Decline In Testicular Function Research Articles

Icariin alleviates the injury of Sertoli cell junction function by upregulating PKR pathway via ERα/c-fos signaling in aged mice

Ethnopharmacological relevenaceSertoli cells are vital to maintain spermatogenesis and their function decline during aging. Epimedium has the effects of tonifying kidney-yang, strengthening bones and muscles, and expelling wind and dampness, and is commonly used in the treatment of kidney-yang deficiency, impotence and spermatorrhea. Icariin is the main active ingredients from Epimedium exhibiting delaying aging effects and improving male reproductive dysfunction. Whereas, it remains poorly understood how icariin alleviates age-associated decline in testicular function by protecting against the damage of junction function of Sertoli cells. Aim of the studyThis study aimed to evaluate the improvement effect of icariin on Sertoli cell junction function damage and explore the underlying mechanisms. Materials and methodsMale C57BL/6 mice and mouse Sertoli cell line TM4 cells were utilized to assess the improvement effect of icariin on aging-associated Sertoli cell junction function injury. H&E staining, transmission electron microscopy, qPCR, Western blot, molecular docking, siRNA transfection, and immunofluorescence were performed in this study. ResultsDietary administration of icariin remarkly attenuated age-associated deterioration in spermatogenic function as evidenced by elevated testicular weight and index, sperm concentration and sperm viability. In addition, icariin protected Sertoli cell junction function from age-associated damage as proven by increased Sertoli cell numbers, improved tight junction ultrastructure, and upregulated junction-related proteins (ZO-1, Occludin and β-Catenin). Moreover, icariin significantly upregulated ERα/c-fos signaling and PKR pathway in testicular Sertoli cells. Similarly, in vitro studies revealed that deletion of ERα, c-fos or PKR abolished the improvement effects of icariin on Sertoli cell junction function damage. ConclusionsIcariin effectively mitigates age-associated decline in testicular function by diminished Sertoli cell junction function damage through upregulating PKR pathway via ERα/c-fos signaling. Therefore, attenuating Sertoli cell junction function injury by the upregulation of PKR pathway via ERα/c-fos signaling probably indicates an effective target for the prevention and treatment of testicular spermatogenic function with aging.

Bazi Bushen alleviates reproductive aging in aged male mice

Bazi Bushen (BZBS), a traditional Chinese medicine (TCM), has demonstrated therapeutic efficacy in testicular dysfunction within D-galactose and NaNO2 mouse models. This study aimed to ascertain if BZBS could also mitigate the decline in testicular function associated with natural aging. Therefore, male aged mice were employed to evaluate the preventive effects of BZBS on male reproductive aging. This was achieved by assessing sex hormone production, testicular histomorphology, and spermatogenesis. Relative to the untreated aged control group, BZBS administration elevated the levels of sex hormones and spermatocyte populations and preserved normal testicular structure in aged mice. Notably, spermatogenesis was maintained. Further analyses, including malondialdehyde (MDA) assays and real-time PCR, indicated that BZBS diminished testicular oxidative stress and the inflammatory burden. Corroborating these findings, mice treated with BZBS exhibited reductions in the populations of senescent and apoptotic cells within the seminiferous tubules, suggesting alleviated cellular damage. In contrast, we observed that rapamycin, a drug known for its longevity benefits, induced excessive testicular apoptosis and did not decrease lipid peroxidation. Collectively, our results highlight BZBS’s promising clinical potential in counteracting male reproductive aging, underlining its mechanisms of action.

Icariin Improves Age-Related Testicular Dysfunction by Alleviating Sertoli Cell Injury via Upregulation of the ERα/Nrf2-Signaling Pathway.

