Introduction New onset hyperandrogenism in postmenopausal female is a rare occurrence, presenting with hirsutism or signs and symptoms of virilization. The causes of hyperandrogenism in postmenopausal female can be categorized into tumorous (androgen-secreting ovarian or adrenal tumors) and non-tumorous in origin (Hyperthecosis, Cushing’s syndrome, Acromegaly, Congenital Adrenal Hyperplasia, and iatrogenic). Here we present a case of severe hyperandrogenism of ovarian origin in a postmenopausal female where definite etiology could not be ascertained either by imaging or pathology. Case A 72-year-old female was referred to endocrinology clinic for complaints of worsening alopecia and hirsutism for the past 4 years. History was positive for weight gain of 80 lbs in the last ten years, menstrual irregularities since menarche, and recent deepening of voice. She denied exposure to exogenous androgenic steroid. Physical examination was remarkable for android obesity, severe male pattern alopecia, hirsutism involving face and deepening of voice, no clitoromegaly was noted. Lab evaluation showed elevated total testosterone level 261 ng/dl (normal value: 2-45 ng/dL) and free testosterone 14.1 pg/mL (normal value: 0.2-3.7 pg/mL ). Estradiol level was elevated and FSH and LH were low for a post-menopausal state. 17 hydroxy progesterone, TSH, and 1 mg overnight dexamethasone suppression test were normal ruling out congenital adrenal hyperplasia, thyroid dysfunction and Cushing’s syndrome. IGF-1 was not elevated ruling out acromegaly. DHEAS level was normal and CT abdomen and pelvis showed no evidence of an adrenal tumor, excluding adrenal source of androgen excess. Transvaginal Ultrasound showed normal volume of the ovaries, thickened endometrium and uterine myomas. Given markedly elevated testosterone levels and exclusion of adrenal tumor, suspicion for an ovarian source remained high. An MRI of the pelvis was done that showed 1.9 cm left adnexal cyst. She was then referred to Gynecology and underwent total hysterectomy with bilateral salpingo-oophorectomy. Interestingly surgical pathology was negative for tumor, showed unremarkable ovaries and right fallopian tube, left fallopian tube with hydrosalpinx, and showed atypical hyperplasia of the endometrium. However, testosterone levels decreased to normal two months after surgery; Free testosterone 1.8 pg/ml (normal values: 0.2-3.7 pg/mL), total testosterone 31 ng/dl (normal value: 2-45 ng/dL) indicating removal of ovarian source of testosterone production. Discussion Although relatively rare, severe hyperandrogenism (total testosterone >150 ng/dL, DHEAS >700 mcg/dL, signs of virilization) in postmenopausal women is caused either by adrenal or ovarian androgen secreting tumor or ovarian hyperthecosis, which is characterized by a hyperplastic ovarian stroma. Severity of symptoms, degree of androgen excess followed by imaging studies lead to identification of source of excessive androgen secretion in most cases. Diagnosis of ovarian virilizing tumors can be difficult since size of such tumors is often too small to allow detection on imaging studies, but are generally detected on surgical pathology and therefore bilateral salpingo-oophorectomy is recommended after exclusion of adrenal cause. However, rarely etiology may remain undetermined in some cases with conventional histology as in our patient.

Orientador: Anaglória Pontes / Resumo: Resistência Insulínica (IR) e Hiperandrogenismo (HA) na Síndrome dos Ovários Policísticos (SOP), acompanhada de Acantose Nigricans (AN), denomina-se síndrome de HAIR-AN. Tem sido relacionada com risco aumentado para diabetes mellitus e doença cardiovascular. Estudam-se agentes que melhoram a resistência insulínica na SOP. OBJETIVO: Avaliar a eficácia da metformina em mulheres obesas com síndrome de HAIR-AN. PACIENTES/MÉTODOS: 16 mulheres receberam metformina (850mg/duas vezes ao dia/seis meses). Avaliaram-se: padrão do ciclo menstrual, Índice de Massa Corpórea (IMC), Relação Cintura Quadril, Índice de Ferriman e Gallwey (IFG), acantose nigricans, Teste de Tolerância à Glicose Oral, Área Sob a Curva de Glicemia (ASCG) e Insulina (ASCI), Glicemia/Insulina, Índice de Sensibilidade à Insulina (ISI), Testosterona total e livre, Globulina Carreadora dos Hormônios Sexuais (SHBG), Índice de Androgênios Livres (IAL), Androstenediona, Sulfato de Deidroepiandrosterona, Hormônio Luteinizante/Folículo Estimulante, Prolactina, Estradiol, Estrona, Perfil lipídico e Ultra-sonografia transvaginal. RESULTADOS: Houve melhora dos ciclos menstruais, redução significativa