Dosages of androgenic hormones in adolescent patients with severe acne

SUMMARY OBJECTIVE Acne vulgaris in female adolescents, when severe or accompanied by other signs of androgenization, may represent a sign of hyperandrogenemia often underdiagnosed, which will have harmful consequences for adult life. The objective of this cross-sectional and retrospective study was to demonstrate the incidence of hormonal changes in the cases of female adolescents with severe or extensive acne, with or without other signs of hyperandrogenism, and propose a hormonal research pattern which should be indicated in order to detect early hyperandrogenemia. METHODS The medical records of 38 female patients aged between 9 and 15 years old with grade II and/or III acne were analyzed. The dehydroepiandrosterone sulfate, dehydroepiandrostenedione, and androstenedione, total testosterone, and dihydrotestosterone sulfate hormones were required prior to initiation of treatment. The hormonal dosages were performed in the serum after at least 3 hours of fasting by means of radioimmunoassay tests. RESULTS Of the 38 patients included, 44.7% presented changes in androgen levels (hyperandrogenemia), and the two most frequently altered hormones were DHEA and androstenedione, with the same incidence (23.6%). CONCLUSIONS The correct and early diagnosis provides an effective and agile approach, including antiandrogen therapy, with the purpose of avoiding the reproductive and metabolic repercussions, besides controlling the inflammatory picture and avoid aesthetic complications.

RESUMO OBJETIVO A acne vulgar em adolescentes do sexo feminino, quando grave ou acompanhada de outros sinais de androgenização, pode representar um sinal de hiperandrogenemia muitas vezes subdiagnosticado, que acarretará consequências danosas para a vida adulta. O objetivo deste estudo transversal e retrospectivo foi demonstrar a incidência das alterações hormonais nos casos de adolescentes do sexo feminino com acne grave ou extensa, acompanhada ou não de outros sinais de hiperandrogenismo e propor um padrão de pesquisa hormonal que deve ser indicado com o intuito de detectar precocemente o quadro de hiperandrogenemia. MÉTODOS Foram analisados os prontuários de 38 pacientes do sexo feminino com idades entre 9 e 15 anos, portadoras de quadro de acne grau II e/ou III. Os hormônios sulfato de dehidroepiandrostenediona, dehidroepiandrostenediona, androstenediona, testosterona total e dehidrotestosterona foram solicitados antes do início do tratamento. As dosagens hormonais foram realizadas no soro após pelo menos 3 horas de jejum por meio de exames de radioimunoensaio. RESULTADOS Das 38 pacientes incluídas, 44,7% apresentaram alterações dos níveis de andrógenos (hiperandrogenemia), sendo que os dois hormônios mais frequentemente alterados foram o DHEA e androstenediona, com a mesma incidência (23,6%). CONCLUSÕES O diagnóstico correto e precoce propicia uma abordagem efetiva e ágil, incluindo a terapia antiandrogênica, com a finalidade de evitar as repercussões reprodutivas e metabólicas, além de controlar o quadro inflamatório e evitar complicações estéticas.

Ovarian Leydig cell tumor in a post-menopausal patient with severe hyperandrogenism / Tumor ovariano de células de Leydig em paciente em pós-menopausa com hiperandrogenismo grave

Leydig cell tumors are rare ovarian steroid cell neoplasms. More than 75% of patients show signs of virilization due to overproduction of testosterone. We report a case of an 8-year-old woman with progressive signs of virilization, and presenting vaginal bleeding. Clinical analyses revealed high levels of serum testosterone, delta 4-androstenedione and estradiol, and also inappropriate low levels of gonadotrophins for a post-menopausal woman. Transvaginal ultrasound showed no evidence of ovarian tumor, but pelvic and abdominal computerized axial tomography imaging revealed a left ovarian solid nodule, and no evidence of alteration in the adrenal glands. Total hysterectomy and bilateral salpingoophorectomy were performed. Histopathology and immunohistochemistry confirmed the diagnosis of Leydig cell tumor. After surgery, androgen levels returned to normal, and there was regression of the signs of virilization.

Tumores ovarianos de células de Leydig são neoplasias raras de células ovarianas esteroidogênicas. Mais de 75% dos pacientes apresentam sinais de virilização devido à produção excessiva de testosterona. Relatamos aqui o caso de uma mulher de 81 anos de idade com sinais progressivos de virilização e ocorrência de sangramento vaginal. As análises clínicas mostraram altos níveis de testosterona sérica, delta 4-androstenediona e estradiol, além de níveis inadequadamente baixos de gonadotrofinas para uma mulher em pós-menopausa. O ultrassom transvaginal não apresentou evidências de tumor ovariano, mas a tomografia axial computadorizada da região pélvico-abdominal mostrou um nódulo sólido no ovário esquerdo e nenhuma evidência de alteração nas adrenais. Foi feita uma histerectomia total e salpingooforectomia bilateral. Os exames histopatológicos e a imuno-histoquímica confirmaram o diagnóstico de tumor de células de Leydig. Após a cirurgia, os níveis de androgênios voltaram ao normal, e os sinais de virilização regrediram.

