Hypogonadotropic hypogonadism(HH)represents a relatively rare cause of nonobstructive azoospermia(NOA),but its knowledge is crucial for the clinical andrologists,as it represents a condition that can be corrected with...Hypogonadotropic hypogonadism(HH)represents a relatively rare cause of nonobstructive azoospermia(NOA),but its knowledge is crucial for the clinical andrologists,as it represents a condition that can be corrected with medical therapy in 3 quarters of cases.There are forms of congenital HH,whether or not associated with an absent sense of smell(anosmic HH or Kallmann syndrome,and normosmic HH,respectively),and forms of acquired HH.In congenital HH,complete absence of pubertal development is characteristic.On the other hand,if the deficit occurs after the time of pubertal development,as in acquired HH patients,infertility and typical symptoms of late-onset hypogonadism are the main reasons for seeking medical assistance.Gonadotropin-releasing hormone(GnRH)or gonadotropin replacement therapy is the mainstay of drug therapy and offers excellent results,although a small but significant proportion of patients do not achieve sufficient responses.展开更多
Testosterone affects several organs in the body and is very important for male well-being.Aging men with late-onset hypogonadism(LOH)experience physiologic,psychiatric,and sexual symptoms related to a decline in the s...Testosterone affects several organs in the body and is very important for male well-being.Aging men with late-onset hypogonadism(LOH)experience physiologic,psychiatric,and sexual symptoms related to a decline in the serum concentration of testosterone with age.However,it is well-known that the extent of the decline in testosterone concentration does not correlate with the severity of LOH-related symptoms.Therefore,it is difficult to diagnose and treat patients with LOH.In addition,the symptoms,response to testosterone replacement therapy(TRT),and medical insurance coverage differ among ethnicities and countries.The evaluation of testosterone is essential for the diagnosis and treatment of LOH.The effects of testosterone are determined not only by the serum testosterone concentration but also by the androgen receptor sensitivity.A low number of glutamine repeats is indicative of high androgenic activity,and the number shows ethnicity-related differences(fewer in African American than in Caucasian people and more in East Asian people).The diagnosis of LOH is typically made using subjective symptoms and the serum testosterone concentration.The Aging Male Symptoms scale is widely used to evaluate the symptoms.The normal range of total testosterone concentration varies around the world;therefore,clinicians should follow the guidelines of their regional academic society.The principal treatment for LOH is TRT.There are many types of TRT and other treatment strategies are also available.Thus,physicians should treat LOH according to each patient’s situation,considering related disorders,such as diabetes,osteoporosis,metabolic syndrome,and depression.展开更多
Idiopathic hypogonadotropic hypogonadism is a rare disease that is characterized by delayed/absent puberty and/or infertility due to an insufficient stimulation of an otherwise normal pituitary-gonadal axis by gonadot...Idiopathic hypogonadotropic hypogonadism is a rare disease that is characterized by delayed/absent puberty and/or infertility due to an insufficient stimulation of an otherwise normal pituitary-gonadal axis by gonadotrophin-releasing hormone （GnRH） action. Because reduced or normal luteinizing hormone （LH）/follicle-stimulating hormone （FSH） levels may be observed in the affected patients, the term idiopathic central hypogonadism （ICH） appears to be more appropriate. This disease should be distinguished from central hypogonadism that is combined with other pituitary deficiencies. Isolated ICH has a complex pathogenesis and ~s fivefold more prevalent in males. ICH frequently appears in a sporadic form, but several familial cases have also been reported. This finding, in conjunction with the description of numerous pathogenetic gene variants and the generation of several knockout models, supports the existence of a strong genetic component. ICH may be associated with several morphogenetic abnormalities, which include osmic defects that, with ICH, constitute the cardinal manifestations of Kallmann syndrome （KS）. KS accounts for approximately 40% of the total ICH cases and has been generally considered to be a distinct subgroup. However, the description of several pedigrees, which include relatives who are affected either with isolated osmic defects, KS, or normo-osmic ICH （nlCH）, justifies the emerging idea that ICH is a complex genetic disease that is characterized by variable expressivity and penetrance. In this context, either multiple gene variants or environmental factors and epigenetic modifications may contribute to the variable disease manifestations. We review the genetic mechanisms that are presently known to be involved in ICH pathogenesis and provide a clinical overview of the 227 cases that have been collected by the collaborating centres of the Italian ICH Network.展开更多
Several testosterone preparations are used in the treatment of hypogonadism in the ageing male. These therapies differ in their convenience, flexibility, regional availability and expense but share their pharmacokinet...Several testosterone preparations are used in the treatment of hypogonadism in the ageing male. These therapies differ in their convenience, flexibility, regional availability and expense but share their pharmacokinetic basis of approval and dearth of long-term safety data. The brevity and relatively reduced cost of pharmacokinetic based registration trials provides little commercial incentive to develop improved novel therapies for the treatment of late onset male hypogonadism. Selective androgen receptor modulators （SARMs） have been shown to provide anabolic benefit in the absence of androgenic effects on prostate, hair and skin. Current clinical development for SARMs is focused on acute muscle wasting conditions with defined clinical endpoints of physical function and lean body mass. Similar regulatory clarity concerning clinical deficits in men with hypogonadism is required before the beneficial pharmacology and desirable pharmacokinetics of SARMs can be employed in the treatment of late onset male hypogonadism.展开更多
Late-onset hypogonadism （LOH） has been considered the most common form of male hypogonadism with a prevalence of approximately 1 in 100 men. Diagnosis of LOH should be made in symptomatic men with unequivocally low ...Late-onset hypogonadism （LOH） has been considered the most common form of male hypogonadism with a prevalence of approximately 1 in 100 men. Diagnosis of LOH should be made in symptomatic men with unequivocally low serum testosterone （T） levels. However, its clinical presentation is often insidious and difficult to recognize because it is characterized by nonspecific symptoms that make differential diagnosis with physiological ageing problematic. Sexual dysfunction is the most important determinant for medical consultation and the most specific symptom associated with low T. We therefore analysed a consecutive series of 1734 subjects who attended our unit for sexual dysfunction to investigate the associations between low T （different thresholds）, sexual parameters, medical history data （delayed puberty, pituitary disease or cryptorchidism） and their physical exam results. Metabolic parameters, in particular waist circumference, display the greatest accuracy in detecting low T. We found that only the association of several symptoms and signs could significantly raise the clinical suspicion of low T. Structured inventories, which cluster together symptoms and signs of hypogonadism, can help clinicians suspect androgen deficiency. In particular, structured interviews, such as ANDROTEST, have been demonstrated to have a greater accuracy when compared to self reported questionnaires in detecting low T levels.展开更多
