Evidence that the CAG repeat in the androgen receptor gene is associated with the age-related decline in serum androgen levels in men.

In men over 30 years old, serum levels of testosterone (T) decrease with age. A shorter polymorphic CAG repeat length in exon 1 of the androgen receptor (AR) gene is associated with higher transcription activation by the AR. We determined the number of CAG repeats for 882 men aged between 40 and 70 years from the Massachusetts Male Aging Study (MMAS). MMAS is a population-based random sample survey of men for whom baseline (1987-1989, mean age 53+/-8 years) and follow-up (1995-1997, mean age 61+/-8 years) serum hormone levels were available. Multiple linear regression was used to determine if CAG repeat length would be predictive of hormone levels at follow-up. Hormone levels measured included T, free T, albumin-bound T, dihydrotestosterone (DHT), sex hormone-binding globulin (SHBG) and luteinizing hormone (LH). The CAG repeat length was significantly associated with T (P=0.041), albumin-bound T (P=0.025) and free T (P=0.003) when controlled for age, baseline hormone levels and anthropometrics. Follow-up levels of T decreased by 0.74%+/-0.36 per CAG repeat decrement. Likewise, the percentages of free and albumin-bound T decreased by 0.93%+/-0.31 and 0.71%+/-0.32 per CAG repeat decrement respectively. These results suggest that androgen levels may be modulated by AR genotype.

Physical activity and lipids and lipoproteins in American Indians ages 45-74.

PURPOSE: The Strong Heart Study is a study of cardiovascular disease and its risk factors among American Indian men and women aged 45-74 yr representative of 13 communities from Arizona (AZ), Oklahoma (OK), and North/South Dakota (N/SD). This investigation sought to characterize the amount and type of physical activity and to determine the association between activity and lipids in this population. METHODS: Total physical activity (occupational plus leisure) was assessed with a validated questionnaire. RESULTS: Men and women from OK (21 +/- 19 and 16 +/- 15 h.wk-1; respectively) and N/SD (23 +/- 21 and 17 +/- 17 h.wk-1; respectively) had activity levels that were similar if not lower than the U.S. population with the AZ communities (17 +/- 21 and 10 +/- 14 h.wk-1; respectively) being substantially lower than the other two communities. Total cholesterol (TC), high density lipoprotein cholesterol (HDL-c), and low density lipoprotein cholesterol (LDL-c) levels were lower than the U.S. population. CONCLUSIONS: For most of the population (diabetic men and nondiabetic men and women), activity was significantly associated (P < 0.05) with apolipoprotein (apo) AI after controlling for covariates. With levels of activity as low if not lower than the general U.S. population coupled with high prevalence of obesity and diabetes, efforts to increase physical activity in American Indians are warranted. Hopefully these increases in activity will result in favorable lipid changes as well as decreasing the risk of diabetes which is epidemic in these populations.

Exercise training has little effect on HDL levels and metabolism in men with initially low HDL cholesterol.

Low concentrations of high-density lipoprotein cholesterol (HDL-C) are a recognized risk factor for atherosclerotic cardiovascular disease. Exercise is often recommended to increase HDL-C, but the effect of exercise training on HDL levels and metabolism in subjects with low HDL concentrations is not well defined. The present study compared the HDL response to 12 months of supervised endurance exercise training without weight loss in 17 men aged 26 49 years with initially low ( < 40 mg/dl, N=7) or normal ( > 44 mg/dl, N=10) HDL-C levels. HDL-C levels and HDL apolipoprotein metabolism were assessed while the subjects consumed controlled diets before and after the year of training. Increases in total (5.1+/-2.8 versus 1.9+/-4.2 mg/dl, P=0.08) and HDL2 (3.8+/-2.9 versus 0.4+/-1.1 mg/dl, P=0.01) cholesterol were greater in men with normal initial HDL-C levels. Catabolic rates for HDL apolipoproteins decreased 7-14% and biological half-lives increased 10-15% after exercise training in subjects with normal HDL, but were unchanged in the low HDL-C group. HDL apolipoprotein synthetic rates were not consistently affected by exercise training in either group. Postheparin lipoprotein lipase activity increased 27%, the clearance rate of intravenous triglycerides increased 14%, and apolipoprotein B levels decreased 16% with training in subjects with normal HDL-C but were unchanged in the low HDL-C group. We conclude that the ability to increase HDL-C levels through endurance exercise training is limited in subjects with low initial HDL-C, possibly because exercise training in such subjects fails to alter triglyceride metabolism.

Effect of prolonged exercise training without weight loss on high-density lipoprotein metabolism in overweight men.

