Contrasting bone profiles in PCOS are related to BMI: a systematic review and meta-analysis.

CONTEXT: Controversial results have emerged regarding whether PCOS is protective or increases the risk of bone frailty. OBJECTIVE: This study investigated whether the PCOS condition affects bone parameters of premenopausal women. This is an update for a previous meta-analysis published in 2019. DATA SOURCES: We searched MEDLINE and Embase. STUDY SELECTION: Studies were considered eligible for the update if published in English between the 1st of October 2018 and the 31st of December 2023. The diagnosis of PCOS should be based on NIH criteria, the Rotterdam Consensus, AE-PCOS society criteria, or ICD codes in women over 18 years old. Only records with the Newcastle-Ottawa Scale > 6 were selected for data extraction. DATA EXTRACTION: Data were extracted by two independent reviewers. DATA SYNTHESIS: We identified 31 studies that met the inclusion criteria for qualitative analysis from 3322 studies in the whole period (1990-2023). Overall, cross-sectional studies included 1822 individuals with PCOS and 1374 controls, while cohort studies incorporated 30305 women with PCOS and 101907 controls. Contrasting profiles emerged after stratification using a BMI cutoff of 27 kg/m2. Individuals with PCOS and a BMI <27 kg/m2 exhibited lower vertebral and non-vertebral bone density, reduced bone turnover marker (osteocalcin), and increased bone resorption marker (CTX) levels. Conversely, individuals with PCOS and a BMI >27 kg/m2 exhibited increased vertebral and non-vertebral BMD, with no significant changes in bone formation and resorption markers (except osteocalcin). CONCLUSIONS: The findings of this study alert for a low bone mass, low bone formation, and increased bone resorption PCOS with a BMI <27 kg/m2.

The role of the visceral adiposity index in the assessment of metabolic syndrome of polycystic ovary syndrome patients: a new anthropometric index.

PURPOSE: Polycystic ovary syndrome (PCOS) is a common endocrine disorder often linked to metabolic syndrome (MS), raising the risk of cardiovascular disease and type II diabetes. Certain indicators, such as the lipid accumulation product (LAP) and homeostatic model assessment for insulin resistance (HOMA-IR), can predict MS in PCOS patients. This study aimed to assess the predictive power of the visceral adiposity index (VAI) in comparison to LAP and HOMA-IR as predictors of MS in PCOS patients. METHODS: In this cross-sectional observational study, data from 317 diagnosed PCOS women were analyzed. VAI, LAP, and HOMA-IR were computed as indexes. Participants were categorized into two groups for index accuracy comparison: PCOS patients with and without MS. The data were assessed using a ROC curve. RESULTS: Among PCOS women with MS, 92.3% had abnormal VAI results, 94.5% had abnormal LAP results, and only 50.5% had abnormal HOMA-IR results. Conversely, the majority of PCOS women without MS had normal HOMA-IR (64.6%). When comparing these indexes using the ROC curve, VAI displayed the highest accuracy, followed by LAP and HOMA-IR. CONCLUSION: The VAI index proved to be a superior predictor of metabolic MS in PCOS women when compared to other indexes.

Understanding hirsutism in PCOS.

INTRODUCTION: Hirsutism is a prevalent condition among women and represents a primary clinical feature of polycystic ovary syndrome (PCOS). AREAS COVERED: Our study aims to address the principal challenges associated with this hyperandrogenic manifestation in PCOS women. Our narrative review based on the available indexed literature explored the complexities of establishing mFG cutoff values for various ethnic groups, investigated hirsutism during peri- and postmenopausal stages, and examined the role of oxyandrogens. EXPERT OPINION: Hirsutism may have a negative impact on the quality of life and on the mental health, being associated with anxiety and depression. Future perspectives for its diagnosis include the use of artificial intelligence and the consideration of the distress caused by excessive hair growth.

A comparative study of cardiovascular risk stratification methods in type 1 diabetes mellitus patients.

