Diagnosis and treatment of hypogonadism in men

Androgen deficiency is diagnosed by ascertainment of characteristic signs and symptoms and consistently low testosterone levels, measured preferably in the morning using a reliable assay. The clinical presentation of androgen deficiency varies with the age of its onset, genetic factors, prior treatment, and other host factors. Androgen deficiency can be treated using any one of the approved testosterone formulations after consideration of pharmacokinetics, patient preference, cost, and potential formulation-specific adverse effects. Prostate and breast cancer, erythrocytosis, untreated severe obstructive sleep apnea, congestive heart failure, recent myocardial infarction, and severe lower urinary tract symptoms are contraindications for testosterone therapy. Testosterone therapy should be accompanied by a standardized monitoring plan that includes periodic ascertainment of symptomatic improvement and lower urinary tract symptoms, measurements of testosterone level, hematocrit, and PSA, digital prostate examination, and general health evaluation. While the benefit to risk ratio is generally favorable in healthy young men with classical hypogonadism due to diseases of the testes, pituitary and the hypothalamus, neither the clinical benefits of testosterone therapy on patient-important outcomes nor its long-term risks in older men with age-related decline in testosterone level are known.     

迟发性睾丸功能减退症的睾酮补充治疗

原发性或继发性性腺功能减退的中青年男性往往需要终生睾酮补充治疗（TST）。诊断明确的迟发性睾丸功能减退症（LOH）的中老年男性,也应尝试TST。TST可使情绪紊乱,性功能障碍,肌量、骨量及体能下降等症状好转。可能与TST有关的不良反应包括前列腺疾病风险、红细胞增多症、阻塞性睡眠呼吸暂停综合征、体液潴留等,TST长期治疗的安全性及疗效仍需进一步研究观察。     

Hypogonadism and male obesity: Focus on unresolved questions

Obesity, increasing in prevalence globally, is the clinical condition most strongly associated with lowered testosterone concentrations in men and presents as one of the strongest predictors of receiving testosterone treatment. While low circulating total testosterone concentrations in modest obesity primarily reflect reduced concentrations of sex hormone binding globulin, more marked obesity can lead to genuine hypothalamic‐pituitary‐testicular axis (HPT) suppression. HPT axis suppression is likely mediated via pro‐inflammatory cytokine and dysregulated leptin signalling and aggravated by associated comorbidities. Whether oestradiol‐mediated negative hypothalamic‐pituitary feedback plays a pathogenic role requires further study. Although the obesity‐hypogonadism relationship is bidirectional, the effects of obesity on testosterone concentrations are more substantial than the effects of testosterone on adiposity. In markedly obese men submitted to bariatric surgery, substantial weight loss is very effective in reactivating the HPT axis. In contrast, lifestyle measures are less effective in reducing weight and generally only associated with modest increases in circulating testosterone. In randomized controlled clinical trials (RCTs), testosterone treatment does not reduce body weight, but modestly reduces fat mass and increases muscle mass. Short‐term studies have shown that testosterone treatment in carefully selected obese men may have modest benefits on symptoms of androgen deficiency and body composition even additive to diet alone. However, longer term, larger RCTs designed for patient‐important outcomes and potential risks are required. Until such trials are available, testosterone treatment cannot be routinely recommended for men with obesity‐associated nonclassical hypogonadism. Lifestyle measures or where indicated bariatric surgery to achieve weight loss, and optimization of comorbidities remain first line.     

Dynamic endocrine responses to stress: evidence for energetic constraints and status dependence in breeding male green turtles

During reproduction, male vertebrates may exhibit a continuum of interactions between sex and adrenal steroids during stressful events, the outcome of which may be important in either reducing or promoting male reproductive success. We studied adult male green turtles (Chelonia mydas) to examine if they altered plasma corticosterone (CORT) and androgen levels in response to a standardized capture/restraint stressor as potential mechanisms to maintain reproductive activity during stressful events. At the population level, we found that migrant breeding males had a significantly smaller CORT response to the capture/restraint stressor compared to nonbreeding males and that this decreased response coincided with the generally poorer body condition of migrant breeders. In contrast, plasma androgen levels decreased significantly in response to the capture/restraint stressor in migrant breeding males, but not in nonbreeding and pre-migrant breeding males. For individual migrant breeding males, the magnitude of their CORT and androgen responses to the capture/restraint stressor was highly correlated with their body condition and body length, respectively. Our results demonstrate that male green turtles exhibit complex interactions in their endocrine responses to a capture/restraint stressor and that variation in these interactions is associated with differences in males' reproductive, energetic, and physical state. We hypothesize that interplay between physical status and plasma hormone responses to stressors could have important consequences for male green turtle reproduction.     

Central body fat changes in men affected by post-surgical hypogonadotropic hypogonadism undergoing testosterone replacement therapy are modulated by androgen receptor CAG polymorphism

Background and aimsLittle is known about the effect of androgen receptor (AR) gene CAG repeat polymorphism in conditioning body composition changes after testosterone replacement therapy (TRT). In this study, we aimed to clarify this aspect by focussing our attention on male post-surgical hypogonadotropic hypogonadism, a condition often associated with partial or total hypopituitarism.Methods and resultsFourteen men affected by post-surgical hypogonadotropic hypogonadism and undergoing several replacement hormone therapies were evaluated before and after TRT. Dual-energy X-ray absorptiometry (DEXA)-derived body composition measurements, pituitary-dependent hormones and AR gene CAG repeat polymorphism were considered. While testosterone and insulin-like growth factor-1 (IGF-1) levels increased after TRT, cortisol concentration decreased. No anthropometric or body composition parameters varied significantly, except for abdominal fat decrease. The number of CAG triplets was positively and significantly correlated with this abdominal fat decrease, while the opposite occurred between the latter and Δ-testosterone. No correlation of IGF-1 or cortisol variation (Δ-) with Δ-abdominal fat was found. At multiple linear regression, after correction for Δ-testosterone, the positive association between CAG triplet number and abdominal fat change was confirmed.ConclusionsIn male post-surgical hypogonadotropic hypogonadism, shorter length of AR CAG repeat tract is independently associated with a more marked decrease of abdominal fat after TRT.     

