A rare case of 46, XX (SRY positive) testicular disorder of sex development with growth hormone deficiency: Case report.

RATIONALE: Chromosome karyotype analysis and SRY (sex determined region of Y chromosome) gene detection are routines for the diagnosis of growth hormone deficiency (GHD), but further whole exome gene sequencing occasionally leads to subversive results and unexpected conclusions. PATIENT CONCERNS: We report a single case of a 7-year-old Chinese boy who had stunted growth since he was 1 year old. He was short in height (height Standard Deviation Score (SDS) was less than 2.9), bilateral scrotal dysplasia and delayed bone age. DIAGNOSIS: His growth hormone (GH) stimulation tests showed GHD. His karyotype analysis and polymerase chain reaction (PCR) analyses indicated a 46, XX disorder of sex development (DSD) without the presence of the SRY gene. Nevertheless, considering that female gonad was not observed in the chest and abdominal magnetic resonance imaging, the whole exome gene sequencing was performed. Sequencing data confirmed the presence of SRY gene sequence and two copies of chromosome X. Later, using different primer sequences for PCR, it showed that the SRY gene was positive. The final diagnosis was a rare case of "46, XX (SRY positive) testicular DSD with GHD". INTERVENTIONS: The boy's parents agreed to use recombinant human growth hormone (rhGH) for GHD treatment, the starting dose was 0.035 mg / kg / day. But they disagreed with molecular diagnostics and genomic analysis of the Y chromosome. OUTCOMES: The boy was treated with rhGH for 3 months and his height increased by 2.2 cm. The patient will be followed-up until the end of his puberty. LESSONS: In summary, whole exome gene sequencing overturned the preliminary diagnosis results of karyotype analysis and SRY gene detection, and found that there may be a certain correlation between testicular DSD and GHD.

Costus afer leaf extract protects against testicle damage caused by cyclosporine A in adult male Wistar rats through an antioxidant mechanism.

Cyclosporine A is one of the most widely used drugs in organ transplant and oncology patients. But its use is accompanied by many toxicities. This study aimed to investigate the possible protective effect of Costus afer (C. afer) leaf extract on cyclosporine A-induced testicular toxicity. This study was carried out on 40 adult male Wistar rats were divided into four groups: control, C. afer, cyclosporine A and cyclosporine A+ C. afer groups. The investigations include genital weight, sperm count and characters, serum luteinising hormone (LH) and testosterone, testicular tissue contents of reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSHPx) and lipid peroxidation (MDA). Besides, a histopathological examination of testicular tissue stained with haematoxylin and eosin (H & E) was performed. Cyclosporine A+ C. afer group showed a significant increase in the genital weight, serum testosterone, sperm count, motility and viability. Besides, the extract significantly decreased testicular content of MDA and increased SOD, CAT and GSHPx. C. afer coadministration significantly decreased serum LH and sperm abnormalities and protected against testicular histopathological alterations. The extract showed a protective effect against testicular toxicity associated with cyclosporine A and that was through an antioxidant mechanism.

Evaluation of Serum Insulin-like Factor 3 Quantification by LC-MS/MS as a Biomarker of Leydig Cell Function.

BACKGROUND: The peptide hormone insulin-like factor 3 (INSL3) is a marker for Leydig cell function and the clinical use of serum INSL3 measurements has been suggested by several groups. AIM: (1) To establish a reference range for liquid chromatography-tandem mass spectrometry (LC-MS/MS) of serum INSL3 in healthy boys and men; and (2) to compare the associations of serum INSL3 and testosterone (T) to pubertal stage, lifestyle factors, diurnal variation, body composition, and human chorionic gonadotropin (hCG) stimulation. RESULTS: In a reference range based on LC-MS/MS analysis of serum from 1073 boys and men, INSL3 increased from levels close to the detection limit (0.03 µg/L) in prepubertal boys to a maximum mean level of 1.3 µg/L (95% CI, 0.9-2.7) in young men (19-40 years of age) and decreased slightly in older men (0.1 µg/L per decade). Serum T, but not INSL3, was associated with body mass index or body fat percentage and with alcohol consumption. Smoking was positively associated with serum T, but negatively associated with INSL3. There were significant diurnal variations in both INSL3 and T in men (P < 0.001), but serum INSL3 varied substantially less, compared with serum T (± 11% vs ± 26%). Mean serum INSL3 increased after hCG stimulation, but less than T (+ 17% vs + 53%). In both healthy men and in patients suspected of testicular failure, baseline serum INSL3 was more closely associated to the hCG-induced increase in serum T than baseline T itself. CONCLUSION: Measurement of serum INSL3 by LC-MS/MS has promise as a marker of testicular disorders.

