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January 2011

Recent Literature in Sexual / (except JSM) Publications of the Month:

CDC Updates Its Guidelines on Sexually Transmitted Diseases

The CDC (Centers for Disease Control and Prevention) has issued an update to its 2006 Guidelines for Treatment of Sexually Transmitted Diseases .

The latest material includes:

• evaluation for and ; • recommendations for treating bacterial vaginosis; • diagnostic evaluation following ; • approaches to preventing sexually transmitted diseases.

The update also emphasizes the importance of taking a patient's sexual history "routinely and regularly" and offers guidance for doing so.

Editorial Comment : These new guidelines and recommendations for the management of STS comprises 110 pages with 489 references and represents to date the most updated and comprehensive scientific work regarding all established STDs and Venereal Diseases as well as other diseases related to affections of the genital region suc has ,Ectoparasitic such as Pediculosis and . This marvellous scientifc work also address in comprehensive chapters special topics such as: Sexual Assault and STDs, Partner Management, Prevention Methods, STDs in Special populatios such as children, pregnant women etc.

The authors (lead author Kimberly A Workowski,MD from the Division of STD Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, 10 Corporate Square, Corporate Square Blvd, MS E02, Atlanta, GA 30333. have to be congratulated for that work. This comprehensive paper is a must for every who is dealing in his daily practice with patients suffering from any STDs and related diseases.

And now the good news for all of us: you can download for free these 110 pages under

LINK(S): 2

MMWR Recommendations and Reports guideline (Free)

Analysis of Overall Level of Evidence Behind Infectious Diseases Society of America Practice Guidelines

Dong Heun Lee, MD; Ole Vielemeyer, MD

Arch Intern Med. 2011;171(1):18-22

Background Clinical practice guidelines are developed to assist in patient care. may assume that following such guidelines means practicing evidence-based medicine. However, the quality of supporting literature can vary greatly.

Methods We analyzed the strength of recommendation and overall quality of evidence behind 41 Infectious Diseases Society of America (IDSA) guidelines released between January 1994 and May 2010. Individual recommendations were classified based on their strength of recommendation (levels A through C) and quality of evidence (levels I through III). Guidelines not following this format were excluded from further analysis. Evolution of IDSA guidelines was assessed by comparing 5 recently updated guidelines with their earlier versions.

Results In the 41 analyzed guidelines, 4218 individual recommendations were found and tabulated. Fourteen percent of the recommendations were classified as level I, 31% as level II, and 55% as level III evidence. Among class A recommendations (good evidence for support), 23% were level I ( 1 randomized controlled trial) and 37% were based on expert opinion only (level III). Updated guidelines expanded the absolute number of individual recommendations substantially. However, few were due to a sizable increase in level I evidence; most additional recommendations had level II and III evidence.

Conclusions More than half of the current recommendations of the IDSA are based on level III evidence only. Until more data from well-designed controlled clinical trials become available, physicians should remain cautious when using current guidelines as the sole source guiding patient care decisions.

Editorial Comment: Reading these data related to guidelines/recommendations for infectious diseases that more than half ( 55%) of the studies considered only reached a level of evidence III and that among class A recommendations 37 % were based on expert opinion only,i.e. they have reached at best a level of evidence III justified doubts may raise how valid and useful those guidelines finally are for the practicing physicians , the health insurances and the patients, whose treatment should follow evidence based medicine guidelines. Male Sexual Dysfunktion :

Question for a questionnaire: the International Index of Erectile Function

M İ Öztürk, O Koca, M O Keleş, M Güneş, C Kaya and M I Karaman 3

International Journal of Impotence Research , (13 January 2011

Int J Impotence Res. 2010,publ. online Dec. 30,2010

Abstract

The aim of this study was to analyze the impact of patient age and education level on the comprehension of the Turkish version of Index of Erectile Function (IIEF), and to determine the patient characteristics that make this questionnaire less reliable. In this study, 238 male patients presenting to our clinic were enrolled. The patients were asked to complete the Turkish version of the IIEF questionnaire upon arrival by themselves and then once again during their second visit with the assistance of a physician. ‘Accurate’ comprehension of the IIEF was considered to be the consistency between the ‘self-administered’ and ‘physician- assisted’ IIEF scores. The impact of patient age and education level on the ‘accurate’ comprehension of the IIEF was analyzed. There was a significant difference between the ‘self-administered’ and ‘physician-assisted’ IIEF scores in patients 60 years of age (P=0.045) and primary school graduates (P=0.015). Age 60 years and being primary school graduate are factors lowering the comprehension of the Turkish version of the IIEF by the patients. Older patients and patients with lower education could benefit from the assistance of a physician while completing this questionnaire.

Pistachio diet improves erectile function parameters and serum lipid profiles in patients with erectile dysfunction

M Aldemir, E Okulu, S Neşelioğlu, O Erel and Ö Kayıgil

Abstract

We investigated the effects of Antep pistachio on International Index of Erectile Function (IIEF) scores, penile color Doppler ultrasound (PCDU) parameters and serum lipid levels in patients with ED. A total of 17 married male patients with ED for at least 12 months were included in this prospective study. Patients were put on a 100 g pistachio nuts diet for 3 weeks. IIEF and PCDU were evaluated before and after the pistachio diet. In addition, plasma total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL) and triglyceride were measured before and after dietary modifications from all subjects. Mean IIEF-15 score was 36±7.5 before the diet and 54.2±4.9 after the diet (P=0.001). Similarly, an increase in all five domains of IIEF was observed after the diet (P<0.05). Mean peak systolic velocity values before and after the pistachio diet were 35.5±15.2 and 43.3±12.4 cm s–1, respectively (P=0.018). After the pistachio diet, TC and LDL levels decreased significantly, whereas HDL level increased (P=0.008, 0.007 and 0.001, respectively). We demonstrated that a pistachio diet improved IIEF scores and PCDU 4

parameters without any associated in patients with ED. Furthermore, the lipid parameters showed statistically significant improvements after this diet.

Long-Term Outcomes After Original Antibiotic Impregnated Inflatable Penile Prosthesis Implants: Up to 7.7 Years of Followu

Culley C. Carson III John J. Mulcahy Manya R. Harsch

J.Urol 2010, published online 21 December 2010.

Abstract

Purpose

Although some studies suggest that most infections associated with inflatable penile prosthesis implantation develop within year 1 after , device related infections have been reported 5 years after implantation or later and the infection risk with time is not well characterized. We previously reported a statistically significantly lower infection rate for original inflatable penile prostheses impregnated with antibiotic treatment with minocycline and rifampin vs nonimpregnated inflatable penile prostheses at 1-year followup. Long-term data are now available on infection revision after initial implantation of antibiotic impregnated vs nonimpregnated prostheses.

Materials and Methods

We retrospectively reviewed patient information forms voluntarily filed with the manufacturer after the initial implantation of more than 39,000 inflatable penile prostheses to compare the revision rate due to infection for antibiotic impregnated vs nonimpregnated implants between May 1, 2001 and December 31, 2008. Life table analysis was used to evaluate device survival from revision surgery.

Results

On life table survival analysis initial revision events due to infection were significantly less common in the impregnated vs the nonimpregnated group (log rank p <0.0001). At up to 7.7 years of followup 1.1% of 35,737 vs 2.5% of 3,268 men with impregnated vs nonimpregnated implants underwent initial revision due to infection.

Conclusions

To our knowledge this long-term outcome analysis provides the first substantial clinical evidence of a decrease in costly infection related revision using an antibiotic impregnated inflatable penile prosthesis.

Key Words: , penile prosthesis, antibiotic prophylaxis, infection, reoperation 5

SAbbreviations and Acronyms: AMS, American Medical Systems, ED, erectile dysfunction, FDA, United States Food and Administration, IPP, inflatable penile prosthesis, M/R, minocycline and rifampin, PIF, patient information form

,

The Prevalence of Erectile Dysfunction and Its Relation to Chronic in Chinese Men

Zong-Yao Hao , Hong-Jun Li , Zhi-Ping Wang , Jun-Ping Xing , Wei-Lie Hu , Tao-Fu Zhang , Xian-Sheng Zhang , Jun Zhou , Sheng Tai , and Chao-Zhao Liang *

J.Amdrol. 2011,publ.online 13 January

Objective : This study was performed to evaluate the prevalence of erectile dysfunction and to explore its correlation to chronic prostatitis in China. Methods: A cross-sectional investigation from a large cohort study of Chinese men was used in this survey. A questionnaire consisting of general information regarding socio-demographics, chronic disease history, sexual function, National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI) and International Index of Erectile Function-5 (IIEF-5) was administered to 15,000 Chinese men aged from 15 to 60. The prevalence of erectile dysfunction was determined from the patient's self-evaluation and International Index of Erectile Dysfunction (IIEF-5) score. The eligible individual was both married and had intercourse experience. Results: Totally, there were 12743 respondents, giving a response rate of 84.95%. Among 7372 eligible men, erectile dysfunction prevalence of self-reported and IIEF-5 score was 12.0% and 17.1%, respectively. Among 771 men with prostatitis-like symptoms, erectile dysfunction prevalence of self-reported and IIEF-5 score was 39.3% and 30.1%, respectively. Among 370 men suffering from chronic prostatitis, erectile dysfunction prevalence of self- reported and IIEF-5 score was 40.5% and 35.1%, respectively. The prevalence of self- reported and IIEF-5 score had high correlation with increasing age among all eligible men, men with prostatitis-like symptoms, and men with chronic prostatitis groups (P t < 0.05, P s <

0.05, P cp < 0.05). Erectile dysfunction prevalence of both self-reported and IIEF-5 score was higher in men with prostatitis-like symptoms and with chronic prostatitis than the general group (P s < 0.05, P cp < 0.05). Conclusion: The prevalence of erectile dysfunction was higher in the prostatitis population than in the general population with either self-reported or IIEF-5 score assessment. The prevalence was higher with self-reported than with IIEF-5 assessment in men with prostatitis. Estimates of erectile dysfunction prevalence among men with prostatitis group should not rely on self-reporting alone in that it is likely to overestimate the true prevalence.

