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December 2010

Recent Literature in Sexual Medicine/

Andrology

Original Research

Prevalence of Sexual Activity and Associated Factors in

Men Aged 75 to 95 Years

A Cohort Study

Zoë Hyde, MPH; Leon Flicker, MBBS, PhD; Graeme J. Hankey, MD; Osvaldo P. Almeida, MD, PhD; Kieran A. McCaul, MPH, PhD; S.A. Paul Chubb, PhD; and Bu B. Yeap, MBBS, PhD

+ Author Affiliations

From Western Australian Centre for Health and Ageing, Centre for Medical Research, Western Australian Institute for Medical Research, School of Medicine and Pharmacology, School of Psychiatry and Clinical Neurosciences, University of Western Australia, Crawley; Royal Perth Hospital, Perth; and Fremantle Hospital, Fremantle, Western Australia, Australia.

Ann Int Med 2010, publ.online Dec. 6,2010

Abstract

Background: Knowledge about sexuality in elderly persons is limited, and normative data are lacking.

Objective: To determine the proportion of older men who are sexually active and to explore factors predictive of sexual activity.

Design: Population-based cohort study.

Setting: Community-dwelling men from Perth, Western Australia, Australia.

Participants: 3274 men aged 75 to 95 years.

Measurements: Questionnaires from 1996 to 1999, 2001 to 2004, and 2008 to 2009 assessed social and medical factors. Sex hormones were measured from 2001 to 2004. Sexual activity was assessed by questionnaire from 2008 to 2009.

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Results: A total of 2783 men (85.0%) provided data on sexual activity. Sex was considered at least somewhat important by 48.8% (95% CI, 47.0% to 50.6%), and 30.8% (CI, 29.1% to 32.5%) had had at least 1 sexual encounter in the past 12 months. Of the latter, 56.5% were satisfied with the frequency of activity, whereas 43.0% had sex less often than preferred. In cross-sectional analyses, increasing age, partner's lack of interest, partner's physical limitations, osteoporosis, prostate cancer, diabetes, antidepressant use, and β-blocker use were independently associated with reduced odds of sexual activity. Living with a partner and having a non–English-speaking background were associated with increased odds. In longitudinal analyses, higher testosterone levels were associated with increased odds of being sexually active. Other factors were similar to the cross-sectional model.

Limitations: Response bias may have influenced findings because sexuality can be a sensitive topic. Attrition may have resulted in a healthier-than-average sample of older men.

Conclusion: One half of elderly men consider sex important, and one third report being sexually active. Men's health problems were associated with lack of sexual activity. Key modifiable risk factors include diabetes, depression, and medication use. Endogenous testosterone levels predict sexual activity, but the role of testosterone therapy remains uncertain.

Primary Funding Source: National Health and Medical Research Council of Australia.

Editorial Comment by the ESSM President: Sexuality in the elderly population > 75 years continues to be topic of taboo and therefore reliable reports/studies on that subject are very rarely found in the literature. With that background the authors have to be congratulated to catch up with this taboo topic and provide valid and reliable data on a representative cohort in Australia. Similar to previous reports from Japan and Germany just over ten years ago this study indicates that sexuality remains a topic of interest in about half of this aged male population with nearly half of them being dissatisfied with their current sexual life/performance. One reason more for us, the physicians, seeing and treating this aged population for many other health reasons on a daily basis to overcome our prejudice and to ask even in these aged people about their sexual life and problems.

Dihydrotestosterone Administration Does Not Increase

Intraprostatic Androgen Concentrations or Alter Prostate

Androgen Action in Healthy Men: A Randomized-Controlled

Trial

Stephanie T. Page*, Daniel W. Lin, Elahe A. Mostaghel, Brett T. Marck, Jonathan L. Wright, Jennifer Wu, John K. Amory, Peter S. Nelson, and Alvin M. Matsumoto

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Department of Medicine (S.T.P., E.A.M., J.W., J.K.A., P.S.N., A.M.M.) and Department of Urology (D.W.L., J.L.W.), University of Washington, Seattle, Washington 98195; Division of Public Health Sciences (D.W.L.) and Division of Human Biology and Clinical Research (E.A.M., P.S.N.), Fred Hutchinson Cancer Research Center, Seattle, Washington 98109; and Geriatric Research, Education, and Clinical Center and Department of Medicine (B.T.M., A.M.M.), V.A. Puget Sound Health Care System, Seattle, Washington 98108 To whom correspondence should be addressed. E-mail: page@u.washington.edu.

Journal of Clinical Endocrinology & Metabolism 2010,publ.online 22 Dec. 2010

Context: Concern exists that androgen treatment might adversely impact prostate health in older men. Dihydrotestosterone (DHT), derived from local conversion of testosterone to DHT by 5-reductase enzymes, is the principal androgen within the prostate. Exogenous androgens raise serum DHT concentrations, but their effects on the prostate are not clear.

Objective: To determine the impact of large increases in serum DHT concentrations on intraprostatic androgen concentrations and androgen action within the prostate.

Design: Double-blind, randomized, placebo-controlled.

Setting: Single academic medical center.

Participants: 31 healthy men ages 35–55.

Intervention: Daily transdermal DHT or placebo gel.

Main Outcome Measures: Serum and prostate tissue androgen concentrations and prostate epithelial cell gene expression after 4 wk of treatment.

Results: Twenty-seven men completed all study procedures. Serum DHT levels increased nearly sevenfold, while testosterone levels decreased in men treated with daily transdermal DHT gel but were unchanged in the placebo-treated group (P < 0.01 between groups). In contrast, intraprostatic DHT and testosterone concentrations on d 28 were not different between groups (DHT: placebo = 2.8 ± 0.2 vs. DHT gel = 3.1 ± 0.5 ng/g; T: placebo = 0.6 ± 0.2 vs. DHT gel = 0.4 ± 0.1, mean ± SE). Similarly, prostate volume, prostate-specific antigen, epithelial cell proliferation, and androgen-regulated gene expression were not different between groups.

Conclusions: Robust supraphysiologic increases in serum DHT, associated with decreased serum T, do not significantly alter intraprostatic levels of DHT, testosterone, or prostate epithelial cell androgen–regulated gene expression in healthy men. Changes in circulating androgen concentrations are not necessarily mimicked within the prostate microenvironment, a finding with implications for understanding the impact of androgen therapies in men.

Editorial Comment by the ESSM President: No question this well designed and well done study is a landmark publication because it shows for the first time that even

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7fold increased DHT plasma levels do not have any impact on the intraprostatic DHT- and T- levels. This study should take away the fear regarding a potential negative effect of T-replacement therapy on the prostate tissue either with regard to BPH or PCA development from all these many physicians who refuse their hypogonadal patients T-replacement therapy because of those concerns. This elegant study shows in addition that the up to 3fold elevated DHT levels, we sometimes find in our hypogonadal patients after T-gel replacement therapy, may not harm our patients' prostate health because they finally do not translate into intraprostatic DHT and T-levels.

Male Sexual Dysfunktion:

Basic Research

Vasoactive intestinal polypeptide, an erectile neurotransmitter, improves erectile function more significantly in castrated rats than in normal rats

Min-Guang Zhang1, Zhou-Jun Shen1,5,*, Cun-Ming Zhang1, Wei Wu2, Ping-Jin Gao3, Shan-Wen Chen4, Wen-Long Zhou1

BJU International 2010, Article first published online: 16 DEC 2010

Keywords: androgen;, vasoactive intestinal polypeptide;, erectile

function;,castration;,signaling pathway

OBJECTIVE Androgen is essential for physiological erection. Vasoactive intestinal

polypeptide (VIP) is an important erectile neurotransmitter. While previous studies

demonstrated that VIP expression in the penis was androgen-independent, it remains

controversial whether androgen has any effect on VIP-mediated erection. The present study

aims to investigate the regulatory role of androgen in VIP-mediated erectile effect.

MATERIALS AND METHODS Male SD rats were divided into a control group, a castration

group, and a castration-with-testosterone-replacement group. Four weeks later, each group

was subdivided into low and high-dose VIP subgroups and subjected to intracavernous

injection of 0.5 and 2 µg VIP, respectively. Erectile function was tested by recording

intracavernosal pressure (ICP) and mean arterial blood pressure (MAP) before and after VIP

injection. The expressions of the VIP-receptor (VPAC2), G-protein stimulatory and inhibitory

alpha subunits (Gs- , Gi- ), and PDE3A in rat corpus cavernosum (CC) was qualified by

real-time PCR and Western blot analysis.

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RESULTS Castration reduced erectile function while testosterone restored it. VIP improved

erectile function in a dose-dependent manner. High-dose VIP significantly enhanced erectile

function in castrated rats and there was no difference of ICP/MAP among three groups after

injection of high-dose VIP. Low-dose VIP also resulted in a higher improvement of erectile

function in castrated rats, although the ICP/MAP was lower in these rats than in the other two

groups. VPAC2 and Gs- were up-regulated while Gi- and PDE3A were down-regulated in

CC of castrated rats.

CONCLUSIONS VIP improves erectile function much more significantly in hypogonadal

condition, mainly due to the higher expression of VPAC2, Gs- , and lower expression of Gi-

and PDE3A in CC of castrated rats. Androgen may negatively regulate the erectile effect

of VIP.

