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Objective: To identify the impact of redox imbalance on the clinical evolution of patients with polycystic ovary syndrome and carry out a qualitative and quantitative projection of the benefits of vitamin D supplementation. Data sources: Combinations of the keywords polycystic ovary syndrome, vitamin D, oxidative stress, reactive oxygen species, antioxidant, and free radicals were used in PubMed, Cochrane Library, LILACS, EMBASE, and Web of Science databases. The last search was conducted on August 22, 2023.Selection of studies: Based on the inclusion and exclusion criteria, studies were selected considering a low risk of bias, published in the last 5 years in English, which investigated the effects of vitamin D supplementation in women with PCOS, focusing on oxidative stress markers. Of the 136 articles retrieved, 6 intervention studies (445 women) were included. Data collection: The risk of bias in included studies was assessed using the Jadad scale, and analysis and visualization of continuous data were performed using Review Manager 5.4.1, summarized as standardized mean differences (SMD) with confidence intervals (CI) of 95%. Data synthesis: Vitamin D effectively reduced malondialdehyde (P=0.002) and total testosterone (P=0.0004) levels and increased total antioxidant capacity levels (P=0.01). Although possible improvements in the modified Ferriman-Gallwey hirsutism score, levels of sex hormone-binding globulin, and free androgen index were identified and the results were not statistically significant. Conclusion: Vitamin D is a promising alternative for the treatment of PCOS with a positive influence on the oxidative, metabolic, and endocrine disorders of this syndrome.

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CONTEXT: Controversial results have emerged regarding whether polycystic ovary syndrome (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 October 1, 2018, and December 31, 2023. The diagnosis of PCOS should be based on National Institutes of Health criteria, the Rotterdam Consensus, Androgen Excess & PCOS Society criteria, or International Classification of Diseases 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 2 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 30 305 women with PCOS and 10,1907 controls. Contrasting profiles emerged after stratification using a body mass index (BMI) cutoff of 27 kg/m2. Individuals with PCOS and a BMI <27 kg/m2 exhibited lower vertebral and nonvertebral bone density, reduced bone turnover marker (osteocalcin), and increased bone resorption marker (C-terminal type I collagen) levels. Conversely, individuals with PCOS and a BMI ≥27 kg/m2 exhibited increased vertebral and nonvertebral bone mineral density, with no significant changes in bone formation and resorption markers (except osteocalcin). CONCLUSION: 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.

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INTRODUCTION: In females with congenital adrenal hyperplasia (CAH), the influence of hyperandrogenism and glucocorticoid supplementation on neurocognition is controversial. OBJECTIVES: To identify possible differences in visual working memory and verbal memory in adolescent girls with CAH due to 21-hydroxylase deficiency and matched controls. Moreover, to study if any relationship between variables associated with CAH and the scores of the selected memory tests was present. MATERIAL AND METHODS: In total 39 individuals were studied, female adolescents with CAH and age and pubertal stage matched healthy male and female controls (13 in each group). Sociodemographic, clinical, hormonal, and neurocognitive variables were explored. In female adolescents with CAH, variables related to the disease (age at diagnosis, clinical form, time since diagnosis, and glucocorticoid doses) were correlated with the scores obtained for neurocognitive variables. RESULTS: The mean age was 13.9 ± 3.3 years. In female adolescents with CAH the results were worse compared to controls in Free Recall (p = 0.039) and in Visual Memory Span score (p = 0.016). Age at diagnosis was negatively correlated to number of hits (p = 0.04), number recalled backward (p = 0.03), Visual Memory Span test score (p = 0.04) and Total Free Recall (p = 0.04), i.e., memory was worse with later diagnosis. CONCLUSIONS: Female adolescents with CAH had worse visual working memory compared to matched controls, but not in verbal memory. Age at diagnosis was negatively associated with the memory tests.