The Steno Diabetes Center Copenhagen developed the Steno T1 Risk Engine (ST1RE) to predict cardiovascular events, encompassing fatal and nonfatal ischemic heart disease, ischemic stroke, heart failure, and peripheral arterial disease in type 1 diabetes mellitus(T1DM).The current study investigated the agreement between ST1RE and the Brazilian Society for Endocrinology and Metabology (SBEM) classification. Participants were included in the study if diagnosed with T1DM and had at least one outpatient visit in 2021. Patients with established cardiovascular disease and chronic kidney disease on dialysis were excluded. Clinical parameters were obtained from medical records, such as age, body mass index (BMI), blood pressure, physical activity, current smoking, microvascular target organ damage, levels of low-density lipoprotein cholesterol, creatinine, glycated hemoglobin (HbA1c), and albuminuria.Overall, 92 patients (38 males and 53 females) with an age median (P25; P75) of 33 years (25.5;42.5), BMI of 24.8 + 4.1 kg/m2, and duration of diabetes (mean ± SD) of 23.4 + 9.5 years were evaluated. There were no differences considering the gender for most analyzed variables, but a higher proportion of women exhibited microvascular complications such as microalbuminuria, macroalbuminuria, and retinopathy. Our results show a weak agreement in the 10-year cardiovascular risk estimation between SBEM and ST1RE classifications. According to SBEM criteria, 72.8% of patients were considered high-risk, while only 15.2% of patients received the same classification using ST1RE. The dissimilarities between these two classifications were also evident when age and gender factors were compared. While 60% of patients under 35 years were classified as high risk according to SBEM criteria, only 1.8% received this stratification risk in the ST1RE classification.The results indicate a low agreement between the 10-year cardiovascular event risk classification by SBEM and the classification by ST1RE for type 1 diabetes patients without established cardiovascular disease.

Bone strength is reduced in a neonatal androgenized rat model.

Background: Whether polycystic ovary syndrome (PCOS) affects bone health during a woman's lifespan remains controversial. An androgenized rodent model replicated many metabolic and reproductive features of women with PCOS, and we aimed to use it to investigate the impact of androgens on microarchitecture (by micro-CT), bone mechanical strength, bone formation and resorption markers in rats with intact ovaries (SHAM) who underwent oophorectomy. Methods: Wistar rats (Rattus norvegicus albinus) were employed for the experiments in this study. The protocol of androgenization consisted of the application of 1.25 mg s.c. testosterone propionate beteween days 2-5 of life, while the controls received the same amount of corn oil s.c. as previously established. Androgenized SHAM rats exhibited chronic anovulation identified by vaginal cytology and a reduction in the proportion of corpus luteum in the ovary in comparison to control SHAM rats. The realization of the ovariectomy or SHAM procedure occurred on Day 100 of life. All groups (n = 8) were followed-up for 180 days to address the study endpoints. Results: Micro-CT from androgenized female rats (SHAM) showed a divergence between the trabecular and cortical bone profiles. Compared to SHAM controls, these rats had an increase in trabecular bone mass with a diminution in bone resorption C-terminal telopeptide of type 1 collagen (CTX) (p < 0.05), a concomitant decrease in cortical area and thickness in the femur, and a reduction in the strength of the femur on the mechanical test (p < 0.01). Conclusions: Our results suggest that a reduction in the cortical thickness and cortical area observed in PCOS model rats was associated with a reduced strength of the femur, despite increased trabecular formation. Ovariectomy in the androgenized OVX group limited the progression rate of cortical bone loss, resulting in bone resistance and cortical thickness comparable to those observed in the control OVX group.

Comparison of image-based modified Ferriman-Gallway score evaluation with in-person evaluation: an alternative method for hirsutism diagnosis.