Key words: Erectile Dysfunction • Prostate • Chinese • prevalence • prostatitis-like symptoms

Patients’ preference in the treatment of erectile dysfunction: a critical review of the literature

A Martin Morales, M Casillas and C Turbi

International Journal of Impotence Research , (30 December 2010) 6

Abstract

The increase in the number of safe and effective ED treatments highlights the importance of patients’ preference when choosing a therapeutic option. Several studies assessing these preferences are now available in published literature. This article aims to review and discuss the studies on patients’ preference and the data concerning the reasons for preference for one PDE-5 inhibitor over another. A PubMed search was conducted for manuscripts published within the last 10 years containing the search items ED, preference, sildenafil, tadalafil or vardenafil. Selected articles were discerningly reviewed and summarized (design, limitations and relevance). The articles selected were peer reviewed publications on patients’ preference and ED published in medical literature since 2000. Preference studies that include either two (tadalafil and sildenafil) or three PDE-5 inhibitors (tadalafil, sildenafil and vardenafil), showed that the majority of the patients preferred tadalafil versus either vardenafil or sildenafil. As the treatment of ED has evolved, patients’ preference has become an important aspect of ED , 52–65% of patients prefer tadalafil versus 12–20% vardenafil or 8–30% sildenafil. All founded studies have serious limitations, particularly in terms of dosing differences. Preference for tadalafil was mainly because of the longer duration of action that increases patients’ freedom in sexual life. There is a consistency in patients’ preference for tadalafil over sildenafil or vardenafil across the studies reviewed.

Intraprostatic botulinum toxin type A administration: evaluation of the effects on sexual function

João Silva1, Rui Pinto1, Tiago Carvalho1, Francisco Botelho1, Pedro Silva1, Carlos Silva1,2,3, Francisco Cruz1,2,3,*, Paulo Dinis1

BJU International 2010, publ.online 24 Nov. 2011

Keywords :botulinum toxin;benign prostatic enlargement;prostate;sexual dysfunctionStudy Type – Therapy (case series) Level of Evidence 4

OBJECTIVE

To evaluate the consequences on male sexual function of intraprostatic of botulinum toxin type A (BoNT/A) as a treatment for benign prostatic hyperplasia (BPH). Although BoNT/A is effective in decreasing symptoms of BPH, neuronal impairment caused by the neurotoxin might affect emission/. These aspects have not been evaluated before.

PATIENTS AND METHODS

In all, 16 sexually active men aged >60 years with BPH/benign prostatic enlargement (BPE), International Prostate Symptom Score (IPSS) ≥8 and a maximum urinary flow rate (Qmax) <15 mL/s refractory to standard medical therapy volunteered for the study.

Patients were injected transrectally, under ultrasonographic control, with 200 U of BoNT/A in the prostate. Evaluation was carried out at baseline and 1, 3 and 6 months post-treatment. Erectile function was evaluated using the International Index of Erectile Function – Short Form (IIEF-5) questionnaire. Orgasmic/ejaculatory function and were evaluated using questions 9, 10, 11 and 12 of the IIEF – Long Form. Total testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH) and prolactin were also investigated.

RESULTS 7

The mean age was 73 ± 6 years. The IIEF-5 score was 16.5 ± 6 at baseline, 15.7 ± 6 at 1 month, 16.6 ± 6 at 3 months and 15.7 ± 5 at 6 months (differences nonsignificant). The score for ejaculatory/orgasmic function (questions 9 and 10) remained fairly constant from baseline to the sixth month, 8.3 ± 1.9 and 8 ± 2.1 respectively. The sexual desire score (questions 11 and 12 of the IIEF) also remained little changed from baseline (5.9 ± 1.6) to month 6 (6.1 ± 2). Total serum testosterone, LH, FSH and prolactin did not change during the study.

CONCLUSIONS

Intraprostatic injection of BoNT/A in patients with BPE does not impair erectile, orgasmic or ejaculatory functions and does not change libido. The male hormonal profile is not altered by BoNT/A injection. This facilitates the acceptance of BoNT/A as a treatment for BPH/BPE lower urinary tract symptoms (LUTS) refractory to standard medical management.

Effect of Tipranavir/Ritonavir Combination on the of Tadalafil in Healthy Volunteers.

Garraffo R, Lavrut T M, Ferrando S, Durant J, Rouyrre N, Macgregor TR, Sabo JP, Dellamonica P.

J Clin Pharmacol. 2011 Jan 5. (Epub ahead of print)

Abstract This study evaluated the effects of single-dose administration and steady-state concentrations of tipranavir 500 mg and ritonavir 200 mg (TPV/r) combination on the pharmacokinetics of tadalafil 10 mg (TAD) in an open-label study. Seventeen healthy male volunteers received sequential dosing of the studied product: TAD (day 1) alone in a single dose for 7 days followed by TAD (day 8) in a single dose with TPV/r (500/200 mg twice daily, days 8-18). Pharmacokinetic parameters were determined in a non-compartmental analysis. The geometric mean ratio and 90% confidence interval were used to evaluate drug interactions. The effect of a single dose of TAD on the pharmacokinetics of TPV/r resulted in a small decrease in exposure after either first-dose or steady-state TPV/r (geometric mean ratios [90% confidence interval]: area under the concentration-time curve, 0.85 [0.74-0.97]). In contrast, coadministration of TAD exposure was increased significantly (2.33 [2.02-2.69]) when administered with the first dose of TPV/r but not when TPV/r steady state was reached (1.01 [0.83-1.21]). Antiretroviral activity may not be reduced, but the dose of TAD should be reduced at the start of TPV/r therapy and then a full dose can be resumed after steady state is reached. 8

The correlation between international prostate symptoms score and sexual health inventory in men with lower urinary tract symptoms

Abdul R. Nasir, Ali Akbar Zehri, Farhat Abbas and M. Hammad Ather

Int J Urol Nephrol 2011,publ. online 13 Jan 2011

Abstract

Objective

Lower urinary tract symptoms (LUTS) are common in aging men and are often associated with erectile dysfunction (ED). The International Prostate Symptoms Score (IPSS) and the Sexual Health Inventory for Men (SHIM) are commonly used validated instruments for LUTS and ED, respectively. We explored the correlation between LUTS (assessed by IPSS) and ED (assessed by SHIM) in men over 40 years of age.

Methods

A total of 585 men, 40 years and above, who presented with LUTS were prospectively enrolled into the study at single tertiary academic center. All patients were evaluated using SHIM and IPSS questionnaires. The self-administered IPSS and SHIM questionnaires were translated in the local language (not validated yet) as well. The data were analyzed using SPSS version 13.0. The correlation coefficient between IPSS and SHIM scores were determined, and the scatter diagram was made.

Results and limitations

The mean age (SD) of the group was 59.61 ± 11.75 years. The correlation between age and ED was statistically significant ( P value < 0.001) with coefficient of 0.376. The correlation between age and LUTS was statistically significant ( P value < 0.001) with coefficient of 0.312. Additionally, the correlation between ED and LUTS was statistically significant ( P value < 0.001) with coefficient of 0.336.

Conclusions

We noted a significant correlation between the severity of LUTS and ED, while confirming the earlier established correlation between age, LUTS, and ED. The exact nature of this relationship and its needs to be determined by further studies.

Keywords IPSS – SHIM – Lower urinary tract symptoms and erectile dysfunction 9

Tadalafil administered once daily for lower urinary tract symptoms secondary to benign prostatic hyperplasia: a 1- year, open-label extension study.

Donatucci CF, Brock GB, Goldfischer ER, Pommerville PJ, Elion-Mboussa A, Kissel JD, Viktrup L.

Department of Surgery, Division of , Duke University, Durham, NC, Hudson Valley Urology Center, Poughkeepsie, NYLilly Research Laboratories, Eli Lilly and Co., Indianapolis, IN, USADepartment of Surgery, Division of Urology, St Joseph's London, University of Western Ontario, London, OntarioCan-Med Clinical Research Inc., Victoria, BC, Canada.

