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Giovanni Corona, Giulia Rastrelli, Matteo Monami, André Guay, Jaques Buvat, Alessandra Sforza, Gianni Forti, Edoardo Mannucci and Mario Maggi

Objective

To verify whether hypogonadism represents a risk factor for cardiovascular (CV) morbidity and mortality and to verify whether testosterone replacement therapy (TRT) improves CV parameters in subjects with known CV diseases (CVDs).

Design

Meta-analysis.

Methods

An extensive Medline search was performed using the following words ‘testosterone, CVD, and males’. The search was restricted to data from January 1, 1969, up to January 1, 2011.

Results

Of the 1178 retrieved articles, 70 were included in the study. Among cross-sectional studies, patients with CVD have significantly lower testosterone and higher 17-β estradiol (E2) levels. Conversely, no difference was observed for DHEAS. The association between low testosterone and high E2 levels with CVD was confirmed in a logistic regression model, after adjusting for age and body mass index (hazard ratio (HR)=0.763 (0.744–0.783) and HR=1.015 (1.014–1.017), respectively, for each increment of total testosterone and E2 levels; both P<0.0001). Longitudinal studies showed that baseline testosterone level was significantly lower among patients with incident overall- and CV-related mortality, in comparison with controls. Conversely, we did not observe any difference in the baseline testosterone and E2 levels between case and controls for incident CVD. Finally, TRT was positively associated with a significant increase in treadmill test duration and time to 1 mm ST segment depression.

Conclusions

Lower testosterone and higher E2 levels correlate with increased risk of CVD and CV mortality. TRT in hypogonadism moderates metabolic components associated with CV risk. Whether low testosterone is just an association with CV risk, or an actual cause–effect relationship, awaits further studies.

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Giovanni Corona, Giulia Rastrelli, Matteo Monami, Farid Saad, Michaela Luconi, Marcello Lucchese, Enrico Facchiano, Alessandra Sforza, Gianni Forti, Edoardo Mannucci and Mario Maggi

Objective

Few randomized clinical studies have evaluated the impact of diet and physical activity on testosterone levels in obese men with conflicting results. Conversely, studies on bariatric surgery in men generally have shown an increase in testosterone levels. The aim of this study is to perform a systematic review and meta-analysis of available trials on the effect of body weight loss on sex hormones levels.

Design

Meta-analysis.

Methods

An extensive Medline search was performed including the following words: ‘testosterone’, ‘diet’, ‘weight loss’, ‘bariatric surgery’, and ‘males’. The search was restricted to data from January 1, 1969 up to August 31, 2012.

Results

Out of 266 retrieved articles, 24 were included in the study. Of the latter, 22 evaluated the effect of diet or bariatric surgery, whereas two compared diet and bariatric surgery. Overall, both a low-calorie diet and bariatric surgery are associated with a significant (P<0.0001) increase in plasma sex hormone-binding globulin-bound and -unbound testosterone levels (total testosterone (TT)), with bariatric surgery being more effective in comparison with the low-calorie diet (TT increase: 8.73 (6.51–10.95) vs 2.87 (1.68–4.07) for bariatric surgery and the low-calorie diet, respectively; both P<0.0001 vs baseline). Androgen rise is greater in those patients who lose more weight as well as in younger, non-diabetic subjects with a greater degree of obesity. Body weight loss is also associated with a decrease in estradiol and an increase in gonadotropins levels. Multiple regression analysis shows that the degree of body weight loss is the best determinant of TT rise (B=2.50±0.98, P=0.029).

Conclusions

These data show that weight loss is associated with an increase in both bound and unbound testosterone levels. The normalization of sex hormones induced by body weight loss is a possible mechanism contributing to the beneficial effects of surgery in morbid obesity.