Bronwyn Stuckey

Erectile dysfunction in general medicine practice: prevalence and clinical correlates.

Erectile dysfunction (ED) is a common problem in general medical practice affecting especially the elderly and those with cardiovascular disease and diabetes mellitus. A study was undertaken by questionnaire distributed to consecutive adult male attendees at 62 general medical practices. 1240 completed questionnaires were available for analysis. The mean age of participants was 56.4 y (range 18 – 91 y). 488 men (39.4%) reported ED: 119 (9.6%) ‘occasionally’, 110 (8.9%) ‘often’, and 231 (18.6%) ‘all the time’ (complete ED). Among 707 men aged 40–69 y 240 (33.9%) reported ED and 84 (11.9%) had complete ED. The prevalence of complete ED increased with age, rising from 2.0% in the 40 – 49 y age group to 44.9% in the 70–79 y age group. Only 11.6% of men with ED had received treatment. Hypertension, ischaemic heart disease, peripheral vascular disease and diabetes mellitus were frequently associated with ED. 40% of diabetic men aged 60 y or older had ED all the time.

Assessment and management of polycystic ovary syndrome: summary of an evidence-based guideline.

Helena J Teede, Marie L Misso, Amanda A Deeks, Lisa J Moran, Bronwyn G A Stuckey, Jennifer L A Wong, Robert J Norman and Michael F Costello on behalf of the Guideline Development Groups

Quality of life and psychological morbidity in women with polycystic ovary syndrome: body mass index, age and the provision of patient information are significant modifiers.

Objective  Polycystic ovary syndrome (PCOS) has clinical features and implications for long‐term health that may lead to decreased quality of life (QoL) and psychological morbidity. We studied QoL in women with PCOS, compared the findings with population norms and assessed whether they correlated with reported quality of patient information received.

Erectile dysfunction as a predictor for subsequent atherosclerotic cardiovascular events: Findings from a linked-data study

INTRODUCTION In spite of the mounting interest in the nexus between erectile dysfunction (ED) and cardiovascular (CV) diseases, there is little published information on the role of ED as a predictor for subsequent CV events. AIM This study aimed to investigate the role of ED as a predictor for atherosclerotic CV events subsequent to the manifestation of ED. Method. The investigation involved the retrospective study of data on a cohort of men with ED linked to hospital morbidity data and death registrations. By using the linked data, the incidence rates of atherosclerotic CV events subsequent to the manifestation of ED were estimated in men with ED and no atherosclerotic CV disease reported prior to the manifestation of ED. The risk of subsequent atherosclerotic CV events in men with ED was assessed by comparing these incidence rates with those in the general male population. MAIN OUTCOME MEASURE Standardized incidence rate ratio (SIRR), comparing the incidence of atherosclerotic CV events subsequent to the manifestation of ED in a cohort of 1,660 men with ED to the incidence in the general male population. RESULTS On the basis of hospital admissions and death registrations, men with ED had a statistically significantly higher incidence of atherosclerotic CV events (SIRR 2.2; 95% confidence interval 1.9, 2.4). There were significantly increased incidence rate ratios in all age groups younger than 70 years, with a statistically highly significant downward trend with increase of age (P < 0.0001) across these age groups. Younger age at first manifestation of ED, cigarette smoking, presence of comorbidities and socioeconomic disadvantage were all associated with higher hazard ratios for subsequent atherosclerotic CV events. CONCLUSIONS The findings show that ED is not only significantly associated with but is also strongly predictive of subsequent atherosclerotic CV events. This is even more striking when ED presents at a younger age.

