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Background The dietary management of methylmalonic acidaemia (MMA) is a low-protein diet providing sufficient energy to avoid catabolism and to limit production of methylmalonic acid. The goal is to achieve normal growth, good nutritional status and the maintenance of metabolic stability. Aim To describe the dietary management of patients with MMA across Europe. Methods A cross-sectional questionnaire was sent to European colleagues managing inherited metabolic disorders (IMDs) (n=53) with 27 questions about the nutritional management of organic acidaemias. Data were analysed by different age ranges (0-6 months; 7-12 months; 1-10 years; 11-16 years; >16 years). Results Questionnaires were returned from 53 centres. Twenty-five centres cared for 80 patients with MMA vitamin B12 responsive (MMAB12r) and 43 centres managed 215 patients with MMA vitamin B12 non-responsive (MMAB12nr). For MMAB12r patients, 44% of centres (n=11/25) prescribed natural protein below the World Health Organization/Food and Agriculture Organization/United Nations University (WHO/FAO/UNU) 2007 safe levels of protein intake in at least one age range. Precursor-free amino acids (PFAA) were prescribed by 40% of centres (10/25) caring for 36% (29/80) of all the patients. For MMAB12nr patients, 72% of centres (n=31/43) prescribed natural protein below the safe levels of protein intake (WHO/FAO/UNU 2007) in at least one age range. PFAA were prescribed by 77% of centres (n=33/43) managing 81% (n=174/215) of patients. In MMAB12nr patients, 90 (42%) required tube feeding: 25 via a nasogastric tube and 65 via a gastrostomy. Conclusions A high percentage of centres used PFAA in MMA patients together with a protein prescription that provided less than the safe levels of natural protein intake. However, there was inconsistent practices across Europe. Long-term efficacy studies are needed to study patient outcome when using PFAA with different severities of natural protein restrictions in patients with MMA to guide future practice.

Introduction: In phenylketonuria (PKU), evidence suggests that casein glycomacropeptide supplemented with rate-limiting amino acids (CGMP-AA) is associated with better protein utilisation and less blood phenylalanine (Phe) variability. Aim: To study the impact of CGMP-AA on blood Phe variability using 3 different dietary regimens in children with PKU. Methods: This was a 6-week randomised controlled cross-over study comparing CGMP-AA vs. Phe-free l-amino acids (l-AA) assessing blood Phe and tyrosine (Tyr) variability over 24 h in 19 children (7 boys) with PKU, with a median age of 10 years (6⁻16). Subjects were randomised to 3 dietary regimens: (1) R1, CGMP-AA and usual dietary Phe (CGMP + Phe); (2) R2, CGMP-AA - Phe content of CGMP-AA from usual diet (CGMP - Phe); and (3) R3, l-AA and usual dietary Phe. Each regimen was administered for 14 days. Over the last 48 h on days 13 and 14, blood spots were collected every 4 h at 08 h, 12 h, 16 h, 20 h, 24 h, and 04 h. Isocaloric intake and the same meal plan and protein substitute dosage at standardised times were maintained when blood spots were collected. Results: Eighteen children completed the study. Median Phe concentrations over 24 h for each group were (range) R1, 290 (30⁻580), R2, 220 (10⁻670), R3, 165 (10⁻640) μmol/L. R1 vs. R2 and R1 vs. R3 p < 0.0001; R2 vs. R3 p = 0.0009. There was a significant difference in median Phe at each time point between R1 vs. R2, p = 0.0027 and R1 vs. R3, p < 0.0001, but not between any time points for R2 vs. R3. Tyr was significantly higher in both R1 and R2 [70 (20⁻240 μmol/L] compared to R3 [60 (10⁻200) μmol/L]. In children < 12 years, blood Phe remained in the target range (120⁻360 μmol/L), over 24 h, for 75% of the time in R1, 72% in R2 and 64% in R3; for children aged ≥ 12 years, blood Phe was in target range (120⁻600 μmol/L) in R1 and R2 for 100% of the time, but 64% in R3. Conclusions: The residual Phe in CGMP-AA increased blood Phe concentration in children. CGMP-AA appears to give less blood Phe variability compared to l-AA, but this effect may be masked by the increased blood Phe concentrations associated with its Phe contribution. Reducing dietary Phe intake to compensate for CGMP-AA Phe content may help.

In phenylketonuria, casein glycomacropeptide (CGMP) requires modification with the addition of some essential and semi essential amino acids to ensure suitability as a protein substitute. The optimal amount and ratio of additional amino acids is undefined., Aim: A longitudinal, parallel, controlled study over 12 months evaluating a CGMP (CGMP-AA2) formulation compared with phenylalanine-free L-amino acid supplements (L-AA) on blood Phe, Tyr, Phe:Tyr ratio, biochemical nutritional status and growth in children with PKU. The CGMP-AA2 contained 36 mg Phe per 20 g protein equivalent., Methods: Children with PKU, with a median age of 9.2 y (5-16y) were divided into 2 groups: 29 were given CGMP-AA2, 19 remained on Phe-free L-AA. The CGMP-AA2 formula gradually replaced L-AA, providing blood Phe concentrations were maintained within target range. Median blood Phe, Tyr, Phe:Tyr ratio and anthropometry, were compared within and between the two groups at baseline, 26 and 52 weeks. Nutritional biochemistry was studied at baseline and 26 weeks only., Results: At the end of 52 weeks only 48% of subjects were able to completely use CGMP-AA2 as their single source of protein substitute. At 52 weeks CGMP-AA2 provided a median of 75% (30-100) of the total protein substitute with the remainder being given as L-AA. Within the CGMP-AA2 group, blood Phe increased significantly between baseline and 52 weeks: [baseline to 26 weeks; baseline Phe 270 μmol/L (170-430); 26 weeks, Phe 300 μmol/L (125-485) p = 0.06; baseline to 52 weeks: baseline, Phe 270 μmol/L (170-430), 52 weeks Phe 300 μmol/L (200-490), p < 0.001)]. However, there were no differences between the CGMP-AA2 and L-AA group for Phe, Tyr, Phe:Tyr ratio or anthropometry at any of the three measured time points. Within the CGMP-AA2 group only weight (p = 0.0001) and BMI z scores (p = 0.0001) increased significantly between baseline to 52 weeks. Whole blood and plasma selenium were significantly higher (whole blood selenium [p = 0.0002]; plasma selenium [p = 0.0007]) at 26 weeks in the CGMP-AA2 group compared L-AA. No differences were observed within the L-AA group for any of the nutritional markers., Conclusions: CGMP-AA increases blood Phe concentrations and so it can only be used partly to contribute to protein substitute in some children with PKU. CGMP-AA should be carefully introduced in children with PKU and close monitoring of blood Phe control is essential.

