal alternatives and lifestyle modifications. Therapy should be tailored to personal needs and wishes. The pathway aims to offer a holistic, balanced approach for monitoring middle-aged women, aiming to control health problems effectively and ensure healthy ageing.

Menopausal hormone therapy in women with benign gynaecological conditions and cancer.

The efficacy of menopausal hormone therapy for bothersome menopausal symptoms is well established. However, there are a range of benign and malignant gynaecological conditions that pose a challenge in managing menopausal symptoms. Their hormone-dependent nature either raises concerns about symptom recurrence or malignant disease progression making decisions about menopausal hormone therapy complex for both clinicians and patients. It appears there is a small potential for symptom recurrence with menopausal hormone therapy use in menopausal women with a history of severe endometriosis. Malignant transformation of previous endometriotic lesions is likely to be rare but is not adequately understood. In this setting, combined hormone therapy is preferred, including in woman post-hysterectomy. Uterine fibroids are not a contraindication to menopausal hormone therapy use but women with large fibroids at menopause should have regular follow-up of their fibroids. Generally, menopausal hormone therapy is considered appropriate for women with cervical cancer and most ovarian cancers except for low grade serous tumours. Endometrial cancer requires an individualised discussion. The overall quality of data in this area is poor but suggests women with a low risk of recurrence may consider hormonal therapy, balancing symptom impact with prognosis.

Summarised, verified and accessible: improving clinical information management for potential haematopoietic stem cell transplantation patients.

The Welsh Transplantation and Immunogenetics Laboratory (WTAIL) is responsible for managing patient work-up for haematopoietic stem cell transplantation (HSCT), the only potentially curative option for many haematological and non-haematological conditions. Work-up requires regular communication between WTAIL and the transplanting clinicians, facilitated by weekly multidisciplinary team (MDT) meetings, to agree decisions and proceed through each work-up stage. Effective communication and minimising error are critical, as transplanting cells from a suboptimal donor could have severe or fatal consequences for the patient. We reviewed our HSCT patient management and identified issues including staff dissatisfaction with the inefficiency of the current (paper-based) system and concern about the potential for incidents caused by errors in manual transcription of patient information and tracking clinical decisions. Another driver for change was the COVID-19 pandemic, which prevented the usual face-to-face MDT meetings in which staff would show clinicians the paper records and reports; the shift to online MDT required new ways of sharing data. In this project we developed a new central reference point for our patient management data along with electronic patient summary sheets, designed with an eye to improving safety and efficiency. Over several improvement cycles we tested and refined the summary sheets with staff and clinicians and experimented with videoconferencing to facilitate data sharing. We conducted interviews with staff from which we concluded that the new process successfully reduced transcription and duplication and improved communication with the clinicians during the pandemic. Despite an increase in workload due to build-up of active patient work-up cases during the pandemic, staff reported that the new summaries enabled them to cope well. A key initiative was creation of a 'Task and Finish' group that helped establish continual improvement culture and identified additional areas for improvement which have been followed up in further improvement projects.

Topical estrogens and non-hormonal preparations for postmenopausal vulvovaginal atrophy: An EMAS clinical guide.

INTRODUCTION: Vulvovaginal atrophy (VVA) is a chronic condition caused by estrogen deficiency. It affects around 50% of postmenopausal women, reducing their general and sexual quality of life as well as the quality of their personal relationships. AIM: The aim of this clinical guide is to set out an individualized approach to the management of VVA with topical estrogens and non-hormonal preparations. MATERIALS AND METHODS: Literature review and consensus of expert opinion. SUMMARY RECOMMENDATIONS: An individualized approach is required for the management of VVA. Topical low-dose estrogens are effective and also alleviate urinary incontinence and prevent recurrent urinary tract infections. Women should not be denied long-term use of topical estrogens as long as they feel that this treatment is of benefit to them, because the safety data are reassuring. Non-hormonal preparations (lubricants and moisturizers) should be the first-line treatment for VVA in women taking adjuvant endocrine therapies for cancers considered to be hormone-dependent. They can be used over the long term.