Omega-3 Fatty Acid Supplementation Decreases Liver Fat Content in Polycystic Ovary Syndrome: A Randomized Controlled Trial Employing Proton Magnetic Resonance Spectroscopy

CONTEXT There is an association between nonalcoholic fatty liver disease (NAFLD) and the polycystic ovary syndrome (PCOS). Marine-derived omega-3 fatty acids have favorable effects on cardiovascular risk and could reduce liver fat in NAFLD. OBJECTIVE The primary aim of this study was to examine the effects of omega-3 fatty acids on liver fat in PCOS. The secondary aim was to assess their effects on traditional cardiovascular risk factors. DESIGN AND SETTING We conducted a randomized, crossover study at a tertiary cardiovascular research center. SUBJECTS Twenty-five women with PCOS (mean age, 32.7 yr; mean body mass index, 34.8 kg/m(2)) participated in the study. INTERVENTION We compared 4g/d of omega-3 fatty acids with placebo over 8 wk. MAIN OUTCOME MEASURES The primary outcome measure was hepatic fat content quantified using proton magnetic resonance spectroscopy. Secondary outcome measures included fasting lipids and blood pressure. RESULTS Omega-3 fatty acids significantly decreased liver fat content compared with placebo [10.2 (1.1) vs. 8.4 (0.9)%; P = 0.022]. There was also a reduction in triglycerides [1.19 (1.03-1.47) vs. 1.02 (0.93-1.18) mmol/liter; P = 0.002], systolic blood pressure [124.1 (12.1) vs. 122.3 (14.5) mm Hg; P = 0.018], and diastolic blood pressure [73.2 (8.4) vs. 69.7 (8.3) mm Hg; P = 0.005] with omega-3 fatty acids compared with placebo. Omega-3 fatty acids particularly decreased hepatic fat in women with hepatic steatosis, defined as liver fat percentage greater than 5% [18.2 (11.1) vs. 14.8 (9.3)%; P = 0.03]. CONCLUSIONS Omega-3 fatty acid supplementation has a beneficial effect on liver fat content and other cardiovascular risk factors in women with PCOS, including those with hepatic steatosis. Whether this translates into a reduction in cardiometabolic events warrants further study.

Safety and Efficacy of a Testosterone Metered-Dose Transdermal Spray for Treating Decreased Sexual Satisfaction in Premenopausal Women: A Randomized Trial