Sertoli cells play crucial roles in spermatogenesis and are impaired by aging. Icariin, a flavonoid from Epimedium, has been reported to exhibit anti-aging effects and improve testicular dysfunction in the clinical setting. However, whether icariin improves age-related degeneration of testicular function via protection from Sertoli cell injury remains unclear. In the present study, we evaluated the protective effect of icariin on Sertoli cell injury and explored the possible mechanism(s) in vivo and in vitro. Dietary administration of icariin for 4 months significantly ameliorated the age-related decline in testicular function by increasing testicular and epididymal weights and indices, sperm count and sperm viability, testicular testosterone and estradiol concentrations, and seminiferous tubule diameters and heights. In addition, icariin protected age-related Sertoli cells from injury as evidenced by an analysis of Sertoli cell number, ultrastructure, and function. Such changes were accompanied by upregulation of ERα and Nrf2 signaling in Sertoli cells. Parallel in vitro studies also demonstrated that icariin inhibited untoward effects on the TM4 mouse Sertoli cell line with concomitant upregulation of ERα and Nrf2 signaling. Conversely, ERα siRNA reversed icariin-mediated protection of Sertoli cell injury. Our data suggest that icariin effectively ameliorates age-related degeneration of testicular function by alleviating Sertoli cell injury via the ERα/Nrf2 signal-transduction pathway. Thus, mitigating Sertoli cell damage via the ERα/Nrf2 signaling pathway likely represents a promising strategy for the prevention of age-related testicular dysfunction.

Decline in testicular function in ageing rats: Changes in the unfolded protein response and mitochondrial apoptotic pathway.

Activation of the unfolded protein response (UPR) in the endoplasmic reticulum (ER) and mitochondrial apoptotic pathway serves as a central regulator for maintaining cell function and survival, and is associated with ageing and spermatogenesis. However, changes in UPR activation and mitochondrial apoptotic pathway in the testis during ageing remain unclear. In this study, we hypothesized that UPR activation declines and the mitochondrial apoptotic pathway is activated in the testis during ageing, and these changes are associated with a decline in testicular function. To test this theory, we utilized 6-, 12-, 18-, and 22-month-old Sprague Dawley rats to evaluate the changes in testicular and epididymal weights and indexes, sperm quality, histology, UPR activation, and mitochondrial apoptotic pathway in testicular tissues. The results showed that there was a progressive decline in testicular and epididymal weights and indexes, sperm count, and sperm viability during ageing. Correspondingly, seminiferous tubule diameters and epithelium heights progressively decreased with ageing. Western blot analysis and immunofluorescence staining results revealed that the expression of UPR-related proteins (GRP78, p-PERK, p-eif2α, ATF4, p-IRE1α, ATF6α, and XBP1) progressively decreased in the testis with ageing. In contrast, the expression of ER stress-related pro-apoptotic proteins CHOP, Caspase 12, and p-JNK progressively increased with advancing age. TUNEL staining further confirmed that testicular germ cell apoptosis was significantly increased from month 6 to 22 in rats. Additionally, the relative expression levels of cytochrome c and its downstream molecules including Capsase 9 and Caspase 3 were significantly increased in the testis during ageing. Collectively, our results suggest that impaired UPR activation and increased germ cell apoptosis partly mediated by the UPR and mitochondrial apoptotic pathway might correlate with an age-related decline in testicular function.

Features of the metabolic syndrome in late adolescence are associated with impaired testicular function at 20 years of age.

Features of the metabolic syndrome in late adolescence are associated with impaired testicular function at 20 years of age.

Postoperative outcomes of varicocelectomy and impact of on infertility among sample of patient in Baghdad, Iraq

Background: Varicocele is the possible cause of 35% primary infertility, 70-80 % secondary and it is associated with progressive and duration dependent decline in testicular function. The aim of this study was to assess the postoperative outcome of varicocelectomy and determine positive impact on ability to reduce infertility.Methods: Twenty-five infertile male patients with varicocele, their age range from (20-40) year mean (30 year), were included and evaluated prospectively and retrospectively in Al-Karama teaching hospital from 2013-2016. Patients were divided in present study according to age of patient, degree of varicocele, duration of infertility and type of infertility. Site of varicocele was either left unilateral or bilateral. All the patients were treated surgically using three different approaches; Retroperitoneal approach, Inguinal and Sub inguinal approach and Scrotal approach.Results: It is noticeable that scrotal swelling was the most frequent complication and infection was the second highest. According to the age of patient, it was shown that beneficial effect of the Varicocelectomy was most favourable among younger age group. It is observables that favourable outcome was better among those with secondary fertility. It was found that grade III varicocele was associated with better outcome in terms of pregnancy and sperms motility.Conclusions: Scrotal swelling and infection was the most highly reported complication. Favourable effect of the Varicocelectomy was most among younger age group, secondary fertility and grade III varicocele.

