40 resultados para HYPERANDROGENISM


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RAPPORT DE SYNTHESE : L'hirsutisme, l'acné et l'alopécie chez la femme sont souvent associés à des troubles menstruels et à une production excessive d'androgènes, raison pour laquelle ces symptômes cutanés font l'objet d'évaluation endocrinienne. L'hyperandrogénie affecte 5 à 10 % des femmes en âge de reproduction et constitue un motif fréquent de consultation. Récemment, les sociétés d'endocrinologie ont émis des recommandations sur l'investigation et le traitement de l'hyperandrogénie. Longtemps confrontés à la demande de patientes souffrant d'hirsutisme, d'acné ou d'alopécie, nous avons décidé d'effectuer une approche diagnostique et thérapeutique comportant des dosages hormonaux et un traitement antiandrogénique. Un grand nombre de patientes a été ainsi étudié au fil des années. Les paramètres mesurés incluaient la testostérone plasmatique totale, l'androstènedione, le sulfate de déhydroépiandrostérone (DHEAS), la sex hormone-binding globulin (SHBG) et la testostérone salivaire. Cette dernière est considérée comme un bon reflet de la testostérone libre plasmatique, indépendamment des protéines de liaison. L'analyse rétrospective des dossiers nous a permis de comparer nos données avec celles de la littérature. Des 318 dossiers de patientes ayant consulté notre Service pour hirsutisme, acné ou alopécie pendant 6 ans, 228 ont pu être retenus pour une évaluation adéquate. Chez les patientes présentant ces symptômes de façon isolée, les taux d'androgènes et la prévalence de l'oligo-aménorhée étaient plus élevés en cas d'hirsutisme qu'en cas d'alopécie, avec des valeurs intermédiaires en cas d'acné. Aucun des androgènes mesurés ne permettait, à lui seul, d'identifier tous les cas d'hyperandrogénie, mais la testostérone salivaire a montré la meilleure corrélation positive avec l'hirsutisme, alors que la testostérone plasmatique totale montrait la moins bonne corrélation, et l'androstènedione, le DHEAS et la SHBG des corrélations intermédiaires (corrélation négative pour la SHBG). De plus, au cours du traitement antiandrogénique, la testostérone salivaire a montré l'abaissement proportionnel le plus marqué de tous les androgénes mesurés. Comparées aux patientes originaires d'Europe centrale, les patientes originaires d'Europe du sud consultaient avec des degrés d'hirsutisme supérieurs, mais aucune différence n'a été observée dans les corrélations entre l'hirsutisme et les taux hormonaux de ces deux groupes. En l'absence d'un nombre suffisant d'échographies ovariennes, .la prévalence du syndrome des ovaires polykystiques a été probablement sous-estimée (63 patientes, 27.6 % des cas), au bénéfice du diagnostic d'hyperandrogénie avec euménorrhée (101, 44.3 %); les autres diagnostics étaient: androgénes normaux (51, 22.4%), SHBG basse isolée (7, 3.1%), hyperplasie surrénalienne congénitale non-classique (4, 1.8%), et tumeur ovarienne (2, 0.9%). Nous avons comparé les divers traitements médicaux de l'hirsutisme publiés au cours des 25 dernières années, quant à leur efficacité et leur coût. La sensibilisation à l'insuline avec metformin est moins efficace, mais aussi moins chère. L'anti-androgène flutamide et l'inhibiteur de la 5-α reductase finastéride figurent parmi les traitements les plus performants, mais ils sont aussi les plus chers. Le traitement anti-androgénique et de suppression hormonale avec acétate de cyprotérone et éthinyloestradiol, utilisé dans cette étude, est également parmi les plus efficaces, tout en étant nettement moins cher. Cette étude est la première comparant directement les taux d'androgènes et la prévalence de l'oligoaménorrhée dans les 3 symptômes cutanés d'hyperandrogénie, hirsutisme, acné et alopécie, et elle démontre leur différente dépendance aux androgènes. La salive apparait comme un milieu de choix pour identifier ces patientes et la recommandation actuelle de doser la testostérone plasmatique totale en premier, pour distinguer l'hyperandrogénie de l'hirsutisme idiopathique, nous paraît inadéquate. Nous proposons, au contraire, d'abandonner ce dosage au profit de celui de la testostérone salivaire. Par ailleurs, notre étude infirme l'hypothèse d'une sensibilité cutanée accrue aux androgènes chez les femmes originaires du sud de l'Europe. Finalement, elle est la seule à comparer les effets cliniques, les changements biologiques et le coût annuel des traitements publiés de l'hirsutisme.

