RESUMO
Melatonin acting through the hypothalamus and pituitary regulates testicular function. In addition, direct actions of melatonin at the testicular level have been recently suggested. We have described that melatonin inhibits androgen production in hamster Leydig cells via melatonin subtype 1a (mel1a) receptors and the local corticotrophin-releasing hormone (CRH) system. The initial events of the melatonin/CRH signalling pathway have also been established. Melatonin and all components of the melatonergic/CRH system were also detected in Leydig cells of infertile men. This study attempted to search for additional targets of melatonin in the human testis, and to investigate the effects of melatonin on proliferation and the oxidative state in these novel target cells. To this aim, evaluation of human testicular biopsies of patients suffering from hypospermatogenesis or Sertoli cell only syndrome and cell culture studies were performed. Melatonergic receptors were found in macrophages (MACs) and mast cells (MCs) of the human testis. In biopsies of patients suffering idiopathic infertility, melatonin testicular concentrations were negatively correlated with MAC number per mm(2) and TNFα, IL1ß and COX2 expression, but positively correlated with the expression of the anti-oxidant enzymes SOD1, peroxiredoxin 1 and catalase. Melatonin inhibited proliferation and the expression of pro-inflammatory cytokines and cyclooxygenase 2 (COX2) in both the human non-testicular THP-1 MAC cell line and primary cell cultures of hamster testicular MACs. In the human HMC-1 MC line, melatonin increased the expression of anti-oxidant enzymes and decreased reactive oxygen species (ROS) generation. The results reveal new testicular targets of melatonin and describe anti-proliferative and anti-inflammatory effects of this hormone on testicular MACs. Furthermore, melatonin might provide protective effects against oxidative stress in testicular MCs.
Assuntos
Infertilidade Masculina/metabolismo , Macrófagos/metabolismo , Mastócitos/metabolismo , Melatonina/metabolismo , Testículo/metabolismo , Adulto , Androgênios/biossíntese , Animais , Anti-Inflamatórios , Antioxidantes/metabolismo , Azoospermia/metabolismo , Catalase/biossíntese , Linhagem Celular , Proliferação de Células , Hormônio Liberador da Corticotropina/metabolismo , Cricetinae , Ciclo-Oxigenase 2/biossíntese , Humanos , Interleucina-1beta/biossíntese , Células Intersticiais do Testículo/metabolismo , Macrófagos/citologia , Masculino , Mastócitos/citologia , Oligospermia/metabolismo , Estresse Oxidativo , Peroxirredoxinas/biossíntese , Espécies Reativas de Oxigênio/análise , Receptores de Melatonina/antagonistas & inibidores , Receptores de Melatonina/metabolismo , Síndrome de Células de Sertoli/metabolismo , Transdução de Sinais , Superóxido Dismutase/biossíntese , Superóxido Dismutase-1 , Fator de Necrose Tumoral alfa/biossínteseRESUMO
Una consecuencia clínica de la deficiencia de testosterona en el varón es el descenso de la densidad mineral ósea (DMO), asociado a mayor riesgo de fractura (con la consiguiente morbi-mortalidad en el hombre añoso), y cambios de la composición y el contenido de calcio corporal total. Para cuantificar los efectos de la androgenoterapia sobre la composición corporal y el contenido de calcio corporal, correlacionar los cambios hormonales con los densitométricos y de la composición corporal, y constatar posibles diferencias densitométricas regionales, se incluyeron 15 varones hipogonádicos. Se determinaron variables antropométricas, bioquímicas, densitométricas y de la composición corporal en condiciones basales y bajo la terapia sustitutiva. Como resultado, se logró compensar el déficit androgénico y duplicar la concentración de estradiol. El eugonadismo inducido incrementó la DMO como el contenido del calcio corporal total. Además, redujo el porcentaje de masa grasa corporal total (principalmente abdominal) y aumentó la masa muscular corporal total, con incremento de la relación masa magra/masa grasa, sin cambios del índice de masa corporal. En conclusión, nuestros resultados afirman el papel preponderante de los esteroides sexuales sobre la composición corporal y su rol en el hueso. El hipogonadismo masculino constituye un factor de riesgo para osteoporosis y enfermedad cardiovascular.
