Ferriman-Gallwey score correlates with obesity and insulin levels in polycystic ovary syndrome: an observational study / Correlação da escala de Ferriman-Gallwey com a obesidade e níveis de insulina na síndrome dos ovários policísticos: um estudo observacional

BACKGROUND: The Polycystic Ovary Syndrome (PCOS) is the most common endocrinopathy and one of the main causes of infertility in women. OBJECTIVES: This study aimed to evaluate the correlation between clinical hyperandrogenism assessed by modified Ferriman-Gallwey (F-G) score and metabolic parameters in Polycystic Ovary Syndrome women. METHODS: This observational study included fifty Polycystic Ovary Syndrome subjects. Detailed information about body mass index (BMI) and abdominal circumference (AC) were obtained from each subject. F-G score was applied to assess hirsutism through visual method. Serum levels of insulin, glucose and testosterone were measured. RESULTS: A positive correlation was observed between F-G score with body mass index, abdominal circumference and insulin. CONCLUSIONS: Obesity, mainly abdominal adipose tissue, and insulin levels correlate with hyperandrogenism in Polycystic Ovary Syndrome women, analyzed by F-G score. F-G score could be a marker to evaluate metabolic disorders in Polycystic Ovary Syndrome women.

JUSTIFICATIVA: A Síndrome dos Ovários Policísticos (SOP) é a endocrinopatia mais comum e uma das principais causas de infertilidade em mulheres. OBJETIVOS: O presente estudo teve como objetivo avaliar a correlação entre hiperandrogenismo clínico, avaliado pela escala de Ferriman-Gallwey (FG) modificada e parâmetros metabólicos em mulheres com a Síndrome dos Ovários Policísticos. MÉTODOS: Este estudo observacional incluiu cinquenta mulheres com Síndrome dos Ovários Policísticos. Informações detalhadas sobre o índice de massa corporal (IMC) e circunferência abdominal (CA) foram obtidas de cada participante. A escala FG foi aplicada para avaliar o hirsutismo através do método visual. Níveis séricos de insulina, glicose e testosterona foram também avaliados. RESULTADOS: Observou-se uma correlação positiva entre a escala FG e o índice de massa corporal, circunferência abdominal e insulina. CONCLUSÕES: A obesidade, principalmente o tecido adiposo abdominal, e os níveis de insulina se correlacionam com hiperandrogenismo em mulheres com Síndrome dos Ovários Policísticos, analisados por meio da escala FG. Desta forma, esta escala poderia ser um marcador para avaliar distúrbios metabólicos em mulheres com Síndrome dos Ovários Policísticos.

Polycystic ovarian syndrome.

Polycystic ovarian syndrome (PCOS) is a "multispeciality" disorder suspected in patients with irregular menses and clinical signs of hyperandrogenism such as acne, seborrhoea, hirsutism, irregular menses, infertility, and alopecia. Recently, PCOS has been associated with the metabolic syndrome. Patients may develop obesity, insulin resistance, acanthosis nigricans, Type 2 diabetes, dyslipidemias, hypertension, non-alcoholic liver disease, and obstructive sleep apnoea. Good clinical examination with hematological and radiological investigations is required for clinical evaluation. Management is a combined effort involving a dermatologist, endocrinologist, gynecologist, and nutritionist. Morbidity in addition includes a low "self image" and poor quality of life. Long term medications and lifestyle changes are essential for a successful outcome. This article focuses on understanding the normal and abnormal endocrine functions involved in the pathogenesis of PCOS. Proper diagnosis and management of the patient is discussed.

Hiperandrogenización prenatal en ratas y el metabolismo lipídico en la vida adulta / The role of prenatal hyperandrogenism on lipid metabolism during adult life in a rat model

El síndrome del ovario poliquístico (PCOS) es una afección de alta incidencia en mujeres en edad fértil. Si bien la etiología de la enfermedad se desconoce, se cree que la exposición a andrógenos durante la vida intrauterina generaría reprogramación fetal afectando vías endocrinas y metabólicas que, junto a alteraciones génicas y ambientales, inducirían la aparición de PCOS en etapas muy tempranas de la vida. Es por ello que se buscan marcadores tempranos del desarrollo de PCOS. Utilizando un modelo murino de hiperandrogenización prenatal (HA) recreamos dos fenotipos de PCOS: ovulatorio y anovulatorio. La HA no alteró el colesterol circulante pero disminuyó el colesterol HDL y aumentó el LDL y los triglicéridos (TG) con respecto a los controles. La relación colesterol total/HDL como marcador de riesgo cardiovascular y la relación TG/HDL se vieron incrementadas con respecto a los controles, resultando mayor en el grupo PCOS anovulatorio. El presente trabajo demuestra la importancia de la determinación del perfil lipídico a edades tempranas en poblaciones de riesgo (como es el caso de hijas de madres con PCOS).