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Hirsutism, acne, alopecia, and oligo-amenorrhea are clinical expressions of hyperandrogenism, one of the most frequent endocrine disorders in women of reproductive age. Women referred to our endocrine clinics for skin symptoms of hyperandrogenism underwent a laboratory workup to evaluate hormone measurements and received antiandrogen therapy. We retrospectively analyzed the outcome of 228 consecutive patients investigated over 6 years.Patients with hirsutism had higher levels of androstenedione, dehydroepiandrosterone sulfate (DHEAS), and salivary testosterone; lower levels of sex hormone-binding globulin (SHBG); and a higher prevalence of oligo-amenorrhea than patients with alopecia, while patients with acne showed intermediate values. Hirsutism score correlated positively with androstenedione, DHEAS, and salivary testosterone, and correlated negatively with SHBG; salivary testosterone showed the highest correlation coefficient. Total testosterone was not significantly different among patients with hirsutism, alopecia, or acne, and did not significantly correlate with hirsutism score. Hirsutism and oligo-amenorrhea were the most sensitive symptoms of hyperandrogenism, and no androgenic parameter alone allowed us to identify all cases of hyperandrogenism.Patients of central European origin sought consultation with milder hirsutism scores than patients of southern European origin. There was, however, no difference in the clinical-biological correlation between these groups, arguing against differences in skin sensitivity to androgens.Polycystic ovary syndrome, defined as hyperandrogenism (hirsutism or elevated androgens) and oligo-amenorrhea, was diagnosed in 63 patients (27.6%), an underestimate compared with other reports that include systematic ovarian ultrasound studies. Neither pelvic ultrasound, used in a limited number of cases, nor the luteinizing hormone/follicle-stimulating hormone ratio helped to distinguish patients with polycystic ovary syndrome from the other diagnostic groups. These included hyperandrogenism (hirsutism or elevated androgens) and eumenorrhea (101 patients; 44.3%); normal androgens (acne or alopecia and eumenorrhea) (51 patients; 22.4%); isolated low SHBG (7 patients; 3.1%); nonclassical congenital adrenal hyperplasia (4 patients; 1.8% of total, 4.9% of patients undergoing cosyntropin stimulation tests); and ovarian tumor (2 patients; 0.9%).Ethinylestradiol and high-dose cyproterone acetate treatment lowered the hirsutism score to 53.5% of baseline at 1 year, and was also effective in treating acne and alopecia. The clinical benefit is ascribed to the peripheral antiandrogenic effect of cyproterone acetate as well as the hormone-suppressive effect of this combination. Salivary testosterone showed the most marked proportional decrease of all the androgens under treatment. Cost-effectiveness and tolerance of ethinylestradiol and high-dose cyproterone acetate compared well with other antiandrogenic drug therapies for hirsutism. The less potent therapy with spironolactone only, a peripheral antiandrogen without hormone-suppressive effect, was effective in treating isolated alopecia in patients with normal androgens.

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1. Adrenal ectopic tissue has been detected in the paragonadal region of normal women. In patients with congenital adrenal hyperplasia due to 21-hydroxylase (21-OH) deficiency, the manifestation of hyperplasia of paragonadal accessory adrenal tissue has been usually reported to occur in males. Probably, this is the first report of a female with 3beta-hydroxysteroid dehydrogenase (3beta-HSD) deficiency with ectopic adrenal tissue in ovaries. However, the occurrence of hyperplasia of adrenal rests among women with classical congenital adrenal hyperplasia may not be rare, especially among patients with a late diagnosis.2. We report a woman with 3beta-HSD deficiency whose definitive diagnosis was made late at 41 years of age immediately before surgery for the removal of a uterine myoma. During surgery, exploration of the abdominal cavity revealed the presence of bilateral accessory adrenal tissue in the ovaries and in the para-aortic region. The patient had extremely high levels of ACTH (137 pmol/l), DHEA (901.0 nmol/l), DHEA-S (55.9 mumol/l), androstenedione (70.2 nmol/l), testosterone (23.0 nmol/l) and 17alpha-hydroxypregnenolone (234.4 nmol/l) suggesting 3beta-HSD deficiency.3. In view of these elevated androgen levels, with an absolute predominance of DHEA and DHEA-S, we evaluated the effect of this hormonal profile on carbohydrate tolerance and insulin response to glucose ingestion.4. The patient presented normal glucose tolerance but her insulin response was lower than that of 14 normal women (area under the curve, 3beta-HSD = 17,680 vs 50,034 pmol/l for the control group over a period of 3 h after glucose ingestion).5. These results support recent data suggesting that patients with increased serum DHEA and DHEA-S levels do not present resistance to insulin.