A clinical consequence of testosterone deficiency in males is the reduction of bone mineral density (BMD), associated with a higher risk of fracture (and a subsequent increase in morbi-mortality in elderly men) and with changes in body composition and total body calcium content. In order to quantify the effects of androgen therapy on body composition and body calcium content, and to correlate changes in hormone levels with densitometric changes and changes in body composition changes, as well as to determine potential regional densitometric differences, 15 hypogonadal men were included in the present study. Anthropometric, biochemical, densitometric and body composition variables were analyzed under basal conditions, and under replacement therapy. As a result, androgen deficiency was compensated, and estradiol level was twice as high. Induced eugonadism increased both BMD and total body calcium content. Also, replacement treatment reduced the percentage of total body fat, (primarily abdominal fat) and increased total muscle mass, with an increment of the lean mass/fat mass ratio, and no change in BMI. In conclusion, our results strengthen the preponderant role of sexual steroids on body composition, and its effect on bones. Male hypogonadism is a risk factor for osteoporosis and cardiovascular disease.
RESUMO
The aim of the present study was to establish the serum levels of inhibins and their relationship with the degree of seminal alteration in infertile men. Thirty-six patients with varicocele (Va) and seven non-obstructive azoospermic men (Az) were included. The Va group was divided into two subgroups: Va I (sperm concentration: >20 x 106; n = 21) and Va II (sperm concentration: < 20 x 106; n = 15). Twelve fertile men were included as a control group (Co). Semen analysis and serum follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T), inhibin B and Pro-alphaC levels were determined. Serum inhibin B and T levels were significantly lower and FSH and LH significantly higher in group Az when compared with the Co. Inhibin B was unable to differentiate Va I from Va II groups. However, in Va II an increase in FSH levels was observed. An inverse correlation between inhibin B and FSH, a direct correlation between inhibin B and testosterone, sperm concentration, motility and morphology were found. No such correlations were seen when only the Va group was analysed. The lack of correlation between serum levels of inhibin B, gonadotrophins, sperm concentration and seminal parameters observed in Va, adds other factor to the complex pathophysiology of varicocele. Finally, further studies are needed to elucidate if oligozoospermic patients with varicocele have also an impaired negative feed-back mechanism that regulates FSH synthesis and secretion.
Assuntos
Biomarcadores/sangue , Infertilidade Masculina/sangue , Inibinas/sangue , Varicocele/sangue , Adulto , Hormônio Foliculoestimulante/sangue , Humanos , Infertilidade Masculina/etiologia , Hormônio Luteinizante/sangue , Masculino , Pessoa de Meia-Idade , Oligospermia/sangue , Valores de Referência , Sêmen/química , Sêmen/citologia , Contagem de Espermatozoides , Testosterona/sangue , Varicocele/complicaçõesRESUMO
The clinical genetics and hormonal status of the 46,XX male is well determined. This is a rare condition that affects one out 20,000 male births. This study evaluates 5 infertile patients with no abnormalities in sex definition in whom we noted variants in their phenotype, like small penis, hypospadias, cryptorchidism, flat scrotum, and in some of them small testis. Only one patient had gynecomastia; all patients were azoospermics. Otherwise, serum FSH levels were elevated in only 3 patients and LH in 2. Serum levels of testosterone were low in 3 cases. Karyotype was 46,XX without evidence of mosaicism. PCR of genomic DNA studied revealed only the presence of SRY gene. DNA material in the Y chromosome was similar in all patients, but this did not correlate with the phenotype findings and hormonal levels in all of them. Testing new chromosomal markers should be of great value in the definition of clinical difference.
