Inflammation is a primordial host response to invasion by pathogens or tissue injury. During infection, microbes can activate immune cells through pattern-recognition receptors, such as Toll-like receptors, an evolutiona...Inflammation is a primordial host response to invasion by pathogens or tissue injury. During infection, microbes can activate immune cells through pattern-recognition receptors, such as Toll-like receptors, an evolutionarily conserved family of receptors that mediate innate immunity in a wide range of organisms. Infection also triggers an increase in glucocorticoid levels as part of the stress response. The scenario indicates that these signals have to be well integrated to mount an effective host response to infection and injury. The mechanisms by which innate and adaptive immunity are regulated, as well as the intersection of these responses with glucocorticoids and the glucocorticoid receptor (GR) in the epididymis, an organ essential for the transport, maturation, storage, and protection of the spermatozoa, are not well understood. In this review we bring together recent data demonstrating the cellular and biochemical machinery involved in the response of the adult rat epididymis to a bacterial product challenge. We also illustrate the basic aspects of the expression, localization, function, and regulation of the GR by steroid hormones (androgens and glucocorticoids) within the epididymis. We conclude with considerations of controversial or still unanswered topics about GR, now emerging as a regulatory step in epididymal biology, its functional relationship with androgens and androgen receptor, and the innate immune response of the epididymis. How these topics may be of interest as part of future research in the area, and how they ultimately can help us to better understand the epididymal function under noninflammatory and inflammatory conditions, are also discussed.
Androgens are responsible for maintaining epididymal structure and functions. However, little is known about how androgen action is mediated and the mechanisms underlying the restoration of the integrity of epididymal ce...Androgens are responsible for maintaining epididymal structure and functions. However, little is known about how androgen action is mediated and the mechanisms underlying the restoration of the integrity of epididymal cells after androgen deprivation. We first provide an overview of what is known about androgen action in this tissue and then present data on the initial and sequential roles of androgens in altering cellular architecture and function in an androgen-deprived condition. Using morphometric analysis and the rat model, we identified changes in epithelial cell height and lumen diameter, as well as in the numbers of proliferating cells in different regions and at various time points after androgen withdrawal and replacement. The sequence of gene activation or suppression that occurred in the androgen-deprived tissue was examined upon the readministration of the 2 active metabolites of testosterone, dihydrotestosterone (DHT) and estradiol. Although few genes were regulated by estradiol, many were affected by DHT. Epidermal growth factor (EGF) and insulinlike growth factor-1 (IGF1) appear to play an important role in the early response pathway activated by DHT because of their function in the regulation of the expression of many other genes. The intracellular signaling pathway involved in mediating the action of androgen in restoring epididymal epithelial cell integrity was investigated using the PC-1 epididymal cell line. IGF1 and EGF receptors were found to be important mediators of androgen receptor-mediated activation of the MAPK/ERK pathways. Together, these studies provide a greater understanding of the mechanisms of androgen action in the epididymis.
This study aims to provide further insight into the phenotypic heterogeneity of Klinefelter syndrome (KS) by presenting clinical, hormonal, and genetic data from a large series of Egyptian infertile patients with KS. A r...This study aims to provide further insight into the phenotypic heterogeneity of Klinefelter syndrome (KS) by presenting clinical, hormonal, and genetic data from a large series of Egyptian infertile patients with KS. A retrospective case series of KS patients was studied over a period from January 2003 to April 2010. All patients underwent a complete history and physical examination; color duplex examination; semen analysis; measurement of total testosterone (T), follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), and prolactin (PRL); and chromosomal typing. Mosaic KS diagnosis was confirmed by fluorescence in situ hybridization. The series included 216 KS patients (198 nonmosaic, 16 mosaic, and 2 KS variants). Typical clinical signs of hypoandrogenism were observed in 86% of patients. Gynecomastia affected 20.8% of the patients. Eunuchoidal body proportions, with arm span exceeding height and lower segment length exceeding upper segment length, were detected in 43.9% and 64.4% of the patients, respectively. In all patients, a reduction in testicular size and azoospermia were detected. Normal levels of T, FSH, LH, E2, and PRL were detected in 44.5%, 3.7%, 3.3%, 93.5%, and 91.2% of patients, respectively. Differences were not significant between patients with classic KS and those with mosaic KS in terms of the frequency of clinical signs of hypoandrogenism, gynecomastia, low T concentrations, or high concentrations of FSH, LH, E2, and PRL (all P > .05). The results of the current study emphasize the heterogeneous clinical, hormonal, and genetic phenotype of infertile KS patients. Our findings support the usefulness of cytogenetic studies in infertile patients showing small testicular size and azoospermia, regardless of the presence of other clinical or endocrine findings.
