The safety and efficacy of Avanafil, a new 2^nd generation PDE5i: comprehensive review and meta-analysis

<p><b><i>Introduction</i>:</b> The discontinuation rate with phosphodiesterase type 5 inhibitors (PDE5i) remains very high. Recently, a new PDE5ì, avanafil, has become available worldwide.</p> <p><b><i>Areas covered</i>:</b> All placebo-controlled randomized clinical trials (RCTs) on the effect of avanafil in patients with ED were reviewed and meta-analyzed. So far, 5 different RCTs on avanafil have been published, including 1379 and 605 patients in active and placebo groups, respectively. Avanafil was up to 3-fold superior to placebo in determining successful sexual intercourse. Although head-to-head comparative studies are still lacking, re-analyses of available data, showed that avanafil had comparable efficacy, but lower incidence of drug-related side effects, compared to first-generation PDE5is.</p> <p><b><i>Expert opinion</i>:</b> Avanafil specific and peculiar pharmacological profile, addresses several problems that have been documented with first-generation PDE5is. Avanafil should theoretically guarantee a low dropout incidence by ensuring a natural profile of action and a low incidence of side effects. Longer studies and head-to-heard trials are advisable to clarify these issues.</p

The metabolic role of prolactin: systematic review, meta-analysis and preclinical considerations

Hyperprolactinemia has been proven to induce hypogonadism and metabolic derangements in both genders, while the consequences of prolactin (PRL) deficiency have been poorly investigated. To systematically review and analyze data from clinical studies focusing on the metabolic consequences of abnormally high prolactin levels (HPRL) and low prolactin levels (LPRL). In addition, data from preclinical studies about underlying pathophysiological mechanisms were summarized and discussed. PRL contributes to providing the correct amount of energy to support the mother and the fetus/offspring during pregnancy and lactation, but it also has a homeostatic role. Pathological PRL elevation beyond these physiological conditions, but also its reduction, impairs metabolism and body composition in both genders, increasing the risk of diabetes and cardiovascular events. Hence, hypoprolactinemia should be avoided as much as possible during treatment with dopamine agonists for prolactinomas. Patients with hypoprolactinemia, because of endogenous or iatrogenic conditions, deserve, as those with hyperprolactinemia, careful metabolic assessment.</p

DataSheet_1_The Leydig cell biomarker INSL3 as a predictor of age-related morbidity: Findings from the EMAS cohort.pdf

BackgroundInsulin-like peptide 3 (INSL3) is a constitutive hormone secreted in men by the mature Leydig cells of the testes. It is an accurate biomarker for Leydig cell functional capacity, reflecting their total cell number and differentiation status.ObjectivesTo determine the ability of INSL3 to predict hypogonadism and age-related morbidity using the EMAS cohort of older community-dwelling men.Materials & methodsCirculating INSL3 was assessed in the EMAS cohort and its cross-sectional and longitudinal relationships to hypogonadism, here defined by testosterone (T) Results & discussionWhile INSL3 is an accurate measure of primary hypogonadism, secondary and compensated hypogonadism also indicate reduced levels of INSL3, implying that testicular hypogonadism does not improve even when LH levels are increased, and that ageing-related hypogonadism may combine both primary and secondary features. Unadjusted, serum INSL3, like calculated free testosterone (cFT), LH, or the T/LH ratio reflects hypogonadal status and is associated with reduced sexual function, bone mineral density, and physical activity, as well as increased occurrence of hypertension, cardiovascular disease, cancer, and diabetes. Using multiple regression analysis to adjust for a range of hormonal, anthropometric, and lifestyle factors, this relationship is lost for all morbidities, except for reduced bone mineral density, implying that INSL3 and/or its specific receptor, RXFP2, may be causally involved in promoting healthy bone metabolism. Elevated INSL3 also associates with hypertension and cardiovascular disease. When unadjusted, INSL3 in phase 1 of the EMAS study was assessed for its association with morbidity in phase 2 (mean 4.3 years later); INSL3 significantly predicts 7 out of 9 morbidity categories, behaving as well as cFT in this regard. In contrast, total T was predictive in only 3 of the 9 categories.ConclusionTogether with its low within-individual variance, these findings suggest that assessing INSL3 in men could offer important insight into the later development of disease in the elderly.</p