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International audience; Robust data evaluating the association of preoperative parameters of the patients with quality of life after radical prostatectomy are lacking. We investigated whether clinical and biological preoperative characteristics of the patients were associated with impaired patient-reported quality of life (QoL) and sexual outcomes 1 year after radical prostatectomy. We evaluated patient-reported outcomes among the 1343 men participating in the AndroCan trial (NCT02235142). QoL and erectile dysfunction (ED) were assessed before and 1 year after radical prostatectomy using validated self-assessment questionnaires (Aging Male’s Symptoms [AMS] and the 5-item abridged version of the International Index of Erectile Function [IIEF5]). At baseline, 1194 patients (88.9%) accepted to participate. A total of 750 (55.8%) patients answered the 1-year postoperative questionnaires. Out of them, only 378 (50.4% of responders) provided answers that could be used for calculations. One year after prostatectomy, ED had worsened by 8.0 (95% confidence interval [CI]: 7.3–8.7; P< 0.0001) out of a maximum of 20. The global AMS score has worsened by 2.8 (95% CI: 1.7–3.8; P < 0.0001). ED scores 1 year postsurgery were positively correlated with preoperative age and percentage of fat mass, and negatively correlated with total cholesterol, dehydroepiandrosterone (DHEA), and androstenediol (D5); AMS were poorly correlated with preoperative parameters. QoL and sexual symptoms significantly worsened after radical prostatectomy. Baseline bioavailable testosterone levels were significantly correlated with smaller changes on AMS somatic subscores postprostatectomy. These findings may be used to inform patients with newly diagnosed prostate cancer.

International audience; Purpose: PSA is known to be lowered in obese patients. There is a lack of data regarding patients with prostate cancer. Our objective was to prospectively assess the relationship PSA concentration, PSA mass and BMI in a cohort of patients with localized prostate cancer. Methods: A prospective, multicenter cohort study was conducted including patients undergoing radical prostatectomy. Clinical and biological data were collected for each patient before surgery. Results: A total of 1343 patients were analyzed. Mean age was 64.0 years. Mean weight was 82.2 kg and mean BMI was 26.8 kg/m2. Mean PSA concentration was 8.7 ng/mL and mean PSA mass 29.3 ng. On univariate analysis, an association was found between PSA mass and either BMI, weight and waist circumference. No association was found between PSA concentration and each weight parameters. On multivariate analysis, obesity was not an independent predictor of PSA concentration (p = 0.73). Independent predictors of PSA concentration were cardiovascular disease (negative association, p = 0.034), predominant Gleason 4 (positive association, p < 0.001) and pT3a (positive association, p < 0.001). BMI was an independent predictor of PSA mass (positive association, p = 0.009). PSA mass was negatively associated with TT (p = 0.015) and cardiovascular disease (p = 0.003), and positively associated with BT (p = 0.032), Gleason grade ≥ 4 + 3 (p < 0.001) and pT3a (p < 0.001). Conclusion: In this prospective study of patients with localized prostate cancer, higher BMI was associated with higher PSA mass but not with higher PSA concentration. Screening obese patients with a specific PSA method does not appear to be critical.

Failure rates after first-line treatment of localized prostate cancer (PCa) treatment remain high. Improvements to patient selection and identification of at-risk patients are central to reducing mortality. We aimed to determine if cancer aggressiveness correlates with androgen levels in patients undergoing radical prostatectomy for localized PCa. We performed a prospective, multicenter cohort study between June 2013 and June 2016, involving men with localized PCa scheduled to undergo radical prostatectomy. Clinical and hormonal patient data (testosterone deficiency, defined by total testosterone (TT) levels

The specific involvement of the sex steroids in the growth of the prostatic tissue remains unclear. Sex steroid concentrations in plasma and in fresh surgical samples of benign central prostate were correlated to prostate volume.Monocentric prospective study performed between September 2014 and January 2017. Age, obesity parameters, and both serum and intraprostatic concentrations of sex steroids were collected complying with the latest Endocrine Society guidelines and the steroids assessed by GC/MS. Statistical calculations were adjusted for age and body mass index (BMI).Thirty-two patients, equally divided between normal- and high-volume prostate groups, were included in the analysis. High-volume prostate patients were older, heavier and had higher BMI. Comparison adjusted for age and BMI showed higher DHT concentrations in high-volume prostate. Both normal- and high-volume prostate tissues concentrate sex steroids in a similar way. Comparison of enzymatic activity surrogate marker ratios within tissue highlighted similar TT/E1 and TT/E2 ratios, and higher DHT/E1 ratio and lower DHT/PSA ratio in the high-volume prostates.STERPROSER trial provides evidence for higher DHT concentration in highvolume prostates, that could reflect either higher 5-alpha reductase expression or lower expression of downstream metabolizing enzymes such as 3a-hydoxysteroid dehydrogenase.

Background Currently, there is no consensus regarding the expected concentration levels of intra-prostatic sex steroids in patients with Prostate Cancer (PCa). Our objective was to assess the concentration levels of sex steroids in prostatic tissue and serum, in two cohorts of patients with localized PCa or benign prostatic hyperplasia (BPH). Methods Between September 2014 and January 2017, men selected for radical cystectomy (for bladder cancer) or open prostatectomy (for BPH), and men selected for radical prostatectomy for localized PCa were included. Blood samples were collected at baseline before surgery, and steroid concentrations were assessed following the recommendations of the Endocrine Society. Intra-prostatic samples were collected from fresh surgical samples, and assessed by gas chromatography and mass spectrometry (GC/MS). Permanova analysis was performed. Analyses were adjusted for age, prostate weight, and prostate-specific antigen (PSA) level. Results A total of 73 patients (41 patients with PCa and 32 patients with BPH) were included in this study. Patients with PCa were younger, and had smaller prostate volumes with higher levels of PSA. The levels of Total Testosterone (TT), Di-Hydro-Testosterone (DHT), and Estradiol (E2) in the serum were not significantly different between PCa and BPH. In PCa tissue, TT concentrations were significantly lower (0.11 ng/g vs 0.47 ng/g, P = 0.0002), however its derivative E2 had significantly higher concentrations (31.0 ng/g vs 22.3 ng/g, P = 0.01). DHT tissue concentrations were not significantly different between the two groups (5.55 ng/g vs 5.42 ng/g, P = 0.70). Intra-prostatic TT concentrations were significantly lower in the peripheral zone than in the central zone for the CaP group (0.07 ng/g vs 0.15 ng/g, P = 0.004). Conclusions Patients with PCa had lower intra-prostatic TT and higher E2 concentrations levels compared to the patients with BPH. PCa seem to consume more TT and produce more E2, especially in the peripheral zone.

