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1.
BJOG ; 127(8): 930-939, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32048421

RESUMO

BACKGROUND: There is currently no concise systematic review or meta-analysis addressing cardio-metabolic risk factors in women experiencing infertility. OBJECTIVES: To determine whether infertile women have higher levels of cardiovascular risk factors compared with fertile women. SEARCH STRATEGY: We performed a systematic literature search using PubMed, Embase and CINAHL, Scopus and additional manual and bibliographic searches for relevant articles (end search date 6 November 2019). SELECTION CRITERIA: We selected studies that compared cardio-metabolic risk factors in fertile and infertile women of reproductive age. DATA COLLECTION AND ANALYSIS: At least two authors independently screened potentially eligible studies. MAIN RESULTS: There was an increased presence of several cardio-metabolic risk factors in infertile women compared with fertile women. Infertile women had statistically significant higher body mass index (BMI), increased total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG) compared with fertile women. Fasting glucose, fasting insulin, homeostatic model assessment of insulin resistance (HOMA-IR) and mean arterial pressure were not found to be different between fertile and infertile women. A subgroup analysis revealed that TC, fasting glucose and fasting insulin were increased, and high-density lipoprotein was decreased only in women with polycystic ovarian syndrome compared with fertile women, whereas BMI, TG and LDL-C were statistically significantly increased in women with any indication of infertility compared with fertile women. CONCLUSIONS: Infertile women have a higher level of cardio-metabolic risk factors compared with fertile women. This finding has clinical implications for infertile women in general, and those attempting to conceive through medically assisted reproduction. TWEETABLE ABSTRACT: Infertile women appear to have a higher level of cardio-metabolic risk factors compared with fertile women.


Assuntos
Doenças Cardiovasculares/fisiopatologia , Suscetibilidade a Doenças/fisiopatologia , Hiperandrogenismo/fisiopatologia , Infertilidade Feminina/fisiopatologia , Síndrome Metabólica/fisiopatologia , Síndrome do Ovário Policístico/fisiopatologia , Adulto , Índice de Massa Corporal , Doenças Cardiovasculares/sangue , LDL-Colesterol/sangue , Suscetibilidade a Doenças/sangue , Feminino , Humanos , Hiperandrogenismo/sangue , Hiperandrogenismo/complicações , Infertilidade Feminina/sangue , Infertilidade Feminina/etiologia , Resistência à Insulina/fisiologia , Síndrome Metabólica/sangue , Síndrome do Ovário Policístico/sangue , Síndrome do Ovário Policístico/complicações , Fatores de Risco , Triglicerídeos/sangue
2.
Horm Metab Res ; 51(10): 639-648, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31578050

RESUMO

The aim of the study is to determine the impact of different anthropometric measurements of fat distribution on baseline sex-steroid concentrations and corticosteroidogenic enzyme activity in women with polycystic ovary syndrome compared to those with regular menstrual cycles. The current cross-sectional study included 106 normal cycling controls and 268 polycystic ovary syndrome patients. Patients with polycystic ovary syndrome, diagnosed by Rotterdam criteria, were divided in normoandrogenemic (n=91) and hyperandrogenemic (n=177). Anthropometric, biochemical, and hormone parameters were assessed and correlated with corticosteroidogenic enzyme activities in all three groups. Corticosteroidogenic enzyme activities were calculated using product-to-precursor ratios. Regarding sex-steroids individually, anthropometric parameters correlated with the concentrations of several androgens in polycystic ovary syndrome patients, most of them in patients with biochemical hyperandrogenism. The androgen precursors androstenedione, 17-hydroxyprogesterone, and dehydroepiandrosterone were less correlated with anthropometric parameters. The 17,20 lyase activity, in both Δ4 and Δ5 pathways, correlated with several anthropometric measurements in normo- and hyperandrogenemic polycystic ovary syndrome patients. The 17,20 lyase enzyme activity (Δ4 pathway) also correlated with conicity index, visceral adiposity index, and lipid accumulation product in the control group. 17-Hydroxylase activity positively correlated with waist-height ratio in both polycystic ovary syndrome groups. In contrast, 17-hydroxilase negatively correlated with the conicity index. Anthropometric markers of adiposity are associated with androgen levels and their precursors in blood. Body fat distribution correlates with the activities of some steroidogenic enzyme in both normo-and hyperandrogenemic polycystic ovary syndrome phenotypes. The molecular mechanisms involved in these associations are largely unclear and more investigations are required.


Assuntos
Androgênios/sangue , Biomarcadores/análise , Distribuição da Gordura Corporal , Hiperandrogenismo/fisiopatologia , Síndrome do Ovário Policístico/fisiopatologia , Esteroide 17-alfa-Hidroxilase/metabolismo , Adulto , Idoso , Antropometria , Estudos de Casos e Controles , Estudos Transversais , Feminino , Seguimentos , Humanos , Hiperandrogenismo/metabolismo , Pessoa de Meia-Idade , Síndrome do Ovário Policístico/metabolismo , Prognóstico
3.
Australas J Dermatol ; 60(4): e279-e283, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31168786

RESUMO

Androgenetic alopecia (AGA), one of the most common causes of hair loss in men and women, is an infrequent cause of alopecia in children. In AGA, patients generally start noticing hair thinning after the onset of puberty due to progressive miniaturisation of the hair follicle which leads to vellus transformation of terminal hair. However, the occurrence of prepubertal AGA has rarely been reported in the literature. The pathophysiology of AGA is tightly linked to androgen hormones; prepubertal children do not usually produce significant amounts of adrenal or gonadal androgens. When it does occur, an underlying abnormality should be suspected. Secondary causes of AGA must be excluded when evaluating a patient before the appearance of puberty. Premature puberty, polycystic ovarian syndrome and other causes of hyperandrogenism can present with hair loss in an androgenetic pattern. This article reviews the normal physiology of androgen hormones and their role in the pathophysiology of childhood AGA.


