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   2014| March-April  | Volume 16 | Issue 2  
    Online since March 1, 2014

 
 
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REVIEW
Late-onset hypogonadism: Current concepts and controversies of pathogenesis, diagnosis and treatment
Ilpo Huhtaniemi
March-April 2014, 16(2):192-202
DOI:10.4103/1008-682X.122336  PMID:24407185
Although suppressed serum testosterone (T) is common in ageing men, only a small proportion of them develop the genuine syndrome of low T associated with diffuse sexual (e.g., erectile dysfunction), physical (e.g. loss of vigor and frailty) and psychological (e.g., depression) symptoms. This syndrome carries many names, including male menopause or climacterium, andropause and partial androgen deficiency of the ageing male (PADAM). Late-onset hypogonadism (LOH) describes it best and is therefore generally preferred. The decrease of T in LOH is often marginal, and hypogonadism can be either due to primary testicular failure (low T, high luteinizing hormone (LH)) or secondary to a hypothalamic-pituitary failure (low T, low or inappropriately normal LH). The latter form is more common and it is usually associated with overweight/obesity or chronic diseases (e.g., type 2 diabetes mellitus, the metabolic syndrome, cardiovascular and chronic obstructive pulmonary disease, and frailty). A problem with the diagnosis of LOH is that often the symptoms (in 20%-40% of unselected men) and low circulating T (in 20% of men >70 years of age) do not coincide in the same individual. The European Male Ageing Study (EMAS) has recently defined the strict diagnostic criteria for LOH to include the simultaneous presence of reproducibly low serum T (total T <11 nmol l−1 and free T <220 pmol l−1 ) and three sexual symptoms (erectile dysfunction, and reduced frequency of sexual thoughts and morning erections). By these criteria, only 2% of 40- to 80-year-old men have LOH. In particular obesity, but also impaired general health, are more common causes of low T than chronological age per se. Evidence-based information whether, and how, LOH should be treated is sparse. The most logical approach is lifestyle modification, weight reduction and good treatment of comorbid diseases. T replacement is widely used for the treatment, but evidence-based information about its real benefi ts and short- and long-term risks, is not yet available. In this review, we will summarize the current concepts and controversies in the pathogenesis, diagnosis and treatment of LOH.
  9,148 1,340 70
The relationship between sleep disorders and testosterone in men
Gary Wittert
March-April 2014, 16(2):262-265
DOI:10.4103/1008-682X.122586  PMID:24435056
Plasma testosterone levels display circadian variation, peaking during sleep, and reaching a nadir in the late afternoon, with a superimposed ultradian rhythm with pulses every 90 min reflecting the underlying rhythm of pulsatile luteinizing hormone (LH) secretion. The increase in testosterone is sleep, rather than circadian rhythm, dependent and requires at least 3 h of sleep with a normal architecture. Various disorders of sleep including abnormalities of sleep quality, duration, circadian rhythm disruption, and sleep-disordered breathing may result in a reduction in testosterone levels. The evidence, to support a direct effect of sleep restriction or circadian rhythm disruption on testosterone independent of an effect on sex hormone binding globulin (SHBG), or the presence of comorbid conditions, is equivocal and on balance seems tenuous. Obstructive sleep apnea (OSA) appears to have no direct effect on testosterone, after adjusting for age and obesity. However, a possible indirect causal process may exist mediated by the effect of OSA on obesity. Treatment of moderate to severe OSA with continuous positive airway pressure (CPAP) does not reliably increase testosterone levels in most studies. In contrast, a reduction in weight does so predictably and linearly in proportion to the amount of weight lost. Apart from a very transient deleterious effect, testosterone treatment does not adversely affect OSA. The data on the effect of sleep quality on testosterone may depend on whether testosterone is given as replacement, in supratherapeutic doses, or in the context abuse. Experimental data suggest that testosterone may modulate individual vulnerability to subjective symptoms of sleep restriction. Low testosterone may affect overall sleep quality which is improved by replacement doses. Large doses of exogenous testosterone and anabolic/androgenic steroid abuse are associated with abnormalities of sleep duration and architecture.
