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|Year : 2021 | Volume
| Issue : 2 | Page : 63-64
A bidirectional relationship between metabolic syndrome and hypogonadism in men
TR Bandgar, K Thakkar
Department of Endocrinology, Seth GS Medical College and KEM Hospital, Mumbai, Maharashtra, India
|Date of Submission||14-Feb-2021|
|Date of Decision||24-Feb-2021|
|Date of Acceptance||01-Mar-2021|
|Date of Web Publication||30-Apr-2021|
T R Bandgar
Department of Endocrinology, Seth GS Medical College and KEM Hospital, Mumbai, Maharashtra
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Bandgar T R, Thakkar K. A bidirectional relationship between metabolic syndrome and hypogonadism in men. J Postgrad Med 2021;67:63-4
Hypogonadism in males is characterized by impaired hypothalamo-testicular function, resulting in circulating testosterone levels below the normal range. Congenital hypogonadism (CH) is characterized by absent or arrested puberty in addition to sexual dysfunction, impairment of spermatogenesis, reduction in bone, muscle mass, and strength.
In the current issue of this journal, Reddy and Yadav[ 1] have studied metabolic syndrome (MS) and whole body composition (BC) in young adult males with CH and compared them with healthy age-matched controls; while a subset of the patients (n = 33) were prospectively evaluated for the effects of testosterone replacement.
It is important for the readers to understand the pathophysiology of bidirectional relationship of hypogonadism and MS [Figure 1]. Testosterone deficiency leads to upregulation of lipoprotein lipase, which in turn stimulates uptake of free fatty acids and triglycerides in adipocytes. The proliferation of these adipocytes results ultimately in increase in visceral adipose tissue (VAT). Increased VAT triggers several downstream pathways which contribute to impair metabolic profile and increase insulin resistance. Klinefelter syndrome (KS) is associated with an inherently increased risk of MS and type 2 diabetes due to X chromosome overdosage, over and above that due to hypogonadism. On the other hand, the primary MS and obesity associated with increased VAT result in increased secretion of inflammatory cytokines and leptin, which are known to impair pulsatile secretion of gonadotropin hormone-releasing hormone (GnRH) and gonadotropins from hypothalamus and pituitary, respectively, thus producing hypogonadism. Accumulation of VAT is also associated with increased expression of the enzyme aromatase, and hence, higher conversion of testosterone to estradiol. Increased estradiol levels act directly at the level of hypothalamus to suppress hypothatalamo-pituitary-gonadal (HPG) axis, resulting in hypogonadism.
|Figure 1: Bidirectional inter-related pathophysiology of hypogonadism and MS|
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As far as the metabolic advantages of testosterone replacement in CH are concerned, we usually see improvement in BC, in terms of reduction of fat mass and increase in lean body mass which is well described.,, There is still controversy with regards to improvement in body mass index, insulin sensitivity, and lipid parameters. During routine management, clinical improvement in insulin sensitivity and lipid parameters is commonly observed. It is not clear whether improvement in these parameters are directly related to testosterone therapy or indirectly achieved secondary to loss of fat mass and increased muscle mass. There are no clear recommendations as to when and how frequently patients with CH be screened for components of MS. However, we suggest that adults with isolated hypogonadotropic hypogonadism (IHH) be screened for MS as and when clinically indicated (central abdominal obesity, as seen commonly in Asian Indians). The patients with KS should be screened for components of MS every year despite being adequately replaced with testosterone.
In patients with primary MS, we found the prevalence of hypogonadism of 15% and 10% in Asian Indian type 2 diabetes and non-diabetic cohort, respectively, and do not routinely measure testosterone levels unless there are symptoms or signs suggestive of hypogonadism. As per our experience in patients with type 2 diabetes with hypogonadism, testosterone replacement had no significant effect on the metabolic variables. Nevertheless, testosterone replacement in adults with MS is justified only if hypogonadism is well established and contra-indications are ruled out.
What are the clinical implications of this study by Reddy and Yadav? The authors have provided Indian data on CH, incorporating BC measurement, and the impact of testosterone on it. It highlights the fact that adults with CH should be adequately treated to normalize testosterone levels, not only for the restoration of sexual and reproductive functions but also for metabolic advantages. Similar studies using gonadotropin are also warranted considering the emergence of data favoring early gonadotropin therapy in patients with severe IHH. Certain genetic variants of IHH too (LEP/LEPR, FGFR1/FGF8), are known to increasingly predispose to metabolic disturbances. With availability of genetic analysis, especially next-generation sequencing, evaluation of such metabolic and BC parameters in IHH would be more informative, if correlated with individual genetic subgroups. Finally, whether these metabolic effects would actually culminate in cardiovascular event reduction is not clear. Hence, larger trials with defined end-points such as major adverse cardiovascular events (MACE), and impact of testosterone-based treatment on reduction of MACE are needed.
| :: References|| |
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