Background: In the treatment of phenylketonuria (PKU), there was disparity between UK dietitians regarding interpretation of how different foods should be allocated in a low phenylalanine diet (allowed without measurement, not allowed, or allowed as part of phenylalanine exchanges). This led to variable advice being given to patients., Methodology: In 2015, British Inherited Metabolic Disease Group (BIMDG) dietitians (n = 70) were sent a multiple-choice questionnaire on the interpretation of protein from food-labels and the allocation of different foods. Based on majority responses, 16 statements were developed. Over 18-months, using Delphi methodology, these statements were systematically reviewed and refined with a facilitator recording discussion until a clear majority was attained for each statement. In Phase 2 and 3 a further 7 statements were added., Results: The statements incorporated controversial dietary topics including: a practical 'scale' for guiding calculation of protein from food-labels; a general definition for exchange-free foods; and guidance for specific foods. Responses were divided into paediatric and adult groups. Initially, there was majority consensus (≥86%) by paediatric dietitians (n = 29) for 14 of 16 statements; a further 2 structured discussions were required for 2 statements, with a final majority consensus of 72% (n = 26/36) and 64% (n = 16/25). In adult practice, 75% of dietitians agreed with all initial statements for adult patients and 40% advocated separate maternal-PKU guidelines. In Phase 2, 5 of 6 statements were agreed by ≥76% of respondents with one statement requiring a further round of discussion resulting in 2 agreed statements with a consensus of ≥71% by dietitians in both paediatric and adult practice. In Phase 3 one statement was added to elaborate further on an initial statement, and this received 94% acceptance by respondents. Statements were endorsed by the UK National Society for PKU., Conclusions: The BIMDG dietitians group have developed consensus dietetic statements that aim to harmonise dietary advice given to patients with PKU across the UK, but monitoring of statement adherence by health professionals and patients is required.

Background: In phenylketonuria (PKU), weaning is considered more challenging when compared to feeding healthy infants. The primary aim of weaning is to gradually replace natural protein from breast milk or standard infant formula with solids containing equivalent phenylalanine (Phe). In addition, a Phe-free second stage L-amino acid supplement is usually recommended from around 6 months to replace Phe-free infant formula. Our aim was to assess different weaning approaches used by health professionals across Europe., Methods: A cross sectional questionnaire (survey monkey®) composed of 31 multiple and single choice questions was sent to European colleagues caring for inherited metabolic disorders (IMD). Centres were grouped into geographical regions for analysis., Results: Weaning started at 17-26 weeks in 85% ( n  = 81/95) of centres, >26 weeks in 12% ( n  = 11/95) and < 17 weeks in 3% ( n  = 3/95). Infant's showing an interest in solid foods, and their age, were important determinant factors influencing weaning commencement. 51% ( n  = 48/95) of centres introduced Phe containing foods at 17-26 weeks and 48% ( n  = 46/95) at >26 weeks. First solids were mainly low Phe vegetables (59%, n  = 56/95) and fruit (34%, n  = 32/95).A Phe exchange system to allocate dietary Phe was used by 52% ( n  = 49/95) of centres predominantly from Northern and Southern Europe and 48% (n = 46/95) calculated most Phe containing food sources (all centres in Eastern Europe and the majority from Germany and Austria). Some centres used a combination of both methods.A second stage Phe-free L-amino acid supplement containing a higher protein equivalent was introduced by 41% ( n  = 39/95) of centres at infant age 26-36 weeks (mainly from Germany, Austria, Northern and Eastern Europe) and 37% ( n  = 35/95) at infant age > 1y mainly from Southern Europe. 53% ( n  = 50/95) of centres recommended a second stage Phe-free L-amino acid supplement in a spoonable or semi-solid form., Conclusions: Weaning strategies vary throughout European PKU centres. There is evidence to suggest that different infant weaning strategies may influence longer term adherence to the PKU diet or acceptance of Phe-free L-amino acid supplements; rendering prospective long-term studies important. It is essential to identify an effective weaning strategy that reduces caregiver burden but is associated with acceptable dietary adherence and optimal infant feeding development.