The gold standard for diagnosing hirsutism is based on the modified Ferriman-Gallway (mFG) score, requiring trained and in-person evaluation. Our study aimed to evaluate whether using mobile phone images of the nine mFG areas could offer an alternative way to support the diagnostic of hirsutism. All patients from an endocrine outpatient clinic underwent an initial mFG evaluation by two blinded, trained examiners. Then, images of the nine mFG areas were acquired using a mobile device (48 MP) under standard conditions and artificial illumination. A cutoff mFG score of ≥ 4 (suggested by European Society of Human Reproduction and Embryology) or ≥ 6 (proposed by The Endocrine Society) has been established as the criteria for diagnosing hirsutism. After storage, the individual patients' images were submitted for mFG analysis by three independent, blinded examiners. Overall, 70 females were evaluated; 27.5% of the patients had an mFG score ≥ 4. The mean age ± SEM was 33.2 + 1.13 years. The first consideration was the evaluation of the examiners who analyzed the images. In this group, the inter-rater reliability based on the Fleiss' Kappa identified an agreement of 81.4%, with a Kappa index of 0.75 considered strong for clinical evaluations. For mFG score ≥ 6, the agreement was 77%, and the performance of Kappa Index was 0.62 (moderate). Independently of the cutoffs, the Bland-Altman analysis established a concordance of 0.89 (95% CI [0.83, 0.92]) between the in-person and image-based methods to score mFG. The lower limit of agreement of the estimated mFG scores was - 2.08 (95% CI [- 2.73, - 1.43]), and the upper limit of agreement was 4.14 (95% CI [3.491, 4.79]). We observed acceptable concordance between the image-based and in-person evaluation of mFG scores. Our results support the use of image acquisition of mFG areas as a valid approach for diagnosing hirsutism.

Vitamin D is associated with a low quality of life: a primary care study

Introduction: Some studies have described impairment in quality of life of vitamin-deficient subjects. However, little is known about this association in primary care. This study aimed to evaluate the association between vitamin D deficiency and quality of life in postmenopausal women attending primary care in the municipality of Santa Maria ­ Brazil. Methods: A cross-sectional study was carried out with postmenopausal women over 55 years of age, accompanied in primary care, from March to August 2014. These women were randomly selected among the participants of a cohort study in the municipality of Santa Maria ­ Brazil. Data were collected through a standardized questionnaire, quality of life was assessed using the Short Form-36 Health Survey (SF-36), and 25-hydroxyvitamin D were measured using the ALPCO® ELISA method. Results: Of the total of 78 studied women, 11.54% had vitamin D deficiency. Women with vitamin D deficiency had a poorer quality of life assessed by SF-36. In the regression analysis, both vitamin D deficiency and falls were independently associated with a lower physical component of the SF-36. Conclusion: Vitamin D deficiency is associated with poorer quality of life in the studied postmenopausal women.

Insulin Resistance and Its Association With Osteoporosis in People Living With HIV.

Background: Despite the gain in life expectancy that people living with HIV (PLHIV) have had in the past few years, the disease is accompanied by an increase in the prevalence of noninfectious chronic diseases. PLHIV have a higher prevalence of osteoporosis, fracture, diabetes mellitus, and insulin resistance than the general population. It is unknown if insulin resistance is associated with osteoporosis and fractures in PLHIV. Our study aimed to assess the association between insulin resistance and osteoporosis in PLHIV. Methods: A cross-sectional study was carried out in southern Brazil. PLHIV ages 50 years or older on antiretroviral treatment were included. Insulin resistance was considered present when the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) was higher than expected for the Brazilian population (>2.7). The triglyceride-glucose (TyG) index was also calculated. Results: Of the 101 PLHIV who agreed to participate, 84 underwent insulin and bone mineral density measurements. The prevalence of osteoporosis was 19%. The frequency of insulin resistance calculated by HOMA-IR was 68.2%. Participants with osteoporosis had lower body mass index (BMI) and triglyceride values than those without it. HOMA-IR [4.8(6.6) vs 8.68(9.6), P = 0.013] and TyG [5.0(0.3) vs 5.2 (0.4), P = 0.029]. The association between the total femur t-score disappeared after correction for BMI in the linear regression model. There was no association between vertebral fractures and insulin resistance. Conclusion: In our study, PLHIV with osteoporosis have lower insulin resistance than PLHIV without it. However, this finding appears to be related to lower BMI. The association between insulin resistance and bone in PLHIV appears to be somewhat similar to that of the general population.