Management of urinary incontinence in postmenopausal women: An EMAS clinical guide.

INTRODUCTION: The prevalence of urinary incontinence and of other lower urinary tract symptoms increases after the menopause and affects between 38 % and 55 % of women aged over 60 years. While urinary incontinence has a profound impact on quality of life, few affected women seek care. AIM: The aim of this clinical guide is to provide an evidence-based approach to the management of urinary incontinence in postmenopausal women. MATERIALS AND METHODS: Literature review and consensus of expert opinion. SUMMARY RECOMMENDATIONS: Healthcare professionals should consider urinary incontinence a clinical priority and develop appropriate diagnostic skills. They should be able to identify and manage any relevant modifiable factors that could alleviate the condition. A wide range of treatment options is available. First-line management includes lifestyle and behavioral modification, pelvic floor exercises and bladder training. Estrogens and other pharmacological interventions are helpful in the treatment of urgency incontinence that does not respond to conservative measures. Third-line therapies (e.g. sacral neuromodulation, intravesical onabotulinum toxin-A injections and posterior tibial nerve stimulation) are useful in selected patients with refractory urge incontinence. Surgery should be considered in postmenopausal women with stress incontinence. Midurethral slings, including retropubic and transobturator approaches, are safe and effective and should be offered.

Management of menopausal symptoms and ovarian function preservation in women with gynecological cancer.

Gynecological cancers affect a growing number of women globally, with approximately 1.3 million women diagnosed in 2018. Menopausal symptoms are a significant health concern after treatment for gynecological cancers and may result from oncologic treatments such as premenopausal bilateral oophorectomy, ovarian failure associated with chemotherapy or radiotherapy, and anti-estrogenic effects of maintenance endocrine therapy. Additionally, with the growing availability of testing for pathogenic gene variants such as BRCA1/2 and Lynch syndrome, there is an increasing number of women undergoing risk-reducing oophorectomy, which in most cases will be before age 45 years and will induce surgical menopause. Not all menopausal symptoms require treatment, but patients with cancer may experience more severe symptoms compared with women undergoing natural menopause. Moreover, there is increasing evidence of the long-term implications of early menopause, including bone loss, cognitive decline and increased cardiovascular risk. Systemic hormone therapy is well established as the most effective treatment for vasomotor symptoms and vaginal (topical) estrogen therapy is effective for genitourinary symptoms. However, the role of hormone receptors in many gynecological cancers and their treatment pose a challenge to the management of menopausal symptoms after cancer. Consequently, the use of menopausal hormone therapy in this setting can be difficult for clinicians to navigate and this article aims to provide current, comprehensive guidance for the use of menopausal hormone replacement therapy in women who have had, or are at risk of developing, gynecological cancer to assist with these treatment decisions.

The Mediterranean diet and menopausal health: An EMAS position statement.

INTRODUCTION: Globally, 985 million women are aged 50 and over, leading to increasing concerns about chronic conditions such as cardiovascular disease, osteoporosis, dementia, and cognitive decline, which can adversely affect quality of life and independent living. AIM: To evaluate the evidence from observational studies and randomized trials on the effects of the Mediterranean diet on short- and long-term menopausal health: estrogen deficiency symptoms, cardiovascular disease, osteoporosis, cognitive and mental health, breast cancer, and all-cause mortality. MATERIALS AND METHODS: Literature review and consensus of expert opinion. SUMMARY RECOMMENDATIONS: The Mediterranean diet is a non-restrictive dietary pattern common in the olive-growing areas of the Mediterranean basin. It may improve vasomotor symptoms, cardiovascular risk factors such as blood pressure, cholesterol and blood glucose levels, as well as mood and symptoms of depression. Long-term adherence may: improve cardiovascular risk and events, and death; improve bone mineral density; prevent cognitive decline; and reduce the risk of breast cancer and all-cause mortality.

Menopause symptom management in women with dyslipidemias: An EMAS clinical guide.

