Sleep-induced hypogonadism: A unifying hypothesis linking BPH, OSA, and low testosterone

The age-related decline in testosterone, often termed ’andropause,’ is traditionally viewed as an inevitable consequence of aging. However, emerging evidence suggests this decline is more closely associated with accumulating comorbidities than with age itself. We propose a unifying hypothesis of ’sleep disruption-induced hypogonadism,’ an acquired and potentially reversible condition driven by common age-related pathologies such as benign prostatic hyperplasia (BPH), obstructive sleep apnea (OSA), and chronic pain. These conditions precipitate a vicious cycle where symptoms like nocturia cause chronic sleep fragmentation and circadian dysregulation. This, in turn, suppresses the hypothalamic-pituitary–gonadal (HPG) axis, leading to reduced endogenous testosterone. This hypothesis is supported by extensive correlational data linking sleep disorders to low testosterone and, more compellingly, by interventional studies demonstrating that treatment of underlying sleep disruptors—such as BPH surgery or nocturia medication—can significantly restore testosterone levels. This framework also resolves the paradox of why CPAP therapy often fails to raise testosterone by highlighting the powerful confounding role of obesity. The primary implication of this hypothesis is a proposed paradigm shift in clinical practice: from a focus on hormone replacement to a ’sleep-centric,’ cause-oriented approach. We advocate that the diagnostic workup for low testosterone in aging men should include a primary assessment for and treatment of underlying sleep disorders before considering testosterone replacement therapy, fostering a more integrated, multidisciplinary management strategy.