Higher score of diabetes eating problem survey-revised (DEPS-R) is associated with poor glycemic control among Brazilian patients with type 1 diabetes (T1DM): A brief report.

BACKGROUND AND AIMS: The diabetes eating problem survey-revised (DEPS-R) questionnaire is a specific and valuable tool for assessing disturbed eating behavior in type 1 diabetes mellitus. The literature suggests an association between a higher DEPS-R score and worse metabolic control; however, these figures have not been described in patients from Latin America. METHODS: We evaluated 58 patients with type 1 diabetes mellitus from a Brazilian outpatient clinic using the DEPS-R questionnaire. RESULTS: Overall, 23 participants with a high risk for high eating disorder behaviors exhibited significantly increased hemoglobin A1c levels compared with 35 patients with a DEPS-R score <20. CONCLUSIONS: Our data support that the presence of a DEPS-R score >20 negatively affects the metabolic control of patients with type 1 diabetes mellitus in Brazil.

The influence of prorenin/(pro)renin receptor on progesterone secretion by the bovine corpus luteum.

The aim of this study was to evaluate the role of prorenin/(pro)renin receptor activation on luteal progesterone (P4) secretion. Our hypothesis was that the nonproteolytic activation of (pro)renin receptor [P(RR)] is part of the regulatory mechanism responsible for corpus luteum (CL) function. In the first three experiments, prorenin was found to stimulate the production of P4, which is not inhibited by an angiotensin receptor antagonist (saralasin), but rather by a renin/prorenin inhibitor (aliskiren), a MAPK1/3 inhibitor (PD325901) or an EGFR inhibitor (AG1478), which are evidence of nonproteolytic activation of prorenin. Moreover, prorenin induced phosphorylation of MAPK1/3 in luteal cells. Following these in vitro experiments, a sequence of in vivo experiments was performed demonstrating that the intrafollicular injection of aliskiren in preovulatory follicles impaired P4 secretion in cows that ovulated. Furthermore, all profibrotic genes studied were present in the CL and TGFB1 and FN1 mRNA were upregulated from day 5-10 post-ovulation. During luteolysis, REN was downregulated at 48 h, whereas TGFB1 and SERPINE1 were dramatically upregulated in luteal tissue at 12 h after PGF. In summary, these data are evidence that nonproteolytic activation of (P)RR is involved in luteal function.

Heat stress modulates polymorphonuclear cell response in early pregnancy cows: I. interferon pathway and oxidative stress.

One of the major causes of early pregnancy loss is heat stress. In ruminants, interferon tau (IFNT) is the embryo signal to the mother. Once the interferon signaling pathway is activated, it drives gene expression for interferon-stimulated genes (ISGs) and alters neutrophils responses. The aim of the present study was to evaluate interferon (IFN) pathway, ISGs and gene expression in polymorphonuclear leukocytes (PMN) and oxidative stress in dairy cows under heat stress. Pregnant cows had their estrous cycle synchronized and randomly assigned to a comfort or heat stress group. Blood samples were collected at artificial insemination (AI) and on Days 10, 14 and 18 following AI. Pregnant cows were pregnancy checked by ultrasound on Day 30 and confirmed on Day 60 post-AI. Results are presented as mean ± SEM. The corpus luteum (CL) diameter was not different between groups of pregnant cows; concentration of progesterone of pregnant cows on Day 18 following AI was greater in comfort group compared to heat stressed group. Comfort pregnant cows had higher expression of all analyzed genes from interferon pathway, except for IFNAR1, on both Days 14 and 18. Conversely, heat stressed cows did not show altered expression of IFNT pathway genes and ISGs between Days 10, 14, and 18 after AI. The oxidative stress, determined as malondialdehyde (MDA) levels, was greater in heat stress group on Days 10, 14 and 18, independent of pregnancy status. Heat stress negatively influences expression of ISGs, IFN pathway gene expression in neutrophils, and oxidative stress. Our data suggest that lower conception rates in cows under heat stress are multifactorial, with the association of interferon pathway activation and the unbalanced oxidative stress being main contributing factors.