BJU International 2011, epub ahead of print Jan 18, 2011

Abstract Study Type - Therapy (cohort study) Level of Evidence 2b

OBJECTIVES: To evaluate the 1-year safety of 5 mg of tadalafil once daily in men with lower urinary tract symptoms secondary to benign prostatic hyperplasia (BPH-LUTS); efficacy measures were included to evaluate the maintenance of efficacy after an additional year of treatment. PATIENTS AND METHODS: In total, 427 men who completed a 12-week, placebo- controlled, dose- finding study assessing once-daily tadalafil (2.5, 5, 10 or 20 mg) or placebo elected to continue into the open-label extension period. Safety and efficacy parameters were assessed after 1 month and every 3 months.

RESULTS: In total, 299 patients (69.9%) completed the 1-year, open-label extension period. Treatment-emergent adverse events (TEAEs) were reported by 57.6% of patients, with most TEAEs being mild (44%) or moderate (45%) in severity; the most common TEAEs (≥2%) were dyspepsia, gastro-oesophageal reflux disease, back pain, headache, sinusitis, hypertension and cough. Twenty-two patients (5.2%) discontinued as a result of AEs. During the open-label extension period, mean prostate-specific antigen increased from 1.6 ± 1.3 ng/mL to 1.8 ± 1.4 ng/mL. Mean post-void residual volume was 61.1 ± 60.4 mL at study entry and 42.2 ± 64.1 mL after the open-label extension period. Changes in the 10

total International Prostate Symptom Score (IPSS), IPSS irritative and obstructive subscores, IPSS health-related quality of life and BPH Impact Index were maintained after 1 year. In sexually-active patients with erectile dysfunction, improvements in the International Index of Erectile Function-Erectile Function domain were maintained after 1 year.

CONCLUSIONS: In men with BPH-LUTS, 5 mg of tadalafil once daily during 1 year of treatment was well tolerated and efficacy changes were maintained.

© 2011 THE AUTHORS. BJU INTERNATIONAL © 2011 BJU INTERNATIONAL

Ejaculatory Disorders

The link between penile hypersensitivity and

Michael G. Wyllie, Wayne J.G. Hellstrom

BJU International 2011 , 107, 452–457

Keywords: premature ejaculation (PE); ,hypersensitivity; ,topical desensitizing agents; ,PSD502 Study Type – Aetiology (case control) Level of Evidence 3b

What’s known on the subject? and What does the study add?

Very little is known about the aetiology of premature ejaculation. This analysis shows that many PE patients have a heightened penile sensitivity. This information could result in the design and development of new .

OBJECTIVES To investigate the correlation between penile hypersensitivity and premature ejaculation (PE), as defined by the criteria identified by the International Society of (ISSM). Penile hypersensitivity as a cause of PE is based on historical clinical neurophysiological data and clinical efficacy of the topical desensitizing agent PSD502 in the treatment of PE. PSD502 is a eutectic-like mixture of two local anaesthetics, lidocaine and prilocaine, whose primary action is to reduce neuronal conduction in sensory afferents.

METHODS Historical neurophysiological data was reviewed, together with data from the recent PSD502 clinical trials, including the first published double-blind clinical trial data evaluating a topical 11

desensitizing agent in a population of men with PE, as per the new ISSM definition. The clinical profile of PSD502, based on its local anaesthetic properties, is used as a surrogate index of the role of sensory afferents in the ejaculatory reflex.

RESULTS The published data does not support unequivocally penile hypersensitivity as the cause of PE. Interpretation of the data is hampered by the variability of the populations described as having PE across studies. Data from the PSD502 clinical trials clearly shows that PSD502 increases ejaculatory latency, and improves control and sexual satisfaction when applied topically to men with PE 5 min before intercourse, enabling subjects to delay ejaculation up to six times longer than those who used a placebo.

CONCLUSION The clinical profile of PSD502 lends credibility to the penile hypersensitivity hypothesis for PE. The predominant action of local anaesthetics is to reduce neuronal firing in sensory afferents; the clinical profile of PSD502, which shows improvement of ejaculatory function in the absence of a generalized reduction in penile sensitivity, can most readily be explained based on an underlying hypersensitivity in patients with PE.

Peyronie’s disease

Factors Affecting the Degree of Penile Deformity in Peyronie's Disease: An Analysis of 1001 Patients

Ates Kadioglu *, Oner Sanli , Tolga Akman , Onder Canguven , Memduh Aydin , Fatih Akbulut , and Faruk Kucukdurmaz

J Androl. 2011 Published-Ahead-of-Print January 13, 2011

Only a few studies have investigated the association between the severity of Peyronie's disease (PD) and clinical parameters such as age and associated comorbidities. The aim of this study was to report the relationship between the degree of the curvature of the penis and the clinical parameters among patients with PD. A total of 1001 patients with PD were evaluated retrospectively in terms of penile deformity, erectile status and risk factors for systemic vascular diseases. The degree of curvature was assessed with a protractor during maximum in response to a combined injection and stimulation (CIS) test and/or vacuum device. A modified Kelami classification was used to categorize penile deformities as follows: patients with deformities without a curvature (notching, hourglass and swan neck deformity, Group 1), with mild ( 30°, Group 2), moderate (31-60°, Group 3) or severe curvatures (>60°, Group 4). Chi-square tests, one way ANOVA and univariate and multiple ordinal regression analyses were used for statistical analysis. Penile deformity without curvature was detected in 12.3% of the patients, whereas the curvature was <30° in 39.5%, 30-60° in 34.5% and >60° in 13.5% of the patients. Multiple ordinal identified age (p = 0.013), side of deformity (p = 0.007), erectile dysfunction (p < 0.0001) and diabetes mellitus (DM) (p = 0.001) as significant independent predictors of the severity of the 12 penile curvature. In conclusion, patients' age, side of deformity, erectile function and DM were significantly associated with the degree of curvature.

Key words: Erectile Dysfunction • Penis • Peyronie's disease • curvature • risk factors

Testosterone and Male Hormonal Disorders

Serum testosterone levels and score of chronic mountain sickness in Peruvian men natives at 4340 m

G. F. Gonzales, V. Tapia, M. Gasco, C. Gonzales-Castañeda

Andrologia 2010, Article first published online: 19 JAN 2011 Keywords: Altitude;chronic mountain sickness;excessive erythrocytosis;men;sex steroidsSummary Life at high altitudes (>4000 m) is associated with higher erythropoiesis. Haemoglobin ≥21 g dl −1 is considered as excessive erythrocytosis and is a sign of chronic mountain sickness (CMS). The present study was designed to determine an association between serum testosterone (T) and serum oestradiol (E2) levels with the score of CMS. One hundred and seventeen men natives from low altitude (150 m) and 103 men natives from high altitude (4340 m) were studied. The presence of breathlessness or palpitations, sleep disturbance, cyanosis, dilatation of veins, paraesthesia, headaches, tinnitus and Hb ≥21 g dl −1, have been included for the CMS score. Men living at high altitude had higher CMS score (P < 0.001), serum T (P < 0.05) and serum E2 levels (P < 0.04) and had lower serum luteinising hormone levels (P < 0.005) than men living at sea level. At high altitude, the group with the highest CMS score (≥10) showed higher chronological age, SpO2, serum T and ratio T/E2 than the group with CMS score of ≤4. Some symptoms of CMS as sleep disorders and paraesthesia were more related to high serum T level; cyanosis was more related to higher haemoglobin values. In conclusion, higher serum T levels were associated to higher scores of CMS.

New Immunophenotype of Endothelial Progenitor Cells and Endothelial Microparticles in Patients with Arterial Erectile Dysfunction and Late Onset

Sandro La Vignera *, Rosita Condorelli , Enzo Vicari , Rosario D'Agata , and Aldo Calogero

Journal of Andrology 2011, Published -Ahead-of-Print January 13, 2011 13

Objective: Blood endothelial progenitor cells (EPCs) and microparticles (EMPs) have been proposed as markers of endothelial dysfunction. Aim of this study was to evaluate a new immunophenotype of EPCs and EMPs in patients with arterial erectile dysfunction (ED) and late onset hypogonadism (LOH). Materials and methods: Fifty patients (58.2 ± 0.7 years) with ED and LOH were enrolled in this study. Their EPC and EMP concentrations were compared with those of 20 patients with arterial ED alone (61.2 ± 1.2 years) and of 20 healthy men

(controls) (61.4 ± 1.2 years). EPC (CD45 neg /CD34 pos /CD144 pos ) and EMP

(CD45 neg /CD144 pos /Annexin Vpos ) blood concentrations were evaluated by flow cytometry. Results: Patients with ED and LOH or ED alone had significantly higher blood pressure, triglycerides, homeostasis model assessment index of insulin resistance, and cavernous artery acceleration time and intima-media thickness than controls; whereas IIEF5 score, HDL- cholesterol, and cavernous artery peak systolic velocity and resistance index was lower than controls. Both EPCs and EMPs were significantly higher in patients with ED and LOH compared to patients with ED alone or controls. Patients with ED alone had EPCs and EMPs significantly higher than controls. Conclusions: Patients with ED and LOH showed worse metabolic parameters, cavernous artery parameters, measured by dynamic penile echo color Doppler, and higher EPCs and EMPs compared to patients with ED alone. This suggests that LOH is an additional vascular risk factor and that EPCs and EMPs may be considered predictors of endothelial dysfunction in patients with ED and LOH.