Context Testosterone levels in women gradually decline with age, and supplemental testosterone may improve sexual satisfaction in postmenopausal women. Contribution Sexually active women age 35 to 45 years with low serum free testosterone levels and low sexuality scores were randomly assigned to placebo or 3 doses of transdermal testosterone for 16 weeks. Sexually satisfying encounters increased in all 4 groups. Compared with placebo, the number increased by 0.8 per month with the intermediate dose (P = 0.04) but not with the other doses. Caution The study was too brief to measure adverse events reliably. Implication We need more evidence before prescribing testosterone supplementation to premenopausal women in clinical practice. The Editors Testosterone levels in women decline with age from the midreproductive years (1, 2) and do not change during menopause (2, 3 ). Testosterone therapy seems to improve sexual well-being in postmenopausal women (49), but few comparable data are available for premenopausal women. Women with low testosterone levels after menopause probably had low levels before menopause (3), and sexual well-being before menopause is a strong predictor of postmenopausal sexual well-being (10). These findings suggest that testosterone therapy may benefit women presenting with low libido in their late reproductive years. Premenopausal women often report decreased sexual interest, arousal, and pleasure (11, 12), yet they have few treatment options. In a randomized, placebo-controlled, crossover trial, testosterone administered as a transdermal cream improved sexual function and well-being in premenopausal women with low libido and low testosterone levels (13). However, the study enrolled few patients, efficacy was based on a 30-day recall rather than a daily event diary, and the women took only 1 dose of testosterone. We sought to determine the efficacy and safety of several doses of testosterone, administered transdermally by a metered-dose spray system, in increasing self-reported sexual satisfaction among premenopausal women who had decreased sexual satisfaction. Methods Participants We recruited potential participants by using radio and published press advertisements, and we screened them by telephone for suitability. Enrollment was from September 2003 to May 2004. The inclusion criteria were age 35 to 45 years, premenopausal status (regular menstrual cycles and follicle-stimulating hormone level <40 IU/L), body mass index (BMI) between 18 and 32 kg/m2, sexual activity (1 sexual event per 28 days, alone or with a partner) but with a low sexuality score (Sabbatsberg Sexual Self-Rating Scale [14] score <42), no evidence of severe clinical depression on the Beck Depression Inventory (score <28) (15), and early-morning serum free testosterone levels of 3.8 pmol/L or less (1.1 pg/mL). In addition, each woman had to have experienced a decrease in satisfactory sexual activity of sufficient concern to seek medical advice or treatment and answer yes to each of the following questions: In previous years did you find sexual activity satisfying? Has there been a decline in your satisfaction with sexual activity? Would you like to use a hormonal treatment that may improve the level of satisfying sexual activity? All volunteers had general good health on history and physical examination and had had a Papanicolaou smear within the past year. Volunteers had to have had 3 satisfactory sexual events (SSEs) at most over 28 days at baseline (week 0) and, if in an established relationship, their partner present at least 50% of the time. We excluded women who were planning a pregnancy or were breastfeeding; had relationship problems, poor feelings for their partner, or dyspareunia; had received pharmacotherapy for depression within 8 weeks of screening or were taking medication known to interfere with normal sexual function (such as -blockers and -blockers); or had ever used androgen therapy. We also excluded women with a history of acne or hirsutism or treatment with antiandrogens for hirsutism in the previous 5 years, past cancer other than nonmelanotic skin cancer, uncontrolled hypertension (systolic blood pressure >180 mm Hg or diastolic blood pressure >100 mm Hg), any major chronic major illness that would impair overall health and well-being, genital bleeding of unknown cause, intake of more than 3 standard alcoholic drinks per day or addictions to any drugs or medication within the past 5 years, and use of medications known to interfere with sex steroid metabolism. The use of thyroid hormone was acceptable if the dose was expected to remain stable throughout the study. The protocol required all participants to use a medically acceptable form of contraception, including oral contraceptive pills, and to have a negative pregnancy test result at screening. All women gave voluntary, written informed consent and were specifically advised that the effects of the study doses of testosterone in the setting of pregnancy or breast-feeding were unknown. We stressed the necessity of contraception, and all participants received contraceptive counseling. Women who declined contraception were excluded. We obtained study approval from the human research and ethics committee at each institution. The study met the Clinical Trial Notification requirement of the Therapeutic Goods Administration of Australia and the requirements for an Investigational New Drug Application for the U.S. Food and Drug Administration. Design The study was a multicenter, randomized, double-blind, placebo-controlled trial. Eligible patients were first asked to complete a 4-week diary to characterize baseline sexual function. We invited women who met the eligibility criteria for baseline sexual activity to enter the placebo-controlled treatment stage of 16 weeks followed by 4 further weeks after therapy was discontinued. Treatments Participants were randomly assigned to receive 1 of 3 different doses of testosterone or placebo. The formulation (50 g of testosterone per L) was constant for each active dose, and the dose varied by applying different amounts of formulation with a metered-dose spray (Acrux Limited, West Melbourne, Victoria, Australia) (16). On the basis of previous pharmacokinetic studies, the highest dose (two 90-L sprays) should have increased mean serum free testosterone levels to approximately the 75th percentile of the normal range for premenopausal women (17.3 pmol/L [5.0 pg/mL]). The normal range is 3.8 pmol/L (1.1 pg/mL) to 21.84 pmol/L (6.3 pg/mL). The other study groups received half (one 90-L spray) and one third (one 56-L spray) of the highest dose of testosterone or placebo. Participants randomly assigned to placebo were further randomly assigned to 1 of 3 placebo subgroups (one 90-L spray, two 90-L sprays, or one 56-L spray) that corresponded with the 3 active treatment groups. Because findings were similar in the 3 placebo subgroups, we combined them into 1 group in the analysis. Doses were applied topically to the abdomen once a day for 16 weeks. One multidose applicator was dispensed every 4 weeks. Randomization Computer-generated randomization schedules for each center were created in blocks of 12 without stratification. The study statistician (who was not otherwise involved in the conduct of the study) generated and held the randomization schedules. The randomization sequence was generated by using the Ranuni function (SAS software, SAS Institute, Cary, North Carolina). Each unique code number in the schedule referred to a randomly allocated treatment: either a specific dose of testosterone or 1 of the 3 placebo groups. At each center, the study staff sequentially assigned participants as they became eligible to the next unassigned treatment code on the list and then identified the treatment assignment corresponding to the code number. Both participants and center staff remained blinded to treatment assignment throughout the study. Outcome Measures The primary end point (the frequency of SSEs) was recorded in the 28-day patient diary, which was completed daily and collected at week 16. Secondary end points were the frequency of SSEs recorded in the 28-day patient diaries collected at weeks 4, 8, 12, and 20; frequency of total sexual events at weeks 4, 8, 12, 16, and 20; and mean (over each 28-day evaluation period) composite and subscale scores for the Sabbatsberg Sexual Self-Rating Scale (Appendix Figure) and Psychological General Well-Being Index. The Sabbatsberg Sexual Self-Rating Scale (17) is a multiple-choice questionnaire covering 7 aspects of sexuality: sexual interest, sexual activity, satisfaction of sexual life, experience of sexual pleasure, sexual fantasy, orgasm capacity, and sexual relevancy. This scale has been validated in premenopausal women (14). The range of possible composite scores was 0 (low) to 56 (high). The Psychological General Well-Being Index (18) is a validated, 22-item multiple-choice questionnaire with subscales for anxiety, depressed mood, positive well-being, self-confidence, general health, and vitality. The range of possible composite scores is 0 (most negative affective experience) to 110 (most positive affective experience). Patients self-administered questionnaires at screening; baseline (week 0); and weeks 8, 16, and 20. The Appendix provides details of biological measurements. Appendix Figure. Sabbatsberg Sexual Self-Rating Scale. Reproduced with permission from Acta Obstet Gynecol Scand Suppl. 1977;64:1-91. Safety Assessments We compared the rates of adverse events in the 3 treatment groups with rates in the placebo group. We monitored specific known androgenic side effects, including hirsutism, by using the FerrimanGallwey scale (19) and acne by using the Palatsi scale (20), and we asked participants about voice changes at each visit after baseline. All events known to be consequences of excessive androgen use were classified as treatment-related, and all others were classified