Objectifs Les variations eventuelles du taux de PSA en fonction de l’obesite, chez les hommes porteurs d’un cancer de prostate (CaP) localise, sont peu explorees et pour le moins contradictoires. L’objectif de cette etude etait de confirmer ou infirmer que l’hemodilution, liee a l’obesite, entraine des variations du taux serique et de la masse de PSA en cas de CaP localise. Methodes La cohorte ANDROCAN ( NCT02235142 ), prospective, multicentrique, a recrute de juin 2013 a juin 2016, 1343 hommes porteurs d’un CaP localise, traites par prostatectomie radicale robot-assistee. Les mesures preoperatoires du poids, de la taille, de l’IMC, du pourcentage de masse graisseuse sur balance a impedance, et du PSA dans un laboratoire centralise, ont ete rapportees a l’histologie, confirmee par un anatomopathologiste unique, de la piece operatoire. La masse de PSA a ete calculee a partir du volume plasmatique suivant la formule simplifiee du Baltimore Longitudinal study of aging : volume plasmatique = 1,67 × surface corporelle. Resultats Parmi les 1343 patients, 432, 556 et 224 avaient un IMC 30 ng/mL respectivement. Au total, 912 patients etaient ISUP ≤ 2, d’âge median 63,6 (IQR : 59,50–68,0) ans. Au total, 431 patients etaient ISUP ≥ 3, d’âge median 65,6 (IQR : 61,0–69,1) ans. Les patients ISUP ≥ 3 etaient significativement plus âge. La comparaison des dosages de PSA et des masses de PSA par groupe ISUP est rapporte dans le Tableau 1 . La seule difference significative observait etait entre les masse de PSA des patients ISUP ≤ 2 avec un IMC > 30 vs [25–30]. Conclusion La concentration serique de PSA, en cas de cancer de prostate localise, n’est pas influencee par le poids du sujet. La masse de PSA semble plus discriminante, mais la mesure approchee du volume plasmatique relativise ces resultats.

Objectifs L’impact de la prise des statines sur le cancer de prostate (CaP) localise reste discute et tres diversement apprecie. L’objectif de cette etude a ete de comparer les concentrations des steroides sexuels de patients operes d’un CaP localise en fonction qu’ils soient traites ou non par statines. Methodes Etude prospective (2013–2016), multicentrique, sur 1343 hommes porteurs d’un CaP localise, traites par prostatectomie radicale robot-assistee. Les mesures preoperatoires du poids total et gras, de la taille, de l’IMC, du PSA,FSH, LH, SHBG et par chromatographie gazeuse-spectrometrie de masse de la DHEA, Δ4, Δ5, DHEA sulfate, testosterone totale (TT), bio-disponible (BT), DHT, E1, E2 de patients prenant des statines depuis au moins 6 mois, ont ete comparees a celles de patients ne recevant pas de statines. La probabilite de la difference entre les 2 groupes est obtenue par un test t par randomisation (10 000 iterations) tenant compte d’une eventuelle difference de variance entre groupes. Resultats Les concentration des 285 patients qui prenaient des statines depuis au moins 6 mois, ont ete comparees a celles des 71 patients ne recevant pas de statines ( Tableau 1 ). Le groupe recevant des statines est significativement plus âge ; TT, BT, DHT, Δ 4 y etait significativement plus faibles. Les differences sur E2 et le poids prostatique tangentent la significativite sans l’atteindre. Conclusion La prise de statine, de facon prolongee (≥ 6 mois) est associee a un hypogonadisme franc. Ce parametre devrait etre integre dans le profil metabolique pre-therapeutique des CaP localise.

Objectifs L’impact des traitements du cancer de la prostate localise sur la qualite de vie globale des patients est peu evalue. Nous avons etudie la qualite de vie des patients avant et un an apres prostatectomie totale. Methodes Nous reportons les resultats de l’etude prospective multicentrique ANDROCAN evaluant la qualite de vie des patients avant et un an apres prostatectomie totale. Le questionnaire standardise Aging Male's Symptoms Scale (AMS) mesurait la qualite de vie somatique, psychologique et sexuelle a l’aide de 3 sous-scores et un score global. Resultats Mille cent quatre-vingt-dix-sept sur 1347 (89 %) patients inclus dans l’etude ANDROCAN ont accepte de repondre aux questionnaires AMS avant prostatectomie totale. A un an postoperatoire, 701 (59 %) patients ont ete evalues. L’âge moyen des patients etaient de 63,9 ans (63,6–64,3). Le score global moyen AMS augmentait de 31,8 (31,1–32,5 IC95 %) a 35,9 (35,1–36,7 IC95 %) a un an postoperatoire, traduisant une alteration significative de la qualite de vie globale (p Conclusion La qualite de vie est un sujet d’interet pour la majorite des patients pris en charge pour un cancer de la prostate localise. Une alteration significative de la qualite de vie globale, sexuelle et psychologique etait observee un an apres prostatectomie totale. Les patients ayant un syndrome metabolique avaient un risque plus eleve d’alteration de la qualite de vie.

What's known on the subject? and What does the study add? Hypogonadism affects an estimated 2–4 million men in the USA, but only 5% receive treatment. Testosterone replacement therapy reduces the effects of testosterone deficiency on sexual function, mood and energy in hypogonadal patients. Long-term hypogonadism management requires testosterone treatment to restore serum concentrations of testosterone and its active metabolites, within physiological ranges; a testosterone preparation that achieves physiological plasma concentrations without supra-physiological escape is a preferred option. A previous 1-year study European clinical study showed the efficacy and safety of a transdermal testosterone patch (Testopatch®). The present study shows the long-term (6-year) safety and efficacy of Testopatch in patients with primary or secondary hypogonadism. We show that, over the long-term, Testopatch was associated with no relevant changes in PSA concentration and PSA velocity, or any significant prostate risks (there were no cases of prostate cancer). Objective To assess the change in prostate-specific antigen (PSA) concentrations in patients with primary or secondary hypogonadism, receiving transdermal testosterone. Patients and Methods This was an interventional, 6-year study, conducted in Urology and Endocrinology centres in Belgium, France, Germany, the Netherlands and Spain. Participants were primary (48%) or secondary (52%) hypogonadal patients who received two 60 cm2 testosterone patches (Testopatch®), delivering 4.8 mg of testosterone per day, applied every 2 days. During treatment, total testosterone (TT), dihydrotestosterone, oestradiol and, PSA concentrations were measured in a centralised laboratory every 3 months during the first year, and every 6 months thereafter. Results In all, 200 patients [mean (sd) age 41.0 (12.5) years, body weight 82.5 (13.7) kg, height 177.2 (9.3) cm, body mass index 26.2 (3.4) kg/m2] were treated with transdermal testosterone patches. In all, 161 patients completed the 1-year study and 115 entered into a 5-year study extension; 51 patients completed the sixth year of the study. The mean baseline concentrations of TT and PSA were 1.4 ng/mL and 0.47 ng/mL, respectively; TT serum concentrations >3 ng/mL were achieved in 85% of patients and fluctuated between 4.4 and 6.0 ng/mL. At each successive 6-month time point, mean the PSA values were 0.60, 0.67, 0.76, 0.70, 0.61, 0.68, 0.64, 0.71, 0.75, 0.74, 1.01, 0.78, 0.80 ng/mL, respectively. The mean PSA velocity was negligible (0.00–0.03 ng/mL/year) from 30 months to the end of the trial, except for a value of 0.08 at 60 months. Seven patients had a PSA concentration of >4 ng/mL due to a sharp PSA increase. Six of these patients had prostatitis and PSA concentrations returned to previous levels with appropriate treatment. No prostate cancer was reported during the trial. Conclusion These data support a strong safety profile for Testopatch, even at the highest registered dosage.