Polycystic ovary syndrome (PCOS) is one of the commonest endocrine diseases that affect women in their reproductive ages; however, the etiology of the syndrome remains unknown. A hypothesis proposes that during gestation increased exposure of androgen would induce fetal programming that may increase the risk of PCOS development during the adult life. By means of a prenatally hyperandrogenized (HA) rat model we demonstrated the importance of determining the lipid profile at early ages. HA induced two different phenotypes: ovulatory and anovulatory PCOS. HA did not modify total cholesterol but decreased HDL cholesterol and increased both LDL and tryglicerides (TG) when compared with controls. Both, the ratio total cholesterol: HDL (marker of cardiovascular risk) and TG:HDL (marker of metabolic syndrome) were increased in the HA group with respect to controls. In addition, these abnormalities were stronger in the anovulatory than ovulatory phenotype. Our results point out the need to find early markers of PCOS in girls or adolescents with increased risk to develop PCOS (as in daughters of women with PCOS).

Síndrome do ovário policístico: aspectos atuais das abordagens terapêuticas: parte 2 / Polycystic ovary syndrome: current aspects of the therapeutic interventions: part 2

A segunda parte desta revisão inclui as demais opções de tratamento da síndrome do ovário policístico (SOP). O citrato de clomifeno (CC) é utilizado na dose de 50 a 200 mg/dia durante cinco dias a partir do segundo ao quinto dia do ciclo menstrual. A taxa de ovulação após o tratamento com CC é de aproximadamente 73 por cento e a de gravidez em torno de 36 por cento. Com os análogos do GnRH ocorre redução dos níveis de gonadotrofinas e diminuição da secreção de estrógenos e androgênios. O principal risco da estimulação com gonadotrofinas é a gestação múltipla. Anastrazole e letrozole pertencem à classe dos inibidores da aromatase de terceira geração. As taxas de ovulação e gestação com letrozole variam de 54,5 a 82,4 por cento e 9 a 25 por cento, respectivamente. Não ocorreu diferença significativa nas taxas de ovulação e gestação entre o uso de 2,5 mg de letrozole em comparação com 1 mg de anatrozole. O uso da N-acetilcisteína (NAC) sugere melhora significativa da sensibilidade à insulina em mulheres com SOP. Os contraceptivos hormonais orais combinados permanecem como tratamento predominante para redução do hiperandrogenismo e das irregularidades menstruais em mulheres que não desejam engravidar. Os antiandrógenos são utilizados principalmente para diminuir as queixas de hirsutismo e o efeito será percebido em 9 a 12 meses de tratamento. Muitas mulheres se submetem à cauterização ovariana ou a laser por videolaparoscopia tendo restauração espontânea da ovulação com gravidez subsequente. Porém, os benefícios potenciais destas intervenções tendem a ser atenuados devido à formação de aderências.

The second part of this review includes other treatment options for polycystic ovary syndrome (PCOS). The clomiphene citrate (CC) is used in a dose of 50 to 200 mg/day for five days, begining from the second to fifth day or the menstrual cycle. The ovulation rate after the treatment with CC is approximately 73 percent and the pregnancy rate is about 36 percent. With GnRH analogues, there is a reduction in gonadotrophin levels and a decrease of androgen and estrogen secretion. The major risk due to stimulation with gonadotrophins is the multiple gestation. Anastrozole and letrozole belong to the class of third-generation aromatase inhibitors. The rates of ovulation and pregnancy with letrozole vary from 54.5 to 82.4 percent and from 9 to 25 percent, respectively. There was no significant difference in ovulation and pregnancy rates with the use of 2.5 mg of letrozole compared to 1 mg of anastrozole. The use of N-acetyl Cysteine (NAC) suggests significant improvement in insulin sensibility in women with PCOS. The combined oral hormonal contraceptives are still the predominant treatment to decrease hyperandrogenism and menstrual irregularities in women who do not want to get pregnant. Anti-androgens are used mainly to diminish complaints of hirsutism and the effect will be noted after 9 to 12 months of treatment. Several women undergo ovarian cauterization of with laser by videolaparoscopy having their ovulation spontaneously restored with subsequent pregnancy. However, the potential benefits of these interventions might be attenuated due to adhesion formations.