Key words: Androgen • Andropause • Erectile Dysfunction • Hormone • Penis

Androgen Receptor CAG Repeat Polymorphism Is Not Associated with Erectile Dysfunction Complaints, Gonadal Steroids and Sleep Parameters: Data from a Population- Based Survey

Monica L. Andersen *, Camila Guindalini , Rogério Santos-Silva , Lia R.A. Bittencourt , and Sergio Tufik

Journal of Andrology 2010, publ. online 30 Dec. 2010

Erectile dysfunction (ED) can be affected by androgen levels, which exert their action through the androgen receptor (AR). Androgenic action has been demonstrated to inversely correlate with a polymorphic trinucleotide CAG repeat region in the AR gene. Objectives: We conducted an epidemiologic study to determine the potential association between the CAG repeat polymorphism of the AR gene and ED complaints, gonadal steroids and sleep parameters in a large population-based sample in São Paulo, Brazil. Findings: AR CAG repeat was genotyped in 79 cases in which men had ED complaints and in 340 controls. Sleep and hormonal profiles were measured in all men. There was no association between the AR CAG repeat polymorphism and ED complaints. Moreover, there was no significant correlation among free and total testosterone, estradiol, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels as well as sleep parameters with the CAG repeat length, when evaluating the population as a whole, as well as subdivided into ED and control groups independently. The results were not affected when the data was analyzed in quartiles, divided by the median of the sample, or after correction for population stratification. Conclusions: AR CAG repeat polymorphism is not 14

associated with ED complaints, gonadal steroids and sleep parameters in men from a population-based sample in Brazil.

Key words: Androgen • Erectile Dysfunction • Hormone • Reproductive • CAG polymorphism • FSH • LH • sleep • testosterone

Identification of late-onset hypogonadism in middle-aged and elderly men.

Wu FC, Tajar A, Beynon JM, Pye SR, Silman AJ, Finn JD, O'Neill TW, Bartfai G, Casanueva FF, Forti G, Giwercman A, Han TS, Kula K, Lean ME, Pendleton N, Punab M, Boonen S, Vanderschueren D, Labrie F, Huhtaniemi IT; EMAS Group.

Collaborators (28)

Forti G, Petrone L, Corona G, Vanderschueren D, Boonen S, Borghs H, Kula K, Slowikowska-Hilczer J, Walczak-Jedrzejowska R, Huhtaniemi I, Giwercman A, Wu F, Silman A, O'Neill T, Finn J, Steer P, Tajar A, Lee D, Pye S, Casanueva F, Ocampo M, Lage M, Bartfai G, Földesi I, Fejes I, Punab M, Korrovitz P, Jiang M.

Andrology Research Unit, Developmental and Regenerative Research Group, University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom. [email protected]

Source N Engl J Med. 2010 Jul 8;363(2):123-35. Epub 2010 Jun 16

Comment in:

• N Engl J Med. 2010 Jul 8;363(2):189-91.

• N Engl J Med. 2010 Nov 4;363(19):1867-8; author reply 1868-9.

• N Engl J Med. 2010 Nov 4;363(19):1868; author reply 1868-9.

Abstract BACKGROUND: The association between aging-related testosterone deficiency and late- onset hypogonadism in men remains a controversial concept. We sought evidence-based criteria for identifying late-onset hypogonadism in the general population on the basis of an association between symptoms and a low testosterone level.

METHODS: We surveyed a random population sample of 3369 men between the ages of 40 and 79 years at eight European centers. Using questionnaires, we collected data with regard 15

to the subjects' general, sexual, physical, and psychological health. Levels of total testosterone were measured in morning blood samples by mass spectrometry, and free testosterone levels were calculated with the use of Vermeulen's formula. Data were randomly split into separate training and validation sets for confirmatory analyses.

RESULTS: In the training set, symptoms of poor morning erection, low sexual desire, erectile dysfunction, inability to perform vigorous activity, depression, and fatigue were significantly related to the testosterone level. Increased probabilities of the three sexual symptoms and limited physical vigor were discernible with decreased testosterone levels (ranges, 8.0 to 13.0 nmol per liter [2.3 to 3.7 ng per milliliter] for total testosterone and 160 to 280 pmol per liter [46 to 81 pg per milliliter] for free testosterone). However, only the three sexual symptoms had a syndromic association with decreased testosterone levels. An inverse relationship between an increasing number of sexual symptoms and a decreasing testosterone level was observed. These relationships were independently confirmed in the validation set, in which the strengths of the association between symptoms and low testosterone levels determined the minimum criteria necessary to identify late-onset hypogonadism.

CONCLUSIONS: Late-onset hypogonadism can be defined by the presence of at least three sexual symptoms associated with a total testosterone level of less than 11 nmol per liter (3.2 ng per milliliter) and a free testosterone level of less than 220 pmol per liter (64 pg per milliliter). Are there symptom-specific testosterone thresholds in aging men?

Jakob E. Lackner1,*, Ernst Rücklinger2, Georg Schatzl3, Gerhard Lunglmayr4, Christian W. Kratzik3

BJU International 2011, Article first published online: 13 JAN 2011

Keywords: late-onset hypogonadism; , testosterone thresholds, androgen deficiency symptoms Study Type – Prognosis (retrospective cohort) Level of Evidence 2b

OBJECTIVE 16

• To study the association between specific clinical symptoms (e.g. low libido and erectile dysfunction) and testosterone levels and age in order to define symptom-specific testosterone thresholds.

MATERIALS AND METHODS • Serum samples for testosterone determination were obtained from 675 healthy men.

• Participants underwent urological examination and completed the Aging Males Symptoms scale, the Beck Depression Index and the International Index of Erectile Function. Overall scores and those from individual questions from the questionnaires were evaluated.

• Testosterone levels in men with symptoms were compared with those in men without symptoms.

• The risks of clinical symptoms were evaluated using univariate, multiple multinomial regression analyses and Bonferroni correction.

RESULTS • Significant associations between testosterone levels and a number of androgen deficiency symptoms were seen at testosterone levels of 13.5–14.4 nmol/L, but multiple logistic regression analysis revealed confounding effects with age.

• Symptoms such as loss of libido, lack of vigour and were associated with age rather than with testosterone.

• Erectile dysfunction was reported at testosterone levels between 14.65 nmol/L and 14.8 nmol/L, but was again significantly associated with age rather than testosterone levels.

• The severity of symptoms significantly increased with decreasing testosterone levels using univariate analysis, but only the relationship with psychological symptoms remained significant after Bonferroni correction.

CONCLUSION • In aging males, androgen deficiency symptoms were reported at normal levels of testosterone, but age was an important confounder. Symptom-specific testosterone thresholds could not be defined.

Finasteride-associated male .

Chiba K, Yamaguchi K, Li F, Ando M, Fujisawa M. 17

Division of Urology, Department of Surgery Related, Kobe University Graduate School of Medicine, Kobe, Japan.

Fertil Steril. 2010 publ. online Dec 28.

Abstract OBJECTIVE: To describe a male patient with finasteride-associated infertility.

DESIGN: Case report.

SETTING: Tertiary-care clinic for male infertility.

PATIENT(S): A patient with azoospermia who had been taking finasteride (1-mg dose) for 1 year for androgenic alopecia. He had been diagnosed with oligospermia 5 years before.

INTERVENTION(S): Discontinuation of finasteride.

MAIN OUTCOME MEASURE(S): Improvement of parameters.

RESULT(S): After cessation of finasteride, the patient's semen volume increased immediately, and sperm concentration was up to more than 10 × 10(6)/mL 16 weeks after stopping finasteride. He is now trying to achieve by intrauterine .

CONCLUSION(S): Cessation of finasteride improved spermatogenesis and allowed the couple to attempt less-invasive fertility therapy. In this case, the patient had impaired spermatogenesis before he started the drug. In such patients, the drug may further decrease spermatogenesis. We suggest that drug cessation could be taken into consideration for infertile male patients with impaired semen parameters who are taking finasteride at a 1-mg dose.

Finasteride upregulates expression of androgen receptor in hyperplastic prostate and LNCaP cells: Implications for chemoprevention of .

Hsieh JT, Chen SC, Yu HJ, Chang HC.

Department of Urology, National Taiwan University Hospital and National Taiwan University, College of Medicine, Taipei, Taiwan. 18

Prostate. 2011 Jan 12. [Epub ahead of print]

Abstract BACKGROUND: Although finasteride is recognized for its role as a chemopreventive agent for prostate cancer, higher grades of malignancy have been reported. It is questioned whether blocking of testosterone conversion to dihydrotestosterone (DHT) by finasteride in prostate tissue will change expression of androgen receptor (AR). Therefore, this study evaluated the effects of finasteride on AR expression in prostate tissue and in the LNCaP cell line.

