Onset of effects of testosterone treatment and time span until maximum effects are achieved

Objective: Testosterone has a spectrum of effects on the male organism. This review attempts to determine, from published studies, the time-course of the effects induced by testosterone replacement therapy from their first manifestation until maximum effects are attained. Design: Literature data on testosterone replacement. Results: Effects on sexual interest appear after 3 weeks plateauing at 6 weeks, with no further increments expected beyond. Changes in erections/ejaculations may require up to 6 months. Effects on quality of life manifest within 3-4 weeks, but maximum benefits take longer. Effects on depressive mood become detectable after 3-6 weeks with a maximum after 18-30 weeks. Effects on erythropoiesis are evident at 3 months, peaking at 9-12 months. Prostate-specific antigen and volume rise, marginally, plateauing at 12 months; further increase should be related to aging rather than therapy. Effects on lipids appear after 4 weeks, maximal after 6-12 months. Insulin sensitivity may improve within few days, but effects on glycemic control become evident only after 3-12 months. Changes in fat mass, lean body mass, and muscle strength occur within 12-16 weeks, stabilize at 6-12 months, but can marginally continue over years. Effects on inflammation occur within 3-12 weeks. Effects on bone are detectable already after 6 months while continuing at least for 3 years. Conclusion: The time-course of the spectrum of effects of testosterone shows considerable variation, probably related to pharmacodynamics of the testosterone preparation. Genomic and non-genomic effects, androgen receptor polymorphism and intracellular steroid metabolism further contribute to such diversity

Long-term morphological and hormonal follow-up in a single unit on 115 patients with adrenal incidentalomas

We investigated the natural course of adrenal incidentalomas in 115 patients by means of a long-term endocrine and morphological (CT) follow-up protocol (median 4 year, range 1–7 year). At entry, we observed 61 subclinical hormonal alterations in 43 patients (mainly concerning the ACTH–cortisol axis), but confirmatory tests always excluded specific endocrine diseases. In all cases radiologic signs of benignity were present. Mean values of the hormones examined at last follow-up did not differ from those recorded at entry. However in individual patients several variations were observed. In particular, 57 endocrine alterations found in 43 patients (37.2%) were no longer confirmed at follow-up, while 35 new alterations in 31 patients (26.9%) appeared de novo. Only four alterations in three patients (2.6%) persisted. Confirmatory tests were always negative for specific endocrine diseases. No variation in mean mass size was found between values at entry (25.4±0.9 mm) and at follow-up (25.7±0.9 mm), although in 32 patients (27.8%) mass size actually increased, while in 24 patients (20.8%) it decreased. In no case were the variations in mass dimension associated with the appearance of radiological criteria of malignancy. Kaplan–Meier curves indicated that the cumulative risk for mass enlargement (65%) and for developing endocrine abnormalities (57%) over time was progressive up to 80 months and independent of haemodynamic and humoral basal characteristics. In conclusion, mass enlargement and the presence or occurrence over time of subclinical endocrine alterations are frequent and not correlated, can appear at any time, are not associated with any basal predictor and, finally, are not necessarily indicative of malignant transformation or of progression toward overt disease

Expression and function of G-protein-coupled receptorsin the male reproductive tract

This review focuses on the expression and function of muscarinic acetylcholine receptors (mAChRs), α1-adrenoceptors and relaxin receptors in the male reproductive tract. The localization and differential expression of mAChR and α1-adrenoceptor subtypes in specific compartments of the efferent ductules, epididymis, vas deferens, seminal vesicle and prostate of various species indicate a role for these receptors in the modulation of luminal fluid composition and smooth muscle contraction, including effects on male fertility. Furthermore, the activation of mAChRs induces transactivation of the epidermal growth factor receptor (EGFR) and the Sertoli cell proliferation. The relaxin receptors are present in the testis, RXFP1 in elongated spermatids and Sertoli cells from rat, and RXFP2 in Leydig and germ cells from rat and human, suggesting a role for these receptors in the spermatogenic process. The localization of both receptors in the apical portion of epithelial cells and smooth muscle layers of the vas deferens suggests an involvement of these receptors in the contraction and regulation of secretion.Esta revisão enfatiza a expressão e a função dos receptores muscarínicos, adrenoceptores α1 e receptores para relaxina no sistema reprodutor masculino. A expressão dos receptores muscarínicos e adrenoceptores α1 em compartimentos específicos de dúctulos eferentes, epidídimo, ductos deferentes, vesícula seminal e próstata de várias espécies indica o envolvimento destes receptores na modulação da composição do fluido luminal e na contração do músculo liso, incluindo efeitos na fertilidade masculina. Além disso, a ativação dos receptores muscarínicos leva à transativação do receptor para o fator crescimento epidermal e proliferação das células de Sertoli. Os receptores para relaxina estão presentes no testículo, RXFP1 nas espermátides alongadas e células de Sertoli de rato e RXFP2 nas células de Leydig e germinativas de ratos e humano, sugerindo o envolvimento destes receptores no processo espermatogênico. A localização de ambos os receptores na porção apical das células epiteliais e no músculo liso dos ductos deferentes de rato sugere um papel na contração e na regulação da secreção.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de FarmacologiaUNIFESP, EPM, Depto. de FarmacologiaSciEL