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Transition to menopause has been associated with an increased risk of cardiovascular disease (CVD), attributed mainly to atherogenic dyslipidemia. Whether lipoprotein (a) [Lp(a)], an independent cardiovascular risk factor, also contributes to menopause-associated CVD has not yet been clarified. The aim of this study was to systematically investigate and meta-analyze the best available evidence regarding the effect of menopause on Lp(a) concentrations.A comprehensive search was conducted in PubMed and Scopus databases up to March 8th, 2022. Data were expressed as weighted mean difference (WMD) with 95 % confidence intervals (CI). The ISeventeen studies were included in the qualitative and 15 in the quantitative analysis, yielding 4686 premenopausal and 8274 postmenopausal women. Lp(a) concentrations were lower in premenopausal than in postmenopausal women [WMD -3.77 (95 % CI -5.37, -2.18) mg/dl, p 0.001; ITransition to menopause may increase Lp(a) concentrations, although the effect of aging cannot be excluded by current data.

This project aims to develop eligibility criteria for menopausal hormone therapy (MHT). The tool should be similar to those already established for contraception A consortium of scientific societies coordinated by the Spanish Menopause Society met to formulate recommendations for the use of MHT by women with medical conditions based on the best available evidence. The project was developed in two phases. As a first step, we conducted 14 systematic reviews and 32 metanalyses on the safety of MHT (in nine areas: age, time of menopause onset, treatment duration, women with thrombotic risk, women with a personal history of cardiovascular disease, women with metabolic syndrome, women with gastrointestinal diseases, survivors of breast cancer or of other cancers, and women who smoke) and on the most relevant pharmacological interactions with MHT. These systematic reviews and metanalyses helped inform a structured process in which a panel of experts defined the eligibility criteria according to a specific framework, which facilitated the discussion and development process. To unify the proposal, the following eligibility criteria have been defined in accordance with the WHO international nomenclature for the different alternatives for MHT (category 1, no restriction on the use of MHT; category 2, the benefits outweigh the risks; category 3, the risks generally outweigh the benefits; category 4, MHT should not be used). Quality was classified as high, moderate, low or very low, based on several factors (including risk of bias, inaccuracy, inconsistency, lack of directionality and publication bias). When no direct evidence was identified, but plausibility, clinical experience or indirect evidence were available, "Expert opinion" was categorized. For the first time, a set of eligibility criteria, based on clinical evidence and developed according to the most rigorous methodological tools, has been defined. This will provide health professionals with a powerful decision-making tool that can be used to manage menopausal symptoms.

Endocrinopathies during pregnancy constitute a challenging issue, being prevalent and requiring appropriate management to avoid maternal and fetal complications. This review aims to summarize and present major endocrine problems during pregnancy, the appropriate screening, maternal monitoring and management, fetal monitoring, and follow-up. Glucose metabolism, thyroid function, as well as calcium and vitamin D metabolism are the main endocrine domains that should be screened and monitored during pregnancy. Gestational diabetes mellitus (GDM) is the most prevalent endocrine disease during pregnancy, followed by thyroid disorders. Specific recommendations are provided for the optimal clinical care of pregnant women and their offspring for GDM, thyroid disorders, and calcium and vitamin D disorders.