Assuntos
Alopecia/diagnóstico , Alopecia/fisiopatologia , Androgênios/metabolismo , Criança , Feminino , Folículo Piloso/metabolismo , Humanos , Hiperandrogenismo/fisiopatologia , Masculino , Síndrome do Ovário Policístico/fisiopatologia , Puberdade Precoce/fisiopatologia , Fenômenos Fisiológicos da Pele
4.
PLoS One ; 14(5): e0217095, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31150416

RESUMO

BACKGROUND/AIM: Patients with polycystic ovary syndrome (PCOS), characterized by anovulation, hyperandrogenemia and polycystic ovaries, are still vulnerable to undergo recurrent pregnancy loss and premature labor even though the ovulatory process is pharmacologically recovered. However, its potential mechanism remains unknown. Thus, our aim was to investigate the effect and mechanism of hyperandrogenemia and flutamide (a non-steroidal anti-androgen) on the embryo implantation and pregnancy during mid-pregnancy. METHODS: We used a mouse model in which PCOS-like hyperandrogenemia was induced by subcutaneous injection of testosterone propionate. In this model, we observed the effect of hyperandrogenemia and flutamide on the decidualization, angiogenesis and uNK cells by methods of immunohistochemistry, quantitative PCR, western blotting and Dolichos biflorus agglutinin (DBA) lectin staining. RESULTS: Testosterone and flutamide treatment did not significantly influence the numbers of implanted embryo compared with the control group. However, different doses of testosterone significantly increased the ratio of resorbed /implanted embryo, decreased the level of prl8a2 mRNA and cyclin D3 protein, inhibited the uterine angiogenesis and reduced the numbers of uNK cells, but combined treatment with flutamide markedly decreased the resorbed embryos, increased expressions of prl8a2 mRNA and cyclin D3 protein and angiogenesis and numbers of uNK cells. CONCLUSION: Flutamide treatment can efficiently ameliorate the hyperandrogenemia-induced the disorders in aspects of decidualization, angiogenesis and uNK cells, which further improve the poor endometrial receptivity in PCOS patients.


Assuntos
Decídua/efeitos dos fármacos , Implantação do Embrião/efeitos dos fármacos , Flutamida/farmacologia , Hiperandrogenismo/fisiopatologia , Neovascularização Patológica/tratamento farmacológico , Síndrome do Ovário Policístico/tratamento farmacológico , Útero/efeitos dos fármacos , Antagonistas de Androgênios/farmacologia , Animais , Decídua/citologia , Modelos Animais de Doenças , Feminino , Masculino , Camundongos , Síndrome do Ovário Policístico/induzido quimicamente , Síndrome do Ovário Policístico/metabolismo , Gravidez , Testosterona/administração & dosagem , Útero/citologia
5.
J Pediatr Endocrinol Metab ; 32(6): 549-559, 2019 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-31141485

RESUMO

Study objective Polycystic ovary syndrome (PCOS) in adolescence, a disorder of exclusion, has proved to be a timeless diagnostic challenge for the clinician. Since 1990, several attempts to provide clear diagnostic criteria have been published, most of the time leading to inconsistencies. We attempted to elucidate the controversies and convergences of this subject by conducting a systematic review of the literature concerning official guidelines or proposed criteria for the diagnosis of PCOS in adolescent girls. Design Based on a term search sequence via electronic databases such as Pubmed, Cochrane, Embase, Scopus and a hands-on review of references and learned societies, all available data were classified and analyzed. Single case reports, original studies with adult population or articles with incomplete diagnostic guidelines were excluded. Results Twelve reports dated from 2006 to 2018 fulfilled the inclusion criteria. Seven of them were endorsed or published by learned societies. All suggested a stricter diagnosis than in adulthood. Polycystic ovarian morphology was used as a necessary criterion only in three guidelines, and there was a tendency for a more objective diagnosis of hyperandrogenism, defined either by clinical features or by biochemical hyperandrogenemia, although in one case both were required. Conclusion Irregular menstrual cycles, allowing for an interval of at least 2 years postmenarche, and hyperandrogenism, usually reinforced by biochemical confirmation, are the main accepted features for PCOS diagnosis in adolescence. Discrepancies among endocrine and reproductive medicine societies still remain, although recent intensified attempts at reaching a consensus should allow for more universally accepted diagnostic criteria.


