Late-onset Hypogonadism In Men Research Articles

Association of salivary testosterone levels during the post-awakening period with age and symptoms suggestive of late-onset hypogonadism in men

Background The lack of association between serum testosterone levels and symptoms suggestive of hypogonadism is a significant barrier in the determination of late-onset hypogonadism (LOH) in men. This study explored whether testosterone levels increase after morning awakening, likewise the cortisol awakening response (CAR) in the hypothalamic–pituitary–adrenal (HPA) axis, and whether testosterone levels during the post-awakening period are associated with age and symptoms suggestive of late-onset hypogonadism (LOH) in men. Methods Testosterone and cortisol levels were determined in saliva samples collected immediately upon awakening and 30 and 60 min after awakening, and scores of the Aging Males’ Symptoms (AMS) questionnaire were obtained from 225 healthy adult men. Results A typical CAR (an increase in cortisol level ≥ 2.5 nmol/L above individual baseline) was observed in 155 participants (the subgroup exhibiting typical CAR). In the subgroup exhibiting CAR, testosterone levels sharply increased during the post-awakening period, showing a significant negative correlation with age, total AMS score, and the scores of 11 items on the somatic, psychological, and sexual AMS subscales. Of these items, three sexual items (AMS items #15–17) were correlated with age. Meanwhile, there was no notable increase in testosterone levels and no significant correlation of testosterone levels with age and AMS score in the subgroup exhibiting no typical CAR (n = 70). Conclusions The results indicate that the hypothalamus-pituitary-gonad (HPG) axis responds to morning awakening, and determining testosterone levels during the post-awakening period in men with typical CAR may be useful for assessing HPG axis function and LOH.

MicroRNA profiling reveals the role of miR-133b-3p in promoting apoptosis and inhibiting cell proliferation and testosterone synthesis in mouse TM3 cells.

Late-onset hypogonadism (LOH) is an age-related clinical and biological syndrome in which serum testosterone deficiency is an important characteristic and diagnostic indicator. In this study, we firstly analyzed the difference in the expression level of three miR-133s (including miR-133a-3p, miR-133a-5p, and miR-133b-3p) in rat testis samples, blood samples from mice before and 1 wk after testis removal, and mouse TM3 cells. Secondly, the mimics and inhibitors corresponding to the three miR-133s of mouse were transfected into TM3 cells separately to determine the correlation between the three miRNAs. Finally, using mouse TM3 cells to analyze the effect of miR-133b overexpression or inhibition on the proliferation and apoptosis of mouse testicular Leydig cells, the effect on genes related to testosterone synthesis, and the effect on the level of testosterone in the culture medium. We found that, compared with the testis tissue of newborn rats, miR-133a-5p was increased in adult rats, and miR-133a-3p and miR-133b-3p were decreased. In addition, 1 wk after the testis was removed, the expression levels of these three miRNAs in the blood of adult mice decreased. The correlation of the three miRNAs was summarized, and it was found that miR-133b-3p played an important role in it. In TM3 cells, overexpression of miR-133b-3p suppressed the proliferation and promotes apoptosis of cells, suppressed the expression level of most genes related to cell proliferation and testosterone synthesis, and the concentration of testosterone in the culture medium decreased while these phenomena can be reversed by the inhibition of miR-133b-3p expression. It was found that miR-133b-3p can regulate testosterone production in TM3 cells at least by targeting FSCN1. The above results suggest that miR-133b-3p plays an important role in regulating testosterone synthesis. These findings also provide new candidate diagnostic indicators for late-onset hypogonadism in men and provide new clues for the further study of pathogenesis.