  8,917 936 31
Testosterone deficiency: a historical perspective
Eberhard Nieschlag, Susan Nieschlag
March-April 2014, 16(2):161-168
DOI:10.4103/1008-682X.122358  PMID:24435052
The biological effects of the testes and testosterone are known since antiquity. Aristotle knew the effects of castration and his hypothesis on fertilization is one of the first scientific encounters in reproductive biology. Over centuries, castration has been performed as punishment and to produce obedient slaves, but also to preserve the soprano voices of prepubertal boys. The Chinese imperial (and other oriental) courts employed castrates as overseers in harems who often obtained high-ranking political positions. The era of testis transplantation and organotherapy was initiated by John Hunter in London who transplanted testes into capons in 1786. The intention of his experiments was to prove the 'vital principle' as the basis for modern transplantation medicine, but Hunter did not consider endocrine aspects. Arnold Adolph Berthold postulated internal secretion from his testicular transplantation experiments in 1849 in Göttingen and is thus considered the father of endocrinology. Following his observations, testicular preparations were used for therapy, popularized by self-experiments by Charles-Edouard Brown-Séquard in Paris (1889), which can at best have placebo effects. In the 1920s Sergio Voronoff transplanted testes from animals to men, but their effectiveness was disproved. Today testicular transplantation is being refined by stem cell research and germ cell transplantation. Modern androgen therapy started in 1935 when Enrest Lacquer isolated testosterone from bull testes in Amsterdam. In the same year testosterone was chemically synthesized independently by Adolf Butenandt in Göttingen and Leopold Ruzicka in Basel. Since testosterone was ineffective orally it was either compressed into subcutaneous pellets or was used orally as 17α-methyl testosterone, now obsolete because of liver toxicity. The early phases of testosterone treatment coincide with the first description of the most prominent syndromes of hypogonadism by Klinefelter, by Kallmann, DelCastillo and Pasqualini. In the 1950s longer-acting injectable testosterone enanthate became the preferred therapeutic modality. In the 1950s and 1960s, research concentrated on the chemical modification of androgens in order to emphasize their anabolic effects. Although anabolic steroids have largely disappeared from clinical medicine, they continue to live an illegal life for doping in athletics. In the 1970s the orally effective testosterone undecanoate was added to the spectrum of preparations. Recent transdermal gels and long-acting injectable preparations provide options for physiological testosterone substitution therapy.
  8,479 1,280 21
Lowered testosterone in male obesity: Mechanisms, morbidity and management
Mark Ng Tang Fui, Philippe Dupuis, Mathis Grossmann
March-April 2014, 16(2):223-231
DOI:10.4103/1008-682X.122365  PMID:24407187
With increasing modernization and urbanization of Asia, much of the future focus of the obesity epidemic will be in the Asian region. Low testosterone levels are frequently encountered in obese men who do not otherwise have a recognizable hypothalamic-pituitary-testicular (HPT) axis pathology. Moderate obesity predominantly decreases total testosterone due to insulin resistance-associated reductions in sex hormone binding globulin. More severe obesity is additionally associated with reductions in free testosterone levels due to suppression of the HPT axis. Low testosterone by itself leads to increasing adiposity, creating a self-perpetuating cycle of metabolic complications. Obesity-associated hypotestosteronemia is a functional, non-permanent state, which can be reversible, but this requires substantial weight loss. While testosterone treatment can lead to moderate reductions in fat mass, obesity by itself, in the absence of symptomatic androgen defi ciency, is not an established indication for testosterone therapy. Testosterone therapy may lead to a worsening of untreated sleep apnea and compromise fertility. Whether testosterone therapy augments diet- and exercise-induced weight loss requires evaluation in adequately designed randomized controlled clinical trials.
  6,771 1,005 64
Sex steroids and cardiovascular disease
Bu Beng Yeap
March-April 2014, 16(2):239-247
DOI:10.4103/1008-682X.122357  PMID:24407188
As men grow older, testosterone (T) levels decline and the significance of this change is debated. The evidence supporting a causal role for lower circulating T, or its metabolites dihydrotestosterone (DHT) and estradiol, in the genesis of atherosclerosis and cardiovascular disease (CVD) in men is limited. Observational studies associate low baseline T levels with carotid atherosclerosis, aortic and peripheral vascular disease, and with the incidence of cardiovascular events and mortality. Studies using mass spectrometry suggest that when total T is assayed optimally, calculation of free T might not necessarily improve risk stratification. There is limited evidence to support an association of estradiol with CVD. Interventional studies of T therapy in men with coronary artery disease have shown beneficial effects on exercise-induced myocardial ischemia. However, placebo-controlled, randomized clinical trials (RCTs) of T therapy in men with the prespecified outcomes of cardiovascular events or deaths are lacking. Meta-analyses of randomized controlled trials of T published up to 2010 found no increase in cardiovascular events, mortality, or prostate cancer with therapy. Recently, in a trial of older men with mobility limitations, men randomized to receive a substantial dose of T reported cardiovascular adverse effects. This phenomenon was not reported from a comparable trial where men received a more conservative dose of T, suggesting a prudent approach should be adopted when considering therapy in frail older men with existing CVD. Adequately powered RCTs of T in middle-aged and older men are needed to clarify whether or not hormonal intervention would reduce the incidence of CVD.