Frequent testicular involvement in multibacillary leprosy.

OBJECTIVE: Testicular involvement or atrophy in leprosy is silent, unreported, and under-estimated. The aim of this study was to assess the frequency of testicular atrophy and its consequences through the examination of clinical manifestations, hormonal profile, and semen analysis in leprosy patients. METHODS: A descriptive observational study using a cross-sectional design and consecutive sampling method was conducted from May to July 2018. The study was conducted in Dr. Hasan Sadikin General Hospital, Bandung, Indonesia and included 32 men affected by leprosy and five healthy men as a control group. All patients were subjected to history-taking, dermatological and genital examinations, assessment of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone, and testicular ultrasonography examination. Semen analysis was performed for the 10 patients who consented. RESULTS: Testicular atrophy was observed in 93.75% of patients. Clinical manifestations of testicular atrophy were loss of libido (21.87%), female pubic hair pattern (9.38%), gynecomastia (6.25%), and secondary infertility (6.25%). Hormonal imbalance was seen in 16 patients, and all 10 patients who underwent semen analysis showed an abnormality. CONCLUSIONS: This study showed a high frequency of testicular atrophy, but the symptoms were only present in a few of patients. The assessment of testicular function should be recommended as a routine work-up for leprosy patients.

Sitagliptin protects male albino rats with testicular ischaemia/reperfusion damage: Modulation of VCAM-1 and VEGF-A.

Twisting of the spermatic cord is considered a popular problem in the urological field, which may lead to testicular necrosis and male infertility. Sitagliptin, a glucose-lowering agent, proved to have a vindicatory function in myocardial and renal ischaemia/reperfusion (I/R), but its role in testicular I/R has not yet been studied. The current work investigates its capability to recover the testicular I/R injury with shedding more light on the mechanism of its action. Four groups were used: sham, sham pretreated with sitagliptin, I/R and sitagliptin/I/R-pretreated groups. The outcomes proved that I/R significantly decreased the serum testosterone, with a major increase in oxidative, inflammatory and nitrosative stress, along with a reduction in testicular vascular endothelial growth factor-A level with marked germinal cell apoptosis. However, pretreatment with sitagliptin significantly reversed the profound testicular I/R damaging effects, on the basis of its antioxidant, anti-inflammatory and anti-apoptotic activities with the ability of recuperation of the testicular vascularity.

Pituitary Dysfunction Among Men Presenting with Hypogonadism.

PURPOSE OF REVIEW: Hypogonadism is a common endocrine dysfunction. This review focuses on the most up-to-date guideline for evaluation of pituitary function among men presenting with signs and symptoms of hypogonadism. RECENT FINDINGS: The clinician must differentiate between primary (testicular) and secondary (pituitary-hypothalamic or central) hypogonadisms and be aware of adult-onset hypogonadism. If gonadotropins are low or inappropriately normal, the clinician must consider potential reversible causes in the hypothalamus-pituitary axis. Also, it is critical to understand the pitfalls of testosterone testing. When clinically indicated, evaluation of other pituitary hormone functions as well as pituitary magnetic resonance imaging may be necessary. Furthermore, it is essential to recognize that pituitary incidentalomas are common. Patients with microprolactinoma are more likely to present with symptoms of sexual dysfunction while those with macroprolactinoma are more likely to present with symptoms of mass effect. Some functional pituitary tumors respond to drug therapy while other nonfunctional tumors require surgical intervention. It is important for the clinician to understand the proper work-up of the hypogonadal patient with pituitary dysfunction and when necessary to refer to an endocrinologist or a neurosurgeon.

