infertility, obesity, and hypogonadism are significant factors for osteoporosis in young men

1
Vol. 181, No. 4, Supplement, Wednesday, April 29, 2009 THE JOURNAL OF UROLOGY ® 785 was positive correlation with previous formal education on ionizing radiation. Preliminary data for one-year effective radiation doses relating to urolithiasis episodes has revealed a significant minority of patients recieving over 50mSV annually; doses above that deemed safe for nuclear industry workers. CONCLUSIONS: Physician awareness surrounding radiation doses of common diagnostic and interventional modalities is poor, grossly underestimating the true values. Those who had received formal training performed better. A minority of patients with urolithiasis are receiving doses of radiation associated with increased carcinogenesis. These multiple levels of evidence coupled with the burgeoning role of high-dose modalities such as CT highlights an need to educate clinicians, raise radiation dose awareness and avoid the financial, medico-legal and health delivery implications of patient radiation over-exposure. Source of Funding: None Infertility: Evaluation Podium 46 Wednesday, April 29, 2009 1:00 pm - 3:00 pm 2163 INFERTILITY, OBESITY, AND HYPOGONADISM ARE SIGNIFICANT FACTORS FOR OSTEOPOROSIS IN YOUNG MEN Elena Gimenez*, Alex Bolyakov, Michael Herman, Joseph Kiper, Darius A Paduch, New York, NY INTRODUCTION AND OBJECTIVE: Hypogonadism is common in men presenting with infertility or sexual dysfunction. Low testosterone (T) is a known risk factor for low bone mineral density (LBMD) in older men, but less is known about the prevalence, risk factors, and management of younger men with LBMD. Current recommendations for screening, evaluation and treatment of men with LBMD are derived from studies in older women, or are focused on the treatment of elderly men with hip or spine fractures. The aim of this study was to analyze risk factors for osteopenia (OSTP) and osteoporosis (OSTR) in hypogonadal men younger then 55 presenting with infertility or sexual dysfunction. METHODS: This was a prospective, observational, IRB approved study. A single physician (DAP) evaluated patients (n= 199) referred because of infertility (INF), hypogonadism (HYP), sexual dysfunction (ED), or chronic pelvic pain. Serum T was measured by LC-MS; LH, FSH, prolactin (PRL), and estradiol were evaluated by chemiluminescence. BMD was measured using new generation Prodigy GE DEXA scanner with race, sex, and age adjusted nomograms. OSTP was defined as T or Z score below -1, and OSTR as T or Z <-2.5. The age, height, weight, adjusted BMD, T and Z scores and full hormonal and metabolic workup were recorded. SPSS, JMP, and GraphPad were used for statistical analysis. RESULTS: Full data was available for 156 pts, mean age = 37.7 (95% CI: 30-40). Low BMD was found in 40 % of patients: OSTR in 4 %, and OSTP in 36 %. Mean T level was 264 ng/dL (95%CI: 250-279). T was lower in men with OSTR (200 ng/dL) than in men with normal BMD and osteopenia (283 ng/dL, 264ng/dL), p30), T < 200 ng/dL, FSH above 25 U/L, LH above 14 U/L, and history of infertility. Men with 4 out 5 above risks factors had relative risk of 13.22 for OSTR, and 1.35 for OSTP; p<0.03. Presence of only 1 risk factor lowered the RR of OSTR to 0. Men with obesity had SS lower T level than non-obese men. (229 v. 306 ng/dL; p<0.0002) CONCLUSIONS: Low BMD is common in young hypogonadal men seen in urological practice. Patients with history of infertility, obesity, and severe primary testicular failure are at significant risk of osteoporosis, however neither T, E, FSH, LH nor PRL were able to assess the risk of osteopenia. Hypogonadal men are at high risk for osteopenia and osteoporosis; patients should not be excluded from screening based on moderately low levels of testosterone. Weight modification may improve BMD and circulating testosterone levels. Source of Funding: Solvay and Watson Educational Grant 2164 A HIGH RESOLUTION SCREEN REVEALS UNRECOGNIZED CHROMOSOME ANOMALIES IN CONGENITAL GENITOURINARY DEFECTS ASSOCIATED WITH MALE INFERTILITY Mounia Tannour-Louet, Han Shuo, Sean T. Corbett, Dolores J Lamb*, Houston, TX INTRODUCTION AND OBJECTIVE: State-of-the-art techniques to encrypt submicroscopic chromosomal rearrangements that result from abnormal homologous recombination have shed light on the molecular basis of genomic syndromes causing birth defects and mental retardation. Y chromosome microdeletions are an example of a genomic syndrome causing male infertility. We hypothesize that infertility-associated congenital genitourinary defects (cryptorchidism, hypospadias, ambiguous genitalia) result from similar genomic structural chromosomal defects too small to be seen by routine karyotype. METHODS: A clinically validated chromosome microarray (CMA) and routine karyotype analysis were used to screen for structural chromosomal defects in 98 patients presenting congenital genitourinary defects out of more than 13,000 total tested for birth defects. Parental DNA was analyzed when available to define if the detected genomic imbalances represent a benign polymorphism or a true pathogenic event. Results were confirmed by fluorescent in situ hybridization analysis and/ or by quantitative PCR. RESULTS:While karyotype did not reveal any abnormalities, CMA analysis showed that 30% of the analyzed subjects have submicroscopic chromosomal defects. These imbalances had an average size of 1-2 Mb which is below the resolution of standard karyotyping. Common genomic regions were affected underlying the likelihood of a direct causality of the relative chromosomal aberration to the observed phenotype. Deletions in Yp11.3, 1p36, 9p24 and 22q11 were noted for ambiguous genitalia and duplications in Xq28, 5p15, 10p14 and 16q24 were observed for cryptorchidism and hypospadias patients. These regions of interest encompassed gene- rich loci. In one patient the deletion included WNT4 gene which plays a critical role in the sex determination. CONCLUSIONS: CMA analysis is superior to the routine karyotype for detection of small structural chromosomal defects in patients with congenital genitourinary anomalies causing infertilty. Haplo-insufficient and dosage sensitive genes in the affected genomic regions appear as strong candidates involved in genitourinary tract development. Clinical application of the CMA technique to diagnosis will aid in genetic counselling of patients with congenital genitourinary defects and research will provide increased knowledge of the molecular basis of these infertility related syndromes. Source of Funding: Supported by 1 R01 DK078121 from the National Institutes of Health to DJL and the AUA Foundation (SC, DJL). 2165 A NOVEL APPLICATION OF 1H MAGNETIC RESONANCE SPECTROSCOPY: POTENTIAL FOR NON-INVASIVE IDENTIFICATION OF SPERMATOGENESIS IN MEN WITH NON- OBSTRUCTIVE AZOOSPERMIA. David S Aaronson*, Thomas J Walsh, Rahwa Iman, Paul J. Turek, John Kurhanewicz, San Francisco, CA INTRODUCTION AND OBJECTIVE: 1 in 10 infertile men will have no sperm in the ejaculate due to poor or absent sperm production in the testis, also known as non-obstructive azoospermia (NOA). Some will be able to conceive by extraction of sperm from the testicle combined with in vitro fertilization and intracytoplasmic sperm injection. These men often require testicular biopsy to determine the presence of usable sperm. Biopsy causes some morbidity and has poor sensitivity. 1-H magnetic resonance spectroscopy (MRS) may represent a non-invasive tool for identifying and localizing sperm production in azoospermic men. This technology merges 1-H spectroscopy with magnetic resonance imaging to detect tissue metabolite expression differences in as little as 0.3 ml of tissue. The current study aims to