Assuntos
Hiperandrogenismo/fisiopatologia , Distúrbios Menstruais/fisiopatologia , Síndrome do Ovário Policístico/diagnóstico , Adolescente , Saúde do Adolescente , Feminino , Humanos , Síndrome do Ovário Policístico/terapia
6.
Gac Med Mex ; 155(2): 184-190, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31056603

RESUMO

Polycystic ovary syndrome is the most common endocrine disease in reproductive age, characterized by menstrual alterations, clinical or biochemical hyperandrogenism, and ultrasound-identified ovarian cysts. The neuroendocrine and metabolic alterations that accompany this condition involve the desensitization of the hypothalamus-pituitary-ovary axis, steroidogenesis and hyperandrogenism; recently, the role of insulin resistance has been explored. Hyperandrogenism has been established to be the main cause of polycystic ovary syndrome, due to enzymatic alterations in the steroidogenic pathway that cause luteinizing hormone over-stimulation because of quick pulses generated by gonadotropin-releasing hormones. Various growth factors of and cytokines inhibit the conversion of androgens into estrogens; activin and prostaglandins are also involved, even high levels of insulin participate in the characteristic deregulation of this syndrome.


Assuntos
Hiperandrogenismo/fisiopatologia , Síndrome do Ovário Policístico/fisiopatologia , Feminino , Hormônio Liberador de Gonadotropina/metabolismo , Humanos , Sistema Hipotálamo-Hipofisário/metabolismo , Resistência à Insulina , Hormônio Luteinizante/metabolismo , Sistema Hipófise-Suprarrenal/metabolismo
7.
PLoS One ; 14(5): e0216951, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31083690

RESUMO

Hyperandrogenism is a risk factor of cerebrovascular diseases as androgens can alter markedly the regulation of cerebrovascular tone. We examined the combined impact of androgen excess and vitamin D deficiency (VDD), a common co-morbidity in hyperandrogenic disorders, on remodeling and testosterone-induced vascular responses of anterior cerebral arteries (ACA) in order to evaluate the interplay between androgens and VDD in the cerebral vasculature. Male and female Wistar rats were either fed with vitamin D deficient or vitamin D supplemented diet. Half of the female animals from both groups received transdermal testosterone treatment. After 8 weeks, vessel lumen, wall thickness and testosterone-induced vascular tone of isolated ACA were determined using pressure microangiometry and histological examination. Androgen receptor protein expression in the wall of cerebral arteries was examined using immunohistochemistry. In female rats only combined VDD and testosterone treatment decreased the lumen and increased the wall thickness of ACA. In males, however VDD by itself was able to decrease the lumen and increase the wall thickness. Vascular reactivity showed similar alterations: in females, testosterone constricted the ACA only after combined VDD and hyperandrogenism, whereas in males VDD resulted in increased testosterone-induced contractions in spite of decreased androgen receptor expression. In conclusion, a marked interplay between hyperandrogenism and VDD results in inward remodeling and enhanced testosterone-induced constrictions of cerebral arteries, which might compromise the cerebral circulation and thus, increase the risk of stroke in the long term. In addition, the early cerebrovascular manifestation of VDD appears to require androgen excess and thus, depends on gender.


Assuntos
Androgênios/efeitos adversos , Hiperandrogenismo/fisiopatologia , Acidente Vascular Cerebral/fisiopatologia , Testosterona/efeitos adversos , Deficiência de Vitamina D/fisiopatologia , Administração Oral , Androgênios/administração & dosagem , Androgênios/sangue , Animais , Artéria Cerebral Anterior , Dieta , Modelos Animais de Doenças , Feminino , Expressão Gênica , Humanos , Hiperandrogenismo/sangue , Hiperandrogenismo/induzido quimicamente , Hiperandrogenismo/complicações , Masculino , Ratos , Ratos Wistar , Receptores Androgênicos/genética , Receptores Androgênicos/metabolismo , Risco , Fatores Sexuais , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/induzido quimicamente , Acidente Vascular Cerebral/etiologia , Testosterona/administração & dosagem , Testosterona/sangue , Vasoconstrição/efeitos dos fármacos , Vitamina D/administração & dosagem , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/induzido quimicamente , Deficiência de Vitamina D/complicações
8.
Rev Assoc Med Bras (1992) ; 65(3): 375-383, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30994836

RESUMO

OBJECTIVE: This study aims to evaluate the sleep of subjects with polycystic ovary syndrome (PCOS), with and without hyperandrogenism, in comparison with a healthy control group and examine the effects of hyperandrogenism and obesity on sleep parameters. METHODS: A total of 44 volunteers were recruited to participate in the study. Clinical, biochemical and polysomnographic parameters were used to diagnose PCOS and hyperandrogenism. The evaluation of sleep quality was made using validated questionnaires and polysomnography test. The frequency of obstructive sleep apnea was also compared between the groups. RESULTS: The study revealed that women with PCOS presented poorer subjective sleep quality, increased incidence of snoring and a higher risk of obstructive sleep apnea, based on the Berlin questionnaire. Also, after adjusting for body mass index, PCOS subjects had rapid eye movement (REM) time lower than those in the control group. PCOS women versus those without hyperandrogenism did not differ on any sleep measurement. Women with obstructive sleep apnea were only diagnosed in the PCOS group. CONCLUSIONS: Our results indicate that PCOS impairs subjective sleep quality, as well as objective sleep quality, due to a reduction in REM sleep stage time in women diagnosed with the syndrome. Obesity affected sleep-related parameters but hyperandrogenism had no effect. Only the PCOS group had obstructive sleep apnea diagnosis.