Background: In infants with phenylketonuria (PKU), dietary management is based on lowering and titrating phenylalanine (Phe) intake from breast milk or standard infant formula in combination with a Phe-free infant formula in order to maintain blood Phe levels within target range. Professionals use different methods to feed infants with PKU and our survey aimed to document practices across Europe., Methods: We sent a cross sectional, survey monkey® questionnaire to European health professionals working in IMD. It contained 31 open and multiple-choice questions. The results were analysed according to different geographical regions., Results: Ninety-five centres from 21 countries responded. Over 60% of centres commenced diet in infants by age 10 days, with 58% of centres implementing newborn screening by day 3 post birth. At diagnosis, infant hospital admission occurred in 61% of metabolic centres, mainly in Eastern, Western and Southern Europe. Breastfeeding fell sharply following diagnosis with only 30% of women still breast feeding at 6 months.53% of centres gave pre-measured Phe-free infant formula before each breast feed and 23% alternated breast feeds with Phe-free infant formula. With standard infant formula feeds, measured amounts were followed by Phe-free infant formula to satiety in 37% of centres ( n  = 35/95), whereas 44% ( n  = 42/95) advised mixing both formulas together. Weaning commenced between 17 and 26 weeks in 85% centres, ≥26 weeks in 12% and < 17 weeks in 3%., Discussion: This is the largest European survey completed on PKU infant feeding practices. It is evident that practices varied widely across Europe, and the practicalities of infant feeding in PKU received little focus in the PKU European Guidelines (2017). There are few reports comparing different feeding techniques with blood Phe control, Phe fluctuations and growth. Controlled prospective studies are necessary to assess how different infant feeding practices may influence longer term feeding development.

Background: The definitive dietary management of propionic acidaemia (PA) is unknown although natural protein restriction with adequate energy provision is of key importance., Aim: To describe European dietary practices in the management of patients with PA prior to the publication of the European PA guidelines., Methods: This was a cross-sectional survey consisting of 27 questions about the dietary practices in PA patients circulated to European IMD dietitians and health professionals in 2014., Results: Information on protein restricted diets of 186 PA patients from 47 centres, representing 14 European countries was collected. Total protein intake [PA precursor-free L-amino acid supplements (PFAA) and natural protein] met WHO/FAO/UNU (2007) safe protein requirements for age in 36 centres (77%). PFAA were used to supplement natural protein intake in 81% (n = 38) of centres, providing a median of 44% (14-83%) of total protein requirement. Seventy-four per cent of patients were prescribed natural protein intakes below WHO/FAO/UNU (2007) safe levels in one or more of the following age groups: 0-6 m, 7-12 m, 1-10 y, 11-16 y and > 16 y. Sixty-three per cent (n = 117) of patients were tube fed (74% gastrostomy), but only 22% received nocturnal feeds., Conclusions: There was high use of PFAA with intakes of natural protein commonly below WHO/FAO/UNU (2007) safe levels. Optimal dietary management can only be determined by longitudinal, multi-centre, prospective case controlled studies. The metabolic instability of PA and small patient cohorts in each centre ensure that this is a challenging undertaking.

Background: In Europe, dietary management of isovaleric acidemia (IVA) may vary widely. There is limited collective information about dietetic management., Aim: To describe European practice regarding the dietary management of IVA, prior to the availability of the E-IMD IVA guidelines (E-IMD 2014)., Methods: A cross-sectional questionnaire was sent to all European dietitians who were either members of the Society for the Study of Inborn Errors of Metabolism Dietitians Group (SSIEM-DG) or whom had responded to previous questionnaires on dietetic practice (n = 53). The questionnaire comprised 27 questions about the dietary management of IVA., Results: Information on 140 patients with IVA from 39 centres was reported. 133 patients (38 centres) were given a protein restricted diet. Leucine-free amino acid supplements (LFAA) were routinely used to supplement protein intake in 58% of centres. The median total protein intake prescribed achieved the WHO/FAO/UNU [2007] safe levels of protein intake in all age groups. Centres that prescribed LFAA had lower natural protein intakes in most age groups except 1 to 10 y. In contrast, when centres were not using LFAA, the median natural protein intake met WHO/FAO/UNU [2007] safe levels of protein intake in all age groups. Enteral tube feeding was rarely prescribed., Conclusions: This survey demonstrates wide differences in dietary practice in the management of IVA across European centres. It provides unique dietary data collectively representing European practices in IVA which can be used as a foundation to compare dietary management changes as a consequence of the first E-IMD IVA guidelines availability.

Objectives: To report the sexual activity, the prevalence of sexual problems and related help-seeking behavior among adults in France., Methods: A telephone survey was conducted in 2001 and 2002. Interviews were based on a standardized questionnaire including demographic details, overall health, relationships, and sexual behaviors, attitudes and beliefs., Results: A total of 1500 individuals (750 men, 750 women) aged 40 to 80 years completed the survey. Eighty-one percent of men and 65% of women had engaged in sexual intercourse during the 12 months preceding the interview. Premature ejaculation (16%) and erectile dysfunction (15%) were the most frequently reported sexual problems among men. Lack of sexual interest (21%) and a lack of sexual pleasure (18%) were the most frequently reported ones among women. Only 10% of men and 8% of women had been asked by a doctor about possible sexual problems during a routine visit in the last 3 years., Conclusions: Many middle aged and older men and women in France report continued sexual interest and activity. Although a number of sexual problems are seen in this population, only a minority of individuals seek medical help for these disorders. This is largely due to believing that the problem is not serious, not being bothered by the problem, and/or a lack of awareness of available treatments.