The objective of this study was to determine the effects of low-level laser light exposure on the motility of spermatozoa and on DNA damage. Thirty-three semen samples were collected for routine analysis and were classif...The objective of this study was to determine the effects of low-level laser light exposure on the motility of spermatozoa and on DNA damage. Thirty-three semen samples were collected for routine analysis and were classified as normospermic, oligospermic, or asthenospermic. After routine semen analysis was performed, residual semen was divided into treated and control aliquots. Treated samples were exposed to a 30-second infrared laser pulse of 50 mW/cm(2) at 905 nm, a wavelength thought to increase light-sensitive cytochrome c oxidase in the mitochondrial electron transport chain. Samples were then incubated at 37°C, and aliquots were analyzed at 30 minutes and 2 hours using computerassisted semen analysis. After incubation, 250 μL of each sample was frozen at 280°C until DNA fragmentation analysis by flow cytometry. A significant increase in motility, most prominent in oligospermic and asthenospermic samples (85% increase), was observed 30 minutes after the treatment (P < .0001). No significant increase in DNA damage compared with control samples was observed. Significant changes in sperm motion kinetics were observed. Low-level laser light exposure appears to have a positive short-term effect on the motility of treated spermatozoa and did not cause any increase in DNA damage measured at 2 hours. We conclude that some cases of asthenospermia may be related to mitochondrial dysfunction. The implications of this study in terms of future clinical applications needs further investigation.
We identified an unusual novel nonsense mutation in exon 3 of the androgen receptor (AR) gene in a patient with complete androgen insensitivity that was persistence of Wolffian derivatives. Sequence analysis revealed a s...We identified an unusual novel nonsense mutation in exon 3 of the androgen receptor (AR) gene in a patient with complete androgen insensitivity that was persistence of Wolffian derivatives. Sequence analysis revealed a substitution (C→T) at position 2211 and a deletion of G at position 2213 in exon 3 of the AR gene, resulting in the conversion of arginine(CGG) to a stop codon (TGA) of the AR. Western blotting demonstrated a truncated AR with around 70 kd was expressed. Histology of patient's testes showed that seminiferous tubules were totally filled with Sertoli cells without germ cells. Immunohistochemistry revealed positive AR localization in the nuclei of Sertoli cells and epithelia of efferent ductule and vas deferens. AR immunoexpression was stronger in the epithelia of efferent ductule and vas deferens than in Sertoli cells. The study extends the spectrum of exon 3 mutations in the AR gene.
Posttranscriptional status of messenger RNAs (mRNA) can be affected by many factors, most of which are RNA-binding proteins (RBP) that either bind mRNA in a nonspecific manner or through specific motifs, usually located...Posttranscriptional status of messenger RNAs (mRNA) can be affected by many factors, most of which are RNA-binding proteins (RBP) that either bind mRNA in a nonspecific manner or through specific motifs, usually located in the 3' untranslated regions. RBPs can also be recruited by small noncoding RNAs (sncRNA), which have been shown to be involved in posttranscriptional regulations and transposon repression (eg, microRNAs or P-element-induced wimpy testis-interacting RNA) as components of the sncRNA effector complex. Non-sncRNA-binding RBPs have much more diverse effects on their target mRNAs. Some can cause degradation of their target transcripts and/or repression of translation, whereas others can stabilize and/or activate translation. The splicing and exportation of transcripts from the nucleus to the cytoplasm are often mediated by sequence-specific RBPs. The mechanisms by which RBPs regulate mRNA transcripts involve manipulating the 3' poly(A) tail, targeting the transcript to polysomes or to other ribonuclear protein particles, recruiting regulatory proteins, or competing with other RBPs. Here, we briefly review the known mechanisms of posttranscriptional regulation mediated by RBPs, with an emphasis on how these mechanisms might control spermatogenesis in general.
