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Background erectile dysfunction is associated with mortality, whereas the association between low testosterone (T) and higher mortality remains controversial. Sexual dysfunction and low T often coexist, but the relative importance of sexual symptoms versus low T in predicting mortality is not known. We studied the interrelationships between sex steroids and sexual symptoms with all-cause mortality in a large prospective cohort of European men. Design survival status was assessed in 1,788 community-dwelling men, aged 40–79, who participated in the European Male Ageing Study (EMAS). Sexual symptoms were evaluated via a validated questionnaire (EMAS-SFQ). Sex steroids were measured by mass spectrometry. Cox proportional hazard models were used to study the association between hormones, sexual symptoms and mortality. Results about 420 (25.3%) men died during a mean follow-up of 12.6 ± 3.1 years. Total T levels were similar in both groups, but free T was lower in those who died. Men with three sexual symptoms (erectile dysfunction, reduced morning erections and lower libido) had a higher mortality risk compared with men with none of these symptoms (adjusted hazard ratio (HR) and 95% confidence intervals: 1.75 (1.28–2.40, P  = 0.001)). Particularly, erectile dysfunction and poor morning erections, but not lower libido, were associated with increased mortality (HR 1.40 (1.13–1.74, P  = 0.002), 1.28 (1.04–1.59, P  = 0.023) and 1.12 (0.90–1.39, P  = 0.312), respectively). Further adjusting for total T, free T or oestradiol did not influence the observed risk. Conclusions sexual symptoms, in particular erectile dysfunction, predict all-cause mortality independently of sex steroids and can be an early warning sign of a poor health status. [ABSTRACT FROM AUTHOR]

Introduction. Assessment of male sexual dysfunction has been the focus of substantial scientific effort. Less research has focused on the development of instruments for the measurement of sexual functioning in aging men. Aims. The aims of this study were: (i) to characterize the psychometric properties of a new brief, reliable, and valid measure of male sexual functioning for use in a large population survey of middle-aged and elderly European men; and (ii) specifically, to determine whether the new instrument, the European Male Ageing Study–sexual function questionnaire (EMAS–SFQ), discriminates between men with high and low levels of circulating testosterone (T) (total T, free T, and bioavailable T). Method. One thousand six hundred men aged 40–79 years completed the self-administered EMAS–SFQ, the Beck depression inventory, and provided a blood sample for assessment of sex hormones. Eighty-five men aged 35–74 years completed the EMAS–SFQ twice, 2 weeks apart to examine the test–retest reliability of the instrument. Main Outcome Measures. Scores on the EMAS–SFQ in relation to age and T levels. Results. Principal component analysis showed that the EMAS–SFQ had four distinct domains (overall sexual functioning [OSF], masturbation, sexual functioning-related distress, and change in sexual functioning). The instrument demonstrated excellent internal and test–retest reliability, as well as convergent, divergent, and discriminant validity. Men with the lowest levels of total, free, and bioavailable T reported lower OSF scores compared to men with the highest T levels. Conclusions. The EMAS–SFQ is a valid and reproducible instrument, sensitive to age and T levels. It should be suitable for the assessment of sexual health in population samples of men in epidemiological studies of aging. O'Connor DB, Corona G, Forti G, Tajar A, Lee DM, Finn JD, Bartfai G, Boonen S, Casanueva FF, Giwercman A, Huhtaniemi IT, Kula K, O'Neill TW, Pendleton N, Punab M, Silman AJ, Vanderschueren D, Wu FCW, and the European Male Ageing Study group. Assessment of sexual health in aging men in Europe: Development and validation of the European Male Ageing Study sexual function questionnaire. J Sex Med 2008;5:1374–1385. [ABSTRACT FROM AUTHOR]

Introduction In the last few years, a view that subclinical endocrine disorders represent milder forms of the clinically overt disease has emerged. Accordingly, it has been proposed that compensated hypogonadism represents a genuine clinical subset of late-onset hypogonadism. Aim The aim of the present study is to investigate the associations of compensated hypogonadism with particular clinical and psychological characteristics of male subjects complaining of sexual dysfunction. Methods After excluding documented genetic causes of hypogonadism, an unselected consecutive series of 4,173 patients consulting our unit for sexual dysfunction was studied. Compensated hypogonadism was identified according to the European Male Ageing study criteria: total testosterone ≥10.5 nmol/L and luteinizing hormone >9.4 U/L. Main Outcome Measures Several hormonal, biochemical, and instrumental (penile Doppler ultrasound) parameters were studied, along with results of the Structured Interview on Erectile Dysfunction ( SIEDY) and ANDROTEST. Results One hundred seventy (4.1%) subjects had compensated hypogonadism, whereas 827 (19.8%) had overt hypogonadism. After adjustment for confounding factors, no specific sexual symptoms were associated with compensated hypogonadism. However, compensated hypogonadism individuals more often reported psychiatric symptoms, as detected by Middlesex Hospital Questionnaire score, when compared with both eugonadal and overt hypogonadal subjects (adjusted odds ratios = 1.018 [1.005;1.031] and 1.014 [1.001;1.028], respectively; both P < 0.005). In addition, subjects with compensated or overt hypogonadism had an increased predicted risk of cardiovascular events (as assessed by Progetto Cuore risk algorithm) when compared with eugonadal individuals. Accordingly, mortality related to major adverse cardiovascular events ( MACEs), but not MACE incidence, was significantly higher in subjects with both compensated and overt hypogonadism when compared with eugonadal subjects. Conclusions The present data do not support the concept that compensated (subclinical) hypogonadism represents a new clinical entity. The possibility that subclinical hypogonadism could be a normal response of the hypothalamus-pituitary-testis axis to somatic illness should be considered. Further studies are urgently needed to clarify this latter point. Corona G, Maseroli E, Rastrelli G, Sforza A, Forti G, Mannucci E, and Maggi M. Characteristics of compensated hypogonadism in patients with sexual dysfunction. J Sex Med 2014;11:1823-1834. [ABSTRACT FROM AUTHOR]