Objectifs L’interpretation histologique des pieces de prostatectomie radicale a pour but de confirmer la presence d’un adenocarcinome prostatique, d’en preciser la stadification : pTNM, score de Gleason et etat des marges d’exerese chirurgicale. Ces criteres sont parfois sujets a des interpretation individuelles inter-pathologistes avec des coefficient kappa variant de 0,2 a 0,9. Nous rapportons les resultats de la lecture centralisee des foyers index (plus haut stade et/ou de plus haut grade) des pieces de prostatectomie radicale de l’etude ANDROCAN. Methodes Les pathologistes des centres ayant participe a l’etude ANDROCAN ont transmis pour relecture centralise les lames du foyer index des pieces de prostatectomies radicales (1494 cas sur les 1516 inclus). Les deux pathologistes experts en uropathologie (VM, CR) ont relus de maniere anonymes les lames transmises et ont precise pour chaque cas le score de Gleason, le stade pTNM (2010) et l’etat des marges. En cas de discordance entre les deux relecteurs, une troisieme lecture au microscope a double tete a ete effectuee afin d’obtenir un consensus. Le coefficient de correlation Kappa a ete calcule pour evaluer la reproductibilite interobservateur. Resultats La concordance dans l’interpretation du score de Gleason exact (n = 1211) est de 36,5 % (Kappa = 0,035) avec une sous-evaluation du score dans 24,8 % des cas et une surevaluation du score dans 27,2 % des cas. En regroupant les cas en score de Gleason ≤ 6 ; 3 + 4 ; 4 + 3 et ≥ 8 (n = 1190), la concordance est de 36,8 % (Kappa = 0,025). La concordance pour la predominance de grade 4 et/ou 5 a ete de 57 % (Kappa = –0,003). L’analyse du stade pathologique effectuee dans 1342 cas retrouve une concordance dans 93,5 % des cas (Kappa = 0,86) avec une sous-evaluation du stade dans 2.2 % et une surevaluation du stade dans 4,2 % des cas. L’analyse des marges evaluable pour 1144 cas a montre une concordance dans 96,5 % des cas avec une sous-estimation des marges dans 5,8 % et une sur-estimation dans 16,6 % des cas (Kappa = 0,92) Tableau 1 , Tableau 2 . Conclusion Nos resultats montrent qu’en termes d’analyse interobservateur les pathologistes ayant participe a cette etude ont des coefficient de correlation excellents pour l’evaluation du stade et des marges, superieurs a ceux rapportes dans la litterature (Kappa = 0,58–0,82) mais que l’evaluation du SG et du pourcentage de grade 4/5 reste encore problematique.

Objectifs Les concentrations intraprostatique des steroides sexuels et leurs correlations aux concentration seriques ont fait l’objet d’etudes parcellaire avec des methodologies de dosage critiquables. L’objectif de l’essais STERPROSER a ete rechercher des differences dans les concentrations des steroides sexuels dans le plasma et des echantillons chirurgicaux frais de prostate centrale benigne selon le volume de la prostate. Methodes Etude prospective monocentrique realisee entre septembre 2014 et janvier 2017. L’âge, les parametres de l’obesite et les concentrations seriques et intraprostatiques des steroides sexuels ont ete recueillis et mesures par spectrometrie de masse en phase gazeuse respectant les dernieres directives dans le domaine. Les calculs statistiques ont ete ajustes pour l’âge et l’indice de masse corporelle (IMC). Resultats Trente-deux patients, repartis de maniere egale entre les groupes de prostate de volume normal ( Tableau 1 , Tableau 2 ). Conclusion L’essai STERPROSER fournit des preuves d’une activite plus elevee des enzymes 5-alpha reductase, ce qui conduit a une concentration plus elevee de DHT dans les prostates de volumes eleves. L’activite comparee de l’aromatase selon le volume de la prostate suggere une affinite enzymatique plus elevee de la 5-alpha-reductase pour la testosterone et/ou une affinite enzymatique inferieure de l’aromatase pour la testosterone dans les prostates de volumes eleves.

Resume Tout urologue a appris que le cancer de prostate est initialement androgeno-dependant. Ce n’est cependant que recemment que l’evaluation des androgenes circulants chez le patient atteint d’un cancer de prostate a ete etudiee. Connaitre la fonction gonadique d’un patient atteint de cancer de prostate ne semble effectivement pas denue d’interet. Neanmoins le dosage de la testosterone serique ne fait pas partie des habitudes cliniques. Cet article fait le point sur la maniere dont le dosage de la testosterone s’effectue et sur l’interet pratique de ce dosage dans la prise en charge du cancer de la prostate.

Objectifs Actuellement, il n’existe pas de references sur les concentrations d’androgenes intratissulaires prostatiques attendues chez les patients atteints de cancer de prostate. Notre objectif etait de comparer les concentrations seriques et intraprostatiques des steroides sexuels, aupres de patients atteints de cancer de prostate (CAP) ou d’hypertrophie benigne de prostate (HBP). Methodes Entre septembre 2014 et janvier 2017, des hommes selectionnes pour prostatectomie radicale pour CAP localisee ou pour adenomectomie voie haute pour HBP ont ete inclus. Les echantillons seriques ont ete preleves avant chirurgie, selon les recommandations de la societe internationale d’endocrinologie. Les echantillons intraprostatiques ont ete preleves a partir d’echantillons chirurgicaux frais et evalues par spectrometrie de masse en phase gazeuse, en zone centrale et peripherique. Une analyse permanova a ete realise, ajustee sur l’âge, le volume prostatique et le PSA. Resultats Au total, 41 patients ont ete inclus pour CAP et 32 patients pour HBP. Les patients presentant un CAP etaient plus jeunes, avaient des prostates moins volumineuses et un PSA plus eleve. Dans le serum, les concentrations de testosterone totale (TT), de di-hydro-testosterone et d’oestradiol n’etaient pas significativement differentes selon la presence ou l’absence de cap. Dans le tissu prostatique, les concentrations de tt etaient significativement plus faibles (0,11 ng/mL vs 0,47 ng/mL ; p = 0,0002) et son derive l’oestradiol presentait des concentrations significativement plus elevees (31,0 ng/mL vs 22,3 ng/mL ; p = 0,01) dans le groupe CAP. Les concentrations de TT intraprostatiques etait significativement plus faible dans la zone peripherique que dans la zone centrale pour le groupe CAP (0,07 ng/mL vs 0,15 ng/mL IC 95 % ; p = 0,001) ( Tableau 1 , Tableau 2 ). Conclusion Les patients atteints de cap ont des concentrations de TT intraprostatiques inferieures aux patients atteints d’HBP. Les prostates cancereuses semblent consommer plus de tt et produire plus d’oestradiol, notamment dans la zone peripherique.