The aim of this paper was to find a link between Peyronie disease (PD) and bioavailable testosterone (bT)/free testosterone (fT) blood levels. Subjects with no erectile dysfunction were prospectively studied with respect...The aim of this paper was to find a link between Peyronie disease (PD) and bioavailable testosterone (bT)/free testosterone (fT) blood levels. Subjects with no erectile dysfunction were prospectively studied with respect to 3 parameters: differences in bT/fT between 106 PD patients and 99 healthy controls; differences in plaque area, penile curvature, and pain between 54 PD patients with low bT/fT and 52 PD patients with normal bT/fT; and differences in intraplaque verapamil efficacy between 20 hypogonadal PD patients supplemented with testosterone and 23 hypogonadal PD patients administered a placebo. Medical history, objective examination, and dynamic duplex scanning of the penis, both before and 8 months after the end of the therapy (ie, at the end of the study period), were used to assess PD. Testosterone supplementation was carried out with testosterone buccal adhesive patches 2 × 30 mg/d for the entire study period. bT and fT were significantly lower in PD patients than in control patients. The plaque area was significantly higher in PD patients with low bT/fT than in patients with normal bT/fT. No significant difference emerged when pain or penile deformity were examined. Plaque area and penile curvature improved to a greater extent when intraplaque verapamil injections were associated with testosterone administration than when associated with a placebo. Men with PD had lower bT/fT than healthy controls. In these patients, supplementation with testosterone improved the efficacy of intraplaque verapamil. Plaque area and penile curvature were more severe in hypogonadal PD.
The aim of this study was to develop and to test the standardized aseptic technology of permeable cryoprotectant-free vitrification of human spermatozoa in capillaries (for intracytoplasmic sperm injection [ICSI] or in v...The aim of this study was to develop and to test the standardized aseptic technology of permeable cryoprotectant-free vitrification of human spermatozoa in capillaries (for intracytoplasmic sperm injection [ICSI] or in vitro fertilization [IVF]). To test the effect of vitrification on basic sperm parameters, each of 68 swim-up-prepared ejaculates from oligo-astheno-terato-zoospermic patients were aliquoted and distributed into 3 groups: 1) nontreated control, 2) 10 μL of spermatozoa cryopreserved by slow conventional freezing with glycerol-contented medium, and 3) 10 μL of spermatozoa vitrified in 50-μL plastic capillaries in culture medium with 0.25 M sucrose. Spermatozoa motility (1, 24, and 48 hours after warming), plasma membrane integrity, acrosomal integrity, and spontaneous capacitation-like changes were determined after warming. Aseptic cryoprotectant-free vitrification showed a significantly stronger cryoprotective effect compared with conventional freezing. One hour after warming, motility, plasma membrane integrity, and acrosomal integrity were significantly higher than is observed for conventionally frozen spermatozoa (28% vs 18%, 56% vs 22%, and 55% vs 21%, respectively; P < .05), although lower than in fresh spermatozoa (35%, 96%, and 84%, respectively; P < .05). Capacitation-like changes did not differ significantly between vitrified and conventionally frozen samples (8% vs 9%, respectively; P > .1) (2% in fresh spermatozoa). The newly developed technology of aseptic vitrification of human spermatozoa in capillaries can effectively preserve these cells from cryo-injures. Spermatozoa, vitrified by this technology, are free from seminal plasma owing to swim-up preceding vitrification and are free from permeable cryoprotectants. They are ready for further use immediately after warming without any additional treatment. Therefore, the reported technology has a great potential for use in ICSI/IVF.