Metabolomic markers reveal novel pathways of ageing and early development in human populations

Background Human ageing is a complex, multifactorial process and early developmental factors affect health outcomes in old age. Methods Metabolomic profiling on fasting blood was carried out in 6055 individuals from the UK. Stepwise regression was performed to identify a panel of independent metabolites which could be used as a surrogate for age. We also investigated the association with birthweight overall and within identical discordant twins and with genome-wide methylation levels. Results We identified a panel of 22 metabolites which combined are strongly correlated with age (R2 = 59%) and with age-related clinical traits independently of age. One particular metabolite, C-glycosyl tryptophan (C-glyTrp), correlated strongly with age (beta = 0.03, SE = 0.001, P = 7.0 × 10−157) and lung function (FEV1 beta = −0.04, SE = 0.008, P = 1.8 × 10−8 adjusted for age and confounders) and was replicated in an independent population (n = 887). C-glyTrp was also associated with bone mineral density (beta = −0.01, SE = 0.002, P = 1.9 × 10−6) and birthweight (beta = −0.06, SE = 0.01, P = 2.5 × 10−9). The difference in C-glyTrp levels explained 9.4% of the variance in the difference in birthweight between monozygotic twins. An epigenome-wide association study in 172 individuals identified three CpG-sites, associated with levels of C-glyTrp (P < 2 × 10−6). We replicated one CpG site in the promoter of the WDR85 gene in an independent sample of 350 individuals (beta = −0.20, SE = 0.04, P = 2.9 × 10−8). WDR85 is a regulator of translation elongation factor 2, essential for protein synthesis in eukaryotes. Conclusions Our data illustrate how metabolomic profiling linked with epigenetic studies can identify some key molecular mechanisms potentially determined in early development that produce long-term physiological changes influencing human health and ageing.