Assuntos
Hiperandrogenismo/complicações , Obesidade/complicações , Síndrome do Ovário Policístico/complicações , Apneia Obstrutiva do Sono/etiologia , Transtornos do Sono-Vigília/etiologia , Adolescente , Adulto , Índice de Massa Corporal , Estudos de Casos e Controles , Feminino , Humanos , Hiperandrogenismo/fisiopatologia , Pessoa de Meia-Idade , Obesidade/fisiopatologia , Síndrome do Ovário Policístico/fisiopatologia , Polissonografia , Transtorno do Comportamento do Sono REM/fisiopatologia , Valores de Referência , Medição de Risco , Fatores de Risco , Apneia Obstrutiva do Sono/fisiopatologia , Transtornos do Sono-Vigília/fisiopatologia , Estatísticas não Paramétricas , Inquéritos e Questionários , Testosterona/sangue , Adulto Jovem
9.
Endocrinology ; 160(5): 1193-1204, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30924862

RESUMO

Polycystic ovary syndrome (PCOS) is a common endocrine disorder affecting ∼10% to 15% of reproductive-aged women worldwide. Diagnosis requires two of the following: hyperandrogenism, oligo-ovulation or anovulation, and polycystic ovaries. In addition to reproductive dysfunction, many women with PCOS display metabolic abnormalities associated with hyperandrogenism. Recent studies have reported that the gut microbiome is altered in women with PCOS and rodent models of the disorder. However, it is unknown whether the gut microbiome plays a causal role in the development and pathology of PCOS. Given its potential role, we hypothesized that exposure to a healthy gut microbiome would protect against development of PCOS. A cohousing study was performed using a letrozole-induced PCOS mouse model that recapitulates many reproductive and metabolic characteristics of PCOS. Because mice are coprophagic, cohousing results in repeated, noninvasive inoculation of gut microbes in cohoused mice via the fecal-oral route. In contrast to letrozole-treated mice housed together, letrozole mice cohoused with placebo mice showed significant improvement in both reproductive and metabolic PCOS phenotypes. Using 16S rRNA gene sequencing, we also observed that the overall composition of the gut microbiome and the relative abundance of Coprobacillus and Lactobacillus differed in letrozole-treated mice cohoused with placebo mice compared with letrozole mice housed together. These results suggest that dysbiosis of the gut microbiome may play a causal role in PCOS and that modulation of the gut microbiome may be a potential treatment option for PCOS.


Assuntos
Modelos Animais de Doenças , Microbioma Gastrointestinal/fisiologia , Síndrome do Ovário Policístico/metabolismo , Síndrome do Ovário Policístico/fisiopatologia , Reprodução/fisiologia , Animais , Anovulação/metabolismo , Anovulação/fisiopatologia , Inibidores da Aromatase/farmacologia , Disbiose/fisiopatologia , Feminino , Microbioma Gastrointestinal/efeitos dos fármacos , Abrigo para Animais , Humanos , Hiperandrogenismo/metabolismo , Hiperandrogenismo/fisiopatologia , Letrozol/farmacologia , Camundongos Endogâmicos C57BL , Síndrome do Ovário Policístico/diagnóstico , Reprodução/efeitos dos fármacos
10.
Arch Gynecol Obstet ; 299(5): 1481-1485, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30737584

RESUMO

PURPOSE: Primary and secondary sterility have become an issue of increasing importance due to demographic and social changes in society. Data regarding the association between female androgen levels and the probability of successful conception after fertility treatment are sparse and contradictive. This study was designed to assess this clinical question. METHODS: In this retrospective single-center cohort study concentrations of androgens androstenedione, dehydroepiandrosteronsulfat (DHEAS) and testosterone (ng/ml) were investigated in the serum of patients presenting for sterility at the department of reproductive medicine of Saarland University hospital Homburg between January 2015 and December 2017. Androgen levels were correlated with reproductive outcomes. Statistical analysis was performed with the aid of SPSS version 24. Significance for conception rates in dependence of androgen concentration was assessed using Kruskal-Wallis test (significance was estimated with p < 0.05). RESULTS: The laboratory values of a total of 301 patients were examined (64% primary, 36% secondary sterility). Median age at first visit at the fertility department was 32.7 years (range 20-47 years). 64 pregnancies were observed during the study period (conception rate 21.3%). 23 out of 301 patients (7.6%) suffered from hypoandrogenaemia, 248 (82.4%) had normal androgen levels and 30 (10%) showed hyperandrogenaemia (p = 0.25). Regarding patients in whom fertility treatment was successful 3 (4.7%) showed hypoandrogenaemia, 54 (84.4%) were normoandrogenaemic and 7 (10.9%) had hyperandrogenaemia (p = 0.40 Kruskal-Wallis test). CONCLUSIONS: We found no association between female androgen levels and sterility and reproductive outcomes.