Diminished vascular endothelial function results in decreased vasodilator capacity and is associated with erectile dysfunction (ED) in patients afflicted with type 2 diabetes. The current study was designed to evaluate w...Diminished vascular endothelial function results in decreased vasodilator capacity and is associated with erectile dysfunction (ED) in patients afflicted with type 2 diabetes. The current study was designed to evaluate whether daily use of sildenafil could alter endothelial function and improve penile rigidity in a group of patients with diabetic ED. A double-blind, placebo-controlled, prospective trial was conducted with 24 men with type 2 diabetes who were randomized into 2 groups: one receiving daily sildenafil (50 mg, n = 12) and the other placebo (n = 12) for 10 weeks. Erectile function was captured subjectively using the International Index of Erectile Function (IIEF-5), and endothelial function was objectively monitored via brachial artery flow-mediated dilation. Among the placebo and sildenafil groups, there were no significant differences in average patient age, time from type 2 diabetes diagnosis, duration of ED, or baseline IIEF-5 scores. Past medical histories, including smoking, alcohol consumption, hypertension, and hyperlipidemia, were also similar. At the conclusion of the 10-week trial, patients who received daily sildenafil had significantly improved erectile rigidity as captured by IIEF-5 (P < .001) and increased endothelial function via brachial artery flow-mediated dilation (P < .01). Endothelial function in men with type 2 diabetes was enhanced with daily sildenafil. Improved erectile rigidity and enhanced vascular circulation was noted after 10 weeks of daily sildenafil use.
The complex dynamics of the tumor microenvironment and prostate cancer heterogeneity have confounded efforts to establish suitable preclinical mouse models to represent human cancer progression from early proliferative p...The complex dynamics of the tumor microenvironment and prostate cancer heterogeneity have confounded efforts to establish suitable preclinical mouse models to represent human cancer progression from early proliferative phenotypes to aggressive, androgen-independent, and invasive metastatic tumors. Current models have been successful in capitulating individual characteristics of the aggressive tumors. However, none of these models comprehensively mimics human cancer progression, establishing the challenge in their exploitation to study human disease. The ability to tailor phenotypic outcomes in mice by compounding mutations to target specific molecular pathways provides a powerful tool toward disruption of signaling pathways contributing to the initiation and progression of castration-resistant prostate cancer. Each model is characterized by unique features contributing to the understanding of prostate tumorigenesis, as well as limitations challenging our knowledge of the mechanisms of cancer development and progression. Emerging strategies utilize genomic manipulation technology to circumvent these limitations toward the formulation of attractive, physiologically relevant models of prostate cancer progression to advanced disease. This review discusses the current value of the widely used and well-characterized mouse models of prostate cancer progression to metastasis, as well as the opportunities begging exploitation for the development of new models for testing the antitumor efficacy of therapeutic strategies and identifying new biomarkers of disease progression.
Genetic mechanisms have been implicated as a cause of some cases of male infertility. Recently, 10 novel genes involved in human spermatogenesis, including human SEPTIN12, were identified by expression microarray analysi...Genetic mechanisms have been implicated as a cause of some cases of male infertility. Recently, 10 novel genes involved in human spermatogenesis, including human SEPTIN12, were identified by expression microarray analysis of human testicular tissue. Septin12 is a member of the septin family of conserved cytoskeletal GTPases that form heteropolymeric filamentous structures in interphase cells. It is expressed specifically in the testis. Therefore, we hypothesized that mutation or polymorphisms of SEPTIN12 participate in male infertility, especially Sertoli cell-only syndrome (SCOS). To investigate whether SEPTIN12 gene defects are associated with azoospermia caused by SCOS, mutational analysis was performed in 100 Japanese patients by direct sequencing of coding regions. Statistical analysis was performed in patients with SCOS and in 140 healthy control men. No mutations were found in SEPTIN12 ; however, 8 coding single-nucleotide polymorphisms (SNP1-SNP8) could be detected in the patients with SCOS. The genotype and allele frequencies in SNP3, SNP4, and SNP6 were notably higher in the SCOS group than in the control group (P < .001). These results suggest that SEPTIN12 might play a critical role in human spermatogenesis.
