Expression of LHCG receptors in the human penis.

The aim of this study is to investigate the expression of the luteinizing hormone/choriogonadotropin (LHCG) receptor in the human penis to see, if the luteinizing hormone (LH) effects are possible in the spongious and cavernous tissue of the penis. The number of men with erection disturbances increases significantly simultaneously with the elevated LH concentrations between 40 and 70 years. It is possible that the elevated LH concentrations may influence locally the erectile mechanisms. The precondition for this is the expression of LHCG receptors in the penis. Penile tissue was obtained from three patients undergoing total or partial penectomy due to a rectal cancer with secondary penile metastasis or squamous cell carcinoma of the penis. Immunohistochemistry was used for the detection of the LHCG receptor. Positive immunoreaction for LHCG receptors was discovered in the endothelial cells of cavernous spaces in the corpus cavernosum and corpus spongiosum penis, also in the endothelial cells of the capillary walls in all patients. Our results show that LHCG receptor is expressed in the spongious and cavernous tissue of the human penis. This finding suggests that LH can affect the spongious and cavernous tissue in human and play a significant role in the development of erectile dysfunction among the aging men.

Applications of genomic medicine in the treatment of diseases.

Individualized medicine, based on a detailed mapping of the patient's disease mechanisms, is becoming an essential part of treatment for an increasing number of diseases. In the past few years, the possibility to determine the abnormal genome and transcriptome of diseased cells at a reasonable cost has been the major advance. The vast amount of data accumulated from one patient will set requirements for data extraction tools, in order to have the essential information affecting the treatment of the patient information quickly and reliably at the disposal of attending physicians. A computerized decision support system connected to the information systems of the hospital is an integral part of individualized treatment. Although the application of genomic and other profiling information is challenging, individualization of medication provides great promises more effective and safer treatment.

Genomic data into everyday work of a medical practitioner - digital tools for decision-making.

Recent technological development has enabled fast and cost-effective simultaneous analyses of several gene variants or sequence of even the whole genome. For medical practitioners this has created challenges although genomic information may be clinically useful in new applications such as finding out individual risk for diseases influenced by as many as 50,000 variable DNA regions or in detecting pharmacogenetic risks prior to prescribing a medicine. New digital tools have paved the way for utilization of genomic data via easy access and clear clinical interpretation for both doctor and patient. In this review we describe some of these tools and applications for clinical use.

How Communicating Polygenic and Clinical Risk for Atherosclerotic Cardiovascular Disease Impacts Health Behavior: an Observational Follow-up Study.

BACKGROUND: Prediction tools that combine polygenic risk scores with clinical factors provide a new opportunity for improved prediction and prevention of atherosclerotic cardiovascular disease, but the clinical utility of polygenic risk score has remained unclear. METHODS: We collected a prospective cohort of 7342 individuals (64% women, mean age 56 years) and estimated their 10-year risk for atherosclerotic cardiovascular disease both by a traditional risk score and a composite score combining the effect of a polygenic risk score and clinical risk factors. We then tested how returning the personal risk information with an interactive web-tool impacted on the participants' health behavior. RESULTS: When reassessed after 1.5 years by a clinical visit and questionnaires, 20.8% of individuals at high (>10%) 10-year atherosclerotic cardiovascular disease risk had seen a doctor, 12.4% reported weight loss, 14.2% of smokers had quit smoking, and 15.4% had signed up for health coaching online. Altogether, 42.6% of persons at high risk had made one or more health behavioral changes versus 33.5% of persons at low/average risk such that higher baseline risk predicted a favorable change (OR [CI], 1.53 [1.37-1.72] for persons at high risk versus the rest, P<0.001), with both high clinical (P<0.001) and genomic risk (OR [CI], 1.10 [1.03-1.17], P=0.003) contributing independently. CONCLUSIONS: Web-based communication of personal atherosclerotic cardiovascular disease risk-data including polygenic risk to middle-aged persons motivates positive changes in health behavior and the propensity to seek care. It supports integration of genomic information into clinical risk calculators as a feasible approach to enhance disease prevention.