Purpose There is controversy regarding the optimal statistical method to interpret how robust is a statistically significant result. The fragility index (FI) and the reverse fragility index (RFI) are quantitative measures that can facilitate the appraisal of a clinical trial’s robustness. This study was performed to evaluate the FI and RFI of randomized controlled trials (RCTs) examining nutritional interventions in patients with diabetes mellitus, focusing on cardiovascular outcomes. Methods A systematic search was conducted and relevant RCTs were identified in three databases. RCTs examining nutritional interventions (supplements or dietary patterns) in patients with DM with dichotomous primary endpoints involving cardiovascular outcomes were eligible. Data were extracted to compose 2 × 2 event tables and the FI and RFI were calculated for each comparison, using Fisher’s exact test. Risk of bias (RoB) of the included RCTs was assessed with the Cochrane RoB 2.0 tool. Results A total of 14,315 records were screened and 10 RCTs were included in the analyses. The median FI of the paired comparisons was 3 (IQR: 2–4) and the median RFI was 8 (IQR: 4.5–17). RoB and heterogeneity were low. Conclusions RCTs examining nutritional interventions and cardiovascular outcomes among patients with diabetes mellitus appear to be statistically fragile. Τhe FI and the RFI can be reported and interpreted as an additional perspective of a trial’s robustness. Highlights • In the evidence-healthcare era, assessing how robust statistically significant results are remains a matter of controversy. • Recently, the fragility index (FI) and reverse fragility index (RFI) were proposed to assess the robustness of randomized controlled trials (RCTs) with 2 × 2 comparisons. • When applying the FI and RFI, RCTs examining nutritional interventions and cardiovascular outcomes among patients with diabetes mellitus (DM) appear to be statistically fragile. • Τhe FI and the RFI can be reported and interpreted as an additional perspective of a trial’s robustness. • RCTs implementing nutrition interventions among patients with DM can improve their methodology.

To review and compare the most recently published recommendations on the investigation and management of abnormal uterine bleeding (AUB).A descriptive review of recommendations from the American College of Obstetricians and Gynaecologists (ACOG), the National Institute for Health and Care Excellence (NICE), the Royal Australian and New Zealand College of Obstetricians and Gynaecologists (RANZCOG), the Society of Obstetricians and Gynaecologists of Canada (SOGC) and the International Federation of Gynaecology and Obstetrics (FIGO) on AUB in reproductive-aged women was carried out.There is a consensus that detailed personal and family history along with physical examination are essential in the investigation of menstrual, intermenstrual or postcoital AUB. All the medical societies recommend transvaginal ultrasound as the first-line imaging modality to determine the AUB cause. Moreover, they agree (except for RANZCOG) that, in women with AUB, endometrial biopsy should only be performed if additional risk factors for endometrial cancer are present. Laboratory tests may be helpful in the AUB investigation; however, there are several discrepancies among the recommendations. Regarding AUB management, NICE, ACOG and SOGC agree that the administration of hormonal or non-hormonal medications should be the first-line treatment modality in bleeding disorders and absent or minor structural pelvic pathology. Surgical management should be preferred in cases of identified polyps, large fibroids or unsuccessful pharmacological treatment.Since AUB affects a significant proportion of reproductive-aged women, the main objective is to improve the quality of life of these patients without missing cases of malignancy.

Vitamin supplements are over-the-counter medications consumed by the majority of adults. Given that many supplements may be ineffective and/or associated with adverse events, compliance of the registered trials to the European Medicines Agency (EMA) rule for prompt reporting of the results is of crucial importance for consumers’ health. The present retrospective study was designed to evaluate compliance with the European Union (EU) requirement to post the trial results to the EU Clinical Trials Database (EudraCT) and assess the trial characteristics associated with this compliance. Three independent researchers searched the EudraCT for completed trials on vitamin supplements performed on humans. A total of 144 completed trials involving 40,464 participants fulfilled the inclusion criteria. For 45.7% of these, results were due. Trials funded by the industry had approximately quadruple chances of being published, adjusting for their design, masking, comparator, and participant age group. Moreover, trials testing vitamin supplement safety are more likely to report their findings as compared to vitamin efficacy. Many vitamin supplementation trials registered in the EudraCT failed to report their results and adhere to the EMA regulations. Stricter regulations should be imposed concerning trial results reporting to increase transparency and public trust.