Introduction We previously reported that in male patients consulting for sexual dysfunction, low prolactin ( PRL) levels were associated with metabolic syndrome ( MetS), arteriogenic erectile dysfunction, and incident major cardiovascular events. Aim The aim of this study is to assess the clinical associations of PRL levels in the European Male Ageing Study ( EMAS). Methods EMAS is a prospective, observational cohort of community-dwelling men aged 40-79 years old (mean age 60 ± 11 years old). PRL was available for 2,948 men. Main Outcome Measures Different parameters were evaluated including the Short Form-36 questionnaire, Becks Depression Inventory, the Adverse Life Events Scale, the Physical Activity Scale for the Elderly, and the EMAS sexual function questionnaire ( EMAS-SFQ). Results After the adjustment for confounders, PRL levels were inversely related with worsening of sexual function as compared with the previous year, as derived from change in sexual functioning domain of the EMAS-SFQ (adj. r = −0.043; P = 0.029). The strongest correlation ( Wald = 6.840; P = 0.009) was observed between lower PRL levels and reduced enjoyment of orgasmic experiences. Furthermore, an inverse relationship between PRL levels and stressful life events or depressive symptoms was observed. Low PRL was also negatively associated with an unhealthy metabolic phenotype as well as with the MetS (Wald = 5.229; P = 0.022). In line with these data, low PRL was associated with a lower level of physical activity and feeling unhealthier. Conclusions Low PRL is related to several metabolic, psychological, and sexual unhealthy characteristics in European men. Checking PRL might be useful to stratify men for cardiovascular risk and to encourage appropriate lifestyle changes. Corona G, Wu FC, Rastrelli G, Lee DM, Forti G, O'Connor DB, O'Neill TW, Pendleton N, Bartfai G, Boonen S, Casanueva FF, Finn JD, Huhtaniemi IT, Kula K, Punab M, Vanderschueren D, Rutter MK, Maggi M, and the EMAS Study Group. Low prolactin is associated with sexual dysfunction and psychological or metabolic disturbances in middle aged and elderly men: The European Male Aging Study (EMAS). J Sex Med 2014;11:240-253. [ABSTRACT FROM AUTHOR]

Introduction The relationship between serum prostate-specific antigen ( PSA) and testosterone ( T) levels is still controversial. According to the 'saturation hypothesis,' a significant relationship is apparent only in the low T range. Aim To verify whether, in a large sample of male subjects seeking medical care for sexual dysfunction ( SD), PSA might represent a reliable marker of T levels. Methods A consecutive series of 3,156 patients attending our unit for SD was studied. Among them, only subjects without history of prostate disease and with PSA levels <4 ng/ mL (N = 2,967) were analyzed. Main Outcome Measures Several hormonal and biochemical parameters were studied, along with structured interview on erectile dysfunction ( SIEDY), ANDROTEST, and PsychoANDROTEST. Results Receiver operating characteristic curve analysis for predicting severe hypogonadism ( T < 8 nmol/ L) showed an accuracy of PSA = 0.612 ± 0.022 ( P < 0.0001), with the best sensitivity and specificity at PSA < 0.65 ng/ mL (65.2% and 55.5%, respectively). In the entire cohort, 254 subjects (8.6%) showed T < 8 nmol/ L and, among them, more than half (N = 141, 4.8%) had PSA < 0.65 ng/ mL. After adjusting for age, low PSA was associated with hypogonadism-related features (i.e., delayed puberty, lower testis volume) and associated conditions, such as metabolic syndrome (hazard ratio [ HR] = 1.506 [1.241-1.827]; P < 0.0001), type 2 diabetes ( HR = 2.044 [1.675-2.494]; P < 0.0001), and cardiovascular diseases ( HR = 1.275 [1.006-1.617]; P = 0.045). Furthermore, low PSA was associated with impaired sex- and sleep-related erections. The association between low PSA and hypogonadal symptoms and signs as well as with metabolic syndrome was retained even after adjusting for T levels. Sensitivity and positive predictive values of low PSA increased, whereas specificity and negative predictive value decreased as a function of age. Conclusions PSA is a marker of T concentrations and it may represent a new tool in confirming hypogonadism. The determination of PSA levels might give insights not only on the circulating levels of total T but also on its active fractions. Rastrelli G, Corona G, Vignozzi L, Maseroli E, Silverii A, Monami M, Mannucci E, Forti G, and Maggi M. Serum PSA as a predictor of testosterone deficiency. J Sex Med 2013;10:2518-2528. [ABSTRACT FROM AUTHOR]

Introduction Hypoactive sexual desire is defined as a persistent or recurrent deficient or absent sexual fantasies or desire for sexual activity that should not be comorbid with other medical conditions or with the use of psychoactive medications. Reduced libido is a symptom referring more to a reduction in sexual drive for sexual activity. Aim To investigate the risk factors of primary reduced libido (i.e., not associated with conditions causing loss of libido such as hypogonadism, hyperprolactinemia, psychopathology, and/or psychoactive medications) or secondary reduced libido (i.e., with aforementioned conditions) in male patients with sexual dysfunction. Method A consecutive series of 3,714 men (mean age 53.2 ± 12.5 years) was retrospectively studied. Main Outcome Measures Patient's reduced libido was evaluated using question #14 of structured interview for erectile dysfunction ( SIEDY) ('Did you have more or less desire to make love in the last 3 months?'). Results Reduced libido was comorbid with erectile dysfunction, premature ejaculation, and delayed ejaculation in 38%, 28.2%, and 50%, respectively, whereas it was isolated in 5.1%. Reduced libido prevalence was substantially increased by hypogonadism, almost doubled by psychopathology and universally present in subjects with hyperprolactinemia (secondary reduced libido). Subjects with primary reduced libido are characterized by higher postschool qualification, more disturbances in domestic and dyadic relationships, and an overall healthy body (lower glycemia and triglyceride levels). Accordingly, in patients with primary reduced libido, the risk of major cardiovascular events as calculated with the Progetto Cuore algorithm was lower than in the rest of the sample. Features of hypogonadism- or psychopathology-associated reduced libido essentially reflect their underlying conditions. Comorbidity with other sexual dysfunctions did not affect the main characteristics of primary or secondary reduced libido. Conclusions Primary and secondary reduced libido have different risk factors and clinical characteristics. Recognizing primary or secondary reduced libido will help clinicians to identify comorbidities and to tailor appropriate treatments. [ABSTRACT FROM AUTHOR]

