Figure - available from: Reviews in Endocrine and Metabolic Disorders
This content is subject to copyright. Terms and conditions apply.
Example of flow chart for diagnosis of hypogonadism in middle-aged and older men. Hormonal investigations are performed only in men with suggestive clinical syndrome of hypogonadism. Morning testosterone (T) after overnight fast as initial test. Finding of an unequivocally low total T, if confirmed in a separate, second morning sample, supports the diagnosis of hypogonadism. If total T is only borderline low or when the patient presents with factors known to decrease SHBG levels (e.g. obesity, type 2 diabetes), measure both T and SHBG in the repeat sample: diagnosis of hypogonadism is supported only if the calculated free T (cFT) is also low. All other results fail to confirm the diagnosis of hypogonadism as a likely cause of the patient’s symptoms. Amongst the different cut-off levels for T and cFT proposed in published clinical guidelines for diagnosis of hypogonadism in men, the here considered cut-off levels are on the more stringent side as to reflect the need for a conservative approach to the diagnosis of late onset hypogonadism, prioritizing the shunning of overdiagnosis. Measurement of gonadotropins and prolactin, and other additional investigations; are intended to exclude specific causes once the diagnosis of hypogonadism is established. However, some clinicians may choose for practical reasons to measure gonadotropins and prolactin already together with the second T testing
Source publication
To make the diagnosis of hypogonadism in an ageing man, in absence of rare organic cause often referred to as functional or late onset hypogonadism (LOH), he should present with a clinical syndrome suggestive of androgen deficiency and have consistently low serum testosterone (T) levels. This does not differ from the diagnosis of any other form of...
Citations
... Serum total testosterone concentration, complemented by free testosterone concentration if serum values are borderline and/or in a clinical situation in which testosterone binding might be altered (for example, by obesity or glucocorticoid use), can also be measured to identify those men who are hypogonadal and who might therefore benefit from testosterone supplementation 62,63 . ...
... Reductions in sex steroid production and increases in levels of sex hormone binding globulin (SHBG) reduce the availability of free testosterone in men as they age 63,88 .Testosterone is released from the testes in response to luteinizing hormone stimulation and is converted to oestradiol via aromatase (CYP19A1). Oestradiol is thought to mediate the major downstream effects on bone homeostasis as it acts on osteoclasts, osteoblasts and osteocytes via binding to α and β oestrogen receptors. ...
Historically, osteoporosis has been viewed as a disease of women, with research, trials of interventions and guidelines predominantly focused as such. It is apparent, however, that this condition causes a substantial health burden in men also, and that its assessment and management must ultimately be addressed across both sexes. In this article, an international multidisciplinary working group of the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases presents GRADE-assessed recommendations for the diagnosis, monitoring and treatment of osteoporosis in men. The recommendations are based on a comprehensive review of the latest research related to diagnostic and screening approaches for osteoporosis and its associated high fracture risk in men, covering disease burden, appropriate interpretation of bone densitometry (including the use of a female reference database for densitometric diagnosis in men) and absolute fracture risk, thresholds for treatment, and interventions that can be used therapeutically and their health economic evaluation. Future work should specifically address the efficacy of anti-osteoporosis medications, including denosumab and bone-forming therapies.
... Serum concentrations of SHBG are susceptible to changes in the body and are shown to increase with age [5,6] but decrease in obese [5,7] and type 2 diabetic men [8]. However, altered liver function can also result in altered concentrations of SHBG, including increased levels, which may lead to lower cFT if TT does not increase accordingly [9]. Lymphoma patients are often treated with chemotherapy with potential impact on liver function, and some studies [10][11][12][13][14] but not all [15][16][17] have detected a trend toward increased SHBG concentrations among treated patients. ...