La exposición prenatal a andrógenos como factor de reprogramación fetal / Prenatal exposure to androgens as a factor of fetal programming

Both epidemiological and clinical evidence suggest a relationship between the prenatal environment and the risk of developing diseases during adulthood. The first observations about this relationship showed that prenatal growth retardation or stress conditions during fetal life were associated to cardiovascular, metabolic and other diseases in later life. However, not only those conditions may have lasting effects after birth. Growing evidence suggests that prenatal exposure to steroids (either of fetal or maternal origin) could be another source of prenatal programming with detrimental consequences during adulthood. We have recently demonstrated that pregnant women with polycystic ovary syndrome exhibit elevated androgen levels compared to normal pregnant women, which could provide an androgen excess for both female or male fetuses. We have further tested this hypothesis in an animal model of prenatal androgenization, finding that females born from androgenized mothers have a low birth weight and high insulin resistance, that starts at an early age. On the other hand, males have low testosterone and LH secretion in response to a GnRH analogue test compared to control males and alterations in seminal parameters. We therefore propose that our efforts should be directed to modify the hyperandrogenic intrauterine environment to reduce the potential development of reproductive and metabolic diseases during adulthood.

Sindrome dos ovarios policisticos: contribuicao para o estudo da resistencia a insulina / Polycystic ovary syndrome: contribution for the study of insulin resistance

Apos uma avaliacao inicial, 25 pacientes com sindrome dos ovarios policisticos (SOP) foram submetidas a teste de tolerancia a glicose oral com dosagens de glicose e insulina. Treze pacientes foram tratadas com espironolactona, 200 mg/dia por 6 meses e reavaliadas aos 3 e 6 meses. Concluimos que : 1- a SOP esta associada com a resistencia a insulina; 2- insulinemia de jejum nao e suficiente para o diagnostico; 3- mulheres obesas com acanthosis nigricans sao mais resistentes a insulina e 4- o uso de um antiandrogenio melhora a...

Ovarian activity before and after gonadal suppression by GnRH-a in patients with polycystic ovary syndrome, hyperandrogenism, hyperinsulinism and acanthosis nigricans

Objective. To investigate the ovarian activity before and after gonadal suppression with GnRH-analog in patients with PCO, hyperandrogenism, hyperinsulinism and ancathosis nigricans. Design: Controlled clinical study. Setting: Tertiary academic medical center. Patients: Six patients with clinical findings of PCO, hirsutism and acanthosis nigricans. Interventions. Morning blood samples in the follicular phase to determine the seteroid levels, glucose and insulin curve, comparing to a control group. Administration for 2 consecutive months of a GnRH-analog, comparing, in the study group, the free testosterone levels before and after ovarian suppression. Main Outcome Measure. Determination of insulin levels in PCO, hirsutism and acanthotic patients and the free-testosterone levels before and after gonadal suppression. Results. Insulin levels were significantly higher in the study group when compared to normal women during the glycemic test. We also found a significant decrease in the free-testosterone levels after 2 months of gonadal suppression with GnRH-analog when compared to the initial time. Conclusions. Patients with PCO, hirsutism and acanthosis nicrigans present high levels of in sulin, suggesting an ovarian hyperesponsiveness, which is not sustained when gonadotrophic blockage was achieved.

Efecto de la metformina sobre la resistencia insulínica en mujeres obesas y obesas hiperandrogénicas / Effects of metformin on insulin resistance in obese and hyperandrogenic women

Background: Metformin is a biguanide often used in obese diabetics that improves tissue sensitivity to insulin. Aim:To assess the effects of metformin on tissue insulin sensitivity in obese and byperandrogenic women. Patients and methods: Eight obese and eight obese and eight and hyperandrogenic women received metformin 850 mg orally during 12 weeks. Before and at the end of the treatment period, an insulin tolerance test to measure insulin sensitivity was performed and blood was drawn to measure sex hormone binding globulin (SHBG), dehydroepiandrosterone sulphate (DHEAS), testosterone, triglycerides, total and HDL cholesterol. The free androgen index was calculated for each sample. Results: After metformin treatment, the insulin sensitivity index improved from 0.38 (0.05-0.5) to 0.43 (0.25-0.59) in obese and hyperandrogenic women. SHBG increased and total cholesterol and triglycerides decreased significantly in both groups. No other significant changes were observed. Conclusions: Metformin has a favorable effect on tissue sensitivity to insulin, SHBG and serum lipids in obese and hyperandrogenic women

Marcadores bioquímicos y métodos de cuantificación de insulinorresistencia en mujeres normales, obesas e hiperandrogénicas / Biochemical markers and methods to assess insulin resistance in normal, obese and hyperandrogenic women

