RESUMEN
PURPOSE: To investigate predictors of testicular response and non-reproductive outcomes (height, body proportions) after gonadotropin-induced puberty in congenital hypogonadotropic hypogonadism (CHH). DESIGN: A retrospective analysis of the puberty induction in CHH male patients, undergoing an off-label administration of combined gonadotropin (FSH and hCG). METHODS: Clinical and hormonal evaluations before and during gonadotropin stimulation in 19 CHH patients genotyped by Targeted Next Generation Sequencing for CHH genes; 16 patients underwent also semen analysis after gonadotropins. RESULTS: A lesser increase in testicular volume after 24 months of induction was significantly associated with: (I) cryptorchidism; (II) a positive genetic background; (III) a complete form of CHH. We found no significant correlation with the cumulative dose of hCG administered in 24 months. We found no association with the results of semen analyses, probably due to the low numerosity. Measures of body disproportion (eunuchoid habitus and difference between adult and target height: deltaSDSth), were significantly related to the: (I) age at the beginning of puberty induction; (II) duration of growth during the induction; (III) initial bone age. The duration of growth during induction was associated with previous testosterone priming and to partial forms of CHH. CONCLUSIONS: This study shows that a strong genetic background and cryptorchidism, as indicators of a complete GnRH deficiency since intrauterine life, are negative predictors of testicular response to gonadotropin stimulation in CHH. Body disproportion is associated with a delay in treatment and duration of growth during the induction, which is apparently inversely related to previous androgenization.
Asunto(s)
Estatura/efectos de los fármacos , Gonadotropina Coriónica/uso terapéutico , Criptorquidismo , Hormona Folículo Estimulante/uso terapéutico , Predisposición Genética a la Enfermedad , Hipogonadismo , Adulto , Criptorquidismo/diagnóstico , Criptorquidismo/etiología , Relación Dosis-Respuesta a Droga , Disgenesia Gonadal/tratamiento farmacológico , Disgenesia Gonadal/etiología , Gonadotropinas/uso terapéutico , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Humanos , Hipogonadismo/congénito , Hipogonadismo/genética , Hipogonadismo/terapia , Masculino , Pubertad/efectos de los fármacos , Salud Reproductiva/estadística & datos numéricos , Análisis de Semen/métodos , Análisis de Semen/estadística & datos numéricos , Testículo , Tiempo de Tratamiento/normasRESUMEN
OBJECTIVE: To verify the antagonistic effect of Bushen Tianjing Recipe (BTR) on environmental endocrine disruptors (EEDs) induced gonadal dysgenesis (GD) Sprague-Dawley (SD) male rat model. METHODS: Totally 70 3-week-old male SD rats were randomly divided into seven groups, i.e., the control group (fed with corn oil), the model A group [di-2-ethylhexyl-phthalate (DEHP) 500 mg/kg], the CM A group (fed with DEHP 500 mg/kg + BTR 40 mL/kg), the exposed group B (fed with CYP 80 mg/kg), the CM B group (fed with CYP 80 mg/kg + BTR 40 mL/kg), the model C group [fed with DEHP 500 mg/kg + CYP 80 mL/kg], the CM C group (DEHP 500 mg/kg + CYP 80 mg/kg + BTR 40 mL/kg), respectively, 10 in each group. All were administered with corresponding medication by gastrogavage, once daily, for total 30 days. Rats were killed 24 h after the last administration, and their body weight and wet testis weight were weighed. The coefficient of testis was calculated. The serum testosterone (T) level was measured by chemiluminescent immunoassay. The histopathologic tissue was prepared. The ultrastructural changes of genital cells were observed by electron microscope. RESULTS: Compared with the control group, there was no statistical difference in the body weight increase among all groups (P > 0.05). The time of testicular descent and preputial separation were significantly delayed in each exposed group (P < 0.01). In the exposed group A and the exposed group C, the wet weight of the testes was reduced and serum T level decreased (P < 0.01). The coefficient of testis significantly decreased in the exposed group A (P < 0.01). Compared with corresponding model group, the time of testicular descent and preputial separation were significantly fore-laid in each corresponding CM group (P < 0.01). The weight of the testes, the coefficient of testis, and the serum T level increased in the CM A group (P < 0.01). The serum T level obviously increased in the CM B group (P < 0.05). CONCLUSIONS: The GD rat model was successfully duplicated by using DEHP. EEDs were proved to have significant anti-androgen activities. BTR was verified to have significant antagonistic to its anti-androgen effect.