Introduction Detection of androgen deficiency is at least, based on specific questionnaires, defined by sexual, psychological, and somatic variables. Their relationships with sexual hormone levels are poorly understood. Aim To assess the Aging Male Symptoms (AMS) score and sex hormone levels in normal and complaining men in order to define the relationship between the key parameters related to androgen deficiency. Methods Nine hundred and three men were interviewed via phone by a trained interviewer who completed the questionnaire; 539 men consulting for a checkup in a health center and 471 complaining men, who completed the AMS scale in clinical setting, were selected, after excluding subjects with major and/or chronic diseases, endocrine disorders, psychological dysfunctions, and metabolic syndrome. Main Outcome Measures Total AMS score and psychological, somatic and sexual subscores, as a function of age. Results The AMS questionnaires the were completed in a clinical setting or via calling‐up line were comparable. In both cases, total AMS scores and subscores were significantly dependent of age and were correlated to income. In normal men, the only two parameters that significantly changed with age were the AMS sexual subscore and bioavailable testosterone (BT). Complaining men aged more than 50 years old had a significantly higher total AMS scores, subscores, and BT level than normal men up to 60 years old, and these differences weakened with increasing age. In normal and complaining men, whatever the AMS sexual subscore, any variation in testosterone (T) and BT levels was observed. Conclusions The AMS scale could be defined as a screening test for androgen deficiency symptoms in men between 50 and 65 years of age. The sexual AMS subscore and BT level are the key variables to identify those symptoms; the severity of sexual symptoms can not be explained by a BT level decrease. Raynaud J‐P, Tichet J, Born C, Taieb C, Igigabel P, Giton F, and Fiet J. “Aging Male Symptoms” questionnaire in normal and complaining men. J Sex Med 2008;5:2703–2712.

Seeking insight into the possible role of estrogens in prostate cancer (PCa) evolution, we assayed serum E2, estrone (E1), and estrone sulfate (E1S) in 349 PCa and 100 benign prostatic hyperplasia (BPH) patients, and in 208 control subjects in the same age range (50-74 years). E1 (pmol/L+/-S.D.) and E1S (nmol/L+/-S.D.) in the PCa and BPH patients (respectively 126.1+/-66.1 and 2.82+/-1.78, and 127.8+/-56.4 and 2.78+/-2.12) were significantly higher than in the controls (113.8+/-47.6 and 2.11+/-0.96). E2 was not significantly different among the PCa, BPH, and control groups. These assays were also carried out in PCa patients after partition by prognosis (PSA, Gleason score (GS), histological stage, and surgical margins (SM)). Significantly higher E1S levels were found in PCa with: PSA10 ng/L (3.05+/-1.92) versus PSAor=10 ng/mL (2.60+/-1.55), stage pT3-T4 (2.99+/-1.80) versus pT2 (2.58+/-1.58), and positive (3.26+/-1.95) versus negative margins (2.52+/-1.48). E1 was higher in poor- than in better-prognosis PCa. E2 was significantly higher in PCa with GSor=4+3 (109.5+/-43.8) versus GSor=3+4 (100.6+/-36.5) and increased significantly when GS increased from 3+3 to 4+4. Estrogens, especially E1S appeared to be possible markers of PCa progression. Attempting to identify potential sources of E2 in PCa according to prognosis, as well as in BPH, we found a significant correlation coefficient between E1S and E2 (0.266-0.347) in poor-prognosis PCa and no correlation in BPH (0.026) and better-prognosis PCa (0.013-0.104). It is as though during progression of PCa from good to poor prognosis there were a shift in the E1 to E2 metabolic pathway from predominantly oxidative to predominantly reductive.

The present study assessed pharmacokinetic testosterone time profile and dose proportionality after application of a new matrix testosterone patch (30, 45, and 60 cm2 containing 0.5mg of testosterone per cm2). This open study was a single dose, three-period, crossover trial with a randomised treatment sequence in 24 hypogonadal men, consisting in a single 48-h application of two patches of 2x 30 cm2, 2x 45 cm2, 2x 60 cm2, separated by a 5-day wash-out. Testosterone concentrations were determined during patch application and after patch removal. Dose proportionality was assessed on baseline corrected, dose normalised parameters for C av,corr/D, C max,corr/D and AUC(0-48),corr/D. Testosterone concentrations rose during the first 9h following patch application, remained relatively sustained until 48 h and then decreased abruptly after patch removal, with a half-life of 1.3h. Testosterone levels were maintained above 3 ng/mL for 42-45 h with all patches. C av were 3.39, 4.03 and 4.58 ng/mL and Cmax were 4.33, 5.29 and 6.18 ng/mL according to the doses. AUC 0-48), C av and Cmax were dose dependent with mean ratios within the acceptance range (0.70-1.43). In conclusion, dose linearity was demonstrated between the different strengths of testosterone patches. Application resulted in dose proportional increases in serum T levels in hypogonadal men into the low to mid-normal range within the first hours and achieved steady state for 48 h. During this short term study with three consecutive patch applications, this patch was shown to be efficient, convenient and safe with excellent adhesiveness and skin tolerability, and with no cross-contamination to partner or to environment.