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RESUMEN Los tumores de ovario son raros en pediatría. En este grupo, los tumores de células esteroideas representan el 0,1% de los casos y existen escasos reportes en la literatura. Presentamos el caso de una niña de 11 años con síntomas de engrosamiento de la voz, hirsutismo, acné y clitoromegalia. El análisis de laboratorio mostró niveles elevados de testosterona total y libre, niveles normales de 17-hidroxiprogesterona. La evaluación ecográfica reveló un agrandamiento significativo del ovario izquierdo. La paciente fue sometida a salpingooforectomía izquierda. Este hallazgo fue consistente con un tumor de células esteroideas de ovario. A esto le siguió la reducción gradual de los andrógenos y la mejoría clínica. Los tumores de células esteroideas son raros en pediatría, sin embargo, deben considerarse como diagnóstico diferencial al estudiar pacientes con síntomas de hiperandrogenismo.

ABSTRACT Ovarian tumors are rare in pediatrics. In this group, steroid cell tumors represent 0.1% of total cases and there are few reports in the literature. We present the case of an 11-year-old girl who suffered from deeper voice, hirsutism, acne and clitoromegaly. Analysis showed elevated levels of total and free testosterone, normal levels of 17-hydroxyprogesterone. Ultrasound evaluation revealed significant enlargement of the left ovary. The patient underwent left salpingo-oophorectomy. This finding is consistent with an ovarian steroid cell tumor. This is followed by gradual reduction of androgens and clinical improvement. Steroid cell tumors are rare in pediatrics, however, they should be considered as a differential diagnosis when studying patients with symptoms of hyperandrogenism.

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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.

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Introducción y objetivos: Determinar los hallazgos clínicos y ecográficos en pacientes que presentan menos de 12 folículos ováricos. Método: Estudio observacional (cohorte histórica) con 505 pacientes seleccionadas mediante muestreo consecutivo, entre el 14 de enero del 2019 y el 15 de marzo del 2021, que consultan por diversas alteraciones ginecológicas. Se generan dos grupos de pacientes, las que presentaron uno a tres folículos en uno de los ovarios (n = 377) y las que presentaban 4 a 11 folículos (n = 128). Se midió como resultado primario la presencia de al menos un signo clínico de hiperandrogenismo. Resultados: De 505 pacientes analizadas, al comparar las que presentaron 4 a 11 folículos en uno de los ovarios (n = 377) con las que presentaban 1 a 3 folículos (n = 128), las primeras mostraron mayor presencia de signos de hiperandrogenismo, endometrio en fase lútea de mayor espesor y un patrón menstrual con uno a cuatro días de sangrado menstrual abundante, diferencias todas estadísticamente significativas (p < 0,05). Conclusión: En pacientes con 4 a 11 folículos en uno de sus ovarios, se observaron signos de hiperandrogenismo, similares al síndrome de ovario poliquístico.

Introduction and objectives: Determine the clinical and ultrasound findings in patients who present less than 12 ovarian follicles in the ultrasound count. Method: Observational study (historical cohort) with 505 patients selected by consecutive sampling, between January 14, 2019 and March 15, 2021, who consulted for different gynecological disorders. Two groups of patients were generated: those with 1 to 3 follicles in one of the ovaries (n = 377) and those with 4 to 11 follicles (n = 128). The primary outcome was the presence of at least one clinical sign of hyperandrogenism. Results: Of 505 patients analyzed, when comparing those who presented 4 to 11 follicles in one of the ovaries (n = 377) with those who presented 1 to 3 follicles (n = 128), the first group showed a greater presence of signs of hyperandrogenism, thicker endometrium in luteal phase and a menstrual pattern with one to four days of heavy menstrual bleeding, all differences were statistically significant (p < 0.05). Conclusion: In patients with 4 to 11 follicles in one of their ovaries, signs of hyperandrogenism, similar to polycystic ovary syndrome, were observed.