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

STUDY QUESTION: Are early signs of metabolic disorder in late adolescence associated with features of impaired testicular function many years before the majority seek parenthood? SUMMARY ANSWER: Adolescents with features of metabolic disorder at 17 years, or insulin resistance (IR) at 20 years of age, show impaired testicular function and altered hormone levels compared to those without metabolic disorder. WHAT IS KNOWN ALREADY: Controversial evidence suggests a recent decline in sperm production potentially linked to environmental influences, but its cause remains unclear. Concomitant increases in obesity and diabetes suggest that lifestyle factors may contribute to this decline in testicular function. Although obesity has been associated with adverse testicular function in some studies, it remains unclear whether poor testicular function merely reflects, or causes, poor metabolic health. If metabolic disorder were present in adolescence, prior to the onset of obesity, this may suggest that metabolic disorder maybe a precursor of impaired testicular function. STUDY DESIGN, SIZE, DURATION: The Western Australian Pregnancy Cohort (Raine) Study is a longitudinal study of children born in 1989-1991 who have undergone detailed physical assessments since birth (1454 male infants born). At 17 years of age, 490 boys underwent a hepatic ultrasound examination, serum cytokine assessment (n = 520) and a metabolic assessment (n = 544). A further metabolic assessment was performed at 20 years (n = 608). Testicular assessment was performed at 20 years; 609 had reproductive hormones measured, 404 underwent a testicular ultrasound and 365 produced a semen sample. PARTICIPANTS/MATERIALS, SETTING, METHODS: Testicular volume was estimated by ultrasonography, and semen analysis was performed according to World Health Organization guidelines. Concentrations of LH, FSH and inhibin B (inhB) in serum were measured by immunoassay and total testosterone by liquid chromatography-mass spectrometry.At 17 years of age, a liver ultrasound examination was performed to determine the presence of non-alcoholic fatty liver disease (NAFLD), and serum analysed for the cytokines interleukin-18 and soluble tumour necrosis factor receptor 1 and 2 (sTNFR1, sTNFR2).At 17 and 20 years of age, fasting blood samples were analysed for serum liver enzymes, insulin, glucose, triglycerides (TG), total cholesterol, high density lipoprotein and low density lipoprotein cholesterol, high sensitivity C-reactive protein and uric acid. The homoeostatic model assessment (HOMA) was calculated and approximated IR was defined by a HOMA >4. Anthropometric data was collected and dual energy X-ray absorptiometry measurement performed for lean and total fat mass. As at this young age the prevalence of metabolic syndrome was expected to be low, a two-step cluster analysis was used using waist circumference, TGs, insulin, and systolic blood pressure to derive a distinct high-risk group with features consistent with the metabolic syndrome and increased cardiometabolic risk. MAIN RESULTS AND THE ROLE OF CHANCE: Men at age 17 years with increased cardiometabolic risk had lower concentrations of serum testosterone (medians: 4.0 versus 4.9 ng/mL) and inhB (193.2 versus 221.9 pg/mL) (P < 0.001 for both) compared to those within the low risk metabolic cluster. Men with ultrasound evidence of NAFLD (n = 45, 9.8%) had reduced total sperm output (medians: 68.0 versus 126.00 million, P = 0.044), testosterone (4.0 versus 4.7 ng/mL, P = 0.005) and inhB (209.1 versus 218.4 pg/mL, P = 0.032) compared to men without NAFLD.Men with higher concentrations of sTNFR1 at 17 years of age had a lower sperm output and serum concentration of inhB, with an increase in LH and FSH (all P < 0.05 after adjustment for age, BMI, abstinence and a history of cryptorchidism, varicocele, cigarette smoking, alcohol and drug use), compared to those without an elevated sTNFR1. Multivariable regression analysis, adjusting for confounders, demonstrated that men in the high-risk metabolic cluster at 20 years had a lower serum testosterone and inhB (P = 0.003 and P = 0.001, respectively). A HOMA-IR > 4 was associated with a lower serum testosterone (P = <0.001) and inhB (P = 0.010) and an increase in serum FSH (P = 0.015). LIMITATIONS, REASONS FOR CAUTION: This study is limited by the sample size and multiple comparisons, and causality cannot be proven from an observational study. Due to a 3-year interval between some metabolic assessments and assessment of testicular function, we cannot exclude the introduction of a bias into the study, as some of the participants and their testicular function will not have been fully mature at the 17-year assessment. WIDER IMPLICATIONS OF THE FINDINGS: Irrespective of a proven causation, our study findings are important in that a significant minority of the men, prior to seeking parenthood, presented co-existent features of metabolic disorder and signs of testicular impairment. Of particular note is that the presence of NAFLD at 17 years of age, although only present in a minority of men, was associated with an almost 50% reduction in sperm output at 20 years of age, and that the presence of IR at 20 years was associated with a 20% reduction in testicular volume. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by Australian NHMRC (Grant Numbers 634457, 35351417 and 403981) and received support from the Raine Medical Research Foundation, The Telethon Kids Institute, University of Western Australia, Women and Infants Research Foundation, Curtin University and Edith Cowan University. D.A.D., J.E.D., N.M., L.A.A., R.-C.H., T.A.M., J.K.O., L.J.B. have nothing to declare. R.J.H. is Medical Director of Fertility Specialists of Western Australia, has equity interests in Western IVF, and has received grant support from MSD, Merck-Serono and Ferring Pharmaceuticals. RMcL has equity interests in the Monash IVF Group. R.J.N. has equity interests in FertilitySA, and has received grant support from Merck Serono and Ferring Pharmaceuticals. D.J.H. has received institutional grant funding (but no personal income) for investigator-initiated testosterone pharmacology studies from Lawley and Besins Healthcare and has provided expert testimony to anti-doping tribunals and for testosterone litigation.This abstract was awarded the Fertility Society of Australia clinical exchange award for the oral presentation at ESHRE, Barcelona, in 2018.

