Changes in HDL-cholesterol and lipoprotein Lp(a) after 6-month treatment with finasteride in males affected by benign prostatic hyperplasia (BPH).

Androgen effects on lipoproteins, mainly high density lipoprotein (HDL), could be exerted by a direct interaction of testosterone (T) or dihydrotestosterone (DHT) with liver androgen receptors. To assess if T needs to be converted into DHT to affect lipid metabolism, 13 patients were studied, affected with benign prostatic hyperplasia (BPH) and treated with an inhibitor of 5 alpha-reductase (finasteride). They were compared with 15 untreated controls. At baseline and after 3 and 6 months of therapy, each patient was evaluated as for lipoprotein and hormone concentrations, as well as for nutritional status. Body composition was assessed by anthropometry and bio-impedance analysis (BIA). Treatment was associated with a significant increase of HDL-cholesterol (HDL-C), mainly HDL3 subclass, and lipoprotein(a) (Lp(a)), as well as a decline of DHT, whereas no significant changes were apparent for T, estradiol (E2), sex hormone binding hormone (SHBG) and body composition indexes. However, no significant associations between DHT and lipid relative changes were apparent at bivariate correlation analysis. This finding was confirmed by comparing patient subsets identified by cluster analysis, according to HDL subclass individual responses. Rather, a slight association with E2 for HDL2 (positive) and HDL3 (negative) was found. In conclusion, finasteride can modify HDL and Lp(a) concentrations. However, by the data, these effects cannot be definitively attributed to the changes in DHT synthesis induced by finasteride, since a direct and non-specific interference of the drug on liver metabolism cannot be excluded.

Aging-related decline of gonadal function in healthy men: correlation with body composition and lipoproteins.

OBJECTIVE: To assess if androgen decline in physiological aging contributes to the concomitant changes in body composition and lipoprotein levels. DESIGN: Cross-sectional, observational study. SETTING: A university-based outpatient center. SUBJECTS: The study comprised 206 healthy volunteers (aged 18-95 years). MEASUREMENTS: Blood samples were drawn after an overnight fast for the assay of hormones (free testosterone (FT), estradiol (E2), and sex hormone-binding globulin (SHBG)) and lipids (total cholesterol, triglycerides, high-density lipoprotein cholesterol, and lipoprotein Lp(a)). At the same time, body composition was assessed by both anthropometry (fat mass percentage (FM%) estimated from four measures of skinfold thickness using the Durnin and Womersley equation and the Siri equation) and by bioimpedance analysis (FM% estimated using the Segal or Deurenberg equations, respectively, for subjects younger or older than 62 years). RESULTS: A significant age-related decline was found for FT and E2 concentrations, whereas SHBG levels were related positively with age. No significant association was apparent between hormonal changes and the concomitant modifications of body composition and lipoproteins. Only SHBG showed a significant inverse association between FM% and the waist-to-hip ratio, independent of age. The comparison between older hypogonadal (with FT levels below the lower limit of the normality range assessed in younger subjects) and eugonadal men did not show any significant differences in body composition or lipid profile. CONCLUSIONS: This study suggests that, in men, androgen decline caused by normal aging does not significantly affect some targets of testosterone action, such as body composition and lipid metabolism. Therefore, androgen supplementation in hypogonadal older men cannot be expected to influence nutritional status and body composition to the same extent that it does other main targets of testosterone action, such as sexual activity and muscle strength. However, we cannot exclude that selected subsets of older patients with low testosterone levels, especially if affected by catabolic disease, could benefit from the effects of androgen administration on nutritional status.

Effects of aging on dehydroepiandrosterone sulfate in relation to fasting insulin levels and body composition assessed by bioimpedance analysis.

Insulin can inhibit dehydroepiandrosterone (DHEA) biosynthesis in humans, as suggested by several studies performed in induced or spontaneous hyperinsulinemia. The increased insulin resistance documented throughout aging, with its accompanying hyperinsulinemia, may contribute to the age-related decline in DHEA synthesis. The aim of this study was to assess if the aging-related differences in DHEA sulfate (DHEA-S) serum levels can be associated with differences in fasting insulin levels, as well as body composition. Two hundred fifty-two healthy subjects of both sexes aged 19 to 90 years with a body mass index (BMI) less than 30 (mean +/- SD, 23.5 +/- 2.4) were studied DHEA-S and insulin serum levels were determined by a radioimmunologic procedure; body composition was assessed by anthropometry (fat mass percentage [FM%] estimated from four skinfold thicknesses by Durnin and Womersley and Siri equations [FM%-SKF]) and by bioimpedance analysis (BIA) (FM% estimated by equations developed by Segal et al and Deurenberg et al for subjects < and > 62 years, respectively [FM%-BIA]). DHEA-S levels were significantly and inversely related to age in both sexes. No significant aging-related differences were found in fasting insulin levels, although a trend toward an increase was apparent in the women on simple regression analysis. No significant associations were found between DHEA-S and insulin levels. As for body composition, a positive relationship to age was apparent for FM%-SKF, FM%-BIA, and waist to hip ratio (WHR), whereas BMI and phase angle ([PA] a bioelectric parameter considered an index of the ratio between intracellular and extracellular water) were inversely related to age. Fasting insulin levels were positively related to FM% as estimated by both BIA and anthropometry, independently of age in both sexes; in addition, a positive correlation with WHR and with the subscapular to triceps skinfold thickness ratio (SS/TS) was found in men and women, respectively. No significant correlation was apparent between DHEA-S and body composition indices in men, whereas in women a slight negative correlation between DHEA-S and WHR was documented, and was still significant after adjustment for age and fasting insulin. Stepwise multiple regression analysis confirmed that DHEA-S levels are not related to fasting insulin, but are independently related to age and, in women only, to WHR. Our study suggests that the DHEA-S decline due to aging is independent of fasting insulin, at least in healthy, non-obese people. In addition, it is not related to the aging-dependent changes in body composition in terms of FM% and fat-free mass (FFM) percentage (FFM%). Only in women could changes in fat distribution be slightly associated with DHEA-S decline, although such a relation cannot be accounted for by changes in insulin levels.

Effects of androgen suppression by gonadotropin-releasing hormone agonist and flutamide on lipid metabolism in men with prostate cancer: focus on lipoprotein(a).

No clear relation between lipoprotein(a) [Lp(a)] and endogenous gonadal hormones has been demonstrated. In this study, we compared the effects on Lp(a) of pharmacological castration in 50 patients with prostate cancer who were undergoing therapy with a gonadotropin-releasing hormone agonist (goserelin), with effects on 58 age-matched controls. We also studied 16 untreated patients under baseline conditions and after 3 months of therapy with goserelin alone or combined with an antiandrogen (flutamide). Neither cross-sectional nor prospective studies showed any significant effects of therapy on Lp(a). However, cluster analysis identified a subgroup of patients showing slight but significant increases in Lp(a) concentrations, as well as greater declines of testosterone and estradiol, suggesting that androgen, like estrogen, can exert some slight, though not easily detectable, influence on Lp(a).