The penis in diabetes: structural analysis of connective tissue and smooth muscle alterations in a rabbit model

Marcelo Abidu-Figueiredo, Ilma C. Ribeiro, Mauricio A. Chagas, Luiz E. M. Cardoso,

Waldemar S. Costa, Francisco J. B. Sampaio

BJU International 2010,Article first published online: 16 DEC 2010

Keywords: penis;rabbit;stereology;histology;diabetes;erectile dysfunction

Study Type – Aetiology (case control) Level of Evidence 3b

OBJECTIVE To assess the volumetric density of collagen, elastic system fibres and smooth

muscle cells in the corpus cavernosum (CC), corpus spongiosum (CS) and tunica albuginea

(TA) in the penis of diabetic rabbits.

MATERIALS AND METHODS Twenty-six New Zealand white rabbits were used. Diabetes

was induced at 8 weeks of age in 13 rabbits by i.v. injection of 100 mg/kg of alloxan. The

remaining 13 rabbits served as a control group. After 10 weeks, the rabbits were killed using

sodium thiopenthal. Midshaft penile fragments were obtained and processed by routine

histological techniques. Stereological analysis of collagen, elastic system fibres and smooth

muscle was performed in 5-µm sections by using a M42 test grid system. Data were

expressed as volumetric density (Vv; %). Collagen organization was evaluated by Picrosirius

red staining under polarization.

RESULTS In the TA of diabetic rabbits, thickness increased by 88% (P < 0.001) with an

enhanced collagen turnover. Moreover, the elastic fibre content was 34% higher (P < 0.001).

In the CC of diabetics, collagen was diminished by 45% (P < 0.001) with a more organized

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collagen. The elastic fibres were decreased by 46% (P < 0.001). Diabetes induced a 11%

increase in CS collagen (P < 0.024) with an enhanced collagen turnover. Smooth muscle in

the CC of diabetic rabbits was increased by 40% (P < 0.001), whereas, in the CS, it was

decreased by a similar amount (P < 0.001).

CONCLUSIONS Penile tissues were affected differently by diabetes, possibly as a result of

cellular heterogeneity. These changes could have an impact on blood flow and tissue

resistance, and therefore might adversely affect erection.

Frequent Phosphodiesterase 11A Gene (PDE11A) Defects in Patients with Carney Complex (CNC) Caused by PRKAR1A Mutations: PDE11A May Contribute to Adrenal and Testicular Tumors in CNC as a Modifier of the Phenotype

Rossella Libé, Anelia Horvath, Delphine Vezzosi, Amato Fratticci, Joel Coste, Karine Perlemoine, Bruno Ragazzon, Marine Guillaud-Bataille, Lionel Groussin, Eric Clauser, Marie-Laure Raffin-Sanson, Jennifer Siegel, Jason Moran, Limor Drori-Herishanu, Fabio Rueda Faucz, Maya Lodish, Maria Nesterova, Xavier Bertagna, Jerome Bertherat*, and Constantine A. Stratakis

Institut National de la Santé et de la Recherche Médicale Unité 1016 (R.L., D.V., A.F., K.P., B.R., L.G., X.B., J.B.), Institut Cochin, Centre National de la Recherche Scientifique Unité Mixte de Recherche 8104, Paris, France; Université Paris 5 (R.L., D.V., A.F., K.P., B.R., L.G., X.B., J.B.), Paris, France; Assistance Publique Hôpitaux de Paris (R.L., L.G., X.B., J.B.), Hôpital Cochin, Department of Endocrinology, Reference Center for Rare Adrenal Diseases, 75014 Paris, France; Section on Endocrinology and Genetics (A.H., J.S., J.M., L.D.H., F.R.F., M.L., M.N., C.A.S.), Program on Developmental Endocrinology and Genetics, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892; Assistance Publique Hôpitaux de Paris (J.C.), Hôpital Cochin, Department of Biostatistics, Paris, France; Assistance Publique Hôpitaux de Paris (M.G.B., E.C.), Hôpital Cochin, Oncogenetic Unit, Paris, France; Assistance Publique Hôpitaux de Paris (M.L.R.S.), Hôpital Ambroise Paré, Department of Endocrinologie (F.R.F.), Boulogne sur Seine and University of Versaille St. Quentin, 92210 France; and Laboratory of Molecular Genetics, Pontificia Universidade Catolica do Parana, 80215-901 Curitiba, Brazil

Journal of Clinical Endocrinology & Metabolism 2010,publ.online Nov.3

Background: Carney complex (CNC) is an autosomal dominant multiple neoplasia, caused mostly by inactivating mutations of the regulatory subunit 1A of the protein kinase A (PRKAR1A). Primary pigmented nodular adrenocortical disease (PPNAD) is the most frequent endocrine manifestation of CNC with a great inter-individual variability. Germline, protein-truncating mutations of phosphodiesterase type 11A (PDE11A) have been described to predispose to a variety of endocrine tumors, including adrenal and testicular tumors.

Objectives: Our objective was to investigate the role of PDE11A as a possible gene modifier of the phenotype in a series of 150 patients with CNC.

Results: A higher frequency of PDE11A variants in patients with CNC compared with healthy controls was found (25.3 vs. 6.8%, P < 0.0001). Among CNC patients, those with PPNAD

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were significantly more frequently carriers of PDE11A variants compared with patients without PPNAD (30.8 vs. 13%, P = 0.025). Furthermore, men with PPNAD were significantly more frequently carriers of

PDE11A sequence variants (40.7%) than women with PPNAD (27.3%) (P < 0.001). A higher frequency of PDE11A sequence variants was also found in patients with large-cell calcifying Sertoli cell tumors (LCCSCT) compared with those without LCCSCT (50

vs. 10%, P = 0.0056). PDE11A variants were significantly associated with the copresence of PPNAD and LCCSCT in men: 81 vs. 20%, P < 0.004). The simultaneous inactivation of PRKAR1A and

PDE11A by small inhibitory RNA led to an increase in cAMP-regulatory element-mediated transcriptional activity under basal conditions and after stimulation by forskolin.

Conclusions: We demonstrate, in a large cohort of CNC patients, a high frequency of PDE11A

variants, suggesting that PDE11A is a genetic modifying factor for the development of testicular and adrenal tumors in patients with germline PRKAR1A mutation.

Erectile Dysfunction

Erectile Dysfunction and Later Cardiovascular Disease in Men With Type 2 Diabetes

Prospective Cohort Study Based on the ADVANCE (Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified-Release Controlled Evaluation) Trial G. David Batty, PhD*

, , ,*, Qiang Li, MBiostat , Sébastien Czernichow, MD, PhD , , Bruce

Neal, MD, PhD , Sophia Zoungas, MD, PhD ,||, Rachel Huxley, PhD , Anushka Patel, MD, PhD , Bastiaan E. de Galan, MD, PhD ,¶, Mark Woodward, PhD ,#, Pavel Hamet, MD, PhD**, Stephen B. Harrap, MD, PhD , Neil Poulter, MD, PhD , John Chalmers, MD, PhD ADVANCE Collaborative Group

* Medical Research Council Social and Public Health Sciences Unit, Glasgow, United Kingdom George Institute for International Health, Sydney, Australia UCL Epidemiology and Public Health, London, United Kingdom Department of Public Health, Avicenne Hospital, University of Paris 13, Bobigny, France

|| School of Public Health, Monash University, Melbourne, Australia ¶ Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands # Mount Sinai School of Medicine, New York, New York ** Research Centre, Centre Hospitalier de l'Université de Montréal, Montreal, Quebec, Canada

Department of Physiology, University of Melbourne, Melbourne, Australia Imperial College and St. Mary's Hospital, London, United Kingdom

Manuscript received September 24, 2009; revised manuscript received April 15, 2010, accepted April 30, 2010.

J Am Coll Cardiol, 2010; 56:1908-1913,

Objectives: The aim of this study was to examine the relationship between erectile problems in men and cardiovascular disease (CVD) mortality.

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Background: Although there are plausible mechanisms linking erectile dysfunction (ED) with coronary heart disease (CHD) and stroke, studies are scarce.

Methods: In a cohort analysis of the ADVANCE (Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified-Release Controlled Evaluation) trial population, 6,304 men age 55 to 88 years with type 2 diabetes participated in a baseline medical examination when inquiries were made about ED. Over 5 years of follow-up, during which study members attended repeat clinical examinations, the presence of fatal and nonfatal CVD outcomes, cognitive decline, and dementia was ascertained.

Results: After adjusting for a range of covariates, including existing illness, psychological health, and classic CVD risk factors, relative to those who were free of the condition, baseline ED was associated with an elevated risk of all CVD events (hazard ratio: 1.19; 95% confidence interval: 1.08 to 1.32), CHD (hazard ratio: 1.35; 95% confidence interval: 1.16 to 1.56), and cerebrovascular disease (hazard ratio: 1.36; 95% confidence interval: 1.11 to

1.67). Men who experienced ED at baseline and at 2-year follow-up had the highest risk for these outcomes.

Conclusions: In this cohort of men with type 2 diabetes, ED was associated with a range of CVD events.

Key Words: coronary heart disease • epidemiology • erectile dysfunction • stroke

Genome-Wide Association Study to Identify Single Nucleotide Polymorphisms (SNPs) Associated With the Development of Erectile Dysfunction in African-American Men After Radiotherapy for Prostate Cancer Sarah L. Kerns Ph.D., M.P.H.*, Harry Ostrer M.D.*, Richard Stock M.D.†, William Li

M.D.‡, Julian Moore D.O.†, Alexander Pearlman Ph.D.*, Christopher Campbell B.S.*,

Yongzhao Shao Ph.D.§, Nelson Stone M.D.†, , Lynda Kusnetz B.A.† and Barry S.