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BACKGROUND: Polycystic ovary syndrome (PCOS) is an endocrine disorder characterized by anovulation, hyperandrogenism, and polycystic ovarian morphology. Its etiology is uncertain and one of the hypotheses is that environmental factors, such as the bisphenol A (BPA) endocrine disruptor, may be involved. OBJECTIVE: To investigate the association between exposure to BPA and PCOS. SEARCH STRATEGY: Research was conducted focusing on studies published in English, Portuguese, and Spanish from January 2001 to March 2023 and available in Embase, Medline/PubMed, Rima, Lilacs, Scielo, Google academic, and SCI databases. SELECTION CRITERIA: Studies in humans that evaluated the association between exposure to BPA and a diagnosis of PCOS. DATA COLLECTION AND ANALYSIS: Following PRISMA guidelines, study characteristics and relevant data were extracted. MAIN RESULTS: Selection of 15 case-control and 7 cross-sectional studies with a total of 1682 PCOS patients. The studies were carried out in China, Poland, Turkey, Japan, Greece, Italy, the USA, Iran, Iraq, Egypt, India, Czechia, and Slovakia. A positive relationship between exposure to BPA and PCOS was described in19 studies (1391 [82.70%] of the PCOS patients). The fluids used in the studies were serum, urine, plasma, and follicular fluid. BPA was measured by ELISA and by chromatography (HPLC, HPLC-MS/MS, GC-MS, and GC-MS/MS). Diagnosis of PCOS used Rotterdam criteria in 15, NIH 1999 in 3, AE&PCOS Society in 2, similar to the Rotterdam criteria in 1, and criteria not informed in 1. Androgens were measured in 16 studies; in 12, hyperandrogenism was positively associated with BPA. BPA level was related to body mass index (BMI) in studies. In 15 studies independently of BMI, women with PCOS had higher BPA levels. Carbohydrate metabolism disorders were evaluated in 12 studies and in 6 a positive correlation was found with BPA levels. Lipid profile was evaluated in seven studies and in only one the correlation between lipid profile and BPA levels was present. CONCLUSIONS: Exposure to BPA is positively associated with PCOS, mainly with the hyperandrogenism.

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SUMMARY OBJECTIVE: The objective of this study was to learn more about the prevalence and pathophysiology of depression and anxiety that may be caused by polycystic ovary syndrome and to make plans for taking necessary precautions for this vulnerable group. METHODS: This case-control study was conducted between January 2022 and October 2022. A total of 120 women with polycystic ovary syndrome and 143 controls were included in the study. All healthy volunteers and women with polycystic ovary syndrome were evaluated using self-administered questionnaires and physical examination. Anthropometric data such as weight and height and laboratory value were documented. RESULTS: There was no significant difference between the groups in terms of demographic characteristics. When the Hospital Anxiety and Depression Scale scores of both groups were compared, both depression and anxiety scores were found to be significantly higher in women with polycystic ovary syndrome compared with the control group (OR: 3.319, 95%CI, 1.563-7.047, p<0.001 and OR: 3.238, 95%CI, 1.659-6.315, p<0.001). In the Hospital Anxiety and Depression Scale questionnaire, the rate of irregular menstruation and Ferriman-Gallwey score were statistically significant in women with polycystic ovary syndrome with high depression and anxiety scores. While serum LH levels and LH/FSH ratios were significantly different in women with polycystic ovary syndrome with high depression scores, serum LH, LH:FSH ratios, and serum total testosterone levels were found significant in women with polycystic ovary syndrome with high anxiety scores. CONCLUSION: It is clear that depression and anxiety are more common in patients with polycystic ovary syndrome than in healthy women. Our findings support previous recommendations regarding routine screening for depression and anxiety in this population.

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OBJECTIVE: Spironolactone (SPL) has been used to manage hyperandrogenic manifestations in women with polycystic ovary syndrome (PCOS), but data on the risk of hyperkalemia in this population are scarce. The aim of this study was to evaluate the incidence of hyperkalemia in women with PCOS using SPL in the long term. DESIGN: Single-centre retrospective study. PATIENTS: Inclusion and analysis of 98 treatment periods in 78 women with PCOS (20 of whom were duplicates, returning after treatment interruption for a mean of 38 months) who received SPL for a minimum of 12 months and had at least three measurements of potassium levels over time. MEASUREMENTS: Clinical and hormonal profiles before and during SPL treatment. RESULTS: Mean age was 29.1 (SD: 9.6) years, and body mass index was 32.2 (SD: 8.1) kg/m². Nine patients had diabetes, and 22 had prediabetes. SPL was used in combination with combined oral contraceptive pills in 55 participants and progestin-only pills/long-acting reversible contraception in 28; metformin was added in 35, and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers in 15. Median SPL dose was 100 (range: 50-150) mg. A total of 327 serum potassium measurements were obtained (84 pre-exposure and 243 postexposure). Four potassium measurements were above the reference range before exposure and 19 during exposure. All potassium measurements above the reference range during follow-up were classified as mild hyperkalemia (5.1-5.5 mEq/L). CONCLUSIONS: The present findings suggest that women with PCOS, without kidney or heart disease, using SPL combined with hormonal contraception for managing clinical hyperandrogenism have a low incidence of hyperkalemia and well-tolerated minor adverse effects.