Late-onset hypogonadism is defined as a combination of low testosterone （T） levels and typical symptoms and signs. A major area of uncertainty is whether T concentrations are always really sufficient to fully reflec...Late-onset hypogonadism is defined as a combination of low testosterone （T） levels and typical symptoms and signs. A major area of uncertainty is whether T concentrations are always really sufficient to fully reflect Leydig cell （dys）function. Mild testicular alteration could be diagnosed only by additional biochemical markers, such as luteinizing hormone （LH） and 25-hydroxyvitamin D levels. These markers help in identifying the so-called ＂subclinical＂ hypogonadism （normal T, high LH levels）. Patients with hypogonadism have frequently low levels of 25-hydroxyvitamin D due to impairment of the hydroxylating enzyme CYP2R1 in the testis. However, no data have been published dealing with the best treatment option （cholecalciferol - the Vitamin D precursor, or calcidiol - 25-hydroxylated form of Vitamin D） in these patients. We studied 66 patients with classic hypogonadism （total T [TT] 〈12 nmol I-~, LH 〉 8 IU 1-1） （n = 26） and subclinical hypogonadism （TT 〉 12 nmol I-＊, LH 〉 8 IU I-~） （n = 40） and low 25-hydroxyvitamin D （〈50 nmol I-1）. Subjects received cholecalciferol （5000 IU per week） （n = 20） or calcidiol （4000 IU per week） （n -- 46）, and 25-hydroxyvitamin D and parathyroid hormone （PTH） were evaluated after 3 months of therapy. Supplementation with calcidiol significantly increased 25-hydroxyvitamin D and significantly decreased PI＂H levels in both groups of men with hypogonadism （primary, n = 16 and subclinical, n = 30）, whereas supplementation with cholecalciferol did not modify their levels. This study shows for the first time that the administration of the 25-hydroxylated form of Vitamin D （calcidiol）, and not the administration of the precursor cholecalciferol, restores 25-hydroxyvitamin D levels in subjects with hypogonadism.展开更多
Although suppressed serum testosterone （T） is common in ageing men, only a small proportion of them develop the genuine syndrome of low T associated with diffuse sexual （e.g., erectile dysfunction）, physical （e.g...Although suppressed serum testosterone （T） is common in ageing men, only a small proportion of them develop the genuine syndrome of low T associated with diffuse sexual （e.g., erectile dysfunction）, physical （e.g. loss of vigor and frailty） and psychological （e.g., depression） symptoms. This syndrome carries many names, including male menopause or climacterium, andropause and partial androgen deficiency of the ageing male （PADAM）. Late-onset hypogonadism （LOH） describes it best and is therefore generally preferred. The decrease of T in LOH is often marginal, and hypogonadism can be either due to primary testicular failure （low T, high luteinizing hormone （LH）） or secondary to a hypothalamic-pituitary failure （low T, low or inappropriately normal LH）. The latter form is more common and it is usually associated with overweight/obesity or chronic diseases （e.g., type 2 diabetes mellitus, the metabolic syndrome, cardiovascular and chronic obstructive pulmonary disease, and frailty）. A problem with the diagnosis of LOH is that often the symptoms （in 20%-40% of unselected men） and low circulating T （in 20% of men 〉70 years of age） do not coincide in the same individual. The European Male Ageing Study （EMAS） has recently defined the strict diagnostic criteria for LOH to include the simultaneous presence of reproducibly low serum T （total T 〈11 nmol 1-1 and free T 〈220 pmol 1-1） and three sexual symptoms （erectile dysfunction, and reduced frequency of sexual thoughts and morning erections）. By these criteria, only 2% of 40- to 80-year-old men have LOH. In particular obesity, but also impaired general health, are more common causes of low T than chronological age per se. Evidence-based information whether, and how, LOH should be treated is sparse. The most logical approach is lifestyle modification, weight reduction and good treatment of comorbid diseases. T replacement is widely used for the treatment, but evidence-based information about its real benefits and short- and long-term risks, is not yet available. In this review, we will summarize the current conceets and controversies in the Dathogenesis, diagnosis and treatment of LOH.展开更多
This study sought to investigate late-onset hypogonadism （LOH） in old and middle-aged males in Shanghai communities, using symptom score evaluation systems and measurements of sex hormone levels. One thousand cases ...This study sought to investigate late-onset hypogonadism （LOH） in old and middle-aged males in Shanghai communities, using symptom score evaluation systems and measurements of sex hormone levels. One thousand cases of males aged 40-70 years were investigated. The aging male symptoms （AMS） scale and androgen deficiency in aging males （ADAM） questionnaire were used at the beginning of the investigation, followed by measurement of the sex hormone-related factors （total testosterone （TT）, free testosterone （fT）, sex hormone-binding globulin （SHBG） and bioavailability of testosterone （Bio-T））. There were 977 valid questionnaires. The LOH-positive rates shown by AMS and ADAM were 59.88% and 84.65%, respectively; values increased with the age of the patients. There were 946 results related to sex hormone measurements, which showed the following results： TT was not related to aging （P〉O.05）; levels of SHBG increased with age; and fT and Bio-T decreased with age. There was a significant difference in fT between LOH-positive and LOH-negative patients, as shown by the ADAM. In summary, TT levels were not related to aging, even though SHBG did increase while fT and Bio-T decreased with aging. Clinically, the diagnosis of LOH cannot be based on serum TT level.展开更多
This study aimed to propose an operational definition of late-onset hypogonadism(LOH)that incorporates both clinical symptoms and serum testosterone measurements to evaluate the prevalence of LOH in aging males in Chi...This study aimed to propose an operational definition of late-onset hypogonadism(LOH)that incorporates both clinical symptoms and serum testosterone measurements to evaluate the prevalence of LOH in aging males in China.A population-based sample of 6296 men aged 40 years-79 years old was enrolled from six representative provinces in China.Serum total testosterone(TT),sex hormone-binding globulin(SHBG),and luteinizing hormone(LH)were measured and free testosterone(cFT)was calculated.The Aging Males’Symptoms(AMS)scale was used to evaluate the LOH symptoms.Finally,5078 men were included in this analysis.The TT levels did not decrease with age(P=0.59),and had no relationship with AMS symptoms(P=0.87 for AMS total score,P=0.74 for≥3 sexual symptoms).The cFT levels decreased significantly with age(P<0.01)and showed a negative association with the presence of≥3 sexual symptoms(P=0.03).The overall estimated prevalence of LOH was 7.8%(395/5078)if a cFT level<210 pmol l−1 combined with the presence of≥3 sexual symptoms was used as the criterion of LOH.Among them,26.1%(103/395)and 73.9%(292/395)had primary and secondary hypogonadism,respectively.After adjustment for confounding factors,primary and secondary hypogonadism was positively related to age and comorbidities.Body mass index was an independent risk factor for secondary hypogonadism.The results suggest that the AMS total score is not an appropriate indicator for decreased testosterone,and that the cFT level is more reliable than TT for LOH diagnosis.Secondary hypogonadism is the most common form of LOH.展开更多