do IMC, IFG, glicemia (jejum e 120min), ASCI, testosterona livre e colesterol total.Os níveis de testosterona total, androstenediona e IAL diminuíram significativamente aos quatro meses de tratamento mas retornaram aos valores basais com seis meses. Aumentou (p<0,05) o ISI e a relação glicemia/insulina. CONCLUSÃO: A metformina é eficaz na síndrome de HAIR-AN: reduz o peso, a resistência insulínica, melhora a intolerância à glicose, os ciclos menstruais e o hiperandrogenismo. / Abstract: Insulin Resistance (GO) and Hyperandrogenism (HA) in Polycystic Ovary Syndrome (PCOS), accompanied of Acanthosis Nigricans (A), it denominates HAIR-AN syndrome. It has been related with risk increased for diabetes mellitus and cardiovascular disease. They study agents that improve insuline resistance in PCOS. OBJECTIVE: Evaluate metformin effectiveness in obese women with HAIR-AN syndrome. PATIENTS/METHODS: 16 women received metformin (850mg/two times a day/6 months). They evaluated: menstrual cycle standard, Corporal Mass Index (CMI), Waist Hip Ratio, Ferriman's Index and Gallwey (FIG), acanthosis nigricans, Oral Glucose Tolerance Test, Area under the curves for Glycemia (ASCG) and Insulin (ASCI), Glycemia/Insulin, Insulin Sensitivity Index (ISI), Total and free Testosterone, sex hormone-binding globulin (SHBG), Free Androgens Index (FAI), Androstenedione, Deidroepiandrosterona's Sulfate, luteinizing hormone (LH) and follicle-stimulating hormone (FSH), Prolactine, Estradiol, Estrone, lipidic profile and transvaginal Ultrasonographic. RESULTS: There was menstrual cycles improvement, significant reduction of IMC and IFG, of glycemia of fast and at 120 min, of ASCI, of free testosterone, androstenedione and total cholesterol. The levels of total testosterona, IAL decreased significantly at four treatment months but they returned to the basal values with six months. It increased (p<0,05) ISI and glycemia/insulin. CONCLUSION: Metformin is effective in HAIR-AN syndrome: it reduces the weight, the insulin resistance, improvement the intolerance to the glucose, the menstrual cycles and hyperandrogenism. / Mestre

Made available in DSpace on 2014-06-11T19:26:19Z (GMT). No. of bitstreams: 0 Previous issue date: 2001Bitstream added on 2014-06-13T18:29:58Z : No. of bitstreams: 1 ferraz_mfm_me_botfm.pdf: 1034837 bytes, checksum: 3d3a05a0e4702bf9aa71fa831523d395 (MD5) / Resistência Insulínica (IR) e Hiperandrogenismo (HA) na Síndrome dos Ovários Policísticos (SOP), acompanhada de Acantose Nigricans (AN), denomina-se síndrome de HAIR-AN. Tem sido relacionada com risco aumentado para diabetes mellitus e doença cardiovascular. Estudam-se agentes que melhoram a resistência insulínica na SOP. OBJETIVO: Avaliar a eficácia da metformina em mulheres obesas com síndrome de HAIR-AN. PACIENTES/MÉTODOS: 16 mulheres receberam metformina (850mg/duas vezes ao dia/seis meses). Avaliaram-se: padrão do ciclo menstrual, Índice de Massa Corpórea (IMC), Relação Cintura Quadril, Índice de Ferriman e Gallwey (IFG), acantose nigricans, Teste de Tolerância à Glicose Oral, Área Sob a Curva de Glicemia (ASCG) e Insulina (ASCI), Glicemia/Insulina, Índice de Sensibilidade à Insulina (ISI), Testosterona total e livre, Globulina Carreadora dos Hormônios Sexuais (SHBG), Índice de Androgênios Livres (IAL), Androstenediona, Sulfato de Deidroepiandrosterona, Hormônio Luteinizante/Folículo Estimulante, Prolactina, Estradiol, Estrona, Perfil lipídico e Ultra-sonografia transvaginal. RESULTADOS: Houve melhora dos ciclos menstruais, redução significativa do IMC, IFG, glicemia (jejum e 120min), ASCI, testosterona livre e colesterol total.Os níveis de testosterona total, androstenediona e IAL diminuíram significativamente aos quatro meses de tratamento mas retornaram aos valores basais com seis meses. Aumentou (p<0,05) o ISI e a relação glicemia/insulina. CONCLUSÃO: A metformina é eficaz na síndrome de HAIR-AN: reduz o peso, a resistência insulínica, melhora a intolerância à glicose, os ciclos menstruais e o hiperandrogenismo. / Insulin Resistance (GO) and Hyperandrogenism (HA) in Polycystic Ovary Syndrome (PCOS), accompanied of Acanthosis Nigricans (A), it denominates HAIR-AN syndrome. It has been related with risk increased for diabetes mellitus and cardiovascular disease. They study agents that improve insuline resistance in PCOS. OBJECTIVE: Evaluate metformin effectiveness in obese women with HAIR-AN syndrome. PATIENTS/METHODS: 16 women received metformin (850mg/two times a day/6 months). They evaluated: menstrual cycle standard, Corporal Mass Index (CMI), Waist Hip Ratio, Ferriman's