Assuntos
Androgênios/sangue , Fertilização , Infertilidade Feminina/terapia , Adulto , Feminino , Humanos , Hiperandrogenismo/fisiopatologia , Pessoa de Meia-Idade , Gravidez , Probabilidade , Estudos Retrospectivos , Adulto Jovem
11.
Endocrinology ; 160(3): 699-715, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30657917

RESUMO

Polycystic ovary syndrome (PCOS) is a common cause of female infertility. Hyperandrogenism is both a major symptom and key diagnostic trait of PCOS; however, the direct impact of this androgen excess on ovarian dynamics is unclear. By combining a DHT-induced PCOS mouse model with an ex vivo follicle culture system, we investigated the impact of hyperandrogenism on ovarian function. Ovaries from PCOS mice exhibited the characteristic polycystic ovary morphology with numerous large cystic follicles and no corpora lutea present. Isolation and individual culture of preantral and antral follicles from PCOS mice resulted in slower growth rates during 5 days compared with the follicles isolated from control mice (P < 0.01). In contrast, preovulatory follicles from PCOS mice exhibited a significant increase in growth rate compared with controls (P < 0.01). Preantral follicles from PCOS ovaries maintained comparable follicular health as control follicles, but antral and preovulatory PCOS follicles exhibited reduced follicle health (P < 0.01) and survival rates (P < 0.01). Compared with controls, PCOS females also exhibited a poorer response to hyperstimulation (P < 0.01), impaired oocyte function evident by increased levels of reactive oxygen species (P < 0.01), and a reduction in on-time embryo development (P < 0.01). These results demonstrate that prolonged exposure to androgen excess leads to aberrant follicle development, which persists even after removal from the hyperandrogenic environment, causing perturbed follicular developmental trajectories. These findings indicate that an in vivo hyperandrogenic environment in patients with PCOS may intrinsically induce detrimental effects on follicles and oocytes.


Assuntos
Hiperandrogenismo/fisiopatologia , Folículo Ovariano/fisiopatologia , Síndrome do Ovário Policístico/fisiopatologia , Animais , Modelos Animais de Doenças , Desenvolvimento Embrionário , Feminino , Camundongos Endogâmicos C57BL , Oócitos/metabolismo , Folículo Ovariano/enzimologia , Folículo Ovariano/crescimento & desenvolvimento , Indução da Ovulação , Estresse Oxidativo , Progesterona/metabolismo
12.
Horm Metab Res ; 51(1): 22-34, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30650457

RESUMO

While several studies have documented an increased risk of metabolic disorders in patients with polycystic ovary syndrome (PCOS), associations between androgenic and metabolic parameters in these patients are unclear. We aimed to investigate the relationships between biochemical markers of hyperandrogenism (HA) and metabolic parameters in women with PCOS. In this systematic review and meta-analysis, a literature search was performed in the PubMed, Scopus, Google Scholar, ScienceDirect, and Web of Science from 2000 to 2018 for assessing androgenic and metabolic parameters in PCOS patients. To assess the relationships between androgenic and metabolic parameters, meta-regression analysis was used. A total number of 33 studies involving 9905 patients with PCOS were included in this analysis. The associations of total testosterone (tT) with metabolic parameters were not significant; after adjustment for age and BMI, we detected associations of this androgen with low-density lipoproteins cholesterol (LDL-C) (ß=0.006; 95% CI: 0.002, 0.01), high-density lipoproteins cholesterol (HDL-C) (ß=-0.009; 95% CI: -0.02, -0.001), and systolic blood pressure (SBP) (ß=-0.01; 95% CI: -0.03, -0.00). We observed a positive significant association between free testosterone (fT) and fasting insulin (ß=0.49; 95% CI: 0.05, 0.91); this association remained significant after adjustment for confounders. We also detected a reverse association between fT and HDL-C (ß=-0.41; 95% CI: -0.70, -0.12). There was a positive significant association between A4 and TG (ß=0.02; 95% CI: 0.00, 0.04) after adjustment for PCOS diagnosis criteria. We also found significant negative associations between A4, TC, and LDL-C. Dehydroepiandrosterone sulfate (DHEAS) had a positive association with LDL-C (ß=0.02; 95% CI: 0.001, 0.03) and a reverse significant association with HDL-C (ß=-0.03; 95% CI: -0.06, -0.001). This meta-analysis confirmed the associations of some androgenic and metabolic parameters, indicating that measurement of these parameters may be useful for predicting metabolic risk in PCOS patients.


Assuntos
Hiperandrogenismo/metabolismo , Síndrome do Ovário Policístico/metabolismo , Androgênios/metabolismo , Pressão Sanguínea , Colesterol/metabolismo , Feminino , Humanos , Hiperandrogenismo/genética , Hiperandrogenismo/fisiopatologia , Insulina/metabolismo , Síndrome do Ovário Policístico/genética , Síndrome do Ovário Policístico/fisiopatologia , Testosterona/metabolismo
13.
J Clin Lab Anal ; 33(3): e22699, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30350882