The International Federation of Gynecology and Obstetrics (FIGO) nutrition checklist is a tool for everyday antenatal clinical practice, easy to use by most healthcare professionals, aiming to initiate a conversation regarding gestational weight gain (GWG) and nutrition and identify women who might require further assessment. The present cross-sectional study aimed to apply the FIGO nutrition checklist to pregnant women attending routine antenatal care and identify nutritional risk factors. Pregnant women (n = 200) were recruited from the outpatient pregnancy clinics of two hospitals in Thessaloniki and completed the checklist. The FIGO-diet quality score and the FIGO-nutritional risk score (NRS) were calculated. The results revealed that 99% of the women exhibited at least one nutritional risk factor based on the checklist. The median FIGO diet quality score of the sample was 4.0 (3.0–5.0), with 95% of the participants responding negatively to at least one question, indicating the need for improving diet quality. Improved diet quality was noted in cases of hyperemesis gravidarum and among those receiving vitamin D supplements. A large percentage of the participants (36%) exhibited five or more nutritional risk factors, as indicated by a total FIGO-NRS below 5. Women with low middle-upper arm circumference, indicative of protein-energy malnutrition (20.6% of the sample), exhibited more nutritional risk factors compared with the rest. On the other hand, being in the third trimester of pregnancy was associated with lower nutritional risk and, subsequently, better diet quality.

Background: Pregnancy is a period of physiological and hormonal alterations that can decrease the quality of life (QoL). Women’s subjective perception of QoL is clinically relevant for assessing the effectiveness of interventions and identifying susceptibility to depression. Objective: This review aims to identify, present, and critically appraise the assessment tools of QoL during pregnancy. Methods: A narrative review of the English-language literature was conducted through the PubMed, CENTRAL, Scopus, and Google Scholar electronic databases. Conclusion: Several generic instruments have been proposed, such as pregnancy-specific and disease- specific questionnaires concerning common diseases during pregnancy. Plasma, salivary and hair cortisol, inflammatory, genetic and epigenetic biomarkers and gut microbiome have also been investigated as potential indicators of maternal anxiety. Their use can quantify the association between pregnancy-specific anxiety and QoL. Application of validated assessment tools of QoL during pregnancy could improve QoL, maternal health interventions, and early identification of susceptibility to maternal depression.

Health problems of women experiencing homelessness are driven either from the usual background characteristics of this population, or from the homeless lifestyle. Apart from poverty and unemployment, transition to homelessness is often associated with substance abuse, history of victimization, stress, poor mental health and human immunodeficiency virus (HIV). Water insecurity can undermine bodily hygiene and dental health, posing a greater risk of dehydration and opportunistic infections. Exposure to extreme environmental conditions like heat waves and natural disasters increases morbidity, accelerates aging, and reduces life expectancy. Nutrition-wise, a high prevalence of food insecurity, obesity, and micronutrient deficiencies are apparent due to low diet quality and food waste. Poor hygiene, violence, and overcrowding increase the susceptibility of these women to communicable diseases, including sexually transmitted ones and COVID-19. Furthermore, established cardiovascular disease and diabetes mellitus are often either undertreated or neglected, and their complications are more widespread than in the general population. In addition, lack of medical screening and contraception non-use induce a variety of reproductive health issues. All these health conditions are tightly related to violations of human rights in this population, including the rights to housing, water, food, reproduction, health, work, and no discrimination. Thus, the care provided to women experiencing homelessness should be optimized at a multidimensional level, spanning beyond the provision of a warm bed, to include access to clean water and sanitation, psychological support and stress-coping strategies, disease management and acute health care, food of adequate quality, opportunities for employment and support for any minor dependants.

