Naomi M. Gades

Prevalence of conditions potentially associated with lower urinary tract symptoms in men

Authors from the Mayo Clinic, using data from the Olmsted County study, estimated the frequency of other causes (other than BPH) of LUTS. They found that such other conditions are prevalent, and increase in frequency with age. They concluded that overlooking these conditions can result in misclassification, misdiagnosis and incorrect treatment.

The Associations Between Serum Sex Hormones, Erectile Function, and Sex Drive: The Olmsted County Study of Urinary Symptoms and Health Status Among Men

INTRODUCTION Testosterone replacement therapy has been used in the treatment of sexual dysfunction; however, its use remains controversial, and the effectiveness and long-term health implications are unknown. AIM To evaluate the association between sex hormone serum levels, erectile function, and sexual drive in a population-based sample of men. METHODS A stratified random sample of men residing in Olmsted County, Minnesota, completed a questionnaire containing questions from the Brief Male Sexual Function Inventory (BMSFI), and participated in a clinical exam, which included serum hormone measurements. MAIN OUTCOME MEASURES Levels of sexual drive (libido) and erectile function as assessed by the BMSFI and serum testosterone, bioavailable testosterone, and estradiol measurements. RESULTS Out of 414 men, 294 had a regular sexual partner and androgen measurements at the 14th year of follow-up. Total testosterone and erectile function were significantly correlated even after adjustment for age (r = 0.12, P = 0.04). Conversely, total testosterone was not significantly correlated with sex drive (r = 0.08, P = 0.17). Bioavailable testosterone was significantly correlated with both erectile function and sex drive (r = 0.16, P = 0.01 and r = 0.20, P = 0.001, respectively). However, these associations disappeared after age adjustment (r = 0.04 and r = 0.09). CONCLUSIONS These cross-sectional results suggest the relationship between sex hormones and sexual function is complex, and that the age-related decline in sexual function may be due to age-related declines in levels of bioavailable testosterone rather than total testosterone levels.

Snoring as a risk factor for sexual dysfunction in community men.

INTRODUCTION Severe obstructive sleep apnea has been associated with sexual dysfunction; however, it is unclear whether milder forms of sleep disturbances might also be associated with sexual problems. AIM To evaluate the association between snoring and five measures of sexual dysfunction in a population-based sample of men. METHODS A stratified random sample of men residing in Olmsted County, Minnesota completed a questionnaire containing questions from the Brief Male Sexual Function Inventory (BMSFI) and a sleep questionnaire. MAIN OUTCOME MEASURES Levels of sexual drive (libido), erectile function, ejaculatory function, sexual problem assessment, and sexual satisfaction as assessed by the BMSFI. RESULTS Of 827 men with a regular sexual partner, subjects were divided into categories of heavy (N = 95), moderate (N = 573), and none/mild (N = 159) snoring. Their median age was 64 years (range 51-90). The sexual satisfaction domain score was significantly lower in the heavy snoring group (P value = 0.01). The odds of low sexual satisfaction was 2.3 (95% CI 1.2, 4.1) among the heavy snorers compared with the none/mild snoring group. This association remained statistically significant after adjustment for smoking, medical comorbidities, and mental health status. However, there was no significant difference in ejaculatory function, erectile function, sexual drive, and sexual problem assessment across snoring categories. CONCLUSIONS These data provide evidence of an association between snoring severity and reduced sexual satisfaction in a population of elderly community males. Snoring was not associated with biologic measures of sexual dysfunction.

Longitudinal Evaluation of Sexual Function in a Male Cohort: The Olmsted County Study of Urinary Symptoms and Health Status among Men

INTRODUCTION The presence of erectile or ejaculatory dysfunction may indicate physical problems; however, individual perceptions (e.g., sexual satisfaction) may reflect the degree of concern about these changes. Long-term data showing how changes in multiple sexual function domains track together may be useful in understanding the importance of physical declines vs. sexual satisfaction. AIM The aim of this study was to describe changes in sexual function among a population-based sample of aging men. METHODS A population-based cohort study using data from the Olmsted County Study of Urinary Symptoms and Health Status among Men. Sexual function was assessed biennially from 1996 to 2004 using a previously validated questionnaire in a random sample of 2,213 men. MAIN OUTCOME MEASURES Changes in erectile function, libido, ejaculatory function, sexual problems, and sexual satisfaction. RESULTS Overall, we observed declines in all of the sexual function domains, ranging from an annual decrease of 0.03 point per year for sexual satisfaction to an annual decrease of 0.23 point per year in erectile function. Moderate correlations were observed among all longitudinal changes in sexual function (range in age-adjusted r(s) = 0.14-0.43); however, significantly smaller correlations between changes in the functional domains and changes in sexual satisfaction and problem assessment were observed among older men (range in age-adjusted r(s) = 0.03-0.29). CONCLUSION Overall, these results demonstrate that longitudinal changes in five sexual function domains change together over time in our community-based cohort. Erectile function, ejaculatory function, and sexual drive decrease over time with greater rates of decline for older men. However, older men may be less likely to perceive these declines as a problem and be dissatisfied. These data may prove helpful to patients and clinicians in understanding and discussing changes in multiple aspects of sexual function.

