Research links lower testosterone levels to an increased risk of arthritis

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

Study: Lower serum testosterone is associated with an increased risk of arthritis. Image credits: airdone/Shutterstock.com

Background

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

Studies have shown that androgens activate non-genetic and non-genetic mechanisms, with the most rapid evidence being a rapid increase in intercellular calcium concentration.

Physiological testosterone doses have been shown to improve cartilage production in men with advanced osteoarthritis, and treatment with testosterone replacement improves articular cartilage regeneration in affected individuals.

According to research, androgens are also involved in the formation and development of osteoblasts. However, there is minimal evidence for sex-specific relationships between serological testosterone expression and OA, and the association between plasma testosterone in arthritic individuals and disease progression is not clear.

About the study

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

Data from 10,439 adults who participated in the 2013–2016 National Health and Nutrition Examination Survey (NHANES) were analyzed using multivariable logistic regression modeling, performed to determine odds ratios (ORs).

The model estimates are adjusted for covariates such as age, gender, race, education level, marital status, income, alcohol consumption, smoking status, test reports, laboratory findings, survey responses, and comorbidities (such as diabetes, cardiovascular disease, and hypertension). ).

In addition, generalized additivity modeling and smoothed curve fitting were performed. The database samples were selected using stratified multistage sampling.

Data collection methods include home interviews to collect demographic, nutritional and health-related data, and medical examinations to collect laboratory data [including sex hormone binding globulin (SHBG) and estradiol] and physical assessment data [including body mass index (BMI) and waistline].

Individuals were asked whether they had been diagnosed with arthritis by doctors or other medical professionals, and if so, they were asked to report the type of condition as rheumatoid arthritis, osteoarthritis, or other.

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

Results

Initially, 20,146 individuals were identified, of whom 5,380 and 4,327 were excluded due to missing data on serological testosterone levels and development of arthritis, respectively. Of the 10,439 study participants, 48% were male, with an average age of 47 years and an average serum testosterone level of 215. Of the participants, 27% developed arthritis.

Arthritis patients showed lower serum testosterone than their non-arthritic counterparts, in line with previous studies. The findings from linear regression analysis showed a statistically significant negative association between serological testosterone levels and arthritis.

Similarly, the fourth quarter univariable analyzes using the first quarter as reference showed a significantly lower risk of developing arthritis.

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

Individuals in the top quartile of serum testosterone levels showed a 51% lower risk of developing arthritis compared to individuals in the lowest quartile.

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

Testosterone and estradiol are natural immunosuppressants that suppress antibody and cell-mediated immunity while acting as anti-inflammatory agents. Because women have more active immunity than men, they play a crucial role in lowering men’s susceptibility to autoimmune diseases.

The primary androgen, testosterone, binds to specialized intracellular receptors to create active forms of testosterone receptor complexes. Androgen and estrogen receptors are present in both male and female osteoblasts, and testosterone binds to both to regulate bone calcium.

Decreased testosterone levels can affect cartilage metabolism via ion channels and androgen receptors, resulting in cartilage and KOA breakdown. The activation of androgen receptors (AR) and estrogen receptors (ER) has a profound influence on bone metabolism.

Testosterone increases the glycosaminoglycan content in the extracellular matrix of the chondrocytes, improves the coverage of type II collagen on the cartilage surface and influences the development of the fibrocartilage structures.

Low testosterone levels may be the cause of obesity rather than its consequence, with BMI having a causal influence on serum testosterone in the hypothalamic-pituitary-gonadal axis.

Conclusion

Overall, the study results indicated that lower levels of serum testosterone were associated with an increased risk of developing arthritis.

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

The findings could impact the prevention and treatment of arthritis. However, further research is needed to elucidate the mechanisms underlying the impact of serum testosterone on the development of arthritis.