Asunto(s)
Medicamentos Herbarios Chinos/uso terapéutico , Disruptores Endocrinos/toxicidad , Disgenesia Gonadal/tratamiento farmacológico , Fitoterapia , Animales , Dietilhexil Ftalato/toxicidad , Disgenesia Gonadal/inducido químicamente , Masculino , Ratas , Ratas Sprague-Dawley , Testosterona/sangreRESUMEN
Systemic lupus erythromatosus (SLE) is an autoimmune disease, which affects mainly women in the reproductive age and is influenced by hormonal changes. Therefore, hormone supplementation for patients with SLE either as contraceptives or as postmenopausal supplementation remains a controversial issue. Herein, we report a case of a 22-year-old woman with a history of ovarian agenesis, treated for several years with hormone therapy in order to reduce the risk of osteoporosis and other estrogen-deficient disorders. At the current evaluation, she met 3 of 11 diagnostic criteria for SLE along with a strong familial autoimmune predisposition. Precipitation of SLE in patients treated with hormonal therapy has been previously described. This prompted us to seek alternative drug therapies that prevent both the onset of overt SLE as well as the progression of estrogen-deficient phenomena. This unique case illustrates the dilemma of using hormone therapy in patients at risk to develop SLE and the current therapeutic alternatives.
Asunto(s)
Terapia de Reemplazo de Estrógeno/métodos , Estrógenos , Disgenesia Gonadal/tratamiento farmacológico , Lupus Eritematoso Sistémico/diagnóstico , Ovario/anomalías , Contraindicaciones , Progresión de la Enfermedad , Sustitución de Medicamentos , Estrógenos/efectos adversos , Femenino , Disgenesia Gonadal/complicaciones , Humanos , Lupus Eritematoso Sistémico/inducido químicamente , Lupus Eritematoso Sistémico/complicaciones , Medición de Riesgo , Factores de Riesgo , Adulto JovenRESUMEN
In oocyte donation cycles where hormone replacement is given to recipients, progesterone administration is necessary to induce the luteal phase and synchronize the endometrium with the embryo stage. Most studies suggest that 5-7 days of progesterone are needed to prepare the endometrium for a day-5 embryo transfer and provide optimal implantation rate. This paper reports a case where an agonadal oocyte recipient received only 2 days of progesterone prior to the embryo transfer of a day-5 embryo. She subsequently had a clinical pregnancy and a live birth.
Asunto(s)
Transferencia de Embrión , Disgenesia Gonadal/tratamiento farmacológico , Infertilidad Femenina/terapia , Donación de Oocito , Progesterona/administración & dosificación , Progestinas/administración & dosificación , Adulto , Ectogénesis , Implantación del Embrión/efectos de los fármacos , Femenino , Disgenesia Gonadal/fisiopatología , Humanos , Infertilidad Femenina/etiología , Nacimiento Vivo , Cumplimiento de la Medicación , Embarazo , Progesterona/uso terapéutico , Progestinas/uso terapéutico , Factores de TiempoRESUMEN
The Müllerian inhibiting factor (MIF) is responsible for regression of Müllerian ducts during male sexual differentiation. Mutations in MIF or its type II receptor lead to persistence of the uterus and Fallopian tubes in male children--i.e., persistent Müllerian duct syndrome (PMDS). Both are rare autosomal recessive disorders. We report a 7-month-old male infant who underwent inguinal herniorrhaphy. Remnants of vas deferens and gonads with macroscopic characteristics of ovaries, along with Fallopian tubes and a rudimentary uterus, were found. Karyotype confirmed male sex. Molecular genetics revealed the most frequent MIF type II receptor gene mutation--27 bp deletion. Investigation of the older brother presenting bilateral cryptorchidism at 7 years of age led to similar clinical findings and the same mutation. We report here an MIF type II receptor mutation in two brothers, with the particularity that the surgical findings in the younger son initiated the diagnostic process in both children.