METHODS: Between January and December 2006, we retrospectively selected and evaluated 47 cases of benign prostatic hyperplasia treated with variable duration of finasteride (5 mg QD) before transurethral resection of the prostate. AR expression in prostate tissue was semiquantified by immunostaining and compared with duration of finasteride treatment. An androgen-dependent prostate cancer cell line (LNCaP) was cultured in charcoal/dextran-treated FBS with DHT or testosterone, and treated with finasteride for 1-3 weeks. Samples of total RNA were collected to analyze expression of AR by real-time quantitative reverse transcription polymerase chain reaction.

RESULTS: Immunohistochemical study revealed significant upregulation of ARs by finasteride treatment for 30-180 days. In cell line study, quantitative real-time reverse transcription polymerase chain reaction revealed significant upregulation of ARs treated by finasteride.

CONCLUSIONS: In our study, finasteride influenced AR expression in benign prostate tissue and prostate cancer cell. Before we can use finasteride in chemoprevention with confidence, we still need to clarify the influence of finasteride in ARs and its regulation pathway. Prostate © 2011 Wiley-Liss, Inc.

Interaction between Testosterone and Growth Hormone on Whole-Body Protein Anabolism Occurs in the Liver

Vita Birzniece *, Udo J. Meinhardt *, Margot A. Umpleby, David J. Handelsman and Ken K. Y. Ho 19

Garvan Institute of Medical Research and Department of (V.B., U.J.M, K.K.Y.H.), St. Vincent's Hospital, Sydney, New South Wales 2010, Australia; University of New South Wales (V.B., K.K.Y.H.), Sydney, New South Wales 2052, Australia; Diabetes and Metabolic Medicine (M.A.U.), Postgraduate , University of Surrey, Surrey GU2 7WG, United Kingdom; and ANZAC Research Institute (D.J.H.), Concord Hospital, University of Sydney, Sydney, New South Wales 2139, Australia

Address all correspondence and requests for reprints to: Prof. Ken K. Y. Ho, Pituitary Research Unit, Garvan Institute of Medical Research and Department of Endocrinology, St. Vincent's Hospital, Darlinghurst, New South Wales 2010, Australia. E-mail: [email protected] .

The Journal of Clinical Endocrinology & Metabolism, published online on January 14, 2011

Context : GH and testosterone both exert protein-anabolic effects and may act synergistically. Liver and muscle are major sites of protein metabolism.

Objective : Our objective was to determine whether the site of GH and testosterone interaction on protein metabolism is primarily hepatic or extrahepatic.

Design : In this open-label randomized crossover study, the impact on whole-body protein metabolism of oral (solely hepatic testosterone exposure) and transdermal (systemic testosterone exposure) testosterone replacement in the presence or absence of GH was compared.

Patients and Intervention : Eleven hypopituitary men with GH and testosterone deficiency were randomized to 2-wk treatments with transdermal testosterone (10 mg) or oral testosterone (40 mg), with or without GH replacement (0.6 mg/d). The dose of testosterone administered orally achieves physiological portal testosterone concentrations without spillover into the systemic circulation.

Main Outcome Measures : Whole-body leucine turnover was measured, from which leucine rate of appearance (LRa), an index of protein breakdown, and leucine oxidation (Lox), a measure of irreversible protein loss, were estimated at the end of each treatment.

Results : In the absence of GH, neither transdermal nor oral testosterone affected LRa or Lox. GH therapy significantly increased LRa, an effect equally reduced by transdermal and oral testosterone administration. GH replacement alone did not significantly change Lox, whereas addition of testosterone treatment reduced Lox, with the effect not significantly different between transdermal and oral testosterone.

Conclusion : In the doses used, testosterone stimulates protein anabolism by reducing protein breakdownandoxidation only in the presence ofGH. Because the net effectonprotein metabolism during GH therapy is not different between systemic and solely hepatic testosterone administration, we conclude that the liver is the primary site of this hormonal interaction.

20

STD/AIDS and Venereal Diseases

FDA NEWS RELEASE

For Immediate Release : Dec. 22, 2010 Media Inquiries : Shelly Burgess, 301-796-4651, [email protected] Consumer Inquiries : 888-INFO-FDA

FDA: Gardasil approved to prevent

The U.S. Food and Drug Administration today approved the vaccine Gardasil for the prevention of anal cancer and associated precancerous lesions due to human papillomavirus (HPV) types 6, 11, 16, and 18 in people ages 9 through 26 years.

Gardasil is already approved for the same age population for the prevention of cervical, vulvar, and vaginal cancer and the associated precancerous lesions caused by HPV types 6, 11, 16, and 18 in females. It is also approved for the prevention of genital warts caused by types 6 and 11 in both males and females.

“Treatment for anal cancer is challenging; the use of Gardasil as a method of prevention is important as it may result in fewer diagnoses and the subsequent surgery, radiation or chemotherapy that individuals need to endure,” said Karen Midthun, M.D., director of the FDA’s Center for Biologics Evaluation and Research.

Although anal cancer is uncommon in the general population, the incidence is increasing. HPV is associated with approximately 90 percent of anal cancer. The American Cancer Society estimates that about 5,300 people are diagnosed with anal cancer each year in the United States, with more women diagnosed than men.

Gardasil’s ability to prevent anal cancer and the associated precancerous lesions [anal intraepithelial neoplasia (AIN) grades 1, 2, and 3] caused by anal HPV-16/18 infection was studied in a randomized, controlled trial of men who self-identified as having sex with men (MSM). This population was studied because it has the highest incidence of anal cancer. At the end of the study period, Gardasil was shown to be 78 percent effective in the prevention of HPV 16- and 18-related AIN. Because anal cancer is the same disease in both males and females, the effectiveness data was used to support the indication in females as well.

Gardasil will not prevent the development of anal precancerous lesions associated with HPV infections already present at the time of . For all of the indications for use approved by the FDA, Gardasil's full potential for benefit is obtained by those who are vaccinated prior to becoming infected with the HPV strains contained in the vaccine.

Individuals recommended for anal cancer screening by their health care provider should not discontinue screening after receiving Gardasil.

As of May 31, 2010, more than 65 million doses of Gardasil had been distributed worldwide, since its approval in 2006 according to the manufacturer, Merck and Co. Inc, of Whitehouse Station, N.J. The most commonly reported adverse events include fainting, pain at the injection site, headache, nausea, and fever. Fainting is common after injections and , especially in adolescents. Falls after fainting may sometimes cause serious , such as head injuries. This can be prevented by keeping the vaccinated person seated for up to 15 minutes after vaccination. This observation period is also recommended 21 to watch for severe allergic reactions, which can occur after any .

For more information:

Gardasil Product Page 1

News Release, Sept. 12, 2008 – FDA Approves Expanded Uses for Gardasil to Include Preventing Certain Vulvar and Vaginal Cancers 2

News Release, Oct. 16, 2009 – FDA Approves New Indication for Gardasil to Prevent Genital Warts in Men and Boys 3

Association Between Sexually Transmitted Diseases and Young Adults' Self-reported

Ralph J. DiClemente, PhD a,b,c , Jessica McDermott Sales, PhD a,b , Fred Danner, PhD d, Richard A. Crosby, PhD e,f aRollins School of , and cDivision of Infectious Diseases, , and , Department of , School of Medicine, Emory University, Atlanta, Georgia; bEmory Center for AIDS Research, Atlanta, Georgia; dDepartment of Educational, School, and Counseling Psychology, and eCollege of Public Health, University of Kentucky, Lexington, Kentucky; and

PEDIATRICS 2010, publ.online 11 January 2010

fRural Center for AIDS and STD Prevention, Indiana University, Bloomington, Indiana

OBJECTIVE Self-reported behavior has been the cornerstone of sexual health research and clinical practice, yet advances in sexually transmitted disease (STD) screening provide researchers with the opportunity to objectively quantify sexual risk behaviors. However, the extent to which young adults' laboratory-confirmed STD results and self-reported sexual behaviors are consistent has not been assessed in a nationally representative sample.

PATIENTS AND METHODS Data are derived from participants who completed wave 3 in the National Longitudinal Study of Adolescent Health. Young adults (N = 14 012) completed an audio computer-assisted self-interviewing survey and provided a urine specimen to detect the presence of trachomatis and , and a polymerase chain reaction assay to detect .

RESULTS More than 10% of young adults with a laboratory-confirmed positive STD result reported abstaining from in the 12 months before assessment and STD testing. After controlling for several sociodemographic factors, self-reported sex (versus those who reported abstinence) in the previous 12 months was significantly associated with testing positive, but the odds of testing positive were only slightly more than twofold (adjusted odds ratio: 2.11 [95% confidence interval: 2.097–2.122]).

CONCLUSIONS Findings indicate discrepancy between young adults' positive STD status and self-reported sexual behavior. No significant correlates of discrepant reporting were identified. From a clinical standpoint, the discrepancies between STD positivity and self- 22 reported sexual behavior observed in this nationally representative sample suggest that routine STD screening may be beneficial and necessary to reduce STD morbidity among young adults.