INTRODUCTION: Dyslipidemias are common and increase the risk of cardiovascular disease. The menopause transition is associated with an atherogenic lipid profile, with an increase in the concentrations of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), apolipoprotein B (apoB) and potentially lipoprotein (a) [Lp(a)], and a decrease in the concentration of high-density lipoprotein cholesterol (HDL-C). AIM: The aim of this clinical guide is to provide an evidence-based approach to management of menopausal symptoms and dyslipidemia in postmenopausal women. The guide evaluates the effects on the lipid profile both of menopausal hormone therapy and of non-estrogen-based treatments for menopausal symptoms. MATERIALS AND METHODS: Literature review and consensus of expert opinion. SUMMARY RECOMMENDATIONS: Initial management depends on whether the dyslipidemia is primary or secondary. An assessment of the 10-year risk of fatal cardiovascular disease, based on the Systematic Coronary Risk Estimation (SCORE) system, should be used to set the optimal LDL-C target. Dietary changes and pharmacological management of dyslipidemias should be tailored to the type of dyslipidemia, with statins constituting the mainstay of treatment. With regard to menopausal hormone therapy, systemic estrogens induce a dose-dependent reduction in TC, LDL-C and Lp(a), as well as an increase in HDL-C concentrations; these effects are more prominent with oral administration. Transdermal rather than oral estrogens should be used in women with hypertriglyceridemia. Micronized progesterone or dydrogesterone are the preferred progestogens due to their neutral effect on the lipid profile. Tibolone may decrease TC, LDL-C, TG and Lp(a), but also HDL-C concentrations. Low-dose vaginal estrogen and ospemifene exert a favorable effect on the lipid profile, but data are scant regarding dehydroepiandrosterone (DHEA). Non-estrogen-based therapies, such as fluoxetine and citalopram, exert a more favorable effect on the lipid profile than do sertraline, paroxetine and venlafaxine. Non-oral testosterone, used for the treatment of hypoactive sexual desire disorder/dysfunction, has little or no effect on the lipid profile.

European Menopause and Andropause Society (EMAS) and International Gynecologic Cancer Society (IGCS) position statement on managing the menopause after gynecological cancer: focus on menopausal symptoms and osteoporosis.

INTRODUCTION: Worldwide, it is estimated that about 1.3 million new gynecological cancer cases are diagnosed each year. For 2018, the predicted annual totals were cervix uteri 569,847, corpus uteri 382,069, ovary 295,414, vulva 44,235 and va​gina 17,600. Treatments include hysterectomy with or without bilateral salpingo-oophorectomy, radiotherapy and chemotherapy. These can result in loss of ovarian function and, in women under the age of 45, early menopause. AIM: The aim of this position statement is to set out an individualized approach to the management, with or without menopausal hormone therapy, of menopausal symptoms and the prevention and treatment of osteoporosis in women with gynecological cancer. MATERIALS AND METHODS: Literature review and consensus of expert opinion. SUMMARY RECOMMENDATIONS: The limited data suggest that women with low-grade, early-stage endometrial cancer may consider systemic or topical estrogens. However, menopausal hormone therapy may stimulate tumor growth in patients with more advanced disease, and non-hormonal approaches are recommended. Uterine sarcomas may be hormone dependent, and therefore estrogen and progesterone receptor testing should be undertaken to guide decisions as to whether menopausal hormone therapy or non-hormonal strategies should be used. The limited evidence available suggests that menopausal hormone therapy, either systemic or topical, does not appear to be associated with harm and does not decrease overall or disease-free survival in women with non-serous epithelial ovarian cancer and germ cell tumors. Caution is required with both systemic and topical menopausal hormone therapy in women with serous and granulosa cell tumors because of their hormone dependence, and non-hormonal options are recommended as initial therapy. There is no evidence to contraindicate the use of systemic or topical menopausal hormone therapy by women with cervical, vaginal or vulvar cancer, as these tumors are not considered to be hormone dependent.

European Menopause and Andropause Society (EMAS) and International Gynecologic Cancer Society (IGCS) position statement on managing the menopause after gynecological cancer: focus on menopausal symptoms and osteoporosis.