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Vol. 181, No. 4, Supplement, Wednesday, April 29, 2009 THE JOURNAL OF UROLOGY® 785

was positive correlation with previous formal education on ionizing radiation. Preliminary data for one-year effective radiation doses relating to urolithiasis episodes has revealed a significant minority of patients recieving over 50mSV annually; doses above that deemed safe for nuclear industry workers.

CONCLUSIONS: Physician awareness surrounding radiation doses of common diagnostic and interventional modalities is poor, grossly underestimating the true values. Those who had received formal training performed better. A minority of patients with urolithiasis are receiving doses of radiation associated with increased carcinogenesis. These multiple levels of evidence coupled with the burgeoning role of high-dose modalities such as CT highlights an need to educate clinicians, raise radiation dose awareness and avoid the financial, medico-legal and health delivery implications of patient radiation over-exposure.

Source of Funding: None

Infertility: Evaluation

Podium 46

Wednesday, April 29, 2009 1:00 pm - 3:00 pm

2163INFERTILITY, OBESITY, AND HYPOGONADISM ARE SIGNIFICANT FACTORS FOR OSTEOPOROSIS IN YOUNG MEN

Elena Gimenez*, Alex Bolyakov, Michael Herman, Joseph Kiper, Darius A Paduch, New York, NY

INTRODUCTION AND OBJECTIVE: Hypogonadism is common in men presenting with infertility or sexual dysfunction. Low testosterone (T) is a known risk factor for low bone mineral density (LBMD) in older men, but less is known about the prevalence, risk factors, and management of younger men with LBMD. Current recommendations for screening, evaluation and treatment of men with LBMD are derived from studies in older women, or are focused on the treatment of elderly men with hip or spine fractures. The aim of this study was to analyze risk factors for osteopenia (OSTP) and osteoporosis (OSTR) in hypogonadal men younger then 55 presenting with infertility or sexual dysfunction.

METHODS: This was a prospective, observational, IRB approved study. A single physician (DAP) evaluated patients (n= 199) referred because of infertility (INF), hypogonadism (HYP), sexual dysfunction (ED), or chronic pelvic pain. Serum T was measured by LC-MS; LH, FSH, prolactin (PRL), and estradiol were evaluated by chemiluminescence. BMD was measured using new generation Prodigy GE DEXA scanner with race, sex, and age adjusted nomograms. OSTP was defined as T or Z score below -1, and OSTR as T or Z <-2.5. The age, height, weight, adjusted BMD, T and Z scores and full hormonal and metabolic workup were recorded. SPSS, JMP, and GraphPad were used for statistical analysis.

