RESUMO
To investigate the nature of neuroendocrine disturbances of the hypothalamo-pituitary-gonadal axis in idiopathic male infertility, we studied 14 infertile men with oligoasthenozoospermia (OLIGO) and 15 age-, body mass index-, and community-matched euspermic controls by blood withdrawal at 10-min intervals for 12 h to encompass basal (8-h) and exogenous GnRH-stimulated (4-h) pulsatile release of LH and FSH (by immunoradiometric assay) as well as testosterone (by RIA). Deconvolution analysis was used to estimate endogenous LH and FSH half-lives, secretory burst frequency, amplitude, duration, and mass. OLIGO men exhibited normal serum concentrations of total, free, and percent dialyzable testosterone and estradiol, but distinct dynamic alterations within the LH and FSH axes; namely (P < 0.05), 1) a prolonged half-life of LH (OLIGO, 95 +/- 19 min; control, 80 +/- 9.3 min) and a reduced half-life of FSH (OLIGO, 260 +/- 79 min; control, 320 +/- 93 min); 2) a low LH, but normal FSH, secretory burst frequency (OLIGO, 12 +/- 3.4; control, 15 +/- 3.0 LH pulses/day); 3) a decreased serum testosterone peak frequency (OLIGO, 16 +/- 4.3; control, 21 +/- 3.2 peaks/day); and 4) an amplified mass of LH (1.1- to 1.3-fold higher in OLIGO) and FSH (2.4- to 2.7-fold higher in OLIGO) secreted per burst basally as well as after GnRH injection. These disturbances were readily distinguishable from the neuroendocrine dysregulation described in other states of male hypogonadotropism (e.g. uremia, fasting, and aging).
Assuntos
Hormônio Foliculoestimulante/metabolismo , Infertilidade Masculina/fisiopatologia , Hormônio Luteinizante/metabolismo , Oligospermia/fisiopatologia , Periodicidade , Adulto , Hormônio Liberador de Gonadotropina , Humanos , Masculino , Testosterona/metabolismoRESUMO
OBJECTIVE: To explore the clinical usefulness of the antiandrogen flutamide in the treatment modality for hirsutism in women. DESIGN: Nine women with hirsutism were assessed before and then monthly for 3 months on a regimen of flutamide 250 mg three times a day as the sole therapeutic agent. Blood samples were taken at each assessment time for a battery of androgenic parameters. SETTING: Patients were followed in the Out-Patient Department of the Hospital das Clinicas, Sao Paulo, Brazil. Hormonal assays were performed in the Hormone Laboratories of Hospital das Clinicas and the Endocrine Research Laboratory at Newark Beth Israel Medical Center, Newark, New Jersey. PATIENTS: Nine women with moderate hirsutism were treated with flutamide. Six women were previously diagnosed as having idiopathic hirsutism, and three women were diagnosed as having polycystic ovary syndrome. INTERVENTION: All women were treated with flutamide 250 mg three times a day for 3 months. MAIN OUTCOME MEASURE: Improvement of hirsutism was assessed using the Ferriman-Gallwey hair density index. Side effects of drug therapy (deterioration of menses and dry skin) were explored. Androgen parameters included testosterone (T), sex hormone-binding globulin, bound, nonbound, and free T, androstanediol glucuronide, and others. RESULTS: After 3 months of flutamide alone, Ferriman-Gallwey scores improved in seven of nine women with mean scores decreasing from 28.1 +/- 0.6 to 24.5 +/- 0.6. None of the androgenic parameters changed during this period of time. Follicle-stimulating hormone and luteinizing hormone response to gonadotropin-releasing hormone was unchanged after flutamide. CONCLUSION: Flutamide favorably influenced hirsutism in women, with differences noted after only 3 months of therapy. More prolonged and detailed studies of this drug as the sole therapeutic agent for treatment of hirsutism seems warranted.
Assuntos
Flutamida/uso terapêutico , Hirsutismo/tratamento farmacológico , Adulto , Análise de Variância , Androstano-3,17-diol/análogos & derivados , Androstano-3,17-diol/sangue , Androstenodiona/sangue , Desidroepiandrosterona/análogos & derivados , Desidroepiandrosterona/sangue , Sulfato de Desidroepiandrosterona , Estradiol/sangue , Feminino , Hirsutismo/sangue , Hirsutismo/etiologia , Humanos , Síndrome do Ovário Policístico/diagnóstico , Globulina de Ligação a Hormônio Sexual/metabolismo , Testosterona/sangue , Resultado do TratamentoRESUMO
Cyproterone acetate given as a single intramuscular dose of 300 mg monthly for 6 months resulted in significant reduction of hirsutism without appreciable side effects. This regimen resulted in decreased levels of luteinizing hormone (LH) and estradiol in the eight women studied. No significant changes were observed in total serum testosterone (T) levels, however, there was a reduction in sex hormone binding globulin (SHBG), resulting in lowered SHBG-bound T, and an increase in non-SHBG-T over this time. Serum androstanediol glucuronide levels decreased in three of four women, although not to normal levels.