This study examined the effect of exercise training without weight loss on high-density lipoprotein (HDL) metabolism in overweight men. We evaluated HDL metabolism using 125I-radiolabeled autologous HDL in 17 overweight men aged 40 +/- 7 years (mean +/- SD) before and after 1 year of exercise training. Subjects consumed defined diets in a metabolic kitchen during the metabolic studies. They performed endurance exercise under supervision for 1 hour four times weekly and maintained their pretraining body weight. Maximal oxygen uptake (VO2max) increased 27% (P < .001) with exercise training. HDL-cholesterol (HDL-C) and apolipoprotein (apo) A-I increased 10% and 9%, respectively (P < .001 for both), whereas triglycerides and apo B decreased 7% and 10%, respectively (P < .05). Postheparin lipoprotein lipase increased 11% (P = NS). Hepatic triglyceride lipase activity (HTGLA) decreased 12% (P < .05). The fractional catabolic rate (FCR) of HDL protein and of apo A-I decreased 5% and 7%, respectively (P < .05 for both). The synthetic rate of apo A-I increased 13% (P < .01). Increased HDL after exercise training is associated with both decreased HDL protein catabolism and increased HDL apo A-I synthesis. Weight loss is not required to increase HDL-C with exercise training in overweight men, but without weight loss, even prolonged exercise training produces only modest changes in HDL-C concentrations.

Variations in plasma volume affect total and low-density lipoprotein cholesterol concentrations during the menstrual cycle.

Serum lipids are known to vary during the menstrual cycle. To determine if changes in plasma volume contribute to this effect, we determined serum lipids, lipoproteins, and estimated changes in plasma volume in 18 premenopausal women at the start of and at 5-day intervals after menstruation. Eleven men served as a comparison group. Changes in plasma volume were estimated from changes in hemoglobin and hematocrit. Total and low-density lipoprotein (LDL) cholesterol (mean +/- SD) increased 15 +/- 14 mg/dL (9% +/- 10%) and 11 +/- 13 (11% +/- 14%) within 10 days after the start of menstruation (P < .05) and then decreased toward baseline during the rest of the cycle. High-density lipoprotein (HDL) cholesterol increased 3 mg/dL, or 5%, (P < .05) on days 10 and 15 after menstruation. Plasma volume decreased 4% +/- 9% (P < .06) 10 days after the start of menstruation, and this maximum decrease in plasma volume coincided with peak increases in total, LDL, and HDL cholesterol. Except for an 8-mg/dL increase in LDL cholesterol at day 5, lipid changes were no longer significant after adjusting for changes in plasma volume. We conclude that alterations in plasma volume account for approximately half of the increase in total and LDL cholesterol during the menstrual cycle.

Effect of doxazosin or atenolol on exercise performance in physically active, hypertensive men.

The effects of doxazosin or atenolol on exercise capacity in 15 male distance runners (mean age +/- SD 43 +/- 10 years) were compared in a double-blind, crossover study. Subjects performed a maximal treadmill test and a timed 2-mile run before and after each drug treatment. Cardiac output was determined by acetylene rebreathing at rest and at 30%, 50%, and 75% of maximal oxygen consumption. Oxygen consumption was determined at the above-mentioned workloads and at maximal effort. Both drugs were titrated to produce similar reductions in blood pressure and the final doses of atenolol and doxazosin were 43 +/- 22 and 6 +/- 6 mg, respectively. Atenolol reduced cardiac output (p < 0.05) and heart rate (p < 0.001) at rest and at all exercise intensities compared with the prior placebo phase, whereas doxazosin increased cardiac output at rest and at 50% effort (p < 0.05). Consequently, cardiac output was higher (p < 0.01) with doxazosin than with atenolol at rest and at 30% and 50% effort. Heart rate was higher with doxazosin (p < 0.01) during all exercise workloads. Despite these changes in cardiovascular function, there were no significant differences between the effect of the 2 study drugs on maximal oxygen consumption or 2-mile run times. We conclude that atenolol decreases rest and exercise heart rate and cardiac output compared with doxazosin, but that at modest doses neither drug adversely affects exercise performance in male hypertensive runners.

Lipoprotein lipase activity and plasma triglyceride clearance are elevated in endurance-trained women.

Numerous studies have examined factors regulating high-density lipoprotein cholesterol (HDL-C) levels in male endurance athletes, but few studies have examined HDL-C regulation in female athletes. The present study compared lipid and lipoprotein concentrations, postheparin lipolytic activities, and the clearance rate (K2) of triglycerides following an intravenous fat infusion in 12 female distance runners (aged 33 +/- 9 years, mean +/- SD) and 13 sedentary women (33 +/- 9 years). Runners were leaner and had greater maximum oxygen uptake values than controls. Runners also had nonsignificantly lower triglyceride (53 +/- 15 v 65 +/- 13 mg/dL) and higher HDL-C (62 +/- 14 v 52 +/- 8 mg/dL, P = .06). Lipoprotein lipase activity (LPLA) was 33% greater (P < .05) and fat clearance (K2) was 27% faster (P < .01) in the trained women, and LPLA correlated directly with K2 (r = .61) and HDL-C (r = .62) in this group (P < .05 for both). K2 was directly related to HDL-C in the athletes (r = .57, P = .06), and also when the active and sedentary women were combined (r = .43, P < .05). These results suggest that increased LPLA and enhanced plasma triglyceride clearance may contribute to the HDL-C levels of physically active premenopausal women.