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1.
Gynecol Endocrinol ; 40(1): 2352136, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38733359

RESUMEN

OBJECTIVE: This study aimed to investigate the impact of serum androgen levels on metabolic profiles in patients with polycystic ovary syndrome (PCOS). METHODS: We included 216 patients with PCOS and 216 healthy individuals selected as the control group. According to the measured serum androgen levels, patients with PCOS were divided into the hyperandrogenism group and non-hyperandrogenism group. Clinical metabolic indicators were assessed and compared between the two groups. Additionally, we assessed the correlation between androgen levels and clinical metabolic indicators. RESULTS: The body mass index, waist-to-hip ratio, mF-G score, and acne score, as well as T, LH, LSH/FSH, FPG, Cr, UA, TG, TC, and LDL-C levels were significantly higher in the PCOS group than in the control group. The incidence of hyperandrogenism and clinical hyperandrogenism in the PCOS group was significantly higher than that in the control group. Regarding clinical hyperandrogenism, hirsutism, acne, and acanthosis nigricans were significantly more common in the PCOS group than in the control group. Serum androgen levels were significantly correlated with the mF-G score, acne score, FSH, glucose concentration at 30 min, glucose concentration at 60 min, glucose concentration at 120 min, FINS, N120, HOMA-IR, HbA1c, AUCG, UA, TG, and hHDL-Clevels. CONCLUSION: Elevated serum androgen levels are commonly observed in patients with PCOS and are associated with multiple metabolic abnormalities. Therefore, it is recommended to regularly monitor glucose and lipid metabolism-related indicators in patients with PCOS who have elevated androgen levels.


Asunto(s)
Andrógenos , Hiperandrogenismo , Síndrome del Ovario Poliquístico , Humanos , Síndrome del Ovario Poliquístico/sangre , Síndrome del Ovario Poliquístico/metabolismo , Femenino , Adulto , Hiperandrogenismo/sangre , Andrógenos/sangre , Adulto Joven , Estudios de Casos y Controles , Índice de Masa Corporal , Metaboloma/fisiología , Acné Vulgar/sangre , Resistencia a la Insulina/fisiología
2.
Am J Reprod Immunol ; 91(5): e13854, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38716832

RESUMEN

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common endocrine-metabolic disorder characterized by oligo-anovulation, hyperandrogenism, and polycystic ovaries, with hyperandrogenism being the most prominent feature of PCOS patients. However, whether excessive androgens also exist in the ovarian microenvironment of patients with PCOS, and their modulatory role on ovarian immune homeostasis and ovarian function, is not clear. METHODS: Follicular fluid samples from patients participating in their first in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment were collected. Androgen concentration of follicular fluid was assayed by chemiluminescence, and the macrophage M1:M2 ratio was detected by flow cytometry. In an in vitro model, we examined the regulatory effects of different concentrations of androgen on macrophage differentiation and glucose metabolism levels using qRT-PCR, Simple Western and multi-factor flow cytometry assay. In a co-culture model, we assessed the effect of a hyperandrogenic environment in the presence or absence of macrophages on the function of granulosa cells using qRT-PCR, Simple Western, EdU assay, cell cycle assay, and multi-factor flow cytometry assay. RESULTS: The results showed that a significantly higher androgen level and M1:M2 ratio in the follicular fluid of PCOS patients with hyperandrogenism. The hyperandrogenic environment promoted the expression of pro-inflammatory and glycolysis-related molecules and inhibited the expression of anti-inflammatory and oxidative phosphorylation-related molecules in macrophages. In the presence of macrophages, a hyperandrogenic environment significantly downregulated the function of granulosa cells. CONCLUSION: There is a hyperandrogenic microenvironment in the ovary of PCOS patients with hyperandrogenism. Hyperandrogenic microenvironment can promote the activation of ovarian macrophages to M1, which may be associated with the reprogramming of macrophage glucose metabolism. The increased secretion of pro-inflammatory cytokines by macrophages in the hyperandrogenic microenvironment would impair the normal function of granulosa cells and interfere with normal ovarian follicle growth and development.


Asunto(s)
Andrógenos , Líquido Folicular , Células de la Granulosa , Hiperandrogenismo , Macrófagos , Síndrome del Ovario Poliquístico , Humanos , Síndrome del Ovario Poliquístico/metabolismo , Síndrome del Ovario Poliquístico/inmunología , Femenino , Células de la Granulosa/metabolismo , Macrófagos/inmunología , Macrófagos/metabolismo , Hiperandrogenismo/metabolismo , Adulto , Líquido Folicular/metabolismo , Andrógenos/metabolismo , Células Cultivadas , Activación de Macrófagos , Microambiente Celular , Técnicas de Cocultivo , Diferenciación Celular
3.
Nat Rev Dis Primers ; 10(1): 27, 2024 Apr 18.
Artículo en Inglés | MEDLINE | ID: mdl-38637590

