Primary gonadal failure in men selectively amplifies the mass of follicle stimulating hormone (FSH) secreted per burst and increases the disorderliness of FSH release patterns: reversibility with testosterone replacement

The neuroendocrine mechanisms by which primary gonadal failure in men increases mean serum FSH concentrations (castration-like response) are not known. To investigate the testosterone-dependent mechanisms of the FSH castration response: (i) blood was sampled at 10-min intervals for 24 h for later FSH assay in seven normal middle-aged men and in six patients with primary testicular failure, during testosterone withdrawal and after 6 weeks of parenteral testosterone replacement; (ii) using a specific two-site IRMA, serum FSH concentrations were measured, since this assay correlates well with an in-vitro Sertoli cell bioassay; (iii) multiparameter deconvolution analysis was then applied to estimate the frequency, amplitude, duration, and mass of underlying FSH secretory bursts, and the half-life of endogenous FSH, and (iv) approximate entropy was calculated to quantify the relative orderliness of FSH release over 24 h. Mean (+/- SEM) 24-h serum FSH concentrations were 3.9 +/- 0.8 IU/L in control subjects and 39 +/- 10 IU/L in unreplaced hypogonadal patients (p = 0.034). Deconvolution analysis revealed similar estimated mean FSH half-lives of 346 +/- 40 min (control) and 321 +/- 47 min (untreated patients), and indistinguishable FSH secretory burst frequencies, namely, 20 +/- 0.95 (normal) and 21 +/- 1.3 (patients) pulses per 24 h. In contrast, the daily production rate of FSH was markedly increased in testosterone-withdrawn hypogonadal men at 117 +/- 25 vs. 9.3 +/- 1.8 IU/L/day (control) (p < 0.01). This was due to a 10-fold higher calculated maximal rate (amplitude) of FSH secretion achieved within each FSH release episode (normal 0.078 +/- 0.02 vs. gonadal failure 0.74 +/- 0.087 IU/L/min, p < 0.01), yielding a 10-fold increase in the mass of FSH secreted per burst (control 0.53 +/- 0.06 vs. patients 5.3 +/- 0.81 IU/L, p < 0.01). In contrast, the mean half-duration of FSH secretory bursts was unaltered in unreplaced hypogonadal men at 8.2 +/- 2.2 min (control) vs. 7.0 +/- 1.0 min (patients). Approximate entropy (ApEn), a scale- and model-independent statistic designed to quantify the orderliness or regularity of hormone release, revealed greater irregularity of serum FSH concentrations in the hypoandrogenic state: ApEn = 1.8 +/- 0.025 (testosterone-withdrawn) vs. 1.6 +/- 0.037 (control) (p < 0.05). Parenteral testosterone replacement for 6 weeks significantly decreased mean serum FSH concentrations by reducing the daily FSH secretion rate and FSH secretory burst amplitude and mass, and concomitantly restored the orderliness of FSH release patterns. Testosterone treatment did not change FSH secretory burst half-duration, number, interburst interval, or half-life. It is concluded that primary gonadal failure in men evokes FSH hypersecretion which is marked by more disorderly FSH release patterns and a selectively amplified mass of FSH secreted per burst. These hypergonadotrophic mechanisms are, to a significant extent, testosterone-suppressible.     

Quantitative and qualitative changes in serum luteinizing hormone after injectable testosterone undecanoate treatment in hypogonadal men

Aim: To clarify the immuno-active LH (i-LH) and bioactive LH (b-LH) responses and qualitative changes in the cir-culating LH to testosterone undecanoate (TU) injection. Methods: Eight men with Klinefelter's syndrome were re-cruited for the study. They received crossover injections of TU at doses of 500 and 1000 mg. Serum i-LH and b-LHlevels before and at various time intervals after TU injection were measured and the serum i-LH, b-LH, b-LH/i-LH(B/I) and testosterone/sex hormone-binding globulin (T/SHBG) ratio in LH-responders and LH non-responders werecompared. Results: A parallel suppression of serum i-LH and b-LH was consistent with their overall high correlationbetween each other ( r = 0.84, P < 0. 001). Mean serum i-FSH levels were decreased by TU injection at both doseswithout dose-response effects. LH-responders had lower baseline serum i-LH and b-LH, and higher E_2 levels and T/SHBG ratio. There was a quantitative change in serum LH as induced by TU without qualitative change within LH-re-sponder     

Modulation of immunoradiometric and bioactive follicle stimulating hormone secretion and clearance in young and elderly men during treatment with tamoxifen or flutamide.