Endogenous testosterone and brachial artery endothelial function in middle-aged men with symptoms of late-onset hypogonadism.

In aging men, serum endogenous testosterone is inversely associated with common carotid intima-media thickness (IMT) and directly with beneficial plasma lipid levels; however, the relationship to endothelial function is poorly characterized. We examined the association between serum testosterone and endothelium-dependent brachial artery flow-mediated dilatation (FMD) in middle-aged to elderly men. A group of 83 men aged 40?69 years (mean 55.9 ± 7.5 [SD]) with andropausal symptoms were studied. We measured their serum lipids, testosterone, luteinizing hormone, mean carotid IMT and brachial artery FMD by high resolution B-mode ultrasound. Brachial FMD correlated inversely with vessel diameter (r = -0.38, p = 0.0004), alcohol consumption (r = -0.22, p = 0.047) and serum testosterone (r = -0.27, p = 0.01), but not with luteinizing hormone. In multivariate analysis, FMD was explained by testosterone (ß = -0.17, p = 0.0226), high density lipoprotein cholesterol (ß = 4.17, p = 0.0312) and vessel diameter (ß = -4.37, p < 0.0001) when adjusted for age, body mass index, triglycerides, blood pressure, carotid IMT, smoking, alcohol consumption, cardiovascular diseases and use of lipid lowering medication (HMG-CoA reductase inhibitors). In middle-aged to elderly men, there is an inverse correlation between serum testosterone and brachial FMD. These data suggest that testosterone may have an adverse effect on systemic endothelial function.

Expression of insulin signaling transmitters and glucose transporters at the protein level in the rat testis.

Insulin receptor substrate (IRS) proteins are key mediators in insulin signaling from the insulin receptor. It takes place through receptor-mediated tyrosine phosphorylation of IRS proteins. The aim of the present article is to demonstrate the distribution of IRS 1-3, glucose transporters 1-4 (GLUT 1-4), signal regulatory protein 1alpha (SIRP1alpha), PKB, and PI 3-kinase in the rat testis to see if signal transduction mediated by these proteins is active in testicular cells. Wistar rats were used as donors of testis tissue. Expression of these genes was studied at the protein level by using immunohistochemistry and Western blotting. IRS-1, IRS-2, GLUT 1, GLUT 2, GLUT 3, and SIRP1alpha were strongly expressed in the Sertoli cells (except GLUT 1), early spermatocytes, peritubular myoid cells, macrophage-like interstitial cells, and testicular endothelial cells in all the testes investigated by immunohistochemistry. IRS-2 was also expressed in the Leydig cells. Immunoblotting experiments demonstrated the presence of about 26-67 kDa reactive with anti- IRS-1, IRS-2, GLUT 1, GLUT 2, GLUT 3, PKB, and SIRP1alpha. The present results suggest that proteins like insulin and certain cytokines using IRS-1, IRS-2, GLUT 1, GLUT 2, GLUT 3, PKB, and SIRP1alpha in their signal transduction can have effects on the different types of testicular cells in the rat.

Increased carotid atherosclerosis in andropausal middle-aged men.