In the current study, we report the prevalence of male testosterone deficiency in a cohort of 60 male long-term survivors of malignant lymphoma with normal total testosterone but in the lower part of the reference level. Testosterone deficiency was defined as subnormal concentrations of total testosterone or subnormal concentrations of calculated free testosterone. The aim was to clarify whether total testosterone was sufficient for identification of testosterone deficiency in male survivors of malignant lymphoma. Hormonal analyses taken at follow-up were compared with samples taken at diagnosis for a subgroup of 20 survivors, for evaluation of changes in hormones over time. Another group of 83 similar survivors of malignant lymphoma with testosterone in the high end of reference levels were also used for comparison, to identify groups of increased risk of testosterone deficiency. A total group of 143 survivors were therefore included in the study. Our findings indicate that for screening purposes an initial total testosterone is sufficient in some survivors because sexual hormone binding globulin concentration was found stable over time. However, 15% were found with subnormal calculated free testosterone. Survivors intensely treated for Hodgkin lymphoma and older survivors were identified as high-risk groups for testosterone deficiency necessitating endocrinological attention during follow-up. Some evidence of pituitary downregulation was also found, because of uncompensated decreases in testosterone concentration over time. In conclusion, longitudinal measurements of total testosterone alone do not seem adequate for the screening of testosterone deficiency for all long-term lymphoma survivors.
... More severe and prolonged TD may result in regression of secondary sex characteristics, anemia, muscle wasting, osteoporosis, oligospermia, and abdominal adiposity [40]. Notable sexual symptoms include decreased libido, decreased sexual activity, decreased frequency of morning erections, and erectile dysfunction [41]. Psychological symptoms can include decreased energy, depressed mood, sleep disturbances, and poor concentration and memory [42]. ...
Purpose of Review
The purpose of this review is to analyze the link between testosterone replacement therapy (TRT) and adverse cardiovascular (CV) events.
Recent Findings
A few published studies suggest a link between TRT and CV events. These studies contained flaws, and many other studies reveal a reduction in CV events. Hypogonadism is associated with increased mortality in men with CVD. TRT in hypogonadal men can improve many CVD risk factors, reduce QT interval prolongation, lead to better outcomes in heart failure patients, and slow the progression of atherosclerosis.
Summary
The use of TRT to achieve physiologic testosterone concentrations in men does not pose a threat to CV health and has demonstrated a cardioprotective effect.
... Serum testosterone and its precursors, including pregnenolone, are lower in overweight and obese men compared with men with a normal BMI [78]. The symptoms and signs of low androgen levels include sexual dysfunction, infertility, reduced body hair, fatigue, gynecomastia, and altered body composition (increased body fat and decreased muscle mass) [77,79,80]. Moreover, low testosterone levels independently predict the risk of prostate cancer [81]. ...
Steroid hormone levels are closely related to the endogenous circadian rhythm induced by sleep–wake and dark–light cycles. Shift work that disrupts the circadian rhythm may influence the levels of steroid hormones. The association between shift work and alterations in female sex steroid hormone levels has been studied, but little is known about testosterone and its precursor pregnenolone levels in male shift workers. The present study investigated serum pregnenolone and testosterone levels in a group of shift and daytime male workers. All participants were sampled at the beginning of the morning shift. Lower levels of serum pregnenolone and total testosterone were found in the shift workers compared to the daytime workers. Variations in pregnenolone levels may have consequences for well-being, and they might produce consequences for the levels of hormones downstream of the steroid hormone cascade, such as testosterone. The low levels of testosterone found in shift workers demonstrate the perturbative effect of shift work on testosterone serum levels, which may be independent and/or related to pregnenolone synthesis.
Insulin-like peptide 3 (INSL3) is a circulating biomarker for Leydig cell functional capacity in men, also indicating Leydig Cell Insufficiency (LCI) and potential primary hypogonadism. Using results from large cohort studies we explore sources of biological and technical variance, and establish a reference range for adult men. It is constitutively secreted with little within-individual variation and reflects testicular capacity to produce testosterone. The main INSL3 assays available indicate good concordance with low technical variance; there is no effect of ethnicity. INSL3 declines with age from 35 years at about 15% per decade. Like low calculated free testosterone, and to a lesser extent low total testosterone, reduced INSL3 is significantly associated with increasing age-related morbidity, including lower overall sexual function, reflecting LCI. Consequently, low INSL3 (≤0.4 ng/ml; ca. <2 SD from the population mean) might serve as an additional biochemical marker in the assessment of functional hypogonadism (late-onset hypogonadism, LOH) where testosterone is in the borderline low range. Excluding individuals with low LCI (INSL3 ≤ 0.4 ng/ml) leads to an age-independent (> 35 years) reference range (serum) for INSL3 in the eugonadal population of 0.4 − 2.3 ng/ml, with low INSL3 prospectively identifying individuals at risk of increased future morbidity.