Asunto(s)
Criptorquidismo/genética , Disgenesia Gonadal/genética , Mutación , Receptores de Péptidos/genética , Receptores de Factores de Crecimiento Transformadores beta/genética , Secuencia de Bases , Niño , Criptorquidismo/cirugía , Disgenesia Gonadal/tratamiento farmacológico , Disgenesia Gonadal/cirugía , Humanos , Lactante , Masculino , Isoformas de Proteínas , Eliminación de Secuencia , Hermanos , SíndromeRESUMEN
This is a report of a 16 year-old 46,XY male who was reassigned female and had feminizing surgery during infancy because of what was judged to be inadequate genital masculinization. This patient had a dysgenetic testis that was shown to be producing testosterone during infancy. Although initially the reassignment appeared to be successful, psychological problems became progressively more severe during childhood to incapacitation by age 10 years. After it was verified that he had a male sexual identity, reassignment as male began, initially by living as a boy, then with testosterone therapy. Staged phalloplasty surgery was begun at age 16 years. Currently he has an adult-sized penis, although its function is not yet clear. Sadly, none of the steps to align his sex assignment to his perception as male has significantly alleviated his psychological issues and he continues to be severely impaired and socially compromised. Major issues include the crippling psychiatric disease that is resistant to psychotherapy and surgical problems with phalloplasty after surgery at infancy that involved reduction of the phallus with recession of the glans to the typical clitoral location. The glans was left intact at the anterior base of the phallus. Genital responsiveness during sexual activity and satisfaction are as yet unknown.
Asunto(s)
Conducta del Adolescente , Trastornos de la Conducta Infantil/etiología , Identidad de Género , Genitales Masculinos/anomalías , Disgenesia Gonadal/psicología , Transexualidad/complicaciones , Adaptación Psicológica , Adolescente , Niño , Trastornos de la Conducta Infantil/psicología , Femenino , Genitales Masculinos/cirugía , Disgenesia Gonadal/tratamiento farmacológico , Disgenesia Gonadal/cirugía , Humanos , Masculino , Testosterona/uso terapéutico , Transexualidad/tratamiento farmacológico , Transexualidad/psicología , Transexualidad/cirugíaRESUMEN
A prospective, multicenter study of patients with Ullrich-Turner syndrome (UTS) was conducted to estimate the prevalence of autoantibodies to tissue transglutaminase (tTg), thyroid stimulating hormone receptor (TSH-R), thyroglobulin (TG) and thyroid peroxidase (TPO) in relation to adult height after long-term growth hormone (GH) treatment. Out of 347 near-adult (> 16 years) patients with UTS from 96 German centers, whose longitudinal growth was documented within the Pharmacia International Growth Study (KIGS), 188 returned for a standardized follow-up visit at a median chronological age of 18.7 (16.0-23.6) years (bone age > 15 years). Serum samples of 120 patients were obtained for central measurements of TSH, thyroxine (T4) and free T4 and autoantibodies by standard immunoassays. Information regarding thyroid disease, karyotype and anthropometric data was extracted from the KIGS database. Thirty-six percent of the patients with UTS had positive TG and/or TPO autoantibodies and 4% had positive tTg autoantibodies, whereas 2% had positive TG and/or TPO autoantibodies as well as positive tTg autoantibodies. TSH-R autoantibodies were undetectable in all patients. The detection of autoantibodies was unrelated to a specific karyotype. Median height standard deviation scores (SDS, UTS) at start of GH treatment (0.43; -1.07, 1.85) and at follow-up (1.36; -0.11, 2.57) were comparable in all patients independent of their antibody status. The total deltaheight SDS, however, was higher in patients with negative autoantibody titers (1.08; -0.03, 2.25) compared to those with positive antibody titers (0.68; -0.44, 1.82; p < 0.01). Our study confirms the high prevalence of autoantibodies in patients with UTS predisposing them to autoimmune thyroid disease and celiac disease, and indicates for the first time that autoimmune pathologies may interfere with GH therapy and thus compromise final height. Therefore, medical care for patients with UTS should routinely include screening for these autoimmune disorders in order to assure early detection and appropriate treatment.
