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Introduction: Pregnant women can choose from different prenatal genetic tests throughout their maternity journey. We aim to investigate the clinical, societal, and economic determinants influencing the selection of different options (non-invasive, invasive, or both). Methods: A systematic survey focusing on maternity pathways was launched by the Region of Tuscany, Italy, to collect data on pregnant women's experience, outcomes and satisfaction levels. Drawing from this survey, we retrospectively analyzed data on women who filled out the second-trimester questionnaire between March 2019 and February 2023 (n = 27,337), providing complete data on relevant variables. Logistic regression models were applied to identify the factors contributing to a higher likelihood of opting for non-invasive prenatal testing (NIPT) and invasive testing. Results: Among the participants, 42.7 % chose only NIPT, 3.8 % opted for invasive tests exclusively, 1.3 % underwent both tests, and 52.2 % did not pursue any genetic testing. NIPT was more often chosen by older, Italian, highly educated, nulliparous women, who perceived better health, were employed (versus unemployed), had higher economic status, planned pregnancy, received hospital-based care (versus counseling center), under gynecologist supervision (versus midwife), not opted for combined testing and received pregnancy vaccinations. Conversely, invasive testing was more prevalent among older women but less common among those who were nulliparous, had Italian nationality, and had a perceived better health status. This group also tended to experience unplanned and high-risk pregnancy, did not take folate during pregnancy, received public hospital-based assistance, less frequently chose combined tests or NIPT, and had frequent delays in examinations. Conclusions: Various factors beyond clinical considerations influence the selection of a prenatal test. Therefore, NIPT pathways should include balanced, high-quality information about benefits and limitations, ensuring laboratory specialists' active and integrated involvement in decision-making.
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BACKGROUND AND OBJECTIVE: Pelvic organ prolapse (POP) affects 40% of women, with a 12%-19% lifetime surgical risk. Italy showed high practice variation in POP surgery, possibly impacting equity of access to healthcare services, a central goal of Beveridge-like health systems. According to the literature, unwarranted variation, influenced by physician attitudes or resource allocation, must be reduced. We aimed to identify determinants influencing women's choice when asked whether they prefer surgical or conservative POP management. DESIGN, SETTING AND POPULATION: In this nationwide prospective study, we distributed a Qualtrics questionnaire via social media to any Italian women over 18 years old who voluntarily decided to participate in the survey. INTERVENTION: A grade 3 POP scenario was presented. Women were asked how likely they would have surgery. Each woman randomly received only 1 question out of 11: 1 question was the reference question ('How likely would you have surgery?') while 10 questions contained a potential determinant influencing woman's choice ('How likely would you have surgery if ?'). OUTCOME: The outcome was the chance of choosing surgery expressed as a percentage. We analysed the effect of each factor on the outcome by using adjusted beta regression models. RESULTS: Respondents (n=222) opted for surgery with a median probability of 61.5%. Factors significantly increasing the chance of choosing surgery were advice from physicians, the presence of a trusted physician during hospitalisation, surgical approach with low complication rates, uterine-sparing surgery, the absence of postoperative abdominal scars and nearby hospital. CONCLUSIONS: Our findings provide health managers and policy-makers with new evidence to better understand women's decision-making and partly capture the determinants of unwarranted variation. These inputs may also be used as attributes for a future discrete choice experiment.
