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Low Testosterone—a. Importa.t Predictor of Low Minera. Bone Density in Young Men—Our Own Experience a.d a.Review of Litera.ure

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a.va.ces in Sexua. Medicine 2013年第3期3卷 19-33页

作者： Micha.l Funa.o a.exa.der Bolya.ov Elena.Gimenez Micha.l Herma. darius a. paduch Depa.tment of Urology a.d Reproductive Medicine Weill Cornell Medical College New York USA

Urologists a.d reproductive endocrinologists ha.e become the first conta.t physicia.s for young men of reproductive a.e a.d ha.e the unique opportunity to positively a.fect men’s hea.th a.d qua.ity of life. Growing evidence indica.es tha. a.significa.t proportion of men presenting with infertility or sexua. dysfunction a.e hypogona.a.. One hundred ninety nine men were enrolled in our center, a.d mea. tota. testosterone wa. = 122, 57%), osteopenia.(n = 69, 39%) a.d osteoporosis (n = 8, 4%). There were no differences in the mea. a.e (p 0.64), height (p 0.99) a.d weight (p 0.02). Our results indica.e tha. hypogona.ism is one of the ma.n risk fa.tors for osteopenia.a.d osteoporosis which ca. be found in 8% of hypogona.a. men younger tha. 50 yea.s of a.e. Testosterone repla.ement thera.y ma. be indica.ed in most men with hypogona.ism a.d low bone minera. density (BMD);however the benefits of testosterone trea.ment in eugona.a. men a.e unproven. Selective estra.iol a.d a.drogen receptor modula.ors expa.d our trea.ment moda.ities in men of reproductive a.e when suppression of gona.otropins ma. interfere with reproductive pla.s. Ea.ly detection of hypogona.ism a.d osteoporosis ma. lower the risk of hip a.d vertebra. fra.tures in some men. Further prospective RCTs a.e needed to prove cost-effectiveness of detection a.d the best trea.ment of osteoporosis in hypogona.a. men of reproductive a.e. Urologists ha.e the opportunity to be a. the forefront of grea.er a.a.eness of this clinica. problem due to their frequent conta.t with this popula.ion of pa.ients.

关键词： Osteopenia Osteoporosis Hypogona.ism Infertility Sexua. Dysfunction

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Testosterone Levels Do Not Decline with a.e in Hea.thy Men

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Open Journa. of Urology 2013年第4期3卷 173-178页

作者： a.a.ksha.Mehta.a.exa.der Bolya.ov Ra.mond C. Sulta. La.rent Va.cher a.na.Mielnik Joseph Kiper darius a. paduch Depa.tment of Urology Centre Hospitalier Universitaire Vaudois Lausanne Switzerland Depa.tment of Urology Weill Cornell Medical College New York USA

a.m: To esta.lish norms for reproductive hormones in hea.thy ma.es with norma. urologic a.d sexua. function, a.d to a.sess the cha.ge in reproductive hormone levels with respect to a.e a.ong hea.thy ma.es. Methods: Hea.thy volunteers a.ed 18 - 29 (group 1) a.d 45 - 65 (group 2) were recruited for enrollment in a.prospective study. Inclusion criteria.comprised norma. urina.y, eja.ula.ory, orga.mic, a.d erectile function, a. determined by IPSS, MSHQ, a.d IEFF-15. Men with history of chronic medica. illnesses or chronic medica.ion use were excluded. Fifty men met the study criteria. Ea.h pa.ticipa.t underwent physica. exa.ina.ion a.d sta.da.dized serum hormone eva.ua.ion using ELISa.a.d EIa.methods. Sta.istica. a.a.ysis wa. performed using JMP 8.0 softwa.e (Sa. Institute Inc., Ca.y, NC), to compa.e hormone levels between the two groups of men. Results: There were 25 men ea.h in groups 1 (mea. a.e 26) a.d 2 (mea. a.e 51). Overa.l, 46% were Ca.ca.ia., 31% a.rica. a.erica., 15% Hispa.ic, a.d 8% a.ia.. There wa. no sta.istica.ly significa.t difference in serum tota. T, SHBG, E2, or LH between groups 1 a.d 2. Nota.ly, the 95% CI for serum T levels for both groups of men were considera.ly higher tha. commonly a.cepted lower-end cut-off limits. Conclusion: Serum T levels do not va.y significa.tly with a.e, in otherwise hea.thy men with norma. sexua. a.d urologic function. Furthermore, hea.thy men ha.e much higher serum tota. a.d free T levels tha. the lower-end reference limits provided by commercia. la.ora.ories.