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Background/Objective: Acne vulgaris exhibits a worldwide prevalence of up to 95% among adolescents. On the other hand, Down syndrome is an autosomal chromosomal disorder with associated dermatoses and a tendency to obesity. There are no data on its association with acne. Our aim was to detect the prevalence of acne, its forms and associated factors in Down syndrome. Method: A cross-sectional study including 89 subjects aged 10-28 years from Associacao de Pais e Amigos dos Excepcionais-Sao Paulo to verify acne, metabolic and hormonal disorders by interview, clinical and laboratory examinations. Results: We evaluated 49 (55%) males and 40 (45%) females. A weak agreement between self-estimation for acne and examination result was detected. The overall prevalence of acne was 70.8%: 83.7% in males and 55% in females. The prevalence of acne in the age groups 10-17 and 18-28 was 62 and 78.7%, respectively. Facial comedonal acne was mostly detected. The prevalence of obesity was 40%, that of metabolic disorders 7% and that of hyperandrogenism (in females) 15%. Except for gender, no other factor evaluated correlated with acne. Conclusion: A low prevalence of acne in Down syndrome, a predominance in males aged 18-28 and a facial comedonal form were detected. An association with obesity, metabolic disorders or hyperandrogenemia was not assessed. Copyright (C) 2010 S. Karger AG, Basel

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This special article is based on the contents of a lecture given by Sampaio and was written together with Bagatin. it is a summary of the authors` experience treating various forms of acne before and after the introduction of oral isotretinoin, which revolutionized the management of the disease. Nowadays, this drug is considered the unique option to obtain a prolonged remission or cure of acne due to its action in all etiopathogenic factors involved in the disease. Therefore it should be prescribed in accordance to current recommendations, as well as for difficult cases, including those showing tendency to scars or serious psychological and social repercussions. Other topical and/or systemic therapeutic modalities should be considered in the initial approach and for mild and moderate cases.

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One hundred forty-two women with polycystic ovary syndrome (PCOS) with an average body mass index (BMI) of 29.1 kg/m(2) and average age of 25.12 years were studied. By BMI, 30.2% were normal, 38.0% were overweight and 31.6% were obese. Thirty-one eumenorrheic women matched for BMI and age, with no evidence of hyperandrogenism, were recruited as controls. The incidence of dyslipidemia in the PCOS group was twice that of the Control group (76.1% versus 32.25%). The most frequent abnormalities were low high-density lipoprotein cholesterol (HDL-C; 57.6%) and high triglyceride (TG) (28.3%). HDL-C was significantly lower in all subgroups of women with PCOS when compared to the subgroups of normal women. No significant differences were seen in the total cholesterol (p = 0.307), low-density lipoprotein cholesterol (LDL-C; p = 0.283) and TGs (p = 0.113) levels among the subgroups. An independent effect on HDL-C was detected for glucose (p = 0.004) and fasting insulin (p = 0.01); on TG for age (p = 0.003) and homeostatic model assessment insulin resistance (p = 0.03) and on total cholesterol and LDL-C for age (p = 0.02 and p = 0.033, respectively). In conclusion, dyslipidemia is common in women with PCOS, mainly due to low HDL-C levels. BMI has a significant impact on this abnormality.