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Tratamiento Conservador , Prioridad del Paciente , Prolapso de Órgano Pélvico , Humanos , Femenino , Prolapso de Órgano Pélvico/cirugía , Prolapso de Órgano Pélvico/terapia , Prolapso de Órgano Pélvico/psicología , Italia , Persona de Mediana Edad , Estudios Prospectivos , Encuestas y Cuestionarios , Anciano , Adulto , Conducta de ElecciónRESUMEN
Background: To assess the equivalence of tranexamic acid (TRAN) versus synthetic oxytocin (OXY) in reducing post-partum blood loss, in full-term patients (37-42 weeks), at low risk of post-partum hemorrhage, with vaginal childbirth. Methods: Phase III, randomized (1:1), open-label, longitudinal, multi-center, prospective clinical trial (Prot. n 63209, ClinicalTrials.gov Identifier: NCT02775773). From January 7, 2020, to June 30, 2023, a total of 256 women were enrolled at two general urban community hospitals in Italy, serving a multi-ethnic patient population with National Health Insurance. The primary outcome was to explore a potential equivalence between the two treatments (OXY and TRAN) in preventing total blood loss. Therefore, we randomized 231 women into two groups: Group A (OXY), 127 women who were administered 10UI intramuscularly within 5 min from childbirth; Group B (TRAN), 104 women to whom 1-g slow intravenous infusion was administered within 5 min from childbirth. Findings: At the time of delivery, mean blood loss for OXY group versus TRAN group was 269.12 mL versus 263.88 mL, respectively, with equivalence between the two groups. Similarly, there was equivalence in total blood loss between the OXY and the TRAN group (397.66 mL versus 405.64 mL, respectively. No statistical differences between Hb levels at admission and discharge in the two groups were reported. No difference was found in terms of additional uterotonic and surgical therapies between the two groups of patients. Neither group showed thrombotic complications at check-up performed after 7 days or after a questionnaire regarding adverse effects, subjected after 40 days. Interpretation: The study shows the equivalence of tranexamic acid versus synthetic oxytocin in post-partum blood loss prophylaxis in term patients at low risk of PPH with vaginal childbirth. The safety profiles of OXY and TRAN were similar. Funding: None.
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The efficacy of hyaluronic acid instillations as therapy for patients with Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS) has been demonstrated in some clinical studies, with response rates up to 70%. The aim of the study is to investigate the change in symptoms and quality of life in female patients with IC/BPS after intravesical instillations of hyaluronic acid used as first-line treatment. A retrospective single-center cohort study was conducted. Female patients, whose symptoms were compatible with the diagnosis of IC/BPS as defined by the International Continence Society, were treated with a variable number of intravesical instillations of a hyaluronic acid-based drug. Three validated questionnaires were administered by telephone to all patients, before the beginning of the treatment and 6 months after the last administration of the drug. A total of 50 patients with symptoms compatible with the diagnosis of IC/BPS were included in the study. The median number of instillations performed is 4. For all questionnaires, the median value was significantly reduced following treatment with intravesical instillations (p = 0.000). The present study has shown that intravesical hyaluronic acid treatment results in both statistically and clinically significant symptomatic improvement, thereby improving the quality of life of patients with IC/BPS.
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AIMS: Guidelines recommend target doses (TD) of heart failure (HF) with reduced ejection fraction (HFrEF) medications regardless of sex. Differences in pharmacokinetics and pharmacodynamics may explain heterogeneity in treatment response, adverse reactions, and tolerability issues across sexes. The aim of this study was to explore sex-based differences in the association between TD achievement and mortality/morbidity in HFrEF. METHODS AND RESULTS: Patients with HFrEF and HF duration ≥6 months registered in the Swedish HF Registry between May 2000 and December 2020 (follow-up until December 2021) were analysed. Treatments of interest were renin-angiotensin system inhibitors (RASI) or angiotensin receptor-neprilysin inhibitors (ARNI), and beta-blockers. Multivariable Cox regression models were performed to explore the risk of cardiovascular mortality or hospitalization for HF across dose categories in females versus males. A total of 17 912 patients were analysed (median age 77.0 years, interquartile range [IQR] 70.0-83.0), 29% were female. Over a median follow-up of 1.33 years (IQR 0.29-3.22), for RASI/ARNI there was no significant difference in outcome for females achieving 50-99% versus 100% of TD (hazard ratio 0.92, 95% confidence interval 0.83-1.03), whereas males showed a gradual lowering in risk together with the achievement of higher % of TD (p-interaction = 0.030). For beta-blockers the achievement of TD was associated with the lowest risk of outcome regardless of sex. CONCLUSIONS: Our findings suggest that females and males might differently benefit from the same dose of RASI/ARNI, and do represent a general call for randomized controlled trials to consider sex-specific up-titration schemes when testing HFrEF treatments in need of up-titration.