Six normal, 6 obese and 12 hyperandrogenic women of similar ages, were studied. In two consecutive days, the ITT and the IVGTT were performed and a basal blood sample was obtained to measure SHBG, DHEAS and IGFBP-1. Insulin sensitivity was calculated as the blood glucose slope in the ITT and with the minimal model of Bergman in the IVGTT. Insulin sensitivity, measure with ITT was 0.58 (0.53-0.63) in normal, 0.38(0.05-0.59) in obese and 0.20(0.0-0.36) in hyperandrogenic women. The figures for the IVGTT were 7.97(4.1-15.4), 2.41 )0.81-4.89) and 1.1 (0.46-1.88), respectively. Both methods had a positive correlation coefficient of 0.792 (p 0.09). IGFBP-1 values were 3.0, 2.1 and 1.6 ng/ml respectively (p 0.05). DHEAS values were 132, 190 and 206 ug/dl, respectively (ND). ITT is a sample and reliable method to asses insulin sensitivity. SHBG discriminates subjects with different levels of insulin sensitivity

Hiperandrogismo e/ou anovulaçäo crônica de causa näo definida: ênfase no papel da insulina / Hyperandrogenism and or chronic unovulation with undefined cause: enphasis in the insulin rule

Comparamos clinicamente 55 mulheres hirsutas e 45 mulheres sem manifestaçöes de excesso de hormônios androgênios, com o objetivo de avaliar diferenças clínicas na fase do desenvolvimento puberal. Para determinar se existe relaçäo entre insulinemia, nível de androgênio, ciclo menstrual e morfologia ovariana, selecionamos as primeira 27 pacientes hirsutas devido a hiperandrogenismo e/ou anovulaçäo crônica de causa näo definida (15 com ciclos regulares [grupo 1] e 12 com ciclos irregulares [grupo 2]), e realizamos dosagem dos androgênios, nível de insulina (jejum e após 2 horas da ingesta de 75g de dextrosol) e ultra-sonografia pélvica. Consideramos ovários policísticos quando havia mais de 10 cistos periféricos envoltos por estroma aumentado e ovários multicísticos quando havia mais de 10 cistos periféricos sem aumento de estroma. Observamos que as mulheres com hirsutismo tiveram desenvolvimento da menarca e pubarca mais cedo; o hirsutismo e a irregularidade menstrual surgiram na época do desenvolvimento puberal e observamos relaçao entre oligomenorréia nos primeiros ciclos e a persistência da irregularidade até na vida adulta. Considerando apenas as hirsutas com índice de massa corporal (IMC) maior do que 25, observamos que as pacientes do grupo 2 apresentaram maior nível de testoterona, LH e volume ovariano em relaçäo as pacientes do grupo 1. Observamos correlaçao entre testosterona e nsulinemia de jejum. Ovários policísticos foram mais freqëntes no grupo 2 e ovários multicísticos no grupo 1. Concluímos que as pacientes com hirsutismo com ciclos irregulares apresentam uma tendência a apresentarem maior insulinemia e ovários policísticos e as pacientes hirsutas com ciclos regulares menor insulinemia e ovários multicísticos.

Prueba de tolerancia a la insulina: un método útil para determinar resistencia insulínica en mujeres hiperandrogénicas obesas / Insulin tolerance test: a useful method for insulinic resistance determination in obese hyperandrogenic women

Five healthy women aged 27ñ7 years old with a body mass index of 21ñ2 kg/m² and 6 hyperandrogenic women aged 25ñ4 years old with a body mass index of 40ñ5 kg/m² were studied after a 10 hours fast. For the insulin tolerance test, 0.1 U/Kg of crystalline insulin were injected intravenously and blood samples were drawn to measure glucose at -5,0,3,5,10 and 15 min. after the injection. Insulin resistance was calculated using the slope of descending blood glucose levels (SIû). For the intravenous glucose tolerance test, 29 blood glucose samples were obtained after an intravenous injection of 0,3 g glucose/kg followed by an injection of 0.02 U/kg of crystalline insulin. Insulin sensitivity (SI²) was calculated using Bergman's minimal model. Healthy women had a SIû of 0.58 (range 0.53-0.63) and a SI² of 7.9x10-4x min-û/uU/ml (range 4.15-9.11). For hyperandrogenic women were 0.18 (range 0.06-0.29) and 0.9x10-4xmin-û/uU/ml (range 0.46-1.79) respectively. Both methods had a positive correlation coefficient of 0.859 (p<0.001). In conclusion, insulin tolerance test is a good method to measure insulin resistance and has a good correlation with the frequently sampled intravenous glucose tolerance test