Hypogonadism in the male

The hypogonadism of man and its causes are described in short form. A scheme of the gradual diagnostics explains the possibilities of the diagnostic approach. At the same time is dealt with the therapeutic measures and their indications.     

ALCOHOL AND ENDOCRINE SYSTEMS INTERACTION—PART II Biochemical Mechanisms That Contribute to Alcohol-Induced Hypogonadism in the Male

The above review has presented most if not all of the available evidence supporting a role for alcohol and acetaldehyde as putative environmental Leydig cell toxins for man and animals. Despite a considerable data base and much progress, particularly in the last decade, much yet remains to be learned concerning this phenomenon. It is hoped that this review, and this symposium, will contribute to future progress in this area by providing a basis for new and provocative observations and hypotheses to be tested by a new generation of clinical investigators.     

Hypogonadism in hereditary hemochromatosis

Hypogonadism, usually hypogonadotropic in origin, is the most common nondiabetic endocrinopathy in hereditary hemochromatosis (HH). Early studies, usually evaluating small numbers of patients with advanced HH, report prevalence rates of 10-100%. The clinical presentation of HH has changed in recent years as a result of increased awareness and screening. We assessed the prevalence of hypogonadism in a large group of patients with HH diagnosed in a single center over the past 20 yr, the period of follow-up spanning the time before and after widespread screening was introduced and the HFE gene was recognized. Abnormally low plasma testosterone levels, with low LH and FSH levels, were found in nine of 141 (6.4%) male patients tested. Eight of nine (89%) had associated hepatic cirrhosis; three of nine (33%) had diabetes. Inappropriately low LH and FSH levels were found in two of 38 females (5.2%) in whom the pituitary-gonadal axis could be assessed. This is the largest detailed study of hypogonadism reported in HH. The lower prevalence of hypogonadism compared with other reported series reflects the earlier diagnosis of HH in an unselected group of patients attending a single center. Patients with lesser degrees of hepatic siderosis at diagnosis are unlikely to develop hypogonadism.     

Efficacy and Outcome Predictors of Gonadotropin Treatment for Male Congenital Hypogonadotropic Hypogonadism: A Retrospective Study of 223 Patients

Gonadotropin induces masculinization and spermatogenesis in men with congenital hypogonadotropic hypogonadism (CHH). However, large cohort studies for the efficacy and reliable predictors of this therapy need to be conducted. The aim of this study was to investigate the efficacy of gonadotropin treatment in a large cohort of male CHH patients and analyze putative predictors for successful spermatogenesis.This retrospective study included 223 CHH azoospermic patients without puberty development treated between 2005 and 2014. All patients received combined human chorionic gonadotropin (HCG) and human menopausal gonadotropin (HMG) and were followed up for >6 months (5109 person-months). Serum total testosterone level, testicular size, spermatogenesis, and pregnancy outcome were recorded at each visit.After gonadotropin therapy, testicular size was enlarged from 2.1 ± 1.6 to 8.1 ± 4.6 mL (P < 0.001) and serum total testosterone was elevated from 0.9 ± 0.5 to 15.1 ± 8.2 nmol/L (P < 0.001). Spermatogenesis (>0/mL) occurred at a median period of 15 months (95% confidence interval 13.5–16.5). Larger basal testicular volume (P = 0.012) and noncryptorchidism history (P = 0.028) are independent predictors for earlier sperm appearance. Sixty four percent (143/223) of patients succeeded in producing sperms and the average time for initial sperm detection was 14 ± 8 months. However, their sperm concentrations (11.7 [2.1, 24.4] million/mL) and sperm progressive motility (A + B 36.9% ± 20.2%) are significantly lower than World Health Organization standards. Of the 34 patients who desired for fathering children, 19 patients impregnanted their partners during the treatment.Gonadotropin therapy induces spermatogenesis in male CHH patients. A larger basal testicular size and noncryptorchidism history are favorable indicators for earlier spermatogenesis.     

Hypogonadism following long-term treatment with diethylstilbestrol

The authors describe the abnormalities of gonadal function developing in a patient with prostate cancer who had received estrogen therapy continuously for 6 years. The pretreatment prostate biopsy showed well developed acini consistent with normal androgenization and adenocarcinoma. Twelve years later, 6 years after discontinuation of estrogen treatment, the patient presented with severe hypogonadism, gynecomastia, and primary hypothyroidism. Testicular biopsies showed ghosts of seminiferous tubules with absence of Leydig cells, and prostatic biopsies showed atrophic acini without evidence of malignancy. Despite undetectable serum testosterone levels, serum gonadotropins were inappropriately normal and responded minimally to gonadotropin-releasing hormone (GnRH) administration. Replacement therapy with levothyroxine did not correct gonadal dysfunction. Thus, prolonged estrogen therapy may result in irreversible testicular destruction and loss of the feed-back response of the hypothalamic pituitary gonadal axis.     

Hypogonadism in untreated male normoprolactinaemic acromegalics

Hypogonadism is a distinct feature of acromegaly, even in the absence of hyperprolactinaemia. In 10 untreated male acromegalics, aged 24 to 46 yr, without evidence of any other disturbance of anterior pituitary function, low testosterone values were found in the presence of a normal reaction of pituitary gonadotrophins following GnRH administration. In three patients, one injection of 5000 IU hCG resulted in a sharp rise in testosterone. Although we were unable to elicit a similar reaction pattern of the GnRH-gonadotrophins-testosterone axis following administration of biosynthetic methionyl-hGH, it is suggested that suppression of testicular function in untreated acromegaly without other endocrine disturbances may be partly caused by increased somatostatin production.     

Hypogonadism in male outpatients with sarcoidosis

Hypogonadism is assumed to be present in sarcoidosis. Nevertheless, a comparison of circulating sex hormone concentrations of male sarcoidosis patients with those of healthy men has never been done. Moreover, it remains unknown if hypogonadism may contribute to a reduced muscle function, exercise intolerance, diminished vitality and depressed mood in male sarcoidosis patients. Pulmonary function, muscle function, exercise tolerance, vitality, mood, circulating sex hormone concentrations and C-reactive protein were assessed in 30 male sarcoidosis patients and 26 age-matched men with a normal pulmonary function. On average, patients had a restrictive pulmonary function, worse inspiratory and quadriceps muscle function, functional exercise intolerance, diminished vitality, depressed mood and increased systemic inflammation. Moreover, patients had significantly lower circulating (free) testosterone concentrations, while circulating sex hormone-binding globulin tended to be lower (p=0.0515). Circulating gonadotrophin concentrations were comparable. Non-significant relationships were found between sex hormones, clinical outcomes and C-reactive protein in patients with sarcoidosis. A significant number of male outpatients with sarcoidosis (46.7%) had low circulating testosterone concentrations, which was most probably caused by hypogonadotrophism. The clinical relevance of hypogonadism in male outpatients with sarcoidosis, however, remains currently unknown. Indeed, poor inspiratory and quadriceps muscle function, exercise intolerance, diminished vitality and depressed mood were not related to hypogonadism in these patients.