RESUMEN

Despite affecting ~11-13% of women globally, polycystic ovary syndrome (PCOS) is a substantially understudied condition. PCOS, possibly extending to men's health, imposes a considerable health and economic burden worldwide. Diagnosis in adults follows the International Evidence-based Guideline for the Assessment and Management of Polycystic Ovary Syndrome, requiring two out of three criteria - clinical or biochemical hyperandrogenism, ovulatory dysfunction, and/or specific ovarian morphological characteristics or elevated anti-Müllerian hormone. However, diagnosing adolescents omits ovarian morphology and anti-Müllerian hormone considerations. PCOS, marked by insulin resistance and hyperandrogenism, strongly contributes to early-onset type 2 diabetes, with increased odds for cardiovascular diseases. Reproduction-related implications include irregular menstrual cycles, anovulatory infertility, heightened risks of pregnancy complications and endometrial cancer. Beyond physiological manifestations, PCOS is associated with anxiety, depression, eating disorders, psychosexual dysfunction and negative body image, collectively contributing to diminished health-related quality of life in patients. Despite its high prevalence persisting into menopause, diagnosing PCOS often involves extended timelines and multiple health-care visits. Treatment remains ad hoc owing to limited understanding of underlying mechanisms, highlighting the need for research delineating the aetiology and pathophysiology of the syndrome. Identifying factors contributing to PCOS will pave the way for personalized medicine approaches. Additionally, exploring novel biomarkers, refining diagnostic criteria and advancing treatment modalities will be crucial in enhancing the precision and efficacy of interventions that will positively impact the lives of patients.


Asunto(s)
Diabetes Mellitus Tipo 2 , Hiperandrogenismo , Síndrome del Ovario Poliquístico , Embarazo , Adulto , Adolescente , Femenino , Humanos , Síndrome del Ovario Poliquístico/complicaciones , Síndrome del Ovario Poliquístico/diagnóstico , Diabetes Mellitus Tipo 2/complicaciones , Calidad de Vida , Hormona Antimülleriana
4.
Gynecol Endocrinol ; 40(1): 2326102, 2024 Mar 02.
Artículo en Inglés | MEDLINE | ID: mdl-38654639

RESUMEN

BACKGROUND: Polycystic Ovary Syndrome (PCOS) is the most frequent endocrine disorder in female adults, and hyperandrogenism (HA) is the typical endocrine feature of PCOS. This study aims to investigate the trends and hotspots in the study of PCOS and HA. METHODS: Literature on Web of Science Core Collection (WoSCC) from 2008 to 2022 was retrieved, and bibliometric analysis was conducted using VOSviewer and CiteSpace software. RESULTS: A total of 2,404 papers were published in 575 journals by 10,121 authors from 2,434 institutions in 86 countries. The number of publications in this field is generally on the rise yearly. The US, China and Italy contributed almost half of the publications. Monash University had the highest number of publications, while the University of Adelaide had the highest average citations and the Karolinska Institute had the strongest cooperation with other institutions. Lergo RS contributed the most to the field of PCOS and HA. The research on PCOS and HA mainly focused on complications, adipose tissue, inflammation, granulosa cells, gene and receptor expression. CONCLUSION: Different countries, institutions, and authors should facilitate cooperation and exchanges. This study will be helpful for better understanding the frontiers and hotspots in the areas of PCOS and HA.


Asunto(s)
Bibliometría , Hiperandrogenismo , Síndrome del Ovario Poliquístico , Síndrome del Ovario Poliquístico/epidemiología , Humanos , Femenino , Hiperandrogenismo/epidemiología , Investigación Biomédica/tendencias , Investigación Biomédica/estadística & datos numéricos
5.
Pediatr Ann ; 53(4): e115-e120, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38574069

RESUMEN

Acne is a common skin condition in adolescent patients but much less common in childhood. Pediatric providers should be familiar with the varying presentations in the pediatric population and recognize when additional physical signs of hyperandrogenism are present. This article details the pathogenesis and presentation of acne in infancy, mid-childhood, and preadolescence. The differential diagnosis is discussed and recommendations for initial workup, referral, and treatment are provided. [Pediatr Ann. 2024;53(4):e115-e120.].


Asunto(s)
Acné Vulgar , Hiperandrogenismo , Adolescente , Niño , Humanos , Acné Vulgar/diagnóstico , Acné Vulgar/etiología , Acné Vulgar/terapia , Diagnóstico Diferencial , Derivación y Consulta
6.
Mol Hum Reprod ; 30(5)2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38603629

