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.     

The relationship of serum testosterone to erectile function in normal aging men

PURPOSE: We evaluated the variation in serum testosterone in normal aging men and its relationship with erectile function. MATERIALS AND METHODS: In a study that was not community based and during a free screening program for prostate cancer 1,071 men were invited to complete a sexual activity questionnaire, that is the abridged 5-item version of the International Index of Erectile Function (IIEF-5), as a diagnostic tool for erectile dysfunction. Possible scores on the IIEF-5 are 1 to 25 and erectile dysfunction was classified into 5 categories based on the scores, namely severe-1 to 7, moderate-8 to 11, mild to moderate-12 to 16, mild-17 to 21 and none-22 to 25. Serum total testosterone was measured between 8:00 and 10:00 a.m. in all men. RESULTS: Of the 1,071 men 965 (90.1%) were included in this study, of whom 88% were white and 12% were black. Mean age was 60.7 years. In this sample the prevalence of all degrees of erectile dysfunction was estimated to be 53.9%. The degree of erectile dysfunction was mild in 21.5% of cases, mild to moderate in 14.1%, moderate in 6.3% and severe in 11.9%. According to age the erectile dysfunction rate was 36.4% in the 40 to 49, 42.5% in the 50 to 59, 58.1% in the 60 to 69, 79.4% in the 70 to 79 and 100% in the 80 years and older groups (p <0.05). The variation in mean serum total testosterone in the age groups was not statistically significantly different (p >0.05). Pearson coefficients of age and total testosterone did not reveal any significant correlation (r = 0.00376, p = 0.907), similar to IIEF-5 score and total testosterone (r = 0.0163, p = 0.612). However, analysis of the variables IIEF-5 and age showed a statistically significant inverse or negative relationship (r = -0.3449, p <0.05). CONCLUSIONS: Erectile dysfunction showed a clear association with aging but no consistent correlation of total testosterone with erectile condition was identified.     

Mast cells in testicular biopsies of azoospermic men

This work aimed at identifying mast cells in testicular biopsies from 10 normal fertile controls, 20 patients with obstructive azoospermia and 70 patients with nonobstructive azoospermia. The biopsies were stained with haematoxylin and eosin stain for tubular-modified Johnson score and with toluidine blue stain for mast cells. Two populations of mast cells, peritubular and interstitial, were demonstrated in all sections with varied counts. Testicular sections with Sertoli cell only and spermatogenic arrest patterns demonstrated a significant increase in both peritubular and interstitial mast cells compared with other groups, whereas obstructive azoospermia demonstrated a nonsignificant increase compared with the controls. Mast cell count was significantly correlated negatively with Johnson score for both peritubular (P = 0.001) and interstitial (P = 0.001) populations. Whether these results could be a cause or an effect, a special role might be assigned to mast cells in the pathogenesis of disturbed spermatogenesis.     

The effect of long-term treatment with crude cotton seed oil on pituitary and testicular function in men

In a previous study, compensatory dysfunction of the Leydig cell was identified in men in whom spermatogenesis had failed to recover after gossypol treatment. In this study, LHRH- (100 micrograms i.v.) and hCG (3000 IU i.m.)-stimulation tests were conducted in four controls and in 45 men who had used crude cotton seed oil as their cooking oil. The patients were divided into two groups: group A--17 men with normospermia or oligospermia and group B--28 men who were azoospermic. The basal serum LH and FSH concentrations were within the normal range in group A, whereas those in group B were increased markedly. There was no significant difference in testosterone levels between the two groups, although the levels were significantly lower than in the controls. The response of LH and FSH to LHRH, and of testosterone to hCG stimulation, were within the normal range in group A, whereas in group B the response to the LHRH test was increased significantly while their response to the hCG test was reduced markedly. It was concluded that the functions of the pituitary and Leydig cells remained unchanged in group A after long-term use of crude cotton seed oil, and that once azoospermia has occurred, it is followed by total testicular failure as indicated by the responses to LHRH and hCG tests.     

Haemodialysis and testicular function

Gonadal dysfunction in men with chronic renal failure is well established. However, the effect of haemodialysis on the function of the testis has not been studied in detail, so we have investigated the effect of haemodialysis by measuring the plasma levels of testosterone and dihydrotestosterone, SHBG binding capacity and salivary levels of testosterone. Plasma levels of testosterone, dihydrotestosterone and salivary testosterone levels were significantly lower in patients on haemodialysis than in controls. There was also a reduction in 5α-reductase activity as evidenced by a reduced 5α DHT/T ratio. SHBG levels were comparable to those found in eugonadal men. No differences were found in the parameters studied before and after 6 h haemodialysis. It is concluded that haemodialysis is not of obvious benefit to gonadal function.     