  7,056 618 5
Human androgen deficiency: insights gained from androgen receptor knockout mouse models
Kesha Rana, Rachel A Davey, Jeffrey D Zajac
March-April 2014, 16(2):169-177
DOI:10.4103/1008-682X.122590  PMID:24480924
The mechanism of androgen action is complex. Recently, significant advances have been made into our understanding of how androgens act via the androgen receptor (AR) through the use of genetically modified mouse models. A number of global and tissue-specific AR knockout (ARKO) models have been generated using the Cre-loxP system which allows tissue- and/or cell-specific deletion. These ARKO models have examined a number of sites of androgen action including the cardiovascular system, the immune and hemopoetic system, bone, muscle, adipose tissue, the prostate and the brain. This review focuses on the insights that have been gained into human androgen deficiency through the use of ARKO mouse models at each of these sites of action, and highlights the strengths and limitations of these Cre-loxP mouse models that should be considered to ensure accurate interpretation of the phenotype.
  4,764 730 10
Differential expression of 5-alpha reductase isozymes in the prostate and its clinical implications
Kai Wang, Dong-Dong Fan, Song Jin, Nian-Zeng Xing, Yi-Nong Niu
March-April 2014, 16(2):274-279
DOI:10.4103/1008-682X.123664  PMID:24457841
The development of human benign or malignant prostatic diseases is closely associated with androgens, primarily testosterone (T) and dihydrotestosterone (DHT). T is converted to DHT by 5-alpha reductase (5-AR) isozymes. Differential expression of 5-AR isozymes is observed in both human benign and malignant prostatic tissues. 5-AR inhibitors (5-ARI) are commonly used for the treatment of benign prostatic hyperplasia (BPH) and were once promoted as chemopreventive agents for prostate cancer (PCa). This review discusses the role of the differential expression of 5-AR in the normal development of the human prostate and in the pathogenesis and progression of BPH and PCa.
  4,902 591 8
Androgens and estrogens in skeletal sexual dimorphism
MichaŽl Laurent, Leen Antonio, Mieke Sinnesael, Vanessa Dubois, Evelien Gielen, Frank Classens, Dirk Vanderschueren
March-April 2014, 16(2):213-222
DOI:10.4103/1008-682X.122356  PMID:24385015
Bone is an endocrine tissue expressing androgen and estrogen receptors as well as steroid metabolizing enzymes. The bioactivity of circulating sex steroids is modulated by sex hormone-binding globulin and local conversion in bone tissue, for example, from testosterone (T) to estradiol (E2) by aromatase, or to dihydrotestosterone by 5α-reductase enzymes. Our understanding of the structural basis for gender differences in bone strength has advanced considerably over recent years due to increasing use of (high resolution) peripheral computed tomography. These microarchitectural insights form the basis to understand sex steroid influences on male peak bone mass and turnover in cortical vs trabecular bone. Recent studies using Cre/LoxP technology have further refi ned our mechanistic insights from global knockout mice into the direct contributions of sex steroids and their respective nuclear receptors in osteoblasts, osteoclasts, osteocytes, and other cells to male osteoporosis. At the same time, these studies have reinforced the notion that androgen and estrogen defi ciency have both direct and pleiotropic effects via interaction with, for example, insulin-like growth factor 1, inflammation, oxidative stress, central nervous system control of bone metabolism, adaptation to mechanical loading, etc., This review will summarize recent advances on these issues in the fi eld of sex steroid actions in male bone homeostasis.
  4,733 709 14
Androgens and prostate disease
Lori A Cooper, Stephanie T Page
March-April 2014, 16(2):248-255
DOI:10.4103/1008-682X.122361  PMID:24407178
A growing body of literature has established the anabolic benefi ts of testosterone (T) therapy in hypogonadal men. However, there remains a paucity of data regarding the risks of exogenous androgen use in older men and the potential for adverse effects on the prostate gland. Whether T therapy in older, hypogonadal men might worsen lower urinary tract symptoms or exacerbate, unmask, or even incite prostate cancer development has tempered enthusiasm for T therapy, while known prostatic disease has served as a relative contraindication to T therapy. Androgens are necessary for the development and maintenance of the prostate gland. However, epidemiologic studies do not consistently fi nd a positive relationship between endogenous serum androgen concentrations and the risk of prostate disease. Recent data demonstrate that 5α-reductase inhibitors decrease the risk of low-grade prostate cancer, suggesting that modifying androgen metabolism may have beneficial effects on prostate health, yet similar reductions in high-grade disease have not been observed, thereby questioning the true clinical benefits of these agents for chemoprevention. Knowing how to best investigate the relationship between androgens and the development of prostate disease given the lack of large, randomized trials is difficult. Accumulating data challenges the assumption that alterations in serum androgens have parallel effects within the prostate hormonal environment or change androgen-regulated processes within the gland. Long-term intervention studies are needed to truly ascertain the effects of androgen manipulation on prostate tissue and disease risk. However, available data do not support the notion that restoring serum androgens to normal physiologic ranges drives prostate disease.