RESUMEN

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women of reproductive age, but its pathology has not been fully characterized and the optimal treatment strategy remains unclear. Cellular senescence is a permanent state of cell-cycle arrest that can be induced by multiple stresses. Senescent cells contribute to the pathogenesis of various diseases, owing to an alteration in secretory profile, termed 'senescence-associated secretory phenotype' (SASP), including with respect to pro-inflammatory cytokines. Senolytics, a class of drugs that selectively eliminate senescent cells, are now being used clinically, and a combination of dasatinib and quercetin (DQ) has been extensively used as a senolytic. We aimed to investigate whether cellular senescence is involved in the pathology of PCOS and whether DQ treatment has beneficial effects in patients with PCOS. We obtained ovaries from patients with or without PCOS, and established a mouse model of PCOS by injecting dehydroepiandrosterone. The expression of the senescence markers p16INK4a, p21, p53, γH2AX, and senescence-associated ß-galactosidase and the SASP-related factor interleukin-6 was significantly higher in the ovaries of patients with PCOS and PCOS mice than in controls. To evaluate the effects of hyperandrogenism and DQ on cellular senescence in vitro, we stimulated cultured human granulosa cells (GCs) with testosterone and treated them with DQ. The expression of markers of senescence and a SASP-related factor was increased by testosterone, and DQ reduced this increase. DQ reduced the expression of markers of senescence and a SASP-related factor in the ovaries of PCOS mice and improved their morphology. These results indicate that cellular senescence occurs in PCOS. Hyperandrogenism causes cellular senescence in GCs in PCOS, and senolytic treatment reduces the accumulation of senescent GCs and improves ovarian morphology under hyperandrogenism. Thus, DQ might represent a novel therapy for PCOS.


Asunto(s)
Senescencia Celular , Células de la Granulosa , Síndrome del Ovario Poliquístico , Quercetina , Síndrome del Ovario Poliquístico/metabolismo , Síndrome del Ovario Poliquístico/patología , Femenino , Senescencia Celular/efectos de los fármacos , Humanos , Animales , Células de la Granulosa/metabolismo , Células de la Granulosa/efectos de los fármacos , Células de la Granulosa/patología , Quercetina/farmacología , Ratones , Fenotipo Secretor Asociado a la Senescencia , Adulto , Dasatinib/farmacología , Modelos Animales de Enfermedad , Senoterapéuticos/farmacología , Hiperandrogenismo/patología , Hiperandrogenismo/metabolismo , Interleucina-6/metabolismo , Deshidroepiandrosterona/farmacología
7.
Mol Cell Endocrinol ; 588: 112234, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38588858

RESUMEN

Hyperandrogenic disorders, such as polycystic ovary syndrome, are often associated with metabolic disruptions such as insulin resistance and hyperinsulinemia. Studies in sheep, a precocial model of translational relevance, provide evidence that in utero exposure to excess testosterone during days 30-90 of gestation (the sexually dimorphic window where males naturally experience elevated androgens) programs insulin resistance and hyperinsulinemia in female offspring. Extending earlier findings that adverse effects of testosterone excess are evident in fetal day 90 pancreas, the end of testosterone treatment, the present study provides evidence that transcriptomic and phenotypic effects of in utero testosterone excess on female pancreas persist after cessation of treatment, suggesting lasting organizational changes, and induce a male-like phenotype in female pancreas. These findings demonstrate that the female pancreas is susceptible to programmed masculinization during the sexually dimorphic window of fetal development and shed light on underlying connections between hyperandrogenism and metabolic homeostasis.


Asunto(s)
Páncreas , Testosterona , Transcriptoma , Animales , Femenino , Ovinos , Transcriptoma/efectos de los fármacos , Transcriptoma/genética , Embarazo , Páncreas/metabolismo , Páncreas/efectos de los fármacos , Masculino , Efectos Tardíos de la Exposición Prenatal/metabolismo , Resistencia a la Insulina , Hiperandrogenismo/metabolismo , Hiperandrogenismo/genética , Desarrollo Fetal/efectos de los fármacos , Caracteres Sexuales
8.
Hum Reprod ; 39(5): 1072-1077, 2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38514450