OBJECTIVES: This study examined the association between carotid artery intima-media thickness (IMT), serum sex hormone levels, and andropausal symptoms in middle-aged men. BACKGROUND: Male sex hormones may play a dual role in the pathogenesis of atherosclerosis in men by carrying both proatherogenic and atheroprotective effects. METHODS: We studied 239 40- to 70-year-old men (mean +/- SD: 57 +/- 8 years) who participated in the Turku Aging Male Study and underwent serum lipid and sex hormone measurements. Ninety-nine men (age 58 +/- 7 years) were considered andropausal (i.e., serum testosterone <9.8 nmol/l or luteinizing hormone [LH] >6.0 U/l and testosterone in the normal range), and in both situations, they had subjective symptoms of andropause (a high symptom score in questionnaire). Three were excluded because of diabetes. The rest of the men (age 57 +/- 8 years) served as controls. Carotid IMT was determined using high-resolution B-mode ultrasound, and serum testosterone, estradiol (E2), LH, and sex hormone-binding globulin were measured using standard immunoassays. RESULTS: Andropausal men had a higher maximal IMT compared with controls in the common carotid (1.08 +/- 0.34 vs. 1.00 +/- 0.23, p < 0.05) and in the carotid bulb (1.44 +/- 0.48 vs. 1.27 +/- 0.35, p = 0.003). Common carotid IMT correlated inversely with serum testosterone (p = 0.003) and directly with LH (p = 0.006) in multivariate models adjusted for age, total cholesterol, body mass index, blood pressure, and smoking. CONCLUSIONS: Middle-aged men with symptoms of andropause, together with absolute or compensated (as reflected by high normal to elevated LH) testosterone deficiency, show increased carotid IMT. These data suggest that normal testosterone levels may offer protection against the development of atherosclerosis in middle-aged men.

A multicenter phase IIb study of a novel combination of intramuscular androgen (testosterone decanoate) and oral progestogen (etonogestrel) for male hormonal contraception.

The effect of a novel combination of oral etonogestrel (ENG) and im testosterone decanoate (TD) on suppression of gonadotropins and spermatogenesis as a potential lead for male contraception was investigated. Healthy male volunteers were randomized into two groups receiving 300 microg ENG daily and 400 mg TD every 4 (n = 55) or 6 (n = 57) wk for 48 wk. At wk 48, all men except one in the 6-wk group suppressed sperm concentration to less than 1 million/ml. Faster suppression occurred in the 4-wk group. Gonadotropins were suppressed in both groups and most consistently in the 4-wk group. During treatment, trough testosterone levels increased into the normal range in the 4-wk group but remained just below normal in the 6-wk group. All peak levels were within the normal range. After treatment cessation, recovery of sperm counts and gonadotropins to normal levels occurred in both groups. Minor effects on weight and cholesterol were noted. Fourteen subjects withdrew because of an adverse event with those possibly related to the study medication reported more frequently in the 6-wk group (nine vs. one). In conclusion, the combination of 300 microg ENG with 400 mg TD every 4 wk was superior in terms of efficacy, hormone profiles, and safety. This represents a promising approach to male hormonal contraception.

Expression of insulin receptor substrates 1-3, glucose transporters GLUT-1-4, signal regulatory protein 1alpha, phosphatidylinositol 3-kinase and protein kinase B at the protein level in the human testis.

Insulin receptor substrates (IRS) mediate the biological actions of insulin, growth factors and cytokines. This action is via receptor-mediated tyrosine phosphorylation of IRS proteins. The aim of present study was to demonstrate the distribution of IRS-1-3, the glucose transporter class I subfamily (GLUT-1-4), signal regulatory protein 1alpha (SIRP1alpha), protein kinase B (PKB) and phosphatidylinositol kinase (PI3-K) in the human testis to determine whether signal transduction mediated by these proteins is active in testicular cells. In the present study, the expression of IRS-1-3, GLUT-1-4, SIRP1alpha, P13-K and PKB was studied in the human testis at the protein level using immunohistochemistry and western blotting. A positive immunoreaction for IRS-1 was found in the human testis in peritubular myoid cells and macrophage-like interstitial cells. A positive immunoreaction for GLUT-3 was found in the human testis in Sertoli cells, peritubular myoid cells, early spermatocytes, macrophage-like interstitial cells and cells in the small vessels walls. Western blotting demonstrated IRS-1, IRS-2 and GLUT-3 proteins in the human testis. Expression of IRS-3, GLUT-1, GLUT-2, GLUT-4, SIRP1alpha, P13-K and PKB was not detected in the human testis. The results of the present study suggest that proteins like insulin and certain cytokines using IRS-1, IRS-2 and GLUT-3 in their signal transduction pathways can have effects on different cell types of the testis in humans.