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

Positive (statistically significant) findings are easily produced in nutrition research when specific aspects of the research design and analysis are not accounted for. To address this issue, recently, a pledge was made to reform nutrition research and improve scientific trust on the science, encompass research transparency and achieve reproducibility. The aim of the present meta-epidemiological study was to evaluate the statistical significance status of research items published in three academic journals, all with a focus on clinical nutrition science and assessing certain methodological/transparency issues. All research items were published between the years 2015 and 2019. Study design, primary and secondary findings, sample size and age group, funding sources, positivist findings, the existence of a published research protocol and the adjustment of nutrients/dietary indexes to the energy intake (EI) of participants, were extracted for each study. Out of 2127 studies in total, those with positive findings consisted of the majority, in all three journals. Most studies had a published research protocol, however, this was mainly due to the randomized controlled trials and not to the evidence-synthesis studies. No differences were found in the distribution of positive findings according to the existence/inexistence of a published research protocol. In the pooled sample of studies, positive findings differed according to study design and more significant findings were reported by researchers failing to report any funding source. The majority of items published in the three journals (65.9%) failed to account for the EI of participants. The present results indicate that there is still room for the improvement of nutrition research in terms of design, analyses and reporting.

Helicobacter pylori (H. pylori) infection and periodontitis are both inflammatory conditions associated with systemic diseases. Researchers have attempted to investigate the correlation between them. This systematic review and meta-analyses were conducted to investigate the association of H. pylori infection in the stomach and/or in subgingival plaque and gingival crevicular fluid with chronic periodontitis. The protocol was created according to the Preferred Reporting Items for Systematic review and Meta-Analysis Protocols (PRISMA-P) statement. The study was designed according to the Cochrane criteria. A comprehensive literature search was performed in MEDLINE, Scopus, and CENTRAL, combined with hand-searching and assessment of gray literature. The meta-analysis of the included studies was made by the Review Manager (RevMan) 5.4 software. The effect measure of the outcome was odds ratios with 95% confidence intervals. Heterogeneity was assessed by chi-square and I2. Four observational studies involving 818 subjects were included in this meta-analysis. The odds of oral H. pylori presence were higher in patients with chronic periodontitis, compared to healthy controls, with an odds ratio of 1.87 (95% confidence interval 0.85–4.10; p = 0.12). The odds of the presence of H. pylori in the stomach also were higher in patients with chronic periodontitis, with an odds ratio of 1.80 (95% confidence interval 0.82–3.95; p = 0.15). There is no evidence for an association between chronic periodontitis and the prevalence of H. pylori, detected either in subgingival plaque and gingival crevicular fluid or in the stomach.

To assess maternal and neonatal outcomes in women with or without preexisting diabetes mellitus (DM) undergoing assisted reproduction technology (ART) treatment. Prospective or retrospective controlled trials reporting on women with or without preexisting DM undergoing ART treatment were considered eligible. Twelve electronic databases were systematically searched up to December 2020. The risk of bias was assessed by the Cochrane Risk OF Bias In Non-randomized Studies of Interventions (ROBINS-I) tool. Each primary outcome was extracted and pooled as maternal- or neonatal-related. Two studies were included in the systematic review, reporting on both maternal- and neonatal-related parameters after ART treatment. Due to the limited data, no meta-analysis was conducted. Preterm birth, placenta previa, and excessive bleeding during pregnancy were observed more often in pregnancies complicated by preexisting DM conceived by ART compared with pregnancies without DM. There was no difference in the risk for placental abruption between the groups. Regarding the neonatal outcomes, large-for-gestational-age (LGA) embryos and neonatal intensive care unit (NICU) admission were more commonly reported for women with preexisting DM. In one study, preexisting DM was marginally associated with infant mortality. Despite the scarce data, preexisting DM in pregnancies conceived by ART is associated with increased risk for maternal and neonatal complications. Registered in PROSPERO (registration number: 143187).