RESUMEN

STUDY QUESTION: What are the characteristics of adolescents diagnosed with polycystic ovary syndrome (PCOS) based on the 2003 Rotterdam criteria, but who do not meet the diagnosis according to the international evidence-based guideline? SUMMARY ANSWER: Adolescents who had features of PCOS but did not meet the evidence-based guideline adolescent criteria exhibited unfavorable metabolic profiles compared to controls and shared considerable metabolic and hormonal features with adolescents who did meet the adolescent criteria. WHAT IS KNOWN ALREADY: The international evidence-based PCOS guideline recommended that ultrasound should not be used for the diagnosis of PCOS in girls with a gynecological age of <8 years. Thus far, few studies have evaluated the clinical characteristics of the girls diagnosed with PCOS based on the Rotterdam criteria but who do not meet the diagnosis according to the updated guideline. STUDY DESIGN, SIZE, DURATION: This is a retrospective study, and subjects attended for care from 2004 to 2022. PARTICIPANTS/MATERIALS, SETTING, METHODS: Adolescent girls with PCOS diagnosed according to the 2003 Rotterdam criteria and healthy controls. All participants were between 2 and 8 years since menarche. MAIN RESULTS AND THE ROLE OF CHANCE: Of the 315 girls diagnosed with PCOS according to the Rotterdam criteria, those with irregular menstruation (IM)/hyperandrogenism (HA)/polycystic ovary (PCO), IM/HA, HA/PCO, and IM/PCO phenotypes accounted for 206 (65.4%), 30 (9.5%), 12 (3.8%), and 67 (21.3%) participants, respectively. According to the evidence-based guideline, 79 girls (25.1%) with the HA/PCO or IM/PCO phenotypes were not diagnosed with PCOS, and aligned to the international guideline; they were designated as the 'at-risk' group. As expected, the girls meeting the evidence-based guideline adolescent criteria showed the worst metabolic profiles (degree of generalized or central obesity, frequency of insulin resistance, prediabetes or diabetes, and metabolic syndrome) and higher hirsutism scores than the at-risk group or controls. Approximately 90% of the at-risk group were not overweight or obese, which was similar to the controls. However, they showed worse metabolic profiles, with higher blood pressure, triglyceride, and insulin resistance parameters than controls; furthermore, these profiles were similar to those of the girls meeting the adolescent criteria. The at-risk group showed similarly elevated serum LH levels and LH/FSH ratio with the girls meeting adolescent criteria. LIMITATIONS, REASONS FOR CAUTION: We could not evaluate hormonal or ultrasound parameters in controls. WIDER IMPLICATIONS OF THE FINDINGS: Compared to the conventional Rotterdam criteria, the recent international evidence-based guideline-avoiding ultrasound in PCOS diagnosis in adolescents-still gives the opportunity to identify young girls at risk, aligned to the findings in this study. A practical approach to this adolescent population would involve establishing IM or HA (with ultrasound not indicated) and designating 'at-risk' PCOS status with regular check-ups for newly developed or worsening PCOS-related symptoms or metabolic abnormalities, with subsequent reassessment including ultrasound or anti-Müllerian hormone, once 8 years post-menarche. STUDY FUNDING/COMPETING INTEREST(S): No funding was received in support of this study. The authors have no conflicts of interest to disclose. TRIAL REGISTRATION NUMBER: N/A.


Asunto(s)
Hiperandrogenismo , Síndrome del Ovario Poliquístico , Humanos , Síndrome del Ovario Poliquístico/diagnóstico , Síndrome del Ovario Poliquístico/complicaciones , Femenino , Adolescente , Estudios Retrospectivos , Hiperandrogenismo/diagnóstico , Guías de Práctica Clínica como Asunto , Niño , Ultrasonografía , Resistencia a la Insulina , Estudios de Casos y Controles
9.
Clín. investig. ginecol. obstet. (Ed. impr.) ; 51(1): [100911], Ene-Mar, 2024. graf, tab
Artículo en Español | IBECS | ID: ibc-229786

RESUMEN

El síndrome del ovario poliquístico (SOP), es una endocrinopatía femenina reconocida como un trastorno heterogéneo caracterizado por un hiperandrogenismo y una disfunción ovulatoria que conlleva problemas de fertilidad. Además, las pacientes suelen presentar una sintomatología asociada como la resistencia a la insulina, la intolerancia a la glucosa, la obesidad central y/o el síndrome metabólico que pueden inducir a un aumento del riesgo de enfermedad cardiovascular. Dado que uno de los principales objetivos del tratamiento del SOP es reducir las consecuencias metabólicas relacionadas con la obesidad, la resistencia a la insulina y el síndrome metabólico, las intervenciones dietéticas dirigidas a este propósito pueden resultar eficaces en el tratamiento de este padecimiento. Se ha llevado a cabo una búsqueda bibliográfica en diferentes bases de datos como Web of Science (WOS), PubMed y Google Académico estableciendo unos criterios de búsqueda previamente definidos. Se han elegido 11 trabajos para su revisión completa y análisis crítico. Entre las diferentes intervenciones que se han utilizado, se han seguido estrategias dietéticas como la Dietary Approaches to Stop Hypertension (DASH), modificaciones en los hidratos de carbono (HC), la inclusión de algún alimento determinado en el patrón dietético habitual y/o los cambios en el estilo de vida. De los resultados obtenidos, destacan las mejoras propiciadas en los marcadores corporales con un régimen DASH, los beneficios promovidos por dietas con modificaciones en los HC, en la resistencia insulínica (IR) y los marcadores hormonales, así como los efectos favorables en las manifestaciones clínicas relacionadas con el hiperandrogenismo, fomentados por el consumo de soja y las modificaciones en el estilo de vida (LSM).(AU)


Polycystic ovary syndrome (PCOS) is a female endocrinopathy recognized as a heterogeneous disorder characterized by hyperandrogenism and ovulatory dysfunction that leads to fertility problems. In addition, patients usually present with associated symptoms such as insulin resistance, glucose intolerance, central obesity and/or metabolic syndrome that can induce an increased risk of cardiovascular disease. Since one of the main goals of PCOS is to reduce the metabolic consequences related to obesity, insulin resistance, and the metabolic syndrome, targeted dietary interventions may be effective in treating PCOS.A bibliographic search has been carried out in different databases such as Web of Science, Pubmed and Google Scholar, establishing previously defined search criteria. Eleven have been chosen for full review and critical analysis. Among the different interventions that have been used, dietary strategies have been followed such as the dietary approaches to stop hypertension (DASH), modifications in carbohydrates, the inclusion of a certain food in the usual dietary pattern and/or lifestyle modifications. Of the results obtained, we highlight the improvements in body markers with a DASH diet, the benefits promoted by diets with modifications in carbohydrates, in insulin resistance and hormonal markers and favorable effects on clinical manifestations related to hyperandrogenism, fostered by soy consumption and lifestyle modifications.(AU)