Androgen receptor gene exon 1 CAG repeat polymorphism in Finnish patients with childhood-onset type 1 diabetes.

OBJECTIVE: Animal models suggest that androgen receptor gene polymorphisms might affect disease predisposition in human immune-mediated diabetes. The aim of this study was to investigate the effect of the human androgen receptor gene exon 1 CAG repeat polymorphisms on type 1 diabetes (T1D) susceptibility. DESIGN AND METHODS: A combined strategy of case-control and family-based approaches was used. Affected sibling pair families (n=120), nuclear families (n=645) and cohorts of sporadic cases (n=208) and controls (n=1381) were genotyped for androgen receptor gene exon 1 CAG repeat polymorphism. An automated fluorescence-based DNA fragment-sizing method was used. RESULTS: The distribution of CAG repeat alleles did not differ significantly between patients and controls. However, short repeat alleles (7-14) were more prevalent among cases in girls compared with controls (8.77% vs 5.91%; P=0.03). Long repeat alleles (19-28) were less frequent among HLA DR3-positive diseased boys than in DR3-positive control boys (32.6% vs 40.6%; P=0.011). The differences were not significant after adjustment for multiple comparisons. Transmission of CAG repeat alleles was not different from expected in the total material. However, transmissions to girls deviated from the expected value significantly (extended transmission disequilibrium test (ETDT) 37.82; P=0.0016). A decreased transmission of the alleles with 13, 20 and 26 repeats to girls was observed (T%0, P=0.046; T%25.5, P=0.0003, T%0, P=0.025). CONCLUSION: The results do not support a common role for the androgen receptor gene exon 1 CAG repeat in T1D susceptibility; however, an effect of a disease variant in linkage disequilibrium could be detected.

Selective ovary resistance to insulin signaling in women with polycystic ovary syndrome.

OBJECTIVE: Insulin resistance is a common feature of both polycystic ovary syndrome (PCOS) and non-insulin-dependent diabetes mellitus (NIDDM); however, the persistent reproductive disturbances appear to be limited to the former, suggesting that insulin resistance in the ovary itself may confer this susceptibility. DESIGN: Prospective study. SETTING: University-affiliated department. PATIENT(S): Forty-four women undergoing IVF treatment, of whom 11 had polycystic ovaries and 33 had normal ovulation (NO). INTERVENTION(S): The various effects and signaling of insulin and insulin-like growth factor-1 (IGF-1) were examined in cultured ovarian granulosa cells treated with troglitazone (1 microg/mL) or with vehicle by reverse transcription-polymerase chain reaction, western blot, and in vitro functional analyses. MAIN OUTCOME MEASURE(S): Glycogen and DNA syntheses, mRNA and protein expression, and cellular localization of insulin/IGF-1 receptors and insulin receptor substrates (IRSs). RESULT(S): There were significant decreases in insulin-stimulated glucose incorporation into glycogen in PCOS cells, which is a metabolic action of insulin. However, IGF-1 stimulation was found to be greater in PCOS cells at all experimental concentrations with respect to thymidine incorporation compared with NO cells, which is a mitogenic action. Troglitazone increased the insulin-induced glycogen synthesis but reduced the IGF-1-augmented responses of DNA synthesis in PCOS cells to the range within those of NO granulosa cells. We then found that troglitazone treatment reversed the expression imbalance between IRS-1 and IRS-2 in PCOS cells. CONCLUSION(S): There is a selective defect in insulin actions in PCOS granulosa cells, which suggests ovarian insulin resistance, and this metabolic phenotype is associated with an enhanced IGF-1 mitogenic potential. Troglitazone could divergently alter expression of various IRS molecules and insulin actions and could be used as an ovarian insulin sensitizer and mitogen/steroidogenic inhibitor in PCOS.

The Aging Males' Symptoms (AMS) scale: update and compilation of international versions.