ABSTRACT Introduction. The category of impaired fasting glucose (IFG) denotes a state of nondiabetic hyperglycemia, considered a risk factor for the further development of diabetes mellitus (DM) and cardiovascular (CV) diseases. Aim. The aim of the present study is to evaluate the impact of IFG on sexual health in men. In addition, its effect on CV morbidity and mortality will also be addressed. Methods. A consecutive series of 3,451 men (mean age 57.3 ± 10.1 years) attending our outpatient clinic for sexual dysfunction was retrospectively studied. A subset of this sample (N = 1,687) was enrolled in a longitudinal study. Main Outcome Measures. Several clinical, biochemical (including testosterone), and instrumental (penile color Doppler ultrasound) factors were evaluated. IFG was defined by fasting glucose concentrations between 5.6 and 6.9 mmol/L (100-125 mg/dL). A higher threshold (6.1-6.9 mmol/L, 110-125 mg/dL) was also considered. Results. Among the patients studied, 747 (21.7%) had DM. In addition, 659 (19.1%) subjects were classified as IFG. Patients with IFG, however defined, more often had severe ED, reduced penile blood flow, and overt hypogonadism when compared with patients with normal glucose levels. In addition, men with ED and IFG show poorer blood pressure and lipid profile with an overall increase in CV risk. Unadjusted incidence of major adverse CV events was significantly associated with baseline DM, whereas there was a trend toward higher risk also for IFG, but this did not reach statistical significance. Conversely, both IFG and DM were significantly associated with a higher risk of fatal and nonfatal cerebral events. Conclusions. Checking glucose and testosterone levels is mandatory in subjects with ED because testosterone substitution in impotent IFG subjects might ameliorate not only their sexual life but also their overall health. Corona G, Rastrelli G, Balercia G, Lotti F, Sforza A, Monami M, Forti G, Mannucci E, and Maggi M. Hormonal association and sexual dysfunction in patients with impaired fasting glucose: A cross-sectional and longitudinal study. J Sex Med 2012;9:1669-1680. [ABSTRACT FROM AUTHOR]

Background: The association between aging-related testosterone deficiency and late-onset hypogonadism in men remains a controversial concept. We sought evidence-based criteria for identifying late-onset hypogonadism in the general population on the basis of an association between symptoms and a low testosterone level. Methods: We surveyed a random population sample of 3369 men between the ages of 40 and 79 years at eight European centers. Using questionnaires, we collected data with regard to the subjects' general, sexual, physical, and psychological health. Levels of total testosterone were measured in morning blood samples by mass spectrometry, and free testosterone levels were calculated with the use of Vermeulen's formula. Data were randomly split into separate training and validation sets for confirmatory analyses. Results: In the training set, symptoms of poor morning erection, low sexual desire, erectile dysfunction, inability to perform vigorous activity, depression, and fatigue were significantly related to the testosterone level. Increased probabilities of the three sexual symptoms and limited physical vigor were discernible with decreased testosterone levels (ranges, 8.0 to 13.0 nmol per liter [2.3 to 3.7 ng per milliliter] for total testosterone and 160 to 280 pmol per liter [46 to 81 pg per milliliter] for free testosterone). However, only the three sexual symptoms had a syndromic association with decreased testosterone levels. An inverse relationship between an increasing number of sexual symptoms and a decreasing testosterone level was observed. These relationships were independently confirmed in the validation set, in which the strengths of the association between symptoms and low testosterone levels determined the minimum criteria necessary to identify late-onset hypogonadism. Conclusions: Late-onset hypogonadism can be defined by the presence of at least three sexual symptoms associated with a total testosterone level of less than 11 nmol per liter (3.2 ng per milliliter) and a free testosterone level of less than 220 pmol per liter (64 pg per milliliter). N Engl J Med 2010;363:123-35. [ABSTRACT FROM AUTHOR]

Introduction. We have recently reported that the perceived loss of a partner's sexual desire is independently associated with an increased incidence of major cardiovascular events in patients with erectile dysfunction (ED). No study has ever evaluated the specific impact of men's perception of women's sexual desire on male sexual function and lifestyle attitudes in ED subjects. Aim. To evaluate the clinical correlates of the perception of a partner's sexual desire [hypoactive sexual desire (HSD)] in a consecutive series of subjects seeking medical care for ED. Methods. A consecutive series of 2,303 heterosexual male patients (mean age 58.1 ± 10.5) was studied. Main Outcome Measures. Patients were interviewed with the Structured Interview on Erectile Dysfunction (SIEDY) structured interview. They also completed the Middlesex Hospital Questionnaire, a brief questionnaire for the screening of the symptoms of mental disorders. Results. Among the patients studied, 458 (19.9%) reported a mild loss of their partner's desire, 302 (13.1%) a moderate reduction of libido, while 118 (5.1%) complained of a complete absence of sexual interest on the part of their partner. After adjustment for confounding factors, the perceived women's HSD was associated with different sexual, lifestyle, and relational factors. In particular, more extra-marital affairs, a longer and more hostile couple relationship, as well as a stressful job and both alcohol and smoking abuse were all significantly associated with perceived women's HSD. In addition, the perceived women's moderate to severe HSD was significantly associated with severe ED and less frequent sexual intercourse. Finally, partner HSD was significantly associated with a stepwise increase of free-floating anxiety and depressive symptoms (adj. r = 0.081, P < 0.05 and 0.158, P < 0.0001, respectively). Conclusions. Perceived sexual interest ( éros) on the part of the woman can be seen for men not only as a fun and enjoyable behavior, but also a safe strategy for improving a man's overall health and life expectancy. Corona G, Bandini E, Fisher A, Elisa M, Boddi V, Balercia G, Sforza A, Forti G, Mannucci E, and Maggi M. Psychobiological correlates of women's sexual interest as perceived by patients with erectile dysfunction. J Sex Medical 2010;7:2174–2183. [ABSTRACT FROM AUTHOR]