Background: The Global Study of Sexual Attitudes and Behaviours was a survey of 27 500 men and women in 29 countries. Here we report the sexual activity, the prevalence of sexual difficulties and related help-seeking behaviour among participants in Australia., Methods: A telephone survey was conducted in Australia in 2001-2002, with interviews based on a standardised questionnaire. A total of 1500 individuals (750 men and 750 women) aged 40 to 80 years completed the survey. The questionnaire covered demographic information, overall health, and sexual behaviours, attitudes and beliefs., Results: Overall, 83% of men and 74% of women had engaged in sexual intercourse during the 12 months preceding the interview, and 38% of all men and 29% of all women engaged in sexual intercourse more than once a week. Early ejaculation (23%), erectile difficulties (21%) and a lack of sexual interest (18%) were the most common male sexual difficulties. The most frequently reported female sexual difficulties were: lack of sexual interest (33%), lubrication difficulties (26%) and an inability to reach orgasm (25%). Older age was a significant predictor of male erectile difficulties and of lubrication difficulties in women. Only a minority of men and women had sought help for their sexual difficulty(ies) from a health professional., Conclusions: Many middle-aged and older adults in Australia report continued sexual interest and sexual activity. Several sexual difficulties are highly prevalent in this population, but those experiencing these difficulties rarely seek medical help. This may be because they do not perceive such difficulties as serious or sufficiently upsetting.

Objectives: To study sexual activity, the prevalence of sexual dysfunction, and related help-seeking behaviour patterns among middle-aged and older people in the UK and Europe., Subjects and Methods: A telephone survey was conducted using a structured questionnaire covering demographics, health, relationships, and sexual behaviour, attitudes and beliefs. In the UK, 1500 individuals completed the survey., Results: Overall, 69% of men and 56% of women reported having sexual intercourse during the past year. The most common male sexual problems, i.e. early ejaculation (20%) and erectile dysfunction (18%), were more common in the UK than in other European regions. The most common female sexual problems, i.e. a lack of sexual interest (34%) and a lack of pleasure in sex (25%), were also more common in the UK than in other European regions. Only 26% of men and 17% of women had discussed their sexual problem(s) with a doctor., Conclusion: Many people in the UK maintain sexual interest and activity into middle age and beyond. Although they experience sexual problems, few seek medical help. This might be because they do not perceive such problems as serious or sufficiently upsetting, and/or are not aware of available treatments.

To study the sexual activity and the prevalence of sexual dysfunctions and related help seeking behaviour, among people in Europe aged 40-80 years. A telephone survey was carried out in 2001-2002 in Sweden, the UK, Belgium, Germany, Austria, France, Spain and Italy, of 4,977 men and 5,023 women, using a structured, standardized questionnaire Eighty-three percent of men and 66% of women had sexual intercourse during the year preceding the interview. The sexual dysfunctions most frequently reported were early ejaculation (11%) and erectile dysfunction (8%) in men; and a lack of sexual interest (18%), an inability to reach orgasm (13%) and lubrication difficulties (11%) in women. Of the 23% of men and 32% of women who reported sexual dysfunction, 26% had consulted a physician, with considerable between-country differences. Sexual activity is widespread among adult middle-aged and elderly people, but many experience sexual dysfunctions and few seek medical care.

We conducted a telephone survey during 2001-2002 to investigate sexual behavior, sexual dysfunction, and related help-seeking behavior in five Anglophone countries. In total, 5,998 individuals (2,992 men and 3,006 women) aged 40-80 years in the United States, Canada, the United Kingdom, Australia, and New Zealand completed the survey. The majority of subjects were sexually active, and although many men and women had experienced sexual dysfunctions, few had sought medical care for these dysfunctions. Further investigation is required to determine whether national differences in the prevalence of sexual dysfunctions are due to genetic predisposition, health factors, cultural perception or socioeconomic situation.

Subjective sexual well-being refers to the cognitive and emotional evaluation of an individual's sexuality. This study examined subjective sexual well-being, explored its various aspects, examined predictors across different cultures, and investigated its possible associations with overall happiness and selected correlates, including sexual dysfunction. Data were drawn from the Global Study of Sexual Attitudes and Behaviors, a survey of 27,500 men and women aged 40-80 years in 29 countries. The cross-national variation of four aspects of sexual well-being (the emotional and physical satisfaction of sexual relationships, satisfaction with sexual health or function, and the importance of sex in one's life) was explored using cluster analysis, and relationships among sexual well-being, general happiness, and various correlates were examined using ordinary least squares regression and ordered logistic regression. Results from the cluster analysis identified three clusters: a gender-equal regime and two male-centered regimes. Despite this cultural variation, the predictors of subjective sexual well-being were found to be largely consistent across world regions.

Introduction: Although there is considerable interest in the prevalence and impact of sexual problems worldwide, to date only male erectile dysfunction has been studied systematically in Asian countries., Aim: To study the prevalence of sexual problems and associated help-seeking patterns, among mature adults in Korea and to compare the results with those obtained in other Southeast Asian and East Asian countries., Methods: As part of the Global Study of Sexual Attitudes and Behaviors (GSSAB), a survey was conducted in Korea during 2001 and 2002. Sampling was based on an intercept methodology and 1,200 individuals (600 men and 600 women) aged 40-80 years completed the survey out of 3,691 eligible subjects (response rate of 32.5%)., Main Outcome Measures: General health, relationships, and sexual behaviors, attitudes, and beliefs., Results: Ninety-one percent of men and 71% of women had engaged in sexual intercourse during the 12 months preceding the interview. Early ejaculation (33%) and erectile difficulties (32%) were the sexual problems most frequently reported by Korean men; these conditions were more common in Korea than in other Asian regions. Increasing age, physical inactivity, smoking, and prostate disease were significant correlates of erectile difficulties. The sexual problems most frequently reported by women in Korea were lack of sexual pleasure (37%) and inability to reach orgasm (31%). Only 2% of men and women in Korea had talked to a medical doctor about their sexual problems., Conclusions: Middle-aged and older adults in Korea regard sex as an important part of life and report continued sexual activity. Several sexual problems are highly prevalent in this population, but very few individuals seek medical help for these disorders. This is largely due to believing that the problem is not serious, not being bothered by the problem, difficulties regarding access to or affordability of medical care, and/or a lack of awareness of available treatments.