BACKGROUND: The interest of clinical research in aging males increased in recent years and thereby the interest to measure health-related quality of life (HRQoL) and symptoms of aging men. The Aging Males' Symptoms scale (AMS) became the most commonly used scale to measure HRQoL and symptoms in aging males in many countries worldwide. The aim of this paper is to review the current state of the instrument particularly concerning versions of the scale in different languages in the light of the quality of the translation process. AMS VERSIONS AVAILABLE: Most of the translations were performed following international methodological recommendations for linguistic & cultural adaptation of HRQoL instruments. Mainly the English version was used as source language for the translation into Dutch, Spanish, Portuguese, Italian, Swedish, and Japanese (attached as additional PDF-files). Preliminary versions that were derived only from forward translations are of secondary quality and available in Finnish, Flemish, and Russian. It is recommended to complete the translation process for the latter languages before using them in international studies. TRANSLATIONS IN PROCESS: The AMS scale is in the process of consensus finding of two existing French versions, and the versions in the Korean, Thai, and Indonesian languages have not yet been completed in the translation process. CONCLUSION: The AMS scale is obviously a valuable tool for assessing health related quality of life in aging men, because it is used worldwide. It is a standardized scale according to psychometric norms. Most of the currently available language versions were translated following international standards for linguistic and cultural translation of quality of life scales. Assistance is offered to help interested parties in the translation process.

Analysis of 508 infertile male patients in south-western Finland in 1980-2000: hormonal status and factors predisposing to immunological infertility.

OBJECTIVE: To analyse the factors predisposing to male immunological infertility from the hospital records of 508 patients that had been treated for infertility in the Turku University Central Hospital from 1980 to 2000. In addition, the hormonal status was investigated at the beginning of treatment. RESULTS: Patients with a history of mumps, or either a fresh varicocele or a history of varicocele had statistically significant lower levels of MAR antisperm antibodies (ASAs) than patients with no such conditions. Repair of varicocele (either surgical or embolisation), showed a statistically significant enhancement of the total sperm cell counts in ejaculates, but it appeared not to have any influence on other parameters of the semen analysis (mobility and morphology). Of all male infertility patients, 66.3% had normal hormonal status at the beginning of treatment, 12.6% of patients had hypotestosteronemia and 22.1% had subclinical hypogonadism. Patients with subclinical hypogonadism had lower total sperm cell count in ejaculates than patients with normal hormonal status although they had statistically significant more offspring. In addition, it appeared that mumps orchitis as well as smoking and alcohol abuse are risk factors for subclinical hypogonadism. CONCLUSION: No clear predisposing factor for male immunological infertility could be found. However, patients with subclinical hypogonadism differed from other male infertility patients and thus may form a special group among the male infertility patients.

Immunohistochemical detection of glucose transporters class I subfamily in the mouse, rat and human testis.

A family of glucose transporters (GLUT) mediates the cellular uptake of glucose at the plasma membrane by facilitated diffusion. We investigated the presence of isoforms GLUT1-4 of class I subfamilies in different types of cells in the mouse, rat and human testis by indirect immunofluorescence technique. Immunocytochemical analyses demonstrated that GLUT1 was expressed in the rat testis, GLUT2 in the mouse and rat testis, GLUT3 in the mouse, rat and human testis and GLUT4 was not presented in the testis at all. A very intensive positive immunoreaction for GLUT3 was found in Sertoli cells, peritubular myoid cells, macrophage-like interstitial cells, testicular endothelial cells and early spermatocytes. GLUT3 positive cells were not found in the luminal part of Sertoli cells, spermatids or Leydig cells. The present results suggest that glucose uptake in different testicular cells is mediated by GLUT1, GLUT2 and GLUT3 and the GLUT3 was the prominent glucose transporter type in the testicular cells.

Expression of luteinizing hormone receptors in the mouse penis.