Asunto(s)
Humanos , Femenino , Síndrome del Ovario Poliquístico , Hiperandrogenismo , Infertilidad , Trastornos de la Menstruación , Hirsutismo , Ginecología , Obstetricia , Ovario/anomalías , Ovario/lesiones , Salud de la Mujer
10.
Sci Rep ; 14(1): 6230, 2024 03 14.
Artículo en Inglés | MEDLINE | ID: mdl-38486090

RESUMEN

Gestational hyperandrogenism is a risk factor for adverse maternal and offspring outcomes with effects likely mediated in part via disruptions in maternal lipid homeostasis. Using a translationally relevant sheep model of gestational testosterone (T) excess that manifests maternal hyperinsulinemia, intrauterine growth restriction (IUGR), and adverse offspring cardiometabolic outcomes, we tested if gestational T excess disrupts maternal lipidome. Dimensionality reduction models following shotgun lipidomics of gestational day 127.1 ± 5.3 (term 147 days) plasma revealed clear differences between control and T-treated sheep. Lipid signatures of gestational T-treated sheep included higher phosphoinositides (PI 36:2, 39:4) and lower acylcarnitines (CAR 16:0, 18:0, 18:1), phosphatidylcholines (PC 38:4, 40:5) and fatty acids (linoleic, arachidonic, Oleic). Gestational T excess activated phosphatidylethanolamines (PE) and PI biosynthesis. The reduction in key fatty acids may underlie IUGR and activated PI for the maternal hyperinsulinemia evidenced in this model. Maternal circulatory lipids contributing to adverse cardiometabolic outcomes are modifiable by dietary interventions.


Asunto(s)
Enfermedades Cardiovasculares , Hiperandrogenismo , Hiperinsulinismo , Embarazo , Femenino , Ovinos , Animales , Fosfatidiletanolaminas , Fosfatidilinositoles , Testosterona , Ácidos Grasos , Homeostasis
11.
Int J Mol Sci ; 25(6)2024 Mar 11.
Artículo en Inglés | MEDLINE | ID: mdl-38542179

RESUMEN

MicroRNAs (miRNAs) are single-stranded, non-coding RNAs that regulate mRNA expression on a post-transcriptional level. Observational studies suggest an association of serum miRNAs and polycystic ovary syndrome (PCOS), a common heterogeneous endocrinopathy characterized by hyperandrogenism (HA), oligo- or amenorrhea (OM) and polycystic ovaries. It is not known whether these miRNA profiles also differ between PCOS phenotypes. In this pilot study, we compared serum expression profiles between the four PCOS phenotypes (A-D) and analyzed them both in PCOS (all phenotypes) and in phenotypes with HA by quantitative-real-time PCR (qRT-PCR). The serum expression of miR-23a-3p was upregulated in phenotype B (n = 10) and discriminated it from phenotypes A (n = 11), C (n = 11) and D (n = 11, AUC = 0.837; 95%CI, 0.706-0.968; p = 0.006). The expression of miR-424-5p was downregulated in phenotype C (n = 11) and discriminated it from phenotypes A, B and D (AUC = 0.801; 95%CI, 0.591-1.000; p = 0.007). MiR-93-5p expression was downregulated in women with PCOS (all phenotypes, n = 42) compared to controls (n = 8; p = 0.042). Phenotypes with HA (A, B, C; n = 32) did not show differences in the analyzed expression pattern. Our data provide new insights into phenotype-specific miRNA alterations in the serum of women with PCOS. Understanding the differential hormonal and miRNA profiles across PCOS phenotypes is important to improve the pathophysiological understanding of PCOS heterogeneity.


Asunto(s)
Hiperandrogenismo , MicroARNs , Síndrome del Ovario Poliquístico , Humanos , Femenino , Síndrome del Ovario Poliquístico/metabolismo , Proyectos Piloto , Hiperandrogenismo/genética , MicroARNs/genética , MicroARNs/metabolismo , Fenotipo
12.
Gynecol Endocrinol ; 40(1): 2331072, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38547923

RESUMEN

OBJECTIVE: To highlight the challenges in diagnosing 46, XY disorder of sex development related to MYRF mutation. METHODS: We present an unusual case of a 12-year-old female child came for enlargement of clitoris and initially diagnosed as partial androgen insensitivity syndrome (AIS). RESULTS: On examination, the patient's vulva was found virilized with 3cm-long clitoris. Her peripheral blood karyotype was 46, XY. The ultrasound showed an empty pelvis and hormone results confirmed hyperandrogenism. Therefore, the partial AIS was suspected, but the following whole exon sequencing indicates a pathological missense mutation in MYRF. Further investigation and surgery did not reveal any brain, heart, lung or diaphragm lesions related to MYRF, but only maldeveloped internal genitalia and a persistent urachus. Her serum testosterone dropped to normal after surgical removal of the remaining ipsilateral testis and epididymitis without spermatogenesis as shown by pathology. CONCLUSION: Due to the karyotype, hyperandrogenism, empty pelvis but a virilism after puberty, the patient was initially diagnosed as partial AIS. This misleading clinical diagnose will not be verified as the MYRF mutation if without the whole exon sequencing, particularly in the absence of obvious brain, heart, lung and diaphragm lesions as in this case.