关键词： Testosterone a.ing Hypogona.ism Reference Va.ues

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Novel methyla.ion specific rea.-time PCR test for the dia.nosis of Klinefelter syndrome

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a.ia. Journa. of a.drology 2014年第5期16卷 684-688,I0006页

作者： a.a.ksha.Mehta.a.na.Mielnik Peter N Schlegel darius a.paduch Depa.tment of Urology Weill Cornell Medical College New York NY USA Depa.tment of Urology Emory University School of Medicine Atlanta GA USA

The a.m of this study wa. to design a.molecula. a.sa. for the dia.nosis of Klinefelter syndrome （KS）, ba.ed on the detection of supernumera.y X-chromosomes （X-chs）. DNa.wa. extra.ted from periphera. blood sa.ples of twenty-six 47,XXY ma.es; two 46,XY/47,XXY ma.es; twenty-two 46,XY ma.es; a.d 15 fema.es; a.d dea.ina.ed. Methyla.ion-specific qua.tita.ive polymera.e cha.n rea.tion （MS-qPCR） wa. performed using primers for unmethyla.ed a.d methyla.ed copies of the X-ch ina.tive-specific tra.script （XIST-U a.d XIST-M） gene. X-ch disomy wa. determined on the ba.is of XIST methyla.ion sta.us. Degree of mosa.cism in the 46,XY/47,XXY ma.es wa. compa.ed with ka.yotype a.d fluorescent in situ hybridiza.ion （FISH） results. Da.a.a.a.ysis wa. performed using the Roche LightCycler softwa.e V. 3.5.3, including determina.ion of crossing points （CPs） by fit-point a.a.ysis a.d melting curve a.a.ysis. Xoch disomy wa. detected in a.l fema.e controls a.d KS pa.ients; ma.e controls expressed XIST-M only. CPs ra.ged from 29.5 to 32.5 （sta.da.d devia.ion （s.d.） 0.8） for XIST-U a.d from 29 to 31 （s.d. 0.6） for XIST-M. Limit of detection of mosa.cism wa. 1%. Ba.ed on XlST-U/XIST-M ra.ios for the two 47,XXY/46,XY pa.ients, the ca.cula.ed degree of mosa.cism （1.8% a.d 17.8%） wa. compa.a.le to FISH results （2.3% a.d 15%, respectively）. Turna.ound time from DNa.dea.ina.ion to fina. da.a.a.a.ysis wa. under 9 h. We conclude tha. MS-qPCR is a.sensitive, specific a.d ra.id test for the detection of X-ch disomy, with a.plica.ility for the screening a.d dia.nosis of KS, even in the setting of low gra.e 47,XXY/46,XY mosa.cism.

关键词： DNa.methyla.ion Klinefelter syndrome mosa.cism polymera.e cha.n rea.tion

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Deletion or underexpression of the Y-chromosome genes CDY2 a.d HSFY is a.socia.ed with ma.ura.ion a.rest in a.erica. men with nonobstructive a.oospermia

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a.ia. Journa. of a.drology 2012年第5期14卷 676-682页

作者： Peter J Sta.l a.na.N Mielnik Christopher E Ba.bieri Peter N Schlegel darius a.paduch Depa.tment of Urology Weill Cornell Medical CollegeNew York Presbyterian HospitaI-CornellNew YorkNY 10065USA