Overweight, obesity, and metabolic syndrome (MetS) have become epidemic conditions affecting 39%, 13%, and 20% of the population respectively. The aim of this article is to review the literature on the association of obesity and MetS with the risk of cancer. We also explore the effect of lifestyle modifications, such as diet, physical activity, and antidiabetic medications, on cancer incidence. Increased body mass index (BMI) has been associated with a multitude of site-specific cancers, reaching relative risk (RR) 1.54 [95% confidence interval (CI) 1.47-1.61] per 5 unit increase for endometrial cancer, as well as with overall cancer risk (RR 1.03, 95% CI 1.02-1.05). Central adiposity measured by waist circumference or waist-to-hip ratio has been suggested as a stronger predictor than BMI for several cancers, such as colorectal cancer. Metabolic Syndrome has been consistently and positively associated with the risk of very common cancers like colorectal (RR 1.34, 95% CI 1.24-1.44), endometrial (RR 1.62, 95% CI 1.26-2.07) and postmenopausal breast cancer (RR 2.01, 95% CI 1.55-2.60). Hyperglycemia and subsequently T2DM have been also shown to increase the risk of cancer. Nevertheless, these risk factors are modifiable and therefore implementing lifestyle modifications could prevent an important number of cancer cases. Adherence to cancer prevention guidelines, including maintaining a healthy weight, having regular physical exercise (RR 0.58-0.90 for different cite specific cancers) and following a healthy dietary pattern (RR 0.74-0.94 for different cite specific cancers) have a protective effect on the risk of cancer. The strength of this review is the presentation of the best evidence, as the data derive mainly from meta-analyses. Public health policies should focus on the modification of risk factors and future research is needed to reveal the pathophysiological links between these risk factors and cancer to develop more efficient prevention and treatment strategies.

The 2015 American Thyroid Association risk stratification system (ATA RSS) is used in patients with differentiated thyroid carcinoma (DTC) to assess their risk of persistent/recurrent disease. Our aims were to validate the 2015 ATA RSS in a registry of DTC patients and to examine whether the addition of factors not included in it, such as pre-radioactive iodine therapy stimulated thyroglobulin (pre-RAI sTg), gender, and age could increase its predictive ability. We studied 403 patients with DTC, treated at a tertiary center from 1990 to 2018 and subjected to total thyroidectomy. All patients had received RAI therapy, except those with low-risk papillary microcarcinoma. Of our patients, 81.9% were women and 91.1% had papillary thyroid carcinoma. After a median follow-up of 5.0 years, 53 cases of persistent and 21 cases of recurrent disease were recorded. The proportion of variance explained (PVE) regarding the outcome (presence or absence of recurrent/persistent disease) using the 2015 ATA RSS alone was 18.3% (persistence) and 16.9% (recurrence), increasing to 74.4% and 52.0%, respectively, when pre-RAI sTg was added to the logistic regression model. Gender and age were not associated with the disease outcome. In ROC analysis, pre-RAI sTg had a high predictive value for persistent (AUC 0.983, 95% CI 0.962–1.000) and recurrent disease (AUC 0.856, 95% CI 0.715–0.997). The optimal cut-offs and sensitivity, specificity, and positive and negative predictive value for pre-RAI sTg were the following: for persistence 12.75 ng/ml, 100%, 90.5%, 64%, and 100%, and for recurrence 8.05 ng/ml, 77.8%, 85.5%, 36.8%, and 97%. The 2015 ATA RSS displayed moderate performance in predicting recurrent/persistent disease in patients with DTC, which improved with the inclusion of pre-RAI sTg values; pre-RAI sTg was an independent predictor of the disease outcome, with high negative prognostic value.

Gestational diabetes mellitus (GDM) is associated with an increased risk for maternal and fetal complications. Patients with GDM have an increased cardiovascular risk in later life. The aim of this study was to investigate cardiac autonomic nervous system (ANS) function at rest and during exercise in women with GDM vs. women with uncomplicated pregnancies. Thirty-six normotensive pregnant women (21 with GDM and 15 age- and parity-matched women with an uncomplicated pregnancy) were enrolled in this case–control study. Continuous beat-by-beat blood pressure (BP) measurements were recorded during rest, intermittent handgrip exercise, and recovery (via photoplethysmography, Finapres®). Heart rate variability (HRV) (Kubios®) was used for the assessment of autonomic nervous system function. The groups were similar in age, gestational week, and handgrip strength. At rest, no differences in HRV indices [root mean square of successive differences (RMSSD), standard deviation Poincare plot 1, and 2 (SD1, SD2), SD2/SD1 ratio] were detected between women with GDM and women with an uncomplicated pregnancy. However, during exercise, a different pattern in the HRV responses was detected: in the control group, RMSSD and SD1 (indices of parasympathetic function) significantly decreased (p

