Dehydroepiandrosterone supplementation in elderly men: a meta-analysis study of placebo-controlled trials.

CONTEXT: Age-related dehydroepiandrosterone (DHEA) deficiency has been associated with a broad range of biological abnormalities in males. OBJECT: Our objective was to meta-analyze all double-blind, placebo-controlled randomized trials (RCTs) investigating the effect of oral DHEA (DHEA supplementation) in comparison with placebo on sexual and metabolic outcomes in elderly men. DATA SOURCE: An extensive Medline Embase and Cochrane search was performed including the following words: DHEA, RCTs, and males. STUDY SELECTION: Only double-blind placebo-controlled trials performed in elderly men were included. DATA EXTRACTION: Data extraction was performed independently by 2 of the authors (A.S. and V.G.), and conflicts were resolved by the third investigator (G.C.). The quality of RCTs was assessed using the Cochrane criteria. RESULTS: Of 220 retrieved articles, 25 were included in the study. The available RCTs enrolled 1353 elderly men, with a mean follow-up of 36 weeks. DHEA supplementation was associated with a reduction of fat mass (standardized mean difference of -0.35 [-0.65 to -0.05]; P = .02). However, the association with fat mass disappeared in a multivariate regression model after adjusting for DHEA-related metabolite increases such as total testosterone and estradiol. In contrast to what was observed for fat mass, no effect of DHEA supplementation in comparison with placebo was observed for various clinical parameters including lipid and glycemic metabolism, bone health, sexual function, and quality of life. CONCLUSIONS: The present meta-analysis of intervention studies shows that DHEA supplementation in elderly men can induce a small but significant positive effect on body composition that is strictly dependent on DHEA conversion into its bioactive metabolites such as androgens or estrogens.

Sperm DNA fragmentation induced by cryopreservation: new insights and effect of a natural extract from Opuntia ficus-indica.

OBJECTIVE: To analyze the effect of cryopreservation on sperm DNA fragmentation (SDF) in two cytometric sperm populations, PI(brighter) and PI(dimmer), and to test the effects of Opuntia ficus-indica (OFI) extracts, which contain antioxidants and flavanoids, and of resveratrol on cryopreservation of human semen. DESIGN: In vitro prospective study. SETTING: Institutional study. PATIENT(S): Twenty-one normozoospermic men undergoing semen analysis for couple infertility. INTERVENTION(S): Cryopreservation using the routine method in the presence of OFI extracts or resveratrol. MAIN OUTCOME MEASURE(S): Measurement of SDF by TUNEL/PI flow cytometric method to evaluate sperm motility (by automated motion analysis, CASA system) and viability (by eosin/nigrosin staining) in the two populations of sperm PI(br) and PI(dim). RESULT(S): Cryopreservation induced an increase of SDF only in the PI(br) sperm population. The increase was negatively dependent on the basal values of SDF in the same population. Addition of OFI extracts and resveratrol to the cryopreservation medium slightly but statistically significantly reduced SDF in the PI(br) population without affecting the deleterious effect of cryopreservation on sperm motion parameters or viability. CONCLUSION(S): The increase of SDF in the PI(br) population, which is unrelated to semen quality, suggests that caution must be taken in using cryopreserved semen, as morphologically normal and motile sperm may be damaged. The addition of substances with multifunctional properties such as OFI extracts to cryopreservation medium is only slightly effective in preventing the dramatic effects on SDF.

Frailty in relation to variations in hormone levels of the hypothalamic-pituitary-testicular axis in older men: results from the European male aging study.

OBJECTIVES: To explore the associations between frailty and reproductive axis hormones (as an important regulatory system) in middle aged and older men. DESIGN: Cross-sectional. SETTING: The European Male Aging Study. PARTICIPANTS: Three thousand two hundred nineteen community-dwelling European men aged 40 to 79. MEASUREMENTS: Interviewer-assisted questionnaires to assess physical activity, health status, and mood were administered. Testosterone (T), luteinizing hormone (LH), follicle-stimulating hormone (FSH), dehydroepiandrosterone sulfate (DHEAS), and sex hormone-binding globulin (SHBG) were measured in a fasting morning blood sample. Frailty was assessed as an index (FI) according to the number (out of 43 possible) of health deficits (symptoms, signs, and functional impairments). Relationships between FI and hormone levels (as outcomes) were explored using regression models. RESULTS: Mean FI was 0.12 ± 0.11 (range 0-0.67) was highest in the oldest group. After adjustment for confounders, higher levels of FI were significantly associated with lower levels of total T, free T, and DHEAS and higher levels of gonadotropins and SHBG; a 1-standard deviation cross-sectional increase in FI was associated with a regression coefficient of -0.30 nmol/L (95% confidence interval (CI)=-0.53 to -0.07) decrease in total T and 0.66 U/L (95% CI=0.48-0.83) increase in LH. CONCLUSIONS: The associations between high FI, high gonadotropins, and well-maintained circulating T suggest that these changes are markers of aging-related disruptions of multiple physiological regulation, of which alterations in pituitary-testicular function represent a sensitive marker rather than an underlying pathogenic mechanism for frailty.

Testosterone regulates PDE5 expression and in vivo responsiveness to tadalafil in rat corpus cavernosum.

OBJECTIVES: To investigate the effect of testosterone on PDE5 expression and PDE5 inhibitor tadalafil in vivo responsiveness in a rat model. METHODS: PDE5 expression was localized by immunohistochemistry in the rat corpus cavernosum (CC) and quantified by both real-time RT-PCR and Western blot analysis in several tissues. In the in vivo study, control, castrated and testosterone (T) supplemented castrated rats were treated with acute or chronic oral tadalafil. Erectile function was evaluated by monitoring intracavernous pressure (ICP) following electro-stimulation (ES) of the cavernous nerve and intracavernous injection of NO donor, sodium nitroprusside (SNP). RESULTS: Rat CC expressed the highest PDE5 mRNA level. PDE5 was specifically immunolocalized in endothelial and smooth muscle cells. Surgical castration induced a significant reduction of PDE5 gene and protein expression (p<0.05), and ES response at all stimulation frequencies (p<0.001). T supplementation completely restored PDE5 expression, erectile response to ES and responsiveness to PDE5 inhibitor. Both acute and chronic tadalafil treatment were ineffective in ameliorating the ES response in castrated rats. Injection of increasing concentrations of SNP in castrated rats resulted in a statistically significant increase in ICP/MAP ratio as that observed in intact rats. In addition, tadalafil did not amplify the SNP effect in castrated rats at all the doses tested (0.06-6 nmoles). CONCLUSIONS: Our findings demonstrate that testosterone positively regulates PDE5 expression and in vivo responsiveness to PDE5 inhibitor, tadalafil, in the rat CC.