Assuntos
Transtornos do Desenvolvimento Sexual/genética , Genitália Masculina , Adulto , Criptorquidismo , DNA/análise , Estradiol/sangue , Feminino , Hormônio Foliculoestimulante/sangue , Genes sry/genética , Ginecomastia , Humanos , Hipospadia , Infertilidade/genética , Hormônio Luteinizante/sangue , Masculino , Oligospermia , Pênis , Fenótipo , Reação em Cadeia da Polimerase , Prolactina/sangue , Escroto , Testículo , Testosterona/sangueRESUMO
Testosterone serum levels may influence the lipoprotein metabolism and possibly atherogenic risk. Our aim was to investigate the effects of long-term testosterone supplementation in hypogonadal men on multiple lipoprotein markers. 18 Hypogonadal men were studied before and after 3, 6, and 18 (n = 7) months of treatment with testosterone enanthate. During treatment, serum testosterone and estradiol increased, reaching normal levels (p < 0.0001 and 0.003, respectively). This was associated with a decrease in HDL cholesterol (from 1.40 +/- 0.10 mmol/l to 1.22 +/- 0.08 mmol/l, p < 0.001) after six months at the expense of HDL2 cholesterol (p < 0.01), as well as apoprotein A1 (from 139 +/- 3.4 mg/dl to 126 +/- 3.0 mg/dl, p < 0.005). Hepatic lipase activity increased (p < 0.05) and correlated positively with testosterone (r = 0.56, p < 0.02) and negatively with HDL cholesterol (r = - 0.58, p < 0.02). Total and LDL cholesterol, triglycerides, and apoprotein B did not increase. Among the seven patients who completed 18 months of treatment, triglycerides, total cholesterol, LDL and HDL cholesterol, as well as total cholesterol/HDL cholesterol ratio values did not differ from baseline while apoprotein A1 (p < 0.03) and HDL cholesterol (p < 0.015) remained decreased and hepatic lipase unchanged. Restoration of testosterone levels in hypogonadal men in this study did not reveal unfavorable changes based on total cholesterol/HDL cholesterol and LDL cholesterol/apoprotein B ratios, which are both atherogenic risk markers. Whether the changes in light of lipoprotein metabolism will adversely influence cardiovascular risk over time remains to be determined.
Assuntos
Hipogonadismo/tratamento farmacológico , Lipoproteínas/sangue , Testosterona/análogos & derivados , Testosterona/efeitos adversos , Adulto , Apolipoproteína A-I/sangue , Apolipoproteínas B/sangue , Constituição Corporal , Índice de Massa Corporal , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Estradiol/sangue , Humanos , Lipase/sangue , Masculino , Pessoa de Meia-Idade , Testosterona/administração & dosagem , Testosterona/sangue , Fatores de Tempo , Triglicerídeos/sangueRESUMO
We studied the evolution of 150 pregnancies corresponding to 114 women (16-39 years old) with primary hypothyroidism. Fifty-one pregnancies (34%) were conceived under hypothyroidism: 16 overt (X +/- standard deviation [SD], thyroxine [T4]: 2.44 +/- 0.7 microg/dL; thyrotropin [TSH]: 33.4 +/- 8.82 mIU/L), and 35 subclinical hypothyroidism (T4: 6.93 +/- 1.88 microg/dL; TSH: 12.87 +/- 8.43 mIU/L); 99 pregnancies were conceived under euthyroidism while undergoing thyroid therapy. When treatment with levothyroxine was inadequate, the outcome of pregnancy was abortion in 60% of overtly hypothyroid patients and in 71.4% of subclinically hypothyroid patients, premature delivery in 20% and 7.2% respectively, and term delivery in 20% and 21.4%, respectively. When treatment was adequate, 100% of overtly hypothyroid patients and 90.5% of subclinically hypothyroid patients carried pregnancies to term; there were no abortions in any of the groups. Abortions, premature and term deliveries in patients who were euthyroid on levothyroxine at the time of conception were 4%, 11.1% and 84.9% respectively. Of the patients receiving levothyroxine therapy before conception, 69.5% had to increase the dose (mean increase 46.2 +/- 29.6 microg/d). Of 126 evaluated newborns, 110 were delivered at term while 16 were premature. Eight newborns, 4 were premature, had congenital malformations (6.3%), and 4 died. Our results show that the evolution of pregnancies did not depend on whether the hypothyroidism was overt or subclinical but mainly on the treatment received. The adequate treatment of hypothyroidism during gestation minimizes risks and generally, makes it possible for pregnancies to be carried to term without complications.