Introduction. Concern about a testosterone (T)-induced prostate-specific antigen (PSA) increase is often perceived as one of the main limitations in treating hypogonadism even when it is symptomatic, such as in subjects with sexual dysfunction (SD). Aim. The aim of this study was to evaluate the relationship between T and PSA levels in subjects with SD. Methods. We retrospectively evaluated the relationship between T and PSA in 2,291 subjects seeking medical care at our outpatient clinic for SD (sample A). The analysis was then repeated in a selected subpopulation of 1,421 subjects apparently free from prostatic diseases (sample B). Main Outcome Measures. The specific association between PSA levels, circulating androgens, and different clinical signs and symptoms of hypogonadism, as assessed by ANDROTEST structured interview, was evaluated. Results. In both samples A and B, subjects with higher PSA levels reported a lower prevalence of hypogonadism-related symptoms and signs, as well as higher total testosterone (TT), and analogue and calculated free T. However, when the association between PSA and T was evaluated as a function of T deciles, the upper nine groups had similar PSA values, with the lowest demonstrated a significantly reduced PSA (the lowest vs. the rest of the sample: 0.61[0.38–1.23] ng/mL vs. 0.86[0.57–1.44] ng/mL, and 0.51[0.30–0.94] ng/mL vs. 0.73[0.52–1.10] ng/mL, respectively, for samples A and B; both P < 0.0001). Furthermore, when the relationship between hypogonadism (TT < 8 nmol/L) and PSA levels was evaluated according to age, it was significant only in younger subjects, but not in the older ones. Conclusions. Our data demonstrated that PSA is unrelated to T concentration across most of the T range, except for the most severely T deficient, and that a significant relationship between T and PSA is seen in younger but not in older men. Corona G, Boddi V, Lotti F, Gacci M, Carini M, De Vita G, Sforza A, Forti G, Mannucci E, and Maggi M. The relationship of testosterone to prostate-specific antigen in men with sexual dysfunction. J Sex Med 2010;7:284–292. [ABSTRACT FROM AUTHOR]

Introduction. Couple sexual dysfunction is a common, but not often studied, problem. Aim. We have previously reported that disturbance in the relational domain, as measured by SIEDY Scale 2 (exploring, as reported by the patient, menopausal symptoms, partner's medical illness interfering with sexual activity, and reduced partner desire and climax), is associated with different sexual dysfunctions, such as hypoactive sexual desire, erectile dysfunction (ED), delayed ejaculation, and psychological disturbances. As all of these symptoms could be associated with hypogonadism, we have investigated the possible relationship between androgen levels and an unhappy couple relationship. Methods. A consecutive series of 2,302 (mean age 53.2 ± 12.5 years) male patients with ED was studied. Main Outcome Measures. Several hormonal parameters were investigated, along with penile Doppler ultrasound (PDU) and the Structured Interview on Erectile Dysfunction (SIEDY) and ANDROTEST. Higher ANDROTEST score identifies a higher prevalence of hypogonadism-related symptoms and signs. Results. SIEDY Scale 2 score was associated with decreased intercourse frequency, severe ED, lower dynamic peak systolic velocity at PDU, and clinical (ANDROTEST score) and biochemical (low total and free testosterone) hypogonadism, even after adjusting for cofounders, such as patient's and partner's age, waist circumference, and smoking habit. Alternative models were explored using these different factors as dependent variables in order to evaluate the specific relationship among the parameters studied. Multiple logistic regression analysis indicated that low penile blood flow and decreased intercourse frequency are bi-directionally coupled to poor relational domain, while the association with hypogonadism was mediated through sexual hypoactivity or inertia. Conclusions. Our data suggest that, in subjects consulting for sexual dysfunction, a deterioration of the couple's relationship is associated with impairment in sexual activities, which, in turn, can lead to a mild hypogonadism. Any speculation on pathogenetic relationships should be confirmed through prospective studies or intervention trials. Corona G, Mannucci E, Lotti F, Boddi V, Jannini EA, Fisher AD, Monami M, Sforza A, Forti G, and Maggi M. Impairment of couple relationship in male patients with sexual dysfunction is associated with overt hypogonadism. J Sex Med 2009;6:2591–2600. [ABSTRACT FROM AUTHOR]