Rosenstein Ph.D.†, ¶, ,

Department of Urology, Mount Sinai School of Medicine, New York, NY

† Department of Radiation Oncology, Mount Sinai School of Medicine, New York, NY

‡ Department of Radiation Oncology, Queens/Elmhurst Hospital Center, Jamaica, NY

* Department of Pediatrics, New York University School of Medicine, New York, NY

§ Division of Biostatistics, New York University School of Medicine, New York, NY

¶ Department of Radiation Oncology, New York University School of Medicine, New York,

NY

International Journal of Radiation Oncology*Biology*Physics 2010, 78: 1292-1300

Purpose

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To identify single nucleotide polymorphisms (SNPs) associated with erectile dysfunction (ED)

among African-American prostate cancer patients treated with external beam radiation

therapy.

Methods and Materials

A cohort of African-American prostate cancer patients treated with external beam radiation

therapy was observed for the development of ED by use of the five-item Sexual Health

Inventory for Men (SHIM) questionnaire. Final analysis included 27 cases (post-treatment

SHIM score ≤7) and 52 control subjects (post-treatment SHIM score ≥16). A genome-wide

association study was performed using approximately 909,000 SNPs genotyped on

Affymetrix 6.0 arrays (Affymetrix, Santa Clara, CA).

Results

We identified SNP rs2268363, located in the follicle-stimulating hormone receptor (FSHR)

gene, as significantly associated with ED after correcting for multiple comparisons

(unadjusted p = 5.46 × 10−8, Bonferroni p = 0.028). We identified four additional SNPs that

tended toward a significant association with an unadjusted p value < 10−6. Inference of

population substructure showed that cases had a higher proportion of African ancestry than

control subjects (77% vs. 60%, p = 0.005). A multivariate logistic regression model that

incorporated estimated ancestry and four of the top-ranked SNPs was a more accurate

classifier of ED than a model that included only clinical variables.

Conclusions

To our knowledge, this is the first genome-wide association study to identify SNPs

associated with adverse effects resulting from radiotherapy. It is important to note that the

SNP that proved to be significantly associated with ED is located within a gene whose

encoded product plays a role in male gonad development and function. Another key finding

of this project is that the four SNPs most strongly associated with ED were specific to

persons of African ancestry and would therefore not have been identified had a cohort of

European ancestry been screened. This study demonstrates the feasibility of a genome-wide

approach to investigate genetic predisposition to radiation injury.

Author Keywords: Radiation injury; Prostate cancer; Genome-wide association study; African American; Admixture

Hormonal profile, the PROGINS polymorphism, and erectile dysfunction complaints: data from a population-based survey

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Monica L. Andersen, Ph.D. Tathiana A. Alvarenga, M.S., Diego R. Mazzotti, B.S., Camila Guindalini, Ph.D., Renata Pellegrino, M.S., Karina F. Barrueco, B.S., Rogerio Santos-Silva, Ph.D., Lia R. Bittencourt, M.D., Ph.D., Sergio Tufik, M.D., Ph.D.

Objective

To evaluate a potential association among the hormonal profile, PROGINS polymorphism, and erectile dysfunction (ED) complaints in a large population-based sample in Sao Paulo, Brazil.

Fertility Sterility 2010, published online 22 November 2010.

Design

Population-based questionnaire study.

Setting

Interviews, sleep recording, and blood sample were conducted in a sleep institute.

Patient(s)

The total study participants included 467 men.

Intervention(s)

General information was obtained through interviews, and a blood sample was collected for hormone levels, DNA extraction, and PROGINS genotyping.

Main Outcome Measure(s)

The effect of progesterone and the PROGINS polymorphism on the risk of developing ED were measured by questionnaire and blood sample.

Result(s)

Progesterone, prolactin, testosterone, and estradiol levels did not differ between the genotype groups (T1/T1 and T1/T2+T2/T2). No significant genotypic or allelic differences were found between individuals with ED complaints and controls. Multivariate logistic regression analyses including age, body mass index, hypertension, diabetes, apnea-hypopnea index, and genetic ancestry estimation, as well as the PROGINS polymorphism, confirmed the lack of association between the T2 allele carriers and the risk of ED (odds ratio = 0.80; 95% confidence interval = 0.40–1.62).

Conclusion(s)

This is the first study to demonstrate the genotypic and allelic frequencies of the PROGINS polymorphism in a large population-based sample of men. The results do not support a direct role for the PROGINS polymorphism in the risk of developing ED; however, further examination of other variants within PR gene will be necessary to completely rule out an effect.

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Key Words: Sleep, progesterone, PROGINS, erectile dysfunction, prolactin, testosterone, erection

Corpus cavernosum electromyography: could it be a

parameter to predict ageing?

M. Aldemir, K. Ağras, K. Ener, D. Dehni, Ö. Kayıgil

Andrologia,2010 ,42: 343–348,

Keywords:Ageing;corpus cavernosum;electromyography;erectile dysfunction

Summary

In this study, we investigated whether electromyography of corpus cavernosum (CC-EMG) results vary with age and whether CC-EMG could be a parameter to predict ageing of cavernous smooth muscle. Recordings of electrical activity of corpus cavernosum (EACC) were retrospectively investigated in 134 patients with erectile dysfunction. Penile colour Doppler ultrasonography and cavernosometry were also performed for all of the patients. The total number and duration of EACC and amplitudes between positive and negative peaks were compared between the flask state for 10 min and after intracavernosal papaverine injection. The mean age of the 47 patients in group 1 was 35.2 ± 6.3 years (range, 23–44), the mean age of the 45 patients in group 2 was 51.1 ± 3.1 years (range, 45–56) and the mean age of the 42 patients in group 3 was 61.8 ± 4.6 years (range, 57–77). Total IIEF-5 score was 7.6 ± 2.1 in group 1, 7.9 ± 2.4 in group 2 and 7.9 ± 2.1 in group 3. There were no statistically significant differences among the groups regarding electrical potential frequencies, durations and amplitudes of electromyographic recordings. Conclusion: We do not think that CC-EMG findings could be used efficiently as a predictor of ageing.

The application of digital pulse amplitude tonometry to the

diagnostic investigation of endothelial dysfunction in men

with erectile dysfunction

A. Aversa, D. Francomano, R. Bruzziches, M. Pili, M. Natali, G. Spera, A. Lenzi

Andrologia 2010 Article first published online: 28 NOV 2010

Keywords:Arterial stiffness;early detection;penile duplex ultrasound;peripheral arterial tonometry;reactive hyperaemia;vascular risk factors

Abstract

The application of digital pulse amplitude by fingertip peripheral arterial tonometry (PAT) device in patients with erectile dysfunction (ED) has never been performed. We investigated the diagnostic value of reactive hyperaemia (RH) and augmentation index (AI) as evaluated using PAT in men with ED of any origin. A total of 40 patients underwent diagnostic investigation for ED, including dynamic penile duplex ultrasound (PDU) and PAT device. Moreover, 30 patients without ED served as controls. According to PDU cutoff at 35 cm/sec, patients were divided into vascular (n = 30) and nonvascular (n = 10) ED aetiology.

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Moreover, controls with (n = 10) or without (n = 20) vascular risk factors (VRFs) were studied in a separate analysis. Average RH-PAT was not different in men with or without ED (P = 0.56) independently of VRFs. The AI was higher in men with ED compared with the controls (P < 0.0001) as well as when controlled for the presence or absence of VRFs (P < 0.0001). An inverse relationship between AI and PSV was also found (r2 = −0.72, P < 0.0001). In conclusion, an increased AI but not an impaired RH-PAT is present in men with vascular ED independently of VRFs and may represent an early detection of vascular impairment that may precede endothelial dysfunction in populations at low risk for developing vascular ED.

Oncology

Glans Resurfacing for the Treatment of Carcinoma In Situ of the Penis: Surgical Technique and Outcomes

Majid Shabbir, Asif Muneer, Jas Kalsi, Chitranjan J. Shukla, Evangelos Zacharakis, Giulio Garaffa, David Ralph, Suks Minhas.

Eur Urol 2010, Volume 59, issue 1, pages e1-e4, January 2011

Abstract

Background

The management of carcinoma in situ (CIS) of the penis is controversial, with relatively high local recurrence rates after minimally invasive therapies.

Objective

Report the surgical technique and outcome of partial glans resurfacing (PGR) and total glans resurfacing (TGR) as primary treatment modalities for CIS of the glans penis.

Design, setting, and participants

Between 2001 to 2010, 25 patients with biopsy-proven CIS underwent TGR (n = 10) or PGR (n = 15), defined as <50% of the glans requiring resurfacing. All patients were surveyed clinically every 3 mo for 2 yr and every 6 mo thereafter.

Surgical procedure

Excision of the glans epithelium and subepithelium of either the entire glans or the locally affected area, with a macroscopic clear margin. The penis was then reconstructed using a split skin graft.

Measurements

Positive surgical margin (PSM) rates and rates of recurrence and progression were collated. Complications, cosmesis, and patient satisfaction were evaluated.

