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Background: COVID-19 has led to significant global mortality, with Peru being among the countries most affected. While pre-existing comorbidities have been linked to most cases, the exact distribution of fatalities within the country remains unclear. We aimed to assess deaths attributed to cardiovascular diseases (CVD) before and during the COVID-19 pandemic across various regions and provinces in Peru. Methods: An observational georeferencing study was designed. Peru faced four waves of COVID-19 over three years, with variable impacts across its three regions (Coast, Highlands, and Jungle). Deaths related to cardiovascular diseases, such as heart failure (HF), arrhythmia, acute myocardial infarction (AMI), strokes, and acute coronary syndrome, were examined as primary variables. The study period spanned pre-pandemic years (2017-2019) and pandemic years (2020-2021), utilizing death data from the National Death Information System (SINADEF). The georeferencing analysis was conducted using ArcGIS v10.3. Results: A total of 28,197 deaths were recorded during the study period, with significant increases during the pandemic (2020-2021). Cardiovascular deaths were disproportionately higher during the pandemic, totaling 19,376 compared to 8,821 in the pre-pandemic period (p < 0.001). AMI and HF were the leading causes of mortality, showing significant increases from the pre-pandemic (5,573 and 2,584 deaths) to the pandemic period (12,579 and 5,628 deaths), respectively. Deaths due to CVD predominantly affected individuals aged over 60, with significant increases between the two study periods (7,245 vs. 16,497 deaths, p = 0.002). Geospatial analysis revealed regional disparities in CVD mortality, highlighting provinces like Lima and Callao as COVID-19 critical areas. The substantial increase in cardiovascular deaths during the COVID-19 pandemic in Peru showed distinctive patterns across regions and provinces. Conclusions: Geospatial analysis identified higher-risk areas and can guide specific interventions to mitigate the impact of future health crises. Understanding the dynamic relationship between pandemics and cardiovascular health is crucial for effective public health strategies.
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STUDY QUESTION: Do alterations in pro- and anti-angiogenic estrogen metabolites in follicular fluid (FF) contribute to the follicular growth arrest and anovulation associated with polycystic ovary syndrome (PCOS)? SUMMARY ANSWER: FF of PCOS women with anovulation have reduced levels of pro-angiogenic estrogen metabolites (EMs) and vascular endothelial growth factor (VEGF) compared to that of fertile women with regular menstrual cycles, but exogenous gonadotropins increase the pro-angiogenic EMs and VEGF levels in PCOS women. WHAT IS KNOWN ALREADY: PCOS is characterized by the arrest of follicular development that leads to chronic anovulation. Follicular arrest is generally associated with elevated plasma levels of luteinizing hormone (LH), androgens and anti-Mullerian hormone (AMH). There is also reduced angiogenesis in the follicles of PCOS women compared to those of normal cycling women. It is known that angiogenesis is a critical factor during follicular development. We and other investigators have explored the role of EMs in ovarian angiogenesis, particularly in human corpus luteum function, showing that 4-hydroxyestrone (4-OHE1) and 16-ketoestradiol (16-kE2) have pro-angiogenic effects while 2-methoxyestradiol (2-ME2) and 2-methoxyestrone (2-ME1) have anti-angiogenic effects. Additionally, 2-hydroxyestradiol (2-OHE2), which is produced in the ovary, has proliferative and pro-angiogenic properties. We hypothesized that EMs could be involved in angiogenesis necessary for ovarian follicular development in fertile women, and that dysregulation of these factors may contribute to follicular arrest in PCOS. The relationship between EMs, VEGF and AMH in the pathophysiology of follicular arrest in PCOS has not been previously studied at a follicular level in anovulatory women without ovulation induction. STUDY DESIGN, SIZE, DURATION: This is a comparative experimental study of serum and FF collected from different sized follicles (antral Ë10 mm and dominant Ë16 mm) of women with and without ovarian stimulation. The study included women with regular menstrual cycles who were proven to be fertile (n = 20) and PCOS women with follicular arrest who were candidates for ovarian drilling (n = 17), as well as other patients requiring ovarian stimulation, i.e. control women undergoing IVF for male factor infertility (n = 12) and PCOS women undergoing IVF (n = 17). In vitro studies were carried out on granulosa-lutein cells (GCs) obtained from subsets of women undergoing IVF for male factor infertility (n = 6) and PCOS women undergoing IVF (n = 6). GCs were maintained in culture for up to 6 days. PARTICIPANTS/MATERIALS, SETTING, METHODS: Intrafollicular estradiol, estrone and EMs concentrations were determined by high performance liquid chromatography-mass spectrometry. Testosterone in serum was measured by RIA, and LH, FSH and sex hormone-binding globulin in serum were measured with IRMA kits. AMH was determined in serum and FF by enzyme linked immunosorbant assay (ELISA). VEGF levels were measured in FF and conditioned medium by ELISA. Conditioned medium were obtained from cultured GCs. The angiogenic potential was assessed by in vitro angiogenic assays. MAIN RESULTS AND THE ROLE OF CHANCE: Pro-angiogenic EMs (4-OHE1, 16-kE2 and 2-OHE2) and VEGF were lower in FF of antral follicles of PCOS women with follicular arrest compared those of fertile women with ovulatory cycles (P < 0.05). In contrast, higher concentrations of AMH were found in FF of antral follicles from PCOS women with follicular arrest compared to those of fertile women with ovulatory cycles (P < 0.05). Exogenous gonadotropins used in IVF increased pro-angiogenic EMs and VEGF production in PCOS women, reaching similar profiles compared to control women receiving gonadotropins in their IVF treatment for male factor infertility. The pro-angiogenic EM 2-OHE2 increased the angiogenic potential and VEGF levels of GCs from PCOS women compared to the basal condition (P < 0.05). These findings suggest that there is a role for pro-angiogenic EMs in the control of follicular VEGF production. LIMITATIONS, REASONS FOR CAUTION: The limitations include the possibility that in vitro analysis of GCs might not reflect the in vivo mechanisms involved in the pro-angiogenic action of 2-OHE2 since GCs obtained at the time of oocyte retrieval belong to a very early stage of the luteal phase and might not be representative of GCs during follicular growth. Therefore, our findings do not conclusively rule out the possibility that other in vivo mechanisms also account for defective angiogenesis observed in PCOS. WIDER IMPLICATIONS OF THE FINDINGS: The present study highlights the significance of EMs, angiogenic factors and AMH and their interaction in the pathophysiology of follicular development in PCOS. This study provides new insights into the role of pro-angiogenic factors in follicular arrest in PCOS. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by CONICYT/FONDECYT 1140693 and NIH grant R01HD083323. All authors declare no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.
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Síndrome do Ovário Policístico , Hormônio Antimülleriano , Estrogênios , Feminino , Líquido Folicular , Humanos , Masculino , Fator A de Crescimento do Endotélio VascularRESUMO
STUDY QUESTION: Can the high rate and associated burden of unintended pregnancy (UP) and adolescent pregnancy in Latin America and the Caribbean (LAC) be reduced through wider access to and use of long-acting reversible contraceptive (LARC) methods? SUMMARY ANSWER: Studies show that impoved access to and use of LARC methods is an effective tool for reducing the high rates of UP, unsafe abortion and abortion-related complications, and maternal deaths (as well as reducing their social and financial burden), and we have provided recommendations to help achieve this in LAC. WHAT IS KNOWN ALREADY: LAC comprises 46 countries with 650 million inhabitants, and shows large disparities in socioeconomic development, access to health services and attention to sexual and reproductive health rights. The exercise of these rights and universal access to sexual and reproductive health (SRH) programmes is a key strategy for improving maternal health by reducing the number of UPs, the rate of women's and child mortality and morbidity, and the number of unsafe abortions. The implementation of SRH programmes in the region has contributed to a decrease in pregnancy rates of more than 50% over 40 years. However, despite this progress, the numbers of UP and adolescent pregnancies are still among the highest worldwide, which can be attributed in large part to the low prevalence of use of LARC methods. STUDY DESIGN