Introduction. The relationship between testosterone (T) and psychopathology in subjects with sexual dysfunction has not been completely clarified. Aim. To evaluate the association between T levels and different psychopathological symptoms and traits in men seeking treatment for sexual dysfunction. Methods. A consecutive series of 2,042 heterosexual male patients (mean age 51.8 ± 13) consulting an outpatient clinic for sexual dysfunction was retrospectively studied. Main Outcome Measures. Several hormonal, biochemical, and instrumental parameters were investigated, including testis volume (Prader orchidometr) and penile blood flow (penile Doppler ultrasound). Patients were interviewed, prior to the beginning of any treatment, with the previously validated Structured Interview on Erectile Dysfunction (SIEDY), and ANDROTEST (a structured interview for the screening of hypogonadism in patients with sexual dysfunction). They also completed the Middlesex Hospital Questionnaire (MHQ) a brief self-reported questionnaire for the screening of the symptoms of mental disorders in nonpsychiatric setting. Results. T levels showed a negative correlation with depressive and anxiety (somatized and phobic) symptoms. Conversely, histrionic/hysterical traits were strongly and positively associated with elevated T. Men with histrionic/hysterical traits had higher androgenization, as suggested by both higher total and free T, higher testis volume and a lower ANDROTEST score. They were also characterized by better self-reported sexual functioning and penile blood flow. Accordingly, when SIEDY scales were considered, SIEDY scale 2 (relational domain) was significantly lower in subjects with histrionic/hysterical traits further indicating a more satisfying sexual relationship. Conclusions. In men consulting for sexual dysfunction, histrionic/hysterical personality is associated with higher androgenization and better sexual functioning. Hysteria, previously considered as a typically feminine psychopathological trait (the uterine theory), should now be considered as an index of better masculine sexual well-being. Bandini E, Corona G, Ricca V, Fisher AD, Lotti F, Sforza A, Faravelli C, Forti G, Mannucci E, and Maggi M. Hysterical traits are not from the uterus but from the testis: A study in men with sexual dysfunction. J Sex Med 2009;6:2321–2331. [ABSTRACT FROM AUTHOR]

Introduction. The physiological role of prolactin (PRL) in male sexual behavior is poorly understood. Conversely, the association between PRL pathological elevation in both reproductive and sexual behavior is well defined. Aim. The aim of the present study is to assess the correlates of normal PRL (PRL < 735 mU/L or 35 ng/mL), in male subjects consulting for sexual dysfunction. Methods. A consecutive series of 2,531 (mean age 52.0 ± 12.9 years) subjects was investigated. Patients were interviewed using the structured interview on erectile dysfunction (SIEDY), a 13-item tool for the assessment of erectile dysfunction (ED)-related morbidities. Middlesex Hospital Questionnaire was used for the evaluation of psychological symptoms. Main Outcome Measures. Several hormonal (testosterone, thyroid stimulation hormone, and PRL) and biochemical parameters (glycemia and lipid profile) were studied, along with penile Doppler ultrasound (PDU) and SIEDY items. Results. After adjustment for confounders anxiety symptoms decreased across PRL quartiles (I: <113 mU/L or 5 ng/mL; II: 113–156 mU/L or 5.1–7 ng/mL; III: 157–229 mU/L or 7.1–11 ng/mL; IV: 229–734 mU/L or 11.1–34.9 ng/mL). Patients in the lowest PRL quartile showed a higher risk of metabolic syndrome (MetS; odds ratio [OR] = 1.74 [1.01–2.99], P < 0.05), arteriogenic ED (peak systolic velocity at PDU < 35 cm/sec; OR = 1.43 [1.01–2.03], P < 0.05), and premature ejaculation (PE; OR = 1.38 [1.02–1.85]; P < 0.05). Conversely, comparing subjects with PRL-secreting pituitary adenomas (N = 13) with matched controls, no significant difference was observed, except for a higher prevalence of hypoactive sexual desire in hyperprolactinemia. Conclusions. Our findings demonstrate that, in subjects consulting for sexual dysfunction, PRL in the lowest quartile levels are associated with MetS and arteriogenic ED, as well as with PE and anxiety symptoms. Further studies are advisable in order to confirm our preliminary results in different populations. Corona G, Mannucci E, Jannini EA, Lotti F, Ricca V, Monami M, Boddi V, Bandini E, Balercia G, Forti G, and Maggi M. Hypoprolactinemia: A new clinical syndrome in patients with sexual dysfunction. J Sex Med 2009;6:1457–1466. [ABSTRACT FROM AUTHOR]

Introduction. Sexual dysfunctions are often present in subjects with mood disturbances; however. antidepressants can induce per se sexual dysfunctions. Aim. To explore the relationship between the use of selective serotonin reuptake inhibitors (SSRIs), non-SSRIs antidepressants and benzodiazepines (BDZ), hormonal parameters, and reported sexual dysfunction (as assessed by the Structured Interview on Erectile Dysfunction [SIEDY]) in male subjects with comparable psychopathological symptoms (as assessed by the Middlesex Hospital Questionnaire [MHQ] a self-reported test for the screening of mental disorders in a non-psychiatric setting). Methods. A consecutive series of 2,040 (mean age 51 ± 13 years) male patients with sexual dysfunction was studied. Main Outcome Measures. Several hormonal and biochemical parameters were investigated, along with SIEDY and the MHQ. Results. Higher prolactin was observed only in patients using SSRIs, whereas no other hormonal difference was found after adjustment for confounders. Use of SSRIs was associated with a twofold risk for patient hypoactive sexual desire and with a higher impairment of reported erectile function. However, no difference in penile blood flow was observed. A very high risk (sevenfold) for delayed ejaculation (DE) was observed in SSRI users. Interestingly, the association with the mild, but not severe, form of DE was observed also in subjects using non-SSRI antidepressants (3.35 [1.48–7.59]; P < 0.005). Different life stressors and relational parameters were also associated with SSRI use. SSRI users reported less enjoyment with masturbation and decreased partner desire and climax. Conversely, a lack of significant association was observed among BDZ or non-SSRI antidepressant users and all the aforementioned life-stressors and relational parameters. Conclusions. SSRIs can negatively affect all the steps of the male sexual response cycle (desire–arousal–excitement–orgasm). SSRI-associated sexual dysfunction has a deleterious effect on both auto- and couple-erotic performances. Conversely, other antidepressants and BDZ are less often associated with sexual impairment. Corona G, Ricca V, Bandini E, Mannucci E, Lotti F, Boddi V, Rastrelli G, Sforza A, Faravelli C, Forti G, and Maggi M. Selective serotonin reuptake inhibitor-induced sexual dysfunction. J Sex Med 2009;6:1259–1269. [ABSTRACT FROM AUTHOR]