Disorder of hypothalamic-pituitary-gonadal axis induced by abusing of anabolic-androgenic steroids for short time: A case report.

The aim of this study was to evaluate the hypothalamic-pituitary-gonadal axis functionality on a bodybuilding competitioner before, during and after the use of anabolic-androgenic steroids. A young healthy man was followed up for 4 months. The subject reported his drug administration protocol through periodic interviews and performed laboratory tests to monitor the function of his hypothalamic-pituitary-gonadal axis. Time 1 (before the steroids use) shows all hormones levels (follicle-stimulating hormone = 4,2 mUI/ml, luteinising hormone = 3,7 mUI/ml and total testosterone = 5,7 ng/ml) within reference values. In Time 2, after 8 weeks on steroids abuse, a complete hypothalamic-pituitary-gonadal axis derangement is evident with noticeable negative feedback (follicle-stimulating hormone = 1,47 mUI/ml, luteinising hormone = 0,1 mUI/ml and total testosterone = 1,47 ng/ml). At the third moment (40 days after Time 2), we can see a tendency to recovery, however, the serum levels of the investigated hormones were still considerably lower than the baseline values. At the end, we could conclude that the use of anabolic-androgenic steroids, at supraphysiological dosages, even for a short time (8 weeks), causes severe disorder in the hypothalamic-pituitary-gonadal axis. The endogenous testosterone synthesis was severely compromised by important decline in serum luteinising hormone levels.

Protective effects of the hydroalcoholic extract of Fumaria parviflora on testicular injury induced by torsion/detorsion in adult rats.

This study was designed to determine the effects of daily oral administration (250 mg/kg) of the hydroalcoholic extract of Fumaria parviflora (FP) for 14 days on the sperm parameters, oxidative stress parameters, serum testosterone levels, expression of Bax and Bcl-2 genes, and apoptosis index of germ cells after testicular torsion-detorsion (ischaemia-reperfusion, IR) injury model in rats. Twenty-eight adult male Wistar rats were divided randomly into four groups of seven each: sham operation, torsion-detorsion (TD), TD plus the hydroalcoholic extract FP (TDFP) and only FP without TD application (FP). Testicular torsion was created by rotating the left testis 720° in a counterclockwise direction; then, after 4 hr, detorsion was performed. The Johnson's score, mean seminiferous tubule diameter (MSTD) and height (thickness) of seminiferous tubule epithelium (HST) were significantly increased in TDFP and FP groups as compared to TD group. The gene expression of Bcl-2, level of serum testosterone hormone and antioxidant parameters-GPx and SOD-were significantly higher in TDFP and FP groups than TD group. The index of apoptosis, the gene expression of Bax and the level of MDA were significantly higher in TD group than TDFP and FP groups. Therefore, F. parviflora could decrease oxidative stress induced by testicular torsion-detorsion.

