The relationship between depression and benign prostatic hyperplasia in middle-aged and elderly men in India: a large-scale population study

Benign prostatic hyperplasia (BPH), characterized by urinary retention and incontinence, is the most prevalent urologic condition in elderly men. The occurrence of BPH often manifests once male individuals reach the age of 40 and exhibits an upward trend as time progresses. Specifically, it impacts around 25% of males in their 50 s, 33% of males in their 60 s, and 50% of males in their 80 s [1, 2]. Bladder Outlet Obstruction occurs when the prostate physically compresses the urethra as a consequence of an increase in stromal cells and prostate epithelial cells, which also led to lower urinary tract symptoms (LUTS) including obstructive voiding symptoms and irritable voiding symptoms [3].

Depression is a significant global health concern, posing a substantial danger to the overall welfare of about 350 million individuals globally, with a special emphasis on elderly people [4]. Based on pertinent academic investigations, it has been observed that depression has a negative impact on cognitive functioning and overall quality of life. Additionally, individuals affected by depression have an elevated possibility of developing chronic comorbidities, including cardiovascular disease and diabetes [5, 6]. Therefore, it is crucial to investigate the prospective geriatric diseases associated with depression.

Various risk factors, including metabolic syndrome, overweight, sex hormone levels, and inflammation, have been recognized as contributors to the higher prevalence of BPH [3]. In addition, depression may have an impact on the body's hormone metabolism and systemic inflammation [7‐9]. Previous research has shown a notable association between the level of severe depressive symptoms and a decline in overall testosterone levels within the male bloodstream [10]. And depression may activate fundamental inflammatory signaling networks that might lead to the proliferation of prostatic cells, subsequently causing hyperplasia of the prostate. The potential influence of depression on prostate health may be attributed to changes in circadian rhythm control, fluctuations in sex hormone levels, and modifications in nervous system feedback mechanisms. Both of these illnesses are frequently observed in elderly males, but their association remains obscure. The negative effects of BPH may contribute to depression, and vice versa, depression may trigger the development of BPH in the mechanism mentioned previously [11]. Limited research has provided a few possibilities. Xiong found that depression may be associated with LUTS suggestive of BPH in a study involving 5125 participants [11]. Despite this, insufficient evidence exists to elucidate the association between BPH and depression. Therefore, the objective of this investigation was to investigate any potential associations between depression and the occurrence of BPH. As one of the illnesses impacting the quality of life of middle-aged and older men, the widespread incidence of BPH exacerbates their suffering as well as the economic and medical burden on our society [12]. Our results might help to create new approaches to avoiding BPH and improving the quality of life for elderly people.

Currently, the worldwide trend toward aging is intensifying, with a growing percentage of the population being elderly [11]. As a large population with a severe aging problem, India is seeing a significant increase in its population, with a notable rise in the proportion of those aged 60 and over projected to occur between 2001 and 2031. This demographic shift is expected to result in an almost twofold increase, reaching around 20 percent by the middle of the century [16]. Common co-occurrence of depression and BPH in the elderly population necessitates additional research to confirm the validity of their association. The LASI, India's first research on aging conducted in 2017–2018 to investigate the physiological, economic, social, and psychological aspects of India's aging process, allowed us to explore the connection between these factors.

Numerous studies have examined the detrimental impact of BPH on quality of life, mainly about general health status and mental health [17, 18]. These studies consistently showed a significant amount of psychiatric morbidity among BPH patients. However, there are few studies on the reverse relationship between depression and BPH, which merits investigation. Several prior studies have established a correlation between depression and BPH symptoms [11, 17, 19], but their findings are difficult to generalize due to many drawbacks. Johnson et al. [19] found that male individuals with depression had American Urological Association Symptom Index scores that were 156% higher than patients without depression. However, they only took into account socioeconomic confounding variables such as education level and income, ignoring other clinical factors that cause LUTS. In addition, due to the statistical design, the cohort size of this study was limited, which might lead to a certain deviation in the conclusion. A prospective cohort investigation conducted by Xiong et al. [11] demonstrated that depressed participants in 2011 displayed higher risks of suffering LUTS/BPH in 2013 than the nondepressed group in a 1351 matched follow-up study. However, they also only adjusted for limited socioeconomic confounding factors such as age and education level, not considering patients’ physical status and history of chronic diseases. Patients with moderate to severe depression (compared to those reporting little depression) had a greater risk of experiencing lower urinary tract symptoms, according to a short-term prospective research done by Chung et al. on 2,890 Chinese males older than 65 years old [17]. However, this study only included elderly men aged ≥ 65 years, and the relationship between depression and prostatic hyperplasia in middle-aged men has not been explored.

Using LASI data, we analyzed the association between depression and BPH in middle- and elderly-aged adults. This research is the broadest population-based investigation on the link between depression and BPH in older individuals in low- and middle-income countries (LAMICs) in recent years. Furthermore, we took into account age, caste, residence, marital status, level of education, tobacco consumption, alcohol consumption, physical activity, body mass index, and a number of other chronic diseases as confounders in our analysis of the association between depression and BPH. Middle-aged and older people with more serious depressive symptoms were more likely to have BPH. After controlling for these possible confounding variables, there was still an association between depression and BPH, which may be connected to age and other diseases.

Although this study confirmed a link between depression and BPH, the mechanism behind this relationship is still unclear. This association may be a result of hormone metabolism and systemic inflammation. According to Gold's research [9], patients with depression have a dysregulated CRH/HPA axis, and hypersecretion of CRH can cause sustained hypercortisolism and excessive activation of the sympathetic nervous system, both of which exacerbate lower urinary tract symptoms due to BPH by affecting urethral smooth muscle via sympathetic innervation [20]. Systemic inflammation is another crucial potential mechanism. Previous research has demonstrated that major depressive disorder patients are in a proinflammatory state, with elevated levels of innate immune plasma mediators such as IL-6, TNF-a, and C-reactive protein [8, 9, 21]. These substances of general inflammation can end up with the proliferation of epithelial and stromal prostatic cells, followed by BPH [22]. Consequently, systemic inflammation, which mediates the association between depression and BPH, might contribute to an increase in BPH prevalence rate.

Although this research was conducted on a nationwide investigation, it did have a few limitations. Firstly, the majority of BPH diagnoses were based on self-report instead off more objective examinations such as prostatic ultrasonography, which might impact the diagnosis. As this was a cross-sectional study, it is plausible that the causal association between BPH and depression was not precisely determined; however, forthcoming prospective and intervention research could give a more comprehensive explanation. Lastly, certain covariables may be susceptible to recollection bias.

Our research found that BPH was significantly linked to the presence of depressive symptoms among middle-aged and elderly Indian men. Given the tremendous pace of population aging, it is essential that male individuals who are experiencing symptoms of depression prioritize their prostate health now in order to ensure their life quality. Furthermore, our research also demonstrated that middle-aged and older men with depressive symptoms had an increased likelihood of developing BPH. In addition, further prospective studies are necessary to elucidate this correlation and explore potential mechanisms.