Background: Bioavailable testosterone (BT) is measured [assayed BT (aBT)] or calculated (cBT) in the diagnosis of hypogonadism in men. The cBT depends, however, on the values of the association constants of total testosterone (TT) for sex hormone–binding globulin (SHBG; Ks) and albumin (Ka), and its use therefore remains controversial. Methods: In 503 selected, untreated healthy men, 20–74 years old, we measured TT, dihydrotestosterone (DHT), and androstenediol (5-diol) by GC-MS, SHBG by RIA, and BT after ammonium sulfate precipitation or by calculation according to the law of mass action. Results: A slight decrease in TT, significant decreases in BT and 5-diol, no variation in DHT, and an increase in SHBG were observed with age. In young males (≤39 years), the lower normal limits were between 2.30 and 2.72 nmol/L for aBT and 8.50 nmol/L for TT. For Ks = 1 × 109 L/mol and Ka = 3.6 × 104 L/mol, the lower cBT limit was found to be 2-fold higher than for aBT. With optimized Ks = 1.9 × 109 L/mol and Ka = 2.45 × 104 L/mol, cBT values close to aBT were obtained. When 5-diol was included in the model as a competitive SHBG inhibitor, the correlation between cBT and aBT was better and the cBT:aBT ratios vs 5-diol were less biased. Conclusion: Lower normal serum aBT concentration in normal men appears to be between 2.30 and 2.72 nmol/L. Much higher serum cBT concentrations are associated with use of different association constants that may be inappropriate. When using the optimized binding constants, taking age-related 5-diol values into consideration slightly improves prediction of cBT.

To compare histological feature of prostate cancer (PCa) according androgenic status in patients who underwent radical prostatectomy (RP). Between March 2007 and September 2013, we prospectively analysed 937 patients who were referred to our centre for RP. Clinical, pathological and biological data have been prospectively collected. Preoperative total testosterone (TT) and bioavailable testosterone (BT) serum determinations were carried out. The threshold for low serum testosterone was set at TT

PURPOSE To compare histological features of prostate cancer according to both obesity, defined by a body mass index (BMI) ≥30 kg/m2, and androgenic status in patients who underwent radical prostatectomy. MATERIALS AND METHODS Between March 2007 and September 2013, clinical, pathological and biological data were prospectively collected for patients referred for radical prostatectomy in a single European center. Preoperative total testosterone (TT) and bioavailable testosterone (bioT) serum determinations were performed. The threshold for hypogonadism was set at TT

Background: Bioavailable testosterone (BT), circulating testosterone not bound to sex hormone–binding globulin (SHBG), is thought to easily penetrate cells. We compared BT measurements obtained by assays with those obtained by calculation with different testosterone association constants. Methods: We obtained sera from 2 groups of hypogonadal men [group 1 (G1), 1421 samples; group 2 (G2), 170 samples] and a group of healthy men [group 3 (G3), 109 samples]. We added minute doses of [3H]testosterone to the sera, precipitated the SHBG-bound fraction of testosterone with ammonium sulfate (50% saturation), and then assayed serum BT (ABT) as %BT × total. Calculated BT (CBT) was determined with theoretical association constants of testosterone for SHBG (Ks = 1 × 109 L/mol) and albumin (Ka = 3.6 × 104 L/mol) and paired optimal Ks and Ka values obtained by use of Microsoft Excel software. Results: CBT calculated with theoretical constants differed from ABT by >30% in 85.7% (G1), 84.1% (G2), and 77.9% (G3) of samples, and the mean CBT/ABT ratios were 1.57 (G1), 1.85 (G2), and 1.50 (G3) in spite of fairly good correlations. CBT calculated with paired optimal Ks and Ka differed from ABT by Conclusions: To obtain CBT values as close as possible to ABT, optimal paired association constants determined for each studied population must be used instead of the theoretical association constants. Considering the uncertainty of calculating BT, however, use of the ammonium sulfate precipitation method for determining BT is advisable.

Objectives: Sexual function is one of the aspects in the treatment of lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) that has gained increasing attention. We compared the influence on men's sexuality of Permixon, a lipido-sterolic extract of Serenoa Repens, with Tamsulosin and Finasteride using a specific validated questionnaire exploring patient's sexual functions. Methods: A database was created comprising patients from 3 main double-blind, randomized studies - Permixon vs. Finasteride, Permixon vs. Tamsulosin and Permixon 160mg vs. 320mg including a total of 2511 patients. Three hundred fifty four were on Tamsulosin, 545 on Finasteride and 1612 patients on Permixon. LUTS were assessed using the I-PSS questionnaire. Peak flow rates and prostate volume were recorded. The MSF-4 questionnaire, including 4 items that explore the patient's interest in sex, quality of erection, achievement of orgasm and ejaculation, was used across the studies. This questionnaire was demonstrated as highly reproducible and both psychometrically and clinically valid across different cultures. Correlation coefficients were given to assess the linear relationship between continuous variables. Results: At 3 months, there were no statistically significant differences between the three treatment groups in terms of I-PSS or Qmax evolutions (all p values>0.05). At 6 months, as compared to pretreatment data, there was a slight increase in sexual disorders in Tamsulosin (+0.3) and Finasteride (+0.8) treated patients while it slightly improved with Permixon therapy (−0.2). Ejaculation disorders were the most frequently reported side effects after Tamsulosin or Finasteride (both +0.2 on the specific MSF-4 question 4). There was no correlation between the evolution of the MSF-4 scores and the evolution in I-PSS neither in patients treated with Permixon, Finasteride or Tamsulosin. However, there was a slight correlation between the MSF-4 score at baseline and the I-PSS at baseline ( r 2 =0.032). Although there was a correlation between the MSF-4 and age at baseline ( r 2 =0.1452), there was no correlation between the evolution in MSF-4 during therapy and the age of the patients. Conclusion: The present study demonstrates that Permixon therapy has no negative impact on male sexual function. Both Finasteride and Tamsulosin had a slight impact on sexual function, especially on ejaculation, although these effects were rare and in line with previous reports about these two drugs.

A new time-resolved fluoroimmunoassay (TR-FIA) of testosterone in serum is described, using a biotinylated testosterone tracer, with a long spacer arm between biotin and testosterone, coupled to the C3 of the testosterone: a biotinylaminodecane carboxymethyloxime testosterone. This tracer affords a great sensitivity of the standard curve, because a amount of 0.3 pg of testosterone can be significantly measured on the testosterone standard curve. The "functional" sensitivity is at least equal to 21 pg/ml of serum. The specificity of the assay is insured by a celite chromatographic step on new minicolumns before immunoassay. The variation coefficient of inter-series reproducibility measured on low and normal testosterone levels in untreated and testosterone treated hypogonadal men were between 2.17 and 5.07%. The accuracy test, (overload and dilution tests) gave satisfying results. Moreover, in a comparison with GCMS, it appeared that the correlation coefficient was 0.992 and no significant difference could be exhibited between the two methods. Consequently, this specific, sensitive reproducible and easy to use method is well suited to the measurement of testosterone in clinical and pharmacological conditions.