Polymorphism rs2274911 of GPRC6A as a Novel Risk Factor for Testis Failure.

CONTEXT: The G protein-coupled receptor GPRC6A is an emerging effector with multiple endocrine roles, including stimulation of T production from the testis. Recently, two men with an inactivating mutation (F464Y) of GPRC6A have been identified, and they showed primary testicular failure and deranged spermatogenesis. Furthermore, one of them also reported cryptorchidism at birth. In addition, a polymorphism (rs2274911, Pro91Ser) in GPRC6A is associated with prostate cancer, a typical androgen-sensitive cancer. OBJECTIVE: To study the possible association between rs2274911 polymorphism and male fertility and/or cryptorchidism. Design, Patients, Settings: A total of 611 subjects, including 343 infertile patients, 197 normozoospermic controls, and 71 cryptorchid newborns, were retrospectively selected. METHODS: Sequencing analysis for rs2274911 polymorphism and F464Y mutation, and serum levels of FSH, LH, and T were assessed. In vitro functional studies for rs2274911 and F464Y were also performed. RESULTS: Homozygous subjects for the risk allele A of rs2274911 had a 4.60-fold increased risk of oligozoospermia and 3.52-fold increased risk of cryptorchidism. A significant trend for increased levels of LH in the GA and AA genotypes, compared with GG homozygotes, was detected in men with azoospermia/cryptozoospermia (P for trend = .027), further supporting an association with primary testicular failure. The mutation F464Y was found in one cryptorchid child (one in 71; 1.41%). Functional studies showed that the A allele of rs2274911 and the F464Y substitution were associated with lower exposition of the receptor on the cell membrane and a reduced downstream phosphorylation of ERK1/2 with respect to wild type. CONCLUSION: Our results suggest that GPRC6A inactivation or sub-function contributes to reduced exposure to androgens, leading to cryptorchidism during fetal life and/or low sperm production in adulthood.

Leydig cell clustering and Reinke crystal distribution in relation to hormonal function in adult patients with testicular dysgenesis syndrome (TDS) including cryptorchidism.

OBJECTIVE: Testicular dysgenesis syndrome (TDS) comprises testicular germ cell cancer, cryptorchidism and some cases of male infertility and hypospadias, which can be linked to impairment of intrauterine gonadal development. Among histological signs of TDS, large Leydig cell (LC) clusters (micronodules) are frequently present. This study aimed to investigate possible associations of LC micronodules with the presence of Reinke crystals and hormonal function of LCs, the latter primarily reflected by serum concentrations of luteinising hormone (LH) and testosterone, in patients with TDS. DESIGN: A retrospective study of 101 andrological patients with TDS (infertility with and without a history of cryptorchidism or presence of germ cell neoplasia in situ) and 20 controls with normal testis histology and LC-function. Archived testicular biopsies were re-evaluated for the presence of LC micronodules and Reinke crystals and the findings were correlated with testis size and serum concentrations of LH, follicle-stimulating hormone (FSH), testosterone, inhibin B, estradiol and sex hormone binding globulin (SHBG). RESULTS: TDS patients with bilateral LC micronodules had significantly lower concentrations of LH, FSH and inhibin B, a lower testosterone/LH-ratio and smaller testis sizes compared to TDS-patients lacking this feature. Presence of LC micronodules was correlated with a lower number of Reinke crystals, while cryptorchid testes had a significantly higher number of crystals than normally descended TDS testes. CONCLUSION: LC micronodules appear to be a compensatory mechanism caused by androgenic failure and are presumably driven by high concentrations of LH. A relative paucity of Reinke crystals in LCs within micronodules in normally descended TDS testes may be a feature of recently renewed immature Leydig cells. The increased number of Reinke crystals in LCs in testes that were either undescended at birth or are persistently undescended could indicate an impairment of LC renewal in cryptorchidism.