Participação dos androgênios adrenais na síndrome dos ovários policísticos / Adrenal androgen participation in the polycystic ovary syndrome

OBJETIVO: reavaliar a função adrenal em pacientes com síndrome dos ovários policísticos, após a introdução dos critérios de Roterdã. MÉTODOS: estudo descritivo de corte transversal, incluindo 53 pacientes com média de idade de 26±5,1 anos. Glicose, hemoglobina glicada, lipídios, estradiol, progesterona, 17-OHP4, DHEAS, FSH, LH, TSH, PRL, androstenediona, tiroxina livre, insulina, testosterona total, SHBG e índice de androgênios livres foram estimados. Resistência à insulina, examinada pelo modelo homeostático, foi admitida com índice >2,8. A resposta adrenal à cortrosina foi avaliada pelo incremento hormonal observado após 60 minutos e área sobre a curva. RESULTADOS: entre as 53 pacientes elegíveis, hiperandrogenismo bioquímico foi encontrado em 43 (81,1 por cento). Trinta e três delas, com idade de 25,1±5,0 anos, apresentaram hiperandrogenismo adrenal (62,2 por cento), pesavam 74,9±14,9 kg; tinham IMC de 28,8±6,0 e razão cintura/quadril de 0,8±0,1. DHEAS foi >6,7 nmol/L em 13 (39,4 por cento) e androstenendiona >8,7 nmol/L em 31 (93,9 por cento). Cortisol, 17-OHP4, A e progesterona tiveram incremento de 153 por cento, 163 por cento, 32 por cento e 79 por cento, respectivamente. O modelo usado para avaliar a resistência á insulina foi >2,8 em 14 (42,4 por cento). Não foi encontrada correlação entre as concentrações de insulina ou estradiol com as de cortisol ou androgênios. CONCLUSÕES: a utilização de múltiplos parâmetros hormonais revela alta prevalência de hiperandrogenismo bioquímico na SOP, sendo que as adrenais têm participação em dois terço dos casos. Níveis de estradiol e insulina não influenciam a secreção adrenal de androgênios e cortisol.

PURPOSE: to reassess the adrenal function of patients with PCOS after the introduction of the Rotterdam's criteria. METHODS: descriptive and cross-sectional study including 53 patients 26±5.1 years old. Glucose, glycosylated hemoglobin, lipids, estradiol, progesterone, 17-OHP4, DHEAS, FSH, LH, TSH, PRL, androstenedione, free thyroxine, insulin, total testosterone, SHBG, and free androgen index were measured. Insulin resistance was considered to be present with a homeostatic model assessment index >2.8. The adrenal response to cortrosyn was assessed by the hormonal rise observed at 60 minutes, and by the area under the response curve. RESULTS: biochemical hyperandrogenism was found in 43 of 53 eligible patients (81.1 percent). Thirty-three women had adrenal hyperandrogenism (62.2 percent). The weight of these 33 women, aging 25.1±5.0 years, was 74.9±14.9 kg, BMI was 28.8±6.0 and the waist/hip ratio was 0.8±0.1. DHEAS was >6.7 nmol/L in 13 (39.4 percent) and androstenendione was >8.7 nmol/L in 31 (93.9 percent). The increments in 17-OHP4, cortisol, A, and progesterone were 163 percent, 153 percent, 32 percent, and 79 percent, respectively. The homeostatic insulin resistance model was >2.8 in 14 (42.4 percent). Insulin and estradiol were not correlated with cortisol or androgens. CONCLUSIONS: the use of multiple endocrine parameters showed a high prevalence of biochemical hyperandrogenism in patients with PCOS. Two thirds of the patients had adrenal hyperandrogenism, and estradiol and insulin did not influence adrenal secretion.