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Antagonistas Adrenérgicos beta , Antagonistas de Receptores de Angiotensina , Insuficiencia Cardíaca , Sistema de Registros , Humanos , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/fisiopatología , Femenino , Masculino , Anciano , Suecia/epidemiología , Antagonistas Adrenérgicos beta/uso terapéutico , Antagonistas Adrenérgicos beta/administración & dosificación , Factores Sexuales , Antagonistas de Receptores de Angiotensina/administración & dosificación , Antagonistas de Receptores de Angiotensina/uso terapéutico , Pronóstico , Volumen Sistólico/fisiología , Anciano de 80 o más Años , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/administración & dosificaciónRESUMEN
OBJECTIVE: To investigate the epidemiology of pregnancy-related urinary incontinence (UI) and the related risk factors, focusing also on women's characteristics related to maternity pathway utilization. METHODS: In this prospective cohort study, we used patient-reported data obtained from the systematic survey on the maternity pathway that all pregnant women in Tuscany, Italy, can join. We selected 8410 women who completed-between March 2019 and November 2022-all five follow-up questionnaires from the first trimester until 12 months postpartum, each including a UI-specific patient-reported outcome measure. We performed panel regression models to explore the related risk factors. RESULTS: Prevalence of UI was 4.4% at the first trimester, 23.7% at the third trimester, and 15.6%, 12.6%, and 12.4% at 3, 6, and 12 months postpartum. UI occurrence and severity were higher in older, overweight/obese, and unemployed women. High-risk pregnancy and discomfort during pregnancy were risk factors. Receiving a cesarean section reduced the risk, while spontaneous tears, episiotomy, and high birth weight increased it. Women who experienced delays in pregnancy examinations because of long waiting times and women who had planned pregnancy had a higher risk, while performing during-pregnancy pelvic-floor-muscle training was protective. CONCLUSION: Besides confirming the classic risk and protective factors for UI, we also found novel determinants related to the proper maternity pathway utilization.
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Cesárea , Incontinencia Urinaria , Femenino , Embarazo , Humanos , Anciano , Cesárea/efectos adversos , Estudios de Cohortes , Estudios Prospectivos , Factores Protectores , Periodo Posparto , Incontinencia Urinaria/epidemiología , Incontinencia Urinaria/etiología , Factores de Riesgo , Embarazo de Alto Riesgo , Diafragma PélvicoRESUMEN
Objective: The use of episiotomy during operative vaginal birth (OVB) is rather debated among operators and in literature. It is also important to evaluate the indications for which episiotomy is performed. In fact, the consequences of an episiotomy can be invalidating for patients with long-lasting results. The aim of this study is the evaluation of the role of episiotomy during OVB with the vacuum extractor and its correlation with Obstetric Anal Sphincter Injuries (OASIs).Methods: On of 9165 vaginal births, a total of 498 OVB (5.4%) were enrolled in a longitudinal prospective observational study. The incidence of OASIs was evaluated in our population after OVB performed with the vacuum extractor, during which the execution of episiotomy was performed indicated by clinician in charge.Results: OASIs occurred in 4% of the patients (n = 20). Episiotomy was performed in 39% of them (n = 181). OASIs incidence was 6% (n = 17) in the No Episiotomy and 1.8% (n = 3) in Episiotomy group (p<.001). Performance of episiotomy during OVB determined a protective effect against OASIs (p = 0.025 in full cohort and p = 0.013 in the primiparous group). An expulsive phase under one hour was an almost significant protective factor (p = 0.052).Conclusions: The use of episiotomy during OVB was associated with much lower OASIs rates in nulliparous women with a vacuum extraction; OR 0.23 (CI 95% 0.07-0.81) p = 0.037 in nulliparous women and the number necessary to treat was 18 among nulliparous women to prevent 1 OASIs. A further risk factor that emerged from the analysis is a prolonged expulsive period, whereas fundal pressure does not seem to have a statistically significant influence.
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Complicaciones del Trabajo de Parto , Embarazo , Humanos , Femenino , Estudios Longitudinales , Estudios Retrospectivos , Complicaciones del Trabajo de Parto/epidemiología , Complicaciones del Trabajo de Parto/etiología , Complicaciones del Trabajo de Parto/prevención & control , Canal Anal/lesiones , Parto Obstétrico/efectos adversos , Factores de RiesgoRESUMEN
OBJECTIVES: To assess influenza and Tdap (tetanus, diphtheria, pertussis) vaccine coverage during pregnancy, explore key socioeconomic and maternity pathway-related predictors of vaccination, and detect specific patterns of vaccination uptake. METHODS: The authors cross-sectionally analyzed self-reported data obtained from the systematic survey on the maternity pathways of Tuscany. They selected all pregnant women that completed from March 2019 to June 2022 the third-trimester questionnaire (n = 25 160), which included two dichotomous items on influenza and Tdap vaccination, as well as socioeconomic and pathway-related questions. Multilevel logistic models were performed to assess vaccination predictors and cluster analysis to identify vaccination patterns. RESULTS: Vaccination coverage was higher for pertussis (56.5%) than for influenza (18.9%). The main predictors of vaccination were high socioeconomic status, attending private gynecologists, and receiving vaccine information. Three clusters were identified: cluster 1 included women receiving both Tdap and influenza vaccines; cluster 2 included women receiving no vaccinations; and cluster 3 included women receiving only the pertussis vaccine. Although women from cluster 3 were of middle to low education status, vaccine information was the main adherence determinant also in this group. CONCLUSIONS: Health workers and policymakers should focus on groups of pregnant women less prone to vaccination to promote vaccination information and encourage wider uptake and coverage.