RESUMO

BACKGROUND: To investigate the correlation between hyperandrogenism (HA) and insulin resistance (IR) in women with polycystic ovary syndrome (PCOS) by measuring serum total testosterone (TT) using a liquid chromatography and tandem mass spectrometry assay (LC-MS/MS). METHODS: This cohort study included 332 patients with PCOS, 63 patients with IR and 276 with controls. TT levels were measured by LC-MS/MS and chemiluminescent immunoassay (CLIA); glucose and insulin levels were determined by an oral glucose tolerance test (OGTT). RESULTS: Compared with CLIA, LC-MS/MS differentiated more cases with high TT levels among the non-PCOS subjects with IR In patients with PCOS, LC-MS/MS-based TT levels or a combination with the mFG score detected a significantly higher incidence of HA in subjects with IR identified by hyperinsulinemia (HIN), HOMA-IR or impaired fasting glucose (IFG) than in those without IR Conversely, the IR rates demonstrated by HIN, HOMA-IR, or IFG were remarkably higher in the LC-MS/MS-defined high TT subgroup than in the normal TT subgroup. However, the CLIA platform could not discern a difference in HA incidence between IR and non-IR subgroups or in IR rate between high and normal TT populations. ROC curves also proved that HIN, HOMA-IR, and IFG were positive contributors to HA as measured by LC-MS/MS CONCLUSIONS: The correlation between HA and IR has always been underestimated, partly owing to the less accurate methods previously used to measure TT. HIN, HOMA-IR, and IFG are likely to contribute to the development of HA from a clinical perspective.


Assuntos
Cromatografia Líquida/métodos , Hiperandrogenismo , Resistência à Insulina/fisiologia , Síndrome do Ovário Policístico , Espectrometria de Massas em Tandem/métodos , Adolescente , Adulto , Glicemia/análise , Estudos de Casos e Controles , Jejum , Feminino , Humanos , Hiperandrogenismo/complicações , Hiperandrogenismo/epidemiologia , Hiperandrogenismo/fisiopatologia , Síndrome do Ovário Policístico/sangue , Síndrome do Ovário Policístico/complicações , Síndrome do Ovário Policístico/epidemiologia , Síndrome do Ovário Policístico/fisiopatologia , Adulto Jovem
14.
Microvasc Res ; 122: 78-84, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30502364

RESUMO

Vitamin D (VitD) hypovitaminosis and androgen excess (AE) are both risk factors for cardiovascular diseases in fertile women. However, the possible early interaction between AE and VitD status is not clear. Our goal was to describe how VitD status influences early changes in the biomechanical reactivity of small coronary arterioles in adult female rats after transdermal testosterone treatment. Forty-six adolescent, 90-110-gram-weighed female Wistar rats were randomly grouped into 4 groups. Twenty-four animals received an optimal VitD-supplemented diet, from which 12 animals underwent transdermal testosterone treatment. Twenty-two animals received a VitD-deficient diet, from which 11 were treated with testosterone. At 8 weeks of treatment, invasive arterial blood pressure was registered after in vivo cannulation of carotid artery. Arteriolar end and side branches (200 µm diameter) of the left anterior descendent coronary artery (LAD) were obtained and examined with pressure arteriography in vitro. Similar segments were removed for histological examination. The inner and outer radii of the arterioles were measured using video-microscopy. Normal myogenic tone, maximal passive vasorelaxation and vasoconstriction of the arterioles were measured and statistically analyzed. The vessels' maximal smooth muscle relaxant potential, thromboxane-induced contraction capacity and normal myogenic tone were significantly influenced by actual VitD status. A lower relaxation capacity and increased wall thickness were observed in VitD-deficient groups, which could cause rigidity of the coronary arterioles and elevate cardiovascular risk. Supplementation of VitD could improve myogenic tone and relaxation and hold cardiovascular benefits.


Assuntos
Arteríolas/fisiopatologia , Vasos Coronários/fisiopatologia , Tecido Elástico/fisiopatologia , Hiperandrogenismo/fisiopatologia , Vasoconstrição , Vasodilatação , Deficiência de Vitamina D/fisiopatologia , Animais , Arteríolas/efeitos dos fármacos , Arteríolas/patologia , Fenômenos Biomecânicos , Colecalciferol/farmacologia , Vasos Coronários/efeitos dos fármacos , Vasos Coronários/patologia , Modelos Animais de Doenças , Módulo de Elasticidade , Tecido Elástico/efeitos dos fármacos , Tecido Elástico/patologia , Feminino , Hiperandrogenismo/patologia , Ratos Wistar , Remodelação Vascular , Rigidez Vascular , Vasoconstrição/efeitos dos fármacos , Vasoconstritores/farmacologia , Vasodilatação/efeitos dos fármacos , Vasodilatadores/farmacologia , Deficiência de Vitamina D/tratamento farmacológico , Deficiência de Vitamina D/patologia
16.
Pharmacol Rep ; 71(1): 96-104, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30508725

RESUMO

BACKGROUND: Peroxisome proliferator-activated receptor gamma (PPARG) is a nuclear factor that may act on the early development of ovarian follicles and on follicular steroidogenesis. However, the exact mechanism of PPARG action remains unknown. We have previously found that androgen excess alters early ovarian function and the PPARG system. The aim of the present study was to evaluate whether PPARG activation (using the synthetic ligand pioglitazone (PGZ)) ameliorates the alterations in early ovarian function induced by androgen excess. METHODS: Female prepubertal rats were treated with equine chorionic gonadotropin (eCG) to induce folliculogenesis, together with dehydroepiandrosterone (DHEA) to induce hyperandrogenism and/or PGZ to evaluate PPARG activation. We assessed i) very early ovarian folliculogenesis, ii) PPARG activation, iii) ovarian steroidogenic enzymes, iv) the estradiol/testosterone ratio, v) the ovarian inflammatory status and vi) oxidative stress. RESULTS: PGZ prevented the inactivation of ovarian PPARG induced by androgen excess by increasing PPARG itself and the gene expression of PPARG-coactivator 1 alpha (PGC1A), and by decreasing the gene expression of nuclear co-repressor (NCOR). PGZ also prevented the altered ovarian steroidogenesis, pro-inflammatory status and oxidative stress induced by androgen excess. CONCLUSIONS: Our findings suggest that PPARG activation plays important roles in modulating early ovarian function, and highlight the importance of understanding the role(s) of PPARG activation in the ovary, and the possible involvement in the treatment of ovarian pathologies, and/or the impact in regulating/improving fertility.


