Interplay Between Psychological Stress, Testosterone Suppression, and Gonadotropin Alterations in Male Infertility

Abstract

Background: The extreme form of male infertility is idiopathic non-obstructive azoospermia (iNOA), the disease, which is identified by the inhibition of spermatogenesis and has no known etiology. Colonial evidence is emerging that psycho-stress can be related to reproductive activity by neuroendocrine process; although there is scarce information on the relationship between psycho-stress and hormonal, infertility risk, especially in developing states like Pakistan.

Objective: To test the connection among psychological stress, hormonal parameters as well as lifestyle factors in patients with non-obstructed azoospermia of idiopathic etiology against fertile controls.

Methods: The study was a case-control study carried in the Iqra Medical complex and Farooq Hospital of Punjab, Pakistan, between the period of January and December 2025. There were 57 participants composed of 35 patients with non-obstructive idiopathic azoospermia and 22 fertile controls. Demographic information, lifestyle and clinical parameters were documented. Hormonal tests were done on follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone, prolactin and estradiol. The level of psychological stress was measured, the Perceived Stress Scale (PSS), and anxiety and depression measures were used. Statistical processing was done by the use of the SPSS version 25. The independent t-tests and chi-square tests were performed to compare groups, whereas the analysis through logistic regression was performed to determine the factors that predicted infertility. The receiver operating characteristic (ROC) analysis was conducted in order to assess diagnostic capabilities of stress scores.

Results: The patients with iNOA showed much higher perceptions of stress, anxiety, and depression ratings than the controls (p < 0.01). The patients had significantly lower levels of testosterone and higher levels of FSH. The significant predictors of infertility were perceived stress (OR = 1.22, p < 0.001) and elevated FSH (OR = 1.28, p = 0.006) and low testosterone (OR = 0.75, p = 0.002) in the logistic regression analysis, but physical activity had the effect of protection (OR = 0.68, p = 0.005). The analysis of ROC showed that iNOA is well diagnostically predicted by stress (AUC = 0.82). The regression model accounted about 49 percent of variation in the infertility status.

Conclusion: Men develop a lot of psychological stress and hormonal imbalance with idiopathic non-obstructive azoospermia than the fertile controls. A study that further supported the presence of a biopsychosocial model of the aetiology of male reproductive dysfunction was that psychological stress was an independent predictor of infertility. Psychological assessment and lifestyle changes could contribute positively to the management of infertility.