Endogenous Sex Steroid Hormones, Lipid Subfractions, and Ectopic Adiposity in Asian Indians

Kim, Catherine; Kong, Shengchun; Krauss, Ronald M.; Stanczyk, Frank Z.; Reddy, Srinivasa T.; Needham, Belinda L.; Kanaya, Alka M.

doi:10.1089/met.2015.0063

Cited by 5 publications

(4 citation statements)

References 31 publications

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“…For example, the increase in fat levels in the hips and breasts of women is related to estrogen levels. [51] Our mediation MR analysis indeed confirms that the use of HMGCR inhibitor, as lipid-lowering drugs, can lower testosterone levels in men by affecting fat distribution in certain parts of the body (such as arms and feet), and obesity factors also play an important role in this.…”

Section: Discussionsupporting

confidence: 68%

Association between genetically proxied HMGCR inhibition and male reproductive health: A Mendelian randomization study

Yan,

Xu,

et al. 2023

Medicine

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Background: The causal associations between statin use and male sex hormone levels and related disorders have not been fully understood. In this study, we employed Mendelian randomization for the first time to investigate these associations. Methods: In two-sample Mendelian randomization framework, genetic proxies for hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) inhibition were identified as variants in the HMGCR gene that were associated with both levels of gene expression and low density lipoprotein cholesterol (LDL-C). We assessed the causal relationship between HMGCR inhibitor and 5 sex hormone levels/2 male-related diseases. Additionally, we investigated the association between 4 circulating lipid traits and outcomes. The “inverse variance weighting” method was used as the primary approach, and we assessed for potential heterogeneity and pleiotropy. In a secondary analysis, we revalidated the impact of HMGCR on 7 major outcomes using the summary-data-based Mendelian randomization method. Results: Our study found a significant causal association between genetic proxies for HMGCR inhibitor and decreased levels of total testosterone (TT) (LDL-C per standard deviation = 38.7mg/dL, effect = −0.20, 95% confidence interval [CI] = −0.25 to −0.15) and bioavailable testosterone (BT) (effect = −0.15, 95% CI = −0.21 to −0.10). Obesity-related factors were found to mediate this association. Furthermore, the inhibitor were found to mediate a reduced risk of prostate cancer (odds ratio = 0.81, 95%CI = 0.7–0.93) by lowering bioavailable testosterone levels, without increasing the risk of erectile dysfunction (P = .17). On the other hand, there was a causal association between increased levels of LDL-C, total cholesterol, triglycerides (TG) and decreased levels of TT, sex hormone-binding globulin, and estradiol. Conclusions: The use of HMGCR inhibitor will reduce testosterone levels and the risk of prostate cancer without the side effect of erectile dysfunction. LDL-C, total cholesterol, and TG levels were protective factors for TT, sex hormone-binding globulin, and estradiol.

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Section: Discussionsupporting

confidence: 68%

Association between genetically proxied HMGCR inhibition and male reproductive health: A Mendelian randomization study

Yan,

Xu,

et al. 2023

Medicine

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“…SHBG is inversely related to IR via insulin-reducing hepatic SHBG production in in vitro studies (Plymate et al 1988), and associations of cardiovascular risk factors with SHBG may be reflective of SHBG as a potential surrogate marker of insulin resistance. However, lower SHBG was previously associated with a more atherogenic lipid profile consisting of smaller LDL, lower medium LDL and higher triglycerides, VLDL and IDL assessed using ion mobility spectrometry in n = 42 South Asian Indian women (Kim et al 2015) with these findings persisting after adjustment for visceral adiposity and surrogate markers of IR. In keeping with this, in the general population, SHBG is associated with DM2 independent of surrogate measures of IR (Haffner et al 1993, Kalyani et al 2009, and SHBG, but not testosterone, is associated with the prevalence or incidence of subclinical atherosclerosis (Calderon-Margalit et al 2010) in women independent of factors including age, BMI, insulin or clinical lipid measurements.…”

Section: Discussionmentioning

confidence: 92%

The association of the lipidomic profile with features of polycystic ovary syndrome