The development of multicellular organisms is controlled by sequential activation of a hierarchy of regulatory genes, which encode transcription factors having DNA-binding motifs. We previously identified a testis-specif...The development of multicellular organisms is controlled by sequential activation of a hierarchy of regulatory genes, which encode transcription factors having DNA-binding motifs. We previously identified a testis-specific zinc finger transcriptional factor, Ovol2/MOVO, as a mouse homologue of Drosophila Ovo. Because mice deficient in Ovol2/Movo die during early embryogenesis, its function in male germ cells has remained unknown. We have recently succeeded in preparing anti-Ovol2/MOVO antiserum for immunohistochemical use. In the present study, we demonstrated that Ovol2/MOVO protein started to be expressed in male germ cells at 2 weeks after birth and that Ovol2/MOVO expression was restricted to the XY body in spermatocytes at the pachytene stage. In a reporter assay, Ovol2/MOVO repressed the histone H1t promoter activity in the spermatogenic cell line GC-2spd. These results suggest that Ovol2/MOVO may play an important role in the XY body during spermatogenesis, possibly in the processes of XY body formation and meiotic sex chromosome inactivation.
The purpose of this study was to examine the effects of natural honey supplementation on seminal plasma cytokines, oxidative stress biomarkers, and antioxidants during 8 weeks of intensive cycling training in male road c...The purpose of this study was to examine the effects of natural honey supplementation on seminal plasma cytokines, oxidative stress biomarkers, and antioxidants during 8 weeks of intensive cycling training in male road cyclists. Thirty-nine healthy nonprofessional male road cyclists aged 18-28 years participated in this study. The participants were randomly assigned to exercise + supplement (E + S, n = 20) and exercise (E, n = 19) groups. All subjects participated in 8 weeks of intensive cycling training. Ninety minutes before each training session, subjects in the E + S group supplemented with 70 g of honey, whereas subjects in the E group received 70 g of an artificial sweetener. All subjects had an initial semen sampling at baseline (T(1)). The next 6 semen collections were collected immediately (T(2)) and 12 (T(3)) and 24 hours (T(4)) after the last training session in week 4, as well as immediately (T(5)) and 12 (T(6)) and 24 hours (T(7)) after the last training session in week 8, respectively. In the E group, 8 weeks of intensive cycling training significantly increased seminal interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor (TNF)-α, reactive oxygen species (ROS), and malondialdehyde (MDA) levels (P < .008) and significantly decreased the levels of seminal superoxide dismutase (SOD), catalase, and total antioxidant capacity (TAC) (P < .008). Significantly less elevation in seminal IL-1β, IL-6, IL-8, TNF-α, ROS, and MDA levels (P < .008) and significant increases in seminal SOD, catalase, and TAC concentrations were observed after the honey supplementation in the E + S group (P < .008). It may be possible that honey supplementation following long-term intensive cycling training would be effective in attenuating the probable aggravating effects of intensive cycling training on spermatogenesis and fertility capacity in road cyclists.
Penile schwannoma is a rare encapsulated nerve sheath tumor of the peripheral nerve in the penis. Here, we report a case of multiple, painful, beadlike, nodular tumors in the penis of a 40-year-old man. The nodules showe...Penile schwannoma is a rare encapsulated nerve sheath tumor of the peripheral nerve in the penis. Here, we report a case of multiple, painful, beadlike, nodular tumors in the penis of a 40-year-old man. The nodules showed well-defined margins and hypoechoic areas on gray-scale ultrasonograms. They showed high signal intensity on fat-saturated T2-weighted magnetic resonance imaging (MRI) and intense enhancement on gadolinium-enhanced T1-weighted MRI, compatible with their myxoid content. The nodules pressed against the tunica albuginea and some caused inward indentation, which we considered as indirect evidence of the tumor location. In conclusion, the MRI characteristics and location of the nodules together enable presurgical diagnosis of penile schwannomas, which is especially useful in asymptomatic patients and those unwilling to undergo surgery.