Поздний гипогонадизм у мужчин, больных сахарным диабетом 2-го типа, и его роль в развитии сердечно-сосудистых заболеваний (обзор литературы)

Тестостерон является гормоном, который играет ключевую роль в углеводном, жировом и белковом метаболизме у мужчин. Снижение уровней тестостерона, связанное с возрастом, которое усиливается развитием и прогрессированием сопутствующей патологии, прежде всего сахарного диабета 2-го типа, ожирения, дислипидемии, может иметь существенное влияние на возникновение сердечно-сосудистых заболеваний у мужчин и повышение риска преждевременной смертности. В работе представлен анализ современных литературных данных о распространенности позднего гипогонадизма и его влиянии на развитие сердечно-сосудистой патологии у мужчин. Проведен анализ исследований, представленных в поисковой базе данных и базе данных MedLine, по ключевым словам «тестостерон», «мужчина», «поздний гипогонадизм» и «сердечно-сосудистые заболевания». Показана контраверсийность ряда гипотез о роли андрогенодефицита в развитии сердечно-сосудистой патологии у мужчин. Однако определено, что в большинстве работ показана связь андрогенодефицита с развитием метаболических нарушений, которые являются факторами развития метаболического синдрома, ожирения, сахарного диабета 2-го типа. В свою очередь, данные сопутствующие заболевания являются прямыми факторами, приводящими к раннему возникновению и прогрессированию сосудистой патологии и связанной с ней смертностью у мужчин старших возрастных групп. Проведение терапии тестостероном необходимо у мужчин с сахарным диабетом 2-го типа и подтвержденным клинически и лабораторно дефицитом тестостерона при условии соблюдения стандартов ее безопасности. Ввиду неоднозначных результатов исследований влияния тестостерона на развитие сердечно-сосудистых заболеваний данный вопрос требует дальнейшего изучения.

Associations between smoking, sex hormone levels and late-onset hypogonadism in men differ depending on age.

Few studies have investigated whether associations between smoking, sex hormone levels, and symptoms of late-onset hypogonadism (LOH) in men are affected by age. This multi-center, cross-sectional study involving 6,296 men aged 40-79 years was conducted between June 1, 2013 and August 31, 2016 in 6 provinces of China. Total testosterone, free testosterone, and Aging Males’ Symptoms scale (AMS) scores were compared depending on smoking status and the number of cigarettes smoked. Total testosterone was higher in smokers than in non-smokers in all except the 70-79 year old subgroup. Free testosterone was higher in smokers than non-smokers for the 40-49 and 50-59 year old subgroups, but not the 60-69 and 70-79 year old subgroups. Total testosterone was positively associated with number of cigarettes consumed in smokers aged 40-49 and 50-59 years. Sexual and somatic AMS scores were higher in current and ex-smokers than in non-smokers in all age subgroups from 40 to 79 years and were negatively associated with cigarette consumption in smokers aged 40-49 years. These results indicate that, as men age, the positive association between smoking and testosterone weakens, while the positive association between smoking and LOH symptoms becomes stronger.

Association of gonadal hormones and sex hormone binding globulin with risk of diabetes: A cohort study in middle-aged and elderly Chinese males.

Late-onset hypogonadism in men is related to the development of diabetes. The association of gonadal hormones, sex hormone binding globulin with diabetes has been studied in various studies. However, there is no cohort study on the relationship between gonadal hormone, sex hormone binding globulin and diabetes in Chinese. We aimed to provide an insight into the possible association in middle-aged and elderly Chinese males. We included a population sample of 673 subjects aged 40years or older. Total testosterone (TT), sex hormone binding globulin (SHBG), follicle-stimulating hormone (FSH) and luteinising hormone (LH) were detected. The homeostasis model assessment of insulin resistance (HOMA-IR) was calculated to estimate insulin sensitivity. Diabetes was diagnosed according to the 2010 American Diabetes Association criteria. With an average follow-up time of 3.2±0.5years, 9.8% of participants had developed diabetes. The prevalence of diabetes was decreased according to increasing SHBG quartiles (Q1:13.1%, Q2: 12.0%, Q3: 11.2%, Q4: 3.0%, P for trend<.0001) and TT (Q1:16.0%, Q2: 7.9%, Q3: 9.0%, Q4: 6.4%, P for trend<.0001). The ORs of diabetes for increasing SHBG quartiles were 4.52 (95% CI 1.40-14.57), 4.32 (95% CI 1.33-14.06), 3.89 (95% CI 1.21-12.50) and 1.00 (reference) respectively. But the odds of prevalent diabetes were not increased in different quartiles of TT, FSH and LH. In subgroup analyses, the relationship between SHBG and risk of incident diabetes was significantly increased in the population aged over 60, without insulin resistance and with eGFR<90mL/min per 1.73m2 . Compared with gonadal hormones, a lower level of SHBG is independently associated with the risk of diabetes in middle-aged and elderly Chinese males.