RESULTS: Full data was available for 156 pts, mean age = 37.7 (95% CI: 30-40). Low BMD was found in 40 % of patients: OSTR in 4 %, and OSTP in 36 %. Mean T level was 264 ng/dL (95%CI: 250-279). T was lower in men with OSTR (200 ng/dL) than in men with normal BMD and osteopenia (283 ng/dL, 264ng/dL), p30), T < 200 ng/dL, FSH above 25 U/L, LH above 14 U/L, and history of infertility. Men with 4 out 5 above risks factors had relative risk of 13.22 for OSTR, and 1.35 for OSTP; p<0.03. Presence of only 1 risk factor lowered the RR of OSTR to 0. Men with obesity had SS lower T level than non-obese men. (229 v. 306 ng/dL; p<0.0002) CONCLUSIONS: Low BMD is common in young hypogonadal men seen in urological practice. Patients with history of infertility, obesity, and severe primary testicular failure are at significant risk of osteoporosis, however neither T, E, FSH, LH nor PRL were able to assess the risk of osteopenia. Hypogonadal men are at high risk for osteopenia and osteoporosis; patients should not be excluded from screening based on moderately low levels of testosterone. Weight modification may improve BMD and circulating testosterone levels.

Source of Funding: Solvay and Watson Educational Grant

2164A HIGH RESOLUTION SCREEN REVEALS UNRECOGNIZED CHROMOSOME ANOMALIES IN CONGENITAL GENITOURINARY DEFECTS ASSOCIATED WITH MALE INFERTILITY

Mounia Tannour-Louet, Han Shuo, Sean T. Corbett, Dolores J Lamb*, Houston, TX

INTRODUCTION AND OBJECTIVE: State-of-the-art techniques to encrypt submicroscopic chromosomal rearrangements that result from abnormal homologous recombination have shed light on the molecular basis of genomic syndromes causing birth defects and mental retardation. Y chromosome microdeletions are an example of a genomic syndrome causing male infertility. We hypothesize that infertility-associated congenital genitourinary defects (cryptorchidism, hypospadias, ambiguous genitalia) result from similar genomic structural chromosomal defects too small to be seen by routine karyotype.

METHODS: A clinically validated chromosome microarray (CMA) and routine karyotype analysis were used to screen for structural chromosomal defects in 98 patients presenting congenital genitourinary defects out of more than 13,000 total tested for birth defects. Parental DNA was analyzed when available to define if the detected genomic imbalances represent a benign polymorphism or a true pathogenic event. Results were confirmed by fluorescent in situ hybridization analysis and/or by quantitative PCR.

RESULTS: While karyotype did not reveal any abnormalities, CMA analysis showed that 30% of the analyzed subjects have submicroscopic chromosomal defects. These imbalances had an average size of 1-2 Mb which is below the resolution of standard karyotyping. Common genomic regions were affected underlying the likelihood of a direct causality of the relative chromosomal aberration to the observed phenotype. Deletions in Yp11.3, 1p36, 9p24 and 22q11 were noted for ambiguous genitalia and duplications in Xq28, 5p15, 10p14 and 16q24 were observed for cryptorchidism and hypospadias patients. These regions of interest encompassed gene- rich loci. In one patient the deletion included WNT4 gene which plays a critical role in the sex determination.

CONCLUSIONS: CMA analysis is superior to the routine karyotype for detection of small structural chromosomal defects in patients with congenital genitourinary anomalies causing infertilty. Haplo-insufficient and dosage sensitive genes in the affected genomic regions appear as strong candidates involved in genitourinary tract development. Clinical application of the CMA technique to diagnosis will aid in genetic counselling of patients with congenital genitourinary defects and research will provide increased knowledge of the molecular basis of these infertility related syndromes.

Source of Funding: Supported by 1 R01 DK078121 from the National Institutes of Health to DJL and the AUA Foundation (SC, DJL).

2165A NOVEL APPLICATION OF 1H MAGNETIC RESONANCE SPECTROSCOPY: POTENTIAL FOR NON-INVASIVE IDENTIFICATION OF SPERMATOGENESIS IN MEN WITH NON-OBSTRUCTIVE AZOOSPERMIA.

David S Aaronson*, Thomas J Walsh, Rahwa Iman, Paul J. Turek, John Kurhanewicz, San Francisco, CA

INTRODUCTION AND OBJECTIVE: 1 in 10 infertile men will have no sperm in the ejaculate due to poor or absent sperm production in the testis, also known as non-obstructive azoospermia (NOA). Some will be able to conceive by extraction of sperm from the testicle combined with in vitro fertilization and intracytoplasmic sperm injection. These men often require testicular biopsy to determine the presence of usable sperm. Biopsy causes some morbidity and has poor sensitivity.

1-H magnetic resonance spectroscopy (MRS) may represent a non-invasive tool for identifying and localizing sperm production in azoospermic men. This technology merges 1-H spectroscopy with magnetic resonance imaging to detect tissue metabolite expression differences in as little as 0.3 ml of tissue. The current study aims to