Signs of testicular insufficiency in adrenomyeloneuropathy and neurologically asymptomatic X-linked adrenoleukodystrophy: a retrospective study

X-linked adrenoleukodystrophy (X-ALD) is characterized by central nervous system demyelination, and impaired steroidogenesis in the adrenal cortex and testis. Most patients develop adrenocortical insufficiency. We studied retrospectively the frequency and severity of testicular dysfunction in 26 men with X-ALD. Twenty-one had adrenomyeloneuropathy and five patients were neurologically asymptomatic. In addition to obtaining a routine history and physical examination, we studied plasma levels of testosterone, sex hormone binding globulin, the free androgen index, and the plasma concentrations of dehydroepiandrosterone-sulphate, LH and FSH. In a subset of patients, the testosterone response to hCG and the LH and FSH responses to GnRH were also determined. Clinical signs of gonadal dysfunction were manifested by diminished libido (46%), largely overlapping with erectile dysfunction (58%), and failure of the testes to descend (15%). Physical examination revealed diminished body sexual hair (50%), gynaecomastia (35%), and small testes (12%). Laboratory studies showed low plasma total testosterone levels in 12%, and an insufficient increase after stimulation with hCG in 88% (15 of 17 patients tested). Plasma LH concentration was increased in 16%, and the plasma FSH level was elevated in 32%. The response of LH concentrations to GnRH stimulation was abnormally high in 47% (nine of 19 patients studied), and the response of FSH levels was too low in 16% (three of 19 patients tested). In conclusion, in a retrospective study of 26 men' with X-ALD, in 20 some signs of clinical hypogonadism were found. Plasma testosterone values were generally in the normal range, but upon testing of the hypothalamo-pituitary-testis axis some abnormalities became apparent.     

Preserving fertility in the hypogonadal patient: an update

An increasing number of young and middle-aged men are seeking treatment for symptoms related to deficient levels of androgens (hypogonadism) including depression, loss of libido, erectile dysfunction, and fatigue. The increase in prevalence of testosterone supplementation in general and anabolic steroid-induced hypogonadism specifically among younger athletes is creating a population of young men who are uniquely impacted by the testicular end-organ negative consequences of exogenous steroid use. Exogenous testosterone therapy can alter the natural regulation of the hypothalamic-pituitary-gonadal axis leading to impaired spermatogenesis with azoospermia being a serious possible result, thus rendering the individual infertile. For men of reproductive age who suffer from hypogonadal symptoms, preservation of fertility is an important aspect of their treatment paradigm. Treatment with human chorionic gonadotropin (hCG) has shown the ability not only to reverse azoospermia brought on by testosterone supplementation therapy but also to help maintain elevated intratesticular testosterone levels. In addition, selective estrogen receptor modulators, often used with hCG have been shown both to elevate total testosterone levels and to maintain spermatogenesis in hypogonadal men.     

Hypophyseal-Gonadal Dysfunction in Men with Non-Alcoholic Liver Cirrhosis

Seven males with liver cirrhosis associated with hepatitis and one with schistosomal liver fibrosis were studied for hypophyseal gonadal dysfunction and compared to six age matched controls. Cirrhotics as a group had higher serum 17 beta estradiol levels (22.1 +/- 6.3 vs 7.8 +/- 0.8 pg/ml, p less than 0.05) which did not rise after four days of human chorionic gonadotropin (hCG) stimulation. Conversely, there was an adequate rise in serum testosterone level after hCG stimulation (332.8 +/- 99.7 ng/dl baseline to 887.6 +/- 67.1 ng/dl, p less than 0.01). Compared to the controls, cirrhotics had lower baseline serum follicle stimulating hormone (FSH) (3.6 +/- 1.7 vs. 10.2 +/- 1.5 mIu/ml, p less than 0.02) and higher serum prolactin (13.5 +/- 2.5 vs. 6.8 +/- 1.0 ng/ml, p less than 0.05). Pituitary dynamic function testing in cirrhotics revealed blunted response of luteinizing hormone (LH) and FSH, to luteinizing hormone releasing hormone (LHRH) in four out of eight subjects tested. We conclude that the mechanism of hypogonadism in non-alcoholic cirrhosis is mostly hypogonadotropic in origin rather than primary gonadal injury which is common in alcoholic cirrhosis.     