Assuntos
Hipotireoidismo/complicações , Complicações na Gravidez , Aborto Espontâneo/epidemiologia , Adolescente , Adulto , Anormalidades Congênitas/epidemiologia , Hipotireoidismo Congênito , Feminino , Idade Gestacional , Humanos , Hipertireoidismo/epidemiologia , Hipotireoidismo/tratamento farmacológico , Recém-Nascido , Recém-Nascido Prematuro , Gravidez , Resultado da Gravidez , Tireotropina/sangue , Tiroxina/administração & dosagem , Tiroxina/sangue , Tiroxina/uso terapêuticoRESUMO
Circulating human Prolactin (PRL) exists in different variants related to posttranslational modifications, dimerization or association with other serum proteins. Compared to monomeric prolactin these variants usually have little or no biologic activity and include BigBig (BB PRL), Big (B PRL), and Glycosylated forms (G PRL). The aim of the present study was to assess levels of BB PRL, B PRL, little PRL (L PRL) and G PRL in hyperprolactinemic patients with no menstrual alterations or galactorrhea. L PRL, B PRL, and BB PRL were identified by gel filtration chromatography on Sephadex G-100; G PRL and NG PRL were identified by chromatography on Concanavalin A Sepharose. PRL was measured by IRMA DPC. Eleven women, aged 22-50 yrs, were studied for: breast dysplasia (1), controlled hypothyroidism (3), dysmenorrhea (3), microadenoma follow-up (2), and gynecological control (2). Pituitary MRI was normal in all but one patient, who had a microadenoma discovered by Magnetic Resonance Imaging. Six patients had normal L PRL levels, and their hyper PRL was due to excess BPRL or BB PRL. Five patients had increased L PRL levels, but excess G PRL. Patients harboring molecular PRL variants do not present the symptoms typical of the hyperprolactinemic syndrome. Furthermore in patients with clinically controlled prolactinomas the presence of PRL variants should be ruled out to avoid an unnecessary increase of dopamine agonist dosage.
Assuntos
Hiperprolactinemia/genética , Prolactina/metabolismo , Processamento de Proteína Pós-Traducional/fisiologia , Adulto , Bioensaio , Cromatografia de Afinidade , Cromatografia em Gel , Feminino , Glicosilação , Humanos , Linfoma/metabolismo , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Peso Molecular , Prolactina/biossíntese , Células Tumorais CultivadasRESUMO
We studied the effects of sildenafil on nocturnal penile erections. We prospectively evaluated 36 patients with organic or psychogenic impotence and 5 normal, potent men. All patients completed 3 sessions of consecutive nights using the RigiScan Plus device. The first two nights the patients were asked to take placebo before the session and to take 50 mg of sildenafil before the third session. In the organic impotence group the use of sildenafil induced a significant improvement in time of rigidity 60-100%, rigidity and tumescence activity unit values and rigidity and tumescence activity unit values per hour in the tip and base. In the psychogenic impotence group it caused significant improvement only in rigidity activity unit per hour in the tip. In the potent men, changes were statistically insignificant. Sildenafil improves nocturnal penile erectile activity in organic impotence. Our study shows that phosphodiesterase inhibitors can improve penile erections not induced by sexual stimulation.
Assuntos
Ritmo Circadiano , Disfunção Erétil/tratamento farmacológico , Disfunção Erétil/fisiopatologia , Ereção Peniana/efeitos dos fármacos , Inibidores de Fosfodiesterase/uso terapêutico , Piperazinas/uso terapêutico , Adulto , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores de Fosfodiesterase/efeitos adversos , Piperazinas/efeitos adversos , Purinas , Valores de Referência , Citrato de Sildenafila , SulfonasRESUMO
The 45,X karyotype is usually associated with Turner syndrome, while male phenotype is exceptional. The authors report a 45,X male patient with normal external genitalia and sex behavior, but who was azoospermic. He had a normally developed musculature and pilose distribution, testicular volume of 15 mL and no gynecomastia but clinical stigmata of Turner syndrome (short stature, short neck and 4th metacarpal bones) and azoospermia. Hormonal plasma levels of testosterone, estradiol, prolactin, and gonadotrophins were within the normal range as was the response of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) (30 and 60 min) after 100 microg iv of LH-RH administration. Testicular biopsy could not be performed. Karyotype was 45,X without evidence of mosaicism. Polymerase chain reaction of genomnic DNA studied with 12 different sequences of Y chromosome revealed only the presence of SRY gene (testis determining factor). It is possible that SRY/autosomal translocation had occurred in this patient. The study of 45,X male should be of great value in elucidating the complex mechanisms involved in normal male sex differentiation.