Index and Gallwey (FIG), acanthosis nigricans, Oral Glucose Tolerance Test, Area under the curves for Glycemia (ASCG) and Insulin (ASCI), Glycemia/Insulin, Insulin Sensitivity Index (ISI), Total and free Testosterone, sex hormone-binding globulin (SHBG), Free Androgens Index (FAI), Androstenedione, Deidroepiandrosterona's Sulfate, luteinizing hormone (LH) and follicle-stimulating hormone (FSH), Prolactine, Estradiol, Estrone, lipidic profile and transvaginal Ultrasonographic. RESULTS: There was menstrual cycles improvement, significant reduction of IMC and IFG, of glycemia of fast and at 120 min, of ASCI, of free testosterone, androstenedione and total cholesterol. The levels of total testosterona, IAL decreased significantly at four treatment months but they returned to the basal values with six months. It increased (p<0,05) ISI and glycemia/insulin. CONCLUSION: Metformin is effective in HAIR-AN syndrome: it reduces the weight, the insulin resistance, improvement the intolerance to the glucose, the menstrual cycles and hyperandrogenism.

BACKGROUND: Polycystic ovary syndrome is the most common endocrine disorder affecting reproductive-aged women. It is diagnosed using a combination of menstrual irregularity, clinical and/or biochemical hyperandrogenism and polycystic ovary morphology upon ultrasound. Hyperandrogenism in females may clinically manifest as hirsutism, acne, alopecia, or other masculinization of features. Assessing total/free testosterone, dehydroepiandrosterone sulfate, and 17-hydroxyprogesterone provides biochemical evidence of hyperandrogenism. OBJECTIVE: To determine self-reported clinical signs of androgen excess using data from the Ovulation and Menstruation Health (OM) Study, a diverse, multi-ethnic cohort study being conducted at Boston University School of Medicine. METHODS: Data was collected from participants enrolled in the Ovulation and Menstruation Health Study pilot cohort. This epidemiologic survey captured demographics, menstrual cycle patterns, PCOS histories, reproductive histories and manifestations of androgen excess in a diverse patient population. Participants were women ages 18-45 who had the capacity to ovulate/menstruate at the time of the study, had no history of chemotherapy, radiation, or surgical menopause, and were not pregnant at the time of the study. To assess androgen excess, participants were asked to self-report hair growth in nine body areas, acne on the face and back and hair loss on the scalp. The nine body areas were scored using the modified Ferriman-Gallwey (mFG) scoring system. Reference images created by a medical illustrator were used for hirsutism and alopecia grading while clear descriptions were provided for grading acne severity. Clinical hirsutism was defined as total mFG score of ≥ 8, or ethnic specific cutoff for East Asian (≥ 2) and Southeast Asian (≥ 3) women. Alopecia was defined as scalp hair loss ≥ 2. For participants that consented to medical record validation total, free and bioavailable testosterone lab levels were assessed for biochemical hyperandrogenism evaluation. RESULTS: Beginning August 9, the day the study opened to the public, 249 participants completed the pilot survey questionnaire. These participants were 66.8% white (n=165), 6.5% Hispanic or Spanish origin (n=16), 10.5% Black or African-American (n=26), 1.6% East Asian (n=4), 2.0% Southeast Asian (n=5), 2.4% South Asian (n=6), and 10.9% were of mixed ethnic backgrounds (n=27). 22.5% (55/245) of these women had clinical hirsutism by total mFG score. Mean total mFG scores were highest in women who were South Asian at 13.8±9.1 (n=6) and Hispanic at 8.6±8.7 (n=16). Moderate-severe acne was reported in 23.6% (58/246) of respondents, 24.8% (41/165) of white women, 26.7% (4/15) of Hispanic women, 15.4% (4/26) of Black women, 0.0% (0/4) of East Asian women, 20.0% (1/5) of Southeast Asian women, 50% of South Asian women (3/6) and 20% (5/25) of women of mixed ethnicities. 9.4% (23/246) of all pilot women reported alopecia, highest in Black (26.9%, 7/26) and East Asian women (25%, 1/4). Among women that had a PCOS diagnosis there was a higher presence of clinical hirsutism, higher acne severity, and higher prevalence of alopecia when compared to non-PCOS women. In addition, 33%(4/12) of the 44 women that consented to medical record validation had total testosterone levels above the normal range. CONCLUSIONS: This pilot population demonstrated an ethnic dependent pattern of development for hirsutism, acne and alopecia. Additionally, women who had a PCOS diagnosis were more likely to report having the clinical signs of androgen excess than those without a diagnosis. / 2020-06-14T00:00:00Z

