Biomedical subjects

Alan G Meehan

Publications and source records attributed to Alan G Meehan.

4 recordsLinked to original sources

PubMed2006

The age related decrease in testosterone is significantly exacerbated in obese men with the metabolic syndrome. What are the implications for the relatively high incidence of erectile dysfunction observed in these men?

PURPOSE: We examined pooled baseline data from 2 lipid treatment studies to evaluate the relationship among total serum testosterone levels, obesity and the metabolic syndrome in aging men. MATERIALS AND METHODS: Baseline total serum testosterone, lipid, glycemic and anthropometric data were obtained from 864 men (mean age 52 years) participating in 2 lipid treatment studies. Inclusion criteria for the 2 studies included low-density lipoprotein cholesterol 130 to 160 mg/dl and triglycerides 350 mg/dl or less. RESULTS: For all patients as well as the nonmetabolic syndrome and the metabolic syndrome cohorts, testosterone decreased with increasing body mass index (p < 0.0001 for Pearson correlation coefficient in all 3 cohorts). Mean baseline total serum testosterone levels in obese and severely obese aging men with the metabolic syndrome were around 150 and 300 ng/dl, respectively, less than that in aging, lean men with no metabolic syndrome. The relative contributions of each of the individual National Cholesterol Education Program Adult Treatment Panel III components of the metabolic syndrome to low serum testosterone in aging men was examined using multiple linear regression modeling. Based on these analyses the presence of diabetes or fasting serum glucose greater than 110 mg/dl, body mass index 30 kg/m or greater, and triglycerides 150 mg/dl or greater each appeared to have a clinically relevant association with low serum testosterone. CONCLUSIONS: This study demonstrated that aging men with obesity and the metabolic syndrome have a significant decrease in total serum testosterone levels compared to aging, metabolically healthy men. These data suggest that the well established association between erectile dysfunction and pre-diabetes/diabetes (particularly in obese pre-diabetic/diabetic patients) may involve a hormonal component.

Age Factors↗

PubMed2006

Combination therapy with doxazosin and finasteride for benign prostatic hyperplasia in patients with lower urinary tract symptoms and a baseline total prostate volume of 25 ml or greater.

PURPOSE: We examined data from the Medical Therapy of Prostatic Symptoms trial to determine the relationship between baseline TPV and the effect of medical therapy in men with LUTS secondary to BPH. MATERIALS AND METHODS: A total of 3,047 patients with LUTS were randomized to placebo, 4 to 8 mg doxazosin, 5 mg finasteride or the combination of doxazosin and finasteride. Average treatment duration was 4.5 years The primary outcome was time to overall clinical progression of BPH, defined as a confirmed 4 point or greater increase in AUA SS, acute urinary retention, incontinence, renal insufficiency or recurrent urinary tract infection. Secondary outcomes were the need for invasive therapy for BPH, and changes in AUA SS and the maximum urinary flow rate with time. TPV was measured by transrectal ultrasound at baseline and study end. RESULTS: In patients with a small prostate (baseline TPV less than 25 ml) combination therapy was no better than doxazosin alone for decreasing the risk of clinical progression of BPH and need for invasive therapy as well as improving AUA SS and the maximum urinary flow rate. However, in patients with moderate size (25 to less than 40 ml) or enlarged (40 ml or greater) glands combination therapy led to a clinical benefit in these outcomes that was superior to that of doxazosin or finasteride. CONCLUSIONS: Combination therapy with doxazosin and finasteride led to a greater decrease in the risk of clinical progression of BPH than either drug alone in patients with LUTS with a baseline TPV of 25 ml or greater.

Aged↗

PubMed2006

Baseline factors as predictors of clinical progression of benign prostatic hyperplasia in men treated with placebo.

PURPOSE: We analyzed data from the placebo arm of the MTOPS trial to determine clinical predictors of BPH progression. MATERIALS AND METHODS: A total of 3,047 patients with LUTS were randomized to either placebo, doxazosin (4 to 8 mg), finasteride (5 mg), or a combination of doxazosin and finasteride. Average length of followup was 4.5 years. The primary outcome was time to overall clinical progression of BPH, defined as either a confirmed 4-point or greater increase in AUA SS, acute urinary retention, incontinence, renal insufficiency, or recurrent urinary tract infection. We analyzed BPH progression event data from the 737 men who were randomized to placebo. RESULTS: The rate of overall clinical progression of BPH events in the placebo group was 4.5 per 100 person-years, for a cumulative incidence (among men who had at least 4 years of followup data) of 17%. The risk of BPH progression was significantly greater in patients on placebo with a baseline TPV of 31 ml or greater vs less than 31 ml (p <0.0001), a baseline PSA of 1.6 ng/dl or greater vs PSA less than 1.6 ng/dl (p = 0.0009), a baseline Qmax of less than 10.6 ml per second vs 10.6 ml per second or greater (p = 0.011), a baseline PVR of 39 ml or greater vs less than 39 ml (p = 0.0008) and baseline age 62 years or older vs younger than 62 years (p = 0.0002). CONCLUSIONS: Among men in the placebo arm, baseline TPV, PSA, Qmax, PVR and age were important predictors of the risk of clinical progression of BPH.

Adrenergic alpha-Antagonists↗

PubMed2006

Pharmacokinetics and pharmacodynamic effects of the oral DPP-4 inhibitor sitagliptin in middle-aged obese subjects.

Sitagliptin (MK-0431) is an oral, potent, and selective dipeptidyl peptidase-IV (DPP-4) inhibitor developed for the treatment of type 2 diabetes. This multicenter, randomized, double-blind, placebo-controlled study examined the pharmacokinetic and pharmacodynamic effects of sitagliptin in obese subjects. Middle-aged (45-63 years), nondiabetic, obese (body mass index: 30-40 kg/m2) men and women were randomized to sitagliptin 200 mg bid (n = 24) or placebo (n = 8) for 28 days. Steady-state plasma concentrations of sitagliptin were achieved within 2 days of starting treatment, and >90% of the dose was excreted unchanged in urine. Sitagliptin treatment led to approximately 90% inhibition of plasma DPP-4 activity, increased active glucagon-like peptide-1 (GLP-1) levels by 2.7-fold (P < .001), and decreased post-oral glucose tolerance test glucose excursion by 35% (P < .050) compared to placebo. In nondiabetic obese subjects, treatment with sitagliptin 200 mg bid was generally well tolerated without associated hypoglycemia and led to maximal inhibition of plasma DPP-4 activity, increased active GLP-1, and reduced glycemic excursion.

Adenosine Deaminase↗