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ABSTRACT Objective The aim of this study was to evaluate the efficacy of a self-assessment questionnaire for hirsutism using the latest cutoff values recommended by the Endocrine Society (ES) for Latin-American women and by the European Society for Human Reproduction and Embryology (ESHRE). Subject and methods Female premenopausal outpatients (n = 188) completed a self-assessment questionnaire, scoring hair presence across the nine areas evaluated by the modified Ferriman-Gallwey (mFG) scale. The results were compared with clinician-assessed scores rated independently by two trained physicians. Scores in the Hirsuta questionnaire, derived from self-assessment of five areas of the mFG scale, were also evaluated. Results The ethnic composition of the sample was as follows: 23.1% white, 25.8% black, 48.9% mixed, and 2.1% other backgrounds (Indigenous, Asian). The participants had age and BMI of (mean ± standard deviation) 33.7 ± 9.9 years and 29.8 ± 7.21 kg/m2, respectively. The most common areas of excessive hair growth were the chin, upper and lower abdomen, and thighs. Relative to clinician-assessed mFG scores, self-assessed mFG scores had an accuracy of 80% using ES criteria for hirsutism diagnosis, with a sensitivity of 95.45%, specificity of 56.25%, positive predictive value of 30.10%, and negative predictive value of 98.40%. Self-assessed mFG had lower accuracy (71%) for diagnosing hirsutism when the ESHRE criteria were applied. Conclusions Self-assessed mFG had low specificity, limiting its application. The results of this study do not support the use of the self-assessed mFG or Hirsuta scores for diagnosing hirsutism in a clinical setting, although both scoring systems may be useful for screening hirsutism in epidemiological studies.

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Abstract Objective To identify the impact of redox imbalance on the clinical evolution of patients with polycystic ovary syndrome and carry out a qualitative and quantitative projection of the benefits of vitamin D supplementation. Data sources Combinations of the keywords polycystic ovary syndrome, vitamin D, oxidative stress, reactive oxygen species, antioxidant, and free radicals were used in PubMed, Cochrane Library, LILACS, EMBASE, and Web of Science databases. The last search was conducted on August 22, 2023.Selection of studies: Based on the inclusion and exclusion criteria, studies were selected considering a low risk of bias, published in the last 5 years in English, which investigated the effects of vitamin D supplementation in women with PCOS, focusing on oxidative stress markers. Of the 136 articles retrieved, 6 intervention studies (445 women) were included. Data collection The risk of bias in included studies was assessed using the Jadad scale, and analysis and visualization of continuous data were performed using Review Manager 5.4.1, summarized as standardized mean differences (SMD) with confidence intervals (CI) of 95%. Data synthesis Vitamin D effectively reduced malondialdehyde (P=0.002) and total testosterone (P=0.0004) levels and increased total antioxidant capacity levels (P=0.01). Although possible improvements in the modified Ferriman-Gallwey hirsutism score, levels of sex hormone-binding globulin, and free androgen index were identified and the results were not statistically significant. Conclusion Vitamin D is a promising alternative for the treatment of PCOS with a positive influence on the oxidative, metabolic, and endocrine disorders of this syndrome.