Item does not contain fulltext OBJECTIVE: To compare the efficacy of the lipido-sterolic extract of Serenoa repens, Permixon, to that of the a-blocker, tamsulosin, in the treatment of severe low urinary tract symptoms (LUTS) of benign prostatic hyperplasia (BPH). METHODS: In a 12-month, double-blind, randomized study that showed equivalent efficacy of Permixon 320 mg/day and tamsulosin 0.4 mg/day ("PERMAL study"), 685 BPH patients with IPSS > 10 had been analyzed for efficacy. Of these, the 124 patients with severe LUTS (IPSS > 19) at randomization were retained for this subset analysis. After a 4-week run-in period, 59 and 65 patients had been randomized to tamsulosin and Permixon groups, respectively. Both treatment groups were compared regarding the evolution from baseline of total IPSS and its irritative and obstructive subscores. LUTS-related QpL, prostate volume, Qmax and MSF-4 (sexual activity questionnaire) at different time points over 1 year An analysis of variance of changes from baseline to end point was performed for all the parameters. The over-time evolutions of total, irritative and obstructive IPSS were further compared using a variance analysis for repeated measurements. RESULTS: At 12 months, total IPSS decreased by 7.8 with Permixon and 5.8 with tamsulosin (p = 0.051); the irritative symptoms improved significantly more (p = 0.049) with Permixon (- 2.9 versus - 1.9 with tamsulosin). The superiority of Permixon in reducing irritative symptoms appeared as soon as month 3 and was maintained up to month 12 (p = 0.03). CONCLUSION: Permixon 320 mg/day was shown to be slightly superior to tamsulosin 0.4 mg/day in reducing LUTS in severe BPH patients after 3 months and up to 12 months of treatment.

Objectifs Dans le cancer localise de la prostate (PCa), l’impact des concentrations des steroides sexuels sur l’agressivite du cancer est debattu, certains auteurs rapportant une association a la testosteronemie totale (TT), biodisponible (BT) ou a l’estradiol (E2). Nous avons compare les profils seriques preoperatoires des hormones sexuelles et les caracteristiques pathologiques chez les patients atteints de PCa localises selon la predominance du grade de Gleason 4 sur la piece de prostatectomie. Methodes Une nouvelle grande etude de cohorte prospective de 1343 patients (âge : 63,9 ans, taille : 175 cm, poids : 82,2 kg, IMC : 26,8 30 kg/m 2 , circonference abdominale : 101 cm) ayant un PCa localise, recrutes dans 4 centres urologiques en France, de 6/2013 a 6/2016. Les parametres du syndrome metabolique (SM) ont ete recueillis. Le dosage de TT, BT, T libre (freeT), DHT, Δ5, Δ4, E1 et E2 ont ete effectue par spectrometrie de masse en phase gazeuse. Une evaluation centralisee des donnees pathologiques (predominance du grade de Gleason 4 [PrdGP4] stade) a ete effectuee. Resultats La cohorte a ete divisee en 2 groupes : – le 1 er groupe se composait de patients ayant predominance du grade 3 de Gleason [i.e. scores de Gleason ≤ 7 (3 + 4)] ; – le 2nd avait une predominance du grade 4 de Gleason [i.e. scores de Gleason ≥ 7 (4 + 3)]. Les patients ayant les cancers les plus agressifs (PrdGP4) etaient significativement plus âges et avaient un PSA superieur. Les concentrations de TT et d’E2 ne differaient pas entre les deux groupes. En revanche, celles de BT et de Free T etaient inferieures chez les patients PrdGP4. Une difference significative dans la concentration de SHBG entre les patients a PrdGP4 et ceux a PrdGP3 a ete observee, conferant a la SHBG un role cle dans la selection des patients a haut risque d’un PCa agressif ( Tableau 1 ). Conclusion L’etude ANDROCAN, plus importante etude de cohorte prospective mondiale sur l’association entre les concentrations des steroides sexuels et les caracteristiques du CaP localises, montre qu’une diminution de la BT definie une population a risque de PCa agressif. Par consequent, pour la prise de decision therapeutique, en plus de la TT, la BT devrait etre evaluee pour la prise en charge du PCa localise. En revanche, l’E2 n’a pas lieu d’etre prise en consideration.

The effects of the polypeptide hormone prolactin (PRL) in the development and regulation of benign prostate hyperplasia (BPH) and also in prostate cancer are not very well characterized. This study examines the action of PRL, either alone or in association with androgens [testosterone (T) or dihydrotestosterone (DHT)], in the rat prostate gland. The effects of PRL and androgens were investigated after 30 and 60 days in control, castrated, castrated with a substitutive implant of T or DHT, and sham-operated Wistar rats. To enhance PRL release, we induced hyperprolactinemia by administering chronic injections of sulpiride (40 mg · kg−1 · day−1). Chronic hyperprolactinemia induces enlargement and inflammation of the lateral rat prostate without any histological changes on ventral and dorsal lobes. We also demonstrate that hyperprolactinemia induces Bcl-2 overexpression in the lateral rat prostate and that this could inhibit the level of apoptosis. The in vivo model established here is a useful in vivo approach for studying the hormonal regulation of normal and pathological prostate development.

BACKGROUND To determine the mechanism by which prostate volume increases during the development of BPH and to evaluate the effect of LSESr (Permixon®), a phytotherapeutic agent, we investigated apoptosis and cell proliferation in the stroma and epithelium of normal prostate and of BPH tissues from patients treated with or without LSESr. METHODS MIB-1 staining and the in situ end-labeling assay were used to evaluate the proliferative-apoptotic balance in normal prostates and in BPH tissues. Quantitative assessment was performed using an image analysis system. RESULTS In normal prostates, there was no significant difference between apoptotic and proliferative indices. Cell numbers and proliferative indices were higher in BPH than in normal prostates, while apoptosis values were similar. In the BPH treated group, LSESr significantly inhibited proliferation and induced cell death in both epithelium and stroma. CONCLUSIONS Induction of apoptosis and inhibition of cell proliferation are likely to be the basis for the clinical efficacy of LSESr. Prostate 45:259–266, 2000. © 2000 Wiley-Liss, Inc.