Empagliflozin in South Asians with type 2 diabetes: Real world data on effects on cardiometabolic parameters,safety and determinants of response to therapy from a diabetes practice in Sri Lanka

AimsSGLT2 inhibitors provide cardiovascular and renal protection in people with type 2 diabetes (T2DM). Real-world data on their effect on improving glucose and cardiovascular risk factors, and adverse effects in South Asians are limited.MethodsWe retrospectively analyzed clinical, demographic, anthropometric and biochemical data among adults with T2DM, commenced on empagliflozin and followed up for at least one month in a diabetes clinic in Colombo.ResultsAmong 1523 participants (men 49.6 %, age 54.9 (± 10.8) years, diabetes duration 11.5 (± 7.6) years, body mass index 28.2 (± 4.5 kg/m²), over a median follow up of 12 months (range: 1–24 months), reduction in HbA1c, weight, systolic blood pressure (SBP) and urine albumin-creatinine ratio were evident within the first month. Benefits sustained up to two-years (mean changes from baseline: HbA1c ? 0.31 (± 1.49), weight ? 1.14 (± 4.17), SBP ? 3.44 (± 21.75), UACR ? 19.84 (± 108.22) follow up. eGFR declined by the third month, returned to baseline by 12th and remained stable over 24 months. Higher baseline HbA1c, weight and SBP predicted greater decline in HbA1c, weight and SBP respectively. Weight reduction independently predicted the SBP reduction. Eighteen participants per 100 patient-years discontinued therapy due to adverse effects: genital mycotic infections and features of hypovolaemia were the commonest. We observed only two events of diabetic ketoacidosis.ConclusionsEmpagliflozin effectively improves glucose, weight and SBP and retards progression of renal impairment in South Asians with T2D. Genital mycotic infections and hypovolaemia were the commonest reasons for discontinuation. Careful patient selection and advice can avoid other sinister complications.     

Need for improvements in clinical practice to retain patients in pre-antiretroviral therapy care: Data from rural clinics in North West Province,South Africa

We examined current challenges with patient engagement in HIV prevention and care in South Africa by assessing the procedures of eight public health clinics in the North West Province. Procedures consisted of (1) an inventory/audit of the HIV Counseling and Testing, pre-antiretroviral therapy (pre-ART), and antiretroviral therapy (ART) patient registers; (2) extraction of data from a convenience sample of 39 HIV-positive patient files; and (3) 13 key informant interviews with clinic staff to characterize retention and re-engagement practices for patients. Incomplete registers revealed little evidence of follow-up services, particularly for pre-ART patients. The more detailed examination of patient files indicated substantial disparities in the proportion of pre-ART versus ART patients retained in care. Key informant interviews contextualized the data, with providers describing multiple procedures for tracking and ensuring service delivery for ART patients and fewer procedures to retain pre-ART patients. These findings suggest that enhanced strategies are needed for ensuring continued engagement in HIV care, with a particular emphasis on improving the retention of pre-ART patients. The preventive benefits of ART scale-up may not be achieved if improvements are not made in the proportion of earlier-stage HIV-positive patients who are successfully engaged in care.     

A comprehensive framework for navigating patient care in systemic sclerosis: A global response to the need for improving the practice of diagnostic and preventive strategies in SSc

Systemic sclerosis (SSc), the most lethal of rheumatologic conditions, is the cause of death in >50% of SSc cases, led by pulmonary fibrosis followed by pulmonary hypertension and then scleroderma renal crisis (SRC). Multiple other preventable and treatable SSc-related vascular, cardiac, gastrointestinal, nutritional and musculoskeletal complications can lead to disability and death.Vascular injury with subsequent inflammation transforming to irreversible fibrosis and permanent damage characterizes SSc. Organ involvement is often present early in the disease course of SSc, but requires careful history-taking and vigilance in screening to detect. Inflammation is potentially reversible provided that treatment intensity quells inflammation and other immune mechanisms. In any SSc phenotype, opportunities for early treatment are prone to be under-utilized, especially in slowly progressive phenotypes that, in contrast to severe progressive ILD, indolently accrue irreversible organ damage resulting in later-stage life-limiting complications such as pulmonary hypertension, cardiac involvement, and malnutrition.A single SSc patient visit often requires much more physician and staff time, organization, vigilance, and direct management for multiple organ systems compared to other rheumatic or pulmonary diseases. Efficiency and efficacy of comprehensive SSc care enlists trending of symptoms and bio-data. Financial sustainability of SSc care benefits from understanding insurance reimbursement and health system allocation policies for complex patients. Sharing care between recognised SSc centers and local cardiology/pulmonary/rheumatology/gastroenterology colleagues may prevent complications and poor outcomes, while providing support to local specialists.As scleroderma specialists, we offer a practical framework with tools to facilitate an optimal, comprehensive and sustainable approach to SSc care. Improved health outcomes in SSc relies upon recogntion, management and, to the extent possible, prevention of SSc and treatment-related complications.