The secretion and clearance of immunoactive and bioactive follicle-stimulating hormone (FSH) in healthy young men (N = 10) and elderly men (N = 7) during blockade of endogenous sex steroid hormones with tamoxifen, an antiestrogen, and flutamide, an antiandrogen, was investigated. To this end, subjects underwent blood sampling basally every 10 minutes for 24 hours, and then received 2 consecutive intravenous pulses of synthetic gonadotropin releasing hormone (GnRH; 10 micrograms and 100 micrograms) every 2 hours. This paradigm was repeated on two subsequent visits, in which subjects received either flutamide HCl, a specific nonsteroidal competitive antagonist of the androgen receptor (750 mg daily for 3 days), or tamoxifen, a selective antagonist of the estrogen receptor (20 mg daily for 9 days). Serum immunoactive FSH concentrations were measured in each sample by immunoradiometric assay (IRMA). Serum bioactive FSH concentrations were determined by an in vitro bioassay (rat granulosa cell aromatase system) on 24-hour serum pools. Deconvolution analysis was used to analyze both the FSH IRMA 24-hour time series and FSH release after GnRH. Comparisons between young and elderly men of the basal state showed significantly increased 24-hour mean serum immunoactive and bioactive FSH concentrations and significantly decreased free testosterone concentrations in elderly men. By deconvolution analysis, elderly men had a significant decrease in FSH secretory burst duration, and an increase in FSH half-life and FSH secretory burst amplitude compared with younger men. In response to sex steroid receptor blockade in young men, there was a significant increase in mean serum bioactive FSH concentrations during antiandrogen treatment, but not during antiestrogen treatment.(ABSTRACT TRUNCATED AT 250 WORDS)     

Are published normal ranges of serum testosterone too high? Results of a cross‐sectional survey of serum testosterone and luteinizing hormone in healthy men

OBJECTIVE: To derive normal ranges of serum testosterone and luteinizing hormone (LH) concentrations in healthy men, and thus evaluate whether testosterone replacement therapy is prescribed inappropriately. SUBJECTS AND METHOD: The study comprised 266 healthy male volunteers (aged 18-75 years) who were defined as healthy by strict eligibility criteria. Subjects had a body mass index (BMI) of 18.6-32.2 kg/m2, smoked 0-10 cigarettes/day, and had an alcohol intake 0-40 units/week (one unit = 8 g ethanol). We measured serum testosterone and LH concentrations in the morning (08.00-09.00 hours) and evening (20.00-21.00 hours). RESULTS: Morning normal ranges of testosterone for men aged < or = 40 years were 10.07-38.76 nmol/L (2.90-11.18 microg/L), and for men age > or = 40 years, 7.41-24.13 (2.14-6.96); the respective evening normal ranges were 6.69-31.51 (1.93-9.09) and 6.46-21.93 (1.86-6.33). Both morning and evening serum testosterone declined significantly with increasing age and BMI. LH was significantly higher in the morning than in the evening, but did not vary between the age groups or with BMI. The calculated normal ranges of LH were 0.9-7.0 IU/L (morning) and 0.7-6.8 IU/L (evening). CONCLUSIONS: The lower limit of normal for serum testosterone was 3-4 nmol/L (0.86-1.15 microg/L) lower than that of published ranges. The results have important implications for the diagnosis of hypogonadism and use of testosterone replacement therapy.     

Feedback inhibition of gonadotropins by testosterone in men with hypogonadotropic hypogonadism: comparison to the intact pituitary-testicular axis in primary hypogonadism

Men with hypogonadotropic hypogonadism (HH) due to hypothalamic-pituitary disease present with low serum testosterone levels combined with undetectable, low, or normal gonadotropin levels. Treatment consists of testosterone replacement to reverse the symptoms of androgen deficiency. The aim of this study was to examine the dynamics and feedback inhibition of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in relation to testosterone in 38 men with HH treated with testosterone. Findings were compared with 11 men with primary hypergonadism (PH). Testosterone replacement led to a suppression of FSH levels from 2.8 IU/L at baseline to 1.1 IU/L and to a suppression of LH levels from 2.3 to 0.8 IU/L. There was a linear correlation between levels of FSH and LH (after natural log transformation for both) and testosterone levels in both the HH and PH groups. However, the differences in intercepts and slopes between the groups were significant. To determine whether nonsuppressed FSH or LH during testosterone replacement reduces the probability of eugonadism, as reflected by normal testosterone levels, gonadotropin levels were measured and categorized as low (<0.5 IU/L), medium (0.5-2 IU/L), and high levels (>2 IU/L). The higher FSH or LH levels were found to significantly decrease the chance for achieving eugonadism. In conclusion, in men with HH due to hypothalamic-pituitary disease or injury, the pituitary-testicular hormonal axis maintains its physiological negative feedback between testosterone and gonadotropins. Thus, gonadotropin levels in men with HH might be useful, together with testosterone concentrations, for assessing the adequacy of androgen replacement.     