  4,419 505 5
ORIGINAL ARTICLES
Histone methyltransferase SETDB1 is required for prostate cancer cell proliferation, migration and invasion
Yi Sun, Min Wei, Shan-Cheng Ren, Rui Chen, Wei-Dong Xu, Fu-Bo Wang, Ji Lu, Jian Shen, Yong-Wei Yu, Jian-Guo Hou, Chuan-Liang Xu, Jiao-Ti Huang, Ying-Hao Sun
March-April 2014, 16(2):319-324
DOI:10.4103/1008-682X.122812  PMID:24556744
SETDB1 has been established as an oncogene in a number of human carcinomas. The present study was to evaluate the expression of SETDB1 in prostate cancer (PCa) tissues and cells and to preliminarily investigate the role of SETDB1 in prostate tumorigenesis in vitro. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC) were used to detect the expression of SETDB1 in PCa tissues, adjacent normal tissues, benign prostatic hyperplasia (BPH) tissues, PCa cell lines and normal prostate epithelial cells. The results suggested that SETDB1 was upregulated in human PCa tissues compared with normal tissues at the mRNA and protein levels. The role of SETDB1 in proliferation was analyzed with cell counting kit-8, colony-forming efficiency and flow cytometry assays. The results indicated that downregulation of SETDB1 by siRNA inhibited PCa cell growth, and induced G0/G1 cell cycle arrest. The PCa cell migration and invasion decreased by silcencing SETDB1 which were assessed by using in vitro scratch and transwell invasion assay respectively. Our data suggested that SETDB1 is overexpressed in human PCa. Silencing SETDB1 inhibited PCa cell proliferation, migration and invasion.
  4,352 502 21
REVIEW
Selective androgen receptor modulators for the treatment of late onset male hypogonadism
Christopher C Coss, Amanda Jones, Michael L Hancock, Mitchell S Steiner, James T Dalton
March-April 2014, 16(2):256-261
DOI:10.4103/1008-682X.122339  PMID:24407183
Several testosterone preparations are used in the treatment of hypogonadism in the ageing male. These therapies differ in their convenience, flexibility, regional availability and expense but share their pharmacokinetic basis of approval and dearth of long-term safety data. The brevity and relatively reduced cost of pharmacokinetic based registration trials provides little commercial incentive to develop improved novel therapies for the treatment of late onset male hypogonadism. Selective androgen receptor modulators (SARMs) have been shown to provide anabolic benefit in the absence of androgenic effects on prostate, hair and skin. Current clinical development for SARMs is focused on acute muscle wasting conditions with defi ned clinical endpoints of physical function and lean body mass. Similar regulatory clarity concerning clinical deficits in men with hypogonadism is required before the beneficial pharmacology and desirable pharmacokinetics of SARMs can be employed in the treatment of late onset male hypogonadism.
  3,720 508 6
Challenges and improvements in testosterone and estradiol testing
Hubert W Vesper, Julianne C Botelho, Yuesong Wang
March-April 2014, 16(2):178-184
DOI:10.4103/1008-682X.122338  PMID:24407184
Assays that measure steroid hormones in patient care, public health, and research need to be both accurate and precise, as these criteria help to ensure comparability across all clinical and research applications. This review addresses major issues relevant to assay variability and describes recent activities by the US Centers for Disease Control and Prevention (CDC) to improve assay performance. Currently, high degrees of accuracy and precision are not always met for testosterone and estradiol measurements; although technologies for steroid hormone measurement have advanced significantly, measurement variability within and across laboratories has not improved accordingly. Differences in calibration and specificity are discussed as sources of variability in measurement accuracy. Ultimately, a combination of factors appears to cause inaccuracy of steroid hormone measurements, with nonuniform assay calibration and lack of specificity being two major contributors to assay variability. Within-assay variability for current assays is generally high, especially at low analyte concentrations. The CDC Hormone Standardization (HoSt) Program is improving clinical assays, as evidenced by a 50% decline in mean absolute bias between mass spectrometry assays and the CDC reference method from 2007 to 2011. This program provides the measurement traceability to CDC reference methods and helps to minimize factors affecting measurement variability.
  3,493 635 32
Androgen effects on skeletal muscle: implications for the development and management of frailty
Matthew DL O'Connell, Frederick CW Wu
March-April 2014, 16(2):203-212
DOI:10.4103/1008-682X.122581  PMID:24457838
Androgens have potent anabolic effects on skeletal muscle and decline with age in parallel to losses in muscle mass and strength. This loss of muscle mass and function, known as sarcopenia, is the central event in development of frailty, the vulnerable health status that presages adverse outcomes and rapid functional decline in older adults. The potential role of falling androgen levels in the development of frailty and their utility as function promoting therapies in older men has therefore attracted considerable attention. This review summarizes current concepts and definitions in muscle ageing, sarcopenia and frailty, and evaluates recent developments in the study of androgens and frailty. Current evidence from observational and interventional studies strongly supports an effect of androgens on muscle mass in ageing men, but effects on muscle strength and particularly physical function have been less clear. Androgen treatment has been generally well-tolerated in studies of older men, but concerns remain over higher dose treatments and use in populations with high cardiovascular risk. The first trials of selective androgen receptor modulators (SARMs) suggest similar effects on muscle mass and function to traditional androgen therapies in older adults. Important future directions include the use of these agents in combination with exercise training to promote functional ability across different populations of older adults, as well as more focus on the relationships between concurrent changes in hormone levels, body composition and physical function in observational studies.