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El síndrome de ovario poliquístico es un trastorno endocrino-genético-ginecológico que afecta principalmente a mujeres en edad fértil, con manifestaciones de hiperandrogenismo e infertilidad en etapas tempranas de la vida. Este trabajo tiene por objetivo describir el diagnóstico y tratamiento del síndrome de ovario poliquístico. cuya fisiopatología no ha sido del todo comprendida, de ahí que su diagnóstico continúe siendo por exclusión. Los criterios del consenso de Rotterdam han logrado mejorar la uniformidad diagnóstica; sin embargo, se hace necesario un diagnóstico individualizado, en el cual debe incluirse el estudio de la morfología de los ovarios. Aunque la literatura sugiere la asociación de esta entidad con la presencia de obesidad, resistencia a la insulina e hiperinsulinismo, no se incluyen como parte de los criterios diagnósticos actualmente. El tratamiento incluye cambios en los estilos de vida, unidos a inhibidores de la producción de andrógenos por los ovarios, inhibidores de la acción de los andrógenos y los sensibilizadores a la insulina; se establecerá según los intereses reproductivos de la paciente.

Polycystic ovary syndrome is an endocrine-genetic-gynecological disorder that mainly affects women of childbearing age, with manifestations of hyperandrogenism and infertility in early stages of life. This work aims to describe the diagnosis and treatment of polycystic ovary syndrome whose pathophysiology has not been fully understood, hence its diagnosis continues to be by exclusion. The Rotterdam consensus criteria have managed to improve diagnostic uniformity; however, an individualized diagnosis is necessary, which must include the study of the morphology of the ovaries. Although the literature suggests the association of this entity with the presence of obesity, insulin resistance and hyperinsulinism, they are not currently included as part of the diagnostic criteria. Treatment includes changes in lifestyle, together with inhibitors of androgen production by the ovaries, inhibitors of androgen action and insulin sensitizers; It will be established according to the patient´s reproductive interests.

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PCOS is an endocrine disorder characterized by chronic anovulation, hyperandrogenism, and polycystic ovaries. Its etiology is uncertain. It is debated whether BPA would be a component of the environmental factor in the etiology of PCOS. Contamination by BPA can occur from food packaging (exposure during the diet) and through skin absorption and/or inhalation. It can be transferred to the fetus via the placenta or to the infant via breast milk, and it can be found in follicular fluid, fetal serum, and amniotic fluid. The phenolic structure of BPA allows it to interact with Estrogen Receptors (ERs) through genomic signaling, in which BPA binds to nuclear ERα or Erß, or through nongenomic signaling by binding to membrane ERs, prompting a rapid and intense response. With daily and constant exposure, BPA's tendency to bioaccumulate and its ability to activate nongenomic signaling pathways can alter women's metabolic and reproductive function, leading to hyperandrogenism, insulin resistance, obesity, atherogenic dyslipidemia, chronic inflammatory state, and anovulation and favoring PCOS. The harmful changes caused by BPA can be passed on to future generations without the need for additional exposure because of epigenetic modifications. Not only high BPA levels can produce harmful effects, but at low levels, BPA may be harmful when exposure occurs during the most vulnerable periods, such as the fetal and neonatal periods, as well as during the prepubertal age causing an early accumulation of BPA in the body. Learning how BPA participates in the pathogenesis of PCOS poses a challenge and further studies should be conducted.

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Congenital adrenal hyperplasia (CAH) is a common genetic disorder in endocrinology, especially its milder clinical presentation, often caused by a partial or total deficiency of the 21-hydroxylase enzyme located in the adrenal cortex. CAH is characterized by the overproduction of androgen, along with variable degrees of cortisol and aldosterone deficiency. The age at diagnosis can provide some information about underlying mutations, with those diagnosed at birth/early infancy more likely to have severe enzymatic defects, which may include adrenal insufficiency, sexual development disorders, short stature in adulthood, hirsutism, and a higher risk for metabolic syndrome and infertility. Non-classic CAH, a milder form of CAH, is usually manifested later in life and is a common differential diagnosis of Polycystic Ovary Syndrome and should be actively evaluated during initial studies of clinical or biochemical hyperandrogenism. The main goals of CAH treatment are hormone supplementation for severe cases, controlling adrenal androgen overproduction to minimize long-term side effects, managing fertility and genetic counseling, and optimizing patients' quality of life.