SIZE DURATION: This is a position paper with the objective of reviewing the magnitude and burden of UP in LAC, as well as available LARC methods and barriers to their access, with the goal of increasing knowledge and awareness among healthcare professionals (HCP), policymakers and the general public about the potential to reduce UP rates through the increased use of LARC. PARTICIPANTS/MATERIALS SETTING METHOD: We searched the electronic databases of PubMed and EMBASE to identify studies published up to May 2017. We also searched for websites regarding LAC, LARC methods, and UP including, for example, those from the United Nations, the World Health Organization, Pan American Health Organization, the Alan Guttmacher Institute and the United States Agency for International Development. Studies were included if they investigated mainly UP and their consequences as well as the use of LARC methods in the region. During 3 days of meetings, the importance of the studies identified and the appropriateness of inclusion were discussed. MAIN RESULTS AND THE ROLE OF CHANCE: LAC is not one unit and shows great ethnic diversity as well as economic and cultural differences among the various countries. These differences must be taken into account when developing policies related to disseminating information and combatting misinformation regarding the use of LARC among different audiences, such as adolescents and young women, nulligravidas, indigenous populations and women with disabilities. Furthermore, only some governments have made efforts to increase accessibility to LARC methods, and there is a need to implement training programmes for HCPs, launch education campaigns for the general public, increase access and review the cost-benefit analyses specific to LARC, which have already demonstrated that the upfront cost of LARC is less than the cummulative expense of short-term contraceptives. Recommendations to achieve these goals are presented. LIMITATIONS REASONS FOR CAUTION: Knowledge and awareness of the contraceptive method itself and of the mix of individual countries in the region is essential to the development of specific strategies and actions, tailored to each particular country situation, aimed at increasing access to modern contraceptive methods, especially LARC. WIDER IMPLICATIONS OF THE FINDINGS: Healthcare systems in LAC should consider LARC as a primary option for decreasing UP and adolescent pregnancy. Disseminating information, increasing awareness of their efficacy, removing barriers and improving access to LARC methods are the urgent actions recommended for government, academia, professional organizations, insurance companies and policymakers in order to address this major public health problem in LAC. STUDY FUNDING/COMPETING INTERESTS: This manuscript was supported by a grant from the Americas Health Foundation (AHF), a 501(c)3 nonprofit organization dedicated to improving healthcare throughout the Latin American Region. LB and IM received additional support from the São Paulo Research Foundation (FAPESP) award # 2015/20504-9. The authors declare no conflict of interest.
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Hyperandrogenemia and hyperinsulinemia are observed in women with diabetes during pregnancy. The effect of diabetes on anti-Müllerian hormone (AMH) levels during pregnancy is unclear. The aim of this study was to determine the AMH levels in women with type 2 diabetes (T2D) and gestational diabetes (GD) compared to healthy (C) pregnant women during the second half of gestation. A prospective study of 69 pregnant women with T2D (N: 21), GD (N: 24) and C (N: 24) were followed up during the second half of pregnancy. Clinical assessments and blood samples were collected at 26.7 (25-27.8); 34 (32-34.9) and 37.5 (37-40) weeks of gestation. AMH, sexual steroids, insulin, homeostatic model assessment of insulin resistance, HbA1c levels were measured. AMH levels were similar between T2D, GD and C (p = .07). A decline of AMH levels during the second half of gestation was observed in the three groups (p < .0001). AMH levels were negatively associated with age (p < .001). A positive association between AMH and testosterone (p < .05) was found in all groups. A progressive decline of AMH levels is observed in diabetic and healthy women during the second half of pregnancy. Testosterone levels are an independent factor that influences AMH levels during pregnancy. However, AMH levels are not affected by the presence of diabetes during gestation.