Background Gynecomastia (GM) is the benign proliferation of glandular tissue in the male breast. It is a common condition, which may occur physiologically and shows three age peaks during a male's lifespan: infancy, puberty, and senescence. An underlying pathology may be revealed in 45%-50% of adult men with GM, such as aggravating medications, systemic diseases, obesity, endocrinopathies, or malignancy. Objective To discuss the role of imaging in the evaluation of GM and its contribution to therapeutic decision-making. Materials/methods The current literature was reviewed through PubMed, Scopus, and CENTRAL electronic databases to identify the best available evidence concerning imaging modalities in patients with GM. Results Most male breast lesions can be diagnosed on clinical grounds; however, in certain cases, when physical examination is inconclusive, imaging may be helpful. Discussion The main purpose of evaluating a patient with GM is to establish the diagnosis and differentiate true GM from pseudogynecomastia, exclude breast cancer, and detect the possible cause. GM is seen in mammography as a subareolar opacity and three mammographic patterns of GM are described: nodular, dendritic, and diffuse, corresponding to florid GM of early onset, fibrous persistent GM, and GM due to exogenous estrogen administration, respectively. In ultrasound (US), florid GM is depicted as a disk-shaped, hypoechoic area underlying the areola, whereas echogenicity of the lesions increases as fibrosis develops. Data on the use of MRI in the evaluation of the male breast and GM are still limited. Imaging findings can be classified according to the BIRADS (breast imaging reporting and data system) based on their malignant potential. Conclusion Both mammography and US are sensitive and specific to diagnose GM and distinguish it from breast cancer. When clinical findings are suggestive of malignancy or imaging findings are inconclusive, a histological confirmation should be sought.

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. Sistema de Investigacion y Desarrollo (SINDE) ; Vice-Rectorado de Investigacion & Postgrado (VRIP) of the Universidad Catolica de Santiago de Guayaquil, Guayaquil, Ecuador

Polycystic ovary syndrome (PCOS) is a common cause of anovulatory infertility. According to the latest guidelines, letrozole should be considered as the first-line pharmacological treatment for women with WHO Group II anovulation or PCOS. However, the use of letrozole as an ovulation induction agent is not FDA or EMA approved, and its use is “off-label.” The main concern with respect to letrozole regards its potential teratogenic effect on the fetus. To determine whether the probability of ovulation is higher with letrozole as compared to clomiphene citrate (CC) in anovulatory women with PCOS. Randomized controlled trials (RCTs) comparing letrozole versus CC used for ovulation induction in infertile women with PCOS followed by timed intercourse (TI) or intrauterine insemination (IUI) were included in this meta-analysis. Primary outcome was ovulation. Secondary outcomes were live birth, clinical pregnancy, miscarriage, multiple pregnancy, and congenital anomalies. Subgroup analysis included patients who received letrozole or CC as first-line treatment, and patients with PCOS diagnosed according to the Rotterdam criteria. Twenty-six RCTs published between 2006 and 2019, involving 4168 patients who underwent 8310 cycles of ovulation induction, were included. The probability of ovulation was significantly higher in letrozole as compared to CC cycles (RR: 1.148, 95% CI: 1.077 to 1.223, 3017 women, 19 trials, I2: 47.7%, low-quality evidence). A higher probability of ovulation is expected in infertile patients with PCOS treated with letrozole as compared to CC. The higher ovulation rate might have contributed to the higher clinical pregnancy and live birth rate. This finding is also true for patients who were administered letrozole as first-line treatment. CRD42019125166