[TESTICULAR DEFICIT SYNDROME IN MEN WITH TYPE 2 DIABETES AND OBESITY].

The aim of the study was to examine the level of sex and pituitary hormones in men of older age groups suffering from type 2 diabetes with visceral-abdominal obesity and without it. The study involved 89 men aged 46-76 years with type-2 diabetes. We analyzed the levels of sex hormones (total and free testosterone, estradiol) and lutenizing hormone levels in the blood of men in the survey, depending on the presence/absence of obesity and androgen deficiency. Average levels total and free testosterone were significantly reduced in patients of all groups surveyed. The lowest level of androgens observed in patients with type 2 diabetes, obesity and androgen. Mid E2 levels only in patients with type 2 diabetes and obesity showed a tendency to increase. Coefficient of T/E2 was significantly reduced in patients with type 2 diabetes and obesity (63,00±8,20) and to a lesser extent in patients with type 2 diabetes without obesity (112,40±8,16) compared the control group (136,40±11,30). The results indicate the presence of not only absolute, but relative androgendeficiency in men with type 2 diabetes.

The effect of melatonin on procarbazine induced testicular toxicity on rats.

Procarbazine (P) is an effective chemotherapeutic drug especially used in lymphoma treatment; however testicular toxicity is a limiting factor. Various ways of treatment were tried to preserve testicular function including hormonal treatment, antioxidant treatment, and sperm cryopreservation but resulted with low rates of satisfaction. Procarbazine is a well known agent causing sterility even in the first doses of chemotherapy. Antioxidants such as N acetylcysteine and ascorbate have been used for protective purposes and were very successful. Melatonin (M) is another powerful antioxidant and we aimed to use M for the protection of P induced testicular toxicity in this study. Procarbazine was given peroral by gavage once a week at a dose of 62.5 mg/kg/week for 4 weeks (total dose: 250 mg/kg) (P group) and in procarbazine + melatonin (PM) group, 10 mg/kg melatonin was intraperitoneally administered daily for five days a week for 4 weeks (total 20 days). The experiment ended at day 90. In the P and PM groups the testicle width, length, and weight, sperm A and sperm AB properties (Sperm A: sperms straight line progressive, Sperm B: sperms straight slow progressive, Sperm AB: Sperm A + Sperm B), spermatogonia, Sertoli cells, seminiferous tubule, and germinative layer thickness were lowered as compared with the control group. However, there were no significant differences between the P and PM groups in regard to these parameters. Melatonin preserved Sertoli cell and spermatogonia function. The testosterone and follicle-stimulating hormone (FSH) levels were also preserved. Melatonin significantly decreased malondialdehyde (MDA) levels and preserved the antioxidant enzyme levels such as glutathione peroxidase (GPx) and nitrite nitrate (NO2-/NO3-). Melatonin may protect testicular functions in P treated patients and is open to consideration during chemotherapy since it appears to be without any side effects.

Antioxidants enhance the recovery of three cycles of bleomycin, etoposide, and cisplatin-induced testicular dysfunction, pituitary-testicular axis, and fertility in rats.

OBJECTIVE: To investigate the effects of an antioxidant cocktail (AC) on bleomycin, etoposide, and cisplatin (BEP)-induced testicular dysfunction. DESIGN: In vivo study. SETTING: Research laboratory. ANIMAL(S): Adult male and female Sprague-Dawley rats. INTERVENTION(S): The rats were treated with three cycles of 21 days each of therapeutically relevant dose levels of BEP (0.75, 7.5, and 1.5 mg/kg) with or without the AC (a mixture of α-tocopherol, L-ascorbic acid, Zn, and Se). MAIN OUTCOME MEASURE(S): Sperm parameters, fertility, serum hormone levels (ELISA), testicular histopathology, and expression of proliferating cell nuclear antigen (PCNA), and transferrin (Western blotting and immunohistochemistry) were evaluated at the end of treatment and a 63-day recovery period. RESULT(S): At the end of treatment, the AC improved BEP-induced decrease in sperm motility and increase in abnormality but had no effect on reduced sperm count, fertility, and tubular atrophy, although it up-regulated germ cell proliferation. The AC normalized reduced inhibin B levels, but had no effect on decreased transferrin and testosterone and elevated LH levels. At the end of the recovery period, the AC enhanced the expression of PCNA and transferrin, repopulation of germ cells, LH-testosterone axis, and fertility, but had no effect on reduced FSH and elevated inhibin B levels. CONCLUSION(S): The antioxidants protect and then enhance the recovery of testicular and reproductive endocrine functions when administered concomitantly with BEP therapy. The AC may be beneficial to regain testicular functions after chemotherapy.