In this study, we investigated the essential criteria for late-onset hypogonadism （LOH） syndrome based on the presence of symptoms associated with low testosterone levels in Han Chinese men. Blood tests for total te...In this study, we investigated the essential criteria for late-onset hypogonadism （LOH） syndrome based on the presence of symptoms associated with low testosterone levels in Han Chinese men. Blood tests for total testosterone （TT） and sex hormone-binding globulin （SHBG） were performed, and the aging male symptoms （AMS） questionnaire was conducted in a randomly selected cohort composed of 944 Chinese men aged 40 to 79 years from nine urban communities. Three sexual symptoms （decreased ability/frequency of sexual activity, decreased number of morning erections, and decreased libido） were confirmed to be related to the total and free testosterone levels. The thresholds for TT were approximately 12.55 nmol l^-1 for a decreased ability/frequency to perform sex, 12.55 nmol l^-1 for decreased frequency of morning erections, and 14.35 nmol l^-1 for decreased sexual desire. The calculated free testosterone （CFT） thresholds for these three sexual symptoms were 281.14, 264.90, and 287.21 pmol l^-1, respectively. TT 〈13.21 nmol l^-1 （OR =1.4, 95%Ch 1.0-1.9, P= 0.037） or CFT 〈268.89 pmol l^-1 （OR - 1.5, 95%Ch 1.1-20, P=0.020） was associated with an increase in the aforementioned three sexual symptoms. The prevalence of LOH was 9.1% under the criteria, including all three sexual symptoms with TT levels 〈13.21 nmol l^-1 and CFT levels 〈268.89 pmol l^-1. Our results may improve the diagnostic accuracy of LOH in older men.展开更多
Both pulsatile gonadotropin-releasing hormone （GnRH） infusion and combined gonadotropin therapy （human chorionic gonadotropin and human menopausal gonadotropin [HCG/HMG]） are effective to induce spermatogenesis in...Both pulsatile gonadotropin-releasing hormone （GnRH） infusion and combined gonadotropin therapy （human chorionic gonadotropin and human menopausal gonadotropin [HCG/HMG]） are effective to induce spermatogenesis in male patients with congenital hypogonadotropic hypogonadism （CH H）. However, evidence is lacking as to which treatment strategy is better. This retrospective cohort study included 202 patients with CHH： twenty had received pulsatile GnRH and 182 had received HCG/HMG. Patients had received therapy for at least 12 months. The total follow-up time was 15.6 ± 5.0 months （range： 12-27 months） for the GnRH group and 28.7 ± 13.0 months （range： 12-66 months） for the HCG/HMG group. The median time to first sperm appearance was 6 months （95% confidence interval [CI]： 1.6-10.4） in the GnRH group versus 18 months （95% Ch 16.4-20.0） in the HCG/HMG group （P〈 0.001）. The median time to achieve sperm concentrations 〉5 x 106 m1-1 was 14 months （95% Ch 5.8-22.2） in the GnRH group versus 27 months （95% Ch 18.9-35.1） in the HCG/HMG group （P 〈 0.001）, and the median time to concentrations 〉10 x 106 m1-1 was 18 months （95% Ch 10.0-26.0） in the GnRH group versus 39 months （95% CI unknown） in the HCG/HMG group. Compared to the GnRH group, the HCG/HMG group required longer treatment periods to achieve testicular sizes of 〉4 ml, 〉8 ml, 〉12 ml, and 〉16 ml. Sperm motility （a ＋ b ＋ c percentage） evaluated in semen samples with concentrations 〉1 × 106 ml-1 was 43.7% ± 20.4% （16 samples） in the GnRH group versus 43.2% ± 18.1% （153 samples） in the HCG/HMG group （P= 0.921）. Notably, during follow-up, the GnRH group had lower serum testosterone levels than the HCG/HMG group （8.3 ±4.6 vs 16.2 ± 8.2 nmol 1-1, P 〈 0.001）. Our study found that pulsatile GnRH therapy was associated with earlier spermatogenesis and larger testicular size compared to combined gonadotropin therapy. Additional prospective randomized studies would be required to confirm these findings.展开更多
Although idiopathic hypogonadotropic hypogonadism （IHH） has traditionally been viewed as a life-long disease caused by a deficiency of gonadotropin-releasing hormone neurons, a portion of patients may gradually rega...Although idiopathic hypogonadotropic hypogonadism （IHH） has traditionally been viewed as a life-long disease caused by a deficiency of gonadotropin-releasing hormone neurons, a portion of patients may gradually regain normal reproductive axis function during hormonal replacement therapy. The predictive factors for potential IHH reversal are largely unknown. The aim of our study was to investigate the incidence and clinical features of IHH male patients who had reversed reproductive axis function. In this retrospective cohort study, male IHH patients were classified into a reversal group （n = 18） and a nonreversal group （n = 336）. Concentration of gonadotropins and testosterone, as well as testicle sizes and sperm counts, were determined. Of 354 IHH patients, 18 （5.1%） acquired normal reproductive function during treatment. The median age for reversal was 24 years old （range 21-34 years）. Compared with the nonreversal group, the reversible group had higher basal luteinizing hormone （LH） （1,0±0.7 IU 1-1 vs 0.4±0.4 IU 1-1, P 〈 0.05） and stimulated LH （28.3 ± 22.6 IU 1-1 vs 1.9 ±1.1 IU 1-1, P 〈 0.01） levels, as well as larger testicle size （5.1 ±2.6 ml vs 1.5± 0.3 ml, P〈 0.01）, at the initial visit. In summary, larger testicle size and higher stimulated LH concentrations are favorite parameters for reversal. Our finding suggests that reversible patients may retain partially active reproductive axis function at initial diagnosis.展开更多
In the past, the indications for varicocelectomy are primarily for infertility with abnormal semen parameters, testicular hypotrophy/atrophy in adolescents, and/or pain. The surgical treatment of varicocele for hypogo...In the past, the indications for varicocelectomy are primarily for infertility with abnormal semen parameters, testicular hypotrophy/atrophy in adolescents, and/or pain. The surgical treatment of varicocele for hypogonadism is controversial and debated. Recently, multiple reports in the literature have suggested that varicocele is associated with hypogonadism and varicocele repair can increase testosterone levels. Men with hypogonadal symptoms should have at least two serum testosterone levels. Microsurgical varicocelectomy may be beneficial for men with clinically palpable varicoceles with documented hypogonadism. In this review, we summarize the most recent literature linking varicocele to hypogonadism and sexual dysfunction and the impact of repair on serum testosterone levels. We performed a search of the published English literature. The key words used were ＂varicocele and hypogonadism＂ and ＂varicocele surgery and testosterone.＂ We included published studies after 1998. We, also, evaluated the effect of surgery on the changes in the serum testosterone level regardless of the indication for the varicocele repair.展开更多
Klinefelter syndrome （KS） （47, XXY） is the most abundant sex-chromosome disorder, and is a common cause of infertility and hypogonadism in men. Most men with KS go through life without knowing the diagnosis, as on...Klinefelter syndrome （KS） （47, XXY） is the most abundant sex-chromosome disorder, and is a common cause of infertility and hypogonadism in men. Most men with KS go through life without knowing the diagnosis, as only 25% are diagnosed and only a few of these before puberty. Apart from hypogonadism and azoospermia, most men with KS suffer from some degree of learning disability and may have various kinds of psychiatric problems. The effects of long-term hypogonadism may be difficult to discern from the gene dose effect of the extra X-chromosome. Whatever the cause, alterations in body composition, with more fat and less muscle mass and diminished bone mineral mass, as well as increased risk of metabolic consequences, such as type 2 diabetes and the metabolic syndrome are all common in KS. These findings should be a concern as they are not simply laboratory findings; epidemiological studies in KS populations show an increased risk of beth hospitalization and death from various diseases. Testosterone treatment should be offered to KS patients from early puberty, to secure a proper masculine development, nonetheless the evidence is weak or nonexisting, since no randomized controlled trials have ever been published. Here, we will review the current knowledge of hypogonadism in KS and the rationale for testosterone treatment and try to give our best recommendations for surveillance of this rather common, but often ignored, syndrome.展开更多