Assuntos
Desidroepiandrosterona , Hiperandrogenismo/prevenção & controle , Folículo Ovariano/efeitos dos fármacos , PPAR gama/agonistas , Pioglitazona/farmacologia , Animais , Proteínas Correpressoras/genética , Proteínas Correpressoras/metabolismo , Modelos Animais de Doenças , Estradiol/metabolismo , Feminino , Hiperandrogenismo/induzido quimicamente , Hiperandrogenismo/metabolismo , Hiperandrogenismo/fisiopatologia , Mediadores da Inflamação/metabolismo , Ligantes , Folículo Ovariano/metabolismo , Folículo Ovariano/patologia , Folículo Ovariano/fisiopatologia , Estresse Oxidativo/efeitos dos fármacos , PPAR gama/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Testosterona/metabolismo
17.
J Clin Endocrinol Metab ; 104(5): 1841-1854, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30544235

RESUMO

CONTEXT: Skeletal muscle molecular mechanisms underlying insulin resistance in women with polycystic ovary syndrome (PCOS) are poorly understood. OBJECTIVE: To provide insight into mechanisms regulating skeletal muscle insulin resistance in women who are lean with PCOS. PARTICIPANTS AND METHODS: A hyperinsulinemic-euglycemic clamp with skeletal muscle biopsies was performed. Thirteen women who are lean who have hyperandrogenism and PCOS and seven age- and body mass index-matched healthy control subjects were enrolled. Skeletal muscle protein expression and phosphorylation were analyzed by Western blotting and intramuscular lipid content was measured by thin-layer chromatography. RESULTS: Women with PCOS had 25% lower whole-body insulin sensitivity and 40% lower plasma adiponectin concentration than in control subjects. Intramuscular triacylglycerol, sn-1.3 diacylglycerol, and ceramide contents in skeletal muscle were higher (40%, 50%, and 300%, respectively) in women with PCOS than in control subjects. Activation of insulin signaling did not differ between groups. In women with PCOS, the insulin-stimulated glucose oxidation was reduced and insulin-stimulated dephosphorylation of pyruvate dehydrogenase (PDH) Ser293 was absent. AMP-activated protein kinase (AMPK) α2 protein expression and basal Thr172 phosphorylation were 45% and 50% lower in women with PCOS than in control subjects, respectively. CONCLUSIONS: Whole-body insulin resistance in women who are lean who have hyperandrogenism and PCOS was not related to changes in the proximal part of the insulin signaling cascade in skeletal muscle despite lipid accumulation. Rather, reduced insulin sensitivity was potentially related to plasma adiponectin levels playing a modulating role in human skeletal muscle via AMPK. Furthermore, abnormal PDH regulation may contribute to reduced whole-body metabolic flexibility and thereby insulin resistance.


Assuntos
Hiperandrogenismo/fisiopatologia , Resistência à Insulina , Insulina/metabolismo , Músculo Esquelético/fisiopatologia , Síndrome do Ovário Policístico/fisiopatologia , Magreza/fisiopatologia , Proteínas Quinases Ativadas por AMP/metabolismo , Adiponectina/metabolismo , Adulto , Biomarcadores/metabolismo , Índice de Massa Corporal , Estudos de Casos e Controles , Feminino , Seguimentos , Técnica Clamp de Glucose , Humanos , Cetona Oxirredutases/metabolismo , Masculino , Fosforilação , Prognóstico
18.
Reprod Biol Endocrinol ; 16(1): 119, 2018 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-30454060

RESUMO

BACKGROUND: There is limited literature investigating the effects of body mass index (BMI) and androgen level on in vitro fertilization (IVF) outcomes with a gonadotropin-releasing hormone (GnRH)-antagonist protocol in polycystic ovary syndrome (PCOS). Androgen-related variation in the effect of body mass index (BMI) on IVF outcomes remains unknown. METHODS: In this retrospective study, 583 infertile women with PCOS who underwent IVF using the conventional GnRH-antagonist protocol were included. Patients were divided into four groups according to BMI and androgen level: overweight- hyperandrogenism(HA) group, n = 96, overweight-non-HA group, n = 117, non-overweight-HA group, n = 152, and non-overweight-non-HA group, n = 218. RESULTS: A significantly higher number of oocytes were retrieved, and the total Gn consumption as well Gn consumption per day was significantly lower, in the non-overweight groups than in the overweight groups. The number of available embryos was significantly higher in the HA groups than in the non-HA groups. Clinical pregnancy rate was of no significant difference among four groups. Live-birth rates in the overweight groups were significantly lower than those in non-overweight-non-HA group (23.9, 28.4% vs. 42.5%, P<0.05). The miscarriage rate in overweight-HA group was significantly higher than that in non-overweight-non-HA group (45.2% vs. 14.5%, P<0.05). Multivariate logistic regression analysis revealed that BMI and basal androstenedione (AND) both acted as significantly influent factors on miscarriage rate. The area under the curve (AUC) in receiver operating characteristic (ROC) analysis for BMI and basal AND on miscarriage rate were 0.607 (P = 0.029) and 0.657 (P = 0.001), respectively, and the cut-off values of BMI and basal AND were 25.335 kg/m2 and 10.95 nmol/L, respectively. CONCLUSIONS: In IVF cycles with GnRH-antagonist protocol, economic benefits were seen in non-overweight patients with PCOS, with less Gn cost and more retrieved oocytes. BMI and basal AND were both significantly influential factors with moderate predictive ability on the miscarriage rate. The predictive value of basal AND on miscarriage was slightly stronger than BMI.