Results and limitations

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Mean follow-up was 29 mo (range: 2–120 mo). There were no postoperative complications, and 24 of 25 patients (96%) had complete graft take with excellent cosmesis. Overall, 12 of 25 patients (48%) had PSMs. Only 7 of 25 (28%) required further surgery, 2 of 25 (8%) for extensive CIS at the margin and 5 of 25 (20%) for unexpected invasive disease. Additional surgery consisted of further resurfacing in 4 of 25 cases (16%) or glansectomy in 3 of 25 cases (12%). Those undergoing further surgery had no further compromise to their oncologic outcome. The overall local recurrence rate was 4%. There were no cases of progression.

Conclusions

Glans resurfacing is a safe and effective primary treatment for CIS. The procedure maintains a functional penis without compromising oncologic control, while ensuring that definitive histopathlogy is obtained. Glans resurfacing has a low risk of recurrence and progression. Patients need to be warned that approximately 28% will require further surgery for PSM or understaging of their primary disease, although the need for further surgery does not compromise oncologic control.

Take Home Message

Glans resurfacing is a safe and effective primary treatment for carcinoma in situ. It maintains a functional penis without compromising oncologic control, and provides definitive histopathlogy. It has a low risk of recurrence and progression, and has no worse outcome if further surgery is required.

Keywords: Penile Cancer, Surgery, Carcinoma in situ, Glans resurfacing.

Changes in Penile Length After Robot-Assisted Laparoscopic Radical Prostatectomy.

Engel JD, Sutherland DE, Williams SB, Wagner KR.

1 Department of Urology, George Washington University Hospital , Washington, District of Columbia.

J Endourol. 2010 Nov 29. [Epub ahead of print]

Abstract

Abstract Background and Purpose: Radical prostatectomy is commonly performed for the treatment of patients with prostate cancer. Several studies have demonstrated a reduction in penile size after open radical retropubic prostatectomy. The objective of this study is to describe changes in penile length after after robot-assisted laparoscopic radical prostatectomy (RALRP). Patients and Methods: We performed a randomized, open label, multicenter study in men with normal erectile function who underwent bilateral nerve-sparing radical prostatectomy. We evaluated changes in measured stretched penile length (SPL), a secondary end point of the study, in a subset of men from a single site who underwent RALRP by one surgeon. They were randomized to either intraurethral alprostadil 125 to 250 μg daily or oral sildenafil citrate 50 mg daily for 9 months. SPL was measured from pubic bone to coronal sulcus using a semirigid ruler before surgery and at 1, 3, 6, 9, 10, and 11 months. Results: A total of 127 patients were enrolled and 94 completed the 11-month follow-up. The mean patient age was 56.5 years. Baseline mean SPL (cm) before surgery was 11.77 and decreased to 11.13 at 1 month (P < 0.0001). A trend toward recovery of SPL was seen at 3 and 6 months. Mean SPL was not significantly different from baseline at 9, 10, and 11 months. Conclusions: This report describes changes in SPL over time after RALRP

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for prostate cancer. The expected decrease in length was observed shortly after surgery, but, by 9 months, penile length had returned to the preoperative measurement

Is a return to baseline sexual function possible? An analysis of

sexual function outcomes following laparoscopic radical

prostatectomy

Adam W. Levinson, Hugh J. Lavery, Nicholas T. Ward, Li-Ming Su and Christian P. Pavlovich

World J Urol. 2010, publ. online 24 Nov. 2010

Abstract

Objectives

Outcome measures following radical prostatectomy are not standardized. Though excellent

potency rates are widely reported, few studies address a return to baseline function. We

analyze validated sexual health-related quality-of-life outcomes by a strict definition, a return

to baseline function, and compare them to less stringent, yet more frequently referenced,

categorical definitions of potency.

Methods

Patients undergoing laparoscopic radical prostatectomy from April 2001 to September 2007

completed the Expanded Prostate Cancer Index Composite (EPIC) questionnaire at baseline

and 3, 6, 12, and 24 months postoperatively. We defined a return to baseline as a recovery

to greater than one-half standard deviation of the studied population below the patient’s own

baseline (clinically detectable threshold). We compared these outcomes to a categorical

definition of potency involving intercourse frequency. To limit confounders, we performed

subset analyses of preoperatively potent men who received bilateral nerve preservation.

Factors predictive of return to baseline function were assessed in multivariable analysis.

Results

A total of 568 patients met inclusion criteria. Mean age and follow-up were 57.2 years and

16.9 months, respectively. Using the categorical definition, 85% of preoperatively potent men

with bilateral nerve preservation were “potent” at 24 months; however, only 27% returned to

their baseline sexual function. In multivariable analyses baseline function, number of nerves

spared, and age were independent predictors of a return to baseline function.

Conclusion

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While most preoperatively potent men who receive bilateral nerve preservation engage in

intercourse postoperatively, few return to their baseline sexual function. We believe that

these data provide context for the expectations of patients who elect extirpative therapy.

Keywords Radical prostatectomy - Sexual function - Quality of life - Outcomes

assessment - Laparoscopy - Prostate cancer - Erectile dysfunction

Nerve-sparing radical prostatectomy with nightly low-dose sildenafil : Rehabilitation of erectile function.

[Article in German]

Bannowsky A, Schulze H, van der Horst C, Jünemann KP.

Klinik für Urologie und Kinderurologie, Universitätsklinikum Schleswig-Holstein,Campus Kiel,

Kiel, Deutschland, andreas.bannowsky@klinikum-os.de

Urologe A. 2010 Nov 26. [Epub ahead of print]

Abstract

OBJECTIVE: The purpose of this study was to evaluate the effect of low-dose sildenafil (25

mg) for rehabilitation of erectile function after nerve-sparing radical prostatectomy.

PATIENTS AND METHODS: In a prospective study, 43 sexually active patients underwent

nerve-sparing retropubic radical prostatectomy. Rigiscan® measurement of nocturnal penile

tumescence and rigidity (NPTR) was carried out 7-14 days after surgery. A group of 23

patients with preserved nocturnal erections received sildenafil 25 mg/day at night to support

recovery of erectile function. A control group of 18 patients underwent follow-up without PDE-

5 inhibitors. Evaluation using the IIEF-5 questionnaire was performed 6, 12, 24, 36, 52 and

78 weeks after the operation.

RESULTS: Of 43 patients, 41 (95%) showed 1-5 erections during the first night after catheter

removal. In the group receiving daily sildenafil, the mean IIEF-5 score decreased or

increased from 20.8 preoperatively to 3.6 at 6 weeks, 3.8 at 12 weeks, 5.9 at 24 weeks, 9.6

at 36 weeks, 14.1 at 52 weeks and 19.3 at 78 weeks after prostatectomy. In the control

group, the mean preoperative IIEF-5 score of 21.2 decreased or increased to 2.4 at 6 weeks,

3.8 at 12 weeks, 5.3 at 24 weeks, 6.4 at 36 weeks, 9.3 at 52 weeks and 13.2 at 78 weeks.

Statistical evaluation showed significant differences regarding the IIEF-5 score and recovery

period of erectile function between the groups (p<0.001), with potency rates of 92 vs 68%.

CONCLUSION: The measurement of NPTR after nerve-sparing radical prostatectomy

showed erectile function as early as the first night after catheter removal. In cases of early

penile erections, daily low-dose PDE-5 inhibitors lead to a significant

improvement/acceleration of erectile function recovery.

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Risk of colorectal cancer in men on long-term androgen

deprivation therapy for prostate cancer

Silke Gillessen, Arnoud Templeton, Giancarlo Marra, Yong-Fang Kuo, Emanuele Valtorta and Vahakn B. Shahinian

+ Author Affiliations

Affiliations of authors: Department of Medical Oncology, Kantonsspital, St Gallen, Switzerland (SG, AT); Department of Medicine, Institute of Molecular Cancer Research, University of Zurich, Zurich, Switzerland (GM, EV); Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX (Y-FK); Department of Internal Medicine, University of Michigan, Ann Arbor, MI (VBS)

JNCI J Natl Cancer Inst (2010) First published online: November 10, 2010

Abstract

Background Androgen deprivation with gonadotropin-releasing hormone (GnRH) agonists or orchiectomy is a common but controversial treatment for prostate cancer. Uncertainties remain about its use, particularly with increasing recognition of serious side effects. In animal studies, androgens protect against colonic carcinogenesis, suggesting that androgen deprivation may increase the risk of colorectal cancer.

Methods We identified 107 859 men in the linked Surveillance, Epidemiology, and End Results (SEER)–Medicare database who were diagnosed with prostate cancer in 1993 through 2002, with follow-up available through 2004. The primary outcome was development of colorectal cancer, determined from SEER files on second primary cancers. Cox proportional hazards regression was used to assess the influence of androgen deprivation on the outcome, adjusted for patient and prostate cancer characteristics. All statistical tests were two-sided.

Results Men who had orchiectomies had the highest unadjusted incidence rate of colorectal cancer (6.3 per 1000 person-years; 95% confidence interval [CI] = 5.3 to 7.5), followed by men who had GnRH agonist therapy (4.4 per 1000 person-years; 95% CI = 4.0 to 4.9), and men who had no androgen deprivation (3.7 per 1000 person-years; 95% CI = 3.5 to 3.9). After adjustment for patient and prostate cancer characteristics, there was a statistically significant dose–response effect (Ptrend = .010) with an increasing risk of colorectal cancer associated with increasing duration of androgen deprivation. Compared with the absence of these treatments, there was an increased risk of colorectal cancer associated with use of GnRH agonist therapy for 25 months or longer (hazard ratio [HR] = 1.31, 95% CI = 1.12 to 1.53) or with orchiectomy (HR = 1.37, 95% CI = 1.14 to 1.66).