The production of testosterone occurs within the Leydig cells of the testes. When production fails at this level from either congenital, acquired, or systemic disorders,the result is primary hypogonadism. While numero...The production of testosterone occurs within the Leydig cells of the testes. When production fails at this level from either congenital, acquired, or systemic disorders,the result is primary hypogonadism. While numerous testosterone formulations have been developed, none are yet fully capable of replicating the physiological patterns of testosterone secretion. Multiple stem cell therapies to restore androgenic function of the testes are under investigation. Leydig cells derived from bone marrow, adipose tissue, umbilical cord, and the testes have shown promise for future therapy for primary hypogonadism. In particular, the discovery and utilization of a group of progenitor stem cells within the testes, known as stem Leydig cells(SLCs), has led not only to a better understanding of testicular development, but of treatment as well. When combining this with an understanding of the mechanisms that lead to Leydig cell dysfunction, researchers and physicians will be able to develop stem cell therapies that target the specific step in the steroidogenic process that is deficient. The current preclinical studies highlight the complex nature of regenerating this steroidogenic process and the problems remain unresolved. In summary, there appears to be two current directions for stem cell therapy in male primary hypogonadism. The first method involves differentiating adult Leydig cells from stem cells of various origins from bone marrow, adipose, or embryonic sources. The second method involves isolating, identifying, and transplanting stem Leydig cells into testicular tissue. Theoretically, in-vivo re-activation of SLCs in men with primary hypogonadism due to age would be another alternative method to treat hypogonadism while eliminating the need for transplantation.展开更多
We conducted an analysis of the Kallmann syndrome 1 （KAL-1） genotype in 17 patients with Kallmann syndrome （KS）, 9 patients with normosmic idiopathic hypogonadotropic hypogonadism （nlHH） and 20 age-matched norma...We conducted an analysis of the Kallmann syndrome 1 （KAL-1） genotype in 17 patients with Kallmann syndrome （KS）, 9 patients with normosmic idiopathic hypogonadotropic hypogonadism （nlHH） and 20 age-matched normal men in Northwestern China. To do this, we used multiplex PCR analysis with exon-flanking primers and automated sequencing techniques with peripheral blood DNA samples. Intragenic deletions were found at the KAL-1 locus in two KS patients. One case with an atrial septal defect exhibited an intragenic deletion of exon 6. Another KS patient with cryptorchidism had intragenic deletions of exons 5 and 6. For the nlHH patients, no abnormalities were observed in the exonic and flanking sequences of KAL-1. This report describes two intragenic deletions of KAL-1 in two KS patients and suggests that KAL-1 deletion might be more prevalent in KS patients with other congenital organ abnormalities than those described previously in other series from Northwestern China.展开更多
The aim of this study was to evaluate the relationship between lower urinary tract symptoms （LUTSs）, erectile dysfunction （ED） and symptomatic late-onset hypogonadism （SLOH） in ageing men in the Aegean region of...The aim of this study was to evaluate the relationship between lower urinary tract symptoms （LUTSs）, erectile dysfunction （ED） and symptomatic late-onset hypogonadism （SLOH） in ageing men in the Aegean region of Turkey. Five hundred consecutive patients 〉40 years old who had been in a steady sexual relationship for the past 6 months and were admitted to one of six urology clinics were included in the study. Serum prostate-specific antigen and testosterone levels and urinary flow rates were measured. All patients filled out the International Prostate Symptom Score and Quality of Life （IPSS-QoL）, International Index of Erectile Function （IIEF） and Aging Males＇ Symptoms （AMS） scale forms. Of the patients, 23.9% had mild LUTSs, 53.3% had moderate LUTSs and 22.8% had severe LUTSs. The total testosterone level did not differ between groups. Additionally, 69.6% had ED. The presence of impotence increased with increasing LUTS severity. Symptomatic late-onset hypogonadism （AMS 〉27） was observed in 71.2% of the patients. The prevalence of severe hypogonadism symptoms increased with the IPSS scores. A correlation analysis revealed that all three questionnaire scores were significantly correlated. In conclusion, LUTS severity is an age-independent risk factor for ED and SLOH. LUTS severity and SLOH symptoms appear to have a strong link that requires etiological and biological clarification in future studies.展开更多
Hypogonadotropic hypogonadism(HH)is a rare disease in which medical treatment has a high success rate to achieve fertility.This study aimed to an a lyze the efficacy of horm one replacement therapy and determi ne pred...Hypogonadotropic hypogonadism(HH)is a rare disease in which medical treatment has a high success rate to achieve fertility.This study aimed to an a lyze the efficacy of horm one replacement therapy and determi ne predictive factors for successful spermatogenesis and spontaneous pregnancy in patients with idiopathic HH.A total of 112 patients with low testosterone(T),luteinizing hormone(LH)and follicle-stimulating hormone(FSH),and normal prolactin levels were diagnosed with HH and administered LH and FSH analogs as hormone replacement therapy.During treatment,96(85.7%)patients had sperm present in ejaculate samples.Among these patients,72 were married and wanted a child.Of these 72 patients,48(66.7%)of couples had pregnancies from natural conception.After initiation of treatment,the mean time for the appearance of sperm in semen was 9.48 months.There were no significant differences between baseline FSH,T,and LH levels;however,older age,larger testicular size,and low rate of undescended testes were favorable factors for successful spermatogenesis.Larger testicular size and older age were also the main predictive factors for natural conception.We found that patients with undescended testes had a younger age,smaller testes,and lower T levels compared with patients exhibit!ng descended testes.The rate of sperm found in the ejaculate was not significantly decreased in patients with undescended compared with descended testis(73.7%vs 87.6%,P=0.261).The medical approach for males with HH and azoospermia provides a successful treatment modality in regard to successful spermatogenesis and achievement of pregnancy.展开更多
Male hypogonadism associated with obesity is a very prevalent condition and is increasing in parallel with the epidemic prevalence of obesity. Low testosterone levels promote higher fat mass with reduced lean mass. Ma...Male hypogonadism associated with obesity is a very prevalent condition and is increasing in parallel with the epidemic prevalence of obesity. Low testosterone levels promote higher fat mass with reduced lean mass. Male hypogonadism is related to an increase in associated cardiometabolic complications, such as hypertension, type 2 diabetes mellitus, the metabolic syndrome, and cardiovascular disease. Its influence as a comorbidity of obesity is becoming more evident and should be evaluated and treated in at-risk patients. Mechanisms involved in this relationship include body composition changes, the presence of adipokines, insulin resistance, and other factors, some of which are still unknown. Weight loss and treatment to replace testosterone levels improve the metabolic profile and quality of life in patients with obesity and hypogonadism; these beneficial effects depend on treatment modality and duration of therapy. The use of testosterone replacement therapy may be indicated, as it has not been shown to increase cardiovascular risk, and retrospective studies suggest a reduction in events in men with metabolic syndrome and type 2 diabetes.展开更多