Assuntos
Aborto Espontâneo/metabolismo , Androstenodiona/metabolismo , Índice de Massa Corporal , Síndrome do Ovário Policístico/metabolismo , Aborto Espontâneo/etiologia , Adulto , Feminino , Fertilização In Vitro/métodos , Hormônio Liberador de Gonadotropina/antagonistas & inibidores , Antagonistas de Hormônios/farmacologia , Humanos , Hiperandrogenismo/fisiopatologia , Infertilidade Feminina/etiologia , Infertilidade Feminina/metabolismo , Infertilidade Feminina/terapia , Oócitos/citologia , Oócitos/efeitos dos fármacos , Sobrepeso/fisiopatologia , Síndrome do Ovário Policístico/complicações , Gravidez , Taxa de Gravidez , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
19.
Reprod Biol Endocrinol ; 16(1): 108, 2018 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-30449281

RESUMO

This article is a review that addresses the following topics, divided by paragraphs. The first paragraph investigates the effects of physical activity on ovarian function, analyzing in particular the changes concerning the serum concentrations of follicle-stimulating hormone, luteinizing hormone, prolactin, growth hormone, thyroid hormones, leptin, ghrelin, neuropeptide Y. The second paragraph analyzes the effects of doping on the hypothalamic-pituitary-ovarian axis. Finally, the last paragraph analyzes the PCOS category, evaluating the effects of hyperandrogenism in relation to athletic performance.


Assuntos
Doping nos Esportes , Fertilidade/fisiologia , Ovário/fisiologia , Esportes/fisiologia , Feminino , Hormônios/sangue , Humanos , Hiperandrogenismo/sangue , Hiperandrogenismo/fisiopatologia , Sistema Hipotálamo-Hipofisário/fisiologia , Síndrome do Ovário Policístico/sangue , Síndrome do Ovário Policístico/fisiopatologia
20.
Adv Clin Chem ; 86: 71-125, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30144842

RESUMO

Androgens can have variable effects on men and women. Women may be evaluated for androgen excess for several reasons. Typically, young premenopausal women present with clinical symptoms of hirsutism, alopecia, irregular menses, and/or infertility. The most common cause of these symptoms is polycystic ovary syndrome. After menopause, even though ovaries stop producing estrogen, they continue to produce androgen, and women can have new onset of hirsutism and alopecia. Laboratory evaluation involves measurement of the major ovarian and adrenal androgens. In women, age, phase of the menstrual cycle, menopausal status, obesity, metabolic health, and sex hormone-binding proteins significantly affect total-androgen levels and complicate interpretation. This review will summarize the clinically relevant evaluation of hyperandrogenemia at different life stages in women and highlight pitfalls associated with interpretation of commonly used hormone measurements. Hypogonadism in men is a clinical syndrome characterized by low testosterone and/or low sperm count. Symptoms of hypogonadism include decreased libido, erectile dysfunction, decreased vitality, decreased muscle mass, increased adiposity, depressed mood, osteopenia, and osteoporosis. Hypogonadism is a common disorder in aging men. Hypogonadism is observed rarely in young boys and adolescent men. Based on the defects in testes, hypothalamus, and/or pituitary glands, hypogonadism can be broadly classified as primary, secondary, and mixed hypogonadism. Diagnosis of hypogonadism in men is based on symptoms and laboratory measurement. Biomarkers in use/development for hypogonadism are classified as hormonal, Leydig and Sertoli cell function, semen, genetic/RNA, metabolic, microbiome, and muscle mass-related. These biomarkers are useful for diagnosis of hypogonadism, determination of the type of hypogonadism, identification of the underlying causes, and therapeutic assessment. Measurement of serum testosterone is usually the most important single diagnostic test for male hypogonadism. Patients with primary hypogonadism have low testosterone and increased luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Patients with secondary hypogonadism have low testosterone and low or inappropriately normal LH and FSH. This review provides an overview of hypogonadism in men and a detailed discussion of biomarkers currently in use and in development for diagnosis thereof.


Assuntos
Hiperandrogenismo/diagnóstico , Hipogonadismo/diagnóstico , Androgênios/análise , Animais , Biomarcadores/análise , Feminino , Humanos , Hiperandrogenismo/patologia , Hiperandrogenismo/fisiopatologia , Hipogonadismo/patologia , Hipogonadismo/fisiopatologia , Masculino , Testosterona/análise
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