健康成年男子黄体生成素脉冲释放分析

对７名健康男子每１０分钟采血一次，历时２４小时，测定血清ＬＨ浓度并进行脉冲分析。结果平均ＬＨ脉冲频率为１６．９±２．１次／２４ｈ，周期为８７±ｌ０ｍｉｎ／次，脉冲间期为３０～３００分钟不等，幅度为１．０±０．６ＩＵ／Ｌ。采血间期为５分钟的另外３名健康男子１２小时ＬＨ脉冲频率为１０．３±０．９次，周期为６９±８分钟，间期为６２±３７分钟，幅度为１３±０．４ＩＵ／Ｌ。采血间期和设定的脉冲阈值不同对ＬＨ脉冲频率和脉冲周期均有影响，但对平均浓度和脉冲幅度的影响不明显     

Pituitary Gonadal Function in Infertile Men with Varicocele

Infertile men with varicocele or idiopathic infertility were compared with a control group. Spermocytograms were taken and the following radioimmunological plasma analyses carried out: testosterone, FSH and LH before and after 50 micrograms LRH, Prolactin (PRL) before and after 200 micrograms TRH; in addition, 8 patients with varicoceles and 3 controls received LRH intravenously (0.4 microgram/min.) for 4 hours. The binding of [125I] human chorionic gonadotrophin (hCG) to testicular tissue obtained by biopsy from 10 infertile men was also investigated. Of the parameters studied, no differences were found between the unilateral or bilateral varicoceles. In the two groups of infertile men, sperm motility and percentage normal forms were similar and significantly lower than in controls. As compared to the controls, in the groups of infertile men, basal LH and testosterone levels were no different but basal FSH levels was increased, basal PRL was higher (p less than 0.05) in the varicocele group. Responses of the LH, FSH and PRL to LRH and TRH stimulations were generally higher in infertile men than in controls. As compared to the idiopathic infertile men, testosterone levels and responses of plasma FSH to LRH injection were lower in varicocele group. Moreover, in infertile men with varicocele, age was correlated negatively with sperm motility and testosterone level and it was correlated positively with LH response to LRH injection. For each patient, testicular tissue was able to specifically bind [125I]hCG, but in some cases of varicoceles, hCG binding capacity was different in the two testes and seemed higher than that observed in men with obstructive azoospermia. These results suggest: 1) dysfunction in both spermatogenesis and Leydig cells with a compensatory hyperfunction of the pituitary gland in infertile men with varicocele; 2) worsening in Leydig cells and tubular lesions with longer duration of varicocele; and 3) absence of any gross abnormality in hCG binding to its specific receptors in the testis of men with varicocele. These data suggest varicoceles may play a causal role in infertility.     

Hormone profile in hyperprolactinemic infertile men

Serum levels of FSH, LH, prolactin, testosterone, and estradiol in 46 infertile men with hyperprolactinemia were compared with the same in 50 infertile and 30 fertile men with normal serum prolactin levels. Serum FSH levels in hyperprolactinemic men were significantly higher than in the other groups, indicating disturbance of spermatogenic process among those men. Significantly raised serum LH levels were in infertile men with serum prolactin over 1000 U/liter. All men with hyperprolactinemia had significantly lower serum testosterone levels than other infertile and fertile men. Although serum testosterone was not under the lower limit of normal range and high LH levels demonstrated disturbance of Leydig cell function in hyperprolactinemic infertile men, serum estradiol levels were not different among investigated groups. Azoospermic men with raised serum prolactin had higher serum FSH and LH levels than oligospermic men with hyperprolactinemia. These data demonstrated disturbance in hypothalamopituitary-testicular axis in infertile men with hyperprolactinemia. Further studies of prolactin in males with reproductive failure could probably clear this problem.     