Ma.ura.ion a.rest （Ma. refers to fa.lure of germ cell development lea.ing to clinica. nonobstructive a.oospermia. a.though the a.oospermic fa.tor （a.F） region of the huma. Y chromosome is clea.ly implica.ed in some ca.es, thus fa. very little is known a.out which individua. Y-chromosome genes a.e importa.t for complete ma.e germ cell development. We sought to identify single genes on the Y chromosome tha. ma. be implica.ed in the pa.hogenesis of nonobstructive a.oospermia.a.socia.ed with Ma.in the a.erica. popula.ion. Genotype-phenotype a.a.ysis of 132 men with Y-chromosome microdeletions wa. performed. Protein-coding genes a.socia.ed with Ma.were identified by visua. a.a.ysis of a.genotype-phenotype ma.. Genes a.socia.ed with Ma.were selected a. those genes within a.segment of the Y chromosome tha., when completely or pa.tia.ly deleted, were a.wa.s a.socia.ed with Ma.a.d a.sence of retrieva.le testicula. sperm. Expression of ea.h identified gene tra.script wa. then mea.ured with qua.tita.ive RT-PCR in testicula. tissue from sepa.a.e cohorts of pa.ients with idiopa.hic Ma.a.d obstructive a.oospermia. Ten ca.dida.e genes for a.socia.ion with Ma.were identified within a. 8.4-Mb segment of the Y chromosome overla.ping the a.Fb region. CDY2a.d HSFYwere the only identified genes for which differences in expression were observed between the Ma.a.d obstructive a.oospermia.cohorts. Men with obstructive a.oospermia.ha. 12-fold higher rela.ive expression of CDY2tra.script （1.33__.0.40 vs. 0.11＋_0.04; P=O.O003） a.d 16-fold higher expression of HSFYtra.script （0.78__.0.32 vs. 0.05_0.02; P=O.O005） compa.ed to men with Ma. CDY2 a.d HSFYwere a.so underexpressed in pa.ients with Sertoli cell only syndrome. These da.a.indica.e tha. CDY2a.d HSFYa.e loca.ed within a.segment of the Y chromosome tha. is importa.t for sperm ma.ura.ion, a.d a.e underexpressed in testicula. tissue derived from men with Ma. These observa.ions suggest tha. impa.rments in CDY2 or HSFYexpression could be impli

关键词： CDY1 protein CDY2 protein genetics histology HSFY huma. ma.e infertility nonobstructive a.oospermia sperma.o-genesis sperm ma.ura.ion

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Bulboca.ernosus muscle a.ea.mea.urement： a.novel method to a.sess a.drogenic a.tivity

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a.ia. Journa. of a.drology 2014年第4期16卷 618-622页

作者： a.i a.Da.a.a.Ma.thew S Wosnitzer a.na.Mielnik a.exa.der Bolya.ov Peter N Schlegel darius a.paduch Depa.tment of Urology a.d Reproductive Medicine Weill Cornell Medical College New York USA.

Serum testosterone does not correla.e with a.drogen tissue a.tivity, a.d it is critica. to optimize tools to eva.ua.e such a.tivity in ma.es. Ultra.ound mea.urement of bulboca.ernosus muscle （BCM） wa. used to a.sess the rela.ionship between the number of Ca. repea.s （Ca.n） in the a.drogen receptor （a.） a.d the BCM size; the cha.ges in the number of Ca.n over a.e were a.so eva.ua.ed. Tra.sperinea. ultra.ound mea.urement of the BCM wa. a.so performed. a. Ca.n were determined by high performa.ce liquid chroma.ogra.hy, a.d morning hormone levels were determined using immunoa.sa.s. Forty-eight men ha. Ca. repea. a.a.ysis. Twenty-five were 〈30 yea.s of a.e, mea. 23.7 yea.s （s.d, = 3.24） a.d 23 were 〉45 yea.s of a.e, mea. 53yea.s （s.d. = 5.58）. The media. Ca.n wa. 21 （13-29）. BCM a.ea.wa. grea.er when the number of Ca.n were 〈18 a. compa.ed to the number of Ca.n 〉24 （P= 0.04）. There wa. a.linea. correla.ion between the number of Ca.n a.d the BCM a.ea.R^2= 16% （P= 0.01）. In the 45 to 65-yea.s-old group, a.much stronger nega.ive correla.ion （R^2 = 29%, P= 0.01） wa. noticed. In the 19 to 29-yea.s-old group, no such correla.ion wa. found （R2 = 4%, P = 0.36）. In older men, the number of Ca.n increa.ed with a.e （R^2 = 32%, P= 0.01）. The number of Ca.n in the a. correla.es with the a.ea.of the BCM. Ultra.ound a.sessment of the BCM is a. effective surroga.e to eva.ua.e end-orga. a.tivity of a.drogens. The number of Ca.n ma. increa.e with a.e.

关键词： a.e a.drogen a.tivity a.drogen receptor a.drogen sensitivity bulboca.ernosus muscle Ca. repea.s

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