Polycystic ovarian syndrome (PCOS) is the most prevalent female endocrine disorder affecting between 5-15% of women. Characterized by a combination of polycystic ovaries, androgen excess, and abnormal ovulation, untreated PCOS may progress to metabolic abnormalities and increase the risk of adverse health outcomes. Adult PCOS is evaluated using the Rotterdam Consensus Criteria, which requires two of three clinical findings. PCOS is a condition of exclusion, and it is essential to consider differential pathologies before diagnosis. PCOS is a heterogeneous condition, and treatment is fitted to the symptoms that each individual experiences. The physiological effects of PCOS present during puberty, typically around the average age of menarche. The exact etiology of PCOS is unknown, and preventing and curing the condition is not yet possible. Metabolic disturbances caused by PCOS, including insulin resistance and increased blood glucose level, are treated with similar methods as diabetes type 2. Insulin sensitizing agents are used to treat insulin resistance caused by PCOS. The primary treatment for insulin resistance in this population is metformin (Glucophage) due to its relatively safe use and effectiveness in normalizing insulin sensitivity and assisting with normalizing weight. The correlation of PCOS with insulin resistance, central obesity, and metabolic syndrome highlights the importance of diet and exercise supplementation for this population. Weight loss of only 5% in obese and overweight PCOS patients can significantly improve PCOS symptoms, including insulin resistance, androgen levels, and fertility. Exercise alone helps increase the sensitivity of skeletal muscle to insulin and decreases metabolic syndrome risk. The effect of PCOS on the hypothalamic-pituitary-gonadal axis can be detrimental to ovulation and implantation of a fertilized egg. Treatments that suppress the HPG-axis cannot be continued during attempts to become pregnant and throughout pregnancy. Ovulation-inducing agents can improve the rate of ovulation and increase fertility; however, some women may become resistant to these treatments. Clomiphene citrate (Clomid) is often the primary drug used to induce ovulation; however, monotherapy with letrozole has shown greater improvements in pregnancy and live birth rates. Gonadotropins may also be successful treatments, but there is an accompanied increased risk of ovarian hypersensitivity syndrome and multiple pregnancies. Laparoscopic ovarian drilling may help decrease androgen production in the ovary and briefly increase pregnancy capability. During pregnancy, metformin may help decrease the risk of gestational diabetes; however, the long-term effect of fetal exposure to metformin is not well studied. Cosmetic symptoms of PCOS, including hirsutism and acne vulgaris, may cause severe social stress. PCOS women are at additional risk of depression and anxiety. Cosmetic and mental health concerns, combined with the stress caused by the high prevalence of infertility in PCOS, highlight the need for psychological help to be considered in improving the overall quality of life. Combining cognitive behavioral therapy with treatments may help PCOS women maintain treatment and improve their quality of life. The most effective treatment may require modification throughout a patient’s life due to the variance in gonadocorticoid levels throughout a female’s life. Post-menopausal women continue to have excess androgens and estrogens in circulation. High levels of ovarian and adrenal production of gonadocorticoids combined with decreased circulating binding globulins can lead to stress on the metabolic and cardiovascular systems in PCOS after menopause. Continuous levels of increased triglycerides increase the risk for atherosclerosis and adverse cardiac events. PCOS women have an increased risk of endometrial and ovarian cancer, while a link between breast cancer and PCOS is widely disputed. There is 1.66 times higher risk for cardiovascular events, including 1.96 times greater risk for stroke in women with PCOS compared to non-PCOS women when controlled for weight. As we begin to understand the increased risk factors for hypertension, hyperlipidemia, and cardiovascular stress with PCOS, it is crucial to understand how to diagnose and treat PCOS patients in the early stages of the disorder. Irregularities in typical puberty and menarche in adolescents increase the difficulty of diagnosis and may delay a diagnosis.