Androgen replacement therapy （ART） efficacy on late-onset hypogonadism （LOH） has been widely investigated in Western countries; however, it remains controversial whether ART can improve health and prolong active l...Androgen replacement therapy （ART） efficacy on late-onset hypogonadism （LOH） has been widely investigated in Western countries; however, it remains controversial whether ART can improve health and prolong active lifestyles. We prospectively assessed long-term ART effects on the physical and mental statuses of aging men with LOH in Japan. The primary endpoint was health-related quality of life assessed by questionnaires. Secondary endpoints included glycemic control, lipid parameters, blood pressure, waist circumference, body composition, muscular strength, International Prostate Symptom Scores （IPSS）, International Index of Erectile Function-5 （IIEF-5） scores, and serum prostate-specific antigen levels. Of the 1637 eligible volunteers, 334 patients 〉 40 years with LOH were randomly assigned to either the ART （n = 169） or control groups （n = 165）. Fifty-two weeks after the initial treatment, ART significantly affected the role physical subdomain of the short form-36 health survey （SF-36） scale （P= 0.0318）. ART was also associated with significant decreases in waist circumstance （P = 0.002） and serum triglyceride （TG） （P = 0.013） and with significant increases in whole-body and leg muscle mass volumes （P= 0.071 and 0.0108, respectively）, serum hemoglobin （P 〈 0.001）, IPSS voiding subscore （P = 0.0418）, and the second question on I IEF-5 （P = 0.0049）. There was no significant difference between the groups in terms of severe adverse events. In conclusion, in patients with LOH, long-term ART exerted beneficial effects on Role Physical subdomain of the SF-36 scale, serum TG, waist circumstance, muscle mass volume, voiding subscore of IPSS, and the second question of IIEF-5. We hope our study will contribute to the future development of this area.展开更多
文摘Hypogonadotropic hypogonadism(HH)represents a relatively rare cause of nonobstructive azoospermia(NOA),but its knowledge is crucial for the clinical andrologists,as it represents a condition that can be corrected with medical therapy in 3 quarters of cases.There are forms of congenital HH,whether or not associated with an absent sense of smell(anosmic HH or Kallmann syndrome,and normosmic HH,respectively),and forms of acquired HH.In congenital HH,complete absence of pubertal development is characteristic.On the other hand,if the deficit occurs after the time of pubertal development,as in acquired HH patients,infertility and typical symptoms of late-onset hypogonadism are the main reasons for seeking medical assistance.Gonadotropin-releasing hormone(GnRH)or gonadotropin replacement therapy is the mainstay of drug therapy and offers excellent results,although a small but significant proportion of patients do not achieve sufficient responses.
文摘Testosterone affects several organs in the body and is very important for male well-being.Aging men with late-onset hypogonadism(LOH)experience physiologic,psychiatric,and sexual symptoms related to a decline in the serum concentration of testosterone with age.However,it is well-known that the extent of the decline in testosterone concentration does not correlate with the severity of LOH-related symptoms.Therefore,it is difficult to diagnose and treat patients with LOH.In addition,the symptoms,response to testosterone replacement therapy(TRT),and medical insurance coverage differ among ethnicities and countries.The evaluation of testosterone is essential for the diagnosis and treatment of LOH.The effects of testosterone are determined not only by the serum testosterone concentration but also by the androgen receptor sensitivity.A low number of glutamine repeats is indicative of high androgenic activity,and the number shows ethnicity-related differences(fewer in African American than in Caucasian people and more in East Asian people).The diagnosis of LOH is typically made using subjective symptoms and the serum testosterone concentration.The Aging Male Symptoms scale is widely used to evaluate the symptoms.The normal range of total testosterone concentration varies around the world;therefore,clinicians should follow the guidelines of their regional academic society.The principal treatment for LOH is TRT.There are many types of TRT and other treatment strategies are also available.Thus,physicians should treat LOH according to each patient’s situation,considering related disorders,such as diabetes,osteoporosis,metabolic syndrome,and depression.
文摘Idiopathic hypogonadotropic hypogonadism is a rare disease that is characterized by delayed/absent puberty and/or infertility due to an insufficient stimulation of an otherwise normal pituitary-gonadal axis by gonadotrophin-releasing hormone （GnRH） action. Because reduced or normal luteinizing hormone （LH）/follicle-stimulating hormone （FSH） levels may be observed in the affected patients, the term idiopathic central hypogonadism （ICH） appears to be more appropriate. This disease should be distinguished from central hypogonadism that is combined with other pituitary deficiencies. Isolated ICH has a complex pathogenesis and ~s fivefold more prevalent in males. ICH frequently appears in a sporadic form, but several familial cases have also been reported. This finding, in conjunction with the description of numerous pathogenetic gene variants and the generation of several knockout models, supports the existence of a strong genetic component. ICH may be associated with several morphogenetic abnormalities, which include osmic defects that, with ICH, constitute the cardinal manifestations of Kallmann syndrome （KS）. KS accounts for approximately 40% of the total ICH cases and has been generally considered to be a distinct subgroup. However, the description of several pedigrees, which include relatives who are affected either with isolated osmic defects, KS, or normo-osmic ICH （nlCH）, justifies the emerging idea that ICH is a complex genetic disease that is characterized by variable expressivity and penetrance. In this context, either multiple gene variants or environmental factors and epigenetic modifications may contribute to the variable disease manifestations. We review the genetic mechanisms that are presently known to be involved in ICH pathogenesis and provide a clinical overview of the 227 cases that have been collected by the collaborating centres of the Italian ICH Network.
文摘Several testosterone preparations are used in the treatment of hypogonadism in the ageing male. These therapies differ in their convenience, flexibility, regional availability and expense but share their pharmacokinetic basis of approval and dearth of long-term safety data. The brevity and relatively reduced cost of pharmacokinetic based registration trials provides little commercial incentive to develop improved novel therapies for the treatment of late onset male hypogonadism. Selective androgen receptor modulators （SARMs） have been shown to provide anabolic benefit in the absence of androgenic effects on prostate, hair and skin. Current clinical development for SARMs is focused on acute muscle wasting conditions with defined clinical endpoints of physical function and lean body mass. Similar regulatory clarity concerning clinical deficits in men with hypogonadism is required before the beneficial pharmacology and desirable pharmacokinetics of SARMs can be employed in the treatment of late onset male hypogonadism.
文摘Late-onset hypogonadism （LOH） has been considered the most common form of male hypogonadism with a prevalence of approximately 1 in 100 men. Diagnosis of LOH should be made in symptomatic men with unequivocally low serum testosterone （T） levels. However, its clinical presentation is often insidious and difficult to recognize because it is characterized by nonspecific symptoms that make differential diagnosis with physiological ageing problematic. Sexual dysfunction is the most important determinant for medical consultation and the most specific symptom associated with low T. We therefore analysed a consecutive series of 1734 subjects who attended our unit for sexual dysfunction to investigate the associations between low T （different thresholds）, sexual parameters, medical history data （delayed puberty, pituitary disease or cryptorchidism） and their physical exam results. Metabolic parameters, in particular waist circumference, display the greatest accuracy in detecting low T. We found that only the association of several symptoms and signs could significantly raise the clinical suspicion of low T. Structured inventories, which cluster together symptoms and signs of hypogonadism, can help clinicians suspect androgen deficiency. In particular, structured interviews, such as ANDROTEST, have been demonstrated to have a greater accuracy when compared to self reported questionnaires in detecting low T levels.