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PURPOSE: To summarize the effects of metformin treatment on markers of hyperandrogenism in patients diagnosed with polycystic ovary syndrome (PCOS). METHODS: A systematic review, with meta-analysis, of randomized placebo-controlled clinical trials that evaluated the effects of metformin treatment in adult patients with PCOS on the levels of hyperandrogenism markers was conducted. The literature search, data extraction, risk of bias, and the assessment of certainty of evidence were performed independently by two reviewers using a structured form. The results were combined by applying the random effect, and the effect measure presented as a standardized mean difference (SMD). Significant values were considered as p < 0.05 with 95% CI. Furthermore, sensitivity analyses were performed in order to explore possible heterogeneity between studies. RESULTS: Were included 18 studies in the quantitative evaluation and 17 studies (23 reports) in the quantitative evaluation. A significant reduction in total testosterone levels was seen in the metformin-treated group when compared to the control group after combining the results by the sensitivity analysis [SMD: - 0.46 (95% CI: - 0.89 to - 0.02)]. Therefore, FAI values were also regulated by metformin treatment. CONCLUSION: We showed that metformin proved to be effective in reducing total testosterone levels, and the same was observed for free androgen index (FAI) values-a measure influenced by testosterone levels. The protocol of this study was registered at Prospero (CRD42021235761).

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Prenatal androgen exposure induces fetal programming leading to alterations in offspring health and phenotypes that resemble those seen in women with Polycystic Ovary Syndrome. It has been described that prenatal androgenization affects the reproductive axis and leads to metabolic and endocrine disorders. Adipose tissue plays a crucial role in all these functions and is susceptible to programming effects. Particularly, gonadal adipose tissue is involved in reproductive functions, so dysfunctions in this tissue could be related to fertility alterations. We aimed to investigate the extent to which prenatal hyperandrogenization is able to alter the functionality of gonadal adipose tissue in female adult rats, including lipid metabolism, adipokines expression, and de novo synthesis of steroids. Pregnant rats were treated with 1 mg of testosterone from day 16 to day 19 of pregnancy, and female offspring were followed until 90 days of age, when they were euthanized. The prenatally hyperandrogenized (PH) female offspring displayed two phenotypes: irregular ovulatory (PHiov) and anovulatory (PHanov). Regarding lipid metabolism, both PH groups displayed disruptions in the main lipid pathways with altered levels of triglyceride and increased lipid peroxidation levels. In addition, we found that Peroxisome Proliferator-Activated Receptors (PPARs) alpha protein expression was decreased in both PH phenotypes (p < 0.05), but no changes were found in PPARγ protein levels. Furthermore, regarding adipokines, no changes were found in Leptin and Adiponectin protein levels, but Chemerin protein levels were decreased in the PHiov group (p < 0.05). Regarding de novo synthesis of steroids, the PHanov group showed increased protein levels of Cyp17a1 and Cyp19, while the PHiov group only showed decreased protein levels of Cyp19 (p < 0.05). These results suggest that prenatal androgen exposure affects females' gonadal adipose tissue in adulthood, disturbing different lipid pathways, Chemerin expression, and de novo synthesis of steroids.

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Abstract PCOS is an endocrine disorder characterized by chronic anovulation, hyperandrogenism, and polycystic ovaries. Its etiology is uncertain. It is debated whether BPA would be a component of the environmental factor in the etiology of PCOS. Contamination by BPA can occur from food packaging (exposure during the diet) and through skin absorption and/or inhalation. It can be transferred to the fetus via the placenta or to the infant via breast milk, and it can be found in follicular fluid, fetal serum, and amniotic fluid. The phenolic structure of BPA allows it to interact with Estrogen Receptors (ERs) through genomic signaling, in which BPA binds to nuclear ERα or Erβ, or through nongenomic signaling by binding to membrane ERs, prompting a rapid and intense response. With daily and constant exposure, BPA's tendency to bioaccumulate and its ability to activate nongenomic signaling pathways can alter women's metabolic and reproductive function, leading to hyperandrogenism, insulin resistance, obesity, atherogenic dyslipidemia, chronic inflammatory state, and anovulation and favoring PCOS. The harmful changes caused by BPA can be passed on to future generations without the need for additional exposure because of epigenetic modifications. Not only high BPA levels can produce harmful effects, but at low levels, BPA may be harmful when exposure occurs during the most vulnerable periods, such as the fetal and neonatal periods, as well as during the prepubertal age causing an early accumulation of BPA in the body. Learning how BPA participates in the pathogenesis of PCOS poses a challenge and further studies should be conducted.