The aim of this study on testosterone (T) metabolism in benign prostatic hyperplasia (BPH) and prostatic cancer was to compare the formation of metabolites in freshly isolated epithelial cells and in cells of long-term cultures (2 passages) and to identify the 5alpha-reductase (5alpha-R) and 17beta-hydroxysteroid dehydrogenase (17beta-HSD) isoforms responsible for metabolite formation. Androst-4-enedione (A), dihydrotestosterone (DHT) and 5alpha-androstanedione (5alpha-A) formation were measured by high-performance liquid chromatography coupled to a Flo-one HP radioactivity detector. Enzyme isoforms were studied by Northern blot analysis and reverse transcriptase-polymerase chain reaction (RT-PCR). T conversion into A by 17beta-HSD, rather than reduction into DHT by 5alpha-R, was by far the predominant activity in cultured epithelial cells. The metabolic profile did not differ substantially between BPH and cancer cells. Long-term cell culture led to an increase in A formation compared with the level recorded in freshly isolated cells, with no significant incidence on the relative DHT level. According to RT-PCR results, both 5alpha-R isoforms (1 and 2) and 2 17beta-HSD isoforms (2 and 3) are present in epithelial cell cultures and in tissues. According to Northern blot analyses, the mRNAs for 5alpha-R2 and 17beta-HSD4 are expressed in tissue and those for 5alpha-R1 and types 2 and 4 17beta-HSD in isolated cell cultures. Moreover, finasteride, a specific 5alpha-R2 inhibitor, inhibits DHT and 5alpha-A formation in long-term cell culture of adenocarcinoma epithelial cells plated on Matrigel, suggesting a 5alpha-R2 expression. Thus, although 5alpha-R2 is present in freshly isolated epithelial cell cultures and in long-term epithelial cells cultured on Matrigel and predominates in prostate tissue, it is the 5alpha-R1 isoform that is preferentially expressed in epithelial cell cultures.

Objective: To assess the effect of the lipidosterolic extract of Serenoa repens (LSESr) on in vitro cell proliferation in biopsies of human prostate Material and Methods: Cell proliferation was assessed by incorporation of [3H]thymidine followed by historadiography. Results: Basic fibroblast growth factor (b-FGF) induced a considerable increase in human prostate cell proliferation (from +100 to +250%); the glandular epithelium was mainly affected, minimal labeling being recorded in the other regions of the prostate. Similar results were observed with epidermal growth factor (EGF), although the increase in cell proliferation was not recorded in some cases. Lovastatin, an inhibitor of hydroxymethylglutaryl coenzyme A, antagonized both the basal proliferation and the growth factor-stimulated proliferation of human prostate epithelium (EGF, mean inhibition ≈80–95%; b-FGF, mean inhibition ≈40–90%). Geraniol, a precursor of both farnesyl pyrophosphate and geranylgeranyl pyrophosphate, and farnesol, the precursor of farnesyl pyrophosphate, increased cell proliferation only in some prostate specimens, this effect being antagonized by lovastatin. LSESr did not affect basal prostate cell proliferation, with the exception of two prostate specimens in which a significant inhibition of basal proliferation was observed with the highest concentration of LSESr (30 µg/ml). In contrast, LSESr inhibited b-FGF-induced proliferation of human prostate cell cultures; this effect was significant for the highest concentration of LSESr (30 µg/ml). In some prostate samples, a similar inhibition was also noted with lower concentrations. Unsaturated fatty acids (UFA), in the range 1–30 ng/ml, did not affect the basal prostate cell proliferation, only a slight increase in cell proliferation was noted in 1 prostate specimen. UFA (1, 10 or 30µg/ml) markedly inhibited the b-FGF-induced cell proliferation down to the basal value. Lupenone, hexacosanol and the unsaponified fraction of LSESr markedly inhibited the b-FGF-induced cell proliferation, whereas a minimal effect on basal cell proliferation was noted. Conclusions: Despite the large variability in the response of the prostate samples to b-FGF, these results indicate that LSESr and its components affect the proliferative response of prostate cells to b-FGF more than their basal proliferation.

INTRODUCTION AND OBJECTIVES: Predominance of Gleason grade 4 is a prognostic factor of the first order in prostate cancer. The objective of this study was to evaluate the performance of the prostate biopsy (PB) to determine the predominance of Gleason grade 4. METHODS: From March 2007 to September 2012, 786 patients had a PB before a radical prostatectomy in the same center. Gleason score determined by the PB was compared to that established in the analysis of the prostatectomy specimen. RESULTS: With PB, the Gleason score was over-assessed, properly assessed, or underestimated in 9.4%, 48.4% and 42.2% of cases respectively. The sensitivity and specificity of the PB to determine the predominance of Gleason grade 4, were 43.7% and 94.6% respectively. The positive predictive value and negative predictive value were 78.7% and 78.8% respectively. The risk of not diagnosing the predominance of Gleason grade 4 was 56.3%. CONCLUSIONS: The Gleason score was determined accurately by the PB in only one case out of two. More over the risk of being unawared of Gleason grade 4 predominant was estimated at 56.3%. Thus the overall risk of underestimation of Gleason score should be known and taken into account in treatment option.

BACKGROUND Controversy regarding the relative efficacy of treatments for the relief of the symptoms of benign prostatic hyperplasia (BPH). METHODS This was a 6-month double-blind randomized equivalence study that compared the effects of a plant extract (320 mg Permixon®) with those of a 5α-reductase inhibitor (5 mg finasteride) in 1,098 men with moderate BPH using the International Prostate Symptom Score (IPSS) as the primary end-point. RESULTS Both Permixon® and finasteride decreased the IPSS (−37% and −39%, respectively), improved quality of life (by 38 and 41%), and increased peak urinary flow rate (+25% and +30%, P = 0.035), with no statistical difference in the percent of responders with a 3 ml/sec improvement. Finasteride markedly decreased prostate volume (−18%) and serum PSA levels (−41%); Permixon® improved symptoms with little effect on volume (−6%) and no change in PSA levels. Permixon® fared better than finasteride in a sexual function questionnaire and gave rise to less complaints of decreased libido and impotence. CONCLUSIONS Both treatments relieve the symptoms of BPH in about two-thirds of patients but, unlike finasteride, Permixon® has little effect on so-called androgen-dependent parameters. This suggests that other pathways might also be involved in the symptomatology of BPH. © 1996 Wiley-Liss, Inc.

We compare testosterone (T) metabolism in primary cultures of epithelial cells and fibroblasts separated from benign prostate hypertrophy (BPH) and prostate cancer tissues. In all cultures, androstenedione (delta 4) formed by oxidation of T by 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) represented 80% of the metabolites recovered. The amounts of 5 alpha-dihydrotestosterone (DHT), formed by reduction of T by 5 alpha-reductase (5 alpha-R), were small: 5 and 2% (BPH) and 8 and 15% (adenocarcinoma) for epithelial cells and fibroblasts, respectively. Northern blot analysis of total RNA from epithelial cells (BPH or adenocarcinoma) attributed the reductive activity to the 5 alpha-reductase type 1 isozyme and oxidative activity to the 17 beta-HSD type 2. In cancer fibroblasts, only little 17 beta-HSD type 2 mRNA was detected. The 5 alpha-reductase inhibitors, 4-MA (17 beta-(N,N-diethyl)carbamoyl-4-methyl-4-aza-5 alpha-androstan-3-one) and finasteride, inhibited DHT formation with a preferential action of 4-MA on epithelial cells (BPH or adenocarcinoma) and of finasteride on fibroblasts from adenocarcinoma. Neither inhibitor acted on delta 4 formation. On the other hand, the lipido-sterol extract of Serenoa repens (LSESr, Permixon) inhibited the formation of all the T metabolites studied [IC50 S = 40 and 200 micrograms/ml (BPH) and 90 and 70 micrograms/ml (adenocarcinoma) in epithelial cells and fibroblasts, respectively]. These results have important therapeutic implications when selecting appropriate treatment options for BPH.