Lipids and testicular function

We studied 19 male patients with primary hyperlipoproteinaemia, a control group of 28 healthy men and 44 infertile males before any treatment was undertaken. Spermiogram, seminal biochemical studies, measurements of plasma hormone levels and lipid determinations were carried out. Most hyperlipoproteinaemic patients showed abnormalities in the spermiograms and the mean values were lower than in the controls except for semen volume. Seminal biochemical determinations were normal in the majority and the hormone profile showed some abnormal values, mainly for E₂. Lipid abnormalities were more common in azoospermic infertile men and mean lipid levels were higher. Correlation studies suggest that high levels ofC and/or Tg are associated with poor semen quality and higher FSH levels. The results of our studies suggest that high lipid levels exert adverse direct effects at the testicular level.     

Retroperitoneal anomalies in men with testicular germ cell tumours

OBJECTIVES: To assess whether vascular and other retroperitoneal anomalies are more frequent during retroperitoneal lymph node dissection (RPLND) for metastatic testicular tumours (when retroperitoneal masses persist after chemotherapy) than would be expected, based on the initial observations from one centre with a large experience of RPLND in the UK. PATIENTS AND METHODS: A prospective series of 278 consecutive patients treated with RPLND for testicular tumours comprised the sample population. For each patient the presence or absence of four factors from the history was recorded. Each patient then underwent RPLND. During surgery, a template was constructed of the anatomy of the retroperitoneum and the information stored. Eight different retroperitoneal anatomical anomalies were identified in the sample population; the incidence of each was then compared with the largest available study of a normal population, and differences analysed statistically. RESULTS: Of the 278 patients who had RPLND, 55 had 59 anomalies (21%), found by history and as retroperitoneal vascular and urological anomalies; cryptorchidism was present in 7.6%, 9.5 times the incidence in the control population (P < 0.01). A left-sided inferior vena cava was present in 3.6% of patients, 21 times the incidence in the control population (P < 0.001); a retro-aortic left renal vein in 3.2%, four times that in the control population (P < 0.05); and ipsilateral renal agenesis had an incidence of 1% in the test population, 11 times greater than in the control population (P < 0.01). CONCLUSIONS: This prospective study of 278 RPLNDs provides evidence that some retroperitoneal anatomical anomalies are associated with testicular germ cell tumours. The link between maldescent and testicular tumours, rather than an isolated association, should be considered as part of a spectrum of retroperitoneal anomalies that occur in these men.     

Semen cryopreservation after orchidectomy in men with testicular cancer

OBJECTIVE: To assess the feasibility of semen cryopreservation after orchidectomy in patients with testicular tumour. PATIENTS AND METHODS: The quality of semen samples was investigated in 36 men with testicular tumour (mean age 31.7 years, range 20-49) who were referred to our infertility centre for semen cryopreservation. For each patient, the number of straws, semen volume, number of spermatozoa, and sperm motility before and after freezing were evaluated. RESULTS: Fifteen patients (42%) banked sperm before and 21 (58%) after orchidectomy; the delay was >7 days in 19 patients (53%). The mean age, histological diagnosis and tumour stage did not differ significantly whatever the time of cryopreservation. Semen quality did not differ significantly in patients who cryopreserved sperm before or after orchidectomy and there were no significant differences in sperm values whatever the delay before preservation. Semen quality was the same in patients with seminoma or nonseminoma tumour. CONCLUSION: These findings indicate that spermatogenesis of the contralateral testis is sufficient for successful semen cryopreservation after orchidectomy. Urologists should be encouraged to increase the awareness among oncology teams and patients about the new developments in preserving fertility for patients with cancer.     