The role of testosterone in erectile function and dysfunction

Erectile response is centrally and peripherally regulated by androgens. Severe hypogonadism in men usually results in loss of libido and potency which can be restored by androgen administration.It was originally thought that androgens exert their effects on libido and that effects on erections were secondary to effects on libido. It is now clear that androgens are necessary for the maintenance of the anatomical and physiological substrate of erections. Restoring testosterone levels to normal is required in cases of erectile dysfunction.It was long assumed that sexual functions required androgen levels below or at the low end of reference values of testosterone. It is now clear that there are individual differences while the threshold increases with aging.The administration of PDE-5-inhibitors is not always sufficient to restore erectile potency in men, and administration of testosterone improves the therapeutic response to PDE-5-inhibitors considerably.Erectile dysfunction is strongly age-related, and it is evident that its etiology is multi-factorial. It is intriguing that testosterone is interrelated with a number of etiological factors such as obesity, diabetes mellitus and atherosclerosis.     

Infertility and hypergonadotropic hypogonadism as first evidence of hereditary apolipoprotein A-I amyloidosis

PURPOSE: We report that primary infertility and hypergonadotropic hypogonadism in young patients may be caused by testicular amyloidosis and it is associated with the presence of a mutation in the apoA-I gene, resulting in the replacement of proline for leucine at residue 75 of the protein. MATERIALS AND METHODS: Ten patients presenting with infertility, gynecomastia, decreased libido, erectile dysfunction or a family history of amyloidosis underwent clinical evaluation, hormone assays, semen analysis, ultrasonographic investigation of the testicles, testicular biopsy and DNA sequencing of the apoA-I gene. RESULTS: All patients showed azoospermia and 9 had increased testicular volume. Massive amyloid deposition was observed in all testicular biopsies and the apoA-I mutation of replacement of proline for leucine at residue 75 of the protein was noted. Five patients showed hypergonadotropic hypogonadism and 5 had normal testosterone values with high gonadotropin levels. CONCLUSIONS: Nonobstructive azoospermia and macro-orchidism with or without hypogonadism may be caused by hereditary apoA-I amyloidosis in young patients. Testicular amyloidosis can be the first manifestation of this systemic disease. Specific staining for amyloid deposits and genetic analysis of apoA-I mutations are recommended in young, infertile patients with macro-orchidism. Finally, surveillance in asymptomatic mutation carriers is suggested to evaluate the opportunity to implement sperm retrieval and start androgen replacement therapy when necessary.     

Testosteron und erektile Dysfunktion

Primary hypogonadism represents a classic but rare cause of erectile dysfunction (ED) in men. Therapy with testosterone as monotherapy is therefore unlikely to cure ED in the typical ED patient. However, recent developments indicate a much greater role of testosterone in erectile function than has been supposed in the past. Serum testosterone levels decline in men with increasing age. Aging men might develop late-onset hypogonadism (LOH) associated with characteristic symptoms. Typical symptoms of LOH are represented by decreased libido and sexual function, osteoporosis, altered distribution of body fat, overall reduction in physical strength, and alterations in the general mood. Experimental and clinical studies over the last few years have also pointed out that hypogonadism results in characteristic alterations of the erectile tissue of the penis. These alterations might be reversible in response to hormone therapy with testosterone. Particularly testosterone might be a helpful supportive therapy in cases where PDE-5 antagonists have tended to lose their effectiveness on the erectile tissue in the treatment of ED.     

Responses of serum testosterone levels to human chorionic gonadotrophin stimulation in patients with Klinefelter''s syndrome after long-term androgen replacement therapy

Responses of serum testosterone levels to repeated daily injections of 5000 IU hCG for 4 days were studied in 24 patients with Klinefelter's syndrome. Eighteen patients were untreated, and 8 had been given previous treatment with depot testosterone 100 mg intramuscularly every 2-3 weeks for an average duration of 4.7 years. Among them, 4 patients were examined both before and after the therapy. The hCG test was performed at least 2 weeks (0.5-12 months) after the last injection of depot testosterone in the treated patients. Mean basal testosterone level of the treated patients, 139 +/- 98 ng/dl (Mean +/- SD), was not significantly different from that of the untreated patients, 172 +/- 110 ng/dl. Maximum stimulated testosterone level in the treated patients, 170 +/- 107 ng/dl (P less than 0.05). These results suggest that long-term androgen administration may decrease the functional reserve of Leydig cells in patients with Klinefelter's syndrome.     