Programmed cell death in varicocele-bearing testes

Accelerated apoptosis is a significant factor in the pathophysiology of male infertility disorders associated with abnormal spermatogenesis. This study aimed to investigate apoptosis in varicocele-bearing testes. Sixty four men with varicocele (18 fertile and 46 infertile) were studied compared with eight men with obstructive azoospermic as controls. Apoptosis was assessed in testicular biopsy specimens using terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling (TUNEL) method as well as electron microscopy. The results demonstrated that the occurrence of apoptotic changes comprised all types of germ cells but not affecting Sertoli cells. Mean tubular apoptotic indices of fertile or infertile men with varicocele were significantly higher than controls (mean ± SD 4.55 ± 1.03%, 6.29 ± 1.82% versus 2.71 ± 0.45%, P  < 0.05). Mean Leydig cells apoptotic indices of infertile men with varicocele were significantly higher than those of fertile men without varicocele as well as controls (1.18 ± 0.38%, 0.68 ± 0.15%, 0.31 ± 0.21%, P  < 0.05). Apoptotic indices were nonsignificantly correlated with Johnsen score, testicular volume or varicocele grade. It is concluded that testicular apoptosis is increased in varicocele-associated men either fertile or infertile who may be implicated in associated spermatogenic dysfunction.     

Serum inhibin pro alphaC in infertile men.

Specific assays have been developed for bioactive inhibin dimers, inhibin A and B, and inhibin alpha-subunit precursor pro alphaC. To better understand the role of serum inhibin pro alphaC in infertile men, the authors measured these forms of inhibin in sera from 39 infertile men and analyzed inhibin relationships with serum gonadotropins, testosterone, and estradiol. All subjects had oligozoospermia. Inhibin A levels were undetectable in all subjects. Inhibin B concentrations were 117 +/- 59 pg/mL. Inhibit B concentrations correlated negatively with serum FSH (r = .584, p < .0001) and positively with sperm count (p < .01) and bilateral testicular volume (r = .607, p < .0001). The concentration of pro alphaC was 556 +/- 236 pg/mL (normal range, 446 +/- 28). Inhibin pro alphaC showed no correlation with serum FSH, LH, testosterone, sperm concentration, and bilateral testicular volume. In addition, inhibin pro alphaC was not correlated with inhibin B. Pro alphaC is unlikely to be a useful marker for spermatogenesis in infertile men compared with inhibin B.     

Endocrine and reproductive health status of men who had experienced short-term radiation exposure at Chernobyl

Hormonal and semen parameters in 416 men aged 25–45 years were examined: 328 were men who cleaned the territory around the Chernobyl nuclear reactor (called `liquidators') and 88 were healthy age-matched controls. The dose of radiation received by the liquidators was 0.16 ± 0.08 Gy. LH, FSH, prolactin, testosterone and cortisol levels were assayed using WHO -matched reagents. Semen analyses were performed according to the WHO Manual (1992 ). The mean concentration of all hormones in liquidators and controls were within the WHO-defined normal range. The mean levels of LH and cortisol in liquidators were significantly lower ( p  = 0.013 and p  < 0.001, respectively) and testosterone significantly higher ( p  = 0.023) than in controls. The variations in hormone levels in liquidators were not correlated with the acquired doses of radiation as measured by personal dosimeters (film badges). Semen parameters in a sub-group of 70 liquidators were within the normal WHO-defined range. The percentage of normal forms of spermatozoa in liquidators (35.0 ± 13.1%) was significantly lower ( p  < 0.015) than in a control group (42.8 ± 8.9%). The study has shown that exposure of men to relatively short-term radiation did not cause long-lasting disruption of their endocrine status and spermatogenesis. The study was 7–9 years retrospective and it is therefore impossible to infer what the immediate effects of the radiation exposure were on these parameters.     