The objective of this study was to determine the clinical pregnancy rate with 2 inseminations compared to a single intrauterine insemination (IUI) in a given cycle using frozen-thawed donor sperm. This was a retrospectiv...The objective of this study was to determine the clinical pregnancy rate with 2 inseminations compared to a single intrauterine insemination (IUI) in a given cycle using frozen-thawed donor sperm. This was a retrospective study at a university practice; patients were women using donor sperm. We conducted a comparison of single IUI, intracervical insemination (ICI) followed by an IUI on the next day, and double IUI (2 consecutive days); clinical pregnancy rate was the main outcome measure. The cycle-specific and total pregnancy rates were not significantly different between the 3 protocol groups (306 cycles). The average pregnancy rate over 3 cycles was 10.2% for IUI, 15.3% for ICI/IUI, and 13.7% for IUI/IUI (P = .47). After controlling for repeated measures per subject and age, gravidity, and use of Clomid, there was no significant difference between protocols. The ICI/IUI (odds ratio [OR] = 1.70; 95% confidence interval [CI], 0.83-3.51) and IUI/IUI (OR = 1.5; 95% CI, 0.52-4.33) protocols appeared more likely to result in a clinical pregnancy than the single IUI protocol. Current information on the optimal number of inseminations per cycle using donor sperm is limited. Our large study using 3 protocols found an increase in pregnancy rate with the addition of either an ICI or IUI to a single IUI protocol in a natural or Clomid cycle but did not meet statistical significance. Additional prospective studies are needed to better counsel patients using donor sperm.
The aim of this study was to evaluate conventional semen parameters (density, morphology, and progressive motility) and the flow-cytometric parameters of DNA fragmentation, mitochondrial membrane potential, phosphatidyls...The aim of this study was to evaluate conventional semen parameters (density, morphology, and progressive motility) and the flow-cytometric parameters of DNA fragmentation, mitochondrial membrane potential, phosphatidylserine externalization, and chromatin compactness in patients with varicocele before and after varicocelectomy. Thirty men (26.5 ± 3.2 years old, range 20-32 years) with oligoasthenoteratozoospermia and grade 3 left varicocele were selected (without other causes of male infertility). Each of them underwent sperm analysis and flow cytometric evaluation before and 4 months after subinguinal microsurgical varicocelectomy (SMV). After varicocelectomy, men had significantly higher sperm density, progressive motility, and normal forms compared with baseline. They also had a significantly lower percentage of spermatozoa with low mitochondrial membrane potential. After SMV, they showed a significantly lower percentage of spermatozoa with phosphatidylserine externalization, an early sign of apoptosis. Significantly decreased percentages of spermatozoa with abnormal chromatin compactness and spermatozoa with DNA fragmentation were found after SMV compared with baseline. Subinguinal microsurgical varicocelectomy improves sperm function in oligoasthenoteratozoospermia secondary to grade 3 left varicocele. Improvements are seen in conventional parameters and biofunctional parameters not routinely evaluated.