Asunto(s)
Síndrome de Resistencia Androgénica , Hiperandrogenismo , Proteínas de la Membrana , Desarrollo Sexual , Factores de Transcripción , Niño , Femenino , Humanos , Masculino , Síndrome de Resistencia Androgénica/diagnóstico , Síndrome de Resistencia Androgénica/genética , Mutación , Receptores Androgénicos/genética , Desarrollo Sexual/genética , Factores de Transcripción/genética , Proteínas de la Membrana/genética
13.
Obesity (Silver Spring) ; 32(4): 678-690, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38439205

RESUMEN

OBJECTIVE: Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism, insulin resistance, and hepatic steatosis (HS). Because dietary essential amino acid (EAA) supplementation has been shown to decrease HS in various populations, this study's objective was to determine whether supplementation would decrease HS in PCOS. METHODS: A randomized, double-blind, crossover, placebo-controlled trial was conducted in 21 adolescents with PCOS (BMI 37.3 ± 6.5 kg/m2, age 15.6 ± 1.3 years). Liver fat, very low-density lipoprotein (VLDL) lipogenesis, and triacylglycerol (TG) metabolism were measured following each 28-day phase of placebo or EAA. RESULTS: Compared to placebo, EAA was associated with no difference in body weight (p = 0.673). Two markers of liver health improved: HS was lower (-0.8% absolute, -7.5% relative reduction, p = 0.013), as was plasma aspartate aminotransferase (AST) (-8%, p = 0.004). Plasma TG (-9%, p = 0.015) and VLDL-TG (-21%, p = 0.031) were reduced as well. VLDL-TG palmitate derived from lipogenesis was not different between the phases, nor was insulin sensitivity (p > 0.400 for both). Surprisingly, during the EAA phase, participants reported consuming fewer carbohydrates (p = 0.038) and total sugars (p = 0.046). CONCLUSIONS: Similar to studies in older adults, short-term EAA supplementation in adolescents resulted in significantly lower liver fat, AST, and plasma lipids and thus may prove to be an effective treatment in this population. Additional research is needed to elucidate the mechanisms for these effects.


Asunto(s)
Hígado Graso , Hiperandrogenismo , Resistencia a la Insulina , Síndrome del Ovario Poliquístico , Adolescente , Femenino , Humanos , Hiperandrogenismo/complicaciones , Insulina , Lipoproteínas VLDL , Obesidad/complicaciones , Síndrome del Ovario Poliquístico/tratamiento farmacológico , Síndrome del Ovario Poliquístico/complicaciones
14.
J Ovarian Res ; 17(1): 69, 2024 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-38539230

RESUMEN

Polycystic ovary syndrome (PCOS) is a common reproductive and metabolic condition in women of childbearing age and a major cause of anovulatory infertility. The pathophysiology of PCOS is complex. Recent studies have reported that apart from hyperandrogenism, insulin resistance, systemic chronic inflammation, and ovarian dysfunction, gut microbiota dysbiosis is also involved in PCOS development and may aggravate inflammation and metabolic dysfunction, forming a vicious cycle. As naturally occurring plant secondary metabolites, polyphenols have been demonstrated to have anticancer, antibacterial, vasodilator, and analgesic properties, mechanistically creating putative bioactive, low-molecular-weight metabolites in the human gut. Here, we summarize the role of gut microbiota dysbiosis in the development of PCOS and demonstrate the ability of different polyphenols - including anthocyanin, catechins, and resveratrol - to regulate gut microbes and alleviate chronic inflammation, thus providing new insights that may assist in the development of novel therapeutic strategies to treat women with PCOS.


Asunto(s)
Microbioma Gastrointestinal , Hiperandrogenismo , Resistencia a la Insulina , Síndrome del Ovario Poliquístico , Femenino , Humanos , Síndrome del Ovario Poliquístico/complicaciones , Microbioma Gastrointestinal/fisiología , Polifenoles/farmacología , Polifenoles/uso terapéutico , Disbiosis/complicaciones , Resistencia a la Insulina/fisiología , Inflamación/tratamiento farmacológico , Inflamación/metabolismo
15.
Eur J Obstet Gynecol Reprod Biol ; 295: 104-110, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38354601