Objectives: To study sexual activity, the prevalence of sexual difficulties and related help-seeking behaviors, among mature adults in Canada., Materials and Methods: A telephone survey (random digit dialed) was conducted in Canada in 2001 to 2002. Interviews were based on a standardized questionnaire, including demographics, general health, relationships, and sexual behaviors, attitudes and beliefs. The survey was completed by a total of 1007 individuals (500 men and 507 women) aged 40 to 80 years in Canada., Results: Overall, 83% of men and 71% of women had engaged in sexual intercourse during the 12 months preceding the interview, and 42% of men and 36% of women engaged in sexual intercourse more than once a week. Early ejaculation (23%) and erectile difficulties (16%) were the sexual problems most frequently reported by men. The sexual problems most frequently reported by women were a lack of sexual interest (30%) and lubrication difficulties (24%). Older age (60 to 80 years compared with 40 to 49 years) and diagnoses of depression and diabetes were all significant predictors of erectile difficulties in men. More than 75% of men and women had sought no help for their sexual problem(s) from a health professional., Conclusions: Many middle aged and older adults in Canada report continued sexual interest and activity. Although a number of sexual problems are highly prevalent in this population, few individuals seek medical help for these problems. This may be partly because they are not sufficiently bothered by the problem or do not think that it is serious.

To study sexual activity, the prevalence of sexual dysfunction and related help-seeking behaviours among mature adults in Spain, a telephone survey was conducted in Spain in 2001-2002. This was completed by 750 men and 750 women aged 40-80 years. Eighty-eight percent of men and 66% of women had engaged in sexual intercourse during the 12 months preceding the interview. Early ejaculation (31%) and lack of sexual interest (17%) were the most common male sexual problems. A lack of sexual interest (36%) and an inability to reach orgasm (28%) were the most common female sexual problems. Approximately 80% of men and women with a sexual problem had not sought help from a health professional. Many men and women in Spain report continued sexual interest and activity into middle age and beyond. Although a number of sexual problems are highly prevalent, few people seek medical help.

The Global Study of Sexual Attitudes and Behaviors was a survey of 27,500 men and women aged 40 to 80 years in 29 countries. Here we report the sexual activity, the prevalence of sexual problems and related help-seeking behaviour among subjects in Germany. A telephone survey was conducted in 2001 and 2002, using a standardised questionnaire covering demographics, general health, relationships, and sexual behaviours, attitudes and beliefs. A total of 1,500 individuals in Germany (750 men and 750 women) completed the survey. Eighty-six percent of men and 66% of women had engaged in sexual intercourse during the year preceding the interview. The most common male sexual problems were early ejaculation (15%), a lack of sexual interest, erectile dysfunction and non-pleasurable sex (each 8%). The most common female sexual problems were a lack of sexual interest (18%), non-pleasurable sex (14%) and lubrication difficulties (13%). Most sexual problems were less common among men and women in Germany than in other European regions. Increasing age was a significant predictor of a lack of sexual interest and erectile difficulties in men. Only 18% of men and 15% of women had talked to a doctor about their sexual problem(s). In conclusion, many middle-aged and older German adults reported continued sexual interest and activity. Overall, sexual problems were less prevalent in Germany compared with other European regions. Of those who experienced sexual problems, however, few had sought medical help. This was often due to a lack of perception of a problem.

Context and Objective: Relatively little is known about the usual frequency of sexual activity and how older individuals cope with sexual problems. The objective was to study sexual activity, prevalence of sexual problems and related help-seeking behaviors among middle-aged and older men and women in Brazil., Design and Setting: Population survey, by Fundação Oswaldo Cruz., Methods: Interviews were held with 1,199 Brazilians aged 40-80 years (471 men and 728 women). The standardized questionnaire investigated demographics, general health, sexual behavior, attitudes and beliefs., Results: Overall, 92.6% of men and 58.3% of women had had sexual intercourse during the preceding year. More than half of the men and women had done so more than once a week. Early ejaculation (30.3%) was the commonest male sexual problem, followed by inability to reach orgasm (14.0%), erectile difficulties (13.1%) and lack of sexual interest (11.2%). For women, the commonest sexual problems were lubrication difficulties (23.4%) and lack of sexual interest (22.7%). Depression was a significant correlate of sexual problems, for men and women. More women than men had sought help for sexual problem(s) from a healthcare professional., Conclusions: The findings highlight the importance of encouraging greater use of available healthcare services, including consultation with a medical doctor regarding sexual health. This should not only enable men and women to maintain satisfactory sexual function well into their later years, but may also result in overall improvement in the quality of healthcare.