In the surgical correction of tuberous breast deformity, implants and regional flaps play a prominent role. Lately, fat grafting has been used as an alternative, but there is evidence that patient satisfaction is higher after correction with implants compared with lipofilling. We report a tuberous breasts correction series of ten cases, enrolled between 2015 and 2018. Percutaneous fasciotomies and fat grafting were performed by the Body-Jet technique. Analysis of outcomes was undertaken with BREAST-Q surveys. The breast satisfaction scores increased from 0 to 75 (p < 0.01), the psychological well-being scores from 20 to 70 (p < 0.01) and the sexual well-being scores from 18.5 to 58 (p = 0.02), while the physical well-being scores remained stable (from 68 to 63, p = 0.2). The median outcome satisfaction score was 86. Scores of patient-reported outcomes after lipofilling can reach and even exceed those of patients corrected with implants, at the cost of more interventions. Fat grafting is beginning to establish itself as a true alternative in the treatment of tuberous breast deformity in patients with the appropriate fat deposits. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine Ratings, please refer to Table of Contents or online Instructions to Authors www.springer.com/00266 .

Background: Type 2 Diabetes Mellitus (T2DM) is a chronic metabolic disorder with increasing prevalence and a significant burden of long-term complications. Glucagon-like Peptide-1 receptor agonists (GLP-1 RAs) are a novel treatment option for T2DM, exerting optimal effects on glucose control and weight loss, and pleiotropic actions. Pharmacogenetics, a promising research field of precision medicine, investigates how gene variations can affect individual response to drug therapy, assuming that the diverse genetic architecture of patients with T2DM could be partly associated with the considerable inter-individual variability in the therapeutic response to GLP-1 RAs. This review aims to summarize current evidence related to T2DM risk variants, affecting the incretin pathway, focus on the pharmacogenetics of the GLP-1 RA liraglutide, and discuss their potential clinical implications in the management of this complex disorder. Methods: A literature search was performed using electronic biomedical databases, and the findings of key studies are summarized and discussed in this narrative review. Results: Available evidence suggests the involvement of genetic polymorphisms in GLP-1 Rgene in variation in glycemic response, metabolic parameters and gastric emptying in people treated with liraglutide. Polymorphisms in CNR1, CTRB1/2, TMEM114 and CHST3 loci were also shown to be implicated in the disturbance of the incretin homeostasis in T2DM. These findings warrant further investigation by future studies. Conclusion: Robust findings from pharmacogenetic studies might be used to identify good responders to liraglutide treatment, in terms of both glycemic and weight control, thus reinforcing the patient-centered approach of T2DM management.

Sport is historically designated by the binary categorization of male and female that conflicts with modern society. Sport’s governing bodies should consider reviewing rules determining the eligibility of athletes in the female category as there may be lasting advantages of previously high testosterone concentrations for transwomen athletes and currently high testosterone concentrations in differences in sex development (DSD) athletes. The use of serum testosterone concentrations to regulate the inclusion of such athletes into the elite female category is currently the objective biomarker that is supported by most available scientific literature, but it has limitations due to the lack of sports performance data before, during or after testosterone suppression. Innovative research studies are needed to identify other biomarkers of testosterone sensitivity/responsiveness, including molecular tools to determine the functional status of androgen receptors. The scientific community also needs to conduct longitudinal studies with specific control groups to generate the biological and sports performance data for individual sports to inform the fair inclusion or exclusion of these athletes. Eligibility of each athlete to a sport-specific policy needs to be based on peer-reviewed scientific evidence made available to policymakers from all scientific communities. However, even the most evidence-based regulations are unlikely to eliminate all differences in performance between cisgender women with and without DSD and transwomen athletes. Any remaining advantage held by transwomen or DSD women could be considered as part of the athlete’s unique makeup.