Avaliação antropométrica e metabólica de parentes de primeiro grau do sexo masculino de mulheres com síndrome do ovário policístico / Anthropometric and metabolic evaluation of first-degree male relatives of women with polycystic ovary syndrome

OBJETIVO: avaliar as características clínicas e laboratoriais de parentes de primeiro grau do sexo masculino de pacientes com diagnóstico confirmado de síndrome de ovários policísticos (SOP) e comparar os achados com um grupo controle sem história familiar de SOP. MÉTODOS: foram selecionados aleatoriamente 28 homens com idade entre 18 e 65 anos que possuíam parentesco de primeiro grau com mulheres diagnosticadas com SOP e 28 controles pareados por idade, cintura e índice de massa corporal (IMC). RESULTADOS: homens com parentesco de 1º grau com mulheres com SOP comparados ao Grupo Controle apresentaram níveis mais elevados de triglicerídeos (189,6±103,1 versus 99,4±37,1; p<0,0001), HOMA-IR (Homeostase Model Assesment) (3,5±9,1 versus 1,0±1,0; p=0,0077) e glicemia (130,1±81,7 versus 89,5±7,8; p=0,005), além de menores níveis da globulina ligadora de hormônios sexuais (SHBG) (23,8±13,8 versus 31,1±9,1; p=0,003). Os níveis de SHBG se correlacionaram independentemente com os níveis de triglicérides. Os parentes de 1º grau também apresentavam mais sinais clínicos de hiperandrogenismo. CONCLUSÕES: parentes de primeiro grau do sexo masculino das pacientes com SOP apresentam maior grau de dislipidemia e de resistência à insulina, além de níveis mais baixos de SHBG com mais sinais clínicos de hiperandrogenismo. Esses achados sugerem que a resistência à insulina pode ter origem hereditária em indivíduos com história familiar de SOP, independentemente de parâmetros antropométricos.

PURPOSE: to evaluate clinical and laboratory characteristics of first-degree male relatives of patients with a confirmed diagnosis of polycystic ovary syndrome (PCOS) and to compare the findings with a control group with no family history of PCOS. METHODS: we randomly selected 28 male individuals aged 18 to 65 years who were first-degree relatives of women diagnosed with PCOS and 28 controls matched for age, waist and body mass index (BMI). RESULTS: men with 1st degree kinship with women with PCOS had higher levels of triglycerides (189.6±103.1 versus 99.4±37.1, p<0.0001), Homeostasis Model Assessment (HOMA-IR) (3.5±9.1 versus 1.0±1.0, p=0.0077) and glucose (130.1±81.7 versus 89.5±7.8, p=0.005), and lower levels of sex hormone binding globulin (SHBG) (23.8±13.8 versus 31.1±9.1, p=0.003). SHBG levels correlated independently with triglyceride levels. These individuals also had more clinical signs of hyperandrogenism. CONCLUSIONS: male individuals who are first-degree relatives of patients with PCOS have a higher degree of dyslipidemia and insulin resistance, lower levels of SHBG, and more evident clinical signs of hyperandrogenism. These findings suggest that insulin resistance may be of hereditary origin in individuals with a family history of PCOS regardless of anthropometric parameters.

Metformin improves insulin sensitivity and hyperandrogenemia in Egyptian hirsute patients with polycystic ovary syndrome

PCOS is a heterogeneous clinical syndrome characterized by a spectrum of symptomatology, pathology and laboratory findings. It is now accepted that polycystic ovary syndrome has important long-term health implications, including metabolic disorders and increased risk factors for cardiovascular disease like insulin resistance, abdominal obesity, dyslipidemia, hypertension and markers of abnormal vascular function. The aim of this work was to study the effect of metformin on the clinical, metabolic and endocrine parameters in hirsute women secondary to polycystic ovary syndrome. The study was conducted on 30 Egyptian hirsute patients suffering from polycystic ovary syndrome. Clinical examination included anthropometric measurements [BMI and WHR] and Ferriman and Gallwey scoring for hirsutism. Fasting serum insulin and fasting blood glucose were measured from which insulin resistance [IR] was assessed by HOMA. The glucose to insulin ratio [GIR] was calculated. Lipid profile was estimated. Serum luteinizing hormone [LH] and follicle stimulating hormone [FSH] were estimated in the early follicular phase. Total serum testosterone and sex hormone-binding globulin [SHBG] were measured. Ultrasonographgy was done on the pelvis for examination of the ovaries. The patients were instructed to do diet and physical exercise. They received metformin 1500 mg/day for 6 successive months. Clinical, metabolic and endocrine parameters were reevaluated after the medication. A significant 31% improvement in the frequency of the menstrual cycle was observed. Hirsutism improved by 19%. BMI was reduced by 8%. WHR decreased by 2.3%. Insulin resistance decreased by 54%. Total serum cholesterol, LDL-cholesterol, serum triglyceride and total cholesterol/H DL-cholesterol ratio showed slight decrease [3%, 6%, 9% and 9%, respectively], while HDL-cholesterol showed a slight increase by 7%. Total serum testosterone decreased by 32% and LH/FSH ratio improved by 28%. SHBG levels increased by 9%. There was a positive correlation between BMI and HOMA-IR, serum cholesterol and serum TG. There was a highly significant positive correlation between BMI and FBG as well as fasting serum insulin and HOMA-IR. On the other hand, there was a significant negative correlation between BMI and GIR. A highly significant positive correlation was found between BMI and total cholesterol and TG. Also, there was a significant positive correlation between BMI and total cholesterol/HDL-cholesterol ratio. Again, BMI showed a highly significant positive correlation with LH/FSH ratio. There was a highly significant positive correlation between WHR and the frequency of the menstrual cycle and fasting serum insulin. There was a significant positive correlation between WHR and HOMA-IR, serum total cholesterol and TG. There was a significant negative correlation between WHR and SHBG. HOMA-IR showed a significant positive correlation with GIR. Metformin improves insulin sensitivity and hyperandrogenemia in Egyptian hirsute women with polycystic ovary syndrome. This is associated with improvement in menstrual abnormalities. Metformin has additional benefit in reducing hair growth in Egyptian hirsute young women with polycystic ovary syndrome