Lymphatic and testicular artery-sparing laparoscopic varicocelectomy in children and adolescents

Background/aim The ideal operation for the treatment of adolescent varicocele has been debated for many years. The division of lymphatic vessels during varicocelectomy is complicated by hydrocele formation and decline in testicular function. The aim of this study is to report on our series of children who underwent lymphatic and testicular artery-sparing laparoscopic varicocelectomy (LTASLV). Patients and methods Thirty boys with primary left-sided varicocele were subjected to LTASLV. The indications for intervention were scrotal pain and discomfort in 18 cases (60%), hypotrophy in nine cases (30%), and family preference in three cases (10%). An intraparenchymal injection of 2 ml methylene blue was administered after induction of anesthesia. LTASLV was performed for all patients. The main outcome measurements included operative time, hospital stay, development of hydrocele, varicocele recurrence, and testicular atrophy. Results The study included 30 patients with primary left-sided varicocele. Their mean age was 12.25 ± 1.6 years (range 9-16 years). Grade 3 varicocele was present in 21 cases (70%) and grade 2 varicocele was present in nine cases (30%). Stained lymphatics could easily be observed alongside the testicular artery and veins in 28 cases, whereas in two cases, a second injection of methylene blue with lowering of CO 2 pressure was required for visualization. All procedures were completed laparoscopically without conversions or complications. The mean operative time was 40 ± 2.6 min (range 30-50 min). All patients achieved full recovery and were discharged within 24 h. The mean follow-up period was 18 ± 4.3 months (range 10-36 months). Residual varicocele was noted in one case (3.3%) with no hydrocele formation or testicular atrophy. Conclusion This study shows good results with respect to postoperative hydrocele rates. LTASLV resulted in 0% of hydrocele and decreased the risk of varicocele recurrence. However, larger series are necessary.

Microsurgical subinguinal varicocelectomy with testicular delivery

To demonstrate our approach to the microsurgical subinguinal varicocelectomy with testicular delivery. An instructional video demonstrating the surgical procedure in a step-by-step manner, highlighting useful surgical techniques. Not applicable. Patients with male factor infertility. After appropriate patient selection and counseling, varicocelectomy is performed with a subinguinal approach utilizing the surgical microscope. The patient is under general anesthesia and we employ an operating microscope. The patient is positioned supine. Not applicable. A 2.5-cm subinguinal incision was made and the testicle was then delivered. Through the operating microscope at 10-20X magnification, internal spermatic veins were identified and ligated. Smaller veins were taken with electrocautery. The testicular artery was identified using the microdoppler probe. We employ hydrodissection in identifying and isolating the testicular artery. The spermatic cord is then repeatedly examined until no veins other than deferential veins remain. The gubernaculum is also thinned sufficiently so that veins on both sides can be identified and ligated. Testicular delivery was performed and external spermatic veins as well as gubernacular veins ligated. Varicoceles are found in up to 15% of all men, and in up to 40% of infertile men. Varicoceles have negative effects on testicular function. Varicocelectomy improves testicular function and may halt the accelerated rate of decline in testicular function associated with varicoceles. Sperm parameters, serum testosterone levels, and pregnancy rates have all been shown to improve following varicocelectomy. Use of the operating microscope, the microdoppler probe, and black and white sutures aid in efficiency. Testicular delivery is useful to ligate external spermatic veins as well as gubernacular veins.

Alternate indications for varicocele repair: non-obstructive azoospermia, pain, androgen deficiency and progressive testicular dysfunction

Varicocele repair is indicated for infertile men with clinical varicoceles. Some men with scrotal pain, low testosterone, non-obstructive azoospermia, and who are at risk for testicular dysfunction may also benefit from varicocelectomy.

Older age is associated with similar improvements in semen parameters and hormonal outcomes after subinguinal microsurgical varicocelectomy