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Hormônio Antimülleriano/análise , Diabetes Mellitus Tipo 2/sangue , Diabetes Gestacional/sangue , Regulação para Baixo , Resistência à Insulina , Gravidez em Diabéticas/sangue , Testosterona/sangue , Adulto , Biomarcadores/sangue , Índice de Massa Corporal , Estudos de Coortes , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Gestacional/metabolismo , Feminino , Hemoglobinas Glicadas/análise , Humanos , Estudos Longitudinais , Idade Materna , Obesidade/sangue , Obesidade/complicações , Obesidade/metabolismo , Gravidez , Complicações na Gravidez/sangue , Complicações na Gravidez/metabolismo , Segundo Trimestre da Gravidez , Terceiro Trimestre da Gravidez , Gravidez em Diabéticas/metabolismo , Estudos Prospectivos , Adulto JovemRESUMO
BACKGROUND: The ultrasonographic criteria used to identify polycystic ovarian morphology (PCOM) during adolescence have changed over time. Recently, a Worldwide Pediatric Consensus (PedC) defined PCOM using stricter criteria than the previous recommendations of the Rotterdam Consensus (RC) and Androgen Excess-Polycystic Ovarian Syndrome Society (AES/PCOS) criteria. The aim of this study was to determine the prevalence of PCOM in healthy adolescents according to the 3 reported diagnostic criteria and compare the hormonal profile in females with and without PCOM based on the PedC criteria. METHODS: Nonobese adolescents (n = 102) with regular menstrual cycles were studied. Transabdominal ultrasound and hormonal profiles were assessed during the follicular phase. PCOM was defined on the basis of the 3 published criteria. RESULTS: On the basis of the PedC, RC, and AES/PCOS criteria, PCOM was diagnosed in 13, 34, and 24% of adolescents, respectively. Adolescents with and without PCOM according to the PedC criteria had similar androgen levels. Serum anti-Müllerian hormone (AMH) levels were elevated in adolescents with PCOM, irrespective of the criteria used. CONCLUSIONS: Use of the new PedC diagnostic criteria for PCOM results in a lower prevalence of this ultrasonographic pattern in adolescents, but this condition is not associated with hyperandrogenism. Elevated AMH is associated with PCOM in adolescents regardless of the criteria used to determine the ultrasonographic pattern.
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Androgênios/sangue , Síndrome do Ovário Policístico/sangue , Síndrome do Ovário Policístico/diagnóstico por imagem , Síndrome do Ovário Policístico/epidemiologia , Adolescente , Adulto , Estudos Transversais , Feminino , Humanos , Prevalência , UltrassonografiaRESUMO
Higher androgen levels are observed in non-pregnant women with diabetes. Whether this hormonal profile is found during pregnancy is unknown. The aim of this study was to determine the sexual steroids levels in pregnant women with pregestational type 2 (T2D) and gestational diabetes (GD) compared to healthy control (C) pregnant women during the second half of pregnancy. A prospective study of 69 pregnant women with T2D (n = 21), GD (n = 24) and control (C, n = 24) was followed up during the second half of gestation. Clinical assessments and blood samples were collected at 26.7 (25-27.8); 34 (32-34.9) and 37.5 (37-40) weeks of gestation. Androgens, sex hormone-binding globulin (SHBG), estrogens, estradiol/testosterone (E/T) ratio, insulin, glucose, HOMA-IR, were measured. Testosterone, insulin and homeostatic model assessment of insulin resistance (HOMA-IR) levels were higher in T2D compared with C at each sampling point during pregnancy, even after adjusting for BMI and age. Estrogens levels and estradiol/testosterone ratio were lower in T2D and GD compared with C. Hyperandrogenemia, and higher insulin resistance is observed in T2D, but not in GD during pregnancy. Decreased estrogen and E/T ratio found in T2D and GD suggests a diminished aromatase activity during gestation. T2D and GD are associated with specific changes in sexual steroids and insulin resistance levels during pregnancy.