Made available in DSpace on 2014-06-11T19:29:52Z (GMT). No. of bitstreams: 0 Previous issue date: 2008-08-08Bitstream added on 2014-06-13T18:39:57Z : No. of bitstreams: 1 souza_fac_me_botfm.pdf: 470759 bytes, checksum: b7008fa062892d597243273954f53192 (MD5) / Faculdade de Medicina da Unoeste / A obesidade classe III ou mórbida determina um risco significativamente aumentado para complicações metabólicas. Também são referenciadas alterações ginecológicas, como as irregularidades menstruais, o hirsutismo e as alterações hormonais. Avaliação dos aspectos clínicos-epidemiológicoslaboratoriais de pacientes com obesidade classe III, portadoras de distúrbios metabólicos e hormonais. Foram analisadas 58 mulheres com obesidade classe III ou mórbida e divididas em 2 grupos de estudo; sendo um grupo com mulheres obesas grau III sem disfunção menstrual ou hirsutismo, (Grupo C) e outro grupo com mulheres obesas grau III apresentando disfunção menstrual associada ou não a hirsutismo (Grupo E). Foram avaliadas a idade, cor, paridade, estado civil, profissão, nível sócio-econômico, escolaridade, idade da menarca, peso corporal, estatura, índice de massa corpórea, presença de hirsutismo (Índice de Ferriman e Gallwey), medida da circunferência abdominal (CA), medida da circunferência do quadril (CQ), relação cintura-quadril (RCQ), ciclo menstrual, medida da pressão arterial, presença da acantose nigricans, avaliação da resistência a insulina, glicemia de jejum (GJ), colesterol total (CT), HDL-C, LDL-C, triglicerídeos (TG), hormônio tireo-estimulante (TSH), T4 livre, hormônio luteinizante (LH), o hormônio folículo-estimulante (FSH), prolactina (PRL), Testosterona total, sulfato de dehidroepiandrosteron (DHEA-S), a insulina e o HOMA test. Os aspectos clínicos-epidemiológicos não apresentaram diferenças estatísticas. Os parâmetros clínicos e laboratoriais não apresentaram alterações estatisticamente significativas; entretanto, os valores do HOMA test para o grupo E foram significantemente maiores que os pacientes do grupo C. Em mulheres obesas classe III a presença da resistência... / Class-III or morbid obesity determines significantly increased risk for metabolic complications. Gynecologic alterations, such menstrual irregularity, hirsutism and hormonal alterations are also reported. To evaluate the clinical, epidemiological and laboratory aspects of patients with class-III obesity showing metabolic and hormonal disorders. Fiftyeight women with class-III or morbid obesity were evaluated. They were divided into 2 groups: one group comprising grade-III obese women without menstrual dysfunctions or hirsutism (Group C), and another with grade-III obese women showing menstrual dysfunction associated with hirsutism or not (Group E). The following aspects were evaluated age, color, parity, marital status, profession, socioeconomic level, education, age at menarche, body weight, height, body mass index, presence of hirsutism (Ferriman and Gallwey Index), abdominal circumference measurement (AC), hips circumference measurement (HC), waist-to-hip ratio (WHR), menstrual cycle, blood pressure, presence of acanthosis nigricans, evaluation of insulin resistance, fasting glycemia (FG), total cholesterol (TC), HDL-C, LDL-C, triglycerides (TG), thyroidstimulating hormone (TSH), free T4, luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin (PRL), total testosterone, dehydroepiandrosterone sulfate (DHEA-S), insulin and the HOMA test. The clinical and epidemiological aspects did not present statistical differences. The clinical and laboratory parameters did not show statistically significant alterations; however, the HOMA test values for group E were significantly higher than those for patients in group C. In class-III obese women, the presence of insulin resistance can cause menstrual dysfunctions, such as amenorrhea or oligomenorrhea even in the absence of hyperandrogenism, thus suggesting... (Complete abstract click electronic access below)

A síndrome dos ovários policísticos (SOP) constituia causa mais freqüente de infertilidade, anovulação e hiperandrogenismo atualmente. Sua fisiopatogenia é em parte obscura. O hormônio anti-mülleriano (HAM),uma glicoproteína produzida pelas células da granulosa dos folículos pré-antrais e folículos antrais pequenos, parece exercer papel fundamental para seu surgimento, exacerbando o hiperandrogenismo intra-folicular e interferindo no mecanismo de seleção do folículo dominante. Além das alterações ovulatórias, há repercussões metabólicas decorrentes da síndrome, como a resistência à insulina (RI), que afeta entre 45 a 70% das mulheres com SOP em idade reprodutiva. Estratégias para aumentar a sensibilidade à insulina poderiam reduzir o impacto reprodutivo e metabólico da RI. Entre elas, destaca-se a metformina, uma droga anti-diabética oral, cuja utilização levaria a uma melhora dos padrões metabólicos e restabelecimento da ovulação. No presente estudo, foram avaliados a relação entre os níveis séricos de HAM e resistência insulínica antes e após o tratamento com metformina, comparados