Assuntos
Aneuploidia , Reação em Cadeia da Polimerase , Cromossomo X , Cromossomo Y , Adulto , Humanos , Cariotipagem , Masculino , Oligospermia/genética , SêmenRESUMO
Information on the effect of abnormal thyroid function on male reproduction is less available than that for the female. To assess the effects of hyperthyroidism on hypothalamic-pituitary-testicular axis and on spermogram parameters, 25 male patients (19-47 years old) suffering from active Graves' disease were studied. Serum luteinizing hormone (LH), follicle stimulating hormone (FSH), and prolactin (PRL) were measured before and after administration of 100 microg GnRH plus 200 microg thyrotropin-releasing hormone (TRH). Testosterone (T), estradiol (E2), and 17-hydroxyprogesterone (17-OHP) were determined before and after 5000 IU human chorionic gonadotropin (HCG) administration. Serum sex hormone-binding globulin (SHBG), cortisol-binding globulin (CBG), androstenedione and bioavailable testosterone (bioT), and bioavailable estradiol (bioE2) were also measured. Spermograms according to World Health Organization (WHO) criteria were determined in 21 patients. Hormonal and seminal studies were repeated in six patients after 7 to 19 months of euthyroidism achieved after treatment for hyperthyroidism. As a control group, 10 normal men were evaluated. Impaired sexual function, gynecomastia, and low testicular volume were found in 12, 6, and 3 hyperthyroid patients. Mean basal LH was significantly higher than the control group (7.8 +/- 4.7 vs. 5.0 +/- 1.9 mIU/mL, respectively, p < 0.02), with hyperresponse to GnRH. The response of PRL to TRH was lower in patients versus control group (30 minutes: 3.9 +/- 3.4 and 12.0 +/- 2.8 ng/mL, p < 0.01). Basal levels of steroids and SHBG were significantly higher in patients than in normal men (T: 9.3 +/- 3.3 vs. 5.4 +/- 1.6 ng/mL, p < 0.005; E2: 62.2 +/- 25.2 vs. 32.1 +/- 11.0 pg/mL, p < 0.005; 17-OHP: 2.4 +/- 0.9 vs. 1.1 +/- 0.5 ng/mL, p < 0.001; SHBG: 102.3 +/- 37.3 vs. 19.0 +/- 5.0 nmol/L, p < 0.01). The maximal increment of T and 17-OHP after HCG was lower in hyperthyroid patients than in normal men (p < 0.019 and p < 0.001, respectively). Basal bioT was lower in patients than controls (1.7 +/- 0.8 and 3.1 +/- 1.9 ng/mL, p < 0.02). The following incidence of abnormal semen parameters was found: asthenospermia 85.7%, hypospermia 61.9%, oligospermia 42.9%, necrospermia 42.9% and teratospermia 19.0%. In euthyroidism, a normalization of 85% of seminal alterations was observed in the limited number of patients evaluated. Our results confirm that hyperthyroidism causes marked alterations of the gonadotropic and PRL axis and dramatically affects spermatic function. BioT measurement was useful to identify hypoandrogenism in these patients in spite of the high concentration of total testosterone. The restoration of most semen parameters when euthyroidism was achieved suggests that the alterations were induced by the Graves' disease.
Assuntos
Doença de Graves/fisiopatologia , Sistema Hipotálamo-Hipofisário/fisiopatologia , Sêmen/citologia , Testículo/fisiopatologia , Adulto , Estudos de Casos e Controles , Feminino , Hormônios Esteroides Gonadais/sangue , Doença de Graves/complicações , Doença de Graves/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Oligospermia/etiologia , Hormônios Hipofisários/sangue , Prolactina/sangue , Contagem de Espermatozoides , Motilidade dos Espermatozoides , Espermatozoides/anormalidades , Testosterona/sangueRESUMO
We previously showed that recombinant human FSH (R-FSH) in males increased the testosterone (T) concentration in spermatic venous blood (SB). To investigate the effect of R-FSH on spermatic steroid levels and the action of steroid- and LH-free SB on isolated Leydig cells, nine normospermic males were studied during spermatic cord surgery. Peripheral blood and SB samples were collected before and 30 min after iv administration of 150 U R-FSH to measure LH, FSH, T, estradiol, 17alpha-hydroxyprogesterone, and sex hormone-binding globulin, and in SB, androstenedione (delta4) and dehydroepiandrosterone (DHEA) were also measured. LH bioactivity was assessed by in vitro production of T in isolated Leydig cells. The actions of R-FSH and SB (steroid and LH free) were analyzed in the bioassay. Data are expressed as the mean +/- SE. FSH in peripheral blood and SB increased by 411% and 477% after R-FSH administration. R-FSH induced a significant increase in spermatic T (basal vs. 30 min, 326.4 +/- 98.5 vs. 732.4 +/- 152.8 ng/mL; P < 0.047) and in spermatic estradiol (289.5 +/- 66.9 vs. 535.6 +/- 83.4 pg/mL; P < 0.036). The T/delta4 ratio (36.9 +/- 9.2 vs. 74.5 +/- 13.3; P < 0.019) and the T/DHEA ratio (10.8 +/- 1.1 vs. 22.4 +/- 4.9; P < 0.024) increased significantly. In isolated Leydig cells, R-FSH did not change T production, but the SB (steroid and LH free) after R-FSH administration induced an increase in T production (3.3 +/- 0.6 vs. 4.9 +/- 0.6 ng/tube; P < 0.04). LH-like activity was found in a more than 50,000-Da fraction after centrifugation in Amicon filters, even in the presence of anti-LH. These results suggest that R-FSH increases the production of T by Leydig cells through a Sertoli cell-released nonsteroid factor with a molecular mass greater than 50 kDa. The increase in the T/delta4 and T/DHEA ratios indicates that this factor would act by amplifying the LH response through the delta5 pathway and the 17beta-hydroxysteroid dehydrogenase enzyme.