Incidence of fractures in women in the post-menopause: a cohort study in primary care in southern Brazil.

The incidences of total fracture, major fracture, and hip fractures in primary care in Southern Brazil were 22.3, 15.0, and 3.3 per 1000 person/year. The FRAX algorithm showed an adequate discriminatory capacity for the identification of these fractures. OBEJECTIVE: Few studies are evaluating the incidence of fractures in Latin America and Brazil. This study aimed to estimate the incidence of bone fractures in postmenopausal women seen in primary care and evaluate the FRAX algorithm's performance in these women. METHODS: A cohort study was carried out in the municipality of Santa Maria, Southern Brazil. Postmenopausal women aged 55 years and over who attended primary health care were included. The recruitment period was from March 1 to August 31, 2013, and the participants were followed for 5 years. The fracture risk was calculated using the FRAX algorithm. The reported incident fractures were confirmed by imaging studies or surgical reports. RESULTS: Of the 1057 women recruited for the study, 854 were followed. They contributed to 2732 person/year. The mean follow-up time was 3.2 years (SD 1.05). The incidences of total fractures, major fractures, and hip fractures were 22.3, 15.0, and 3.3 per 1000 person/year. The most frequent fracture sites were the wrist, shoulder, and ribs. The fracture predictors were rheumatoid arthritis, previous fracture, and the use of glucocorticoids. The discriminatory capacity of incident fractures calculated by FRAX without the inclusion of BMD was AUC 0.730 (95% CI 0.570, 0.890) for hip fracture and AUC 0.691 (95% CI 0.598, 0.784) for major fractures. CONCLUSION: The FRAX algorithm showed an adequate discriminatory capacity to identify incident fractures in primary care in our study. The incidence of fractures found in our study appears to be lower than that reported in North America and Europe.

Cryoprotectant agents for ovarian tissue vitrification: Systematic review.

Studies on the cryopreservation of ovarian tissue usually compare slow freezing versus vitrification and aim to optimize protocols, evaluate combinations or concentrations of cryoprotectant agents (CPAs), exposure time, and the addition of synthetic polymers. This systematic review aimed to identify the different CPAs used for the vitrification of human or primate ovarian tissue and to compare their results in terms of follicular survival and functional preservation. We searched Pubmed and EMBASE for randomized clinical trials or cohort studies comparing CPAs for human and/or primate ovarian vitrification. The highest rate of morphologically normal follicles after cryopreservation was 98% and was obtained with a combination of 27% ethylene glycol (EG) plus 27% glycerol, in addition to non-permeable synthetic polymers. The use of dimethyl sulfoxide (DMSO) in relatively low concentrations combined with EG and other CPAs yielded more than 90% of intact follicles after vitrification. The methods and outcomes varied largely among studies, making it difficult to combine their results. While there is no definite answer to what is the best combination of CPAs for vitrification of human ovarian tissue, the data reviewed here suggest that current vitrification techniques are able to preserve the integrity of most follicles.

Ovariectomy Improves Metabolic and Oxidative Stress Marker Disruption in Androgenized Rats: Possible Approach to Postmenopausal Polycystic Ovary Syndrome.

Background: This study aims to evaluate metabolic and oxidative stress markers in a postmenopausal rat model of polycystic ovary syndrome (PCOS). Methods: Wistar rats were divided in four groups: control ovariectomized (OVX; n = 9), control SHAM (n = 9), androgenized OVX (n = 10), and androgenized SHAM (n = 10). Female rats were androgenized during the neonatal period and compared with controls. Surgery (ovariectomy or SHAM procedure) was performed at day 100 and euthanasia at day 180 of life. Bodyweight, lipids, glucose, triglyceride glucose (TyG) index, and oxidative stress markers (total oxidant status [TOS], total antioxidant capacity, nitric oxide, ferric-reducing ability of plasma [FRAP], and advanced oxidation protein product) were addressed. Results: Androgenized SHAM rats exhibited a higher total, low-density lipoprotein cholesterol, triglycerides, TyG index (an insulin resistance marker), and increased TOS, FRAP, and albumin in comparison with control SHAM rats. These abnormalities disappeared after ovariectomy despite the fact that ovariectomized androgenized rats became heavier than the other three groups. Conclusion: Ovariectomy improved metabolic and oxidative stress markers in a rat model of PCOS.