Introduction: Ethics describe the ways in which moral life is understood. Morality comprises norms for human conduct, and addresses what is right and what is wrong., Aim: To provide a consensus-based summary of the ethical aspects of sexual medicine., Methods: Over 200 multidisciplinary specialists from 60 countries were divided into 17 consultation committees as part of a process organized by an international consultation on sexual medicine held in Paris, June 28-July 1, 2003 in close alliance with several sexual medicine organizations. Embarking on a study on ethics in sexual medicine, 10 experts from eight countries assembled over a two-year period to develop this consensus-based summary., Main Outcome Measure: Although ethics are recognized as subjective, expert opinion was based on grading of evidence-based medical literature, in addition to cultural and ethical considerations. The process also involved extensive internal committee discussion, public presentation, and debate., Results: Contemporary medical practitioners provide health care for patients from many different cultures from all around the world. Thus, it is recommended that all health professionals working in sexual medicine should above all be able to demonstrate respect, understanding, and tolerance toward the differing moral worldviews of their patients and colleagues, and the societies they represent. In sexual medicine, health professionals have an obligation to respect the autonomy of any individual that they treat, regardless of that individual's religious or socio-cultural tradition, race, gender, or sexual orientation. Sexual rights are a necessary condition for sexual health. Sexual health requires a positive and respectful approach to sexuality and sexual relationships as well as the possibility of having pleasurable and safe sexual experiences, free of coercion, discrimination, and violence. For sexual health to be attained and maintained, the sexual rights of all persons must be respected, protected, and fulfilled., Conclusions: Additional discussion and research on ethics in sexual medicine is needed.

The Global Study of Sexual Attitudes and Behaviors (GSSAB) is an international survey of various aspects of sex and relationships among adults aged 40-80 y. An analysis of GSSAB data was performed to estimate the prevalence and correlates of sexual problems in 13,882 women and 13,618 men from 29 countries. The overall response rate was modest; however, the estimates of prevalence of sexual problems are comparable with published values. Several factors consistently elevated the likelihood of sexual problems. Age was an important correlate of lubrication difficulties among women and of several sexual problems, including a lack of interest in sex, the inability to reach orgasm, and erectile difficulties among men. We conclude that sexual difficulties are relatively common among mature adults throughout the world. Sexual problems tend to be more associated with physical health and aging among men than women.

The Global Study of Sexual Attitudes and Behaviors (GSSAB) investigated various aspects of sex and relationships among 27,500 men and women aged 40-80 years. Here, we report help-seeking behaviours for sexual problems in this population. A questionnaire was administered using the accepted survey method in each country. Although almost half of all sexually active respondents had experienced at least one sexual problem, less than 19% of them (18.0% of men and 18.8% of women) had attempted to seek medical help for their problem(s). The most frequent action taken by men and women was to talk to their partner (39%). Only 9% of men and women had been asked about their sexual health by a doctor in a routine visit during the past 3 years. Although sexual problems are highly prevalent, few men and women seek medical help for these problems. Overall, men and women show similar help-seeking behaviours.

Objectives: To assess the importance of sex and the prevalence of sexual dysfunction among middle-aged and older adults throughout the world. Increasing life expectancy has been accompanied by improvements in the health of the middle-aged and elderly, but little is known about how this has affected their sexual experience., Methods: Data were collected in 29 countries from 27,500 men and women aged 40 to 80 years using a standardized questionnaire (self-completed or by interview). Sexual dysfunction was defined as frequent and persistent problems. They included early ejaculation and erectile difficulties in men, lubrication difficulties and pain during intercourse in women, and a lack of sexual interest, an inability to achieve orgasm, and a feeling of unpleasurable sex in both., Results: More than 80% of the men and 65% of the women had had sexual intercourse during the past year. Of these subjects, the most common dysfunctions were early ejaculation (14%) and erectile difficulties (10%) among the men and a lack of sexual interest (21%), inability to reach orgasm (16%), and lubrication difficulties (16%) among the women. Overall, 28% of the men and 39% of the women said that they were affected by at least one sexual dysfunction., Conclusions: The results of our study indicate that sexual desire and activity are widespread among middle-aged and elderly men and women worldwide and persist into old age. The prevalence of sexual dysfunctions was quite high and tended to increase with age, especially in men. Although major between-country differences were noted, this global study revealed some clear and consistent patterns.

Introduction: Viagra (sildenafil citrate) has a rapid onset of action for the treatment of erectile dysfunction (ED). However, its duration of action has not been thoroughly investigated. Practical knowledge of the time window available for sexual intercourse would be valuable for couples planning sexual activity., Aim: We investigated the duration of action of sildenafil in men with ED., Methods: This was a double-blind, randomized, placebo-controlled, four-way crossover study of 16 men, mean age of 55 years (range, 36-68 years) with ED of no known organic cause. Participants received oral sildenafil (100 mg) or placebo 1, 8, or 12 hours before visual sexual stimulation (VSS). Measurements included the duration of erections of >or= 60% rigidity, assessed by penile plethysmography (RigiScan), and the proportion of sildenafil responders, defined as patients with erections of >or= 60% rigidity for >or= 4 minutes and >or= 50% improvement over erections achieved in their placebo arm. Self-assessed duration of grade 3 (hard enough for penetration) or grade 4 (fully hard) erections was also recorded., Results: At 1, 8, and 12 hours after dosing with sildenafil, the mean duration of erections with >or= 60% rigidity was 26, 11, and 8 minutes, respectively, compared with only 3 minutes after placebo dosing (P < 0.05). However, the mean duration of self-assessed erections was 33, 23, and 16 minutes, respectively, compared with 7 minutes after placebo dosing (P < 0.05), and was greater than that assessed by RigiScan. Of the 69% sildenafil responders at 1 hour, 82% responded at 8 hours and 45% responded at 12 hours after sildenafil administration., Conclusion: Sildenafil improved objective and self-assessed erectile function in men with ED, and the duration of action of sildenafil was longer than that previously reported. These data suggest that sildenafil may be effective in a significant proportion of men with ED up to 12 hours after being taken.