RESUMEN

OBJECTIVE: To explore the distribution of Rotterdam-based PCOS phenotypes and their associations with anthropometric parameters predictive of cardiometabolic risks in Ukrainian referral PCOS women. STUDY DESIGN: It was a cross-sectional study conducted by the Ukrainian Society of Gynecological Endocrinology between September 2021 and January 2022 involving 42 clinics in 10 regional centres representing the major geographical parts of Ukraine. Two hundred obstetrician-gynecologists whose practice facilities corresponded to study criteria were committed to entering records of their PCOS patients aged 20-45 years into the uniform data collection forms. The recorded parameters were: PCOS phenotype with the mandatory assessment of biochemical hyperandrogenism, age, BMI, waist circumference, and hyperandrogenism symptoms. RESULTS: 5254 patients' records were completed. Phenotype A was the most prevalent - 47.7 %, phenotypes B, C, and D were almost equally distributed in the studied population: 17.6 %, 17.4 %, and 17.3 % respectively. The total prevalence of androgenic phenotypes based on the presence of biochemical hyperandrogenism was 82.7 %. The incidence of obesity and hyperandrogenism symptoms, and mean BMI values were higher in phenotypes A and B compared to C and D. At the same time, the presence of 34.1 % and 46.2 % of normal-weight subjects in phenotypes A and B respectively, supports the fact that the excessive BMI is not a universal characteristic of androgenic phenotypes. In younger age groups, phenotypes C and D demonstrated the predominance of normal weight, but in older subgroups, the situation changed: in the age group of 36-45 y.o. compared to 18-25 y.o., the percentage of overweight and obese subjects for the non-classic phenotypes increased more than for the classic ones: C (OR = 3.91, 95 % CI: 2.41-6.38), D (OR = 4.14, 95 % CI: 2.64-6.52), A (OR = 2.30, 95 % CI:1.72-2.08), and B (OR = 2.56, 95 % CI:1.69-3.89). CONCLUSIONS: In thoroughly assessed Ukrainian referral PCOS population the classic phenotypes prevailed as in other clinical cohorts. The classic phenotypes were characterized by the higher rate of adiposity and severity of clinical hyperandrogenism. At the same time, obese, overweight, and normal-weight subjects were present in all phenotypes, and the risk of obesity in non-classic phenotypes was higher in older age groups.


Asunto(s)
Hiperandrogenismo , Síndrome del Ovario Poliquístico , Humanos , Femenino , Anciano , Adulto , Persona de Mediana Edad , Síndrome del Ovario Poliquístico/complicaciones , Síndrome del Ovario Poliquístico/epidemiología , Síndrome del Ovario Poliquístico/diagnóstico , Hiperandrogenismo/epidemiología , Estudios Transversales , Sobrepeso/complicaciones , Sobrepeso/epidemiología , Ucrania/epidemiología , Andrógenos , Fenotipo , Obesidad/complicaciones
16.
Arch Gynecol Obstet ; 309(5): 1707-1723, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38316651

RESUMEN

Polycystic ovary syndrome (PCOS) is a complex endocrine disorder that affects a substantial percentage of women, estimated at around 9-21%. This condition can lead to anovulatory infertility in women of childbearing age and is often accompanied by various metabolic disturbances, including hyperandrogenism, insulin resistance, obesity, type-2 diabetes, and elevated cholesterol levels. The development of PCOS is influenced by a combination of epigenetic alterations, genetic mutations, and changes in the expression of non-coding RNAs, particularly microRNAs (miRNAs). MicroRNAs, commonly referred to as non-coding RNAs, are approximately 22 nucleotides in length and primarily function in post-transcriptional gene regulation, facilitating mRNA degradation and repressing translation. Their dynamic expression in different cells and tissues contributes to the regulation of various biological and cellular pathways. As a result, they have become pivotal biomarkers for various diseases, including PCOS, demonstrating intricate associations with diverse health conditions. The aberrant expression of miRNAs has been detected in the serum of women with PCOS, with overexpression and dysregulation of these miRNAs playing a central role in the atypical expression of endocrine hormones linked to PCOS. This review takes a comprehensive approach to explore the upregulation and downregulation of various miRNAs present in ovarian follicular cells, granulosa cells, and theca cells of women diagnosed with PCOS. Furthermore, it discusses the potential for a theragnostic approach using miRNAs to better understand and manage PCOS.


Asunto(s)
Hiperandrogenismo , MicroARNs , Síndrome del Ovario Poliquístico , Humanos , Femenino , Síndrome del Ovario Poliquístico/metabolismo , MicroARNs/genética , Hiperandrogenismo/genética , Obesidad/genética , Biomarcadores
17.
Medicina (Kaunas) ; 60(2)2024 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-38399531

RESUMEN

Polycystic ovary syndrome (PCOS) manifests a multifactorial pathology characterized by polycystic ovaries, menstrual cycle disorders, varying degrees of hyperandrogenism, and an ad-verse metabolic risk profile. The position of hyperandrogenism in this syndrome has been extensively studied. A multitude of mechanisms place it in the position of cause but also of consequence; therefore, ongoing research efforts are focused on identifying medications that can effectively reduce levels of androgens in women with PCOS. Moreover, lipid abnormalities are common in this population, with up to 70% of patients having dyslipidemia. Statins may have potential therapeutic benefits for women with PCOS, as they have been shown to improve insulin resistance and reduce the risk of cardiovascular disease. In addition, their role in accelerated steroidogenesis by limiting one source of cholesterol, influencing enzymatic activity, and providing several other beneficial mechanisms is widely investigated. This review aimed to provide a comprehensive overview of the pathogenesis of androgen excess and dyslipidemia in PCOS, as well as the therapeutic potential of statins.