Detection of Late-Onset Hypogonadism in Men with Chronic Internal Diseases

Abstract Late-onset hypogonadism (LOH) is a clinical and biochemical syndrome associated with age and featured by typical symptoms and reduced blood testosterone level. Among males aged over 30 years, the incidence of androgen deficiency is 7 to 30%. 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 arterial hypertension, Chronic obstructive pulmonary disease (COPD), metabolic syndrome, Type 2 of diabetes mellitus, dyslipidaemia, adiposity in various General practice (GP) and physician-sexologists’ offices in Latvia, and to determine the influence of chronic diseases on the development of hypogonadism. Males aged 39 years who turned to family doctors at nine GP 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 AMS questionnaires, a group of males exhibiting signs of LOH were isolated (in total 1222 persons). In these patients, we determined blood testosterone and sex-hormone binding globulin (SHBG) levels. Chronic diseases were found in these men in data evaluation of patient medical records, and after performing physical and laboratory examinations. Late-onset hypogonadism was laboratory-diagnosed in 79% of patients with signs of late-onset hypogonadism in accordance with the AMS questionnaires and with concomitant diseases and in 4.7% of patients with signs of late-onset hypogonadism in accordance with the AMS questionnaires and without the aforementioned concomitant diseases. Persons with arterial hypertension, dyslipidaemia, adiposity, metabolic syndrome, COPD and Type 2 of diabetes mellitus had higher chance of developing hypogonadism (p &lt; 0.001). Arterial hypertension, dyslipidaemia, adiposity, metabolic syndrome, COPD statistically significantly (p &lt; 0.001) decreased the level of total testosterone by 0.47, 1.18, 0.36, 0.67, and 0.18 ng/ml, respectively, and decreased the level of free testosterone by 2.52, 2.71, 1,69, 6.77, and 4.58 pg/ml, respectively. Type 2 diabetes mellitus had no statistically significant effect on the level of total and free testosterone (p = 0.95, p = 0.10). The most significant decrease in the level of testosterone was observed in cases of dyslipidemia, COPD and metabolic syndrome. General physicians should pay special attention to patients with this disease, as these patients belong to a group with a high risk of development of expressed LOH syndrome.

A novel function of geranylgeraniol in regulating testosterone production.

Isoprenoids play widely differing roles in various physiological processes in animals and plants. Geranylgeraniol (GGOH) is an isoprenoid found in plants, and is an important metabolic derivative in the isoprenoid/cholesterol synthesis pathway. Earlier studies focused on GGOH's ability to improve the side effects of bisphosphonate therapy by regulating the mevalonate pathway. More recently, the mevalonate pathway-independent effects of GGOH have been described, including anti-inflammatory, anti-tumorigenic, and neuroprotective activities. It is noteworthy that GGOH regulates the steroidogenesis pathway in testis-derived I-10 tumor cells. Testosterone is a hormone produced via steroidogenesis in testicles and plays a role in fetal development and the male reproductive system. GGOH enhanced testosterone and progesterone (its precursor) levels in I-10 cells by activating adenylate cyclase via cAMP/PKA signaling, without altering phosphodiesterase activity. These findings highlight the potential benefits of GGOH as a therapeutic agent for low testosterone levels, such as late-onset hypogonadism in men.

Prevalence of Late-Onset Hypogonadism in Men with Localized and Metastatic Renal Cell Carcinoma