文摘Late-onset hypogonadism is defined as a combination of low testosterone （T） levels and typical symptoms and signs. A major area of uncertainty is whether T concentrations are always really sufficient to fully reflect Leydig cell （dys）function. Mild testicular alteration could be diagnosed only by additional biochemical markers, such as luteinizing hormone （LH） and 25-hydroxyvitamin D levels. These markers help in identifying the so-called ＂subclinical＂ hypogonadism （normal T, high LH levels）. Patients with hypogonadism have frequently low levels of 25-hydroxyvitamin D due to impairment of the hydroxylating enzyme CYP2R1 in the testis. However, no data have been published dealing with the best treatment option （cholecalciferol - the Vitamin D precursor, or calcidiol - 25-hydroxylated form of Vitamin D） in these patients. We studied 66 patients with classic hypogonadism （total T [TT] 〈12 nmol I-~, LH 〉 8 IU 1-1） （n = 26） and subclinical hypogonadism （TT 〉 12 nmol I-＊, LH 〉 8 IU I-~） （n = 40） and low 25-hydroxyvitamin D （〈50 nmol I-1）. Subjects received cholecalciferol （5000 IU per week） （n = 20） or calcidiol （4000 IU per week） （n -- 46）, and 25-hydroxyvitamin D and parathyroid hormone （PTH） were evaluated after 3 months of therapy. Supplementation with calcidiol significantly increased 25-hydroxyvitamin D and significantly decreased PI＂H levels in both groups of men with hypogonadism （primary, n = 16 and subclinical, n = 30）, whereas supplementation with cholecalciferol did not modify their levels. This study shows for the first time that the administration of the 25-hydroxylated form of Vitamin D （calcidiol）, and not the administration of the precursor cholecalciferol, restores 25-hydroxyvitamin D levels in subjects with hypogonadism.
文摘Although suppressed serum testosterone （T） is common in ageing men, only a small proportion of them develop the genuine syndrome of low T associated with diffuse sexual （e.g., erectile dysfunction）, physical （e.g. loss of vigor and frailty） and psychological （e.g., depression） symptoms. This syndrome carries many names, including male menopause or climacterium, andropause and partial androgen deficiency of the ageing male （PADAM）. Late-onset hypogonadism （LOH） describes it best and is therefore generally preferred. The decrease of T in LOH is often marginal, and hypogonadism can be either due to primary testicular failure （low T, high luteinizing hormone （LH）） or secondary to a hypothalamic-pituitary failure （low T, low or inappropriately normal LH）. The latter form is more common and it is usually associated with overweight/obesity or chronic diseases （e.g., type 2 diabetes mellitus, the metabolic syndrome, cardiovascular and chronic obstructive pulmonary disease, and frailty）. A problem with the diagnosis of LOH is that often the symptoms （in 20%-40% of unselected men） and low circulating T （in 20% of men 〉70 years of age） do not coincide in the same individual. The European Male Ageing Study （EMAS） has recently defined the strict diagnostic criteria for LOH to include the simultaneous presence of reproducibly low serum T （total T 〈11 nmol 1-1 and free T 〈220 pmol 1-1） and three sexual symptoms （erectile dysfunction, and reduced frequency of sexual thoughts and morning erections）. By these criteria, only 2% of 40- to 80-year-old men have LOH. In particular obesity, but also impaired general health, are more common causes of low T than chronological age per se. Evidence-based information whether, and how, LOH should be treated is sparse. The most logical approach is lifestyle modification, weight reduction and good treatment of comorbid diseases. T replacement is widely used for the treatment, but evidence-based information about its real benefits and short- and long-term risks, is not yet available. In this review, we will summarize the current conceets and controversies in the Dathogenesis, diagnosis and treatment of LOH.
文摘This study sought to investigate late-onset hypogonadism （LOH） in old and middle-aged males in Shanghai communities, using symptom score evaluation systems and measurements of sex hormone levels. One thousand cases of males aged 40-70 years were investigated. The aging male symptoms （AMS） scale and androgen deficiency in aging males （ADAM） questionnaire were used at the beginning of the investigation, followed by measurement of the sex hormone-related factors （total testosterone （TT）, free testosterone （fT）, sex hormone-binding globulin （SHBG） and bioavailability of testosterone （Bio-T））. There were 977 valid questionnaires. The LOH-positive rates shown by AMS and ADAM were 59.88% and 84.65%, respectively; values increased with the age of the patients. There were 946 results related to sex hormone measurements, which showed the following results： TT was not related to aging （P〉O.05）; levels of SHBG increased with age; and fT and Bio-T decreased with age. There was a significant difference in fT between LOH-positive and LOH-negative patients, as shown by the ADAM. In summary, TT levels were not related to aging, even though SHBG did increase while fT and Bio-T decreased with aging. Clinically, the diagnosis of LOH cannot be based on serum TT level.
文摘This study aimed to propose an operational definition of late-onset hypogonadism(LOH)that incorporates both clinical symptoms and serum testosterone measurements to evaluate the prevalence of LOH in aging males in China.A population-based sample of 6296 men aged 40 years-79 years old was enrolled from six representative provinces in China.Serum total testosterone(TT),sex hormone-binding globulin(SHBG),and luteinizing hormone(LH)were measured and free testosterone(cFT)was calculated.The Aging Males’Symptoms(AMS)scale was used to evaluate the LOH symptoms.Finally,5078 men were included in this analysis.The TT levels did not decrease with age(P=0.59),and had no relationship with AMS symptoms(P=0.87 for AMS total score,P=0.74 for≥3 sexual symptoms).The cFT levels decreased significantly with age(P<0.01)and showed a negative association with the presence of≥3 sexual symptoms(P=0.03).The overall estimated prevalence of LOH was 7.8%(395/5078)if a cFT level<210 pmol l−1 combined with the presence of≥3 sexual symptoms was used as the criterion of LOH.Among them,26.1%(103/395)and 73.9%(292/395)had primary and secondary hypogonadism,respectively.After adjustment for confounding factors,primary and secondary hypogonadism was positively related to age and comorbidities.Body mass index was an independent risk factor for secondary hypogonadism.The results suggest that the AMS total score is not an appropriate indicator for decreased testosterone,and that the cFT level is more reliable than TT for LOH diagnosis.Secondary hypogonadism is the most common form of LOH.