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Diabetes Mellitus Tipo 2/complicações , Diabetes Gestacional/sangue , Hiperandrogenismo/complicações , Hiperinsulinismo/complicações , Resistência à Insulina , Gravidez em Diabéticas/sangue , Adulto , Androstenodiona/sangue , Chile , Sulfato de Desidroepiandrosterona/sangue , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Gestacional/metabolismo , Diabetes Gestacional/fisiopatologia , Regulação para Baixo , Estradiol/sangue , Estriol/sangue , Estrona/sangue , Feminino , Humanos , Hiperandrogenismo/etiologia , Hiperinsulinismo/etiologia , Estudos Longitudinais , Gravidez , Segundo Trimestre da Gravidez , Terceiro Trimestre da Gravidez , Gravidez em Diabéticas/metabolismo , Gravidez em Diabéticas/fisiopatologia , Estudos Prospectivos , Centros de Atenção TerciáriaRESUMO
We evaluated the association of hirsutism and oligomenorrhea (persistent menstrual cycles > 45 days) as screening criteria for the detection of biochemical hyperandrogenism (BH) and polycystic ovaries (PCOM) during adolescence and determined which androgens, granulosa cell hormone, ultrasonographic parameters have the best association with polycystic ovary syndrome (PCOS). Hirsute girls with oligomenorrhea (N = 26 Hirs/Oligo group) and non-hirsute girls with regular cycles (N = 63, C group) were studied. Prevalence of BH and PCOM, diagnostic performance of androgens and ultrasound parameters for PCOS diagnosis were analyzed. BH and PCOM prevalence were higher in the Hirs/Oligo girls than in the C girls (76.9% versus 25.5%; 92.3% versus 33.3%, respectively; p < 0.0001). A complete PCOS phenotype (Hirs/Oligo with BH and PCOM) was observed in 73.1% of the Hirs/Oligo group. The presence of both BH and PCOM was observed in 7.9% of the C group. The parameters with the best diagnostic performance were free androgen index ≥6.1, testosterone ≥2.4 nmol/L, follicle number ≥12 and ovarian volume ≥10 ml anti-Müllerian hormone (AMH) exhibited a low diagnostic accuracy. Hirsutism and persistent menstrual cycle over 45 days are highly associated with BH and PCOM suggesting that the presences of both criteria are necessary for the diagnosis of PCOS during adolescence.
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Hirsutismo/etiologia , Oligomenorreia/etiologia , Síndrome do Ovário Policístico/diagnóstico , Adolescente , Feminino , Humanos , Síndrome do Ovário Policístico/complicações , Adulto JovemRESUMO
OBJECTIVE: To study in vivo the progesterone receptor (PR) expression levels in human granulosa cells (GCs) during the periovulatory period and the affect of the protein kinase A (PKA) pathway on PR expression and cathepsin-L expression-activation. DESIGN: Experimental study. SETTING: University research unit. PATIENT(S): Twenty-five women of reproductive age. INTERVENTION(S): Follicular fluid and GCs obtained from spontaneous cycles before and during the normal luteinizing hormone surge, and samples obtained 36 hours after human chorionic gonadotropin (hCG) administration in patients undergoing in vitro fertilization. MAIN OUTCOME MEASURE(S): To determine PR, cathepsin-L messenger RNA (mRNA) analysis via real-time polymerase chain reaction, and protein of PR, cathepsin-L, and PKA in human GCs. RESULT(S): The Western blot analysis revealed that bands of PR (isoform A) were the most abundant and that mRNA (PR-A and PR-B) have a temporal pattern of expression throughout the periovulatory period. The protein levels of PR and cathepsin-L were up-regulated by hCG. The abundance of PR was diminished in the presence of PKA inhibitor, and cathepsin-L with PR receptor antagonist. CONCLUSION(S): The transient expression of PR in human GCs of the preovulatory follicle suggests that PR and its ligand play a role in the activation of cathepsin-L, which is presumably involved in the degradation of the follicular extracellular matrix during human ovulation.