os níveis séricos de HAM na fase folicular precoce entre pacientes com e sem SOP e correlacionados os níveis de HAM com os níveis séricos de insulina, gonadotrofinas e androgênios. Foram realizadas dosagens séricas de HAM, androgênios e gonadotrofinas em 36 pacientes (16 com SOP e resistência insulínica e 20 eumenorreicas, sendo grupos pareados quanto à idade e índice de massa corpórea). No grupo SOP, foram avaliados níveis de HAM, insulina, glicemia e QUICKI (quantitative insulin check index) antes e depois do tratamento com metformina 1500 mg/dia por oito semanas. Foram encontrados níveis de HAM mais elevados no grupo SOP do que no grupo controle (49,9 ± 6,1 pmol/L versus 4,5 ± 2,1 pmol/L, p < 0,0001), assim como os níveis de hormônio luteinizante (LH) (10,3± 1,5 mUI/L versus 3,5 ±0,5 mUI/L, p=0,0004), testosterona (64,9 ± 5 ng/mL versus 41,1 ±4,7 ng/mL, p=0,0017) e 17-hidroxiprogesterona (17OHP) ( 90 ±16,8ng/ml versus 49,1 ±6,6 ng/ml; p= 0,03). Nas pacientes com SOP, houve correlação positiva forte entre os níveis de HAM pré-tratamento e testosterona (coeficiente r dePearson - R - de 0,83; p<0,0001). Também foi encontrada correlação positiva e significativa entre HAM e LH (R = 0,51; p = 0,04). As demais variáveis não apresentaram correlação significativa com o HAM pré-tratamento. Após o tratamento, houve redução significativa dos níveis de insulina (16,4 ± 2,6 mUI/ml versus 12 ± 1,9 mUI/ml; p=0,0132). Os níveis de HAM tiveram redução, porém sem diferença estatística (49,9 ± 6,1 versus 41,5 ± 5,6 pmol/L; p=0,06). Houve redução significativa nos níveis de testosterona (64,9 ± 5 ng/mL versus 49,3 ± 14 ng/mL). A correlação do HAM com os níveis de testosterona não persistiu após o tratamento com a metformina (R=0,08 e p=0,76). Assim, a manutenção dos níveis séricos de HAM após o uso da metformina, mesmo com a comprovada melhora metabólica e redução dos níveis de gonadototrofinas sugere que o papel do HAM na SOP baseia-se num mecanismo intrínseco ovariano, independente do eixo hipotálmo-hipófise-ovário e não influenciado pela resistência insulínica. / Polycystic ovary syndrome (PCOS) is the most frequent cause of infertility, anovulatory disordes and hyperandrogenism in young women. Its pathophisiology remains unclear and anti-mullerian hormone (AMH), a glycoprotein produced by the granulose cells of early developing follicles, seems to be fundamental to its development, by enhancing the intra-follicular hyperandrogenism and interfering in the selection of a dominant follicle. PCOS also causes metabolic disorders, such as insulin resistance (IR), that affects 45 to 70% of women with PCOS. Strategies to improve insulin sensitivity could reduce the reproductive and metabolic impact of IR.Metformin, a insulin-sensitizing agent, appears to improve the metabolicparameters and reestablish ovulatory cycles. In this study, we evaluated the relationship between anti-mullerian hormone serum levels and IR before and after protracted treatment with meformin; we also compared the anti-mullerian hormone levels in PCOS in the early follicular phase to normo-ovulatory women. The correlation of anti-mullerian hormone levels to insulin, gonatotropins and androgen serum levels was also evaluated. The study included 36 pacients (20 with PCOS and IR and 16 with ovulatory cycles). Anti-mullerian hormone serum levels, insulin, glucose and QUICKI (quantitative insulin check index) were evaluated in patients with PCOS before and after treatment with metformina 1500 mg/day during eight weeks. Anti-mullerian hormone serum levels were higher in PCOS (49,9 ± 6,1 pmol/L versus 4,5 ± 2,1 pmol/L, p < 0,0001), as well as luteinizing hormone (LH) levels (10,3± 1,5 mUI/L versus 3,5 ±0,5 mUI/L, p=0,0004), testosterone (64,9 ± 5 ng/mL versus 41,1 ±4,7 ng/mL, p=0,0017) and 17-ydroxyprogesterone (17OHP) ( 90 ±16,8ng/ml versus 49,1 ±6,6 ng/ml; p= 0,03). In PCOS, there is a positive correlation between anti-mullerian hormoneserum levels and testosterone (R= 0,83; p<0,0001) before treatment; this correlation did not persisted after treatment (R=0,08 e p=0,76). There is also a positive correlation between anti-mullerian hormone serum levels before metformin treatment and LH (R= 0,83; p<0,0001). No correlations were found between anti-mullerian hormone serum levels before treatment and other parameters. After treatment, insulin serum levels reduced (16,4 ± 2,6 mUI/ml versus 12 ± 1,9 mUI/ml; p=0,0132). AMH serum levels also reduced, but therewas no statically significant difference (49,9 ± 6,1 versus 41,5 ± 5,6 pmol/L; p=0,06). Testosterone serum levels decreased significantly (64,9 ± 5 ng/mL versus 49,3 ± 14 ng/mL). No correlation between AMH and testosterone levels was found after treatment (r=0, 08 e p=0, 76). The maintenance of AMH serum levels after treatment with metformin, despite the enhance of metabolic parameters and reduction of the gonadrotopins levels, suggests that AMH acts in the pathophisiology of PCOS by a intra-ovarian mechanism, that does not depend on the neuroendrocine axis and that is not influenced by IR.