文摘In this study, we investigated the essential criteria for late-onset hypogonadism （LOH） syndrome based on the presence of symptoms associated with low testosterone levels in Han Chinese men. Blood tests for total testosterone （TT） and sex hormone-binding globulin （SHBG） were performed, and the aging male symptoms （AMS） questionnaire was conducted in a randomly selected cohort composed of 944 Chinese men aged 40 to 79 years from nine urban communities. Three sexual symptoms （decreased ability/frequency of sexual activity, decreased number of morning erections, and decreased libido） were confirmed to be related to the total and free testosterone levels. The thresholds for TT were approximately 12.55 nmol l^-1 for a decreased ability/frequency to perform sex, 12.55 nmol l^-1 for decreased frequency of morning erections, and 14.35 nmol l^-1 for decreased sexual desire. The calculated free testosterone （CFT） thresholds for these three sexual symptoms were 281.14, 264.90, and 287.21 pmol l^-1, respectively. TT 〈13.21 nmol l^-1 （OR =1.4, 95%Ch 1.0-1.9, P= 0.037） or CFT 〈268.89 pmol l^-1 （OR - 1.5, 95%Ch 1.1-20, P=0.020） was associated with an increase in the aforementioned three sexual symptoms. The prevalence of LOH was 9.1% under the criteria, including all three sexual symptoms with TT levels 〈13.21 nmol l^-1 and CFT levels 〈268.89 pmol l^-1. Our results may improve the diagnostic accuracy of LOH in older men.
文摘Both pulsatile gonadotropin-releasing hormone （GnRH） infusion and combined gonadotropin therapy （human chorionic gonadotropin and human menopausal gonadotropin [HCG/HMG]） are effective to induce spermatogenesis in male patients with congenital hypogonadotropic hypogonadism （CH H）. However, evidence is lacking as to which treatment strategy is better. This retrospective cohort study included 202 patients with CHH： twenty had received pulsatile GnRH and 182 had received HCG/HMG. Patients had received therapy for at least 12 months. The total follow-up time was 15.6 ± 5.0 months （range： 12-27 months） for the GnRH group and 28.7 ± 13.0 months （range： 12-66 months） for the HCG/HMG group. The median time to first sperm appearance was 6 months （95% confidence interval [CI]： 1.6-10.4） in the GnRH group versus 18 months （95% Ch 16.4-20.0） in the HCG/HMG group （P〈 0.001）. The median time to achieve sperm concentrations 〉5 x 106 m1-1 was 14 months （95% Ch 5.8-22.2） in the GnRH group versus 27 months （95% Ch 18.9-35.1） in the HCG/HMG group （P 〈 0.001）, and the median time to concentrations 〉10 x 106 m1-1 was 18 months （95% Ch 10.0-26.0） in the GnRH group versus 39 months （95% CI unknown） in the HCG/HMG group. Compared to the GnRH group, the HCG/HMG group required longer treatment periods to achieve testicular sizes of 〉4 ml, 〉8 ml, 〉12 ml, and 〉16 ml. Sperm motility （a ＋ b ＋ c percentage） evaluated in semen samples with concentrations 〉1 × 106 ml-1 was 43.7% ± 20.4% （16 samples） in the GnRH group versus 43.2% ± 18.1% （153 samples） in the HCG/HMG group （P= 0.921）. Notably, during follow-up, the GnRH group had lower serum testosterone levels than the HCG/HMG group （8.3 ±4.6 vs 16.2 ± 8.2 nmol 1-1, P 〈 0.001）. Our study found that pulsatile GnRH therapy was associated with earlier spermatogenesis and larger testicular size compared to combined gonadotropin therapy. Additional prospective randomized studies would be required to confirm these findings.
文摘Although idiopathic hypogonadotropic hypogonadism （IHH） has traditionally been viewed as a life-long disease caused by a deficiency of gonadotropin-releasing hormone neurons, a portion of patients may gradually regain normal reproductive axis function during hormonal replacement therapy. The predictive factors for potential IHH reversal are largely unknown. The aim of our study was to investigate the incidence and clinical features of IHH male patients who had reversed reproductive axis function. In this retrospective cohort study, male IHH patients were classified into a reversal group （n = 18） and a nonreversal group （n = 336）. Concentration of gonadotropins and testosterone, as well as testicle sizes and sperm counts, were determined. Of 354 IHH patients, 18 （5.1%） acquired normal reproductive function during treatment. The median age for reversal was 24 years old （range 21-34 years）. Compared with the nonreversal group, the reversible group had higher basal luteinizing hormone （LH） （1,0±0.7 IU 1-1 vs 0.4±0.4 IU 1-1, P 〈 0.05） and stimulated LH （28.3 ± 22.6 IU 1-1 vs 1.9 ±1.1 IU 1-1, P 〈 0.01） levels, as well as larger testicle size （5.1 ±2.6 ml vs 1.5± 0.3 ml, P〈 0.01）, at the initial visit. In summary, larger testicle size and higher stimulated LH concentrations are favorite parameters for reversal. Our finding suggests that reversible patients may retain partially active reproductive axis function at initial diagnosis.
文摘In the past, the indications for varicocelectomy are primarily for infertility with abnormal semen parameters, testicular hypotrophy/atrophy in adolescents, and/or pain. The surgical treatment of varicocele for hypogonadism is controversial and debated. Recently, multiple reports in the literature have suggested that varicocele is associated with hypogonadism and varicocele repair can increase testosterone levels. Men with hypogonadal symptoms should have at least two serum testosterone levels. Microsurgical varicocelectomy may be beneficial for men with clinically palpable varicoceles with documented hypogonadism. In this review, we summarize the most recent literature linking varicocele to hypogonadism and sexual dysfunction and the impact of repair on serum testosterone levels. We performed a search of the published English literature. The key words used were ＂varicocele and hypogonadism＂ and ＂varicocele surgery and testosterone.＂ We included published studies after 1998. We, also, evaluated the effect of surgery on the changes in the serum testosterone level regardless of the indication for the varicocele repair.
文摘Klinefelter syndrome （KS） （47, XXY） is the most abundant sex-chromosome disorder, and is a common cause of infertility and hypogonadism in men. Most men with KS go through life without knowing the diagnosis, as only 25% are diagnosed and only a few of these before puberty. Apart from hypogonadism and azoospermia, most men with KS suffer from some degree of learning disability and may have various kinds of psychiatric problems. The effects of long-term hypogonadism may be difficult to discern from the gene dose effect of the extra X-chromosome. Whatever the cause, alterations in body composition, with more fat and less muscle mass and diminished bone mineral mass, as well as increased risk of metabolic consequences, such as type 2 diabetes and the metabolic syndrome are all common in KS. These findings should be a concern as they are not simply laboratory findings; epidemiological studies in KS populations show an increased risk of beth hospitalization and death from various diseases. Testosterone treatment should be offered to KS patients from early puberty, to secure a proper masculine development, nonetheless the evidence is weak or nonexisting, since no randomized controlled trials have ever been published. Here, we will review the current knowledge of hypogonadism in KS and the rationale for testosterone treatment and try to give our best recommendations for surveillance of this rather common, but often ignored, syndrome.