PADAM aus urologischer Sicht

PADAM stands for partial androgen deficiency in the aging male, and it is currently diagnosed with a testosterone level below 3 ng/ml (300 ng/dl or 12 nmol/l), and with symptoms varying according to the individual. The symptoms are a reduction or even loss of libido, a decline in muscle mass and strength, enhancement of visceral fatty tissue-padding, dryness of the skin, apathy, tiredness and distortion of mood right up to depression, and ostalgia due to osteoporosis. Before starting any form of hormonal substitution, which is only indicated if clinical symptoms and testosterone deficiency correlate, it is absolutely essential to exclude prostate cancer by using clinical evaluation and PSA values. Close PSA monitoring is necessary during testosterone substitution. In more than 95% of all patients with erectile dysfunction, the cause is not testosterone deficiency. Even a decreased level of dehydroepiandrosterone (DHEA) in an elderly male needs no replacement. There is also no indication for estradiol therapy in men--except in the rare case of aromatase deficiency.     

Clinical study of hypogonadotropic hypogonadism

Clinical study of eight cases of hypogonadotropic hypogonadism was performed. These cases consisted of five prepubertal cases and three postpubertal cases induced by prolactin-producing hypophyseal tumor. The former five cases had the chief complaints of incomplete development of their external genitalia. The chief complaints in three postpubertal cases were decreased libido in two and infertility in one. The average testicular volumes were 7.8 ml and 20 ml in prepubertal and postpubertal cases, respectively. The basal levels of luteinizing hormone (LH) were within the normal limit in most cases and follicle stimulating hormone (FSH) were low in most cases. There were no differences between the levels of these hormones in prepubertal cases and those in postpubertal cases. The range of basal level of prolactin in blood was 92 mg/ml to 1,070 ng/ml in the postpubertal cases. The basal level of testosterone in blood was low in all cases. Most cases had rather good responses of LH and FSH after the administration of luteinizing hormone releasing hormone. The plasma level of testosterone was elevated after the administration of human chorionic gonadotropin (hCG) in most cases. The appearance of sperm in the semen was observed after the hCG therapy in only one of the prepubertal cases. On the other hand, all the postpubertal cases showed almost normal findings in semen analysis after hormone therapy.     

Testosterone replacement: when is there a role?

Hypogonadism is an uncommon cause of erectile dysfunction. Unfortunately, hypogonadal states in adult males are difficult to diagnose on purely clinical grounds and it is necessary to seek biochemical support. The simplest way to establish the diagnosis of hypogonadism is by determination of serum testosterone levels. Several methods exist but total testosterone determination plus assessment of sex hormone-binding globulin or bio-available testosterone appear to be the most reliable and accessible. Once a diagnostic of hypogonadism has been established in a man with erectile difficulties, a trial of androgen supplementation is warranted if no contraindications exist. Knowledgeable monitoring is essential. In the absence of an adequate response, co-morbidities should be diligently sought out. In the absence of reliable guidelines for androgen administration to patients with erectile failure, a set of recommendations are provided. International Journal of Impotence Research (2000) 12, Suppl 4, S112-S118.     

Serum Prolactin in Male Infertility

Hyperprolactinemia was found only in two out of 71 patients with male infertility and in none of 53 patients with impotentia coeundi indicating that hyperprolactinemia is of minor significance in these patients. There was only a weak negative correlation between hPRL and testosterone in oligozoospermic men. No correlation was found between hPRL and hLH, hFSH, sperm count and sperm motility. Nevertheless measurement of hPRL should be performed in all cases with hypogonadotropic hypogonadism, loss of libido or impotence since these symptoms may be signs of a prolactin-producing pituitary adenoma.     

Brain tumor (germinoma) diagnosed after assessment for male late-onset hypogonadism syndrome: a case report

A 44-year-old man suffered from sleep disturbance, headache, lack of energy and appetite loss. His local doctor recommended he consult our clinic for further examination of late-onset hypogonadism. His aging males' symptoms (AMS) and international index of erectile function (IIEF-5) scores were 62 and 1, respectively. His biochemistry revealed 0.29 mIU/ml luteinizing hormone (LH), 1.36 mIU/ml follicular stimulating hormone (FSH), 0.16 ng/ml total testosterone (TT) and＜0.6 pg/ml free testosterone (FT). Male hypogonadotropic hypogonadism was suspected from these results, He was then referred to a neurosurgeon for discrimination of intracranial disease where magnetic resonance imaging (MRI) revealed multiple intracranial tumors. An open brain biopsy was performed, and germinoma was diagnosed. After 4 courses of anti-cancer chemotherapy, complete remission was achieved. He was followed up endocrinologically by administration of testosterone injections along with other endocrinology replacement treatments. However, MRI 3 months later revealed tumor recurrence in the left lateral ventricle, and he has been receiving radiation therapy.     

