青少年男性性腺功能减退与胰岛素抵抗关系的初步研究

目的:探讨青少年男性血清睾酮水平和胰岛素抵抗之间的关系。方法:采用病例对照的方法。研究组为21例15~30岁性腺功能减退的男性患者,对照组为11例年龄和体重指数(BM I)相匹配的已完成青春期发育的健康男性。所有受试者均测定身高、体重、染色体、骨龄、血清促性腺激素和总睾酮(TT)水平,行3 h口服葡萄糖耐量试验(OGTT)测定0、30、60、120、180 m in的血糖和胰岛素水平。对两组间空腹血糖水平、空腹血清胰岛素水平、OGTT时血糖和胰岛素曲线下面积及HOMA胰岛素抵抗指数(HOMA-IR)进行比较。结果:①研究组平均血清TT水平为(0.9±0.6)nmol/L。其中5例K linefelter综合征患者已有青春期发育,Tanner分级达P3以上,其他16例低促性腺激素型性腺功能减退的患者无青春期发育。②研究组和对照组间的空腹血糖水平、3 h OGTT血糖和胰岛素曲线下面积差异无显著性。③研究组中有3例患者经OGTT诊断为糖耐量受损(IGT)。研究组患者糖负荷后胰岛素分泌高峰均在服糖后30 m in出现。对照组中无IGT或糖尿病患者。④在两组之间,HOMA-IR和空腹胰岛素水平的差异有显著性(P分别为0.021和0.018)。结论:①血清TT水平低下的青少年男性出现糖耐量低减的发生率高于对照组。②血清TT水平低下的青少年男性,空腹胰岛素水平和HOMA-IR均显著高于对照组,提示睾酮缺乏可能导致患者对胰岛素的抵抗。     

Anabolic androgenic steroid-induced hypogonadism,a reversible condition in male individuals? A systematic review

The anabolic–androgenic steroids (AAS) are clinically used as an androgen replacement, in hypogonadism treatment, to induce puberty, and also in the treatment of chronic degenerative diseases. The AAS use out of clinical context is becoming massively, being used merely for aesthetic reasons. AAS abuse may cause severe disarrangement on the HPG axis and generate a significant decrease in testosterone synthesis and secretion by the testes. This review aims to evaluate whether the hypogonadism induced by AAS abuse is reversible and under what circumstances the reversibility is possible. For this, PRISMA guidelines and several databases are used between July and September 2020. Altogether, this systematic review identified and analysed 179 cases of AAS users. Of these, 168 cases had the hypogonadism clearly diagnosed and proven to be linked exclusively to AAS abuse. However, between these 168 cases, only 38 cases presented fully known outcomes and among these, merely in 4, the hypogonadism was completely reversible (2 based on drug therapy) with HPG axis recovery. In conclusion, this review presents evidences that AAS-induced hypogonadism is a seriously underestimated problem, and in the majority of cases, full recovery is very difficult to succeed.     

A de novo hexokinase 1 (HK1) variant presenting as Boucher–Neuhäuser syndrome

Boucher–Neuhäuser syndrome (BNHS) is characterized by chorioretinal dystrophy, hypogonadotropic hypogonadism, and cerebellar dysfunction and atrophy. The disorder has been associated with biallelic pathogenic variants in the patatin-like phospholipase domain-containing protein 6 (PNPLA6) gene. We present an individual with a clinical diagnosis consistent with BNHS who lacked any PNPLA6 variants but on quartet family exome sequencing had a de novo variant in the hexokinase 1 (HK1) gene (NM_000188.2 [GRCh37/hg19]: g.71139826G>A, c.1240G>A, p.Gly414Arg), suggesting genetic heterogeneity for BNHS. Longitudinal follow-up indicated neurological deterioration, neuropsychiatric symptoms, and progressive cerebellar atrophy. The BNHS phenotype overlaps and expands the known HK1 genotypic and phenotypic spectrum. Individuals with variants in HK1 should undergo evaluation for hypogonadotropic hypogonadism, potentially amenable to treatment.     

迟发性睾丸功能减退筛查量表的研究与应用现状

随着迟发性睾丸功能减退(LOH)研究的深入,LOH筛查量表研究逐渐完善。常用筛查量表有AMS量表、ADAM问卷、MMAS问卷,量表的主要作用是筛查或者诊断LOH以及治疗效果的评估,目前研究主要集中在量表的应用、敏感性和特异性的验证、量表评价结果或者某些项目与血清激素水平之间的相关性、不同量表之间的比较等方面。本文综述筛查量表的研究、应用现状,并对其敏感性、特异性进行了总结。     

Successful testis preservation for bilateral testicular tumors with a new chemotherapy-based protocol: Initial results of three cases

The treatment for bilateral testicular tumors is associated with infertility and hypogonadism. We carried out testis-preserving therapy treatment for three patients with synchronous bilateral tumors with seminoma. Our protocol of testis preservation consisted of unilateral orchiectomy for the larger tumor followed by three courses of chemotherapy with a cisplatin, etoposide and bleomycin regimen. All three patients showed no recurrence 24, 24, and 82 months after treatment. The serum testosterone level was maintained around the lower limit of the normal range in all patients without androgen replacement, and sexual function was not impaired. One patient showed oligospermia, preoperatively, and the number of sperm was preserved at a similar level after treatment. Azoospermia was observed in two patients before the treatment, and still persisted after treatment. Testis preservation with a chemotherapy-based new protocol was carried out successfully without recurrence. In addition, our protocol preserved a good quality of life in all patients.     