Asunto(s)
Autoanticuerpos/sangre , Estatura/inmunología , Enfermedad Celíaca/inmunología , Hormona de Crecimiento Humana/uso terapéutico , Síndrome de Turner/tratamiento farmacológico , Síndrome de Turner/inmunología , Adolescente , Adulto , Antropometría , Enfermedad Celíaca/sangre , Enfermedad Celíaca/complicaciones , Aberraciones Cromosómicas , Cromosomas Humanos X , Femenino , Estudios de Seguimiento , Disgenesia Gonadal/sangre , Disgenesia Gonadal/complicaciones , Disgenesia Gonadal/tratamiento farmacológico , Disgenesia Gonadal/inmunología , Humanos , Inmunoglobulinas Estimulantes de la Tiroides , Yoduro Peroxidasa/inmunología , Cariotipificación , Estudios Prospectivos , Receptores de Tirotropina/sangre , Estadísticas no Paramétricas , Tiroglobulina/inmunología , Tiroiditis Autoinmune/sangre , Tiroiditis Autoinmune/complicaciones , Tiroiditis Autoinmune/inmunología , Transglutaminasas/inmunología , Síndrome de Turner/sangre , Síndrome de Turner/complicacionesRESUMEN
Triple-X female characterized by primary amenorrhea and pure gonadal dysgenesis is extremely rare. We present a patient of triple-X syndrome who has not had menarche or the development of the secondary sexual characteristics. She had a hypoplastic uterus and streaked gonads on both sides with a twisted mucinous cystadenoma in the right adnexa.
Asunto(s)
Cromosomas Humanos X , Cistoadenoma Mucinoso/diagnóstico , Disgenesia Gonadal/complicaciones , Neoplasias Ováricas/diagnóstico , Aberraciones Cromosómicas Sexuales , Dolor Abdominal/etiología , Adolescente , Cistoadenoma Mucinoso/complicaciones , Estrógenos/uso terapéutico , Estrógenos Conjugados (USP)/uso terapéutico , Femenino , Disgenesia Gonadal/tratamiento farmacológico , Humanos , Neoplasias Ováricas/complicaciones , Anomalía Torsional/complicacionesRESUMEN
Gonadal dysgenesis with female phenotype is defined as the absence or insufficient development of the ovaries. Hypogonadism or impuberism are variable, depending on the degree of gonadal development. Mayer-Rokitansky-Küster-Hauser syndrome is a rare malformative anomaly (1/5000 women) associating uterine and vaginal aplasia with normal ovaries. We report the case of a 19-year-old woman who presented primary amenorrhea and impuberism. Hormone assay revealed hypergonadotrophic hypogonadism. The karyotype was normal, 46XX. Internal genitalia could not be identified on the pelvic ultrasound. Laparoscopy was undertaken and revealed concomitant ovarian dysgenesis and Mayer-Rokitansky-Küster-Hauser syndrome. There were no other morphological malformations. An association between these two conditions is very exceptional and appears to be coincidental, independent of chromosomal anomalies. Hormone substitution therapy remains the only therapeutic option. Hormone substitution is aimed at triggering the development of secondary sexual characters and prevent osteoporosis. There remains the unsolved problem of infertility.
Asunto(s)
Disgenesia Gonadal/complicaciones , Útero/anomalías , Vagina/anomalías , Adulto , Femenino , Disgenesia Gonadal/tratamiento farmacológico , Terapia de Reemplazo de Hormonas , Humanos , Hipogonadismo/complicaciones , Cariotipificación , Ovario/anomalías , SíndromeRESUMEN
The Mixed Gonadal Dysgenesis represents the 7.6% of all our patients with intersexual states. We report 14 patients who present Mixed Gonadal Dysgenesis. We have studied: diagnosis age; external genitalia description; sex assigned in birth and if has changed; the karyotype; sex chromatine; hormonal study; genitography; internal genitalia and internal Mullerians ducts structures; gonadal histologycal study; surgical treatment and hormonal treatment. The results show that 50% of the cases presents a 46XY karyotype and the other 50% mosaicisme 45XO/46XY. The histological study is very distinctive. A vulvovagynoplasty and clitoroplasty was made in all the cases. Four patients must follow an hormonal treatment after reaching puberal age. Summing up, with patients having ambiguous genitalia we can suspect it consists of a Mixed Gonadal Dysgenesis. The diagnosis must be precocious. And this diagnosis will be based in an ambiguous genitalia, with a karyotype 46XY or 45XO/46XY, the persistence of the internal Müllerian duct structures, and the histological study with a dysgenetic testis. These patients should be raised as females because they can obtain a good morphological and functional development like a normal female.