Women’s involvement in sport has remained a critical issue in society for several decades. Sex verification and drug testing are two methods that have been used to regulate women’s eligibility to compete in international sports competitions based on their testosterone levels. Organizations such as the International Olympic Committee (IOC) and World Anti-Doping Agency (WADA) have published and updated policies and rules that set eligibility criteria for who can compete in women’s sport and under what conditions. However, the academic literature addressing Chinese women’s perspectives on international sex verification and drug testing policies available in English is extremely limited. This study investigates how recent policy revisions regarding doping and sex eligibility rules impact women student- athletes competing in track and field at the university level in China. Using qualitative research methods, this thesis analyzes the impact of recent doping and gender policies on a sample of Chinese female student-athletes. / October 2015

Made available in DSpace on 2014-06-11T19:35:39Z (GMT). No. of bitstreams: 0 Previous issue date: 2009-08-20Bitstream added on 2014-06-13T19:24:59Z : No. of bitstreams: 1 rehme_mfb_dr_botfm.pdf: 2280081 bytes, checksum: b44989e75865f4acff4695729feffce0 (MD5) / A síndrome dos ovários policísticos (SOP) afeta 5 a 8% das mulheres no menacme e é caracterizada pela anovulação crônica e hiperandrogenismo. A obesidade central e a resistência insulínica (RI) são freqüentes na SOP e desempenham um papel fundamental na etiopatogenia da síndrome metabólica (SM). O hiperandrogenismo tem sido questionado como um fator importante no desenvolvimento da SM em mulheres com SOP. Verificar se o hiperandrogenismo influencia no desenvolvimento de síndrome metabólica em pacientes com SOP. Foram avaliados retrospectivamente os dados clínicos, bioquímicos e ultrassonográficos de 180 mulheres com SOP diagnosticadas pelos critérios de Rotterdam e de 70 mulheres com obesidade simples. As pacientes com SOP foram classificadas de acordo com o índice de massa corporal (IMC) em SOP não obesas e SOP obesas. As pacientes obesas simples não apresentaram hiperandrogenismo clínico nem bioquímico. O índice de sensibilidade à insulínica (ISI) foi avaliado pelo HOMA-IR e ISI de Matsuda e DeFronzo. A SM foi diagnosticada pelos critérios do NCEP-ATP III com modificações sugeridas pelo consenso de Rotterdam. A média de idade das pacientes foi de 27,3 + 4,7 no grupo das pacientes SOP não obesas; 28,8 + 5,0 nas SOP obesas e 27,4 + 5,2 nas obesas simples (p=0, 0773), e o IMC foi de 25,1+3,0 kg/m2; 37,0+ 5,5 kg/m2 e 36,0+ 4,2 kg/m2 respectivamente (p<0, 001). A prevalência de RI e SM não diferiu entre as pacientes obesas com e sem SOP e foi significativamente maior do que nas SOP não obesas (p<0, 001). Entretanto a prevalência de SM foi maior nas SOP obesas com hiperandrogenismo... / Polycystic ovary syndrome (PCOS) affects 5-8% of women at menacme and is characterized by chronic anovulation and hyperandrogenism. Central obesity and insulin resistance (IR) are frequent in PCOS and play a leading role in the etiopathogeny of metabolic syndrome (MS). Hyperandrogenism has been suggested as an important factor in the development of MS in women with PCOS. To determine whether hyperandrogenism influences the development of metabolic syndrome in patients with PCOS. Clinical, biochemical and ultrasonographic data on 180 women with PCOS, as diagnosed by the Rotterdam criteria, and 70 women with simple obesity were retrospectively analyzed. According to body mass index, PCOS patients were classified as nonobese with PCOS and obese with PCOS. No clinical or biochemical hyperandrogenism was observed in patients with simple obesity. Insulin sensitivity indices (ISI) were assessed as proposed by HOMA-IR and ISI (Matsuda and De Fronzo). MS was diagnosed based on NCEP-ATP III criteria with modifications suggested by the Rotterdam consensus. Mean age was 27.3 + 4.7 among non-obese patients with PCOS, 28.8 + 5.0 in obese patients with POS, and 27.4 + 5.2 in those with simple obesity (p=0.0773), while BMI was 25.1+3.0 kg/m2, 37.0+ 5.5 kg/m2 and 36.0+ 4.2 kg/m2, respectively (p<0.001). The prevalence of IR and MS did not differ between obese patients with and without PCOS, and was significantly higher in these patients than in non-obese women with PCOS (p<0.001). The prevalence of MS, however, was higher... (Complete abstract click electronic access below)