Introduction. The relationship between extramarital affairs and male sexual dysfunctions (SDs) has not been completely clarified. Aim. The aim of the present study is to describe how the reported presence of extramarital affairs vs. no report differentiates men attending medical care for SDs. Methods. A nonselected series of 2,592 heterosexual (mean age 55 ± 12.5 years) male patients with SD was studied with Structured Interview on Erectile Dysfunction (SIEDY). Furthermore, a complete physical examination and a series of biochemical, hormonal, and penile vascular evaluations were performed. Main Outcome Measures. Several hormonal, biochemical, and instrumental parameters were investigated along with items derived from SIEDY. Results. Infidelity is associated with relational problems within the primary couple, particularly in those with a stable secondary relationship. Furthermore, a higher androgenization is present in men with infidelity. Patients with SD reporting extramarital affairs had higher stress at work, a longer primary relationship span, and higher risk of conflicts within the primal couple and within the family. In addition, infidel men showed a higher risk of partner's illness and partner's hypoactive sexual desire. Among organic factors, a lower prevalence of hypogonadism was observed in infidel men. These subjects showed a better sexual function than the rest of the sample. In addition, they reported a higher intercourse frequency in the previous 3 months (considering both the primary and secondary relationship), a lower prevalence of hypoactive sexual desire (HSD), and a lower feeling of discomfort or guilt about autoerotism. Finally, when SIEDY scales were considered, SIEDY Scale 2 (relational domain) and Scale 3 (intrapsychic domain) scores were significantly higher in infidel subjects when compared with the rest of the sample. Conclusions. Infidelity is associated with relational problems within the primary couple, particularly in those with a stable secondary relationship. Furthermore, a higher androgenization is present in men who commit infidelity. Fisher AD, Corona G, Bandini E, Mannucci E, Lotti F, Boddi V, Forti G, and Maggi M. Psychobiological correlates of extramarital affairs and differences between stable and occasional infidelity among men with sexual dysfunctions. J Sex Med 2009;6:866–875. [ABSTRACT FROM AUTHOR]

Introduction. The reversal of hypogonadotropic hypogonadism (HH), occurring after discontinuation of testosterone therapy in adolescents with delayed puberty and in a small percentage of adults with congenital HH, suggests a role for androgens in favoring a spontaneous recovery of reproductive function. Aim. We investigated the effect of androgens and leptin on gonadotropin-releasing hormone (GnRH) expression and secretion in human GnRH-secreting neuroblasts (FNC-B4). Methods. Quantitative real-time polymerase chain reaction RT-PCR for mRNA expression and radioimmunoassay for GnRH secretion were used. Immunohistochemical studies assessed GnRH protein expression. FNC-B4 migration was analyzed with multiwell Boyden chamber technique. Main Outcome Measures. Effects of the non-aromatizable androgen dihydrotestosterone (DHT) and leptin in FNC-B4 were tested after 24 and 48 hours. Results. Exposure to increasing concentrations of DHT after 24 hours significantly stimulated GnRH mRNA in FNC-B4. This effect was still present after prolonged exposure (48 hours). Similarly, treatment with leptin significantly induced GnRH mRNA after 24 hours, but not at 48 hours. Interestingly, mRNA for leptin receptors (LEPR) was significantly reduced after 48 hours of leptin, while, at this time point, it was stimulated by DHT. Coincubation for 48 hours with leptin and DHT maintained the stimulatory effect on both GnRH and LEPR mRNA, suggesting that DHT could stabilize the leptin effect by preventing downregulation of LEPR. Similar results were obtained for GnRH protein expression analysis. Moreover, both DHT and leptin increased GnRH release into the culture medium. We also found that DHT or leptin treatment significantly increased FNC-B4 basal migration. As we previously found that GnRH stimulates FNC-B4 migration, we hypothesized that this effect could be mediated by DHT- and leptin-induced GnRH release. Accordingly, the GnRH antagonist cetrorelix inhibited DHT- and leptin-induced migration. Conclusion. Our results suggest that androgens (adequate hormonal status) could have a positive effect on GnRH neuronal activity by synergizing with leptin (adequate energy status) in the regulatory mechanisms required for reproductive and sexual fitness. Morelli A, Fibbi B, Marini M, Silvestrini E, De Vita G, Chavalmane AK, Vignozzi L, Filippi S, Forti G, Vannelli GB, and Maggi M. Dihydrotestosterone and leptin regulate gonadotropin-releasing hormone (GnRH) expression and secretion in human GnRH-secreting neuroblasts. J Sex Med 2009;6:397–407. [ABSTRACT FROM AUTHOR]