Conclusion Long-term androgen deprivation therapy for prostate cancer is associated with an increased risk of colorectal cancer.

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Impact of androgen-deprivation therapy on physical

function and quality of life in men with nonmetastatic

prostate cancer.

Alibhai SM, Breunis H, Timilshina N, Johnston C, Tomlinson G, Tannock I, Krahn M, Fleshner NE, Warde P, Canning SD, Klotz L, Naglie G.

MSc, University Health Network, Room EN14-214, 200 Elizabeth St, Toronto, Ontario, Canada, M5G 2C4; shabbir.alibhai@uhn.on.ca.

J Clin Oncol. 2010 Dec 1;28(34):5038-45. Epub 2010 Nov 1

Abstract

PURPOSE This prospective longitudinal study evaluated the effect of androgen deprivation therapy (ADT) on objective and self-reported physical function. PATIENTS AND METHODS Men with nonmetastatic prostate cancer (PC) starting continuous ADT were enrolled in this matched cohort study. Physical function was assessed with the 6-minute walk test (6MWT), grip strength, and the timed-up-and-go (TUG) test, representing endurance and upper and lower extremity strength, respectively. Quality of life (QOL) was measured with the Medical Outcomes Study Short-Form 36 (SF-36) questionnaire. Subjects were assessed at baseline, 3, 6, and 12 months. Two control groups (PC without ADT; no PC), matched on age, education, and baseline function were enrolled. Mixed effects regression models were fitted, adjusting for baseline covariates. Results We enrolled 87 patients on ADT, 86 PC controls, and 86 healthy controls; groups were similar in age (mean, 69.1 years; range, 50 to 87) and physical function. The 6MWT distance remained stable in the ADT group (P = .96) but improved in both control groups (P < .05). Grip strength declined in the ADT group (P = .04), remained stable in PC controls (P = .31), and improved in healthy controls (P = .008). TUG scores remained stable over time and across groups (P > .10). The SF-36 physical function summary score declined in the ADT group (P < .001), but increased in both control groups (P < .001). Negative effects on outcomes were observed within 3 months of starting ADT and were generally independent of age. CONCLUSION Endurance, upper extremity strength, and physical components of QOL are affected within 3 months of starting ADT. Up-front exercise interventions to counteract these losses are warranted.

Androgen Deprivation Therapy and Cataract Incidence

Among Elderly Prostate Cancer Patients in the United

States

Jennifer Beebe-Dimmer PhD, a, , Hal Morgenstern PhDa, Karynsa Cetin MPHa, Cecilia Yee MSa, Monina Bartoces PhDa, Vahakn Shahinian MDa, Jon Fryzek PhDa, John Acquavella PhDa and Kendra L. Schwartz MDa

a Division of Population Studies and Prevention, Karmanos Cancer Institute (J.B.-D., C.Y., K.L.S.), Detroit, MI; Departments of Internal Medicine (J.B.-D., C.Y.) and Family Medicine & Public Health Sciences (M.B., K.L.S.), Wayne State University, Detroit, MI; Departments of Epidemiology and Environmental Health Sciences and Comprehensive Cancer Center (H.M.), University of Michigan School of Public Health, Ann Arbor, MI; University of Michigan

18

Medical School (V.S.), Ann Arbor, MI; and Department of Global Epidemiology, Amgen Inc. (K.C., J.F., J.A.), Thousand Oaks, CA

Annals of Epidemiology. Available online 15 December 2010.

Purpose

The side-effects associated with androgen deprivation therapy (ADT) include weight gain, dyslipidemia, and insulin resistance. As cataracts have been linked to these metabolic abnormalities, an increased risk of cataract may be another adverse consequence of ADT use.

Methods

Using data from the Surveillance, Epidemiology and End Results-Medicare database, we estimated risk of cataract associated with ADT among 65,852 prostate-cancer patients. ADT treatment was defined as at least one dose of a gonadotropin-releasing hormone agonist or orchiectomy within 6 months after prostate cancer diagnosis. The outcome measure was a first claim of cataract diagnosis identified in Medicare claim files. Cox regression was used to estimate hazard ratios (HR) for the effects of ADT treatment, controlling for confounders.

Results

Gonadotropin-releasing hormone agonist use was associated with a modest increase in cataract incidence (HR 1.09, 95% confidence interval 1.06−1.12). Orchiectomy was also associated with an increased risk of cataract among men with no history of cataract prior to prostate cancer diagnosis (HR 1.26, 95% confidence interval 1.07−1.47).

Conclusions

In the first systematic investigation of the association between ADT and cataract, our results suggest an elevation in the incidence of cataract among ADT users. Further study, preferably prospective in design, is needed to provide additional evidence to support or refute these findings.

Key Words: Epidemiology; GnRH Agonist; Lens Opacities; Orchiectomy; Prostate Cancer; SEER-Medicare

Abbreviations: ADT, androgen deprivation therapy; SEER, Surveillance, Epidemiology and End Results; HMO, health maintenance organization; GnRH, gonadotropin-releasing hormone; CI, confidence interval

Peyronie’s disease

The most commonly altered type of Peyronie’s disease

deformity under oral colchicine treatment is lateral

curvature that mostly shifts to the dorsal side

T. Akman1, O. Sanli2, N. Uluocak3, F.

19

Andrologia 2010, first published online: 28 NOV 2010

Keywords:Altered deformity;colchicine;curvature;Peyronie’s disease

Summary

The aim of the present study was to evaluate changes in clinical characteristics of Peyronie’s disease (PD) patients under oral colchicine treatment in comparison with the initial clinical evaluation with a special emphasis on patients with altered deformity after treatment. A total of 118 patients under oral treatment with colchicine for at least 3 months in the acute phase of PD were retrospectively evaluated with combined infection and stimulation test. PD patients were followed up in four groups according to the clinical course of the deformity: improved, remained unchanged, deteriorated deformities or altered localisation of the deformity. Among 116 patients who completed the treatment, penile curvatures improved in 27.6% (n = 32), remained unchanged in 39.7% (n = 46) and deteriorated in 12.1% (n = 14) of the patients after a follow-up of 8.6 ± 3.2 (6–17) months, while localisation of the deformities changed in 20.7% (n = 24) of the patients. In this group, the initial side of the deformities were lateral, ventral, ventrolateral in 41.6% (n = 10), 29.1% (n = 7) and 8.3% (n = 2) of the patients and of hourglass and notching type (n = 4, 16.6%) respectively. Six (60%) patients with lateral, five (71.4%) with ventral curvatures completed their follow-up period with dorsal curvatures. In conclusion, lateral curvature is the most commonly altered deformity that mostly shifts to the dorsal sise of the penis after colchicine therapy.

Medium-term follow-up of plaque incision and porcine small intestinal submucosal grafting for Peyronie's disease

F Staerman1,2, J Pierrevelcin1,2, T Ripert1 and J Menard1

1Department of Urology and Andrology, Robert Debré Academic Hospital, Avenue du Général Koenig, Reims, France

Correspondence: Professor F Staerman, Department of Urology and Andrology, Robert Debré Academic Hospital, Avenue du Général Koenig, Reims 51100, France. E-mail: fstaerman@chu-reims.fr

Int J Impotence Res. 2010 Published online 2 December 2010.

Top of page

Abstract

The best surgical option for the management of severe cases of Peyronie's disease is currently a matter of debate. To determine medium-term outcomes and complications after treatment of severe Peyronie's disease by porcine small intestinal submucosa (SIS) grafts, we retrospectively reviewed 33 consecutive plaque incisions followed by 4-ply SIS grafting in 28 patients (2002–2009). Postoperative complications, penile length preservation, de novo ED, penile curvature correction and curvature recurrence rates were recorded. Median patient age was 54 years (38–69 years). Median preoperative curvature was 90° (30–90°) (stable for at least 6 months). Six patients (21%) had preoperative ED. There were few postoperative complications (no cases of infection, haematoma (n=2), penile hypoesthesia (n=1), patch rejection and migration (n=1)). Subjective penile shortening and de novo ED were observed in 7 (25%) and 3 (11%) patients, respectively. The success rate for the procedure (straight penis or curvature 20° and ability to have intercourse) was 67% (22/33). Four patients achieved curvature correction after a repeat procedure with a new SIS

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graft. Eleven patients experienced recurrence within 3 months of surgery. After a median follow-up of 9 months (3–94), 22 patients (79%) had a satisfactory curvature correction.

Keywords: Peyronie's disease; small intestinal submucosa; graft; penile curvature; surgery

Priapism

ORIGINAL ARTICLE

Posttraumatic high-flow priapism in children treated with

autologous blood clot embolization: long-term results and

review of the literature

Murat Cantasdemir, Fatih Gulsen, Serdar Solak and Furuzan Numan

Pediatric Radiology 2010, Publ. online 3 Dec.2010

Abstract

Background

Usually high-flow priapism is caused by perineal or penile blunt trauma with direct cavernosal artery injury and formation of an arterial-lacunar fistula. Rarely, cavernosal artery injury may result from penetrating trauma. Treatment of high-flow priapism is not considered an emergency because patients are at low risk for permanent complications. For this type of priapism there are several options for treatment including embolization or surgical ligation.

Objective

To describe the technique of superselective transcatheter embolization with the use of autologous blood clot and to discuss the long-term results.