Assuntos
Fatores Biológicos/metabolismo , Hormônio Foliculoestimulante/farmacologia , Células de Sertoli/metabolismo , Testosterona/biossíntese , Adulto , Bioensaio , Humanos , Hormônio Luteinizante/análise , Masculino , Proteínas Recombinantes/farmacologiaRESUMO
Scatchard analysis of prolactin binding sites (PRL-BS) from ejaculated spermatozoa showed a single population of binding sites (apparent association constant: 2.51+/-0.186 nmol/l[-1]) with 0.317+/-0.0743 fmol/10(6) sperm binding sites. Different pools of spermatozoa were incubated with increasing concentrations of several hormones. There was a decrease in [125I]-oPRL binding with purified ovine prolactin (oPRL) and human growth hormone (hGH) which was not observed in the presence of synthetic ACTH and recombinant FSH, suggesting that binding was hormone specific. When the patient's samples were analyzed using the single point assay at saturation concentration, asthenospermic patients showed a significantly higher concentration of binding sites compared to normospermic ones. Both groups of patients displayed similar PRL levels in seminal plasma measured by DELFIA. Moreover, individual values of PRL levels in seminal plasma did not correlate with PRL-BS concentrations. We thus conclude that [125I]-oPRL binding to ejaculated spermatozoa was hormone specific and with similar parameters as seen in other target tissues. PRL-BS concentration in asthenospermic patients was significantly higher than in normospermic but this was not due to different levels of PRL in seminal plasma.
Assuntos
Infertilidade Masculina/metabolismo , Prolactina/metabolismo , Espermatozoides/metabolismo , Hormônio Adrenocorticotrópico/farmacologia , Animais , Sítios de Ligação , Ligação Competitiva , Estudos de Coortes , Hormônio Foliculoestimulante/farmacologia , Hormônio do Crescimento Humano/farmacologia , Humanos , Infertilidade Masculina/patologia , Radioisótopos do Iodo , Masculino , Prolactina/análise , Sêmen/química , OvinosRESUMO
The purpose of the study was to evaluate pulsatile luteinizing hormone (LH) release and intratesticular concentrations of testosterone and oestradiol in infertile men, to determine if alterations in gonadotrophin secretion are associated with changes in the testicular concentrations of steroids. Patients with idiopathic oligo/azoospermia were divided into a high follicle stimulating hormone (FSH) group (n = 5) and a normal FSH group (n = 6). Blood samples were taken every 15 min for 6 h to determine LH, FSH, testosterone, oestradiol, sex hormone binding globulin, bioactive LH and bioavailable testosterone. The patients underwent a bilateral testicular biopsy for histological assessment and to determine testosterone and oestradiol concentrations. Serum measurements were compared with those of seven fertile men. The high FSH group had a higher concentration of serum LH and oestradiol than normal men (P < 0.01) and showed a lower frequency of LH pulses than the normal FSH group and control men (P < 0.01). Intratesticular oestradiol was higher in the high FSH group (P < 0.001), with a lower testosterone/oestradiol ratio (P < 0.01). Patients showed a negative correlation between the serum testosterone/LH ratio and FSH (r = -0.75; P < 0.01) and a positive correlation between the testicular oestradiol concentration and serum FSH (r = 0.86; P < 0.01). The histopathological examination only showed a smaller tube diameter in the high FSH group (P < 0.05). These data seem to indicate that a higher intratesticular concentration of oestradiol with a lower testosterone/oestradiol ratio in the high FSH group could have a deleterious effect on spermatogenesis.