Long-term efficacy and safety of sildenafil was assessed in 1008 patients with erectile dysfunction (ED) enrolled in four flexible-dose (25 - 100 mg), open-label, 36- or 52-week extension studies. After 36 and 52 weeks, 92% and 89% of patients felt that treatment with sildenafil had improved their erections. Responses to a Sexual Function Questionnaire indicated that 52 weeks of sildenafil treatment resulted in clinically significant improvements in the duration and firmness of erections, overall satisfaction with sex life, and the frequency of stimulated erections. Commonly reported adverse events (AEs) were headache, flushing, dyspepsia, and rhinitis, which were generally mild to moderate. Reports of abnormal vision were consistent with previous clinical trials. The occurrence of treatment-related cardiovascular AEs, such as hypertension, tachycardia, and palpitation, was <1%. Discontinuations due to treatment-related AEs were low (2%). Long-term therapy does not diminish the efficacy of sildenafil in patients with ED and remains well tolerated.

Sildenafil citrate (Viagra) has been shown to be an effective treatment for erectile dysfunction (ED) of organic aetiology. This study assessed the efficacy and tolerability of sildenafil for treating ED of psychogenic and mixed psychogenic/organic aetiology. Men with ED of psychogenic and mixed aetiology were randomised in a double-blind, fixed-dose study to placebo (n = 95) or sildenafil 10 mg (n = 90), 25 mg (n = 85), or 50 mg (n = 81) once daily for 28 days. Efficacy was evaluated with two global efficacy questions, a patient log of erectile activity, a sexual function questionnaire and a partner questionnaire. Patients receiving sildenafil had significantly more grade 3 (hard enough for penetration) or grade 4 (fully hard) erections per week than patients receiving placebo, and a greater proportion of patients receiving sildenafil reported that treatment had improved their erections (p < 0.001). Results of the sexual function questionnaire demonstrated significant improvement for patients with ED receiving sildenafil compared with patients receiving placebo for frequency, hardness and duration of erections (p < 0.01), and for enjoyment of sexual intercourse and satisfaction with sex life (p < 0.05). The results of the partner questionnaire were consistent with the results reported by patients and showed that treatment with sildenafil was associated with significant improvement in the partners' own sex lives (p < 0.001). Adverse events were mostly mild to moderate in nature. The commonest adverse events were headache, dyspepsia, flushing, myalgia, arthralgia and flu syndrome. Discontinuations due to treatment-related adverse events were few, ranging from 1.1% to 6.2% for patients receiving different doses of sildenafil and 4.2% for patients receiving placebo. Sildenafil is an effective and well-tolerated treatment for ED of psychogenic or mixed aetiology with once-daily dosing.

Erectile dysfunction is a common and distressing medical condition that is now highly amenable to treatment almost irrespective of the cause. Safe, non-surgical treatments with unequivocal efficacy are psychological therapy, intracorporeal injection of vasoactive drugs, transurethral vasodilators and oral sildenafil, all of which have been reported to have a 50-70% overall response rate. Vacuum constriction devices are acceptable for some, usually older patients and oral yohimbine is thought to have marginal efficacy. Local creams to induce or enhance erectile function are currently being investigated. There is no place for androgen supplementation unless the patient is profoundly hypogonadal. Treatment of hyperprolactinaemia is very effective but is a rare cause of erectile dysfunction. As intercourse may entail an unfamiliar level of physical activity, it is sensible to ensure that the patient is able to climb a flight or two of stairs comfortably without provoking undue breathlessness or chest pain and to provide suitable advice about technique before commencing treatment. Once it is clear to the patients that erectile dysfunction can be satisfactorily overcome, the long-term use of treatments to do so tends to wane. Thus, although the prospect of effective treatment for what had been for many a distressing life sentence has the potential to place new demands on the health service, there is no evidence that restrictions on prescribing will prove economically rational.

Objective: To study the effect of intracorporeal injection (IC) of vasoactive intestinal polypeptide (VIP) and phentolamine mesylate (PM) on men with erectile dysfunction (ED) of nonpsychogenic aetiology., Patients and Methods: The study comprised 236 men with primarily nonpsychogenic ED attending sexual dysfunction clinics at eight institutions. In an initial dose-assessment phase, the men were given IC injections of 25 micrograms VIP combined with PM 1.0 mg (VIP/P-1) or 2.0 mg (VIP/P-2) in a prefilled, single-use auto-injector. The main aetiologies of ED were arteriogenic (38), diabetes mellitus (DM) (39), neurogenic (35), mixed (90), and venous leakage (30). In a placebo-controlled phase, 171 patients were subsequently treated and self-administered up to 12 injections over a 6-month interval., Results: In the dose-assessment phase there was an overall response rate of 82%, with responses by aetiology as follows: arteriogenic (82%), DM (85%), neurogenic (86%), mixed (80%), and venous leakage (77%). In a subgroup of 159 patients who withdrew from previous IC therapies for ED, 64% responded with an erection suitable for intercourse. Of the 171 patients treated in the placebo-controlled phase, 75% responded to VIP/P-1 and 12% to placebo (P<0.001); 66% responded to VIP/P-2 and 18% to placebo (P<0. 001), with a median duration of erection of 56 min. The principal adverse event was transient facial flushing accompanying 40% of 1711 injections. There was no pain after injection and one episode of priapism (0.06%); only seven patients withdrew because of adverse events. Over 88% and 92% of patients were satisfied with the drug and auto-injector, respectively. More than 85% of patients and 77% of partners reported an improved quality of life., Conclusion: The combination of VIP and PM at the dose used is a safe and effective means of treating male ED of primarily nonpsychogenic aetiology.

Alprostadil (prostaglandin E1) is the most widely used, licensed vasoactive agent for intracorporeal injection in the investigation and treatment of erectile dysfunction. It has a good side-effect profile and is effective in between 70 and 80% of patients.