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Catepsina L/metabolismo , Células da Granulosa/enzimologia , Ovulação , Receptores de Progesterona/metabolismo , Adulto , Western Blotting , Catepsina L/genética , Células Cultivadas , Gonadotropina Coriônica/administração & dosagem , Proteínas Quinases Dependentes de AMP Cíclico/antagonistas & inibidores , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Ativação Enzimática , Feminino , Fármacos para a Fertilidade Feminina/administração & dosagem , Líquido Folicular/metabolismo , Células da Granulosa/efeitos dos fármacos , Antagonistas de Hormônios/farmacologia , Humanos , Ovulação/efeitos dos fármacos , Indução da Ovulação , Inibidores de Proteínas Quinases/farmacologia , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Receptores de Progesterona/efeitos dos fármacos , Receptores de Progesterona/genética , Fatores de TempoRESUMO
BACKGROUND: The contraceptive efficacy of emergency contraceptive pills containing levonorgestrel (LNG-EC) has been estimated in most previous studies by judging the day of ovulation from presumptive menstrual cycle data, thus providing poorly reliable estimates. METHODS: In the present study, the efficacy of LNG-EC was determined in 393 cycles by dating ovulation on the basis of reliable hormonal and ovarian parameters validated by a database constructed in a separate study. In addition, the efficacy was determined separately for cycles in which LNG-EC was given before or after ovulation. RESULTS: For the 148 women who had sexual intercourse during the fertile days, the overall accumulated probability of pregnancy was 24.7, while altogether 8 pregnancies were observed. Thus, the overall contraceptive efficacy of LNG-EC was 68%. Among the 103 women who took LNG-EC before ovulation (days -5 to -1), 16 pregnancies were expected and no pregnancy occurred (p<.0001). Among the 45 women who took LNG-EC on the day of ovulation (day 0) or thereafter, 8 pregnancies occurred and 8.7 were expected (p=1.00). These findings are incompatible with the inhibition of implantation by LNG-EC in women. The same cases were also analyzed using the presumptive menstrual cycle data, and important discrepancies were detected between the two methods. CONCLUSION: The efficacy of LNG-EC has been overestimated in studies using presumptive menstrual cycle data. Our results confirm previous similar studies and demonstrate that LNG-EC does not prevent embryo implantation and therefore cannot be labeled as abortifacient.
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Anticoncepcionais Femininos/administração & dosagem , Anticoncepcionais Orais Sintéticos/administração & dosagem , Anticoncepcionais Pós-Coito/administração & dosagem , Levanogestrel/administração & dosagem , Ciclo Menstrual , Ovulação , Adolescente , Adulto , Tratamento de Emergência , Feminino , Humanos , Gravidez , Resultado da Gravidez , Adulto JovemRESUMO
OBJECTIVE: To evaluate ovarian function, especially ovulation rate, in adolescents with McCune-Albright syndrome (MAS) and a history of peripheral precocious puberty. DESIGN: Prospective cross-sectional study. SETTING: Academic center. PATIENT(S): A total of eight adolescents with MAS were compared with 15 healthy adolescents matched by age, Tanner stage and body mass index. INTERVENTION(S): We determined basal gonadotropins, sex steroids, sex hormone binding globulin, anti-Müllerian hormone, glucose and insulin. A leuprolide acetate test was performed to measure luteinizing hormone (LH) and follicle stimulating hormone (FSH) (at 0 and 3 h), and 17B-estradiol, testosterone and 17-OH-progesterone (at 0 and 24 h). Salivary progesterone levels were used to assess ovulation during the 13th, 18th, 23rd and 28th days of each menstrual cycle for three to five consecutive cycles, and one pelvic ultrasound was performed during the follicular phase. MAIN OUTCOME MEASURE(S): Ovulation rate in adolescents with MAS. RESULT(S): The proportion of ovulatory cycles was 52.6% in controls compared with 35.7% in patients with MAS. CONCLUSION(S): The adolescent girls with MAS appear to have a lower ovulatory rate compared with controls.