The role of luteinizing hormone (LH) in the regulation of normal reproductive functions in males and females is quite well established. Besides the expression of LH receptors in the target cells in gonads, it has been found in several extragonadal organs. There is no information about the expression of LH receptors in the penis up to now. The aim of the present study is to investigate the expression of the LH receptor in the mouse penis to see if LH effects are possible in the penis. BALB/c mice were used as donors of normal penis and testis tissue. Immunocytochemistry, Western blotting, and quantitative reverse transcriptase polymerase chain reactions (RT-PCRs) were used for the detection of the LH receptor. Positive immunoreaction for LH receptors was present in the nuclei of urethral epithelium and endothelial cells of cavernous spaces in the corpus cavernosum and corpus spongiosum penis. Western blotting experiments demonstrated the presence of LH antigen at M(r) = 97.4 and 78 kd. Quantitative RT-PCRs confirmed the expression of LH receptor in the penis. Our results show that LH receptor is expressed in the body of the mouse penis; thus, it may directly regulate functions of penile tissue.

Endogenous testosterone and serum lipids in middle-aged men.

BACKGROUND: The role of decreasing testosterone levels influencing lipid metabolism in aging men is not well established. METHODS: We studied 1619 40 to 69-year old men with andropausal symptoms, who underwent measurements of serum testosterone, triglycerides, total-, and HDL-cholesterol. RESULTS: Testosterone (mean 15.25 nmol/l+/-5.43 S.D., range 3.6-45.0 nmol/l) correlated directly with HDL-cholesterol (r=0.24, p<0.0001) and inversely with total cholesterol (r=-0.06, p<0.03), triglycerides (r=-0.30, p<0.0001) and body mass index (r=-0.34, p<0.0001), but not with LDL-cholesterol (r=0.05, p=0.09). In multivariate analyses adjusted for age, body mass index, smoking, alcohol consumption, diabetes and cardiovascular diseases, the significant determinants for serum triglycerides were testosterone (beta=-0.03, p<0.0001), age (beta=-0.01, p<0.0001), body mass index (beta=0.039, p<0.0001) and cardiovascular diseases (beta=0.09, p<0.04). The multivariate correlates of HDL-cholesterol included testosterone (beta=0.007, p<0.0001), body mass index (beta=-0.02, p<0.0001) and alcohol consumption (beta=0.02, p<0.0001). CONCLUSIONS: We conclude that in aging men low testosterone levels are associated with a potentially atherogenic lipid profile including high triglycerides and low HDL-cholesterol.

Smoking and low serum testosterone associates with high concentration of oxidized LDL.

BACKGROUND: The interplay between smoking, oxidized low-density lipoprotein cholesterol (ox-LDL) and gonadal hormones has been scarcely investigated. AIM: To investigate associations in ox-LDL and gonadal hormones in smokers and non-smokers METHODS: Participants (n=164) were obtained from a population cohort of Finnish men aged 40-70 years. The subjects answered a detailed questionnaire on their health behaviour, medication, diseases, and different symptoms, and the hormonal and lipid profiles were measured. RESULTS: Smokers (n=33) had higher levels of ox-LDL (21%) and more free testosterone (12%) (P<0.01 for all) than non-smokers (n=131). The difference between smokers and non-smokers in ox-LDL persisted after controlling for possible confounding factors. When the smokers were divided into two subgroups (n=16 and n=17) according to total testosterone (< or =15 and >15 nmol/L), the ox-LDL in the low-testosterone subgroup was significantly higher (30%) than in the high-testosterone group (P=0.006). Similarly in the corresponding non-smoking subgroups (n=72 and n=59), ox-LDL was significantly higher (11%) in the low-testosterone subgroup than in the high-testosterone subgroup (P=0.012). CONCLUSIONS: Smoking men have significantly more ox-LDL than non-smoking men. Furthermore, if smoking is combined with a low serum testosterone, ox-LDL is even higher. This may suggest a higher risk for atherosclerosis.

Sexual symptoms in aging men indicate poor life satisfaction and increased health service consumption.