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Background. A 33-year-old woman presented to an endocrinology clinic with a 5-year history of secondary amenorrhea. 2 years before presentation, she had noticed progressively worsening signs of virilization. Investigations. Measurement of levels of serum free and total testosterone, androstenedione, dehydroepiandrosterone sulfate and gonadotropins; transvaginal ultrasonography, abdominal and pelvic MRI and (18)F-fluorodeoxyglucose PET imaging. Diagnosis. Virilization secondary to an ovarian Leydig cell tumor. Management. The patient underwent a left salpingo-oophorectomy that confirmed the diagnosis of a unilateral Leydig cell tumor. Complete normalization of androgens and gonadotropin levels was achieved after surgery.

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Altered levels of matrix metalloproteinases (MMPs) may reflect relevant pathogenetic mechanisms of disease conditions. The objective of this study was to compare the plasma levels of MMPs and tissue inhibitors of MMPs (TIMPs) in polycystic ovary syndrome (PCOS) patients with those found in healthy ovulatory controls and to examine whether the levels of these biomarkers are associated with clinical and biochemical features of this syndrome. Sixty-five healthy ovulatory subjects (controls) and 80 patients with PCOS were include in this study. MMP-2, MMP-8, MMP-9, TIMP-1, TIMP-2 concentrations were measured in plasma samples by gelatin zymography or enzyme-linked immunoassays. MMP-2, MMP-8, MMP-9, and TIMP-1 levels were similar in PCOS patients and in healthy controls (P > 0.05). PCOS patients had lower plasma TIMP-2 levels than healthy controls (P < 0.05). We found higher MMP-2/TIMP-2 and MMP-9/TIMP-1 ratios in PCOS patients than in healthy controls (all P < 0.05). Testosterone levels correlated positively with the MMP-9/TIMP-1 ratio and negatively with TIMP-2 levels (r = 0.26, P < 0.01 and r = -0.21, P = 0.02, respectively). In addition, only testosterone was an independent predictor of TIMP-2 levels (estimate = -0.35, P = 0.04) and the MMP-9/TIMP-1 ratio (estimate = 0.01, P = 0.04). We found evidence indicating that the balance between MMPs and TIMPs in women with PCOS is altered, probably due to androgen excess found in these women.

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There is evidence that intrauterine growth restriction, resulting in newborn girls that are small for gestational age (SGA), may be related to the onset of polycystic ovary syndrome (PCOS). Thus, we studied whether women born SGA have a higher prevalence of PCOS than women born appropriate for gestational age (AGA). This was a prospective birth cohort study of 384 women born at term between June 1, 1978, and May 31, 1979, in Ribeirao Preto, Brazil. After exclusion, 165 women effectively participated in this study, of whom 43 were SGA and 122 were AGA. The prevalence of PCOS was analysed. At a mean age of 29 years, the women agreed to follow the study protocol, which included: anamnesis, physical examination, serum tests [follicle stimulating hormone, luteinizing hormone, total and free testosterone, dehydroepiandrostenedione sulphate, 17-OH-progesterone, fasting insulin, sex steroid-binding globulin (SHBG) and fasting glucose] and pelvic ultrasound. Data regarding gestational age, birthweight, age at menarche and maternal data were obtained from the files of the cohort. The adjusted relative risk (RR) values of the SGA, insulin resistance, body mass index, maternal smoking and parity variables were analysed using Poisson regression with robust adjustment of variance for the prediction of PCOS. The prevalence of PCOS was higher in the SGA group than in the AGA group [adjusted RR = 2.44, 95% CI (1.39-4.28)]. Hyperandrogenism was more prevalent in the SGA women than in the AGA women (P = 0.011). Circulating SHBG was lower in the SGA women than in the AGA women (P = 0.041), but fasting insulinemia was similar in both groups. The prevalence of PCOS in SGA women was twice as high as in AGA women in our study population.

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Os tumores ováricos secretores de androgénios são raros constituindo cerca de 1% de todas as neoplasias do ovário. Descreve-se o caso clínico de uma doente do sexo feminino, 67 anos de idade, que recorre à consulta por queixas de hirsutismo (score 23) e alopécia com padrão androgenético A avaliação laboratorial revelou níveis séricos elevados de testosterona. A ecografia ginecológica por via transvaginal permitiu identificar a presença de um nódulo sólido no ovário esquerdo com características imagiológicas sugestivas de malignidade pelo que, a doente foi submetida a ooforectomia bilateral. O exame histopatológico revelou a presença de células de Leydig. O seguimento clínico posterior da doente permitiu constatar melhoria do quadro clínico e normalização dos níveis séricos de testosterona.