Worldwide, it is estimated that about 1.3 million new gynecological cancer cases are diagnosed each year. For 2018, the predicted annual totals were cervix uteri 569 847, corpus uteri 382 069, ovary 295 414, vulva 44 235, and va​gina 17 600. Treatments include hysterectomy with or without bilateral salpingo-oophorectomy, radiotherapy, and chemotherapy. These can result in loss of ovarian function and, in women under the age of 45 years, early menopause. The aim of this position statement is to set out an individualized approach to the management, with or without menopausal hormone therapy, of menopausal symptoms and the prevention and treatment of osteoporosis in women with gynecological cancer. Our methods comprised a literature review and consensus of expert opinion. The limited data suggest that women with low-grade, early-stage endometrial cancer may consider systemic or topical estrogens. However, menopausal hormone therapy may stimulate tumor growth in patients with more advanced disease, and non-hormonal approaches are recommended. Uterine sarcomas may be hormone dependent, and therefore estrogen and progesterone receptor testing should be undertaken to guide decisions as to whether menopausal hormone therapy or non-hormonal strategies should be used. The limited evidence available suggests that menopausal hormone therapy, either systemic or topical, does not appear to be associated with harm and does not decrease overall or disease-free survival in women with non-serous epithelial ovarian cancer and germ cell tumors. Caution is required with both systemic and topical menopausal hormone therapy in women with serous and granulosa cell tumors because of their hormone dependence, and non-hormonal options are recommended as initial therapy. There is no evidence to contraindicate the use of systemic or topical menopausal hormone therapy by women with cervical, vaginal, or vulvar cancer, as these tumors are not considered to be hormone dependent.

EMAS position statement: Predictors of premature and early natural menopause.

INTRODUCTION: While the associations of genetic, reproductive and environmental factors with the timing of natural menopause have been extensively investigated, few epidemiological studies have specifically examined their association with premature (<40 years) or early natural menopause (40-45 years). AIM: The aim of this position statement is to provide evidence on the predictors of premature and early natural menopause, as well as recommendations for the management of premature and early menopause and future research. MATERIALS AND METHODS: Literature review and consensus of expert opinion. RESULTS AND CONCLUSIONS: Strong genetic predictors of premature and early menopause include a family history of premature or early menopause, being a child of a multiple pregnancy and some specific genetic variants. Women with early menarche and nulliparity or low parity are also at a higher risk of experiencing premature or early menopause. Cigarette smoking (with a strong dose-response effect) and being underweight have been consistently associated with premature and early menopause. Current guidelines for the management of premature and early menopause mainly focus on early initiation of hormone therapy (HT) and continued treatment until the woman reaches the average age at menopause (50-52 years). We suggest that clinicians and health professionals consider the age at menopause of the relevant region or ethnic group as part of the assessment for the timing of HT cessation. In addition, there should be early monitoring of women with a family history of early menopause, who are a child of a multiple pregnancy, or who have had early menarche (especially those who have had no children). As part of preventive health strategies, women should be encouraged to quit smoking (preferably before the age of 30 years) and maintain optimal weight in order to reduce their risk of premature or early menopause.

Current management of pelvic organ prolapse in aging women: EMAS clinical guide.

Management of pelvic organ prolapse (POP) is a common and challenging task. Nowadays older women are more active than they were in the past, and the development of POP disrupts quality of life and impairs social and personal activities. The menopausal transition is a time of vulnerability, during which many women start experiencing symptoms and signs of POP. The role of hormonal changes or of hormonal therapies in influencing the development or progression of POP has been explored extensively. The management of POP requires considerable clinical skills. Correct diagnosis and characterization of the prolapse and an identification of the individual woman's most bothersome symptoms are the hallmark of appropriate initial management. Therapy is multimodal and often multidisciplinary, and requires a competence in pelvic medicine and surgery. The integration of hormonal, non-hormonal and surgical strategies is important and needs to be adjusted to changing circumstances on an individualized basis. When surgery is required, optimal management requires clinicians who are familiar with the advantages and disadvantages of all the available strategies and who are able to use these strategies in a tailored manner. Complex cases should be sent to specialist referral centers. Management of POP should be integrated into the practice of healthcare professionals dealing in menopause.