Captopril and telmisartan treatments attenuate cadmium-induced testicular toxicity in rats.

The possible protective effect of captopril, an angiotensin-converting enzyme inhibitor, vs. telmisartan, an angiotensin II-receptor antagonist, was investigated in rats with testicular injury induced by a single i.p. injection of cadmium chloride (2 mg/kg). Captopril (60 mg/kg/day, p.o.) and telmisartan (10 mg/kg/day, p.o.) were given for five consecutive days, starting 3 days before cadmium administration. Both agents significantly increased serum testosterone level, which was reduced by cadmium, suppressed lipid peroxidation, restored the depleted reduced glutathione, decreased the elevations of nitric oxide, tumor necrosis factor-α, and cadmium ion levels, and attenuated the reductions of selenium and zinc ions in testicular tissue resulted from cadmium administration. Immunohistochemical analysis revealed that both captopril and telmisartan significantly reduced the cadmium-induced expression of inducible nitric oxide synthase, nuclear factor-κB, Fas ligand, and caspase-3 in testicular tissue. The differences between the results obtained with captopril and telmisartan were insignificant, suggesting that both drugs equally protected the testicular tissue from the detrimental effects of cadmium.

Testicular functions, chronic groin pain, and quality of life after laparoscopic and open mesh repair of inguinal hernia: a prospective randomized controlled trial.

BACKGROUND: Laparoscopic inguinal hernia repair is still not the gold standard for patients with inguinal hernia. The aim of this study was to compare testicular dysfunction, incidence and factors influencing chronic groin pain, and quality of life after laparoscopic and open mesh repair. METHODS: One hundred twenty patients were studied in a prospective randomized trial. One hundred seventeen patients completed the required follow-up, 60 following laparoscopic repair and 57 following open repair. Testicular functions were assessed by testicular volume, blood flow, and hormones, and quality of life was assessed with Short Form 36 version 2 preoperatively and postoperatively at 3 months. Pain was assessed at different time intervals preoperatively and postoperatively. RESULTS: Preoperative profiles of both groups were well matched. A significant decrease in testicular volume (p = 0.01) and less improvement in blood flow (p = 0.048) was seen after open repair. There was also a significant reduction in serum testosterone level (p = 0.02) with a significant increase in FSH and LH level (p < 0.001); however, there was no testicular atrophy. Incidence and severity of chronic groin pain were significantly less after laparoscopic repair during normal and strenuous activities, though they were similar to those after open repair during rest after 3 months postoperatively. Age, preoperative pain, pain at 1 week, and open repair were found to be independent risk factors for chronic pain on multivariate analysis. Quality of life was significantly better postoperatively in terms of physical functions, role physical, bodily pain, and general health after laparoscopic repair. CONCLUSION: Laparoscopic repair seems favorable in terms of better preservation of testicular functions, lower incidence of acute and chronic groin pain, and significant improvement in quality of life when compared to open repair. Younger age, preoperative pain, pain after 1 week postoperatively, and open mesh repair were found to be significant risk factors for chronic groin pain.

[Human placental alkaline phosphatase (hPLAP) is the most frequently elevated serum marker in testicular cancer]. / Die humane plazentare alkalische Phosphatase (hPLAP) ist der am häufigsten erhöhte Serummarker beim Hodentumor.