With the exception of the domestic cat, all members of the family Felidae are considered either endangered or threatened. Although not yet used for this purpose, spermatogonial stem cell (SSC) transplantation has a high...With the exception of the domestic cat, all members of the family Felidae are considered either endangered or threatened. Although not yet used for this purpose, spermatogonial stem cell (SSC) transplantation has a high potential to preserve the genetic stock of endangered species. However, this technique has not previously been established in felids. Therefore, we developed the necessary procedures to perform syngeneic and xenogeneic SSC transplants (eg, germ cell [GC] depletion in the recipient domestic cats, enrichment and labeling of donor cell suspension, and the transplantation method) in order to investigate the feasibility of the domestic cat as a recipient for the preservation and propagation of male germ plasm from wild felids. In comparison with busulfan treatment, local x-ray fractionated radiation was a more effective approach to depleting endogenous spermatogenesis. The results of both syngeneic and xenogeneic transplants revealed that SSCs were able to successfully colonize and differentiate in the recipient testis, generating elongated spermatids several weeks posttransplantation. Specifically, ocelot spermatozoa were observed in the cat epididymis 13 weeks following transplantation. As donor GCs from domestic cats and ocelots were able to develop and form mature GCs in the recipient environment seminiferous tubules, these findings indicate that the domestic cat is a suitable recipient for SSC transplantation. Moreover, as modern cats descended from a medium-size cat that existed approximately 10 to 11 million years ago, these results strongly suggest that the domestic cat could be potentially used as a recipient for generating and propagating the genome of wild felids.
Urinary concentrations of metabolites of the anti-androgenic xenobiotic di-(2-ethylhexyl) phthalate (DEHP) were previously shown to be weakly associated with serum levels of several hormones in 2 disparate US populations...Urinary concentrations of metabolites of the anti-androgenic xenobiotic di-(2-ethylhexyl) phthalate (DEHP) were previously shown to be weakly associated with serum levels of several hormones in 2 disparate US populations: partners of pregnant women participating in the Study for Future Families and partners in infertile couples from Massachusetts General Hospital infertility clinic. The observed associations between phthalate metabolites and reproductive hormones were robust and insensitive to the characteristics of the subpopulation or the laboratory in which the hormones were measured, despite the fact that these 2 populations span a range of fertility, urinary phthalate metabolites, and reproductive hormone levels. We therefore examined associations between urinary metabolites of DEHP and reproductive hormones-follicle-stimulating hormone, luteinizing hormone, testosterone (T), inhibin B, and estradiol (E(2))-and sex hormone-binding globulin (SHBG) in the pooled population. The magnitude of the associations seen were similar to those reported for each population separately, but effect estimates were more precise because of the increased sample size and the greater range of phthalate metabolite concentrations and hormone levels. Urinary concentrations of 3 metabolites of DEHP [mono(2-ethylhexyl) phthalate (MEHP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), and mono(2-ethyl-5-oxohexyl) phthalate (MEOHP)] were inversely associated with the free androgen index (FAI = T/SHBG) and calculated free testosterone. Urinary concentrations of MEHHP and MEOHP were positively associated with SHBG, and MEHP was inversely associated with E(2). No other phthalate metabolites were associated with serum hormones, consistent with results in each population. Our results in this diverse population suggest that DEHP exposure is robustly associated with some male sex steroid hormones.
The prevalence of erectile dysfunction is high in men of all ages and increases greatly in the elderly. In particular, severity and prevalence both increase with aging. Because erectile dysfunction is a symptom, physicia...The prevalence of erectile dysfunction is high in men of all ages and increases greatly in the elderly. In particular, severity and prevalence both increase with aging. Because erectile dysfunction is a symptom, physicians should diagnose underlying pathologies that might lead to it instead of focusing only on finding a viable treatment. Physical inactivity negatively impacts on erectile function; experimental and clinical exercise interventions have been shown to improve sexual responses and overall cardiovascular health. Several studies have confirmed that combining 2 interventions (Mediterranean diet and physical activity) provides additional benefit to erectile function, likely via reduced metabolic disturbances (eg, inflammatory markers, insulin resistance), decreased visceral adipose tissue, and improvement in vascular function (eg, increased endothelial function). This brief review shows the main clinical evidence of benefits induced by physical activity on erectile and endothelial dysfunction. The literature shows that erectile dysfunction in middle-aged men is often an early event in endothelial damage, and physical activity is able to improve both erectile and endothelial dysfunction. There are conflicting data regarding the effects of exercise on androgen status. In clinical practice it would be recommended to add regular physical activity to balanced diet and drugs to achieve better therapeutic results.