  3,617 439 26
ORIGINAL ARTICLES
Metabolic syndrome and prostate abnormalities in male subjects of infertile couples
Francesco Lotti, Giovanni Corona, Linda Vignozzi, Matteo Rossi, Elisa Maseroli, Sarah Cipriani, Mauro Gacci, Gianni Forti, Mario Maggi
March-April 2014, 16(2):295-304
DOI:10.4103/1008-682X.122341  PMID:24435050
No previous study has evaluated systematically the relationship between metabolic syndrome (MetS) and prostate-related symptoms and signs in young infertile men. We studied 171 (36.5 ± 8.3-years-old) males of infertile couples. MetS was defined based on the National Cholesterol Education Program Third Adult Treatment Panel. All men underwent hormonal (including total testosterone (TT) and insulin), seminal (including interleukin-8 (IL-8), seminal plasma IL-8 (sIL-8)), scrotal and transrectal ultrasound evaluations. Because we have previously assessed correlations between MetS and scrotal parameters in a larger cohort of infertile men, here, we focused on transrectal features. Prostate-related symptoms were assessed using the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) and the International Prostate Symptom Score (IPSS). Twenty-two subjects fulfilled MetS criteria. In an age-adjusted logistic ordinal model, insulin levels increased as a function of MetS components (Wald = 29.5, P < 0.0001) and showed an inverse correlation with TT (adjusted r = -0.359, P< 0.0001). No association between MetS and NIH-CPSI or IPSS scores was observed. In an age-, TT-, insulin-adjusted logistic ordinal model, an increase in number of MetS components correlated negatively with normal sperm morphology (Wald = 5.59, P< 0.02) and positively with sIL-8 levels (Wald = 4.32, P < 0.05), which is a marker of prostate inflammation, with prostate total and transitional zone volume assessed using ultrasound (Wald = 17.6 and 12.5, both P < 0.0001), with arterial peak systolic velocity (Wald = 9.57, P = 0.002), with texture nonhomogeneity (hazard ratio (HR) = 1.87 (1.05-3.33), P < 0.05), with calcification size (Wald = 3.11, P< 0.05), but not with parameters of seminal vesicle size or function. In conclusion, in males of infertile couples, MetS is positively associated with prostate enlargement, biochemical (sIL8) and ultrasound-derived signs of prostate inflammation but not with prostate-related symptoms, which suggests that MetS is a trigger for a subclinical, early-onset form of benign prostatic hyperplasia.
  3,158 433 25
REVIEW
Sex steroids and glucose metabolism
Carolyn A Allan
March-April 2014, 16(2):232-238
DOI:10.4103/1008-682X.122589  PMID:24457840
Testosterone levels are lower in men with metabolic syndrome and type 2 diabetes mellitus (T2DM) and also predict the onset of these adverse metabolic states. Body composition (body mass index, waist circumference) is an important mediator of this relationship. Sex hormone binding globulin is also inversely associated with insulin resistance and T2DM but the data regarding estrogen are inconsistent. Clinical models of androgen deficiency including Klinefelter's syndrome and androgen deprivation therapy in the treatment of advanced prostate cancer confirm the association between androgens and glucose status. Experimental manipulation of the insulin/glucose milieu and suppression of endogenous testicular function suggests the relationship between androgens and insulin sensitivity is bidirectional. Androgen therapy in men without diabetes is not able to differentiate the effect on insulin resistance from that on fat mass, in particular visceral adiposity. Similarly, several small clinical studies have examined the efficacy of exogenous testosterone in men with T2DM, however, the role of androgens, independent of body composition, in modifying insulin resistance is uncertain.