Asunto(s)
Disgenesia Gonadal/tratamiento farmacológico , Disgenesia Gonadal/cirugía , Hormonas Esteroides Gonadales/uso terapéutico , Preescolar , Terapia Combinada , Femenino , Identidad de Género , Genitales/cirugía , Gonadoblastoma/patología , Gonadoblastoma/cirugía , Humanos , Lactante , CariotipificaciónRESUMEN
The aim of this analysis is to evaluate the gonadal function in children with true undescended testes and in those with retractile testes, in order to verify a possible impairment of the testicular steroidogenesis due to the permanent or transitory anomalous position of the gonad outside the scrotum. The authors carried out a prospective study on 29 prepubertal children affected by true undescended testes (monolateral in 20 cases and bilateral in 9), as well as on 25 prepubertal children with retractile testes (monolateral in 10 cases and bilateral in 15), assaying the testosterone (T) levels, basal and 72 hours after stimulus with human chorionic gonadotrophin (HCG) administered in a single dose of 100 U/kg i.m. Further-more, to verify the hypothesis of a possible progressive reduction of the Leydig cells function, particularly in the gonads bilaterally affected, the authors also evaluated the testosterone response to gonadotrophic stimulus compared to age (> 0 < 4 years). This study in agreement with data already published, confirms the normality of gonadal function both in children with mono or bilateral true undescended testes and in those with retractile testes. The lower the age of the subject the higher is the peak of testosterone after stimulus, confirming the active steroidogenesis of the gonads in infants and small children and sustaining the "non quiescence" of this organ during infancy, even in cases of true undescended testes.
Asunto(s)
Gonadotropina Coriónica/uso terapéutico , Criptorquidismo/tratamiento farmacológico , Hormonas Testiculares/biosíntesis , Testosterona/sangre , Factores de Edad , Niño , Preescolar , Criptorquidismo/sangre , Disgenesia Gonadal/sangre , Disgenesia Gonadal/tratamiento farmacológico , Humanos , Lactante , Masculino , Hormonas Testiculares/sangre , Testosterona/biosíntesisRESUMEN
Seventy-nine patients with sexual development retardation were examined, 24 of these suffered from ovarian genesis condition and 55 from central genesis condition. The findings evidence that detection of the uterus and gonads presenting as cords is one of the diagnostic criteria indicating gonadal dysgenesis. Echographic examinations carried out over the course of therapy yield a more accurate picture of ovarian function. No increase in uterine size on the echogram after discontinuation of hormonal therapy and the appearance of follicles in the ovaries after treatment point to normally functioning ovaries and helps specify the origin of sexual development retardation. In sexual development retardation of a central origin ultrasonic scanning helps assess the therapy efficacy and predict its outcome.
Asunto(s)
Disgenesia Gonadal/diagnóstico por imagen , Hipogonadismo/diagnóstico por imagen , Pubertad Tardía/diagnóstico por imagen , Maduración Sexual/fisiología , Adolescente , Niño , Congéneres del Estradiol/uso terapéutico , Femenino , Disgenesia Gonadal/tratamiento farmacológico , Disgenesia Gonadal/fisiopatología , Humanos , Hipogonadismo/tratamiento farmacológico , Hipogonadismo/fisiopatología , Ovario/diagnóstico por imagen , Ovario/efectos de los fármacos , Ovario/fisiopatología , Pubertad Tardía/tratamiento farmacológico , Pubertad Tardía/fisiopatología , Maduración Sexual/efectos de los fármacos , Ultrasonografía/métodos , Útero/diagnóstico por imagen , Útero/efectos de los fármacos , Útero/fisiopatologíaRESUMEN
Eleven teenage boys with bilateral anorchia and 12 with gonadotrophin deficiency were treated by injections of testosterone ester (enanthate) at an initial dose of 100 mg every six to eight weeks, rising to 250 mg every four weeks after three to four years. In the anorchic boys average adult height was 177.1 cm, compared with a mean mid-parental height of 174.4 cm, and mean predicted adult heights of 177.0 cm (Tanner-Whitehouse method) and 178.0 cm (Bayley-Pinneau method). In the patients with gonadotrophin deficiency, mean adult height was 176.9 cm, compared with a mean mid-parental height of 176.1 cm, and mean predicted adults heights of 174.0 cm (Tanner-Whitehouse method) and 177.3 cm (Bayley-Pinneau method). We conclude that this testosterone regimen allows achievement of full growth potential in such patients.
