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Study links lower testosterone levels with increased arthritis risk

In a recent study published in Scientific Reports, researchers determined the connection between serological testosterone levels and arthritis amongst United States (US) adults.

Study: Lower serum testosterone is related to increased likelihood of arthritis. Image Credit: airdone/Shutterstock.com


Arthritis is a joint disease that affects the hyaline articular cartilage, surrounding tissues, and subchondral bone. Hormonal variables, resembling testosterone, have been linked to the expansion and development of knee osteoarthritis (KOA).

Androgens have been proven in studies to activate non-genetic and non-genetic mechanisms, with the fastest evidence being a rapid rise within the intercellular concentration of calcium.

Physiological testosterone dosages have been demonstrated to enhance cartilage production amongst males with advanced-stage osteoarthritis, and testosterone substitute treatment enhances articular cartilage regeneration in affected individuals.

Androgens are also implicated in osteoblast formation and development, in line with research. Nonetheless, there may be minimal evidence of sex-specific relationships between serological testosterone expression and osteoarthritis, and the link between plasma testosterone amongst arthritic individuals and disease progression will not be clear.

In regards to the study

In the current study, researchers investigated the influence of serological testosterone levels on arthritis pathophysiology.

Data from 10,439 adults who participated within the 2013–2016 National Health and Nutrition Examination Survey (NHANES) were analyzed by multivariable logistic regression modeling performed to find out the percentages ratios (ORs).

The model estimations were adjusted for covariates resembling age, gender, race, educational attainment, marital status, income, alcohol intake, smoking status, test reports, laboratory findings, survey responses, and comorbidities (resembling diabetes, cardiovascular diseases, and hypertension).

As well as, generalized additivity modeling and smoothed curve fitting were performed. The database samples were chosen by stratified multiple-stage sampling.

Data collection methods included at-home interviews to gather demographic, dietary, and health-associated data and medical examinations to gather data from laboratory investigations [including sex hormone binding globulin (SHBG) and estradiol] and physical assessment records [including body mass index (BMI) and waistline].

Individuals were queried in the event that they had received an arthritis diagnosis by physicians or other medical professionals, and if yes, were requested to state their condition type as rheumatoid arthritis, osteoarthritis, or other.

The Centers for Disease Control and Prevention (CDC)-designed isotope dilution-liquid chromatography-tandem mass spectrometry (ID-LC-MS) technique was used to determine TT concentrations.


Initially, 20,146 individuals were identified, of whom 5,380 and 4,327 were excluded as a consequence of missing data on serological testosterone levels and arthritis development, respectively. Among the many 10,439 study participants, 48% were male, with a mean age of 47 years and a mean serum testosterone level of 215. Among the many participants, 27% developed arthritis. 

Arthritic individuals showed lower serum testosterone than their non-arthritic counterparts, consistent with previous studies. Linear regression evaluation findings showed a statistically significant negative link between serological testosterone levels and arthritis.

Likewise, the univariable multivariable analyses of Q4, using Q1 for reference, showed a significantly lower risk of arthritis development.

Specifically, sensitivity analyses using quartiles of serum testosterone resulted in odds ratios of 1.0, 0.9, 0.5, and 0.5 for the primary quartile, second quartile, third quartile, and fourth quartile within the fully adjusted model, respectively. 

Individuals within the uppermost quartile of serum testosterone levels showed a 51% lower risk of arthritis development in comparison with individuals belonging to the lowermost quartile.

Smoothed curve fitting showed a non-linear association between arthritis development and serological testosterone levels. The subgroup analyses showed that the negative link between serological testosterone and developing arthritis was more statistically significant amongst older female smokers with comorbidities and body mass index (BMI) values of 30 kg per m2 and better.

Testosterone and estradiol are natural immunosuppressants that suppress antibody- and cell-mediated immunity while acting as anti-inflammatory agents. Because women have more energetic immunity than males, they play a vital role in lowering male susceptibility to autoimmune disorders.

The first androgen, testosterone, binds to specialized intracellular receptors to create energetic types of testosterone receptor complexes. In each female and male osteoblasts, androgen and estrogen receptors are present, and testosterone binds to each to control bone calcium.

Reduced levels of testosterone can influence cartilage metabolism via ion channels and androgen receptors, leading to cartilage degradation and KOA. The activation of androgen receptors (AR) and estrogen receptors (ER) has a profound influence on bone metabolism.

Testosterone increases glycosaminoglycan content within the chondrocyte extracellular matrix, enhances type II collagen covering on the cartilage surface, and influences the spanning development of cartilage fibrous structures.

Low testosterone would be the explanation for obesity reasonably than the final result of it, with BMI having a causal influence on serum testosterone within the hypothalamic-pituitary-gonadal axis.


Overall, the study findings indicated that lower levels of serum testosterone were linked to an increased risk of arthritis development.

The in-depth investigation of the negative and non-linear association between serological testosterone levels and arthritis development was connected with BMI and sex.

The findings might influence arthritis prevention and management. Nonetheless, further research is required to elucidate the mechanisms underlying the impact of serum testosterone on arthritis development.

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