Key Words: young adults • self-report • sexual behavior • national sample

Abbreviations: STD = sexually transmitted disease • aOR = adjusted odds ratio • CI = confidence interval

Human papillomavirus infection in couples undergoing in vitro fertilization procedures: impact on reproductive outcomes

Antonio Perino, M.D. Lucia Giovannelli, Ph.D., Rosaria Schillaci, Ph.D., Giovanni Ruvolo, Ph.D., Francesco Paolo Fiorentino, Ph.D., Pietro Alimondi, M.D., Eleonora Cefalù, Ph.D., Piero Ammatuna, Ph.D

Fertilty and Sterility 2010, publ.online 17 Dec 2010

A prospective study was performed to assess the relationship between human papillomavirus (HPV) infection in 199 infertile couples and outcome of assisted reproductive technologies (ARTs). A highly statistically significant correlation between pregnancy loss rate (proportion of detected by β-hCG that did not progress beyond 20 weeks) and positive HPV DNA testing in the male partner of infertile couples, compared with HPV negatives, was observed (66.7% vs. 15%).

Key Words: , ART, HPV infection, infertility, pregnancy loss

Evidence for the cure of HIV infection by CCR5 32/ 32 stem cell transplantation

Kristina Allers 1,* , Gero Hütter 2, Jörg Hofmann 3, Christoph Loddenkemper 4, Kathrin Rieger 2, Eckhard Thiel 2 and Thomas Schneider 1

1 Department of , Infectious Diseases, and , Medical Clinic I, Campus Benjamin Franklin, Charite - University Medicine Berlin, Germany; 2 Department of , , and , Medical Clinic III, Campus Benjamin Franklin, Charite - University Medicine Berlin, Germany; 3 Institute of Medical Virology, Helmut-Ruska-Haus, Campus Mitte, Charite - University Medicine Berlin, Germany; 4 Institute of /Research Center ImmunoSciences (RCIS), Campus Benjamin Franklin, Charite - University Medicine Berlin, Germany

Blood First Edition Paper, prepublished online December 8, 2010;

Abstract

HIV entry into CD4 + cells requires interaction with a cellular receptor, generally either CCR5 or CXCR4. We have previously reported the case of an HIV-infected patient in whom viral replication remained absent despite discontinuation of antiretroviral therapy after transplantation with CCR5 32/ 32 stem cells. However, it was expected that the long-lived viral reservoir would lead to HIV rebound and disease progression during the process of immune reconstitution. In the present study, we demonstrate successful reconstitution of 23

CD4 + T cells at the systemic level as well as in the gut mucosal immune system following CCR5 32/ 32 stem cell transplantation, while the patient remains without any sign of HIV infection. This was observed although recovered CD4 + T cells contain a high proportion of activated memory CD4 + T cells, i.e. the preferential targets of HIV, and are susceptible to productive infection with CXCR4-tropic HIV. Furthermore, during the process of immune reconstitution, we found evidence for the replacement of long-lived host tissue cells with donor-derived cells indicating that the size of the viral reservoir has been reduced over time. In conclusion, our results strongly suggest that cure of HIV has been achieved in this patient.

Effect of circumcision of HIV-negative men on transmission of human papillomavirus to HIV-negative women: a randomised trial in Rakai, Uganda

Original TextProf Maria J Wawer MD a f †, Dr Aaron AR Tobian MD a c †, Godfrey Kigozi MBChB f, Xiangrong Kong PhD a d, Patti E Gravitt PhD e, David Serwadda MMed f g, Fred Nalugoda MHS f g, Frederick Makumbi PhD f g, Victor Ssempiija ScM f, Nelson Sewankambo MMed f h, Stephen Watya MMed i, Kevin P Eaton BS b, Amy E. Oliver BA b, Michael Z Chen MSc a, Steven J Reynolds MD b j, Prof Thomas C Quinn MD b j, Prof Ronald H Gray MD a f

The Lancet, Volume 377, Issue 9761, Pages 209 - 218

Summary

Background

Randomised trials show that male circumcision reduces the prevalence and incidence of high-risk human papillomavirus (HPV) infection in men. We assessed the efficacy of male circumcision to reduce prevalence and incidence of high-risk HPV in female partners of circumcised men.

Methods

In two parallel but independent randomised controlled trials of male circumcision, we enrolled HIV-negative men and their female partners between 2003 and 2006, in Rakai, Uganda. With a computer-generated random number sequence in blocks of 20, men were assigned to undergo circumcision immediately (intervention) or after 24 months (control). HIV-uninfected female partners (648 of men from the intervention group, and 597 of men in the control group) were simultaneously enrolled and provided interview information and self-collected vaginal swabs at baseline, 12 months, and 24 months. Vaginal swabs were tested for high- risk HPV by Roche HPV Linear Array. Female HPV infection was a secondary endpoint of the trials, assessed as the prevalence of high-risk HPV infection 24 months after intervention and the incidence of new infections during the trial. Analysis was by intention-to-treat. An as- treated analysis was also done to account for study-group crossovers. The trials were registered, numbers NCT00425984 and NCT00124878.

Findings

During the trial, 18 men in the control group underwent circumcision elsewhere, and 31 in the intervention group did not undergo circumcision. At 24-month follow-up, data were available for 544 women in the intervention group and 488 in the control group; 151 (27·8%) women in the intervention group and 189 (38·7%) in the control group had high-risk HPV infection (prevalence risk ratio=0·72, 95% CI 0·60—0·85, p=0·001). During the trial, incidence of high- 24 risk HPV infection in women was lower in the intervention group than in the control group (20·7 infections vs 26·9 infections per 100 person-years; incidence rate ratio=0·77, 0·63— 0·93, p=0·008).

Interpretation

Our findings indicate that male circumcision should now be accepted as an efficacious intervention for reducing the prevalence and incidence of HPV infections in female partners. However, protection is only partial; the promotion of practices is also important.

Funding

The Bill & Melinda Gates Foundation, National Institutes of Health, and Fogarty International Center.

Optimum time to start antiretroviral therapy during HIV- associated opportunistic infections

Lawn, Stephen D a,b ; Török, M Estée c; Wood, Robin a

Current Opinion in Infectious Diseases 2011, 24 - Issue 1 - p 34–42

Abstract

Purpose of review: We review recently published literature concerning the optimum time to start antiretroviral therapy (ART) in patients with HIV-associated opportunistic infections.

Recent findings: In addition to data from observational studies, results from six randomized controlled clinical trials were available by July 2010. The collective findings of these trials were that patients with CD4 cell counts less than 200 cells/μl who start ART within the first 2 weeks of treatment for opportunistic infections including Pneumocystis jirovecii pneumonia, serious bacterial infections or pulmonary have lower mortality when compared to patients starting ART at later time-points. Moreover, patients with pulmonary tuberculosis and CD4 counts of 200–500 cells/μl who started ART during tuberculosis (TB) treatment had improved survival compared to those who deferred ART until after the end of treatment. In contrast, in two separate studies, immediate ART conferred no survival benefit in patients with TB meningitis and was associated with substantially higher mortality risk in patients with cryptococcal meningitis.

Summary: Initiation of ART during the first 2 weeks of treatment for serious opportunistic infections has been shown to be associated with improved survival with the exception of patients with tuberculous meningitis and cryptococcal meningitis. Further clinical trials are ongoing.

Female Sexual Dysfunction

Efficacy of Escitalopram for Hot Flashes in Healthy Menopausal WomenA Randomized Controlled Trial 25

Ellen W. Freeman, PhD; Katherine A. Guthrie, PhD; Bette Caan, DrPH; Barbara Sternfeld, PhD; Lee S. Cohen, MD; Hadine Joffe, MD; Janet S. Carpenter, PhD, RN; Garnet L. Anderson, PhD; Joseph C. Larson, MS; Kristine E. Ensrud, MD; Susan D. Reed, MD, MPH; Katherine M. Newton, PhD; Sheryl Sherman, PhD; Mary D. Sammel, ScD; Andrea Z. LaCroix, PhD

[+] Author Affiliations

Author Affiliations: Departments of /Gynecology and (Dr Freeman) and Center for Clinical Epidemiology and Statistics (Dr Sammel), University of Pennsylvania School of Medicine, Philadelphia; Data Coordinating Center, Fred Hutchinson Cancer Research Center (Drs Guthrie, Anderson, and LaCroix and Mr Larson), University of Washington School of Medicine (Dr Reed), and Group Health Research Institute (Dr Newton), Seattle; Division of Research, Kaiser Permanente, Oakland, California (Drs Caan and Sternfeld); Massachusetts General Hospital, Boston (Drs Cohen and Joffe); School of , Indiana University, Indianapolis (Dr Carpenter); VA Medical Center/University of Minnesota, Minneapolis (Dr Ensrud); and National Institute on Aging, US National Institutes of Health, Bethesda, Maryland (Dr Sherman).

JAMA. 2011;305(3):267-274.

Abstract

Context Concerns regarding the risks associated with estrogen and progesterone to manage menopausal symptoms have resulted in its declining use and increased interest in nonhormonal treatments with demonstrated efficacy for hot flashes.