OBJECTIVE: Varicocelectomy improves testicular function or at least halts the progressive decline in testicular function caused by varicocele. The efficacy of varicocelectomy in older men has not been well studied. DESIGN: Retrospective review of men undergoing microscopic subinguinal varicocelectomy. MATERIALS AND METHODS: Demographics, operative notes, clinical charts, pre and post-operative lab reports were reviewed. Patients were divided into groups based on age at surgery: < 30 years old, 30-39 years old, and ≥ 40 years old. One way ANOVA and a Tukey HSD post-hoc test were applied to continuous variables. Kruskal-Wallis tests were used to compare categorical variables. Paired two-sample t-tests were performed for testosterone levels and semen analysis results. RESULTS: 364 men were included in this study. Over 70% of patients presented with bilateral varicoceles and underwent bilateral varicocelectomy with similar distribution of ages (p=0.88). There were similar levels of testosterone, and baseline semen analysis parameters in all ages. In all age groups, there were significant increases in sperm concentration and total sperm count (all p <0.01). When the analysis was restricted to patients with baseline testosterone ≤400 ng/dl there was a mean increase of 108 ng/dl in the ≥40 age group (n=22), 133 ng/dl in the 30-39 year old age group (n=30) and a 136 ng/dl increase (n=21) in the <30 year old age group with similar mean follow up (p=0.43). CONCLUSION: Subinguinal microsurgical varicocelectomy is associated with significant increases in sperm concentration, total sperm count, and testosterone regardless of the age at surgery. The testosterone increase was greatest in men with baseline serum testosterone ≤400 ng/dl with a mean increase in testosterone levels of over 100 ng/dl. Subinguinal microsurgical varicocelectomy can be offered to older men for infertility and/or androgen deficiency.

Surgical Treatment of Varicocele in Children With Open and Laparoscopic Palomo Technique: A Systematic Review of the Literature

We systematically reviewed the results of varicocelectomy by Palomo procedure in children and adolescents. We performed a search of the English literature through the MEDLINE((R)) database and the Cochrane Central Search library. The key words used were "varicocele and children" and "varicocele and adolescents." Of 264 articles published with data on varicocele surgery in children and adolescents 27 concerned the classic Palomo procedure and 20 dealt with the modified Palomo technique, in which the testicular artery was spared. Laparoscopic Palomo varicocelectomy was compared with the open Palomo technique. Totals of 1,344 and 496 patients were treated with the laparoscopic and open Palomo techniques, respectively. The rates of hydrocele in the open and laparoscopic groups were 9.7% and 6.9%, respectively (p = 0.81). The rate of recurrence was 2.9% in the open group and 4.4% in the laparoscopic group (p = 0.146). A modified Palomo procedure was used in 715 operations and the classic technique in 1,454. Hydrocele was diagnosed in 3.2% of patients in the modified group and 7.7% in the classic group (p <0.001). Varicocele recurred in 4.2% of patients undergoing the modified procedure and 3.4% of those undergoing the classic procedure (p = 0.506). Mean +/- SD testicular catch-up growth was 54.7% +/- 38.9% in the modified group and 66.7% +/- 19.9% in the classic group (p = 0.584). Three studies documented improvement of the quality of semen examination postoperatively compared to a control group of uncorrected cases. No study evaluated the rate of fertility after varicocelectomy. The rate of hydrocele is high with the classic Palomo technique and less with the modified technique. The rate of varicocele recurrence is around 3% to 4% with both procedures. The percentage of testicular catch-up growth is variable.

Laparoscopic Surgery for Varicoceles in Children: An Audit in a Single Centre

Varicoceles are associated with a time dependent decline in testicular function. The pathophysiology and timing of this remains unclear. However surgery for adolescent varicoceles is a relatively common procedure. There are several treatment options for this condition and in 1999 laparoscopic management was commenced at our institute. We performed an audit to compare our results with those reported in the literature. A retrospective case-note review of patients identified from our theater database was performed. We reviewed patient demographics, indications, technique used, grade of surgeon, and outcomes. A review of the literature was carried out to identify a gold standard to compare our results with. Between 1999-2007 we operated on 24 adolescent varicoceles, all left side. Median age was 13.5 years (range 8-16). Indications for surgery included high grade varicocele, discomfort and testicular atrophy. All patients underwent laparoscopic Palomo technique dividing all vessels and lymphatics. The grade of primary operator was consultant (54%) and trainee (46%). Complications included wound infection (4.1%), hydrocele (12.5%), and recurrence (8.3%). We found no consensus view regarding the management of varicoceles in adolescents within the literature; however, our outcomes compared favorably with other published results using the laparoscopic Palomo technique. Laparoscopic management of varicoceles is safe and effective at our institute. The indications and timing of surgery remain varied. The surgery is performed by both consultants and trainees.