Testosterona séiica en trastornos hipertensivos del embarazo / Serum testosterone in hypertensive disorders of pregnancy

OBJETIVO: Se ha comunicado asociación de hiperandrogenemia y preeclampsia; además de confirmarlo se pretende dilucidar si también hay esa asociación con embarazadas con hipertensión arterial crónica esencial (HACE). MÉTODOS: 45 mujeres con gestación de tercer trimestre separadas en 3 grupos: 1) 15 normotensas, 2) 16 preeclámpticas, 3) 14 HACE. Se registró edad, paridad, índice de masa corporal (IMC), presión arterial sistólica y diastólica (mm de Hg), proteinuria en 24 horas, semanas de gestación, y niveles séricos de testosterona total (Tt), RIA de testosterona libre (Tl), proteína ligante sexual (SHBG), índice de andrógenos libres (IAL). RESULTADOS: Los 3 grupos estudiados, normotensas, preeclámpticas y HACE, presentaron los siguientes valores séricos, respectivamente: Tt (nmol/L) 2,3±1,4; 5,2±3,0; 1,9±1,5 (p=0,001). IAL (pmol/L) 0,5±0,3; 1,1±0,9; 0,4±0,2 (p=0,001). No hubo diferencias significativas en Tl (pmol/L) 7,2±4,7; 7,39±4,5; 4,5±2,6; ni en SHBG (nmol/L) 468±112; 503±134; 512±96. CONCLUSIONES: Las embarazadas con HACE presentaron niveles séricos de Tt y de IAL similares a las embarazadas normotensas. En cambio, las mujeres con preeclampsia presentaron niveles de Tt sérica e IAL claramente aumentados en comparación con las embarazadas normotensas. Se concluye que existiría una asociación de hiperandrogenemia con preeclampsia; asociación que no fue encontrada en embarazadas con HACE.

OBJECTIVE: Association between hyperandrogenemia and preeclampsia was communicated. This study was designed to explain if also there is association between hyperandrogenemia and pregnant with essential chronic arterial hypertension (HACE). METHODS: To 45 women with gestation of third trimester were separated in 3 groups: 1) normal arterial pressure (n=15), 2) preeclampsia (n=16), 3) HACE (n=14). It was registered age, parity, body mass index (IMC), systolic and diastolic arterial pressure (mm of Hg), proteinuria in 24 h, weeks of gestation, and seric level of total testosterone (Tt), free testosterone (Tl), free androgen index (IAL). RESULTS: The studied groups, normal arterial pressure, preeclampsia, and HACE, displayed the following serics values, respectively: Tt (nmol/L) 2.3±1.4; 5.2±3.0; 1.9±1.5; (p=0.001). IAL (pmol/L) 0.5±0.3; 1.1±0.9; 0.4±0.2; (p=0.001). Not significant differences were found in: Tl (pmol/L) 7.2±4.7; 7.4±4.5; 4.5±2.6. SHBG (nmol/L) 468±112; 503±134; 512±96. CONCLUSIONS: The pregnant women with HACE presented similar seric level of T than pregnant women with normal arterial pressure. However, the women with preeclampsia displayed significant increased levels of seric Tt and increased IAL. We conclude that the association observed of hyperandrogenemia with preeclampsia was not found in pregnant with HACE.