OBJECTIVES: The deterioration of sexual, physical, and mental performance in aging men has been used to measure the clinical manifestations of androgen decrement. However, their prevalence and relation to coexisting morbidities are unknown. METHODS: All men in Turku, Finland, aged 40 to 69 years (n = 28,622) in 2000 were mailed a questionnaire that included questions on general health, sociobehavioral factors, and the Aging Male Symptoms scale (17 questions, each yielded 1 to 5 points, from 1, no symptoms to 5, very severe). RESULTS: The participation rate was 54% (15,496 returned questionnaires). Moderate or severe sexual symptoms (decreased frequency of erections, libido, and potency) were observed in 20% of men of the youngest age group of 40 to 44 years. The proportion of men with significant symptoms increased linearly with age up to 67% in the oldest age group (65 to 69 years). Other symptoms did not show a similar age trend. On multifactor analysis, sexual symptoms were independently associated with decreased life satisfaction and increased visits to the physician after adjustment for coexisting morbidities. Visits to the physician were up to three times more frequent among men with moderate to severe sexual symptoms than among those with mild or no symptoms. CONCLUSIONS: Sexual symptoms in aging men are common and associated with decreased life satisfaction and an increased number of visits to the physician. These symptoms deserve more attention in the workup of aging male patients, because they offer a simple screening tool to detect impaired well-being associated with increased consumption of health services.

Human papillomavirus DNA is found in the vas deferens.

The role of the male reproductive tract as a reservoir for human papillomavirus (HPV) infection is poorly understood. To analyze the presence of HPV DNA, 27 samples, comprising postvasectomy semen samples and pre- and postejaculation urine samples, were obtained from 18 men recalled for follow-up. HPV DNA was analyzed by nested polymerase chain reaction, confirmed with Southern blot hybridization, cloned, and sequenced. Multiple HPV types were found in different DNA samples of the same men. Five (18.5%) of 27 vas deferens samples contained HPV type 6, 11, or 16. Five (27.8%) of 18 seminal plasma samples (secretions without semen cells) were HPV DNA positive. None of the men had both vas deferens and semen plasma samples HPV positive. Several HPV types can be detected in the male reproductive tract at the same time. This is the first report to show HPV DNA in the vas deferens.

The polymorphic androgen receptor gene CAG repeat, pituitary-testicular function and andropausal symptoms in ageing men.

The activity of androgen receptor (AR) is modulated by a polymorphic CAG trinucleotide repeat in the AR gene. In the present study, we investigated hormonal changes among ageing men, and whether the number of AR CAG triplets is related to the appearance of these changes, as well as symptoms and diseases associated with ageing. A total of 213 41-70-year-old men donated blood for hormone analyses (LH, testosterone, oestradiol and SHBG) and answered questions concerning diseases and symptoms associated with ageing and/or androgen deficiency. Of these men, 172 donated blood for the measurement of the CAG repeat length of AR. The CAG repeat region of the AR gene was amplified by polymerase chain reaction (PCR) and the products were sized on polyacrylamide gels. The repeat number was analysed as a dichotomized variable divided according to cut-off limits of the lowest (< or =20 repeats) and the highest quartile (> or =23 repeats), and as a continuous variable. The proportion of men with serum LH in the uppermost quartile (>6.0 IU/L) with normal serum testosterone (>9.8 nmol/L, above the lowest 10%) increased significantly with age (p = 0.01). There were fewer men with this hormonal condition among those with CAG repeat number in the uppermost quartile (> or =23 repeats) (p = 0.03). These men also reported less decreased potency (p < 0.05). The repeat number was positively correlated with depression, as expressed by the wish to be dead (r = 0.45; p < 0.0001), depressed mood (r = 0.23; p = 0.003), anxiety (r = 0.15; p < 0.05), deterioration of general well-being (r = 0.22; p = 0.004), as well as decreased beard growth (r = 0.49; p < 0.0001). A hormonal condition where serum testosterone is normal but LH increased is a frequent finding in male ageing. Only certain types of age-related changes in ageing men were associated with the length of the AR gene CAG repeat, suggesting that this parameter may play a role in setting different thresholds for the array of androgen actions in the male.