The Role of Varicocele Repair in the New Era of Assisted Reproductive Technology

Infertility affects 10–15% of couples who are trying to conceive, and half of the cases are due to male infertility. Intracytoplasmic sperm injection is increasingly being used to overcome multiple sperm deficiencies. Due to its effectiveness, some have proposed ICSI as a solution for all cases of male infertility, regardless of the cause. Hence, even men with potentially treatable causes of infertility have sought the aid of assisted reproductive technology, rather than undergo specific therapies to treat their infertility. Varicoceles are the most frequent physical finding in infertile men; indeed, they may be responsible for nearly one-third of cases of male infertility. Varicocele management, however, has always been a controversial issue because very few randomized, controlled studies have been performed to examine varicocelectomy as an infertility treatment. Significant evidence suggests that varicoceles have a harmful effect on the testis and that varicocelectomy can not only prevent progressive decline in testicular function but also reverse the damage. However, the degree to which varicocele repair improves pregnancy rates and the success of assisted reproductive technology remains controversial.

Relationship of pubertal gynecomastia with varicocele and various parameters of growth: a seven year prospective study

Gynecomastia is a complex process resulting from many hormonal changes. It is related to either actual or relative decrease in testosterone-to-estrogen ratio. Varicocele is known to be associated with a progressive decline in testicular function. Hence we tried to study their relationship in otherwise clinically healthy males. Furthermore, we analyzed the relationship of gynecomastia with various physical changes occurring during pubertal development of boys so as to explore its pathophysiology and predict its onset or disappearance. Prospective population based study. 131 clinically healthy boys aged 6–8 were followed for 7 years by visiting 3 schools once every year and twice a year as they near their puberty. Children were examined for the presence of gynecomastia (≥1 cm of palpable button of firm subareolar breast tissue) and varicocele (by examining the boys in standing position with help of Valsalva maneuver when appropriate). Remaining clinical examination included height (Siber Hegner anthropometer), weight (beam balance), testicular volumes (Prader orchidometer), and Tanner stage according to pubic hair distribution. Logistic regression analysis was used to determine the risk for developing gynecomastia in those who had varicocele as compared to those without it. Prevalence of gynecomastia and varicocele in our study population was 15.2% (20 of 131) and 22.1% (29 of 131) respectively. Bilateral gynecomastia (13 of 131) was more common than either right (5 of 131) or left sided (4 of 131). In 2 boys, unilateral gynecomastia subsequently became bilateral. Gynecomastia was more frequent in Tanner stages 3 and 4. In 13 boys, gynecomastia subsided on follow up. Mean ± standard deviation of age (years), height (cm), weight (kg), left and right testicular volumes (mL) at which gynecomastia was seen to appear were 12.27 ± 0.86, 157.6 ± 7.3, 46.0 ± 6.7, 8.1 ± 2.9 and 9.3 ± 4.0 respectively. Corresponding values for disappearance of gynecomastia were 13.0 ± 0.86, 164.5 ± 5.6, 48.62 ± 5.8, 12.5 ± 4.2, 13.5 ± 4.0 respectively. In 11 year olds, when gynecomastia was seen for the first time, it was positively correlated with varicocele (odds ratio = 3.039, 95% confidence interval = 1.215 – 7.598). However no significant correlation was seen in subsequent years which may be due to the transient nature of gynecomastia. Adolescent gynecomastia is a transient mid-puberty event. Gynecomastia is more likely to develop in young boys having varicocele.

Is varicocelectomy indicated in subfertile men with clinical varicoceles who have asthenospermia or teratospermia and normal sperm density?