Objective To determine the efficacy and of 10 to 20 mg/d escitalopram, a selective serotonin reuptake inhibitor, in alleviating the frequency, severity, and bother of menopausal hot flashes.

Design , Setting, and Patients A multicenter, 8-week, randomized, double-blind, placebo- controlled, parallel group trial that enrolled 205 women (95 African American; 102 white; 8 other) between July 2009 and June 2010.

Intervention Women received 10 to 20 mg/d of escitalopram or a matching placebo for 8 weeks.

Main Outcome Measures Primary outcomes were the frequency and severity of hot flashes assessed by prospective daily diaries at weeks 4 and 8. Secondary outcomes were hot flash bother, recorded on daily diaries, and clinical improvement (defined as hot flash frequency ≥50% decrease from baseline).

Results Mean (SD) daily hot flash frequency was 9.78 (5.60) at baseline. In a modified intent-to-treat analysis that included all randomized participants who provided hot flash diary data, the mean difference in hot flash frequency reduction was 1.41 (95% CI, 0.13-2.69) fewer hot flashes per day at week 8 among women taking escitalopram (P < .001), with mean reductions of 4.60 (95% CI, 3.74-5.47) and 3.20 (95% CI, 2.24-4.15) hot flashes per day in the escitalopram and placebo groups, respectively. Fifty-five percent of women in the escitalopram group vs 36% in the placebo group reported a decrease of at least 50% in hot flash frequency (P = .009) at the 8-week follow-up. Reductions in hot flash severity scores were significantly greater in the escitalopram group (−0.52; 95% CI, −0.64 to −0.40 vs −0.30; 95% CI, −0.42 to −0.17 for placebo; P < .001). Race did not significantly modify the treatment effect (P = .62). Overall discontinuation due to adverse events was 4% (7 in the active group, 2 in the placebo group). Three weeks after treatment ended, women in the escitalopram 26 group reported a mean 1.59 (95% CI, 0.55-2.63; P = .02) more hot flashes per day than women in the placebo group.

Conclusion Among healthy women, the use of escitalopram (10-20 mg/d) compared with placebo resulted in fewer and less severe menopausal hot flashes at 8 weeks of follow-up.

Trial Registration clinicaltrials.gov Identifier: NCT00894543

KEYWORDS : ESCITALOPRAM, HOT FLASHES, MENOPAUSE, RANDOMIZED CONTROLLED TRIAL, WOMEN'S HEALTH. Mixed topics

Management of osteoporosis in men on androgen deprivation therapy

Robert A. Adler

Maturitas Volume 68, Issue 2, Pages 143-147

Abstract

Osteoporosis is a common consequence of androgen deprivation therapy (ADT) for prostate cancer. Up to 20% of men on ADT for localized prostate cancer will fracture within 5 years. Fortunately, generally safe and effect therapy is available. Although once considered non- controversial, there is some concern about calcium supplementation, but all studies of osteoporosis therapy in men have included calcium. In most older men, serum 25- hydroxyvitamin D levels are likely to be low, although again there is controversy about the ideal level. Many experts believe that all older men, including those on ADT, need to have a level of >30 ng/ml, which is easily accomplished. Bone mineral density (BMD) testing by dual energy X-ray absorptiometry (DXA) is indicated for men on ADT. Interestingly, forearm DXA may be particularly important in ADT men, in addition to spine and hip. Some experts have suggested that men on ADT with a T-score of ≤−1.5 should be treated. Alternatively FRAX or another risk calculator can be used. Oral and intravenous bisphosphonates are FDA approved treatments for men with osteoporosis and increase BMD in men on ADT. Potential off-label agents include raloxifene and toremifene. The latter and denosumab have been shown to increase bone density and decrease vertebral fractures in men on ADT. Raloxifene and denosumab are only FDA approved for postmenopausal osteoporosis. Thus, prevention of fractures can be accomplished in this high risk population.

Keywords : Prostate cancer, Androgen deprivation therapy, Osteoporosis, Bisphosphonates, Fracture, SERMs, Denosumab

Is Associated with Teenagers’ Early Sexual Risk- Taking, Autonomy And Relationship with Sexual Partners?

Alison Parkes, Marion Henderson, Daniel Wight, Catherine Nixon

Perspectives on Sexual and 2011,Article first published online: 10 JAN 2011 27

CONTEXT: Extensive research has explored the relationship between parenting and teenagers’ sexual risk- taking. Whether parenting is associated with wider aspects of teenagers’ capacity to form satisfying sexual relationships is unknown.

METHODS: Self-reported data were collected in 2007 from 1,854 students, whose average age was 15.5 years, in central Scotland. Multivariate analyses examined associations between parenting processes and sexual outcomes (delayed first intercourse, use and several measures reflecting the context or anticipated context of first sex).

RESULTS: Parental supportiveness was positively associated with all outcomes (betas, 0.1– 0.4), and parental values restricting intercourse were positively associated with all outcomes except condom use (0.1–0.5). Parental monitoring was associated only with delayed intercourse (0.2) and condom use (0.2); parental rules about TV content were associated with delayed intercourse (0.7) and expecting sex in a relationship, rather than casually (0.8). Frequency of parental about sex and parental values endorsing contraceptive use were negatively associated with teenagers’ delayed intercourse (–0.5 and –0.3, respectively), and parents’ contraceptive values were negatively associated with teenagers’ expecting sex in a relationship (–0.5). Associations were partly mediated by teenagers’ attitudes, including value placed on having sex in a relationship.

CONCLUSIONS: Parents may develop teenagers’ capacity for positive and safe early sex by promoting skills and values that build autonomy and encourage sex only within a relationship. Interventions should promote supportive parenting and transmission of values, avoid mixed messages about abstinence and contraception, and acknowledge that teenagers may learn more indirectly than directly from parents about sex

Management of supernumerary testis in an adult: case report and review

S. P. Nayak, M. P. Sreejayan

Andrologia, first published online 29 Dec 2010

Keywords :Intratubular germ cell neoplasia;polyorchidism;supernumerary testis;testicular cancer;triorchidismSummary

Polyorchidism is a rare congenital anomaly. Approximately 100 cases have been published to date. We report a case of triorchidism in a 20-year-old man who presented to us with inguinal hernia. There is more than 30% incidence of histological abnormalities in polyorchid testes and 4–7% present with malignancy. The management of polyorchidism is controversial. Some authors prefer conservative approach to increase the chances of spermatogenesis and others suggest excision to prevent malignancy. In our case, a biopsy of the testes was performed and was found to be normal. This patient was placed on follow- 28 up with regular self examination, six monthly clinical examination and yearly scrotal sonogram.

Pubertal Presentation in Seven Patients with Congenital Adrenal Hyperplasia due to P450 Oxidoreductase Deficiency

Jan Idkowiak, Stephen O'Riordan, Nicole Reisch, Ewa M. Malunowicz, Felicity Collins, Michiel N. Kerstens, Birgit Köhler, Luitgard Margarete Graul-Neumann, Maria Szarras- Czapnik, Mehul Dattani, Martin Silink, Cedric H. L. Shackleton, Dominique Maiter, Nils Krone, and Wiebke Arlt*

Centre for Endocrinology, Diabetes and Metabolism, School of Clinical and Experimental Medicine (J.I., N.R., C.H.L.S., N.K., W.A.), University of Birmingham, Birmingham B15 2TT, United Kingdom; Developmental Endocrinology Research Group (S.O., M.D.), Clinical and Molecular Genetics, Institute of Child Health, University College London, London WC1E 6BT, United Kingdom; Departments of Biochemistry and Experimental Medicine (E.M.M.) and Metabolic Diseases, Endocrinology, and Diabetology (M.S.-C.), The Children's Memorial Health Institute, 20 04-830 Warsaw, Poland; Departments of Clinical Genetics (F.C.) and Pediatric Endocrinology (M.S.), Children's Hospital at Westmead, 2145 Sydney, Australia; Department of Endocrinology (M.N.K.), University Medical Centre Groningen, 9713 GZ Groningen, The Netherlands; Institute of Experimental Pediatric Endocrinology (B.K.) and Institute of Human Genetics (L.M.G.-N.), Charité, Universitätsmedizin Berlin, 10117 Berlin, Germany; and Department of Endocrinology (D.M.), University Hospital Saint Luc, 1200 Brussels, Belgium

The Journal of Clinical Endocrinology & Metabolism 2010, publ.online Dec.29

Context : P450 oxidoreductase (POR) is a crucial electron donor to all microsomal P450 cytochrome (CYP) enzymes including 17-hydroxylase (CYP17A1), 21-hydroxylase (CYP21A2) and P450 aromatase. Mutant POR causes congenital adrenal hyperplasia with combined glucocorticoid and sex steroid deficiency. P450 oxidoreductase deficiency (ORD) commonly presents neonatally, with disordered sex development in both sexes, skeletal malformations, and glucocorticoid deficiency.

Objective : The aim of the study was to describe the clinical and biochemical characteristics of ORD during .

Design : Clinical, biochemical, and genetic assessment of seven ORD patients (five females, two males) presenting during puberty was conducted.