Testosterone replacement therapy in male hypogonadism is not associated with increase of endothelin-1 levels

Differences in endothelin-1 (ET-1) blood plasma levels were established between healthy men and women. Little is known about vascular effects of testosterone and the interactions between sex hormones and endothelin. In order to study the relationship between ET-1 and testosterone in more detail, we have investigated 33 male patients with various forms of hypogonadism (13 with hypergonadotropic hypogonadism and 20 with hypogonadotropic hypogonadism). Fourteen age-matched healthy males served as controls. The basal ET-1 levels in patients with hypogonadism (0.96 +/- 0.12 fmol/mL) (mean +/- SEM) were significantly higher in comparison with the controls (0.44 +/- 0.04 fmol/mL), p < 0.01. Fifteen individuals of these patients were studied during the therapy with testosterone depot 250 mg i.m. The ET-1 levels decreased in this group from 0.99 +/- 0.22 to 0.78 +/- 0.14 fmol/mL at the third and to 0.76 +/- 0.25 fmol/mL at the sixth month of the medication, respectively. The differences were not significant compared with the initial levels, but the concentrations at the sixth month of the treatment were not statistically different in comparison with the ET-1 levels of the controls. There was no significant difference in lipid data between patients before and during testosterone medication, except for the high-density lipoprotein cholesterol, which decreased at the third month of the treatment. Our results show that plasma ET-1 levels in males with hypogonadism are elevated with a tendency to decrease after testosterone administration. The optimum testosterone is not associated with enhanced cardiovascular risk as far as ET-1 plasma levels and lipids are concerned.     

Hypothalamic-hypophyseal-testicular abnormalities and erectile dysfunction

Forty-five men presenting with erectile dysfunction were evaluated through history and nocturnal penile tumescence, Doppler, and EMG studies. Fifteen were classified as having organic and 30 as having psychogenic impotence. Three men had mild hypergonadotropism with low testosterone levels. One had hyperprolactinemia. No case of hypogonadotropic hypogonadism was detected. Six patients who had psychogenic impotence had low levels of testosterone.     

Acquired hypogonadotropic hypogonadism presenting as decreased seminal volume

A 32-year-old man with decreased ejaculatory volume was found to have acquired hypogonadotropic hypogonadism. Initial evaluation demonstrated castrate levels of testosterone with low serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels. Semen analysis revealed a volume of 0.35 cc and severe oligospermia. Administration of gonadotropin-releasing hormone (GnRH) did not effect an increase in LH or FSH, indicating a pituitary defect. Magnetic resonance imaging revealed a partially empty sella turcica. Treatment with human chorionic gonadotropin (hCG) alone resulted in normalization of testosterone levels, sperm concentration, and semen volume, as well as the successful conception and delivery of a healthy baby girl. The findings from this case demonstrate the importance of considering low serum testosterone levels in the evaluation of low semen volume, as well as the role of hCG alone as an infertility treatment for acquired hypogonadotropic hypogonadism.     

男性性腺功能低减病人尿β-FSH排泄连续测定

目的 :连续观察男性性腺功能低减病人尿卵泡刺激素 β亚单位 (β FSH)的排泄 ,探讨其对男性性腺功能低减的临床分类诊断和病理生理机制研究的意义。　方法 :4例健康成年男性 (年龄分别为 19、2 2、2 7、33岁 )、4例低促性腺激素型性腺功能低减男性病人 (年龄分别为 17、17、19、2 4岁 )和 5例高促性腺激素型性腺功能低减男性病人 (年龄分别为 16、16、17、2 0、2 2岁 ) ,连续留晨尿 30～ 32d ,其中 1例正常男性留取标本 6 3d。酶免法测定尿 β FSH ,以肌酐 (Cr)含量进行校正。　结果 :4例正常成年男性尿 β FSH总平均为 (1.16± 0 .2 0 ) μg/mgCr,均可出现波峰 ,最大峰值为 2 .76 μg/mgCr。 4例低促性腺激素型性腺功能低减男性病人 [Kallmann或特发性低促性腺激素型性腺功能低减 (IHH) ]尿 β FSH分别为 (0 .5 8± 0 .31)、(0 .93± 0 .4 7)、(0 .4 7± 0 .33)、(0 .6 0± 0 .4 0 ) μg/mgCr,曲线上未见明显波动。 5例高促性腺激素型性腺功能低减男性病人 (Klinefelter)尿 β FSH分别为 (3.0 2± 0 .93)、(4.36± 1.12 )、(4.79± 0 .78)、(4.6 4± 1.4 2 )、(3.88± 1.4 2 ) μg/mgCr,曲线上出现显著不规则波动 ,最大峰值达6 .83μg/mgCr。所有病人第二性征发育差 ,血清T水平显著低下。低促性腺激素?     

