Chrono-Nanomedicine at the Barrier: Circadian Rhythms Influence the Delivery of Donepezil Across the BCSFB.

In chronic metabolic diseases such as obesity, dyslipidemia, and type 2 diabetes mellitus (T2DM), subacute chronic inflammation occurs, characterized by cytokine release. These cytokines induce insulin resistance (IR), hypertriglyceridemia, and lower high-density lipoprotein (HDL) cholesterol. Inflammation also alters glucagon-like peptide-1 (GLP-1) fractions (,). Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are now used to manage T2DM and obesity and to improve patient outcomes, with their medium- and long-term effects still under investigation. Metabolic changes associated with diseases such as diabetes and obesity alter hormonal mechanisms, leading to chronic inflammation, oxidative stress, and microvascular dysfunction. These contribute to male fertility disorders like hypogonadism, erectile dysfunction (ED), and altered sperm parameters. The expanded use of GLP-1RAs for weight-loss treatments encourages further exploration into their benefits for treating male infertility in patients with obesity. One recent area of study is their possible benefit in functional hypogonadism, often linked to male infertility, as they have been shown to improve sperm parameters, restore testosterone levels, and enhance microvascular function in ED (,). In this scenario, meta-analyses provide growing evidence that improving metabolism, along with weight loss, could also be effective in reducing the progression of infertility (,). This review aimed to analyze scientific evidence on the mechanisms by which obesity or metabolic issues cause male sexual dysfunction; assess the potential of GLP-1RAs to improve fertility in this context; and examine hormonal changes associated with obesity or diabetes that contribute to hypogonadism, thereby evaluating GLP-1RAs effects in affected men. We present this article in accordance with the Narrative Review reporting checklist (available at ).