Varicocele is the most common treatable cause of male infertility and is associated with progressive decline in testicular function. Varicocelectomy, a commonly performed operation, is indicated in infertile males with varicoceles who have oligospermia, asthenospermia, teratospermia or a combination of these factors. It is not clear if varicocelectomy is indicated if the patients have normal sperm density associated with asthenospermia or teratospermia. We reviewed 167 patients with varicocele-associated male infertility over a 7-year period (December 1999-November 2005). Pre- and post-varicocelectomy seminal fluid analyses, assessed using the World Health Organization criteria, were obtained at intervals of 4-6 months. Wilcoxon signed rank tests were used to evaluate for statistical significance and P < or = 0.05 was considered significant. The mean age of the patients and their spouses were 35 and 28 years, respectively. The mean duration of infertility was 3.2 years (range, 1.5-7.5). Oligospermia, teratospermia, asthenospermia, oligospermia, asthenospermia and teratospermia (OAT) syndrome and azoospermia were found preoperatively in 106 (63.5%), 58 (34.7%), 154 (92%), 118 (71%) and 15 (9%) patients, respectively. Overall, significant improvements in semen volume (P < 0.001), sperm density (P < 0.001), sperm motility (P < 0.001) and sperm vitality (P < 0.001) were obtained after varicocelectomy. There was, however, no significant improvement in sperm morphology after varicocelectomy (P = 0.220). When patients with preoperative oligospermia (sperm density, <20 million/mL) were considered separately, varicocelectomy led to significant improvement in all the semen parameters except the sperm morphology (P = 0.183). Conversely, when varicocele patients with a sperm density of > or =20 million/mL (normospermia) associated with asthenospermia and/or teratospermia were considered separately, they did not show significant improvement in any of the semen parameters after varicocelectomy (P > 0.05). In addition, azoospermic patients did not show significant improvement in any of the semen parameters (P > 0.05) No significant improvement in semen parameters may be obtained in patients with clinical varicocele and preoperative normospermia. It is possible that only patients with preoperative oligospermia may benefit from varicocelectomy. Larger multi-institutional studies are needed to determine more definitively if asthenospermia or teratospermia in normospermic subfertile males with clinical varicoceles are in fact indications for varicocelectomy.

LYMPHATIC SPARING LAPAROSCOPIC VARICOCELECTOMY: A MICROSURGICAL REPAIR

The division of lymphatic vessels during pediatric varicocelectomy is complicated by hydrocele formation, testicular hypertrophy due to intratesticular edema and decline in testicular function. To prevent these complications, we introduced a microsurgical lymphatic sparing dissection into laparoscopic varicocelectomy. We retrospectively compared outcomes in 104 boys who underwent microsurgical laparoscopic repair for grade II to III varicocele between April 1999 and December 2002 to a group of 67 boys operated on using conventional laparoscopy without lymphatic preservation between January 1997 and March 1999. Using 10x to 20x optical magnification, the lymphatic vessels were identified as colorless tubular structures that were easily separated and preserved. After a mean followup of 17 months there was no significant difference in varicocele recurrence between the 2 groups (6.7% vs 8.9%, p = 0.56). Hydrocele formation and testicular hypertrophy occurred significantly less frequently after microsurgical repair (1.9% and 2.9%, respectively, vs 17.9% and 20.1% in the conventional group, p = 0.0003). No major complications were encountered. Preservation of lymphatics in laparoscopic varicocelectomy is technically feasible, and decreases hydrocele formation and the development of testicular hypertrophy. This microsurgical modification is a safe and efficacious alternative for urologists skilled in reconstructive laparoscopy.

Effects of Age on Testicular Function and Consequences of Testosterone Treatment1

Testosterone and gonadotropins. Several studies demonstrate that the serum testosterone concentration declines with increasing age. In one cross-sectional study of 83 healthy men, the free testosterone concentration declined by age 80 to approximately 40% of that at age 20, but because the serum concentration of sex hormone binding globulin (SHBG) increased during this age span, the serum concentration of total testosterone declined only to approximately 80% of that at age 20 (1). In another cross-sectional study of 71 healthy men, aged 26–90 yr, living in similar circumstances, the 33 younger men had a mean free testosterone concentration of 10.7 6 3.4 ng/dL (sd) and the 38 older men had a mean free testosterone concentration of 5.8 ng/dL (P , 0.01) (2). Total serum testosterone concentrations in the two groups were 659 6 201 ng/dL and 490 6 160 ng/dL, respectively (P , 0.01). In a third cross-sectional study in 810 healthy men mostly between 50 and 84 yr old, the serum bioavailable testosterone concentration declined by approximately 55– 60%, but the serum total testosterone concentration did not decline at all (3). In one longitudinal study, 39 healthy men whose mean serum total testosterone concentration was 633 6 22 ng/dL (se) when they enrolled in a study of aging in 1980 had a mean value of 464 6 33 ng/dL in 1994 (4). In another longitudinal study of 890 men, both total testosterone and the ratio of testosterone to SHBG decreased with age (Fig. 1) (5). The decline in testicular function appears to involve a combination of primary and secondary hypogonadism. A gradual increase in the serum concentration of LH indicates a degree of primary hypogonadism. In a cross-sectional study, the mean serum LH concentration in 33 men of an average age of 37 yr was 1.9 6 0.6 ng/mL and in 38 men of an average age of 71 yr was 2.2 6 0.6 ng/mL (2). In a longitudinal study, 39 men whose mean LH was 9.4 6 0.4 (se) mIU/mL when they enrolled in 1980 had a mean value of 13.7 6 1.3 mIU/mL in 1994 (4). However, the findings that LH secretory burst amplitude decreases with increasing age and that this decrease was the most prominent determinant of decreased testosterone secretion indicates a degree of secondary hypogonadism (6). This conclusion is supported by the failure of LH secretion to respond to drug-induced reduction of the serum testosterone concentration in old men as well as in young men (7).