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Vacunas contra Difteria, Tétanos y Tos Ferina Acelular , Vacunas contra la Influenza , Gripe Humana , Tos Ferina , Femenino , Embarazo , Humanos , Gripe Humana/prevención & control , Estudios Transversales , Tos Ferina/prevención & control , Encuestas y CuestionariosRESUMEN
OBJECTIVES: To explore determinants of practice variation in both access, and quality and efficiency of surgical care for pelvic organ prolapse (POP). DESIGN AND SETTING: A retrospective cohort study employing administrative health data from the Tuscany region, Italy. PARTICIPANTS: All women over 40 years hospitalised for apical/multicompartmental POP reconstructive surgery (excluding anterior/posterior colporrhaphy without concomitant hysterectomy) from January 2017 to December 2019. OUTCOMES: We first computed treatment rates just for women residing in Tuscany (n=2819) and calculated the Systematic Component of Variation (SCV) to explore variation in access to care among health districts. Then, using the full cohort (n=2959), we ran multilevel models for the average length of stay and reoperations, readmissions and complications, and computed the intraclass correlation coefficient to assess the individual and hospital determinants of efficiency and quality of care provided by hospitals. RESULTS: The 5.4-fold variation between the lowest-rate (56/100 000 inhabitants) and the highest-rate (302/100 000) districts and the SCV over 10% confirmed high systematic variation in the access to care. Higher treatment rates were driven by greater provisions of robotic and/or laparoscopic interventions, which showed highly variable usage rates. Both individual and hospital factors influenced quality and efficiency provided by hospitals, but just low proportions of variation were explained by hospital and patient characteristics. CONCLUSIONS: We found high and systematic variation in the access to POP surgical care in Tuscany and in quality and efficiency provided by hospitals. Such a variation may be mainly explained by user and provider preferences, which should be further explored. Also, supply-side factors may be involved, suggesting that wider and more uniform dissemination of robotic/laparoscopic procedures may reduce variation.
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Hospitales , Prolapso de Órgano Pélvico , Humanos , Femenino , Estudios Retrospectivos , Italia/epidemiología , Histerectomía , Prolapso de Órgano Pélvico/cirugíaRESUMEN
INTRODUCTION: Although childbirth services were accessible after COVID-19 outbreak, the measures taken by the Italian Government for contagion containment required some restrictions on the presence of trusted persons for mothers, forcing them to isolation during hospitalization. To preserve companionship, the Regional Health Authority of Tuscany issued a resolution providing partners with the possibility to be present during labour and childbirth for non-asymptomatic women. OBJECTIVES: In this study, we: 1) analyse the impact of pandemic on companionship in terms of significant reduction of the possibility for women to be accompanied by a trusted person during labour and childbirth; and 2) ascertain if the regional resolution issued was effective in containing the reduction of companionship. METHODS: We performed an interrupted time series analysis to measure the variation of the possibility for women to be accompanied by a trusted person during labour and childbirth, in response to formalization of lock-down due to COVID-19 outbreak and the introduction of the regional resolution aimed at contrasting negative effects on companionship. RESULTS AND CONCLUSIONS: The ITS analysis showed that there was a significant decrease in the women-reported experience of companionship in the month of the formalization of lock-down, namely March 2020, followed by a slight increase in the upcoming months. A trend reversal was observed after May 2020, when the regional resolution was fully operational.