Primary testicular lesions are associated with testicular germ cell tumors of adult men

The present study aims to establish the nature and frequency of testicular lesions in the parenchyma adjacent to testicular germ cell tumors (TGCT) to improve understanding of the factors involved in the development of testicular cancer. Fifty-three cases of TGCT that were fixed in both neutral-buffered formalin and Bouin solution, allowing for the nuclear characterization of Sertoli cells (SCs), were included in this study. In each case, at least 3 sections of different areas of preserved parenchyma surrounding the TGCT were studied. We found Leydig cell hyperplasia, microlithiasis, angiopathy, adenomatous hyperplasia of the rete testis, SC nodules, SC dysgenesis and involution, SC-only tubules, tubular atrophy, adluminal compartment lesions, hypospermatogenesis associated with spermatocyte sloughing, spermatogonial maturation arrest, and hypertrophic and multinucleated spermatogonia. These lesions were found in regions both adjacent and far away from the tumoral mass, and abnormal seminiferous tubules were found intermingled with those showing complete spermatogenesis, suggesting that these lesions are primary and existed before the development of the tumor. Our study suggests that SCs might play a more important role in the development of testicular tumors than previously thought. Our data supports the hypothesis that there is an abnormal differentiation of SCs, caused either by genetic anomalies or by environmental agents during fetal life. This abnormal SC differentiation may cause not only primary spermatogenesis failure and spermatogenesis arrest at different levels, but may also contribute to the poor differentiation of gonocytes into spermatogonia. The abnormal gonocyte differentiation might favor the development of dysplastic germ cells that may later transform into intratubular germ cell neoplasia, unclassified type.     

Androgen deficiency in aging and metabolically challenged men

Androgen deficiency in aging men is common, and the potential sequelae are numerous. In addition to low libido, erectile dysfunction, decreased bone density, depressed mood, and decline in cognition, studies suggest strong correlations between low testosterone, obesity, and the metabolic syndrome. Because causation and its directionality remain uncertain, the functional and cardiovascular risks associated with androgen deficiency have led to intense investigation of testosterone replacement therapy in older men. Although promising, evidence for definitive benefit or detriment is not conclusive, and treatment of late-onset hypogonadism is complicated.     

Gender issues in heart disease for aging men

Gender-specific issues relating to prevention of heart disease are new and exciting areas for research. It is well established that cardiovascular disease in men is more common than in women, except perhaps in the postmenopausal stage. Estrogens seem to protect women from heart disease in the premenopausal stage. Although androgens might influence cardiovascular risks, its overall effects are uncertain because many interacting factors need to be considered. The synthesis of testosterone in men suppresses hepatic production of apolipoprotein A (apo A), the precursor of the HDL particle. This leads to a 20% reduction in HDL in men compared with women. This difference persists through adulthood and is now thought to explain part of the gender difference in early heart disease. The effect of androgens on the aging process seems however to be positive rather than negative. Cardiovascular risk factors can be reversed with life-style changes in both men and women. Smoking is more common in men than women and is the most preventable risk factor but still more than a quarter of men smoke. Hypertension too is slightly more common in men, affecting one in four men in adult life. Although men are more likely than women to be physically active, 30 to 50% are sedentary. Obesity in men has a centripetal distribution and affects risks for heart disease differently than in women. Finally cardiovascular symptoms can change, especially with aging. All these points will be discussed in this article.     

Engagement in life activities promotes healthy aging in men

Being engaged in life is associated with healthy aging. Various indicators of healthy aging, such as greater longevity, lower incidence of cardiovascular disease, higher levels of subjective well-being and/or reduced levels of depression are associated with higher overall activity levels in general, and more specifically with engagement in social and productive activities. Being physically active and/or engaging in regular exercise has also been positively related with indicators of healthy aging. Physical activity and exercise guidelines have been published for older adults, including frail adults over age 70. Older men can be encouraged to engage in exercise in various ways, including being provided with tangible information on available resources by the health care provider. Motivational interviewing, tailored to the provider–patient relationship, can be a useful tool for the provider to encourage the patient to recognize a need or opportunity for change and take steps to a more active and healthy life.     

Paracrine regulation of testicular function

Spermatogenesis and spermiogenesis are controlled by FSH and testosterone but need also the participation of several paracrine and autocrine mechanisms of regulations. The relationships between peritubular, Sertoli and Leydig cells are currently investigated. High intratesticular testosterone levels are maintained by a binding to a protein called ABP which is synthetized by Sertoli cell and regulated by pituitary FSH. Leydig cell testosterone, peritubular cell P-Mod-S (protein modulating Sertoli function) and Sertoli cell FRP (follicle regulatory protein). Accumulation of testosterone results to aromatase activity modulation. Aromatization is stimulated by FSH, activin, alpha-MSH but is inhibited by aromatase inhibitor, inhibin, FSHBI (FSH binding inhibitor). Other molecules, growing factors, mitogenic factors, energetic substrates are synthetized in the testis under the control of germ cells. Understanding of these mechanisms of intratesticular regulation will permit to discover therapies capable of correcting certain fertility dysfunctions.