Materials and methods

Seven children with a mean age of 10 years suffering from high-flow priapism were treated with superselective transcatheter embolization with autologous blood clot. In all cases, colour Doppler US was performed to demonstrate increased cavernous blood flow with definitive diagnosis established by superselective arteriography. After the angiographic diagnosis, superselective transcatheter embolization of the fistula with autologous blood clot was performed during the same session. The children were followed up on a monthly basis up to 1 year with clinical findings and penile colour Doppler US examinations. After 1 year, they were followed up annually with clinical assessment only. The mean follow-up period was 6.0 years.

Results

21

Following embolization complete detumescence was achieved in all but one child, who was treated with a second embolization 3 d after the initial session. In addition, for one child a second session of embolization was performed due to the recurrence of partial erection during the 1 week period after the initital embolization. In both cases, complete detumescence was achieved after the second embolization, and no recurrence of priapism was observed in the follow-up period.

Conclusion

Selective arterial embolization with autologous clot achieved treatment for high-flow priapism in this study with 100% occlusion rate with a maximum of two sessions and no signs of erectile dysfunction were observed in any of the children during long-term follow-up.

Keywords Priapism - High-flow - Angiography - Child

DAILY PHOSPHODIESTERASE TYPE-5 INHIBITOR THERAPY AS RESCUE FOR RECURRENT ISCHEMIC PRIAPISM AFTER FAILED ANDROGEN ABLATION: A CASE REPORT

Phillip M. Pierorazio , Trinity J Bivalacqua , and Arthur L. Burnett *

J Androl. 2010, publ.online 3 Dec. 2010

* To whom correspondence should be addressed. E-mail: aburnett@jhmi.edu .

Objectives: To discuss the potential for normal hormone regulation and application of chronic phosphodiesterase type 5 (PDE5) inhibition for the management of recurrent ischemic priapism. Findings: A 64-year old man presented with refractory priapism treated with anti-androgen therapy. He was transitioned to and well-controlled on a regimen of daily PDE5 inhibitor use and every other week anti-androgen therapy. Conclusions: Our treatment of recurrent priapism implicates androgens and both biochemical and neurovascular control mechanisms in the penis.

Key words: Androgen • Erectile Dysfunction • Hormone • Penis • Hormone Therapy • Hypogonadism

A Prospective Diary Study of Stuttering Priapism in Adolescents and Young Men with Sickle Cell Anemia: Report of an International Randomized Control Trial; The Priapism In Sickle Cell Study (PISCES study)

B. Olujohungbe *, A. Adeyoju , A. Yardumian , O. Akinyanju , J. Morris , N. Westerdale , Y. Akenova , O. Kehinde , K. Anie , J. Howard , A. Brooks , Verna-Angus Davis , and A. Inati

J.Androl 2010,publ.online 3 Dec. 2010

Priapism is defined as a prolonged, persistent, and purposeless penile erection. It is a common (in 35%) but frequently understated complication in young men and adults

22

with sickle cell disease. We had previously demonstrated an association between stuttering attacks (<4hrs) and an acute catastrophic event with its consequent problems of erectile dysfunction and impotence. We describe a randomized placebo controlled clinical study looking at medical prophylaxis using two oral alpha adrenergic agonists, etilefrine and ephedrine, in preventing stuttering attacks of

priapism. 131 patients were registered into a 2 phase (observational and intervention phase) study and 86 (66%) patients completed Phase A diary charts. 46 patients (59%) completed a 6 month treatment Phase (B) and the remainder was lost to follow up despite persistent efforts to contact them. Various reasons are postulated for the high attrition rates. The drugs were well tolerated with no serious adverse events reported. There was no significant difference between the four treatment groups in the weekly total number of attacks in Phase B (analysis of covariance p=0.99) nor the average pain score per attack after adjusting for attack rates and pain scores in Phase A (analysis of covariance p=0.33). None of the patients who completed the

study required penile aspiration at study sites while on medical prophylaxis. Young men with sickle cell disease are not comfortable engaging with health care providers about issues relating to their sexual health. The full impact of an improved awareness

campaign and early presentation to hospital merits further standardized study. Priapism still contributes seriously to the co-morbidity experienced by this previously inaccessible group of patients and medical prophylaxis with oral alpha adrenergic agonists is feasible. Future international collaborative efforts using some of the lessons learnt in this study should be undertaken.

Key words: Adrenergic agonist • Prophylaxis • Sexual Health

Various Penile Disorders

Tissue Engineering Penoplasty with Biodegradable Scaffold Maxpol-T Co-Grafted Autologous Fibroblasts for Small Penis Syndrome

Zhe Jin , Yi-guang Wu , Yi-ming Yuan , Jing Peng , Yan-qing Gong , Guang-yong Li , Wei-dong Song , Wan-shou Cui , Xue-you He , and Zhong-cheng Xin *

J.Androl.2010, Published-Ahead-of-Print December 16, 2010

In this study, we investigated the safety and efficacy of a Poly acid-co-Glycolide (PLGA) biodegradable scaffold (Maxpol-T) coated by autologous fibroblasts (AF) for penile girth enlargement in small penis syndrome (SPS). Eighty patients with SPS were enrolled in a clinical study at two medical centers; 69 patients completed the study protocol. Scrotal skin was harvested under local anesthesia and the AF were cultured and seeded on a Maxpol-T scaffold; the co-grafted scaffold was implanted under the Buck's fascia of penile shaft via a circumcising incision. Patients were followed up at 1, 3, and 6 months to evaluate penile girth changes. Patient satisfaction was assessed via Visual Analogue Scale (VAS) and score on the International Index of Erection Function Erectile Function Domain (IIEF5). Mean preoperative penile girth in the flaccid and erect state was 8.18 ± 0.83cm and 10.26 ± 1.22cm respectively. At the 6 month post operative follow-up mean penile girth in the flaccid and erect state was increased to 12.19 ± 1.27 cm and 13.18 ± 1.31 cm, respectively (p < 0.001 for change in both flaccid and erect state). Sixty-five patients (94.2%) reported satisfaction with the procedure. Among them, 4 cases (5.8%) were dissatisfied, 7 cases (10.1%) were

23

satisfied, 26 cases (37.7%) were very satisfied and 32 cases (46.4%) were extremely satisfied. All men maintained IIEF-5 scores > 22. Complications included prolonged subcutaneous edema in 3 patients (4.3%) and pinpoint erosion at the suture area in 3 patients (4.3%). Implantation of autologous fibroblasts seeded on a Maxpol-T collagen scaffold holds promise as a safe and novel technique for penile girth enhancement in patients with small penis syndrome.

Testosterone and Male Hormonal Disorders

A safety study of administration of parenteral testosterone

undecanoate to elderly men over minimally 24 months

A. Haider1, L. J. G. Gooren2, P. Padungtod3, F. Saad4,5

Andrologia 2010, Article first published online: 25 NOV 2010

Keywords:Drug safety;polycythaemia;prostate cancer;testosterone undecanoate

Summary

This study investigated the safety of administration of long-acting parenteral testosterone undecanoate (TU) to 122 hypogonadal, mainly elderly men, aged 59.6 ± 8.0 years (range 18–83 years old), with baseline testosterone levels between 5.8 and 12.1 nmol l-1 (mean ± SD = 9.3 ± 1.7). Patients were followed for 24 months. Plasma testosterone rose from 9.3 ± 1.7 to 14.9 ± 4.5 nmol l-1 (P < 0.01) at 3 months, then stabilised at 19.2 ± 4.6 nmol l-1 after 6 months. International Prostate Symptoms Scores and Residual Bladder Volumes decreased significantly (P < 0.01) over the study period. Prostate volume and prostate-specific antigen levels fluctuated over the study period but had not increased significantly after 24 month. Haemoglobin concentrations increased significantly (P < 0.001) over the 24 months while the haematocrit increased significantly (P < 0.001) during the first 15 months and then levelled off. Statistical analysis with expressing values as means ± SD masks excesses above reference values of individual patients. These excesses were noted in low numbers, were permanently present in some but not in other individuals, and did not increase in number over the 24 month study period. Over 24 months treatment with TU appeared acceptably safe, but longer and larger scale studies are needed.

Oral Testosterone With and Without Concomitant Inhibition

of 5α-Reductase by Dutasteride in Hypogonadal Men for 28

Days.

Amory JK, Bush MA, Zhi H, Caricofe RB, Matsumoto AM, Swerdloff RS, Wang C, Clark RV.

University of WashingtonSeattle, Washington.

J.Urol.2010, Epub ahead of print 17 Dec.

Abstract

24

PURPOSE: Co-administration of the 5α-reductase inhibitor dutasteride increases the oral testosterone bioavailability in men with experimentally induced hypogonadism. We examined oral testosterone with and without dutasteride administration in hypogonadal men for 28 days.

MATERIALS AND METHODS: We randomly assigned 43 hypogonadal men to twice daily oral doses of 150, 250 or 400 mg testosterone with 0.25 mg dutasteride, 400 mg testosterone alone or 0.25 mg dutasteride alone for 28 days in a multicenter study. Subjects underwent pharmacokinetic profiling of serum hormones on days 1 and 28. A total of 32 men completed all study procedures.