  2,924 644 9
The role of hypogonadism in Klinefelter Syndrome
Christian HÝst, Anne Skakkeb'k, Kristian A Groth, Anders Bojesen
March-April 2014, 16(2):185-191
DOI:10.4103/1008-682X.122201  PMID:24407186
Klinefelter syndrome (KS) (47, XXY) is the most abundant sex-chromosome disorder, and is a common cause of infertility and hypogonadism in men. Most men with KS go through life without knowing the diagnosis, as only 25% are diagnosed and only a few of these before puberty. Apart from hypogonadism and azoospermia, most men with KS suffer from some degree of learning disability and may have various kinds of psychiatric problems. The effects of long-term hypogonadism may be diffi cult to discern from the gene dose effect of the extra X-chromosome. Whatever the cause, alterations in body composition, with more fat and less muscle mass and diminished bone mineral mass, as well as increased risk of metabolic consequences, such as type 2 diabetes and the metabolic syndrome are all common in KS. These fi ndings should be a concern as they are not simply laboratory fi ndings; epidemiological studies in KS populations show an increased risk of both hospitalization and death from various diseases. Testosterone treatment should be offered to KS patients from early puberty, to secure a proper masculine development, nonetheless the evidence is weak or nonexisting, since no randomized controlled trials have ever been published. Here, we will review the current knowledge of hypogonadism in KS and the rationale for testosterone treatment and try to give our best recommendations for surveillance of this rather common, but often ignored, syndrome.
  2,942 599 25
OPINION
More attention should be paid to the treatment of male infertility with drugs-testosterone: to use it or not?
Hong-Jun Li
March-April 2014, 16(2):270-273
DOI:10.4103/1008-682X.122343  PMID:24435051
  2,692 396 7
EDITORIAL
Male androgen deficiency: a multisystem syndrome
Mathis Grossmann, Frederick C Wu
March-April 2014, 16(2):159-160
DOI:10.4103/1008-682X.122587  PMID:24480923
  2,221 592 2
ORIGINAL ARTICLES
Tissue elasticity displayed by elastography and its correlation with the characteristics of collagen type I and type III in prostatic stroma
Jie Tang, Yan Zhang, Ming-Bo Zhang, Yan-Mi Li, Xiang Fei, Zhi-Gang Song
March-April 2014, 16(2):305-308
DOI:10.4103/1008-682X.122582  PMID:24435054
We investigated the prostate elasticity displayed by elastography and its correlation with the content and distribution of collagen type I (Col1) and type III (Col3). A total of 62 patients underwent transrectal real-time tissue elastography (TRTE) examinations. Targeted biopsies were performed after 12-core systematic biopsy. The tissues corresponding to the elastograms were stained with picric acid-sirius red. The distribution of Col1 and type Col3 was observed, and the collagen volume fraction (CVF) of these two types of collagen fibers was calculated. The CVFs of Col1 in the stiff and soft groups were 0.05 ± 0.02 and 0.02 ± 0.01 (P = 0.002), respectively. The CVFs of Col3 in the stiff and soft groups were 0.05 ± 0.04 and 0.07 ± 0.03 (P = 0.13), respectively. The circular analysis results showed that collagen fibers were disorganized both in the soft and stiff groups. Col1 and Col3 were mainly cross-linked, and some parallelization was observed in the sections. The distributions of Col1 and Col3 were different between the stiff and soft groups (P = 0.03). In conclusion, the texture of the prostate is due to the content of Col1 and its relative correlation with Col3.
  2,421 336 7
Bactericidal/permeability-increasing protein originates in both the testis and the epididymis and localizes in mouse spermatozoa
Zhong-Ping Zhou, Xiao-Yu Xia, Qiang-Su Guo, Chen Xu
March-April 2014, 16(2):309-313
DOI:10.4103/1008-682X.122583  PMID:24457839
Bactericidal/permeability-increasing protein (BPI) is an endogenous antibiotic protein with activity against gram-negative bacteria. In the present study, we examined the expression of BPI in postnatal mouse testes and epididymides as well as the subcellular localization within epididymal spermatozoa. Our results showed that, BPI mRNA was expressed in testis and epididymis independently. Throughout the epididymis, the BPI protein level gradually decreased in the epididymal epithelium in a spatial manner, specialized within the cytoplasm of clear cells in the cauda part. We detected BPI proteins in intact acrosome, implying its testicular origin; on the other hand, after the acrosome reaction, BPI proteins were observed dispersed across the entire sperm head, especially enriched at the equatorial segment. Our findings suggested a dual origin of the BPI that generated both in the testis and epididymis, and associated with mouse spermatozoa. BPI protein might be involved in the dynamics modification of the sperm plasma membrane and also the fertilization process.
  2,395 345 4
RESEARCH HIGHLIGHT
The multiple actions of testosterone in men: nature knows best
John W Funder
March-April 2014, 16(2):266-267
DOI:10.4103/1008-682X.122367  PMID:24385014
In male hormone replacement therapy Finkelstein et al. show that testosterone rather than synthetic "pure" androgens should be prescribed. Testosterone is converted to the superactive androgen dihydrotestosterone and to estradiol, and thus has actions via androgen receptors and both estrogen receptors (ERα, ERβ). Although muscle strength is androgen dependent, estradiol has major physiologic effects in men-on bone, cartilage, and together with androgens, on sexual functioning. Neither dihydrotestosterone nor 'pure' synthetic androgens can be converted to estradiol; those so treated thus risk missing out on the beneficial (and necessary) effects of estrogens in men.