Trabecular Bone is Increased in a Rat Model of Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) in an intricate disorder characterized by reproductive and metabolic abnormalities that may affect bone quality and strength along with the lifespan. The present study analysed the impact of postnatal androgenization (of a single dose of testosterone propionate 1.25 mg subcutaneously at day 5 of life) on bone development and markers of bone metabolism in adult female Wistar rats. Compared with healthy controls, the results of measurements of micro-computed tomography (microCT) of the distal femur of androgenized rats indicated an increased cortical bone volume voxel bone volume to total volume (VOX BV/TV) and higher trabecular number (Tb.n) with reduced trabecular separation (Tb.sp). A large magnitude effect size was observed in the levels of circulating bone formation Procollagen I N-terminal propeptide (P1NP) at day 60 of life; reabsorption cross-linked C-telopeptide of type I collagen (CTX) markers were similar between the androgenized and control rats at days 60 and 110 of life. The analysis of gene expression in bone indicated elements for an increased bone mass such as the reduction of the Dickkopf-1 factor (Dkk1) a negative regulator of osteoblast differentiation (bone formation) and the reduction of Interleukin 1-b (Il1b), an activator of osteoclast differentiation (bone reabsorption). Results from this study highlight the possible role of the developmental programming on bone microarchitecture with reference to young women with PCOS.

Calcium supplementation and cardiovascular disease in postmenopausal women: a study in South Brazil / Suplementação de cálcio e doença cardiovascular em mulheres na pós-menopausa: um estudo no Sul do Brasil

Objective: To evaluate the link between calcium supplementa- tion and cardiovascular disease in postmenopausal women (aged 55 years or older). Methods: A standardized questionnaire was employed to collect data about calcium supplements, eart di- sease, and demographic of women attended at Primary Care in the South Region of Brazil. Generalized linear regression models were performed to evaluate the association and adjust for poten- tial confounders. Results: Overall, 1,057 women completed the questionnaire. Information about calcium supplementation was present in 1,035 questionnaires. The mean ± standard deviation of the age of participants was 67.2±7.6 years. The frequency of calcium supplementation was 18.6%. There was no association between heart failure, stroke, and ischemic heart disease and cal- cium supplementation (prevalence ratio; 95% confidence interval of 0.3; -0.9-0.4, -0.2; -0.8-0.4 and -0.5; -1.0-0.02, respectively. Con- clusions: Our study did not find an association of higher risk of cardiovascular disease in women using calcium supplementation at Primary Care in South Brazil.

Objetivo: Avaliar a ligação entre a suplementação de cálcio e doença cardiovascular em mulheres na pós-menopausa (com 55 anos ou mais). Métodos: Um questionário padronizado foi em- pregado para coletar dados sobre suplementos de cálcio, doenças cardíacas e demográficos de mulheres que frequentavam a Aten- ção Primária na Região Sul do Brasil. Modelos de regressão linear generalizada foram realizados para avaliar a associação e ajustar os potenciais fatores de confusão. Resultados: No total, 1.057 mulheres responderam ao questionário. As informações sobre su- plementação de cálcio estavam presentes em 1.035 questionários. A média ± desvio-padrão da idade dos participantes foi de 67,2 ± 7,6 anos. A frequência de suplementação de cálcio foi de 18,6%. Não houve associação entre insuficiência cardíaca, acidente vas- cular cerebral e doença cardíaca isquêmica e suplementação de cálcio (razão de prevalência; intervalo de confiança de 95% de -0,3; -0,9-0,4, -0,2; -0,8-0,4 e -0,5; -1,0-0,02, respectivamente). Con- clusão: Nosso estudo não encontrou associação de maior risco de doença cardiovascular em mulheres em uso de suplementação de cálcio na Atenção Primária no Sul do Brasil.