Objectifs Epstein et al. ont propose une nouvelle classification histologique des cancers de prostate afin de simplifier et pallier les limites du score de Gleason (SG). L’objectif de cette etude etait de valider ce modele dans une cohorte de patients traites par prostatectomie radicale (PR). Methodes Etude retrospective, monocentrique, incluant tous les patients operes d’une prostatectomie radicale entre janvier 2007 et decembre 2009. Le suivi median a ete de 61,8 mois (3 a 107 mois). Le SG a ete determine sur les biopsies de prostate (PBP) et sur les pieces de PR et valide par deux uropathologistes. Les patients ont ete repartis en fonction des 5 groupes definis par Epstein pour les SG 6, 7 (3+4), 7 (4+3), 8 et 9–10. La survie sans recidive biologique (SSR) etait evaluee en fonction du groupe histologique et de leur origine (PBP ou PR). Resultats Au total, 431 patients ont ete inclus. Les caracteristiques de la population sont detaillees dans le Tableau 1 et la repartition des patients en fonction du grade dans le Tableau 2 . La survie sans recidive biochimique en fonction de la classe histologique et du type de prelevements est renseignee dans la Fig. 1 . La SSR etait superieure dans le groupe 1 par rapport au groupe 2 que ce soit a partir de l’evaluation par PBP ou PR (respectivement p = 0,0005 et p = 0,0248). De meme, la SSR du groupe 2 etait meilleure que celle du groupe 3 ( p = 0,0113, p p = 0,86 et p = 0,11). Conclusion Nos resultats ont ete comparables a ceux de Epstein et al. temoignant d’un pronostic inferieur des patients a partir du groupe 3. Cette classification permet donc de simplifier la classification des cancers de prostate en scindant les SG 7 en 2 groupes, anciennement 7 (3+4) et 7 (4+3), dont le pronostic sont clairement differents.

The present study describes the independent expression of the type 1 and 2 isoforms of human 5 alpha-reductase in the baculovirus-directed insect cell expression system and the selectivity of their inhibition. The catalytic properties and kinetic parameters of the recombinant isozymes were consistent with published data. The type 1 isoform displayed a neutral (range 6-8) pH optimum and the type 2 isoform an acidic (5-6) pH optimum. The type 2 isoform had higher affinity for testosterone than did the type 1 isoform (Km = 0.5 and 2.9 microM, respectively). Finasteride and turosteride were selective inhibitors of the type 2 isoform (Ki (type 2) = 7.3 and 21.7 nM compared to Ki (type 1) = 108 and 330 nM, respectively). 4-MA and the lipido-sterol extract of Serenoa repens (LSESr) markedly inhibited both isozymes (Ki (type 1) = 8.4 nM and 7.2 micrograms/ml, respectively; Ki (type 2) = 7.4 nM and 4.9 micrograms/ml, respectively). The three azasteroids were competitive inhibitors vs substrate, whereas LSESr displayed non-competitive inhibition of the type 1 isozyme and uncompetitive inhibition of the type 2 isozyme. These observations suggest that the lipid component of LSESr might be responsible for its inhibitory effect by modulating the membrane environment of 5 alpha-reductase. Partially purified recombinant 5 alpha-reductase type 1 activity was preserved by the presence of lipids indicating that lipids can exert either stimulatory or inhibitory effects on human 5 alpha-reductase.

We characterized the aggressiveness of prostate cancer by Gleason score and predominant Gleason pattern in relation to preoperative serum testosterone.In a prospective study serum total testosterone was measured preoperatively in patients referred to our department from January 2007 to January 2011 for radical prostatectomy. Gleason score and predominant Gleason pattern were determined in prostate biopsy and prostate tissue specimens.A total of 431 patients were enrolled in the study. In biopsies a predominant Gleason pattern 4 was observed in 72 patients (17%). In prostate specimens the predominant Gleason pattern 4 increased to 132 patients (31%). In the 132 patients total testosterone was lower than in the 299 with predominant Gleason pattern 3 (4.00 vs 4.50 ng/ml, p = 0.001), prostate specific antigen was higher (8.4 vs 6.6 ng/ml, p0.00001), and extraprostatic extension and positive margins were noted more often (49% vs 20% and 23% vs 14%, p0.000001 and 0.02, respectively). The 62 patients with total testosterone less than 3.0 ng/ml were larger (mean 7 kg, p = 0.0001) with a higher body mass index (mean 0.5 kg/m(2), p0.000001). They had a higher percent of Gleason score with predominant Gleason pattern 4 (47% vs 28%, p = 0.002).Low total testosterone is associated with a higher percent of predominant Gleason pattern 4, a signature of prostate cancer aggressiveness. Tumor aggressiveness cannot be accurately estimated by biopsy Gleason score and predominant Gleason pattern. Preoperative total testosterone should be added to prostate specific antigen determination to improve management for prostate cancer.

The following hormones, the plasma protein SHBG, and the tumor markers prostatic acid phosphatase (PAP) and prostate-specific antigen (PSA) were assayed at 18 time-points over 1 month during a double-blind randomized study in 36 stage D2 cancer patients receiving either "buserelin+placebo" or "buserelin+nilutamide (Anandron)": LH, FSH, estradiol, testosterone, dihydrotestosterone, androstenedione, 5-androstene-3,17 beta-diol, dehydroepiandrosterone and its sulfate, cortisol, 17 alpha-hydroxyprogesterone, pregnenolone, 17 alpha-hydroxypregnenolone, and 3 alpha-androstanediol glucuronide. Multivariate analysis of the treatment values (over 10,000 assays) by two complementary methods, correspondence factorial analysis (CFA) and the minimum spanning tree (MST) method, identified those variables within the pathways of androgen metabolism that were correlated over time and, in a comparison of the two treatment groups, identified the enzyme targets of nilutamide action in humans. Whereas nilutamide tended to decrease androstenedione slightly, it affected no other variables including cortisol, except for pregnenolone, 17 alpha-OH-pregnenolone, and 17 alpha-OH-progesterone, which were increased. These increases are indicative of weak inhibition of C17,20 lyase by nilutamide, but, according to the multivariate analysis, are insufficient to account for the more marked and rapid fall in PAP and PSA noted on addition of nilutamide to buserelin that must therefore be explained by another mechanism such as androgen receptor blockade by nilutamide.