Recent Literature in Sexual Medicine/ Andrology

1
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–Englishspeaking 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 DHTand 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 Tlevels.
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
function;,castration;,signaling pathway
intestinal
polypeptide;,
erectile
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 Giand 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, MarieLaure 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 cAMPregulatory 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 SantosSilva, 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, apneahypopnea 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
13
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
Laparoscopic Radical Prostatectomy.
Robot-Assisted
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
14
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
15
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 PDE5 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
improvement/acceleration of erectile function recovery.
lead
to
a
significant
16
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.
17
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
1
Department 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
20
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 antiandrogen 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 , Weidong 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
Disorders
and
Male
Hormonal
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
syndrome;NIH-CPSI;prostatitis
bacterial
prostatitis;chronic
pelvic
pain
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), postmassage 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 shortterm 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
urogenital Chlamydia trachomatis
for
genotyping
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 infectionrelated 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 postPCR 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
ISRCTN50938901.
Randomised
Controlled
Trial
Number
Register
number
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
27
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
hybridization;p16;mcm7;HPV-L1Abstract
carcinoma;human
papillomavirus
in
situ
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
28
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 lowgrade 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,
29
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 comorbidities 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
30
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
31
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.