Peculiarities of the Development and Diagnosis of Late-Onset Hypogonadism in Men in the Case of Chronic Diseases – Arterial Hypertension, Dyslipidaemia, Adiposity, Metabolic Syndrome, Type 2 Diabetes Mellitus, Chronic Obstructive Pulmonary Disease – and Combinations Thereof. Summary of the Doctoral Thesis

Abstract

Late-onset hypogonadism (LOH) is a clinical and biochemical syndrome associated with age, and featured by typical symptoms and reduced blood testosterone level (lower than a reference threshold in young healthy males). Among males aged over 30 years, the incidence of androgen deficiency is 7 to 30 %. With increasing age, the male body undergoes changes leading to reduced concentration of testosterone: a decrease of the number of testosterone-synthesising Leydig cells in the testes, decrease of the density of luteinising hormone receptors, regulatory communication disorders in the hypothalamic-pituitary system, as well as decrease of concentration and reduction of activity of the enzymes responsible for the synthesis of the metabolic pathway of testosterone. With the decrease of testosterone level, chronic diseases develop in the male body. Changes are observed in body constitution: decrease of muscle mass and strength, development of sarcopoenia; increase of body fat, especially around the waist; the development of adiposity, metabolic syndrome, and Type 2 diabetes mellitus are observed. The lipid profile also undergoes changes: LDL and blood triglyceride levels increase, HDL level decreases, leading to the development of CHD and increasing of cardiovascular mortality. The sensitivity to insulin decreases, increasing the risk developming Type 2 diabetes mellitus (T2DM). Bone mineral density decreases, leading to osteoporosis and increased risk of bone fractures. Male sexual function changes as well: libido decreases, erectile dysfunction develops. Cognitive function worsens, dysthymia often develops; haematopoiesis is disturbed. On the other hand, chronic diseases themselves may cause testosterone deficiency, or accelerate its development. For example, in patients with visceral adiposity, adipose cells synthesise biologically active substances that reduce the synthesis of testosterone by taking part in metabolic processes. The frequency of intercourses is decreased in males with reduced libido or erectile dysfunction, which, in turn, facilitates the testosterone deficiency even more. The aim of this study was to investigate the incidence of hypogonadism in patients aged over 40 years with an underlying condition and/or a comorbidity, such as cardiovascular diseases, COPD, metabolic syndrome, T2DM, dyslipidemia, in various GP and physiciansexologists’ offices, as well as to draw up a clinical laboratory criteria regarding the decrease of function of the gonads. In order to meet the objectives, males aged 40 years and over who turned to family doctors at nine GP practices in Latvia due to acute illnesses, exacerbations of chronic diseases, or for preventive examinations, were offered to fill in Aging Male Study (AMS) questionnaires used for the diagnostics of late-onset hypogonadism. Males aged 40 years who visited the office of the physician sexologist Anatolijs Požarskis were offered to fill in the same questionnaires. After compiling the data from the Aging Male Study (AMS) questionnaires, a group of males exhibiting the signs of LOH were isolated. In these patients, we tested blood testosterone and sex-hormone binding globulin (SHBG). By filling in a “Male sexual health questionnaire” developed by us, the symptoms of sexual dysfunctions were analysed in patients who had LOH stated according to laboratory and clinical findings. Chronic diseases were found in these men after the data evaluation in patients’ medical records, and after performing physical and laboratory examinations. Patients having LOH stated according to the AMS questionnaire data, and having the following conditions: arterial hypertension, dyslipidemia, adiposity, metabolic syndrome, Type 2 diabetes mellitus, chronic obstructive pulmonary disease (COPD), and erectile dysfunction were enrolled in the study group. Patients having LOH stated according to the AMS questionnaire data, and not having the mentioned conditions, were enrolled in the control group. Testosterone levels were detected in both the study and the control group, and clinical symptoms of LOH were analysed in both groups for each of comorbidities. The results of our study reveal that in patients with arterial hypertension or dyslipidemia, of Type 2 diabetes mellitus, or adiposity, or metabolic syndrome, or COPD, a faster decrease in serum testosterone level was found as compared to the patients in the control group. Moreover, the most significant decrease was observed in case of dyslipidemia, COPD and metabolic syndrome. The decrease in concentrations of total and free testosterone down to 2.32 ng/ml and 65.4 pg/ml, respectively, or even lower values, is associated with the development of clinical symptoms of androgen deficiency caused by aging, on the background of the underlying pathology. All comorbidities have specificities of LOH clinical picture, however the common feature of all clinical entities are the symptoms of sexual disorders. Based on the results of the study, the criteria of early diagnosis of LOH depending on comorbidity have been developed. These criteria include detecting testosterone level and diagnostics of typical clinical manifestations within the periods that definitely depend on the clinical entity. This will allow to identify this syndrome and to begin treatment in a timely manner. Based on the results of the study, practical recommendations for general physicians have been developed with regard to timely diagnostics of LOH. Patients aged 40 years and over with arterial hypertension, or adiposity, or dyslipidemia, or metabolic syndrome, or Type 2 diabetes mellitus, or COPD should undergo the screening of gonadal function, and they should be purposefully asked about the symptoms of sexual disorders. The treatment and prevention of male adiposity should also be actively addressed. Attaining a normal body weight will help to avoid the development of LOH. GPs shall pay special attention to patients with metabolic syndrome, as well as to patients with COPD, since such patients are in a group of high risks for the development of a pronounced LOH syndrome. The obtained results may be used as the basis for further in-depth research on prevalence, clinical features, and diagnostic options of LOH in wider male population.