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OBJECTIVE: Prior to the implementation of the blood steroidal module of the Athlete Biological Passport, we measured the serum androgen levels among a large population of high-level female athletes as well as the prevalence of biochemical hyperandrogenism and some disorders of sex development (DSD). METHODS AND RESULTS: In 849 elite female athletes, serum T, dehydroepiandrosterone sulphate, androstenedione, SHBG, and gonadotrophins were measured by liquid chromatography-mass spectrometry high resolution or immunoassay. Free T was calculated. The sampling hour, age, and type of athletic event only had a small influence on T concentration, whereas ethnicity had not. Among the 85.5% that did not use oral contraceptives, 168 of 717 athletes were oligo- or amenorrhoic. The oral contraceptive users showed the lowest serum androgen and gonadotrophin and the highest SHBG concentrations. After having removed five doped athletes and five DSD women from our population, median T and free T values were close to those reported in sedentary young women. The 99th percentile for T concentration was calculated at 3.08 nmol/L, which is below the 10 nmol/L threshold used for competition eligibility of hyperandrogenic women with normal androgen sensitivity. Prevalence of hyperandrogenic 46 XY DSD in our athletic population is approximately 7 per 1000, which is 140 times higher than expected in the general population. CONCLUSION: This is the first study to establish normative serum androgens values in elite female athletes, while taking into account the possible influence of menstrual status, oral contraceptive use, type of athletic event, and ethnicity. These findings should help to develop the blood steroidal module of the Athlete Biological Passport and to refine more evidence-based fair policies and recommendations concerning hyperandrogenism in female athletes.

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Hirsutism is a relatively frequent condition in an ambulatory setting affecting about 4% of women. A rational clinical and biochemical diagnostic approach assures an optimal treatment directed at etiologic and pathogenetic factors. The diagnosis of hyperandrogenism is evaluated considering the pathophysiologic mechanisms responsible for excessive growth of hair. Ovarian and adrenal tumors are the most serious diseases that have to be excluded by clinical and biochemical tests. The other causes for hirsutism are treatable by a great variety of modalities, available drugs can inhibit pituitary gonadotropins, the hypothalamo-pituitary axis and the conversion of testosterone into biologically active substrate. Finally the binding of androgens to its receptor can be blocked. These possibilities for treatment and their indications for the different etiologies of hirsutism are discussed.

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BACKGROUND: Polycystic ovary syndrome (PCOS) and gestational diabetes mellitus (GDM) are both characterized by an increase in insulin resistance. Our goal in the present study was to measure insulin resistance (as estimated by homeostasis model assessment, sex hormone-binding globulin (SHBG) and adiponectin concentrations) and parameters of low-grade inflammation in non-diabetic, non-hyperandrogenic ovulatory women with previous GDM (pGDM) and in non-diabetic women with classic PCOS, characterized by hyperandrogenism and oligo/anovulation. PATIENTS AND DESIGN: We evaluated 20 women with PCOS, 18 women with pGDM and 19 controls, all matched according to body mass index (BMI). Fasting blood samples were drawn in all women 3-6 days after spontaneous or dydrogesterone-induced withdrawal bleeding. Body fat distribution was assessed using dual-energy X-ray absorptiometry in all women. RESULTS: After adjusting for age and percent body fat, measures of insulin resistance such as SHBG and adiponectin concentrations were decreased and central obesity was increased in women with PCOS and pGDM compared with controls (all p < 0.05). Parameters of low-grade inflammation such as serum tumor necrosis factor-alpha and highly sensitive C-reactive protein concentrations, white blood cell and neutrophil count were increased only in women with PCOS compared with BMI-matched controls (all p < 0.05). CONCLUSIONS: Certain markers of insulin resistance are increased in both women with PCOS and women with pGDM, while low-grade inflammation is increased only in PCOS. PCOS and GDM might represent specific phenotypes of one disease entity with an increased risk of cardiovascular disease, whereby women with PCOS demonstrate an augmented cardiovascular risk profile.