Female Sexual Function and Dysfunction in the Reproductive Years: The Influence of Endogenous and Exogenous Sex Hormones

INTRODUCTION Sexual function in women in the reproductive age years is under psychological, sociocultural, and relationship influences, as well as the influence of sex hormones. AIM To examine the data relating to sexual function in women in the reproductive age group, particularly the influence of sex hormones. To examine, in particular, the influence of the menstrual cycle, pregnancy, the oral contraceptive pill and endogenous and exogenous testosterone. METHODS Review of the literature on female sexual function, confining the search to the reproductive age range. RESULTS Population studies of sexual function identify sexual disinterest as being the most common sexual complaint in premenopausal women. Most studies of menstrual cyclicity identify a periovulatory increase in sexual desire or activity. All prospective studies of sexuality in pregnancy document a decline in sexual function with progression of pregnancy. Studies of the influence of the oral contraceptive pill on sexual function are contradictory with most prospective controlled studies showing no deleterious effect. Studies of the influence of endogenous androgens on sexuality are also contradictory with one large cross-sectional study showing no correlation, but some case-controlled studies show low androgens in women with sexual dysfunction. Studies of testosterone therapy in premenopausal women are ambiguous, with no clear dose-response effect. CONCLUSIONS Sexual disinterest is prevalent in premenopausal woman despite being hormone replete. The assessment of androgen contribution is hampered by the unreliability of the testosterone assay in the female range. Large cross-sectional and longitudinal studies have not identified a correlation between testosterone and sexual function in women. Sexual dysfunction in the premenopausal age range is common. Sex hormones have a modifying effect on sexual function but social influences and learned responses are as important. The role of testosterone requires further study.

Cardiometabolic risk in polycystic ovary syndrome: a comparison of different approaches to defining the metabolic syndrome

BACKGROUND Polycystic ovary syndrome (PCOS) is associated with insulin resistance and features in common with the metabolic syndrome (MetS)--factors shown to predict cardiovascular risk and type 2 diabetes. We investigated the prevalence and characteristics of the MetS in PCOS by three definitions-World Health Organization (WHO), National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP-III) and International Diabetes Federation (IDF)--and compared that with the background population. METHODS Cross-sectional study of 168 women with PCOS and 883 age-matched controls from the Australian Diabetes, Obesity and Lifestyle (AusDiab) study. RESULTS Prevalence of the MetS in PCOS subjects was 33% by WHO, 37% by NCEP-ATP-III and 40% by IDF criteria, compared with 10% by NCEP-ATP-III and 13% by IDF in controls (P < 0.001). MetS by WHO criteria was not calculated in the AusDiab population. Age was an independent predictor of MetS in PCOS and controls. The prevalence of MetS was significantly higher among those with PCOS (P = 0.027) in obese women (BMI > 30 kg/m(2)), and higher but not significantly so in overweight (BMI 25-30 kg/m(2)) women (P = 0.052). Dehydroepiandrosterone sulphate was associated with a lower risk of the MetS--Odds ratio 0.86 (95% confidence interval, 0.77-0.97, P = 0.011). CONCLUSIONS An approximate 4-fold increase in the prevalence of the MetS in women with PCOS compared with the general population, consistent with the proposed major role of insulin and obesity in the syndrome, implies greater risk of cardiometabolic disease in women with PCOS. However, this estimate is likely to vary according to PCOS definition, ethnicity and different aetiological pathways to PCOS.

Postpartum thyroid dysfunction: clinical assessment and relationship to psychiatric affective morbidity.

Postpartum thyroid dysfunction (PPTD), diagnosed using biochemical criteria, is usually transient with a wide range of reported prevalence rates. The specific clinical and psychiatric morbidity associated with PPTD is still uncertain. The aims of the study were to determine the point prevalence of PPTD in Australian women at 6 months postpartum and to assess the specific clinical and psychiatric morbidity in these women.