  2,160 421 -
Long and noncoding RNAs (lnc-RNAs) determine androgen receptor dependent gene expression in prostate cancer growth in vivo
Richard G Pestell, Zuoren Yu
March-April 2014, 16(2):268-269
DOI:10.4103/1008-682X.122364  PMID:24435053
Hyperactive androgen receptor (AR) activity remains a key determinant of the onset and progression of prostate cancer and resistance to current therapies. The mechanisms governing castrate resistant prostate cancer are poorly understood, but defining these molecular events is essential in order to impact deaths from prostate cancer. Yang et al. demonstrate that two lnc-RNAs known to be overexpressed in therapy resistant prostate cancer, PRNCR1 (also known as PCAT8) and PCGEM1, bound to the AR to enhance ligand-dependent and ligand-independent AR gene expression and proliferation of prostate cancer cells.1 The sequence of these interactions involved the binding of PRNCR1 to the acetylated AR and a subsequent association of DOT1L, which was required for the sequential recruitment of the lncRNA PCGEM1 to the AR amino terminus, which in turn was methylated by DOT1L.
  2,010 478 5
ORIGINAL ARTICLES
Tadalafil treatment had a modest effect on endothelial cell damage and repair ability markers in men with erectile dysfunction and vascular risk
Fiore Pelliccione, Anatolia DíAngeli, Settimio DíAndrea, Arcangelo Barbonetti, Alfonso Pezzella, Stefano Necozione, Stefano Falone, Fernanda Amicarelli, Felice Francavilla, Sandro Francavilla
March-April 2014, 16(2):290-294
DOI:10.4103/1008-682X.122347  PMID:24407182
The number of the circulating angiogenic cells (CACs) and colony forming units (CFUs) derived from cultured circulating mononuclear cells (MNCs) represents a laboratory surrogate for endothelial cell repair ability. The serum of men with erectile dysfunction (ED) and vascular risk factors (VRFs) showed an increased level of endothelial cell damage/dysfunction markers and reduced the numbers of CACs and CFUs derived from the cells of healthy men. We analyzed whether treating men with ED and VRFs with the selective phosphodiesterase type 5 inhibitor tadalafil improved the endothelial cell repair ability and reduced the levels of the serum markers of endothelial cell damage/dysfunction. MNCs from healthy men were cultured with 20% serum from 36 ED patients to obtain CACs and CFUs. The ED patients were evaluated before and after 4 weeks of treatment with tadalafil (20 mg every other day) or with a placebo. The tadalafil treatment improved erectile function (P = 0.0028), but had no effect on the inhibitory effects of serum from ED patients on the CACs and CFUs derived from healthy men. The levels of endothelin-1 (P = 0.011) and tissue type plasminogen activator (P = 0.005) were reduced after treatment compared to baseline and those of the placebo group, whereas no changes were observed in the E-selectin levels. The tadalafil treatment in the ED patients with VRFs resulted in only a modest effect on the laboratory measures of the endothelial cell damage/dysfunction and repair ability. The proposed beneficial effect of phosphodiesterase type 5 inhibition on vascular homeostasis requires further analysis.
  1,977 362 4
The biochemical effects of ischemia-reperfusion injury in the ipsilateral and contralateral testes of rats and the protective role of melatonin
Bekir S Parlaktas, Dogan Atilgan, Huseyin Ozyurt, Yusuf Gencten, Ali Akbas, Fikret Erdemir, Nihat Uluocak
March-April 2014, 16(2):314-318
DOI:10.4103/1008-682X.122202  PMID:24407181
Testicular torsion (TT) is a serious urologic emergency that is observed in adolescent males and that can lead to infertility if left untreated. The ischemia-reperfusion (I/R) injury due to TT has been implicated in the pathogenesis of testicular damage. We investigated the effects of melatonin on oxidative damage in the ipsilateral and contralateral testes of rats induced by unilateral TT. A total of 21 prepubertal male Wistar albino rats were divided into three groups, each consisting of seven rats. In Group 1 (SHAM group): a sham operation to the left testis and bilateral orchiectomy were performed. In Group 2 (I/R group): I/R injury was created by rotating the left testis 720° in a clockwise direction for 2 h and detorsing the testis after 2 h. Group 3 (I/R + MEL group): rats were subjected to I/R injury and one-shot melatonin injection (50 mg kg?1, intraperitoneal (i.p.)). The testes of the rats were excised bilaterally in all groups. The testicular tissue activities of antioxidant catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase enzymes (GSH-Px), and the tissue levels of malondialdehyde (MDA), protein carbonyl (PC) and nitric oxide (NO) were determined. Administration of melatonin caused a signifi cant decrease in lipid peroxidation and enzyme activities in the ipsilateral testis when compared with the control group (P < 0.05). All of the changes in the enzyme activities of the contralateral testis were insignificant (P > 0.05). MDA levels were signifi cantly altered in the contralateral testis (P = 0.009). Melatonin administration decreased the deleterious effects of I/R injury in the ipsilateral torted testes of the rats. The contralateral testes were slightly affected by unilateral TT.