Sildenafil citrate has been shown to be effective in a wide range of patients with erectile dysfunction and has been approved in the United States for this indication. The overall clinical safety of oral sildenafil, a potent inhibitor of phosphodiesterase type 5, in the treatment of erectile dysfunction was evaluated in more than 3700 patients (with a total of 1631 years of exposure worldwide). Safety and tolerability data were analysed from a series of double-blind, placebo-controlled studies and from 10 open-label extension studies of sildenafil in the treatment of erectile dysfunction. A total of 4274 patients (2722 sildenafil, 1552 placebo; age range 19-87 y) received double-blind treatment over a period of up to six months' duration, and 2199 received long-term, open-label sildenafil for up to 1 y. The most commonly reported adverse events (all causes) were headache (16% sildenafil, 4% placebo), flushing (10% sildenafil, 1% placebo), and dyspepsia (7% sildenafil, 2% placebo) and they were predominantly transient and mild or moderate in nature. These adverse events reflect the pharmacology of sildenafil as a phosphodiesterase type 5 inhibitor. No cases of priapism were reported. The rate of discontinuation due to adverse events (all causes) was comparable for patients treated with sildenafil (2.5%) and placebo (2.3%). In open-label extension studies, 90% of patients completed long-term sildenafil treatment, with only 2% withdrawing due to adverse events. Sildenafil is a well-tolerated oral treatment for erectile dysfunction.

There has been a tremendous increase in demand for the treatment of erectile dysfunction in the last 10 years. This has occurred partly because of a greater understanding and awareness by both the general public and clinicians, and also because there now exists a range of effective treatments. The choice of treatments is increasing rapidly and novel delivery systems which may be more patient-friendly than intracavernosal injections are now becoming available. We review the published data on effectiveness and safety of the currently available treatments and discuss recent advances in oral therapy, as these drugs are likely to become available in the near future.

Purpose: Sildenafil, an inhibitor of cGMP-specific phosphodiesterase 5 (PDE5), is currently undergoing evaluation as an oral therapy for penile erectile dysfunction. The aims of this study were to investigate the mechanism of action of sildenafil on the neurogenic relaxation of human corpus cavernosum (HCC) in vitro and to determine the activity of sildenafil against a full range of PDE isozymes., Materials and Methods: Strips of HCC tissue were precontracted with phenylephrine. Relaxation responses resulting from electrical field stimulation (EFS) were then determined in the presence and absence of sildenafil. The effects of sildenafil on PDE1 to 5 prepared from human tissues and PDE6 from bovine retina were determined by measuring the conversion of [3H]-cGMP or [3H]-cAMP to their respective [3H]-5'-mononucleotides., Results: Sildenafil (0.001 to 1 microM) enhanced the EFS-induced, nitric oxide (NO) dependent, relaxation of HCC in a concentration-dependent manner to a maximum of 3 times the pretreatment level at 1 microM sildenafil. Compared with zaprinast, an early PDE5 inhibitor, sildenafil was approximately 240-fold more potent, inhibiting PDE5 from HCC with a geometric mean IC50 of 3.5 nM. For sildenafil, IC50 values for inhibition of PDE1 to 4 were 80 to more than 8500 times greater than that for PDE5 and the IC50 for PDE6 (33 nM) was approximately 9-fold greater., Conclusions: The data support the proposal that enhancement of penile erection by sildenafil in patients with erectile dysfunction involves potentiation of the NO-stimulated cGMP signal mediating relaxation of cavernosal smooth muscle during sexual stimulation. Sildenafil is a potent inhibitor of PDE5 from HCC, with high selectivity for PDE5 relative to other PDE isozymes.

The so-called andropause is an ill-defined collection of symptoms in a group of men who may have low but may also have normal androgen levels. Unlike the proven benefits of hormone replacement therapy in women, the effects of testosterone supplementation in men are equivocal. It may increase sexual interest, but rarely to a level thought adequate by the patient. It has no proven beneficial effect on erectile dysfunction and other possible beneficial effects on haemopoesis, bone metabolism, lipids and fibrinolysis have yet to be demonstrated. With the availability of the testosterone patch, sustained increases in the serum testosterone levels will be readily achieved and could theoretically significantly affect the behaviour of subclinical prostate cancer. At the present time, testosterone replacement therapy in hypogonadal men is of proven clinical benefit; this is not the case, however, for eugonadal men with symptoms attributed to the andropause. The symptoms of the andropause fatigue can readily be explained by stress and there is no scientifically valid, placebo-controlled study that shows any benefit for testosterone supplements in this not uncommon group of patients.

Sildenafil (Viagra, UK-92,480) is a novel oral agent under development for the treatment of penile erectile dysfunction. Erection is dependent on nitric oxide and its second messenger, cyclic guanosine monophosphate (cGMP). However, the relative importance of phosphodiesterase (PDE) isozymes is not clear. We have identified both cGMP- and cyclic adenosine monophosphate-specific phosphodiesterases (PDEs) in human corpora cavernosa in vitro. The main PDE activity in this tissue was due to PDE5, with PDE2 and 3 also identified. Sildenafil is a selective inhibitor of PDE5 with a mean IC50 of 0.0039 microM. In human volunteers, we have shown sildenafil to have suitable pharmacokinetic and pharmacodynamic properties (rapid absorption, relatively short half-life, no significant effect on heart rate and blood pressure) for an oral agent to be taken, as required, prior to sexual activity. Moreover, in a clinical study of 12 patients with erectile dysfunction without an established organic cause, we have shown sildenafil to enhance the erectile response (duration and rigidity of erection) to visual sexual stimulation, thus highlighting the important role of PDE5 in human penile erection. Sildenafil holds promise as a new effective oral treatment for penile erectile dysfunction.