Testosterone Replacement Therapy

Male hypogonadism (HG) can be defined according to its etiology as primary (pHG) when caused by any diseases affecting the testes, or as secondary (sHG) when due to a pituitary or hypothalamic dysfunction. Both fertility and testosterone (T) can be theoretically restored in sHG by removing the precipitating cause and/or by appropriate endocrine therapy. Conversely, only T treatment can be offered to patients with pHG. Symptoms and signs are quite similar independent of the underlying causes. Conversely, the phenotype of the hypogonadal patient is more often affected by the age of hypogonadism onset. Late-onset hypogonadism (LOH) that occurs in adulthood is probably the most common form of HG. In this chapter, the criteria defining LOH and the available T formulations along with their outcomes and main important side effects are analyzed in detail

Obesity paradox in cardiovascular disease: where do we stand?

Salvatore Carbone,1 Justin M Canada,1 Hayley E Billingsley,1,2 Mohammad S Siddiqui,3 Andrew Elagizi,4 Carl J Lavie41VCU Pauley Heart Center, Department of Internal Medicine, Richmond, VA, USA; 2Kinesiology and Health Sciences, College of Humanities & Science, Richmond, VA, USA; 3Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University, Richmond, VA, USA; 4John Ochsner Heart and Vascular Institute, Ochsner Clinical School-the University of Queensland School of Medicine, New Orleans, LA, USAAbstract: Obesity is associated with an increased risk of developing cardiovascular disease (CVD), particularly heart failure (HF) and coronary heart disease (CHD). The mechanisms through which obesity increases CVD risk involve changes in body composition that can affect hemodynamics and alters heart structure. Pro-inflammatory cytokines produced by the adipose tissue itself which can induce cardiac dysfunction and can promote the formation of atherosclerotic plaques. When obesity and HF or CHD coexist, individuals with class I obesity present a more favorable prognosis compared to individuals who are normal or underweight. This phenomenon has been termed the “obesity paradox.” Obesity is defined as an excess fat mass (FM), but individuals with obesity typically also present with an increased amount of lean mass (LM). The increase in LM may explain part of the obesity paradox as it is associated with improved cardiorespiratory fitness (CRF), a major determinant of clinical outcomes in the general population, but particularly in those with CVD, including HF. While increased LM is a stronger prognosticator in HF compared to FM, in patients with CHD excess FM can exert protective effects particularly when not associated with increased systemic inflammation. In the present review, we discuss the mechanisms through which obesity may increase the risk for CVD, and how it may exert protective effects in the setting of established CVD, with a focus on body composition. We also highlight the importance of measuring or estimating CRF, including body composition-adjusted measures of CRF (ie, lean peak oxygen consumption) for an improved risk status stratification in patients with CVD and finally, we discuss the potential non-pharmacologic therapeutics, such as exercise training and dietary interventions, aimed at improving CRF and perhaps clinical outcomes.Keywords: obesity, cardiovascular disease, obesity paradox, body composition, cardiorespiratory fitnes

Obesity and the paradox of mortality and heart failure hospitalization in heart failure with preserved ejection fraction

Background: Limited data exist on the association of obesity with both hospitalization and mortality in patients with heart failure with preserved ejection fraction (HFpEF), especially in the real-world ambulatory setting. We hypothesized that increasing body-mass index (BMI) in ambulatory heart failure with preserved ejection fraction would have a protective effect on these patients leading to decreased mortality and hospitalizations.Methods: We studied the relationship between BMI and the time to all-cause mortality, time to heart failure (HF) hospitalization, and time to all-cause hospitalization over a 2-year follow-up in a national cohort of 2501 ambulatory HFpEF patients at 153 Veterans Affairs medical centers.Results: Compared with normal BMI, overweight (HR 0.72; 95% CI 0.57-0.91), obesity class I (HR 0.59; 95% CI 0.45-0.77), obesity class II (HR 0.56; 95% CI 0.40-0.77), and obesity class III (HR 0.53; 95% CI 0.36-0.77) were associated with improved survival after adjustment for demographics and comorbidities. In contrast, the time to HF hospitalization showed an inverse relationship, with shorter time to HF hospitalization with increasing BMI compared with normal BMI; overweight (adjusted HR 1.30; 95% CI 0.88-1.90), obesity class I (HR 1.57; 95% CI 1.05-2.34), obesity class II (HR 1.79; 95% CI 1.15-2.78), and obesity class III (HR 1.96; 95% CI 1.23-3.12). However, time to first all-cause hospitalization was not significantly different by BMI groups.Conclusions: In a large, national ambulatory HFpEF cohort, despite the presence of the obesity paradox with respect to survival, increasing BMI was independently associated with an increased risk of HF hospitalization and similar risk of all-cause hospitalization. Future longer-term prospective trials evaluating the safety and efficacy of weight loss on morbidity and mortality, in patients with severe obesity and HFpEF are needed