Combined use of androgen and sildenafil for hypogonadal patients unresponsive to sildenafil alone

To investigate the therapeutic effect of androgen on hypogonadal patients unresponsive to sildenafil alone. In total, 32 hypogonadal patients with erectile dysfunction (ED), initially had an inadequate response to sildenafil (100 mg). Oral testosterone undecanoate (Restandol, 80 mg, bid or tid) alone was supplied for 2 months, and if patients could not achieve a satisfactory erection, combined use of testosterone and sildenafil was continued thereafter. Total testosterone (TT), free testosterone (FT), and the parameters of the International Index of Erectile Function (IIEF), International Prostate Symptom Score (IPSS), and uroflow rate (UFR) were assessed. Eleven patients (34.3%) achieved satisfactory erectile function after testosterone replacement only. Another 12 (37.5%) patients experienced satisfactory intercourse after combined therapy. Serum TT and FT levels significantly increased after the use of testosterone alone (415+/-163 vs 220+/-101 ng/dl, P<0.01; 10.4+/-4.6 vs 5.1+/-1.9 ng/dl; P<0.01, respectively) and the combined use of testosterone and sildenafil (498+/-178 vs 220+/-101 ng/dl, P<0.01; 11.7+/-4.6 vs 5.1+/-1.9 ng/dl, P<0.001, respectively); as did the IIEF score (14.8+/-6.8 vs 12.6+/-7.5, P<0.01, 17.5+/-5.2 vs 12.6+/-7.5, P<0.001, respectively). However, no statistical differences were demonstrated for IPSS or UFR. In conclusions, one-third of hypogonadal patients with ED who failed to respond to sildenafil, responded to testosterone alone, another third responded to sildenafil again after normalization of testosterone. So, in hypogonadal patients with ED, androgen supplementation is first-line therapy. If patients are unresponsive to androgen alone or sildenafil alone, combined use may improve erectile function and enhance the therapeutic effect of PDE-5 inhibitors.     

Adult-onset idiopathic hypogonadotropic hypogonadism presented with erectile and ejaculatory disorder

A 37-year-old man who had fathered a child five years previously presented with erectile and ejaculatory disorder. Endocrinological examinations revealed isolated luteinizing hormone-releasing hormone (LHRH) deficiency of hypothalamus, resulting in hypogonadotropic hypogonadism, and no causative abnormality was detected in imaging studies, including magnetic resonance imaging (MRI). Having a diagnosis of adult-onset hypogonadotropic hypogonadism, the patient received pulsatile subcutaneous administration of gonadotropin-releasing hormone (GnRH). Sperm analysis and serum level of testosterone improved to normal in a few months. His wife became pregnant using artificial insemination with her husband's semen 15 months after the beginning of the treatment.     

性腺功能正常和减退男子的睾酮分泌反应

间歇3天分别肌注hCG各2000IU,并分别于0、1、2、3、4、6、24、48、72和96h采血测定睾酮。结果正常成年男子组、垂体瘤组和克氏综合征组睾酮分泌均呈双峰曲线,而青春期前男孩组和IHH组只在第2次注射后才出现第1峰,提示第1峰依赖于先前高水平LH/hCG的作用。间隔96h第2次注射后,各组的第2峰绝对值显著高于第1次注射,这是自我激发的结果,而正常成年男子组第2峰的最大增加值显著低于第1次注射,说明第1次注射引起的Legdig细胞失敏感性仍未完全恢复。     

Recovery of gonadal function after resection of an oligodendroglioma localized in the anterior horn of the lateral ventricle: relation to pulsatile secretion of luteinizing hormone

A 21-year-old man with an oligodendroglioma in the anterior horn of the right lateral ventricle complained of sexual dysfunction and showed lowered concentrations of serum testosterone (1.1 ng/ml) with normal pituitary function. Human chorionic gonadotropin testing revealed a good testosterone response (1.1 to 4.9 ng/ml) and a clomiphene test revealed no gonadotropin response. Pulsatile secretion of luteinizing hormone (LH) was absent preoperatively. After removal of the tumor, serum concentration of testosterone increased to the normal range, LH pulsatility appeared, and the patient had no complaints of sexual dysfunction. In this patient, the loss of LH pulsatility responsible for his hypogonadism was caused by the lateral ventricle tumor compressing the surrounding structures, and this was corrected by tumor resection.