Interventions to reduce the risk of ovarian and fallopian tube cancer: A European Menopause and Andropause Society Postition Statement.

BACKGROUND: Ovarian cancer is a leading cause of female gynecological cancer-related death, and there are no effective screening procedures or early diagnostic approaches. AIMS: To examine risk factors and risk-reducing strategies for both sporadic and familial tumors. MATERIALS AND METHODS: Literature review and consensus of expert opinion. RESULTS AND CONCLUSIONS: In women with a genetic predisposition to ovarian cancer, salpingo-oophorectomy reduces the risk of ovarian malignancy, and to a lesser degree of breast cancer. Opportunistic bilateral salpingo-oophorectomy and bilateral salpingectomy may also prevent epithelial ovarian cancer. In premenopausal women, bilateral salpingectomy should be preferred to tubal ligation, and be performed when hysterectomy is carried out for benign uterine disease. Hysterectomy and the use of combined oral contraceptives and non-steroid anti-inflammatory drugs are also recognized to reduce the risk of ovarian cancer, as do the prevention of obesity and smoking cessation.

Osteoporosis management in patients with breast cancer: EMAS position statement.

Aromatase inhibitors (AIs) are the first-line recommended standard of care for postmenopausal estrogen receptor-positive breast cancer. Because they cause a profound suppression of estrogen levels, concerns regarding their potential to increase the risk of fracture were rapidly raised. There is currently a general consensus that a careful baseline evaluation is needed of the risk of fracture in postmenopausal women about to start treatment with AIs but also in all premenopausal women with early disease. Bisphosphonates have been shown in several phase III trials to prevent the bone loss induced by cancer treatment, although no fracture data are available. Even though they do not have regulatory approval for this indication, their use must be discussed with women at high risk of fracture. Accordingly, several guidelines recommend considering treatment in women with a T-score ≤-2 or those with two or more clinical risk factors. Moreover, recent data suggest that bisphosphonates, especially intravenous zoledronic acid, may have an anticancer effect, in that they reduce bone recurrence as well as extra-skeletal metastasis and breast cancer mortality in postmenopausal women. The anti-RANK ligand antibody denosumab is also emerging as a new adjuvant therapeutic option to prevent AI-induced bone loss. It has been shown to extend the time to first fracture in postmenopausal women treated with AIs. Several issues still need to be addressed regarding the use of these different agents in an adjuvant setting. The purpose of this position statement is to review the literature on antifracture therapy and to discuss the current guidelines for the management of osteoporosis in women with early breast cancer.

Donor-specific antibodies require preactivated immune system to harm renal transplant.

BACKGROUND: It is an unresolved issue why some kidney transplant recipients with pretransplant donor-specific HLA antibodies (DSA) show a high transplant failure rate, whereas in other patients DSA do not harm the graft. We investigated whether help from preactivated T-cells might be necessary for DSA to exert a deleterious effect. METHODS: The impact of pretransplant DSA and immune activation marker soluble CD30 (sCD30) on 3-year graft survival was analyzed in 385 presensitized kidney transplant recipients. FINDINGS: A deleterious influence of pretransplant DSA on graft survival was evident only in patients who were positive for the immune activation marker sCD30. In the absence of sCD30 positivity, 3-year graft survival was virtually identical in patients with or without DSA (83.1±3.9% and 84.3±2.8%, P=0.81). A strikingly lower 3-year graft survival rate of 62.1±6.4% was observed in patients who were both sCD30 and DSA positive (HR 2.92, P<0.001). Even in the presence of strong DSA with ≥5000 MFI, the 3-year graft survival rate was high if the recipients were sCD30 negative. INTERPRETATION: Pretransplant DSA have a significantly deleterious impact on graft survival only in the presence of high pretransplant levels of the activation marker sCD30.