Dropout in a longitudinal, cohort study of urologic disease in community men

BackgroundReasons for attrition in studies vary, but may be a major concern in long-term studies if those who drop out differ systematically from those who continue to participate. Factors associated with dropout were evaluated in a twelve-year community-based, prospective cohort study of urologic disease in men.MethodsDuring 1989–1991, 2,115 randomly selected Caucasian men, ages 40–79 years from Olmsted County, Minnesota were enrolled and followed with questionnaires biennially; 332 men were added in follow-up. A random subset (~25%) received a urologic examination. Baseline characteristics including age, benign prostatic hyperplasia (BPH) symptoms, comorbidities, and socioeconomic factors were compared between subjects who did and did not participate after the twelfth year of follow-up.ResultsOf the 2,447 men, 195 died and were excluded; 682 did not participate in 2002. Compared with men in the 40–49 year age group, men ≥ 70 years of age at baseline had a greater relative odds of dropout, 2.65 (95% CI: 1.93, 3.63). In age-adjusted analyses, relative to men without stroke, men who had suffered a stroke had a higher odds of dropout, age-adjusted OR 3.07 (95% CI: 1.49, 6.33). Presence of at least one BPH symptom was not associated with dropout, (age-adjusted OR 1.12 (95% CI: 0.93, 1.36)).ConclusionThese results provide assurance that dropout was not related to primary study outcomes. However, factors associated with dropout should be taken into account in analyses where they may be potential confounders.

Effects of buprenorphine on body temperature, locomotor activity and cardiovascular function when assessed by telemetric monitoring in rats

We read with great interest, the recent article in Laboratory Animals by IIback et al. (2008). This research adds to the growing research data on buprenorphine as an analgesic in laboratory rodents. The authors’ thoughtful discussion helped put their findings in perspective. As we read the article, however, we felt a couple of points deserved further clarification: First, our article (Gades et al. 2000) was incorrectly cited as having administered a single dose of oral buprenorphine to rats, producing an analgesic effect of 6–8 h. We administered all the opioids in our study subcutaneously. The purpose of our study (Gades et al. 2000) was to determine the magnitude and duration of the analgesic effect of three commonly used opioids: buprenorphine (0.5 mg/kg for rats; 2.0 mg/kg for mice), butorphanol (2.0 mg/kg for rats; 5.0 mg/kg for mice) and morphine (10 mg/kg for rats and mice). We used two standard tests, the hot plate and tail flick assays, to measure opioid analgesia in 62 male Sprague-Dawley rats weighing 200–300 g and 61 male ICR mice weighing 25–35 g. We obtained five baseline measurements and then administered the drugs subcutaneously. Morphine gave the highest analgesic effect and was intermediate in duration (2–3 h in rats and mice) of analgesia. Butorphanol provided the lowest level of and shortest (1–2 h in rats and mice) analgesia. Buprenorphine had an intermediate analgesic effect and the longest duration (6–8 h in rats and 3–5 h in mice). In light of our results, we recommend the use of morphine (with frequent redosing) for severe pain, butorphanol for mild pain of short duration and buprenorphine for mild to moderate pain of increased duration. The dosing intervals suggested by our study are 2–3 h for morphine in both rats and mice, 1–2 h for butorphanol in both rats and mice, 6–8 h in rats and 3–5 h in mice for buprenorphine. We concur with IIback et al. that oral buprenorphine in rodents is not efficacious, however, more appropriate citations would be the studies conducted by Martin et al. (2001) and Thompson et al. (2004, 2006) which showed that oral administration of buprenorphine recommended for postoperative analgesic care does not induce significant analgesia and therefore is not as effective as the standard subcutaneous dose of 0.05 mg/kg. In summary, the results and conclusions shown by IIback et al. (2008) are noteworthy and add to our knowledge about the use of buprenorphine in laboratory rodents. They highlight the fact that oral administration of buprenphine is not as effective as parenteral administration in rodents; however, our study (Gades et al. 2000) did not administer buprenorphine orally to rats but subcutaneously only.

Optimized administration regimen of lopinavir for a myocardial ischaemia reperfusion study in Sprague–Dawley rats

Pharmacokinetics of drugs may differ between small and large mammals (including humans); therefore, drug testing in animal models must be carefully designed. Sprague–Dawley rats were used in cardiac experiments, during which the lopinavir concentration in serum had to match human therapeutic levels (4–10 μg/mL). Lopinavir was administered as a co-formulated drug of lopinavir and ritonavir. It was found that after a single administration of a standard human peroral dose (lopinavir 13.3 mg/kg of body weight), the serum concentration of lopinavir was only one-tenth of the target level. It remained below the minimum target level even after 10-fold the standard dose was administered. After initial pilot tests, a dose escalation study was conducted with oral doses 10- and 15-fold the standard clinical dose of lopinavir (i.e. 133 and 200 mg/kg, respectively). A second administration 2 h later effectively increased and maintained higher concentrations during the experimental ischaemia and reperfusion periods. A dose-dependent increase in serum concentration of the drug was observed. Thus, the target therapeutic serum level of lopinavir in the rats was achieved by administrating 10- to 15-fold the standard human dose twice, separated by a 2 h interval.