ArticleJournal of computer-aided molecular design2026
Impact of physical activity on the hypothalamic-pituitary-gonadal axis in older males: a comparative and AI-based predictive modeling study of demographic factors and stress markers.
Article in Journal of computer-aided molecular design, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Male reproductive problems mark almost 40% of the total infertility issues worldwide. Other than age, BMI, and different kinds of stress, physical inactivity emerges as one of the prominent causes of infertility in males. This cross-sectional study aimed to investigate the impact of physical activity on male hormones regulated by the hypothalamic-pituitary-gonadal (HPG) axis in 200 healthy adult males residing in Hunza, a hilly area of Pakistan. Out of these, 100 were labelled as sedentary and 100 as non-sedentary based on the absence and presence of physical activity (walking or exercise) in their routine. Male hormones, including testosterone, free testosterone (Free T), follicle-stimulating hormone (FSH), Luteinizing hormone (LH), Sex hormone binding globulin (SHBG), Inhibin, dopamine, and stress markers including Malondialdehyde (MDA), Adenosine deaminase (ADA), and Cortisol were measured by ELISA and compared between the two study groups using Mann Whitney U-test. Pearson correlation was calculated between male hormones and age, BMI, MDA, ADA, and Cortisol. Additionally, four machine learning models: linear regression, ridge regression, random forest, and tuned random forest were developed and compared for prediction modelling focusing on biomarkers (male hormones) based on age, BMI, lifestyle, and stress. Male hormones were observed to be significantly elevated in the non-sedentary males compared to the sedentary ones, except for FSH and LH. In addition, Free T exhibited a strong negative correlation with MDA, ADA, and Cortisol. Of the four predictive machine learning models, tuned random forest proved the most effective with the lowest root mean squared error (RMSE) values for Free T and FSH. The current study findings demonstrated that physically active men had increased levels of reproductive hormones, and free T is strongly inhibited by oxidative, immune, and psychological stress.
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