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COVID-19 , Trabajo de Parto , Embarazo , Femenino , Humanos , Control de Enfermedades Transmisibles , Parto , Brotes de EnfermedadesRESUMEN
OBJECTIVE: The Italian healthcare jurisdiction promotes patient mobility, which is a major determinant of practice variation, thus being related to the equity of access to health services. We aimed to explore how travel times, waiting times, and other efficiency- and quality-related hospital attributes influenced the hospital choice of women needing pelvic organ prolapse (POP) surgery in Tuscany, Italy. METHODS: We obtained the study population from Hospital Discharge Records. We duplicated individual observations (n = 2533) for the number of Tuscan hospitals that provided more than 30 POP interventions from 2017 to 2019 (n = 22) and merged them with the hospitals' list. We generated the dichotomous variable "hospital choice" assuming the value one when hospitals where patients underwent surgery coincided with one of the 22 hospitals. We performed mixed logit models to explore between-hospital patient choice, gradually adding the women's features as interactions. RESULTS: Patient choice was influenced by travel more than waiting times. A general preference for hospitals delivering higher volumes of interventions emerged. Interaction analyses showed that poorly educated women were less likely to choose distant hospitals and hospitals providing greater volumes of interventions compared to their counterpart. Women with multiple comorbidities more frequently chose hospitals with shorter average length of stay. CONCLUSION: Travel times were the main determinants of hospital choice. Other quality- and efficiency-related hospital attributes influenced hospital choice as well. However, the effect depended on the socioeconomic and clinical background of women. Managers and policymakers should consider these findings to understand how women behave in choosing providers and thus mitigate equity gaps.
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Hospitales , Prolapso de Órgano Pélvico , Humanos , Femenino , Prolapso de Órgano Pélvico/cirugía , Atención a la Salud , Servicios de Salud , Modelos LogísticosRESUMEN
OBJECTIVE: To explore how the COVID-19 pandemic influenced self-reported occurrence and severity of pregnancy-related urinary incontinence (UI) in the maternity pathways of Tuscany, Italy. METHODS: In this prospective pre-post cohort study, we selected a pre-pandemic (n = 1018) and a post-pandemic (n = 3911) cohorts of women that completed, from the first trimester until 3 months postpartum, three surveys including validated patient-reported outcome measures for UI. Data were obtained from systematic surveys on the maternity pathways of Tuscany from March 2019 to June 2021. We performed panel regression models to explore how UI risk differed between COVID-19 groups. RESULTS: UI occurred less frequently and less severely in post-pandemic patients-especially stress/mixed UI in women never performing pelvic floor muscle training (PFMT)-whereas no difference emerged in women performing during-pregnancy PFMT. During COVID-19, obese women had higher risk of UI, whereas women undergoing operative delivery had lower risk. The post-pandemic group reported more severe UI symptoms at the third trimester, but less severe UI postpartum in women suffering from UI during pregnancy. CONCLUSIONS: During the COVID-19 pandemic, women reported fewer UI symptoms because they might have lacked chances to identify UI symptoms as a result of pandemic-related sedentarism and inactivity. The risk in women performing during-pregnancy PFMT was not increased, but just six of 26 health districts organized remote PFMT sessions, thus revealing limited resilience to the pandemic in Tuscany.
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COVID-19 , Incontinencia Urinaria de Esfuerzo , Incontinencia Urinaria , Femenino , Humanos , Embarazo , Diafragma Pélvico/fisiología , Estudios Prospectivos , Pandemias , Autoinforme , Estudios de Cohortes , Terapia por Ejercicio , COVID-19/epidemiología , Incontinencia Urinaria/epidemiología , Periodo Posparto , Incontinencia Urinaria de Esfuerzo/epidemiologíaRESUMEN
BACKGROUND: In Italy, abortion services are public: therefore, health Institutions should provide clear and easily readable web-based information. We aimed to 1) assess variation in abortion services utilisation; 2) analyse the readability of institutional websites informing on induced abortion; 3) explore whether easier-to-read institutional websites influenced the correct fruition of abortion services. METHODS: We identified from the 2021 administrative databases of Tuscany all women having an abortion, and-among them-women having an abortion with the certification provided by family counselling centres, following the pathway established by law. We assessed variation in total and certified abortion rates by computing the Systematic Component of Variation. We analysed the readability of the Tuscan health authorities' websites using the readability assessment tool READ-IT. We explored how institutional website readability influenced the odds of having certified abortions by running multilevel logistic models, considering health authorities as the highest-level variables. RESULTS: We observed high variation in the correct utilization of the abortion pathway in terms of certified abortion rates. The READ-IT scores showed that the most readable text was from the Florence Teaching Hospital website. Multilevel models revealed that higher READ-IT scores, corresponding to more difficult texts, resulted in lower odds of certified abortions. CONCLUSIONS: Large variation in the proper fruition of abortion pathways occurs in Tuscany, and such variation may depend on readability of institutional websites informing on induced abortion. Therefore, health Institutions should monitor and improve the readability of their websites to ensure proper and more equitable access to abortion.