Assuntos
Estradiol/metabolismo , Infertilidade Masculina/metabolismo , Hormônio Luteinizante/sangue , Testosterona/metabolismo , Adulto , Hormônio Foliculoestimulante/sangue , Humanos , Infertilidade Masculina/sangue , Infertilidade Masculina/patologia , Hormônio Luteinizante/metabolismo , Masculino , Espermatogênese , Testículo/metabolismo , Testículo/patologiaRESUMO
The effect of the antiestrogen tamoxifen (Tx) on the acute and chronic hCG administration was evaluated in patients with hypogonadotropic hypogonadism (HH) and in normal men. An hCG test (5000 IU hCG) was performed before, after two months of hCG administration (2000 IU hCG three times weekly) and after two months of hCG + Tx (2000 IU hCG three times weekly plus 20 mg/day of tamoxifen). Blood samples were obtained before and following 24 and 72 h of every test to determine T, E, 17OHP and SHBG. T increased only in HH with both treatments (X +/- SEM: Basal: 97.9 +/- 19.7; hCG: 237.7 +/- 43.2; hCG +/- Tx: 204.7 +/- 10.7 ng/100 ml). 17OHP rose with hCG alone, but not with hCG + Tx in both groups. E, SHBG and 17OHP/T ratio did not change after treatments. hCG tests: E increased 24 h following hCG administration in every test. The ratio 17OHP/T rose at 24 h in the first and second test but in the third test it did not change. These results support the role of E in the acute hCG-induced Leydig cell desensitization. However, the association of Tx does not improve T serum levels, suggesting that E might not be the unique factor involved in the mechanisms for testicular desensitization.
Assuntos
Gonadotropina Coriônica/uso terapêutico , Hipogonadismo/tratamento farmacológico , Tamoxifeno/farmacologia , 17-alfa-Hidroxiprogesterona , Adulto , Gonadotropina Coriônica/administração & dosagem , Estradiol/sangue , Humanos , Hidroxiprogesteronas/sangue , Hipogonadismo/sangue , Masculino , Globulina de Ligação a Hormônio Sexual/metabolismo , Tamoxifeno/administração & dosagem , Testosterona/sangueRESUMO
Luteinizing hormone-releasing hormone analogues (LH-RHa) offer a novel approach for non-steroidal manipulation of the reproductive endocrine axis. LH-RH agonists are now employed in the management of central precocious puberty (CPP). The aim of the present work is to show the results of one of the first experiences in our country in the therapeutics of this pathology with LH-RHa (Buserelin) both subcutaneously (SC) and intranasally (IN). Five girls with CPP, aged 1.3 to 6.8 years, were selected (Table 1). The doses employed were: 25 micrograms/kg/day in 2 SC applications followed by 1200 micrograms/day IN. In case 4 IN route only was used because she presented an allergic cutaneous reaction to the SC injection and in case 3 only the SC route was employed because of her chronological age. The period of treatment oscillated between 3 and 21 months. In 2 girls 150 mg of medroxyprogesterone was administered before the analogue therapy and it was maintained during a week. In 4 patients a regression of breast development was observed to Tanner's I or II incipient grades and in case 1 only partial involution was noted. In 4 of the 5 patients, annual growth velocity could be evaluated, showing in 3 of them a reduction between 40 and 55% VS pretreatment associated with a desacceleration of the skeletal maturation (Figs. 1, 2). The prediction of adult height increased 2 cm in one case and 4.5 cm in 2 cases; 4/5 girls showed a reduction of FSH, LH and estradiol levels to prepubertal values after 3 months of treatment and in one patient after 6 months of therapy (Fig. 3).(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Busserrelina/administração & dosagem , Puberdade Precoce/tratamento farmacológico , Administração Intranasal , Criança , Pré-Escolar , Feminino , Hormônio Foliculoestimulante/sangue , Humanos , Lactente , Injeções Subcutâneas , Hormônio Luteinizante/sangue , Medroxiprogesterona/uso terapêutico , Puberdade Precoce/sangue , Maturidade Sexual/efeitos dos fármacosRESUMO