RESULTS: Serum testosterone increased in all groups on testosterone compared with that in the dutasteride only group. At the 400 mg dose the combination of testosterone and dutasteride resulted in average testosterone concentrations that were 2.7 and 4.6 times higher than in the testosterone only group on days 1 and 28, respectively (p <0.01). On day 28 average testosterone was 20% to 30% lower in all groups on testosterone and dutasteride, and 50% lower in the testosterone only group compared with day 1. Serum dihydrotestosterone was suppressed in all groups on dutasteride and increased in the testosterone only group.

CONCLUSIONS: Oral testosterone administration resulted in a therapeutic serum testosterone concentration in hypogonadal men. Dutasteride improved the oral bioavailability of testosterone while suppressing dihydrotestosterone. Compared with day 1, testosterone was decreased after 28 days of administration. Additional study is warranted of oral testosterone with dutasteride for testosterone deficiency.

STD/AIDS and Venereal Diseases

Eradication of Chlamydia trachomatis parallels symptom regression in chronic bacterial prostatitis patients treated with a fluoroquinolone–macrolide combination

V. Magri1, E. Marras2, V. Škerk3, A. Markotić3, A. Restelli4, M. C. Garlaschi4, G. Perletti2

Andrologia Volume 42, Issue 6, pages 366–375, December 2010

Keywords:Chlamydia trachomatis;chronic bacterial prostatitis;chronic pelvic pain syndrome;NIH-CPSI;prostatitis

Summary

To investigate the association between eradication of Chlamydia trachomatis (CT) and symptom regression in chronic prostatitis, 55 symptomatic patients were subjected to segmented tests to localise CT in first voided urine (VB1), prostatic secretions (EPS), post-massage voided (VB3) or semen specimens. Patients were divided in three treatment groups: the ‘urethral involvement’ group (‘U’: VB1 positive, EPS/VB3/Semen negative) was treated with 500 mg day−1 azithromycin for 3 days. The ‘prostatitis’ group (‘P’: VB1 negative, EPS/VB3/semen positive) with 4-week levofloxacin–azithromycin combination. A third group,

25

‘U + P’ (VB1, EPS/VB3/semen positive) received both treatments in sequence. In P patients, eradication of CT was paralleled by marked, sustained symptom improvement and by significant decrease of serum prostate-specific antigen (PSA) levels. Compared with U patients, undergoing rapid regression of symptoms related to painful micturition after short-term azithromycin, U + P patients showed symptom and pathogen persistence in VB3/EPS/semen and required additional treatment with 4-week levofloxacin–azithromycin to achieve pathogen eradication, symptom regression, and decrease of PSA. Our results support a causative role of CT in chronic bacterial prostatitis. In the presence of a positive urethral localisation of the pathogen, thorough microbiological investigation together with focused symptom analysis may reveal an underlying chlamydial prostatitis and direct effective therapy with appropriate antibacterial agents.

A high-resolution melting analysis for genotyping urogenital Chlamydia trachomatis

Jian-Hong Lia, Yue-Ping Yina, He-Ping Zhengb, Ming-Ying Zhonga, Rui-Rui Penga, Baoxi Wanga, Xiang-Sheng Chena

DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE 2010, 68, 366-374

Abstract

We have developed a high-resolution melting analysis (HRMA) for the genotyping of Chlamydia trachomatis and applied it specifically to the 11 sexually transmitted infection-related genotypes: D through K and L1 through L3. The variable segment 2 (VS2) was selected as the target for HRMA genotype identification. Eleven C. trachomatis genotypes were amplified by a nested real-time polymerase chain reaction (PCR) in the presence of the LCGreen saturating dye and showed no cross-reaction with 10 pathogenic bacteria or commensals from urogenital tract. The detection limit of HRMA method was 100 elementary bodies (EB)/mL. All of the 11 genotypes can be distinguished from each other by following an HRMA workflow. Genotype F, G, H, I, J, K, L2, and L3 could be directly identified from each other, whereas D, E, and L1 could be distinguished from each other by a second analysis with fewer curves or by heteroduplex formation with a known reference strain. In the validation panel of 36 C. trachomatis-positive urogenital samples genotyped by VS1–VS2 sequencing, nested real-time VS2 PCR followed by HRMA was able to discriminate between all samples correctly. This assay requires no fluorescence-labeled probes or separate post-PCR analysis and provides a simple and rapid approach for genotyping the C. trachomatis strains that are the most commonly sexually transmitted.

Keywords: Chlamydia trachomatis, Genotyping, High-resolution melting analysis

A randomised controlled trial to assess pain with urethral swabs (when indicated use a plastic loop)

Ade Apoola, Maite Herrero-Diaz, Elley FitzHugh, Raj Rajakumar, Apostolos Fakis, Jayne Oakden

+ Author Affiliations

Department of Genito-urinary Medicine, Derby Foundation Hospital NHS Trust, Derby, UK

26

Contributors AA conceived the study; AA, MHD, RR, EF and JO recruited subjects and collected data for study. Statistical analyses were performed by AF. All authors contributed to the paper. AA is the guarantor.

Sex Transm Infect 2010 published Online First 2 December 2010

Abstract

Background Urethral swabs are uncomfortable due to the nature of the mucosa and may be a reason for non-attendance of men at sexually transmitted infection (STI) clinics. This randomised controlled trial describes the extent of discomfort associated with direct urethral sampling, and determines whether this varies by the type of swab used.

Methods Male patients over the age of 16 years having swab tests were invited to participate and were randomly assigned to receive either a gonorrhoea dacron-tipped swab, a chlamydia rayon-tipped swab or a plastic 10 μl urethral loop first for urethral sampling followed by the others sequentially. Discomfort was measured using a 0–100 mm visual analogue scale (VAS).

Findings 129 men having urethral swabs carried out as part of their screening tests for STI were invited to participate in the study and 121 were recruited. The median pain scores (IQR) regardless of sampling method, before and after the urethral sampling were, first 0 mm (0–0) and 50 mm (22–71) (p<0.001), second 9 mm (0–28) and 59.5 mm (38.3–78) (p<0.001) and third 10 mm (0–31) and 58 mm (29.3–80) (p<0.001). Direct urethral sampling was associated with a median pain score of 60.5 mm using a rayon swab, 52 mm using a dacron swab and 25.5 mm using a plastic loop.

Interpretation Direct urethral sampling is associated with discomfort and/or pain in men, which was significantly greater with a swab than a plastic loop. Urine should therefore be the specimen type of choice. When direct urethral sampling is indicated a loop is preferable to a urethral swab.

International Standard Randomised Controlled Trial Number Register number ISRCTN50938901.

Childhood Abuse and Neglect and the Risk of STDs In Early Adulthood

Abigail A. Haydon, Jon M. Hussey, Carolyn Tucker Halpern

Perspectives on Sexual and Reproductive Health 2010, first published online: 23 NOV 2010

CONTEXT: Given the threat posed by STDs in young adulthood, identifying early predictors of STD risk is a priority. Exposure to childhood maltreatment has been linked to sexual risk behaviors, but its association with STDs is unclear.

METHODS: Associations between maltreatment by parents or other adult caregivers during childhood and adolescence and STD outcomes in young adulthood were examined using data on 8,922 respondents to Waves 1, 3 and 4 of the National Longitudinal Study of

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Adolescent Health. Four types of maltreatment (sexual abuse, physical abuse, supervision neglect and physical neglect) and two STD outcomes (self-reported recent and test-identified current STD) were assessed. Multivariate logistic regression analyses, stratified by sex, tested for moderators and mediators.

RESULTS: Among females, even after adjustment for socioeconomic and demographic characteristics, self-report of a recent STD was positively associated with sexual abuse (odds ratio, 1.8), physical abuse (1.7), physical neglect (2.1) and supervision neglect (1.6). Additionally, a positive association between physical neglect and having a test-identified STD remained significant after further adjustments for exposure to other types of maltreatment and sexual risk behaviors (1.8). Among males, the only association (observed only in an unadjusted model) was between physical neglect and test-identified STD (1.6).

CONCLUSIONS: Young women who experienced physical neglect as children are at increased risk of test-identified STDs in young adulthood, and exposure to any type of maltreatment is associated with an elevated likelihood of self-reported STDs. Further research is needed to understand the behavioral mechanisms and sexual network characteristics that underlie these associations.

Etiologic role of human papillomavirus infection in bladder carcinoma

Kazuyoshi Shigehara MD, PhD1, Toshiyuki Sasagawa MD, PhD2,*,†, Shohei Kawaguchi MD1, Takao Nakashima MD, PhD3, Masayoshi Shimamura MD, PhD3, Yuji Maeda MD, PhD1, Hiroyuki Konaka MD, PhD1, Atsushi Mizokami MD, PhD1, Eitetsu Koh MD, PhD1, Mikio Namiki MD, PhD1

Cancer 2010 ,Article first published online: 29 NOV 2010

Keywords: human papillomavirus;bladder carcinoma;human papillomavirus in situ hybridization;p16;mcm7;HPV-L1Abstract

BACKGROUND:

The authors elucidated an etiologic role of human papillomavirus (HPV) infection in carcinoma of the bladder.

METHODS:

One hundred seventeen of 224 patients with bladder carcinoma who were treated between 1997 and 2009 were enrolled in this study. The presence of HPV DNA was tested on frozen carcinoma tissues that were obtained by transurethral resection using a polymerases chain reaction-based method. Localization of HPV was observed on archival tissue specimens by in situ hybridization (ISH) for high-risk HPV DNA. Cyclin-dependent kinase (CDK) inhibitor 2A (inhibits CDK4) (p16-INK4a) and minichromosome maintenance protein-7 (mcm-7)—surrogate markers for high-risk HPV-E7 oncoprotein—and HPV-L1 (capsid) protein expression were evaluated by immunohistochemistry.