BACKGROUND: Testicular cancer is the most frequent cancer in patients between 20 and 40 years of age. Cure rates are very high due to standardised operative treatment as well as additional chemotherapy and radiotherapy according to -histological subtype and tumour stage. Histological subtypes are seminoma, non-seminoma and mixed tumours (partly seminoma and partly non-seminoma). The aim of this study was to determine the value of different tumour markers in the primary diagnosis of testicular cancer. MATERIAL AND METHODS: In a retrospective study we investigated 152 consecutive patients with testicular cancer as well as 75 patients with benign scrotal conditions. In all patients the tumour markers human alkaline phosphatase (hPLAP), alpha-fetoprotein (AFP), human chorionic gonadotropin (hCG) and the enzyme lactate dehydrogenase (LDH) were measured. Statistical analyses included descriptive analysis, boxplots, fourfold table, receiver operating characteristic (ROC), calculation of confidence intervals and analysis of variance (ANOVA). RESULTS: 145 patients with a mean age of 34.3 years were eligible. There were 72 seminomas, 33 non-seminomas and 40 mixed tumours with 69% of patients being in Lugano stage I, 19% in stage II and 11% in stage III. hPLAP, AFP and hCG were statistically significantly higher in patients with testicular cancer compared to patients with benign scrotal conditions (p < 0.005). hPLAP showed the best sensitivity/specificity (51.1%/84.0%) followed by AFP (35.7%/97.1%), hCG (32.6%/98.6%) and LDH (31.4%/97.8%). ROC analysis demonstrated no difference between hPLAP, AFP and hCG in the specificity range of 80-100%. However, a combination of hPLAP, AFP and hCG provided statistically significantly better results than single markers (p < 0.001). CONCLUSION: hPLAP is the most often elevated marker in the serum of patients with testicular cancer and potentially demonstrates a significant benefit for therapy monitoring. In our opinion there is a need to debate the consideration of hPLAP in the usual guide-lines of the cancer societies. The unspecific elevation in smokers must be considered. In this regard, reference values of hPLAP depending on smoking habits could be a solution, but valid data are not yet available.

Prophylactic efficacy of Coriandrum sativum (Coriander) on testis of lead-exposed mice.

Lead poisoning is a worldwide health problem, and its treatment is under investigation. The aim of this study was to access the efficacy of Coriandrum sativum (coriander) in reducing lead-induced changes in mice testis. Animal exposed to lead nitrate showed significant decrease in testicular SOD, CAT, GSH, total protein, and tissue lead level. This was accompanied by simultaneous increase in the activities of LPO, AST, ALT, ACP, ALP, and cholesterol level. Serum testosterone level and sperm density were suppressed in lead-treated group compared with the control. These influences of lead were prevented by concurrent daily administration of C. sativum extracts to some extent. Treating albino mice with lead-induced various histological changes in the testis and treatment with coriander led to an improvement in the histological testis picture. The results thus led us to conclude that administration of C. sativum significantly protects against lead-induced oxidative stress. Further work need to be done to isolate and purify the active principle involved in the antioxidant activity of this plant.

Testicular function of survivors of childhood cancer: a comparative study between ifosfamide- and cyclophosphamide-based regimens.

PURPOSE: This study aimed at comparing gonadal toxicity of ifosfamide versus cyclophosphamide received during childhood. METHODS: The evaluation was based on basal FSH measurement. LH and testosterone were also measured in most of the patients. One hundred patients had received ifosfamide and 59 had received cyclophosphamide. RESULTS: Median age at treatment was 11.2 years. The median interval since treatment was 10.7 years (range 4.1-20.2) and median age at evaluation was 21.4 years (17.5-36.1). The median dose of ifosfamide and of cyclophosphamide was 54 g/m(2) (18-114) and 8.3 g/m(2) (4.6-22), respectively. All but two males had normal testosterone levels. FSH was abnormal in 28/59 patients (47.5%) after receiving cyclophosphamide and was within the normal range in 94/100 patients (94%) after receiving ifosfamide. CONCLUSIONS: These results show that ifosfamide is associated with a lower risk of gonadal damage than cyclophosphamide. The risk of abnormal FSH increased with the cumulative dose of cyclophosphamide.