Background: Cancer-related fatigue is a common symptom in patients with renal cell carcinoma (RCC) and can be similar to the fatigue found in late-onset hypogonadism (LOH). The aim of this study was to investigate the prevalence of LOH in patients with localized RCC (loRCC) and metastatic RCC (mRCC) disease under targeted therapy (TT) and compare the results to findings of epidemiologic studies. Methods: A total of 51 mRCC patients under TT and 33 patients with loRCC undergoing nephrectomy were included. Total testosterone (tT) levels and clinical signs of LOH were recorded (testicular volume, body-mass index (BMI), hip-to-waist ratio, International Index of Erectile Function, IIEF-5, Androgen Deficiency in the Aging Male, ADAM, and quality of life questionnaire-C30). LOH was defined according to current guidelines. Results: Morning tT and calculated free testosterone levels showed no significant difference in patients with mRCC and loRCC (p = 0.551 and p = 0.430). A significant difference was found for clinical signs and symptoms including the ADAM score (p = 0.003), hip-to-waist ratio (p = 0.017) and testicular volume (p < 0.001). IIEF-5 score and BMI were not significantly different. The prevalence of LOH according to the current EAU definition was 13.7 and 15.2% for the mRCC and loRCC cohort, respectively (p = 0.302). Conclusions: LOH was present in a significant proportion of RCC patients. Prevalence rates of LOH were higher in patients with RCC compared to patients without cancer.

Late‐onset hypogonadism in men with systolic heart failure: prevalence, clinical associates, and impact on long‐term survival

Male ageing is characterized by diminished circulating androgens with several adverse psychosomatic consequences and can be aggravated by concomitant chronic diseases. According to the European Male Aging Study (EMAS) Group, late-onset hypogonadism (LOH) refers to testosterone deficiency accompanied by sexual complaints. We investigated the prevalence of LOH in men with systolic heart failure (HF), and its clinical determinants and prognostic consequences. Among 201 men with systolic HF (age: 60 ± 11 years), serum total testosterone (TT) was assessed using an immunoassay, and estimated free testosterone (eFT) was calculated using Vermeulen's formula. LOH was diagnosed when TT &#60; 3.2 ng/mL and eFT &#60; 64 pg/mL were accompanied by three sexual symptoms (decrease in the number of morning erections, reduced potency, and low libido) of at least moderate severity assessed using the Aging Males' Symptoms Scale. Decreased frequency of morning erections, reduced potency, and low libido were experienced by 56%, 62%, and 55% of men with HF, respectively; whereas 67%, 61%, and 44% of subjects complained of at least one, two, and three symptoms, respectively. Hypogonadal TT and eFT were observed in 34% and 47% of patients, respectively; and in 33% subjects, both TT and eFT were reduced. Finally, 30 men with HF (15%) were diagnosed with LOH as compared with 2% in a European male population (EMAS). In a multivariable model, older age and higher serum uric acid were independently associated with greater LOH prevalence (both P &#60; 0.05). Among men aged ≤60 years (but not in those aged >60 years), LOH increased 5-year all-cause mortality in the univariable model; however, when adjusted for HF severity, the association lost its statistical significance. Men with systolic HF commonly report sexual complaints. LOH-the combination of sexual dysfunction and testosterone deficiency-occurs more frequently than in a general male population. LOH does not affect long-term mortality, when adjusted for HF severity.

Late-onset hypogonadism in men with systolic heart failure: prevalence, clinical associates, and impact on long-term survival

Late-onset hypogonadism in men with systolic heart failure: prevalence, clinical associates, and impact on long-term survival

How to recognize late-onset hypogonadism in men with sexual dysfunction.

Late-onset hypogonadism (LOH) has been considered the most common form of male hypogonadism with a prevalence of approximately 1 in 100 men. Diagnosis of LOH should be made in symptomatic men with unequivocally low serum testosterone (T) levels. However, its clinical presentation is often insidious and difficult to recognize because it is characterized by nonspecific symptoms that make differential diagnosis with physiological ageing problematic. Sexual dysfunction is the most important determinant for medical consultation and the most specific symptom associated with low T. We therefore analysed a consecutive series of 1734 subjects who attended our unit for sexual dysfunction to investigate the associations between low T (different thresholds), sexual parameters, medical history data (delayed puberty, pituitary disease or cryptorchidism) and their physical exam results. Metabolic parameters, in particular waist circumference, display the greatest accuracy in detecting low T. We found that only the association of several symptoms and signs could significantly raise the clinical suspicion of low T. Structured inventories, which cluster together symptoms and signs of hypogonadism, can help clinicians suspect androgen deficiency. In particular, structured interviews, such as ANDROTEST, have been demonstrated to have a greater accuracy when compared to self reported questionnaires in detecting low T levels.