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SUMMARY OBJECTIVE: The aim of this study was to compare the distribution of fat tissue in non-obese women with polycystic ovary syndrome and those without the syndrome using dual-energy radiological densitometry. METHODS: This was a case-control study in which we enrolled women aged 14-39 years with polycystic ovary syndrome according to the Rotterdam criteria with a body mass index between 18.5 and 30 kg/m2. The control group comprised women with the same profile, but without polycystic ovary syndrome. Patients were treated at the Endocrinological Gynecology Outpatient Clinic of the Department of Obstetrics and Gynecology of the Irmandade da Santa Casa de Misericórdia de São Paulo between 2019 and 2022. Anthropometric measurements were taken and the assessment of body composition was performed using dual-energy radiological densitometry. RESULTS: The sample comprised 57 women: 37 in the polycystic ovary syndrome group and 20 in the control group. The mean age of the polycystic ovary syndrome group was 24.9 years (±6.9) with a mean body mass index of 60.8 kg/m2 (±8.5), and for the control group, it was 24.2 years (±6.9) with a mean body mass index of 58 kg/m2 (±8.4). Body composition was evaluated using dual-energy radiological densitometry and showed a higher value of trunk fat in the polycystic ovary syndrome group (44.1%, ±9.0) compared to the control group (35.2%, ±11.4), which was statistically significant (p=0.002). CONCLUSION: Our study showed that non-obese polycystic ovary syndrome patients have a higher concentration of abdominal fat, which is a risk factor for increased cardiovascular risk and insulin resistance. ClinicalTrials.gov ID: NCT02467751.

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Polycystic ovary syndrome (PCOS) is an endocrine-metabolic disorder of unknown etiology. Hyperandrogenism (HA) is the main diagnostic criteria for PCOS, in addition to being a risk factor for developing several disorders throughout the patient's life, including pregnancy. However, the impact on offspring is little known. Therefore, the aim of this work was to evaluate the effect of maternal HA on glucose metabolism and hepatic lipid accumulation in adult offspring. We used Balb/c mice treated with dehydroepiandrosterone (DHEA) for 20 consecutive days. The ovary of DHEA-treated mice showed hemorrhagic bodies, an increased number of atretic follicles, and greater expression of genes related to meiotic cell cycle and DNA repair. The DHEA offspring (O-DHEA) had low birth weight, and some pups showed malformations. However, O-DHEA individuals gained weight rapidly, and the differences between them and the control group became significantly greater in adulthood. Moreover, O-DHEA presented higher serum glucose after a 6 h fast and a larger area under glucose, insulin, and pyruvate tolerance test curves. Oil Red O staining showed a more significant accumulation of fat in the liver but no changes in serum cholesterol and triacylglycerol levels. In summary, our results show that HA, induced by DHEA, affects gene expression in oocyte, which in turn generates defects in embryonic development, insulin resistance, and alteration in hepatic gluconeogenesis and lipid metabolism in O-DHEA, thereby increasing the risk of developing metabolic diseases.

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Hirsutism is defined as the presence of terminal hair with male pattern distribution in women. While in the general population, hirsutism affects around 4-11% of women, it is the main manifestation of hyperandrogenism in women with polycystic ovary syndrome (PCOS), with a prevalence estimated at 65-75%. Hirsutism in PCOS is associated with both androgen excess and individual response of the pilosebaceous unit to androgens. The modified Ferriman-Gallwey (mFG) scoring system has been widely used in clinical practice to visually score excessive terminal hair, thus standardizing hirsutism evaluation and facilitating data comparison. Although a universal mFG score cutoff would be useful for comparisons, ethnic variations, as well as skin type and other factors, should be considered when evaluating hirsutism in distinct populations. In turn, androgen levels, measured by conventional techniques, have been shown to correlate poorly with the severity of hirsutism. Indeed, while most women with PCOS and hirsutism also have higher than reference values for serum androgen levels, some of them may not present with biochemical hyperandrogenism, representing a challenge to the diagnosis of PCOS. In this article, we critically review this not uncommon condition in women with PCOS presenting with hirsutism but normal androgen levels.