  1,939 351 20
The optimal timing of post-prostate biopsy magnetic resonance imaging to guide nerve-sparing surgery
Young Hwii Ko, Phil Hyun Song, Ki Hak Moon, Hee Chang Jung, Jun Cheon, Deuk Jae Sung
March-April 2014, 16(2):280-284
DOI:10.4103/1008-682X.122190  PMID:24407179
The goal of our study was to evaluate the impact of the interval between prostate biopsy and magnetic resonance imaging (MRI) on the accuracy of simple tumor localization, which is essential information that enables nerve-sparing surgery. We also sought to determine the optimal timing of a post-biopsy MRI. A total of 184 patients who had undergone MRI before radical prostatectomy at an institution without a predetermined schedule for MRI after a prostate biopsy were enrolled. The mean interval from the biopsy to the MRI was 30.8 ± 18.6 days. The accuracy of the MRI for simplifi ed tumor location (right, left, bilateral and none) was 44.6%. In the group with discordant pathologic and MRI fi ndings, the most common reason recorded was 'MRI predicted a unilateral lesion, but pathology revealed bilateral lesions' (58.3%), followed by 'MRI predicted no lesion, but pathology revealed the presence of a lesion' (32.0%). Multivariable analysis showed that the discordant group had a shorter interval (25.0 ± 14.3 vs 38.1 ± 20.6 days, P < 0.01) preceding the MRI and a higher rate of hemorrhage as observed by MRI (80.4% vs 54.8%, P < 0.01) in comparison with the accordant group. In receiver operating characteristics analysis, the area under the curve of the MRI interval in accurate prediction of the tumor location was 0.707 (P < 0.001). At the MRI interval's cutoff of 28.5 days, the sensitivity was 73.2% and the specificity was 63.7%. When the MRI was performed within 28 days, the accumulated accuracy was only 26.1% (23/88); however, when it was performed after 28 days, the reversely accumulated accuracy was 61.5% (59/96). These data support a waiting period of at least 4 weeks after a biopsy before performing an MRI for the purposes of surgical refinement.
  1,832 345 8
Risk of second primary cancers after testicular cancer in East and West Germany: A focus on contralateral testicular cancers
Carsten Rusner, Brigitte Streller, Christa Stegmaier, Pietro Trocchi, Oliver Kuss, Katherine A McGlynn, Britton Trabert, Andreas Stang
March-April 2014, 16(2):285-289
DOI:10.4103/1008-682X.122069  PMID:24407180
Testicular cancer survival rates improved dramatically after cisplatin-based therapy was introduced in the 1970s. However, chemotherapy and radiation therapy are potentially carcinogenic. The purpose of this study was to estimate the risk of developing second primary cancers including the risk associated with primary histologic type (seminoma and non-seminoma) among testicular cancer survivors in Germany. We identified 16 990 and 1401 cases of testicular cancer in population-based cancer registries of East Germany (1961-1989 and 1996-2008) and Saarland (a federal state in West Germany; 1970-2008), respectively. We estimated the risk of a second primary cancer using standardized incidence ratios (SIRs) with 95% confidence intervals (95% CIs). To determine trends, we plotted model-based estimated annual SIRs. In East Germany, a total of 301 second primary cancers of any location were observed between 1961 and 1989 (SIR: 1.9; 95% CI: 1.7-2.1), and 159 cancers (any location) were observed between 1996 and 2008 (SIR: 1.7; 95% CI: 1.4-2.0). The SIRs for contralateral testicular cancer were increased in the registries with a range from 6.0 in Saarland to 13.9 in East Germany. The SIR for seminoma, in particular, was higher in East Germany compared to the other registries. We observed constant trends in the model-based SIRs for contralateral testicular cancers. The majority of reported SIRs of other cancer sites including histology-specific risks showed low precisions of estimated effects, likely due to small sample sizes. Testicular cancer patients are at increased risk especially for cancers of the contralateral testis and should receive intensive follow-ups.
  1,798 348 9
LETTERS TO THE EDITOR
MicroRNA let-7a: a novel therapeutic candidate in prostate cancer
Xiao-Qin Wu, Cheng Huang, Xin-Hua Liu, Jun Li
March-April 2014, 16(2):327-328
DOI:10.4103/1008-682X.123680  PMID:24480926
  1,673 271 4
A rare complex chromosomal rearrangement in an oligospermic male: a case report and review of the Chinese literature
Ying-Jian Chen, Wei-Wei Zhang, Xiao-Ming Sun, Cheng-Jin Hu
March-April 2014, 16(2):325-326
DOI:10.4103/1008-682X.122335  PMID:24457837
  1,427 272 2
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