CA repeat and RsaI polymorphisms in ERbeta gene are not associated with infertility in Indian men

Oestrogen Receptor β (ERβ) gene plays an important role in the regulation of fertility in both males and females. Polymorphism in CA repeat located in the flanking region of ERβ has been shown to be associated with several diseases, but its association with male infertility has not been analysed so far. However, Rsa I polymorphism (rs1256049) in exon 5 of ERβ has been shown to be associated with male infertility in Caucasian patients. Hence, we have analysed 695 Indian men, including 443 infertile and 252 fertile men to evaluate the association of CA repeat length and Rsa I polymorphisms in male infertility. Our results revealed no significant difference in the distribution of CA repeat length between infertile (mean ± SD 23.24 ± 2.06, median 24) and fertile men (mean ± SD 23.16 ± 2.27, median 24). The analysis of dosage effect by classifying samples into SS (short/short), SL (short/long) and LL (long/long) groups also did not show any significant difference between infertile and fertile men. Similarly, Rsa I polymorphism also did not show any significant difference between infertile and fertile men. Furthermore, the combined analysis of CA repeat and Rsa I polymorphisms by haplotyping showed that the distribution of haplotypes was not significantly different between fertile and infertile men. Our results suggest that CA repeat length and Rsa I polymorphisms in ERβ are not associated with infertility in Indian men.     

Seminal plasma androgen/oestrogen balance in infertile men

The hypothesis that the balance between oestrogen and androgen in seminal plasma is important for normal fertility was investigated. We determined the concentrations of oestradiol and testosterone in blood and seminal plasma from 62 infertile men and 32 normozoospermic men. Infertile men were classified according to semen analysis (concentration, motility and morphology): asthenozoospermia, oligozoospermia and oligoteratoasthenozoospermia. Serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were determined in all participants. For all subjects, mean testosterone levels were lower and mean oestradiol were higher in seminal plasma than in blood. Seminal plasma testosterone levels were lower in the infertile groups vs. control men ( p < 0.0002). Oligpzoospermic and oligoteratoasthenozoospermic men had significantly higher seminal plasma oestradiol levels compared with controls ( p < 0.03). The three infertile groups had significantly lower seminal plasma testosterone/oestradiol ratio than control men ( p < 0.001). Sperm analysis data (concentration, motility and morphology) significantly correlated with seminal plasma testosterone/oestradiol ratio. The findings of elevated seminal plasma oestradiol, decreased testosterone and testosterone/oestradiol ratio in infertile men, and the significant correlation between hormone levels and sperm analysis data suggest that the local balance between androgen and oestrogen is important for spermatogenesis.     

Impact level of dihydrotestosterone on the hypothalamic-pituitary-leydig cell axis in men

Dihydrotestosterone (DHT) the physiologically most potent androgen cannot be aromatised into oestrogen. DHT is used as a treatment for idiopathic gynaecomastia. In order to investigate the different sites of action of DHT on the hypothalamic-pituitary-testicular axis, two groups of adult men were studied. Group I included 10 gonadotropin-releasing hormone (GnRH)-deficient men who were evaluated before and during a pulsatile infusion of GnRH alone for 2 weeks and then in association with DHT given transdermally at doses used in the treatment of gynaecomastia for further two weeks. Luteinizing hormone (LH) pulsatility was assessed at the end of each step of the study. Plasma LH levels were measured every 15 min. Plasma testosterone (T), DHT, oestradiol (E2), free alpha-subunit (FAS) of glycoproteic hormones and LH bioactivity were measured on pooled plasma samples. Group II included 12 healthy men in whom plasma T, DHT and E2 were measured before and then 24, 48 and 72 h after the injection of 5000 IU hCG alone or in combination with either DHT or the pure anti-androgen nilutamide. Two weeks separated each of the 3 hCG testing. In group I, except for bioactive/immunoreactive (B/I) LH ratio which was unchanged, GnRH treatment induced significant rises (p < 0.01) in all plasma hormone levels, LH pulse amplitude and frequency. During treatment with GnRH+DHT, plasma DHT levels increased up to 16.8 +/- 2.5 nm, while plasma hormone levels, B/I LH ratio, LH pulse amplitude and frequency were similar to those obtained with GnRH alone. In group II, the peak of hCG-induced T rise was not modified by either DHT or nilutamide. In contrast, DHT reduced by 50% (p < 0.01) the E2 peak in response to hCG. These data show that DHT exerts no direct action on the pituitary to retroregulate LH secretion and to modify either B/I LH ratio or FAS secretion. Its reducing effect on LH secretion is likely mediated at the hypothalamic level. DHT does not appear to have a physiological influence on Leydig cells steroidogenesis. Administered at therapeutic doses, DHT directly reduces testicular aromatase activity that combined with its antigonadotropic effect leads to the gain in the symptomatic treatment of gynaecomastia.     