Se presenta la experiencia en 5 pacientes de sexo feminino. Sus edades cronológicas oscilaron entre 1,3 y 6,8 años, con edades óseas entre 2,3 y 11,6 años. Las dosis empleadas fueron: 25 microng/kg/dSC y posteriormente 1200 microng/dIN. En 2 niñas se administraron 159 mg de medroxiprogesterona previo al análogo y una semana después. En un caso, se comenzó por via IN por reacción alérgica local a la inyección SC. El tratamiento osciló entre 3 y 21 meses. Se obtuvo una regreión completa del desarrollo mamario en 4 pacientes y parcial en 1. En 4/5 casos se pudo valorar la velocidad de crecimiento anual, observándose una reducción entre el 40 y 55% vs. pretratamiento, asociada a desaceleración de la maduración ósea y a un incremento entre 2 y 4,5cm en la predicción de talla adulta. Durante la terapéutica se obtuvo una reducción de los niveles de LH, FSH y estradiol hasta valores prepuberales, así como una ausencia de respuesta en la prueba de LH-RH. Concluímos que el Buserelin constituiría en recurso altamente efectivo en el tratamiento de esta patoloía, siendo, al igual que otros análogos del LH-RH, recursos útiles que mejorarian la predicción de talla final
Assuntos
Humanos , Lactente , Pré-Escolar , Criança , Feminino , Busserrelina/uso terapêutico , Puberdade Precoce/tratamento farmacológico , Administração Intranasal , Hormônio Foliculoestimulante/sangue , Injeções Subcutâneas , Hormônio Luteinizante/sangue , Maturidade Sexual/efeitos dos fármacos , Medroxiprogesterona/uso terapêuticoRESUMO
Luteinizing hormone-releasing hormone analogues (LH-RHa) offer a novel approach for non-steroidal manipulation of the reproductive endocrine axis. LH-RH agonists are now employed in the management of central precocious puberty (CPP). The aim of the present work is to show the results of one of the first experiences in our country in the therapeutics of this pathology with LH-RHa (Buserelin) both subcutaneously (SC) and intranasally (IN). Five girls with CPP, aged 1.3 to 6.8 years, were selected (Table 1). The doses employed were: 25 micrograms/kg/day in 2 SC applications followed by 1200 micrograms/day IN. In case 4 IN route only was used because she presented an allergic cutaneous reaction to the SC injection and in case 3 only the SC route was employed because of her chronological age. The period of treatment oscillated between 3 and 21 months. In 2 girls 150 mg of medroxyprogesterone was administered before the analogue therapy and it was maintained during a week. In 4 patients a regression of breast development was observed to Tanners I or II incipient grades and in case 1 only partial involution was noted. In 4 of the 5 patients, annual growth velocity could be evaluated, showing in 3 of them a reduction between 40 and 55
VS pretreatment associated with a desacceleration of the skeletal maturation (Figs. 1, 2). The prediction of adult height increased 2 cm in one case and 4.5 cm in 2 cases; 4/5 girls showed a reduction of FSH, LH and estradiol levels to prepubertal values after 3 months of treatment and in one patient after 6 months of therapy (Fig. 3).(ABSTRACT TRUNCATED AT 250 WORDS)
RESUMO
Se presenta la experiencia en 5 pacientes de sexo feminino. Sus edades cronológicas oscilaron entre 1,3 y 6,8 años, con edades óseas entre 2,3 y 11,6 años. Las dosis empleadas fueron: 25 microng/kg/dSC y posteriormente 1200 microng/dIN. En 2 niñas se administraron 159 mg de medroxiprogesterona previo al análogo y una semana después. En un caso, se comenzó por via IN por reacción alérgica local a la inyección SC. El tratamiento osciló entre 3 y 21 meses. Se obtuvo una regreión completa del desarrollo mamario en 4 pacientes y parcial en 1. En 4/5 casos se pudo valorar la velocidad de crecimiento anual, observándose una reducción entre el 40 y 55% vs. pretratamiento, asociada a desaceleración de la maduración ósea y a un incremento entre 2 y 4,5cm en la predicción de talla adulta. Durante la terapéutica se obtuvo una reducción de los niveles de LH, FSH y estradiol hasta valores prepuberales, así como una ausencia de respuesta en la prueba de LH-RH. Concluímos que el Buserelin constituiría en recurso altamente efectivo en el tratamiento de esta patoloía, siendo, al igual que otros análogos del LH-RH, recursos útiles que mejorarian la predicción de talla final (AU)