Treatment for late-onset hypogonadism: the current situation in Japan

Prevention of age-related disability has become very important because the number of people aged 60 years and older is increasing rapidly. Androgen levels decrease with aging and this plays many physiologic roles in various organs. Late-onset hypogonadism (LOH) has received widespread attention in the last few years. LOH symptoms include sexual dysfunction and depression, and the first-line treatment should be hormone replacement therapy (HRT), by which several symptoms of LOH are improved. Although several types of testosterone preparations are available worldwide, the testosterone preparations available in Japan are limited. For this reason, the Clinical Practice Manual for LOH, authored by a collaborative team from the Japanese Urological Association and the Japanese Society for the Study of the Aging Male, recommends HRT with testosterone enanthate, human chorionic gonadotropin (hCG) and ‘Glowmin’, a short-acting testosterone ointment produced in Japan. In this review, we summarize the efficacy of HRT for LOH symptoms and introduce hCG and Glowmin therapy according to the Clinical Practice Manual. However, several studies, including our own, have shown that LOH symptoms are not always related to serum testosterone concentration. Thus, HRT is not adequate as the only treatment option for LOH because eugonadal men with symptoms of LOH comprise 30% of the general population. We discuss the efficacy of Japanese herbal medicines, which have been used for treatment of the menopause and several psychological disorders, particularly in the treatment of eugonadal patients with symptoms of LOH.     

男性迟发性性腺功能减退的诊断、治疗及监测——ISA、ISSAM、EAU、EAA及ASA推荐

ISA、ISSAM、EAU、EAA及ASA关于男性迟发性性腺功能减退的诊断、治疗及监测的推荐指南,为临床医师诊断、治疗成人发病、年龄相关的睾酮缺乏提供了以临床研究为基础的证据.     

Testosterone replacement therapy for older men

Despite intensive research on testosterone therapy for older men, important questions remain unanswered. The evidence clearly indicates that many older men display a partial androgen deficiency. In older men, low circulating testosterone is correlated with low muscle strength, with high adiposity, with insulin resistance and with poor cognitive performance. Testosterone replacement in older men has produced benefits, but not consistently so. The inconsistency may arise from differences in the dose and duration of testosterone treatment, as well as selection of the target population. Generally, studies reporting anabolic responses to testosterone have employed higher doses of testosterone for longer treatment periods and have targeted older men whose baseline circulating bioavailable testosterone levels were low. Most studies of testosterone replacement have reported anabolic that are modest compared to what can be achieved with resistance exercise training. However, several strategies currently under evaluation have the potential to produce greater anabolic effects and to do so in a safe manner. At this time, testosterone therapy can not be recommended for the general population of older men. Older men who are hypogonadal are at greater risk for the catabolic effects associated with a number of acute and chronic medical conditions. Future research is likely to reveal benefits of testosterone therapy for some of these special populations. Testosterone therapy produces a number of adverse effects, including worsening of sleep apnea, gynecomastia, polycythemia and elevation of PSA. Efficacy and adverse effects should be assessed frequently throughout the course of therapy.     

Is discontinuation of hormone replacement therapy possible for patients with late‐onset hypogonadism?

Objective:   The first-line treatment for late-onset hypogonadism (LOH) is hormone replacement therapy (HRT). However, whether lifetime HRT is necessary has not been settled. We evaluated LOH-related symptoms and endocrinologic values after discontinuation of HRT in patients with LOH who had benefited from it.
Methods:   Twenty-five men (mean age 54.2 years, range 40–73) in whom HRT had been effective and who were available for follow-up 3 months after the discontinuation of HRT were studied. LOH-related symptoms were judged according to the Aging Males' Symptoms (AMS) scale and other questionnaires. Laboratory and endocrinologic values and LOH-related symptoms were assessed before HRT, at the end of HRT, and 3 months after its discontinuation.
Results:   Serum testosterone levels increased significantly with HRT. However, they returned to the pretreatment levels after discontinuation of HRT. The total AMS score decreased significantly after HRT, and a significant improvement was maintained 3 months after discontinuation. The somatovegetative and psychological subscores of the AMS also improved, although the sexual subscore did not change significantly. A slight improvement was also observed in the short version of the International Index of Erectile Function (IIEF-5) score and the Self-rating Depression Scale (SDS) score after HRT. However, changes in these scores did not reach statistical significance. No other changes in the endocrinologic profile and no severe adverse effects were seen.
Conclusions:   Improvement in symptoms may remain after discontinuation of HRT in patients with LOH even though their endocrinologic status declines. Our findings may encourage physicians to discontinue HRT if LOH-related symptoms have improved after several months of HRT.