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Aborto Inducido , Información de Salud al Consumidor , Femenino , Humanos , Embarazo , Comprensión , Estudios Transversales , Lectura , Centros Médicos Académicos , InternetRESUMEN
OBJECTIVE: To investigate prevalence and risk factors of pregnancy-related urinary/fecal incontinence (UI/FI) in a large Italian population. METHODS: This is a prospective cohort study analyzing patient-reported outcome (PRO) measures obtained from the systematic longitudinal survey on the maternity pathway of Tuscany from March 2019 to April 2021. Four questionnaires were completed by 6023 women from the beginning of pregnancy until 6 months postpartum, each including two PRO measures-Wexner scale for FI and ICIQ-SF for UI-, and questions investigating sociodemographic/clinical factors. After assessing UI/FI prevalence at each time-point, we run panel regressions to explore the related risk factors. RESULTS: Women reporting UI and FI were, respectively, 24.3% and 6.2% in the third trimester, and 12.6% and 4.2% 6 months postpartum. UI occurrence and severity were higher in highly educated, aged >30, and overweight/obese women. Spontaneous tears or episiotomy were risk factors for postpartum UI, while receiving cesarean-section and performing pelvic-floor-muscle-training during pregnancy were protective, mainly in specific groups. Finally, higher FI prevalence and severity emerged in overweight, aged >40, highly educated, non-Italian women and in those undergoing tears. CONCLUSION: We employed PRO measures to investigate the epidemiology of pregnancy-related UI/FI and detect the main risk groups. Pelvic-floor-muscle-training may be recommended in women with peculiar sociodemographic/clinical features.
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Incontinencia Fecal , Incontinencia Urinaria , Incontinencia Fecal/epidemiología , Incontinencia Fecal/etiología , Femenino , Humanos , Sobrepeso/complicaciones , Medición de Resultados Informados por el Paciente , Embarazo , Estudios Prospectivos , Incontinencia Urinaria/etiologíaRESUMEN
D-Chiro-Inositol (D-Chiro-Ins) is a secondary messenger in the insulin signaling pathway. D-Chiro-Ins modulates insulin secretion, the mitochondrial respiratory chain, and glycogen storage. Due to these actions D-Chiro-Ins has been proposed to correct defective insulin function in a variety of conditions characterized by metabolic dysfunction, such as polycystic ovary syndrome (PCOS), obesity, gestational diabetes and fat accumulation at menopause. Since it is unclear whether D-Chiro-Ins directly acts on adipocytes, we aimed to study D-Chiro-Ins's actions on adipocyte viability, proliferation, differentiation, and insulin-related protein expression using a human adipocyte cell line derived from Simpson-Golabi-Behmel Syndrome (SGBS) which fully differentiates to mature adipocytes. Throughout differentiation, cells were treated with D-Chiro-Ins, 17ß-estradiol (E2) or Insulin. Cell viability and proliferation were not affected by D-Chiro-Ins, then D-Chiro-Ins promoted cell differentiation only during the final days of the process, while E2 enhanced it from the first phases. D-Chiro-Ins stimulated lipid storage and the production of big lipid droplets, thus reducing the content of free fatty acids. We also found that D-Chiro-Ins, either alone or in combination with insulin and E2 increased the expression and activation of insulin receptor substrate-1 (IRS1) and glucose transporter type 4 (GLUT4). In conclusion, this work shows that D-Chiro-Ins plays a direct role in the differentiation and in the function of human adipocytes, where it synergizes with insulin and estrogen through the recruitment of signal transduction pathways involved in lipid and glucose storage. These findings give clear insights to better understand the actions of D-Chiro-Ins on fat metabolism in women in physiology and in a variety of diseases.