Prevalence of late-onset hypogonadism in men with type 2 diabetes mellitus

Late-onset hypogonadism (LOH) or age-associated testosterone deficiency syndrome is defined as a clinical and biochemical syndrome associated with advancing age and characterised by symptoms and a deficiency in serum testosterone levels. This condition may result in significant detriment in the quality of life and adversely affect the function of multiple organ systems. It has been suggested that sex steroid hormones may play a causal role in the development of insulin resistance and type II diabetes. This comparative study was aimed at determining the prevalence of LOH in diabetic men with erectile dysfunction and investigating the effect of testosterone replacement therapy on erectile function and on glycaemic control.

Identification of Late-Onset Hypogonadism in Middle-Aged and Elderly Men

The association between aging-related testosterone deficiency and late-onset hypogonadism in men remains a controversial concept. We sought evidence-based criteria for identifying late-onset hypogonadism in the general population on the basis of an association between symptoms and a low testosterone level. We surveyed a random population sample of 3369 men between the ages of 40 and 79 years at eight European centers. Using questionnaires, we collected data with regard to the subjects' general, sexual, physical, and psychological health. Levels of total testosterone were measured in morning blood samples by mass spectrometry, and free testosterone levels were calculated with the use of Vermeulen's formula. Data were randomly split into separate training and validation sets for confirmatory analyses. In the training set, symptoms of poor morning erection, low sexual desire, erectile dysfunction, inability to perform vigorous activity, depression, and fatigue were significantly related to the testosterone level. Increased probabilities of the three sexual symptoms and limited physical vigor were discernible with decreased testosterone levels (ranges, 8.0 to 13.0 nmol per liter [2.3 to 3.7 ng per milliliter] for total testosterone and 160 to 280 pmol per liter [46 to 81 pg per milliliter] for free testosterone). However, only the three sexual symptoms had a syndromic association with decreased testosterone levels. An inverse relationship between an increasing number of sexual symptoms and a decreasing testosterone level was observed. These relationships were independently confirmed in the validation set, in which the strengths of the association between symptoms and low testosterone levels determined the minimum criteria necessary to identify late-onset hypogonadism. Late-onset hypogonadism can be defined by the presence of at least three sexual symptoms associated with a total testosterone level of less than 11 nmol per liter (3.2 ng per milliliter) and a free testosterone level of less than 220 pmol per liter (64 pg per milliliter).

Risk of late-onset hypogonadism (andropause) in Brazilian men over 50 years of age with osteoporosis: usefulness of screening questionnaires

To analyze the relative risk of late-onset hypogonadism in men with osteoporosis and the usefulness of screening questionnaires. We correlated the Aging Male's Symptoms (AMS), Androgen Deficiency in Aging Male (ADAM) and International Index of Erectile Function (IIEF-5) questionnaires and the laboratory diagnosis of hypogonadism in 216 men aged 50-84 years (110 with osteoporosis and 106 with normal bone density, paired by age and ethnicity). Hypogonadism presented in 25% of the osteoporotic and in 12.2 % of normal bone density men (OR 2.08; IC95%: 1.14-3.79) and was associated with ADAM first question (low libido, p=0.013). Levels of TT below 400 ng/dl correlated with an AMS score above 26 (p=0.0278). IIEF-5 showed no correlation with testosterone levels. Hypogonadism was 2.08 times more prevalent in osteoporotic men. The symptom that best correlated with late-onset hypogonadism was low libido (ADAM 1 positive).

Late-onset hypogonadism in men. Experience from the Turku Male Ageing Study (TuMAS)

Interest has arisen during the last 10 years as to the possible connection between the age-related decline in androgen production and symptoms of ageing in men. A new ageing-related syndrome with several descriptive names, such as andropause, male menopause, Partial Androgen Deficiency of the Ageing Male (PADAM) and Late-Onset Hypogonadism (LOH), has been identified. Intensive research into the subject is currently ongoing in multiple, population-based epidemiological studies to explore the connections between testicular endocrine function and the physical, psychic and sexual symptoms of ageing. One of these studies is the Turku Male Ageing Study (TuMAS), conducted in Turku, Finland. This review summarises the recent key findings in this study, with special reference to the correlation of androgen levels with sexual symptoms and cardiovascular risk factors.