Orientador: Anaglória Pontes / Banca: Tamara Goldberg / Banca: Marcos Felipe Silva de Sá / Banca: José Alcione Macedo Almeida / Banca: Cleusa Cascaes Dias / Resumo: A síndrome dos ovários policísticos (SOP) afeta 5 a 8% das mulheres no menacme e é caracterizada pela anovulação crônica e hiperandrogenismo. A obesidade central e a resistência insulínica (RI) são freqüentes na SOP e desempenham um papel fundamental na etiopatogenia da síndrome metabólica (SM). O hiperandrogenismo tem sido questionado como um fator importante no desenvolvimento da SM em mulheres com SOP. Verificar se o hiperandrogenismo influencia no desenvolvimento de síndrome metabólica em pacientes com SOP. Foram avaliados retrospectivamente os dados clínicos, bioquímicos e ultrassonográficos de 180 mulheres com SOP diagnosticadas pelos critérios de Rotterdam e de 70 mulheres com obesidade simples. As pacientes com SOP foram classificadas de acordo com o índice de massa corporal (IMC) em SOP não obesas e SOP obesas. As pacientes obesas simples não apresentaram hiperandrogenismo clínico nem bioquímico. O índice de sensibilidade à insulínica (ISI) foi avaliado pelo HOMA-IR e ISI de Matsuda e DeFronzo. A SM foi diagnosticada pelos critérios do NCEP-ATP III com modificações sugeridas pelo consenso de Rotterdam. A média de idade das pacientes foi de 27,3 + 4,7 no grupo das pacientes SOP não obesas; 28,8 + 5,0 nas SOP obesas e 27,4 + 5,2 nas obesas simples (p=0, 0773), e o IMC foi de 25,1+3,0 kg/m2; 37,0+ 5,5 kg/m2 e 36,0+ 4,2 kg/m2 respectivamente (p<0, 001). A prevalência de RI e SM não diferiu entre as pacientes obesas com e sem SOP e foi significativamente maior do que nas SOP não obesas (p<0, 001). Entretanto a prevalência de SM foi maior nas SOP obesas com hiperandrogenismo... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Polycystic ovary syndrome (PCOS) affects 5-8% of women at menacme and is characterized by chronic anovulation and hyperandrogenism. Central obesity and insulin resistance (IR) are frequent in PCOS and play a leading role in the etiopathogeny of metabolic syndrome (MS). Hyperandrogenism has been suggested as an important factor in the development of MS in women with PCOS. To determine whether hyperandrogenism influences the development of metabolic syndrome in patients with PCOS. Clinical, biochemical and ultrasonographic data on 180 women with PCOS, as diagnosed by the Rotterdam criteria, and 70 women with simple obesity were retrospectively analyzed. According to body mass index, PCOS patients were classified as nonobese with PCOS and obese with PCOS. No clinical or biochemical hyperandrogenism was observed in patients with simple obesity. Insulin sensitivity indices (ISI) were assessed as proposed by HOMA-IR and ISI (Matsuda and De Fronzo). MS was diagnosed based on NCEP-ATP III criteria with modifications suggested by the Rotterdam consensus. Mean age was 27.3 + 4.7 among non-obese patients with PCOS, 28.8 + 5.0 in obese patients with POS, and 27.4 + 5.2 in those with simple obesity (p=0.0773), while BMI was 25.1+3.0 kg/m2, 37.0+ 5.5 kg/m2 and 36.0+ 4.2 kg/m2, respectively (p<0.001). The prevalence of IR and MS did not differ between obese patients with and without PCOS, and was significantly higher in these patients than in non-obese women with PCOS (p<0.001). The prevalence of MS, however, was higher... (Complete abstract click electronic access below) / Doutor