Moran

Mundra

Teede

et al. 2017

Journal of Molecular Endocrinology

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Polycystic ovary syndrome (PCOS) affects up to 18% of reproductive-aged women with reproductive and metabolic complications. While lipidomics can identify associations between lipid species and metabolic diseases, no research has examined the association of lipid species with the pathophysiological features of PCOS. The aim of this study was to examine the lipidomic profile in women with and without PCOS. This study was a cross-sectional study in 156 age-matched pre-menopausal women (18-45 years, BMI >20 kg/m; = 92 with PCOS, = 64 without PCOS). Outcomes included the association between the plasma lipidomic profile (325 lipid species (24 classes) using liquid chromatography mass spectrometry) and PCOS, adiposity, homeostasis assessment of insulin resistance (HOMA), sex hormone-binding globulin (SHBG) and free androgen index (FAI). There were no associations of the lipidomic profile with PCOS or testosterone. HOMA was positively associated with 2 classes (dihydroceramide and triacylglycerol), SHBG was inversely associated with 2 classes (diacylglycerol and triacylglycerol), FAI was positively associated with 8 classes (ceramide, phosphatidylcholine, lysophosphatidylcholine, phosphatidylethanolamine, lysophosphatidylethanolamine, phosphatidylinositol, diacylglycerol and triacylglycerol) and waist circumference was associated with 8 classes (4 positively (dihydroceramide, phosphatidylglycerol, diacylglycerol and triacylglycerol) and 4 inversely (trihexosylceramide, G ganglioside, alkenylphosphatidylcholine and alkylphosphatidylethanolamine)). The lipidomic profile was primarily related to central adiposity and FAI in women with or without PCOS. This supports prior findings that adiposity is a key driver of dyslipidaemia in PCOS and highlights the need for weight management through lifestyle interventions.

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“…Xu et al reported that serum E2 and sex hormone binding globulin (SHBG) could influence HbA1c levels in non-diabetic populations [ 50 ]. Kim et al showed that E2, testosterone, and SHBG levels are associated with lipid subfractions in adults [ 51 ]. Similar studies have been conducted in children.…”

Section: Discussionmentioning

confidence: 99%

The Relationship between Fat Mass Percentage and Glucose Metabolism in Children and Adolescents: A Systematic Review and Meta-Analysis

et al. 2022

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To assess the relationship between fat mass percentage (FMP) and glucose metabolism in children aged 0–18 years we performed a systematic review of the literature on Medline/PubMed, SinoMed, Embase and Cochrane Library using the PRISMA 2020 guidelines up to 12 October 2021 for observational studies that assessed the relationship of FMP and glucose metabolism. Twenty studies with 18,576 individuals were included in the meta-analysis. The results showed that FMP was significantly associated with fasting plasma glucose (FPG) (r = 0.08, 95% confidence interval (CI): 0.04–0.13, p < 0.001), fasting plasma insulin (INS) (r = 0.48, 95% CI: 0.37–0.57, p < 0.001), and homeostasis model assessment (HOMA)- insulin resistance (IR) (r = 0.44, 95% CI: 0.33–0.53, p < 0.001). The subgroup analysis according to country or overweight and obesity indicated that these associations remained significant between FMP and INS or HOMA-IR. Our results demonstrated that there is a positive relationship between FMP and FPG. Moreover, subgroup analysis according to country or overweight and obesity indicated that FMP is significantly associated with INS and HOMA-IR. This is the first known systematic review and meta-analysis to determine the associations of FMP with glucose metabolism in children and adolescents.

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Endogenous Sex Steroid Hormones, Lipid Subfractions, and Ectopic Adiposity in Asian Indians

Cited by 5 publications

References 31 publications

Association between genetically proxied HMGCR inhibition and male reproductive health: A Mendelian randomization study

Association between genetically proxied HMGCR inhibition and male reproductive health: A Mendelian randomization study

The association of the lipidomic profile with features of polycystic ovary syndrome

The Relationship between Fat Mass Percentage and Glucose Metabolism in Children and Adolescents: A Systematic Review and Meta-Analysis

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