RESULTS:

HPV types 16, 18, 31, 33, 52, and 58, and an unknown HPV type were detected in 18 of 117 samples (15%) from patients with bladder carcinoma. HPV16 was identified in 6 samples, HPV18 was identified in 4 samples, and HPV33 was identified in 3 samples. All were single HPV type infections. HPV was detected in 38% (12 of 28) of histologic grade 1 bladder

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carcinomas, 8.5% (6 of 71) of grade 2 bladder carcinomas, and in 0% (0 of 18) of grade 3 bladder carcinomas. Multivariate analysis indicated that younger age (<60 years; odds ratio [OR], 10.9; 95% confidence interval [CI], 2.6-45.3) and grade 1 tumors (OR, 4.5; 95% CI, 1.2-17.0) were associated with HPV infection. ISH analysis indicated that high-risk HPV DNA was localized in the nuclei of tumor cells of all HPV-positive samples. p16-INK4a and mcm-7 were expressed in 94% and 89% of HPV-positive carcinoma cells, respectively. HPV-L1 protein expression, which suggested reproductive HPV infection, was not observed in any carcinoma.

CONCLUSIONS:

The current results indicated that high-risk HPV is likely to be a causative agent of some low-grade bladder carcinomas that develop in younger patients. Cancer 2010. © 2010 American Cancer Society.

Female Sexual Dysfunction

Sexual rehabilitation in women with spinal cord injury: a critical review of the literature

G Lombardi1, G Del Popolo1, A Macchiarella1, M Mencarini1 and M Celso1

1Neuro-Urology Spinal Unit Department, Careggi University Hospital of Florence, Florence, Italy

Spinal Cord (2010) 48, 842–849

Abstract

Study design: Review article.

Objectives: Critical review of literature on the multiple aspects of sexual rehabilitation in women with spinal cord injury (SCI) from initial recovery to long-term follow-up.

Setting: Neuro-urology Department.

Methods: Studies on sexuality selected from PubMed from 1993 to 2009.

Results: Literature supported by significant statistical analyses reports that females with complete tetraglegia deserved special attention immediately at initial recovery; sexual intercourse is much more difficult for them (as compared with other women with SCI) mainly because of autonomic dysreflexia and urinary incontinence. There are sparse data on predictable factors favoring sexual rehabilitation such as the age SCI was incurred, the importance of one's sexual orientation, and the SCI etiology. Information after initial discharge is based chiefly on questionnaires, which report that as more time passes since the injury, patients attain more sexual satisfaction compared with recently injured women. Studies on neurological changes after SCI,

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and their effect on sexual response, are supported by a significant statistical analysis, but with few SCI patients. One topic reported the effect of sildenafil on sexuality, without benefit. No paper offers any detailed analysis on the sexual impact of medical and psychological treatments related to SCI. Literature reports that some co-morbidities are more prevalent in women with SCI compared with able-bodied women but data on sexual functioning are missing.

Conclusion: To improve sexual rehabilitation services, sexual issues and response require evaluation during periodical check-ups using validated questionnaires administered by a physician ‘guide’ who coordinates professional operators thus providing personalized programmable interventions.

Keywords: female sexual function; spinal cord injury; sexual adjustment

Mixed Sexual Topics

Heterosexual Anal Sex Experiences Among Puerto Rican and Black Young Adults

Marion Carter1,*, Dare Henry-Moss2, Linda Hock-Long3, Anna Bergdall4, Karen Andes5

Perspectives on Sexual and Reproductive Health Volume 42, Issue 4, pages 267–274,

December 2010

CONTEXT: Heterosexual anal sex is not uncommon in the United States, and it poses risk for STDs. However, who engages in it and why are not well understood, particularly among young adults.

METHODS: In 2006–2008, data on sexual health–related topics were collected in surveys (483 respondents) and qualitative interviews (70 participants) with black and Puerto Rican 18–25-year-olds in Hartford and Philadelphia. Bivariate and multivariate analyses of survey data assessed predictors of anal sex with the most recent serious heterosexual partner. Interview transcripts were analyzed for anal sex experiences and reasons for and against engaging in this behavior.

RESULTS: Some 34% of survey respondents had had anal sex; this behavior was more common with serious partners than with casual partners (22% vs. 8%). Black respondents were less likely than Puerto Ricans to report anal sex (odds ratio, 0.3); women were more likely to do so than were men (2.9). In the qualitative cohort, perceptions of anal sex as painful and unappealing were the predominant reasons for not having anal sex, whereas sexual pleasure and, in serious relationships, intimacy were the main reasons for engaging in it. Condom use during anal sex was rare and was motivated by STD or hygiene concerns.

CONCLUSIONS: Heterosexual anal sex is not an infrequent behavior and should be considered in a broad sexual health context, not simply as an indicator of STD risk. Health providers should address it openly and, when appropriate, as a positive sexual and emotional experience.

Growth and Development of Male External Genitalia A Cross-sectional Study of 6200 Males Aged 0 to 19 Years

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Analia Tomova, MD, PhD; Fnu Deepinder, MD; Ralitsa Robeva, MD; Hristina Lalabonova, MD, PhD; Philip Kumanov, MD, PhD; Ashok Agarwal, PhD, HCLD

Arch Pediatr Adolesc Med. 2010;164(12):1152-1157.

Objective To provide estimates of normal variations in penile measurements and testicular volumes, and to establish reference ranges for clinical use.

Design Cross-sectional, population-based study.

Setting Schools, kindergartens, and child care centers in different parts of Bulgaria.

Participants A population of 6200 clinically healthy white males aged 0 to 19 years.

Interventions The study physician chose schools, kindergartens, and child care centers randomly and examined children at random until he reached the required number. Each of the 20 age groups (age range, 0-19 years) had an equal number of males (ie, 310).

Main Outcome Measures The mean (SD) values and fifth, 50th, and 95th percentiles of height (Siber Hegner anthropometer), weight (beam balance), testicular volume (Prader orchidometer), penile length (rigid tape), and penile circumference (measuring tape) from birth to 19 years of age.

Results Testes did not show any increase in size until the onset of puberty at age 11 years, whereas penile growth was gradual after birth. However, both penile and testicular

development demonstrated peak growth from 12 to 16 years of age, which coincided with the maximal male pubertal growth spurt. Data indicate an earlier pubertal development for this study population than that for a similar population several decades ago. Significant differences between urban and rural populations regarding penile length were also noticed.

Conclusions Our study provides the contemporary reference range values for height, weight, testicular volume, and penile length and circumference of males aged 0 to 19 years. Our data show that, even by the end of 20th century, there is still some acceleration of male pubertal development. For the first time are reported somatic differences in genitalia within a population between urban and rural representatives.

Author Affiliations: Clinical Center of Endocrinology and Gerontology, Medical University, Sofia (Drs Tomova, Robeva, and Kumanov), and Medical University, Plovdiv (Dr Lalabonova), Bulgaria; Department of Endocrinology, Diabetes, and Metabolism, Cedars Sinai Medical Center, Los Angeles, California (Dr Deepinder); and Reproductive Research Center, Cleveland Clinic, Cleveland, Ohio (Dr Agarwal).

Long-term biochemical evaluation of the androgen receptor pathway in males with disorders of sex development

C. Schwentner, J. Czyz, J. Seibold, T. Todenhoefer, S. H. Alloussi, H. Klocker, G. Gakis, A. Stenzl, M. Baka-Ostrowska and C. Radmayr

World J Urol. 2010, publ. online 15 Dec. 2010

Abstract

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Purpose

Disorders of sex (DSD) development represent a serious condition. Most of the underlying mechanisms remain unclear. Disturbances within the androgen receptor (AR) pathway frequently account for 46 XY-DSDs. The individual gender-related outcome often is unsatisfactory. We present a long-term AR gene-mutation-associated follow-up in a group of 46 XY-DSD patients.

Methods

Twenty patients (46 XY) who underwent genitoplasty in infancy or early childhood were retrospectively identified. Median follow-up after surgery was 16 years. All were undervirilized at initial presentation. Thirteen had female gender assignment, and 7 were raised as males. A genital skin biopsy and subsequent fibroblast cultures were done. The specific binding of dihydrotestosterone, the thermostability of the receptor hormone complex, and 5-α-reductase activity were measured. AR gene mutations were detected by direct sequencing. The individual outcome was correlated with specific AR mutations.

Results

AR point mutations were detected in 12, 7 were previously unknown. There was no specific androgen binding in 3, reduced affinity in 9, and normal binding in 8 patients. 5-α-Reductase activity was normal in 15, reduced in 4 and completely absent in 1 patient.

Conclusions

Retrospective evaluation revealed previously unknown and established AR gene mutations being associated with a distinct long-term outcome. Identification of the molecular mechanisms causing DSD will likely improve timely diagnosis and therapy. Exact characterization of AR activation and function may offer a treatment modality in affected patients. These data may allow us to give prognostic estimations on the individual outcome adding objective criteria for gender assignment in 46 XY-DSD patients.

Keywords Disorders of sex development - Gender reassignment - Androgen receptor - Genitoplasty - Point mutation

C. Radmayr and M. Baka-Ostrowska are equal senior authors.