文摘The production of testosterone occurs within the Leydig cells of the testes. When production fails at this level from either congenital, acquired, or systemic disorders,the result is primary hypogonadism. While numerous testosterone formulations have been developed, none are yet fully capable of replicating the physiological patterns of testosterone secretion. Multiple stem cell therapies to restore androgenic function of the testes are under investigation. Leydig cells derived from bone marrow, adipose tissue, umbilical cord, and the testes have shown promise for future therapy for primary hypogonadism. In particular, the discovery and utilization of a group of progenitor stem cells within the testes, known as stem Leydig cells(SLCs), has led not only to a better understanding of testicular development, but of treatment as well. When combining this with an understanding of the mechanisms that lead to Leydig cell dysfunction, researchers and physicians will be able to develop stem cell therapies that target the specific step in the steroidogenic process that is deficient. The current preclinical studies highlight the complex nature of regenerating this steroidogenic process and the problems remain unresolved. In summary, there appears to be two current directions for stem cell therapy in male primary hypogonadism. The first method involves differentiating adult Leydig cells from stem cells of various origins from bone marrow, adipose, or embryonic sources. The second method involves isolating, identifying, and transplanting stem Leydig cells into testicular tissue. Theoretically, in-vivo re-activation of SLCs in men with primary hypogonadism due to age would be another alternative method to treat hypogonadism while eliminating the need for transplantation.
文摘We conducted an analysis of the Kallmann syndrome 1 （KAL-1） genotype in 17 patients with Kallmann syndrome （KS）, 9 patients with normosmic idiopathic hypogonadotropic hypogonadism （nlHH） and 20 age-matched normal men in Northwestern China. To do this, we used multiplex PCR analysis with exon-flanking primers and automated sequencing techniques with peripheral blood DNA samples. Intragenic deletions were found at the KAL-1 locus in two KS patients. One case with an atrial septal defect exhibited an intragenic deletion of exon 6. Another KS patient with cryptorchidism had intragenic deletions of exons 5 and 6. For the nlHH patients, no abnormalities were observed in the exonic and flanking sequences of KAL-1. This report describes two intragenic deletions of KAL-1 in two KS patients and suggests that KAL-1 deletion might be more prevalent in KS patients with other congenital organ abnormalities than those described previously in other series from Northwestern China.
文摘The aim of this study was to evaluate the relationship between lower urinary tract symptoms （LUTSs）, erectile dysfunction （ED） and symptomatic late-onset hypogonadism （SLOH） in ageing men in the Aegean region of Turkey. Five hundred consecutive patients 〉40 years old who had been in a steady sexual relationship for the past 6 months and were admitted to one of six urology clinics were included in the study. Serum prostate-specific antigen and testosterone levels and urinary flow rates were measured. All patients filled out the International Prostate Symptom Score and Quality of Life （IPSS-QoL）, International Index of Erectile Function （IIEF） and Aging Males＇ Symptoms （AMS） scale forms. Of the patients, 23.9% had mild LUTSs, 53.3% had moderate LUTSs and 22.8% had severe LUTSs. The total testosterone level did not differ between groups. Additionally, 69.6% had ED. The presence of impotence increased with increasing LUTS severity. Symptomatic late-onset hypogonadism （AMS 〉27） was observed in 71.2% of the patients. The prevalence of severe hypogonadism symptoms increased with the IPSS scores. A correlation analysis revealed that all three questionnaire scores were significantly correlated. In conclusion, LUTS severity is an age-independent risk factor for ED and SLOH. LUTS severity and SLOH symptoms appear to have a strong link that requires etiological and biological clarification in future studies.
文摘Hypogonadotropic hypogonadism(HH)is a rare disease in which medical treatment has a high success rate to achieve fertility.This study aimed to an a lyze the efficacy of horm one replacement therapy and determi ne predictive factors for successful spermatogenesis and spontaneous pregnancy in patients with idiopathic HH.A total of 112 patients with low testosterone(T),luteinizing hormone(LH)and follicle-stimulating hormone(FSH),and normal prolactin levels were diagnosed with HH and administered LH and FSH analogs as hormone replacement therapy.During treatment,96(85.7%)patients had sperm present in ejaculate samples.Among these patients,72 were married and wanted a child.Of these 72 patients,48(66.7%)of couples had pregnancies from natural conception.After initiation of treatment,the mean time for the appearance of sperm in semen was 9.48 months.There were no significant differences between baseline FSH,T,and LH levels;however,older age,larger testicular size,and low rate of undescended testes were favorable factors for successful spermatogenesis.Larger testicular size and older age were also the main predictive factors for natural conception.We found that patients with undescended testes had a younger age,smaller testes,and lower T levels compared with patients exhibit!ng descended testes.The rate of sperm found in the ejaculate was not significantly decreased in patients with undescended compared with descended testis(73.7%vs 87.6%,P=0.261).The medical approach for males with HH and azoospermia provides a successful treatment modality in regard to successful spermatogenesis and achievement of pregnancy.
文摘Male hypogonadism associated with obesity is a very prevalent condition and is increasing in parallel with the epidemic prevalence of obesity. Low testosterone levels promote higher fat mass with reduced lean mass. Male hypogonadism is related to an increase in associated cardiometabolic complications, such as hypertension, type 2 diabetes mellitus, the metabolic syndrome, and cardiovascular disease. Its influence as a comorbidity of obesity is becoming more evident and should be evaluated and treated in at-risk patients. Mechanisms involved in this relationship include body composition changes, the presence of adipokines, insulin resistance, and other factors, some of which are still unknown. Weight loss and treatment to replace testosterone levels improve the metabolic profile and quality of life in patients with obesity and hypogonadism; these beneficial effects depend on treatment modality and duration of therapy. The use of testosterone replacement therapy may be indicated, as it has not been shown to increase cardiovascular risk, and retrospective studies suggest a reduction in events in men with metabolic syndrome and type 2 diabetes.
文摘Androgen replacement therapy （ART） efficacy on late-onset hypogonadism （LOH） has been widely investigated in Western countries; however, it remains controversial whether ART can improve health and prolong active lifestyles. We prospectively assessed long-term ART effects on the physical and mental statuses of aging men with LOH in Japan. The primary endpoint was health-related quality of life assessed by questionnaires. Secondary endpoints included glycemic control, lipid parameters, blood pressure, waist circumference, body composition, muscular strength, International Prostate Symptom Scores （IPSS）, International Index of Erectile Function-5 （IIEF-5） scores, and serum prostate-specific antigen levels. Of the 1637 eligible volunteers, 334 patients 〉 40 years with LOH were randomly assigned to either the ART （n = 169） or control groups （n = 165）. Fifty-two weeks after the initial treatment, ART significantly affected the role physical subdomain of the short form-36 health survey （SF-36） scale （P= 0.0318）. ART was also associated with significant decreases in waist circumstance （P = 0.002） and serum triglyceride （TG） （P = 0.013） and with significant increases in whole-body and leg muscle mass volumes （P= 0.071 and 0.0108, respectively）, serum hemoglobin （P 〈 0.001）, IPSS voiding subscore （P = 0.0418）, and the second question on I IEF-5 （P = 0.0049）. There was no significant difference between the groups in terms of severe adverse events. In conclusion, in patients with LOH, long-term ART exerted beneficial effects on Role Physical subdomain of the SF-36 scale, serum TG, waist circumstance, muscle mass volume, voiding subscore of IPSS, and the second question of IIEF-5. We hope our study will contribute to the future development of this area.