Results: Predominant findings in females were incomplete pubertal development (four of five) and large ovarian cysts (five of five) prone to spontaneous rupture, in some only resolving after combined treatment with estrogen/progestin, GnRH superagonists, and glucocorticoids. Pubertal development in the two boys was more mildly affected, with some spontaneous progression. Urinary steroid profiling revealed combined CYP17A1 and CYP21A2 deficiencies indicative of ORD in all patients; all but one failed to mount an appropriate cortisol response to ACTH stimulation indicative of adrenal insufficiency. Diagnosis of ORD was confirmed by direct sequencing, demonstrating disease-causing POR mutations.

Conclusion : Delayed and disordered puberty can be the first sign leading to a diagnosis of ORD. Appropriate testosterone production during puberty in affected boys but manifest primary hypogonadism in girls with ORD may indicate that testicular steroidogenesis is less 29 dependent on POR than adrenal and ovarian steroidogenesis. Ovarian cysts in pubertal girls may be driven not only by high gonadotropins but possibly also by impaired CYP51A1- mediated production of meiosis-activating sterols due to mutant POR.

Sexual function and fertility issues in cases of exstrophy epispadias complex

MS Ansari, RM Cervellione, JP Gearhart Department of Urology, Division of Pediatric Urology, The James Buschanan Brady Urological Institute, The John Hopkins Hospital, Baltimore, MD, 21287 USA,

Indian J Urol . 2010, 26 : 595-597

Abstract

In patients with EEC, the issues such as sexuality, sexual function and fertility gain more importance once theses patients advance from puberty to adulthood. The aim of this review is to critically examine the available evidence on these issues. A systemic literature search was performed in Medline over the last 25 years using the key words: Exstrophy, sexual function and pregnancy. Search results were limited to studies of patients with exstrophy published in English literature. A total of 1500 publications were found and subsequently screened by title and when appropriate by abstracts. Of these, 40 publications pertinent to the subject were included for the analysis. The publications were supplemented by an additional 15 publications obtained from their bibliographies. The studies were rated according to the guidelines published by the US department of health and . is usually expressed in both the sexes and most of them have adequate sexual function. Urinary diversion in some series seems to result in better ejaculatory hence fertility outcome in male patients. Recent series have shown equally good results with primary reconstruction. Most of the female patients have normal fertility while male patients have significantly low fertility. Most of the male and female patients with EEC have adequate sexual function. Most of the female patients have normal fertility while most of the male patients have significantly low fertility.

Keywords : Exstrophy, epispadias, fertility, pregnancy, sexuality, sexual function

Management of chronic prostatitis/chronic syndrome: a systematic review and network meta-analysis.

Anothaisintawee T, Attia J, Nickel JC, Thammakraisorn S, Numthavaj P, McEvoy M, Thakkinstian A.

Section for Clinical Epidemiology and , Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.

JAMA 2011,305,78-86 30

Abstract CONTEXT: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is common, but trial evidence is conflicting and therapeutic options are controversial.

OBJECTIVE: To conduct a systematic review and network meta-analysis comparing mean symptom scores and treatment response among α-blockers, antibiotics, anti-inflammatory drugs, other active drugs (phytotherapy, glycosaminoglycans, finasteride, and neuromodulators), and placebo.

DATA SOURCES: We searched MEDLINE from 1949 and EMBASE from 1974 to November 16, 2010, using the PubMed and Ovid search engines.

STUDY SELECTION: Randomized controlled trials comparing drug treatments in CP/CPPS patients.

DATA EXTRACTION: Two reviewers independently extracted mean symptom scores, quality-of-life measures, and response to treatment between treatment groups. Standardized mean difference and random-effects methods were applied for pooling continuous and dichotomous outcomes, respectively. A longitudinal mixed regression model was used for network meta-analysis to indirectly compare treatment effects.

DATA SYNTHESIS: Twenty-three of 262 studies identified were eligible. Compared with placebo, α-blockers were associated with significant improvement in symptoms with standardized mean differences in total symptom, pain, voiding, and quality-of-life scores of - 1.7 (95% confidence interval [CI], -2.8 to -0.6), -1.1 (95% CI, -1.8 to -0.3), -1.4 (95% CI, -2.3 to -0.5), and -1.0 (95% CI, -1.8 to -0.2), respectively. Patients receiving α-blockers or anti- inflammatory medications had a higher chance of favorable response compared with placebo, with pooled RRs of 1.6 (95% CI, 1.1-2.3) and 1.8 (95% CI, 1.2-2.6), respectively. Contour-enhanced funnel plots suggested the presence of publication bias for smaller studies of α-blocker . The network meta-analysis suggested benefits of antibiotics in decreasing total symptom scores (-9.8; 95% CI, -15.1 to -4.6), pain scores (-4.4; 95% CI, -7.0 to -1.9), voiding scores (-2.8; 95% CI, -4.1 to -1.6), and quality-of-life scores (-1.9; 95% CI, - 3.6 to -0.2) compared with placebo. Combining α-blockers and antibiotics yielded the greatest benefits compared with placebo, with corresponding decreases of -13.8 (95% CI, - 31

17.5 to -10.2) for total symptom scores, -5.7 (95% CI, -7.8 to -3.6) for pain scores, -3.7 (95% CI, -5.2 to -2.1) for voiding, and -2.8 (95% CI, -4.7 to -0.9) for quality-of-life scores.

CONCLUSIONS: α-Blockers, antibiotics, and combinations of these therapies appear to achieve the greatest improvement in clinical symptom scores compared with placebo. Anti- inflammatory therapies have a lesser but measurable benefit on selected outcomes. However, beneficial effects of α-blockers may be overestimated because of publication bias.

Physical activity and semen quality among men attending an infertility clinic

Lauren A. Wise, Sc.D., Daniel W. Cramer, M.D., Mark D. Hornstein, M.D., Rachel K. Ashby, M.D., Stacey A. Missmer, Sc.D.

Fertility and Sterility, 2010, published online 01 December 2010

Objective

To examine the association between regular physical activity and semen quality.

Design

Prospective cohort study.

Setting

Couples attending one of three IVF clinics in the greater Boston area during 1993–2003. At study entry, male participants completed a questionnaire about their general health, , and physical activity. Odds ratios (ORs) and 95% confidence intervals (CIs) were derived using generalized estimating equations models, accounting for potential confounders and multiple samples per man.

Patient(s)

A total of 2,261 men contributing 4,565 fresh semen samples were enrolled before undergoing their first IVF cycles.

Intervention(s)

None.

Main Outcome Measure(s)

Semen volume, sperm concentration, sperm motility, sperm morphology, and total motile sperm (TMS).

Result(s) 32

Overall, none of the semen parameters were materially associated with regular exercise. Compared with no regular exercise, bicycling ≥5 h/wk was associated with low sperm concentration (OR 1.92, 95% CI 1.03–3.56) and low TMS (OR 2.05, 95% CI 1.19–3.56). These associations did not vary appreciably by age, body mass index, or history of male factor infertility.

Conclusion(s)

Although the present study suggests no overall association between regular physical activity and semen quality, bicycling ≥5 h/wk was associated with lower sperm concentration and TMS.

Key Words : Physical activity, bicycling, sperm motility, sperm count, male infertility, IVF Virtual Azoospermia and Cryptozoospermia--Fresh/Frozen Testicular or Ejaculate Sperm for Better IVF Outcome?

Ron Hauser *, Guy Bibi , Leah Yogev , Ariella Carmon , Foad Azem , Amnon Botchan , Haim Yavetz , Sandra E. Klieman , Ofer Lehavi , Ami Amit , and Dalit Ben-Yosef

J Androl. 2010, publ.online 16 Dec. 2010

Men diagnosed as having azoospermia occasionally have a few mature sperm cells in other ejaculates. Other men may have constant, yet very low quality and quantity of sperm cells in their ejaculates, resulting in poor intracytoplasmic sperm injection (ICSI) outcome. It has not been conclusively established which source of sperm cells is preferable for ICSI when both ejaculate and testicular (fresh or frozen) sperm cells are available. It is also unclear whether there is any advantage of fresh over frozen sperm if testicular sperm is to be used. We used ejaculate and/or testicular (fresh or frozen) sperm cells for ICSI in 13 couples. Five of these couples initially underwent ICSI using testicular sperm extracted by TESE, since the males had total azoospermia, and later cycles with ejaculate sperm cells. Ejaculate sperm cells were initially used for ICSI in the other eight patients, and later with testicular sperm cells. The fertilization rate was significantly higher when fresh or frozen-thawed testicular sperm cells were used than when ejaculated sperm cells were used. Likewise, the quality of the embryos from testicular (fresh and frozen) sperm was used was higher than from ejaculated sperm (65.3% vs. 53.2%, respectively, P < 0.05). The use of fresh testicular sperm yielded better implantation rates than both frozen testicular sperm and ejaculate. Therfore, fresh testicular sperm should be considered first for ICSI in patients with virtual azoospermia or cryptozoospermia, due to their superior fertility.

Key words : Assisted reproduction • ICSI • Infertility • Sperm • Sperm retrieval • cryptozoospermia • virtual azoospermia