Asunto(s)
Dislipidemias , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Hiperandrogenismo , Resistencia a la Insulina , Síndrome del Ovario Poliquístico , Humanos , Femenino , Síndrome del Ovario Poliquístico/complicaciones , Síndrome del Ovario Poliquístico/tratamiento farmacológico , Hiperandrogenismo/complicaciones , Hiperandrogenismo/tratamiento farmacológico , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Dislipidemias/complicaciones , Dislipidemias/tratamiento farmacológico
18.
Medicina (Kaunas) ; 60(2)2024 Feb 09.
Artículo en Inglés | MEDLINE | ID: mdl-38399581

RESUMEN

Background and Objectives: Polycystic ovary syndrome (PCOS) is an endocrine disorder characterized by multiple hormonal and metabolic abnormalities, including insulin resistance, hyperandrogenism, and disturbances in lipid and carbohydrate metabolism. The objective of this study is to assess the quality of life of women diagnosed with polycystic ovary syndrome (PCOS) and to identify any factors within the study group that may impact the scores related to quality of life. Materials and Methods: This research was carried out among women diagnosed with PCOS. An original questionnaire, developed through an online Google Forms survey, was utilized as the research instrument and distributed through social networks and support groups to women facing PCOS. This study encompassed a participant pool of 200 women with PCOS, aged 24 years or older. For the analytical component, Pearson's χ2 test was employed-a nonparametric test designed to assess the relationship between two variables measured on a qualitative scale. The chosen level of statistical significance was set at p < 0.05. Results: The analysis revealed that the quality of life of the women under study was not linked to the duration of the disease or comorbidities. However, a significant association was observed with the inconvenience caused by PCOS symptoms. Women experiencing very bothersome symptoms of PCOS reported a lower quality of life compared to those with symptoms rated as not very bothersome. Despite the majority of women with PCOS rating their quality of life as good or very good, they often find the associated symptoms of PCOS bothersome. Women reporting lower quality of life tend to acknowledge the impact of PCOS on their lives, experience a sense of lack of control over the disease, struggle with depression, and do not accept their physical appearance. Conclusions: Hence, the support from specialists like endocrinologists, gynecologists, and nutritionists becomes crucial for many women dealing with PCOS. Adopting a healthy lifestyle, incorporating a balanced diet, and engaging in regular physical activity can assist in managing the troublesome symptoms of PCOS, thereby enhancing overall quality of life. In instances of emotional difficulties, seeking psychological support is equally important, and the significance of support and acceptance from loved ones should not be overlooked.


Asunto(s)
Hiperandrogenismo , Infertilidad Femenina , Resistencia a la Insulina , Síndrome del Ovario Poliquístico , Humanos , Femenino , Síndrome del Ovario Poliquístico/complicaciones , Calidad de Vida/psicología
19.
Expert Rev Endocrinol Metab ; 19(2): 111-128, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38205927

RESUMEN

INTRODUCTION: Hyperandrogenism is a clinical state consequent to excess androgen production by the ovary, adrenals, or increased peripheral conversion of androgens. The varied manifestations of hyperandrogenism include seborrhea, acne, infertility, hirsutism, or overt virilization of which adult female acne, hirsutism, and female pattern hair loss are of clinical relevance to dermatologists. AREAS COVERED: We limited our narrative review to literature published during period from 1 January 1985 to Dec 2022 and searched PubMed/MEDLINE, Web of Science (WOS), Scopus, and Embase databases with main search keywords were 'Hyperandrogenism,' 'Female,' 'Biochemical,' 'Dermatological', and 'Dermatology.' We detail the common etiological causes, nuances in interpretation of biochemical tests and imaging tools, followed by an algorithmic approach which can help avoid extensive tests and diagnose the common causes of hyperandrogenism. EXPERT OPINION: Based on current data, total testosterone, sex hormone binding globulin, DHEAS, prolactin, free androgen index, and peripheral androgenic metabolites like 3-alpha diol and androsterone glucuronide are ideal tests though not all are required in all patients. Abnormalities in these biochemical investigations may require radiological examination for further clarification. Total testosterone levels can help delineate broadly the varied causes of hyperandrogenism. Serum AMH could be used for defining PCOM in adults.


Asunto(s)
Acné Vulgar , Hiperandrogenismo , Adulto , Humanos , Femenino , Hirsutismo/diagnóstico , Hirsutismo/etiología , Hiperandrogenismo/complicaciones , Hiperandrogenismo/diagnóstico , Andrógenos , Dermatólogos , Testosterona/metabolismo , Alopecia/diagnóstico , Alopecia/etiología , Acné Vulgar/diagnóstico , Acné Vulgar/etiología
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