Introduction. The relationship between obesity and erectile dysfunction (ED) has not been completely clarified. Aim. The aim of this study is to investigate the association between different obesity class (the World Health Organization definition) with several hormonal and instrumental parameters, in a large sample of patients with ED. Methods. A consecutive series of 2,435 (mean age 52.1 ± 13.0 years) male patients with ED was investigated. Main Outcome Measures. Several hormonal and biochemical parameters were studied, along with a structured interview on erectile dysfunction (SIEDY), a psychometric questionnaire (Middle Hospital Questionnaire), and penile doppler ultrasound (PDU). Results. Among patients studied, 41.5% were normal weight, while 42.4%, 12.1% and 4.0% showed a BMI of 25–29.9, 30–34.9 and 35 kg/m2 or higher, respectively. Androgen levels (including sex hormone-binding globuline bound and unbound testosterone) decreased as a function of obesity class, while luteinising hormone levels did not show any significant change. Obesity was significantly associated with a higher organic contribution to ED (as assessed by SIEDY scale 1 score), and worse PDU parameters. At multivariate linear regression analysis, after adjustment for confounders (including metabolic syndrome), low androgens remained associated with BMI, while both basal and dynamic (after prostaglandin E1 [PGE1] stimulation) peak systolic velocity (PSV) at PDU resulted significantly associated with age and elevated blood pressure (Adj. r = −0.179, −0.285 and −0.094, −0.071 for age, hypertension and for basal and dynamic PSV, respectively; all P < 0.05). Conclusions. Obesity is characterized by low levels of androgens in men with ED, after adjustment for comorbidities. Obesity associated comorbidities, particularly hypertension, are the most important determinants of arteriogenic obesity–associated ED. Corona G, Mannucci E, Fisher AD, Lotti F, Petrone L, Balercia G, Bandini E, Forti G, and Maggi M. Low levels of androgens in men with erectile dysfunction and obesity. J Sex Med 2008;5:2454–2463. [ABSTRACT FROM AUTHOR]

Introduction. The role of testosterone (T) in pathogenesis of ejaculatory symptoms has not been completely clarified. Aim. To evaluate the possible contribution of T and hypogonadism in the control of the ejaculatory reflex, comparing subjects with premature ejaculation (PE) or delayed ejaculation (DE) to those without ejaculatory dysfunction. Methods. A consecutive series of 2,437 (mean age 51.9 ± 13.0 years) male patients with sexual dysfunction was studied. Main Outcome Measure. Several hormonal and biochemical parameters were studied, along with the structured interview on erectile dysfunction (SIEDY) structured interview. Hypogonadism were defined when total testosterone (TT) was lower than 10.4 nmol/L. Results. Among the patients studied, 714 (25.9%) and 121 (4.4%) reported PE and DE, respectively. In the youngest age band (25–40 years), subjects with PE reported higher TT and free testosterone (FT) levels when compared to the other groups (subjects with DE or those without PE and DE; P < 0.05 for both). Conversely, in the oldest age band (55–70 years), lower TT and FT levels were observed in DE subjects. Accordingly, patients with PE showed the lowest (12%) and subjects with DE the highest (26%) prevalence of hypogonadism. These differences were confirmed even after adjustment for confounders such as age and libido (HR = 0.75 [0.57–0.99] and 1.83 [1.14–3.94] for PE and DE, respectively; both P < 0.05). Conclusions. Our data seem to suggest that T plays a facilitatory role in the control of ejaculatory reflex. Both central and peripheral mechanisms have been advocated to explain this association. Clinical studies are currently in progress to further establish the role of T in the ejaculatory dysfunction, attempting to revert DE by androgen administration. Corona G, Jannini EA, Mannucci E, Fisher AD, Lotti F, Petrone L, Balercia G, Bandini E, Chiarini V, Forti G, and Maggi M. Different testosterone levels are associated with ejaculatory dysfunction. J Sex Med 2008;5:1991–1998. [ABSTRACT FROM AUTHOR]

Introduction. The physiological role of prolactin (PRL) in male sexual function has not been completely clarified. Aim. The aim of this study is the assessment of clinical features and of conditions associated with hyperprolactinemia in male patients consulting for sexual dysfunction. Methods. A consecutive series of 2,146 (mean age 52.2 ± 12.8 years) male patients with sexual dysfunction was studied. Main Outcome Measures. Several hormonal and biochemical parameters were studied along with validated structured interviews (ANDROTEST and the Structured Interview on Erectile Dysfunction [SIEDY]). Mild hyperprolactinemia (MHPRL; PRL levels of 420–735 mU/L or 20–35 ng/mL) and severe hyperprolactinemia (SHPRL, PRL levels >735 mU/L, 35 ng/mL) were considered. Results. MHPRL and SHPRL were found in 69 (3.3%) and in 32 (1.5%) patients, respectively. Mean age and the prevalence of gynecomastia were similar in the two groups and in subjects with normal prolactin values. MHPRL was not confirmed in almost one-half of the patients after repetitive venous sampling. Hyperprolactinemia was associated with the current use of antidepressants, antipsychotic drugs, and benzamides. SHPRL was also associated with hypoactive sexual desire (HSD), elevated thyrotropin (TSH), and hypogonadism. The association between HSD and SHPRL was confirmed after adjustment for testosterone and TSH levels, and use of psychotropic drugs (hazard ratio [HR] = 8.60[3.85–19.23]; P < 0.0001). In a 6-month follow-up of patients with SHPRL, testosterone levels and sexual desire were significantly improved by the treatment. Conclusions. Our data indicate that SHPRL, but not MHPRL, is a relevant determinant of HSD. Gynecomastia does not help in recognizing hyperprolactinemic subjects, while the use of psychotropic medications and HSD are possible markers of disease. In the case of MHPRL, repetitive venous sampling is strongly encouraged. Corona G, Mannucci E, Fisher AD, Lotti F, Ricca V, Balercia G, Petrone L, Forti G, and Maggi M. Effect of hyperprolactinemia in male patients consulting for sexual dysfunction. J Sex Med 2007;4:1485–1493. [ABSTRACT FROM AUTHOR]

