High C-reactive protein is associated with increased risk of biochemical hypogonadism: a population-based cohort study

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Abstract

Context

Obesity seems to decrease levels of testosterone. It is still unknown what role inflammation plays in the secretion of testosterone in men.

Objective

The objective is to study the association between levels of C-reactive protein and testosterone and its role in predicting biochemical hypogonadism in men.

Design

This was a longitudinal observational study between 2002 and 2014 in Sweden.

Patients or other participants

At the first visit, a random population sample of 1400 men was included, and 645 men fulfilled a similar protocol at a 10-year follow-up visit. After exclusion, 625 men remained to be included in the final analyses.

Main outcome measure(s)

Serum concentrations of testosterone and C-reactive protein (CRP) were measured at both visits. Bioavailable testosterone was calculated. Biochemical hypogonadism was defined as total testosterone levels <8 nmol/L.

Results

At the first visit and in the longitudinal analyses, a strong association was found between high levels of CRP and low levels of calculated bioavailable testosterone even after adjustments for age, waist–hip ratio, hypertension, smoking, type 2 diabetes, and leisuretime physical activity (B = −0.31, 95% CI −0.49 to −0.13, P = 0.001, B = −0.26, 95% CI −0.41 to −0.11, P = 0.001). Similarly, increase with one s. d. in CRP was associated with increased risk of having hypogonadism after adjustment in the final model (odds ratio (OR) 1.76, 95% CI 1.12–2.78, P = 0.015, OR 1.80, 95% CI 1.16–2.78, P =0.008).

Conclusions

In this representative cohort of men in southwestern Sweden, high levels of CRP were longitudinally associated with low concentrations of calculated bioavailable testosterone and increased risk of biochemical hypogonadism.

Related collections

Most cited references 39

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2019 ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD

Francesco Cosentino, Peter Grant, Victor Aboyans … (2019)

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Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation.

K.G.M.M. Alberti, P.Z. Zimmet (1998)

The classification of diabetes mellitus and the tests used for its diagnosis were brought into order by the National Diabetes Data Group of the USA and the second World Health Organization Expert Committee on Diabetes Mellitus in 1979 and 1980. Apart from minor modifications by WHO in 1985, little has been changed since that time. There is however considerable new knowledge regarding the aetiology of different forms of diabetes as well as more information on the predictive value of different blood glucose values for the complications of diabetes. A WHO Consultation has therefore taken place in parallel with a report by an American Diabetes Association Expert Committee to re-examine diagnostic criteria and classification. The present document includes the conclusions of the former and is intended for wide distribution and discussion before final proposals are submitted to WHO for approval. The main changes proposed are as follows. The diagnostic fasting plasma (blood) glucose value has been lowered to > or =7.0 mmol l(-1) (6.1 mmol l(-1)). Impaired Glucose Tolerance (IGT) is changed to allow for the new fasting level. A new category of Impaired Fasting Glycaemia (IFG) is proposed to encompass values which are above normal but below the diagnostic cut-off for diabetes (plasma > or =6.1 to or =5.6 to <6.1 mmol l(-1)). Gestational Diabetes Mellitus (GDM) now includes gestational impaired glucose tolerance as well as the previous GDM. The classification defines both process and stage of the disease. The processes include Type 1, autoimmune and non-autoimmune, with beta-cell destruction; Type 2 with varying degrees of insulin resistance and insulin hyposecretion; Gestational Diabetes Mellitus; and Other Types where the cause is known (e.g. MODY, endocrinopathies). It is anticipated that this group will expand as causes of Type 2 become known. Stages range from normoglycaemia to insulin required for survival. It is hoped that the new classification will allow better classification of individuals and lead to fewer therapeutic misjudgements.

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C-reactive protein concentration and risk of coronary heart disease, stroke, and mortality: an individual participant meta-analysis

George Smith (2010)

Summary Background Associations of C-reactive protein (CRP) concentration with risk of major diseases can best be assessed by long-term prospective follow-up of large numbers of people. We assessed the associations of CRP concentration with risk of vascular and non-vascular outcomes under different circumstances. Methods We meta-analysed individual records of 160 309 people without a history of vascular disease (ie, 1·31 million person-years at risk, 27 769 fatal or non-fatal disease outcomes) from 54 long-term prospective studies. Within-study regression analyses were adjusted for within-person variation in risk factor levels. Results Loge CRP concentration was linearly associated with several conventional risk factors and inflammatory markers, and nearly log-linearly with the risk of ischaemic vascular disease and non-vascular mortality. Risk ratios (RRs) for coronary heart disease per 1-SD higher loge CRP concentration (three-fold higher) were 1·63 (95% CI 1·51–1·76) when initially adjusted for age and sex only, and 1·37 (1·27–1·48) when adjusted further for conventional risk factors; 1·44 (1·32–1·57) and 1·27 (1·15–1·40) for ischaemic stroke; 1·71 (1·53–1·91) and 1·55 (1·37–1·76) for vascular mortality; and 1·55 (1·41–1·69) and 1·54 (1·40–1·68) for non-vascular mortality. RRs were largely unchanged after exclusion of smokers or initial follow-up. After further adjustment for fibrinogen, the corresponding RRs were 1·23 (1·07–1·42) for coronary heart disease; 1·32 (1·18–1·49) for ischaemic stroke; 1·34 (1·18–1·52) for vascular mortality; and 1·34 (1·20–1·50) for non-vascular mortality. Interpretation CRP concentration has continuous associations with the risk of coronary heart disease, ischaemic stroke, vascular mortality, and death from several cancers and lung disease that are each of broadly similar size. The relevance of CRP to such a range of disorders is unclear. Associations with ischaemic vascular disease depend considerably on conventional risk factors and other markers of inflammation. Funding British Heart Foundation, UK Medical Research Council, BUPA Foundation, and GlaxoSmithKline.

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Author and article information

Journal

Journal ID (nlm-ta): Endocr Connect

Journal ID (iso-abbrev): Endocr Connect

Journal ID (hwp): EC

Title: Endocrine Connections

Publisher: Bioscientifica Ltd (Bristol )

ISSN (Electronic): 2049-3614

Publication date (Electronic): 27 May 2022

Publication date Collection: 01 July 2022

Volume: 11

Issue: 7

Electronic Location Identifier: e220141

Affiliations

[1 ]School of Public Health and Community Medicine , Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

Author notes

Correspondence should be addressed to B Daka: bledar.daka@ 123456gu.se

Author information

Amar Osmancevic http://orcid.org/0000-0002-2774-0194

Bledar Daka http://orcid.org/0000-0002-7722-1528

Article

Publisher ID: EC-22-0141

DOI: 10.1530/EC-22-0141

PMC ID: 9254292

PubMed ID: 35904226

SO-VID: 43741a57-21c7-4c54-b6d5-331dd6b192d9

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High C-reactive protein is associated with increased risk of biochemical hypogonadism: a population-based cohort study

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