Differences in the clinical characteristics between young and elderly men with varicocoele

Information concerning the clinical characteristics in elderly men with varicocoele is relatively limited. This study was assessed to evaluate the differences in clinical characteristics between young and elderly patients with varicocoele by retrospective chart review. Between June 2003 and February 2011, 169 young (18-30?years) men and 156 elderly (45-55?years) men with varicocoele, and 30 age-matched men without varicocoele were recruited for this study. All the patients were divided into six groups. Thirty-one infertile patients were assigned to Group 1, 138 fertile patients to Group 2, 35 infertile patients to Group 3 and 121 fertile patients to Group 4. Group 5 (15 young) and 6 (15 elderly) were control groups. The parameters for comparison included body mass index (BMI), semen quality (sperm motility, morphology and density) and pH value, serum concentration of follicle-stimulating hormone (FSH), luteinizing hormones (LH), testosterone, testicular volume, grade of varicocoele and peak retrograde flow (PRF) and maximal vein diameter (MVD) by colour Doppler ultrasound (CDS). Elderly men with varicocoele had a higher incidence of bilateral varicocoele (25.5% vs. 14.8%), but a lower incidence of unilateral right varicocoele (2.6% vs. 7.7%) than young patients with varicocoele. In addition, patients with varicocoele had lower BMI than those without, and infertile young patients with varicocoele had the lowest levels of BMI. Furthermore, infertile patients (Groups 1 and 3) with varicocoele had significantly lower testicular volume and semen pH, lower levels of testosterone, higher levels of FSH and LH and higher PRF than fertile men with varicocoele (Groups 2 and 4). In conclusion, infertile elderly patients with varicocoele had significantly lower levels of testosterone and higher levels of FSH and LH than infertile young men with varicocoele. In addition, infertile elderly patients with bilateral varicocoele (Group 3, n?=?8) had the lowest levels of testosterone.     

Evidence for a stimulatory role of high doses of recombinant human follicle‐stimulating hormone in the treatment of male‐factor infertility

The efficacy of recombinant human follicle‐stimulating hormone (rhFSH) in the treatment of normogonadotropic patients with male‐factor infertility was assessed. Forty‐five infertile men with moderate/severe oligoasthenozoospermia and normal FSH, luteinizing hormone (LH) and testosterone (T) levels were treated with high rhFSH dose (300 IU) on alternate days for ≥4 months. In all, the seminal parameters, endocrine profile (FSH, LH, prolactin (PRL), total and free T and estradiol) and pregnancy rate were evaluated before, during and after rhFSH treatment. Fifteen infertile men were treated with placebo and studied in the same way, as control group. rhFSH treatment induced a marked increase in sperm count and no change in sperm motility, morphology and viability. No changes in seminal parameters were observed in the placebo group. FSH levels increased during treatment with rhFSH and not with placebo. No variations in LH, PRL, free and total T and estradiol were evidenced during treatment. A significant pregnancy rate in rhFSH versus placebo patients was also highlighted. Prolonged treatment with high rhFSH doses leads to increase sperm count and improve the spontaneous pregnancy rate in normogonadotropic infertile patients with oligoasthenozoospermia. rhFSH may represent a rational and useful tool in the treatment of male‐factor infertility.     

Neuroendocrine mechanisms mediating awakening of the human gonadotropic axis in puberty

The hypothalamic gonadotropin-releasing hormone (GnRH) pulse generator presides over the pulsatile and feedback-regulated activities of the pituitary-gonadal axis. Awakening of synchronous activity of the GnRH neuronal ensemble in the earliest stages of puberty heralds the onset of full activation of the reproductive axis in girls and boys. Progression from prepuberty to adulthood in boys is directed by marked (30-fold) amplitude enhancement of pulsatile luteinizing hormone (LH) secretion, as assessed by an ultrasensitive immunofluorometric assay and deconvolution analysis. There is a much less apparent rise in LH secretory burst frequency (approximately 1.3-fold increase). Consequently, human puberty is an amplitudedriven neuroendocrine maturational process. However, less is known about pulsatile follicle-stimulating hormone (FSH) release in puberty. Multiple pathophysiologies that result in hypogonadotropic hypogonadism can converge on a final common mechanism of attenuated hypothalamic GnRH pulse generator output and hence reduced LH (and FSH) secretion. Disturbances may take the form of reduced GnRH pulse frequency and/or attenuated GnRH secretory burst mass. When the pathophysiology of hypogonadism originates exclusively in a failed GnRH pulse generator, then either treatment of the primary disease process where possible (e.g., by refeeding in starvation, improved metabolic control in diabetes mellitus, dopamine agonist treatment in hyperprolactinemia, etc.) and/or treatment with pulsatile GnRH (e.g., in Kallmann's syndrome, isolated hypothalamic lesions, etc.) can provide relevant therapeutic options in children and adults.     