Introduction. Metabolic syndrome (MetS) is a clustering of cardiovascular and metabolic risk factors, often associated with erectile dysfunction (ED) and hypogonadism. Recently, the International Diabetes Federation (IDF) proposed a substantial revision of the National Cholesterol Education Program–Third Adult Treatment Panel (NCEP-ATPIII) MetS criteria, essentially lowering the diagnostic cutoff values. Aim. To investigate the associations between these two recently proposed definitions of MetS with the relative risk of arteriogenic ED and hypogonadism in a large cohort of patients with male sexual dysfunction. Methods. A consecutive series of 1086 patients with sexual dysfunction (mean age 51.9 ± 12.8 years) was studied. Main Outcome Measures. Several hormonal, biochemical, and instrumental (penile Doppler ultrasound) parameters were studied, along with ANDROTEST, a 12-item validated structured interview, specifically designed for the screening hypogonadism in a sexual dysfunction population. In particular, a score >8 is predictive of low testosterone (<10.4 nmol/L) with a sensitivity and specificity of about 70%. Results. The prevalence of MetS was 32.0% and 44.7% according to NCEP-ATPIII and IDF criteria, respectively. After adjustment for confounding factors, only NCEP-ATPIII was significantly associated with dynamic prostaglandin E1-stimulated penile flow (Vpmax, B = −7.7 ± 3.8; P < 0.05). Patients with MetS defined according to both criteria reported lower total and free testosterone levels, higher prevalence of hypogonadism, and higher ANDROTEST score. However, when IDF, but not NCEP-ATPIII, criteria were fulfilled, the prevalence of hypogonadism was significantly lower than that observed in patients fulfilling both criteria (15.6% vs. 34.8%, respectively; P < 0.00001). Conversely, patients fulfilling NCEP-ATPIII, but not IDF, criteria did not show a significant different prevalence of hypogonadism than those positive for both sets of criteria (30.8% vs. 34.8%; P = NS). Conclusions. In patients with ED, NCEP-ATPIII criteria seem to be a better predictor of hypogonadism and impaired penile blood flow than IDF ones. Corona G, Mannucci E, Petrone L, Schulman C, Balercia G, Fisher AD, Chiarini V, Forti G, and Maggi M. A comparison of NCEP-ATPIII and IDF metabolic syndrome definitions with relation to metabolic syndrome-associated sexual dysfunction. J Sex Med 2007;4:789–796. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: The association of low testosterone level and erectile dysfunction (ED) with metabolic syndrome (MS) is receiving increasing attention. The present study determined the psychobiologic characteristics of sexual dysfunction (SD) associated with MS (as defined by the National Cholesterol Education Program''s Adult Treatment Panel III criteria) in a series of 803 consecutive male outpatients. Methods: Several hormonal, biochemical, and instrumental (penile Doppler ultrasound [PDU]) parameters were studied, along with general psychopathology scores (Middlesex Hospital Questionnaire modified [MHQ]). The Structured Interview on Erectile Dysfunction (SIEDY) was also applied. Results: Among the 236 patients (29.4%) diagnosed as having a MS, 96.5% reported ED, 39.6% hypoactive sexual desire (HSD), 22.7% premature ejaculation, and 4.8% delayed ejaculation. Patients with MS were characterised by greater subjective (as assessed by SIEDY) and objective (as assessed by PDU) ED and by greater somatised anxiety than the rest of the sample. The prevalence of overt hypogonadism (total testosterone <8nM) was significantly higher in patients with MS. Among MS components, waist circumference and hyperglycaemia were the best predictors of hypogonadism. Hypogonadal patients with MS showed higher gonadotropin and lower free testosterone levels, suggesting a primary hypogonadism. Among patients with MS, hypogonadism was present in 11.9% and 3.8% in the rest of the sample (p <0.0001) and was associated with typical hypogonadism-related symptoms, such as hypoactive sexual desire, low frequency of sexual intercourse, and depressive symptoms. Conclusions: Our data suggest that MS is associated with a more severe ED and induces somatisation. Furthermore, MS is associated with a higher prevalence of hypogonadism in patients with SD. The presence of hypogonadism can further exacerbate the MS-associated sexual dysfunction, adding the typical hypogonadism-related symptoms (including HSD, 66.7%). Recognising MS associated with hypogonadism is important for both sexual and general health and its serious potential associated risks. [Copyright &y& Elsevier]

Introduction. Detecting hypogonadism, which is important in the general population, becomes crucial in patients with sexual dysfunctions, because hypogonadism can have a causal role for them and testosterone (T) substitution represents a milestone for the therapy. Aim. No inventories are available for the screening of hypogonadism in patients with sexual dysfunction. We wished to set up a brief structured interview providing scores useful for detecting hypogonadism defined as low total T (<10.4 nmol/L, 300 ng/dL) in a symptomatic population (sexual dysfunction). Methods. A minimum set of items was identified within a larger structured interview through iterative receiver-operating characteristic curve analysis, with assessment of sensitivity and specificity for hypogonadism in a sample of 215 patients. Main Outcome Measures. Sensitivity and specificity were verified in a further sample of 664 patients. Correlation of test scores with prostate-specific antigen (PSA), testis volume, and others clinical and psychological parameters, was assessed for concurrent validity. Results. In the validation sample, the final 12-item version of the interview (ANDROTEST ©) had a sensitivity and specificity of 68% and 65%, in detecting low total T (<10.4 nmol/L) and of 71% and 65%, in the screening for low free T (<37 pmol/L). Furthermore, patients with a pathological test (i.e., score >8) showed higher prevalence of hypogonadism-related signs, such as lower testis volume and higher depressive symptoms. Finally, when only younger patients (<54 years, which represents the median age of the sample) were considered, Log10 [PSA] levels were significantly lower in those with ANDROTEST © score >8. Conclusion. ANDROTEST © is a quick and easy-to-administer interview that provides scores for the screening of male hypogonadism in patients with sexual dysfunction. Corona G, Mannucci E, Petrone L, Balercia G, Fisher AD, Chiarini V, Forti G, and Maggi M. ANDROTEST ©: A structured interview for the screening of hypogonadism in patients with sexual dysfunction. J Sex Med 2006;3:706–715. [ABSTRACT FROM AUTHOR]