Asunto(s)
Fármacos para la Fertilidad Femenina/uso terapéutico , Inducción de la Ovulación/métodos , Ensayos Clínicos Controlados Aleatorios como Asunto/métodos , Estadística como Asunto/métodos , Femenino , Fertilización In Vitro/métodos , Hormona Liberadora de Gonadotropina/análogos & derivados , Hormona Liberadora de Gonadotropina/uso terapéutico , Humanos , Leuprolida/uso terapéuticoRESUMEN
OBJECTIVE: To characterize the phenotype of idiopathic hypogonadotropic hypogonadism due to compound heterozygous GnRHR gene mutations (Arg262Gln/Tyr284Cys). DESIGN: Retrospective review. SETTING: Tertiary medical center. PATIENT(S): Family containing four siblings (three female and one male) with complete idiopathic hypogonadotropic hypogonadism. INTERVENTION(S): Baseline and stimulated laboratory studies. One patient received GnRH treatment and one received human menopausal gonadotropins. MAIN OUTCOME MEASURE(S): Clinical phenotype vs. genotype is assessed by endocrine studies, karyotype, pedigree, and review of pathology slides of ovarian neoplasm. RESULT(S): With GnRH stimulation, two patients with idiopathic hypogonadotropic hypogonadism had maximum LH < 10 mIU/mL, and two others had peak LH > 10 mIU/mL. With repeated GnRH stimulation 24 hours later, gonadotropin levels in all patients were increased. Stimulation of thyroid-releasing hormone and tests for insulin-induced hypoglycemia were normal. One affected patient did not ovulate after GnRH treatment, but her sister ovulated with gonadotropin treatment. Another affected sibling had bilateral oophorectomy for seromucinous cystadenomas, and her hypogonadotropic state remained after castration. The man with idiopathic hypogonadotropic hypogonadism and his unaffected brother had a ring chromosome 21. CONCLUSION(S): All patients with complete idiopathic hypogonadotropic hypogonadism had the same GnRHR mutations, but clinical presentations and endocrinologic responses were heterogeneous. Gonadotropin levels remained low in patients with idiopathic hypogonadotropic hypogonadism after castration, and ring chromosome 21 was present, suggesting that sequences from this chromosome could affect the idiopathic hypogonadotropic hypogonadism phenotype.
Asunto(s)
Hormona Liberadora de Gonadotropina/fisiología , Hipogonadismo/genética , Hipogonadismo/fisiopatología , Adulto , Animales , Células COS , Resistencia a Medicamentos/genética , Femenino , Humanos , Masculino , Mutación Missense , Linaje , Fenotipo , Mutación Puntual , Receptores LHRH/genética , Estudios RetrospectivosAsunto(s)
Endometriosis/patología , Adulto , Endometriosis/diagnóstico , Endometriosis/terapia , Femenino , Humanos , LaparoscopíaRESUMEN
The pituitary gonadotropin follicle stimulating hormone (FSH) interacts with its membrane-bound receptor, to produce biologic effects. Traditional functions of FSH include, follicular development and estradiol production in females and the regulation of Sertoli cell action and spermatogenesis in males. FSHbeta knock-out mice and transgenic mice, serve as models for FSH deficiency and excess, respectively. In addition, mutations of both FSHbeta and FSHR genes have been characterized in humans, although phenotypic effects of the ligand appear to be more profound than those of its receptor. FSH is essential for normal puberty and fertility in females, particularly ovarian follicular development beyond the antral stage. In males, FSH is necessary for normal spermatogenesis and when FSH function is completely absent, infertility occurs. With partial FSH deficiency in males, spermatogenesis is affected, but fertility may still be possible. FSH may also be necessary for normal androgen synthesis in males and females.