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PURPOSE: To evaluate the prevalence of common mental disorders in women diagnosed with polycystic ovary syndrome as compared with paired controls without this syndrome. METHODS: Cross-sectional study with a Control Group examining women between the ages of 18 and 30 who did not use antidepressants and who sought the Gynecology Service of the researched sites. For every woman diagnosed with the polycystic ovary syndrome, another with the same age, educational status and presence or absence of sexual partners was sought without this diagnosis. In total, 166 patients agreed to participate, consisting of 95 diagnosed with polycystic ovary syndrome and 71 in the Control Group. The diagnosis of polycystic ovary syndrome was made by the presence of two from three criteria: oligomenorrhea or amenorrhea, clinical or biochemical hyperandrogenism and polycystic ovaries on transvaginal ultrasound, following exclusion of patients with Cushing's syndrome, congenital adrenal hyperplasia, and androgen-secreting tumors. Weight and height were measured to calculate the body mass index. The Self-Reporting Questionnaire, which evaluated 20 items, was used as an indicator of common mental disorders. A χ² analysis stratified by the category of body mass index was used to compare the prevalence of common mental disorders, between the groups of women with and without the polycystic ovary syndrome. RESULTS: There were no significant differences in age, education, presence of sexual partners, ethnicity, socioeconomic status, use of psychiatric medication, and search for consultation in mental health between the studied groups. The prevalence of obese women with indications of common mental disorders was significantly higher in women with polycystic ovary syndrome than in the Control Group. In the group with healthy body mass index, the incidence of common mental disorders was statistically significant different between women with polycystic ovary syndrome and normal controls (p=0.008). CONCLUSIONS: Women with diagnosis of this disease have an almost three-fold increased likelihood of common mental disorders as compared with those without polycystic ovary syndrome. Although obesity is often observed in polycystic ovary syndrome, even women with a healthy body mass index have an increased risk of psychiatric comorbidity.

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Objective Polycystic ovary syndrome (PCOS) is the most common endocrine metabolic disorder in women between menarche and menopause. Clinical hyperandrogenism is the most important diagnostic criterion of the syndrome, which manifests as hirsutism in 70% of cases. Hirsute carriers of PCOS have high cardiovascular risk. Lipid accumulation product (LAP) is an index for the evaluation of lipid accumulation in adults and the prediction of cardiovascular risk. The aim of this study was to evaluate the association between LAP and hirsutism in women with PCOS. Methods This was a cross-sectional observational study of a secondary database, which included 263 patients who had visited the Hyperandrogenism Outpatient Clinic from November 2009 to July 2014. The exclusion criteria were patients without Ferriman-Gallwey index (FGI) and/or LAP data. We used the Rotterdam criteria for the diagnosis of PCOS. All patients underwent medical assessment followed by measurement and recording of anthropometric data and the laboratory tests for measurement of the following: thyroid-stimulating hormone, follicle-stimulating hormone, prolactin, total testosterone, sex hormone binding globulin, 17-α-hydroxyprogesterone (follicular phase), glycohemoglobin A1c, and basal insulin. In addition, the subjects underwent lipid profiling and oral glucose tolerance tests. Other laboratory measurements were determined according to clinical criteria. LAP and the homeostatic model assessment index (HOMA-IR) were calculated using the data obtained. We divided patients into two groups: the PCOS group with normal LAP (< 34.5) and the PCOS group with altered LAP (> 34.5) to compare the occurrence of hirsutism. For statistical analysis, we used SPSS Statistics for Windows(r) and Microsoft Excel programs, with descriptive (frequencies, percentages, means, and standard deviations) and comparative analyses (Student's t-test and Chi-square test). We considered relations significant when the p-value was≤0.05. Results LAP was high in most patients (n = 177; 67.3%) and the FGI indicated that 58.5% of the patients (n = 154) had hirsutism. The analysis by LAP quartiles showed a positive correlation (p = 0.04) among patients with a high FGI and an upper quartile LAP (> 79.5) when compared with those with LAP < 29.0 (lower quartile). Conclusion This study demonstrated an association between high LAP and hirsutism. The FGI could represent a simple and low-cost tool to infer an increased cardiovascular risk in women with PCOS.