Biological activity of luteinizing hormone in uraemic children: spontaneous nocturnal secretion and changes after administration of exogenous pulsatile luteinizing hormone-releasing hormone — preliminary observations

Normal pubertal progression is associated with quantitative and qualitative changes in gonadotrophin release. Uraemic children show a delayed or disturbed puberty. We have therefore examined nocturnal gonadotrophin and sex steroid secretion in seven males and three females [age 11–15 years, pubertal stage (PS) 1-3] with chronic renal failure on conservative treatment. In addition to immunoreactive luteinizing hormone (i-LH) we have measured the biological activity of LH (b-LH). Nine children aged 12–17 years with PS 1-3 and normal renal function served as a control group. In two uraemic children, i-LH, b-LH, follicle stimulating hormone and sex steroids were evaluated before and 7 days after pulsatile LH-releasing hormone (LHRH) administration (150 ng/kg body weight subcutaneously every 120 min). Mean i-LH levels were higher in uraemic children than in controls. An increase in i-LH during sleep was found in all controls and in eight of ten uraemic subjects. Mean b-LH levels were lower during sleep and the b/i LH ratio was reduced in uraemic children with PS 2-3 whether asleep or awake compared with controls. Pulsatile administration of LHRH provoked a rise of i-LH and b-LH levels with an increased b/i LH ratio, suggesting an intact pituitary responsiveness. These preliminary data indicate that the gonadotrophin control of LH is abnormal in uraemic children, and that biopotency of LH secretion might be improved after shortterm pulsatile LHRH administration.     

Histological and hormonal testicular function in oligo/azoospermic infertile men

We characterised and correlated the histological and hormonal aspects of a cohort of 261 azo/oligozoospermic men, applying a quantitative/qualitative evaluation of testicular tissue and serum and intratesticular hormonal measurements. One hundred and 93 azo?oligozoospermic patients were diagnosed as: complete sertoli cell only syndrome (cSCOS), n = 76; focal SCOS, n = 31; maturation arrest, n = 34; hypospermatogenesis, n = 17; mixed atrophy, n = 25; and severe atrophy, n = 10. Normal spermatogenesis was observed in 68 infertile men (controls). Patients with cSCOS, focal SCOS, mixed and severe atrophy had larger LC/clusters (11.5; 11.0; 10.7; 18.9 LC/cluster) than controls (6 LC/cluster; P < 0.001). cSCOS, focal SCOS, mixed and severe atrophy patients had higher FSH, LH and lower T/LH ratio serum levels than the other groups. Intratesticular testosterone concentrations were higher in tissues with complete or focal SCOS (45.6 ng mg^?1 protein) and mixed atrophy (79.0 ng mg^?1 protein) than normal tissues (20.3 ng mg^?1 protein; P = 0.03 and P = 0.007). Considering all subjects, significant correlations were found between T/LH ratio and Leydig cells/cluster (r = 0.510, P < 0.001), FSH levels (r = ?0.692, P < 0.001) and with intratesticular testosterone (r = ?0.354, P = 0.001); these correlations follow the pattern of severity of spermatogenic damage. By a thorough histological evaluation, we validate the concept that the severity of spermatogenic impairment is associated with major morphological and functional disturbance of the Leydig cell compartment.     

Androgen Insensitivity Suspected by Estimation of Serum Hormone Levels in Oligozoospermic and Azoospermic Men

According to higher androgen insensitivity index than in fertile men, the group of 83 men, with high serum LH and high or normal testosterone levels, was separated from 800 infertile men. These patients with high androgen insensitivity index had oligozoospermia (6.38 +/- 3.18 X 10(6)/ml) or azoospermia. They had significantly higher serum LH and testosterone levels than compared groups of infertile and fertile men. Elevated serum FSH levels in infertile men with high androgen insensitivity index showed damage of spermatogenesis. There was completely disturbed hypothalamo-pituitary-testicular axis as the serum prolactin levels were significantly elevated too. There was no significant difference in serum estradiol levels among investigated groups. Using androgen insensitivity index we could identify those men whose infertility is not treatable.