Asunto(s)
Disgenesia Gonadal/tratamiento farmacológico , Gonadotropinas/deficiencia , Testículo/anomalías , Testosterona/uso terapéutico , Adolescente , Adulto , Estatura/efectos de los fármacos , Niño , Preparaciones de Acción Retardada , Crecimiento/efectos de los fármacos , Humanos , Masculino , Pubertad Tardía/tratamiento farmacológico , Estudios RetrospectivosRESUMEN
A successful triplet gestation in a 45,X/46,XY woman is presented. A previously hypoplastic uterus was prepared for implantation by exogenous hormone replacement. Conception was achieved through in vitro fertilization of donor oocytes and transfer of four embryos into a hormonally primed endometrium. This case illustrates that some women with 45,X/46,XY karyotype can have a successful triplet pregnancy. Therefore, a conservative approach during gonadectomy in patients with a Y chromosome may be warranted.
Asunto(s)
Fertilización In Vitro/métodos , Disgenesia Gonadal , Mosaicismo , Embarazo Múltiple , Adulto , Estrógenos/uso terapéutico , Femenino , Disgenesia Gonadal/tratamiento farmacológico , Disgenesia Gonadal/cirugía , Humanos , Embarazo , Embarazo Múltiple/sangre , Progesterona/uso terapéutico , Trillizos , Útero/anomalías , Útero/efectos de los fármacosRESUMEN
Cyclic replacement therapy using estrogen and progesterone was instituted in 28 patients with gonadal dysgenesis and 13 patients with hypopituitarism. When estriol was given at a dose of 2 mg per day, 10 patients (9 gonadal dysgenesis and 1 hypopituitarism) developed hyperreninemia and 3 of the 10 patients (all gonadal dysgenesis) were associated with hypertension. These side effects subsided within 6 months when the therapy was discontinued or the dose of estriol was decreased to 1 mg per day in addition to beta-blocker. Hypercholesterolemia was observed in 8 patients, but not related to high blood pressure. Attention should be paid to plasma renin activity and blood pressure when estrogen and progesterone are given for the development of genitalia in patients with gonadal dysgenesis.
Asunto(s)
Estriol/efectos adversos , Disgenesia Gonadal/tratamiento farmacológico , Hipertensión/inducido químicamente , Hipopituitarismo/tratamiento farmacológico , Progesterona/efectos adversos , Renina/sangre , Adolescente , Adulto , Presión Sanguínea/efectos de los fármacos , Quimioterapia Combinada , Estriol/administración & dosificación , Femenino , Disgenesia Gonadal/sangre , Humanos , Hipopituitarismo/sangre , Cariotipificación , Progesterona/administración & dosificaciónRESUMEN
Fifteen years' experience in a Menstrual Disorder Clinic revealed that gonadal dysgenesis was the commonest cause of primary amenorrhoea. Investigations using Barr Body study and laparoscopic examination were unsatisfactory and inaccurate. The invasive nature of laparoscopy was the likely principal cause for the high default rate in the early years of the Clinic. The availability of hormone radioimmunoassay and cytogenetic study has improved the diagnostic acuity. Gonadal malignancy associated with the "Y" chromosome could also be identified at its early stage. Oestrogen replacement therapy has been found to be beneficial and is associated with little side effects and no endometrial pathology has been identified.