Inhibin and age in men

Normal elderly men are reported to have decreased testicular function despite elevated gonadotrophin levels. We wished therefore to determine if changes in testicular function occur over the age range 19-60 years. Single fasting blood samples were obtained between 0800 and 0900 h. Working men in a large industrial company between the ages of 19 and 60 years participated in the study. FSH, serum immunoreactive inhibin and total testosterone were measured, the latter two as measurements of Sertoli and Leydig cell function respectively. The mean baseline serum immunoreactive inhibin level was significantly lower in men from the older age groups, 31-40 years (479 U/l), 41-50 years (439 U/l) and 51-60 years (415 U/l) than in men from the youngest age group, 21-30 years (613 U/l) while serum FSH was higher in men from the older age groups, 41-50 years (3.7 IU/l) and 51-60 years (6.1 IU/l) than in men from the youngest age group, 21-30 years (2.6 IU/l). There appears to be a change in both FSH and inhibin production, consistent with a primary decline in testicular function. There was no significant difference in testosterone levels between the older age group, age 51-60 years and the younger age group, age 21-30 years. However, testosterone levels were significantly lower in the 41-50 year age group, when compared with the 21-30 year, this significance levelling out at about age 45 years. The data are consistent with the hypothesis that immunoreactive inhibin reflects inhibin bioactivity, and that inhibin plays a role in the feedback control of FSH secretion in men.

The effects of normal aging on the response of the pituitary-gonadal axis to chronic clomiphene administration in men.

Serum androgens decline with age in normal men, despite normal or elevated bioactive serum gonadotropins, suggesting that primary testicular dysfunction occurs with aging. The authors further assessed the question of age-related testicular dysfunction by evaluating whether raising serum gonadotropins above the normal serum range for an extended time in healthy elderly men might result in bringing their gonadal function to a level similar to that found in young adult men. Five elderly (65 to 85 years old) and five young adult men (26 to 33 years old) were given 50 mg of clomiphene citrate (CC) twice a day for 8 weeks to stimulate gonadotropin production. During that time, testosterone (T), non-sex hormone-binding globulin bound T, and estradiol increased significantly in both age groups, while serum inhibin increased significantly only in the young adult men. The increases in serum androgens with CC administration were significantly greater in the young adult men than in the elderly men. These hormone changes occurred in the setting of serum gonadotropins that increased significantly in both age groups, although there was a tendency for the elderly men to have a smaller increase in luteinizing hormone. Despite 8 weeks of stimulation of the pituitary-gonadal axis by CC administration, the elderly men demonstrated significantly diminished testicular responses compared with the young adult men. Sertoli cell function, as determined by inhibin production, was more diminished in the elderly men than was Leydig cell function. These data strengthen the hypothesis that normal aging in men is accompanied by a decline in testicular function.

Does Age Influence the Bioactivity of Follicle-stimulating Hormone in Men?

We measured follicle-stimulating hormone (FSH) by both standard radio-immunoassay (RIA) and bioassay (Bio) methods in 56 men, using a modification of a previously described in vitro granulosa cell bioassay for the determination of the bioactivity of FSH. Thirty-four were young (mean age 25 years), and 22 elderly (mean age 72). No interfering factors such as disease or alcoholism could be identified. The elderly men had higher RIA-FSH levels compared with the younger ones. Bio-FSH demonstrated a similar trend and therefore the Bio/Immuno ratio was practically constant (3.3 +/- 0.6 vs. 2.7 +/- 0.4). We conclude that the age-associated decline in testicular function seen in normal ageing cannot be attributed to a chronic change in FSH activity. Not only is the RIA-FSH elevated among the elderly, it is of the same biological quality as in the younger men. The underlying cause for the testicular function decline is probably at the level of the testis itself.