Andropause: An Under-Recognized Life Event Putting Men’s Vascular-Metabolic Function at Risk

Background: Andropause, also known as "male menopause," is a progressive decline in testosterone levels that occurs with advancing age in men, accompanied by various health issues. Testosterone levels in men typically begin to drop by an average of 1.6% per year starting around the age of 30. Low testosterone is closely associated with arterial stiffness, an early vascular complication. In contrast to menopause, the effects of andropause on the cardiovascular system remain poorly understood. This prevalent knowledge gap has hindered many men from seeking and receiving appropriate treatment. As modern medicine advances, more men will live longer and experience andropause. We hypothesize that arterial stiffness is an early vascular complication that precedes cardiac alterations during andropause. Methods: By using castration as a model of andropause, middle-aged C57Bl/6 male mice were randomly assigned to either the Sham-operated (SHAM) Group (n=5) or the Castrated, surgical bilateral orchidectomy (Andropausal) Group (n=10). Metabolic cages, glucose tolerance, body weight (BW), transthoracic echocardiograms, and intracarotid pulse wave velocity (icPWV), a gold standard for arterial stiffness, were analyzed along the 28-week protocol. Blinded-nesting experiments were performed to evaluate cognition. The gonadal white adipose tissue (gWAT), soleus muscle, and seminal vesicle were isolated and weighed at the terminal experiment. Results: The Andropausal Group showed atrophy of the seminal vesicle (0.112 ± 0.002g vs. 0.532 ± 0.029g controls, p<0.05) and a drop in the serum testosterone levels (0.10 ± 0.05ng/mL vs. 15.95 ± 7.80ng/mL controls, p<0.05), validifying our murine model of andropause. Andropausal mice exhibited weight loss (28.72 ± 0.27g vs. 30.06 ± 0.45g controls, p<0.05), which was accompanied by significant muscle loss (soleus: 0.0094 ± 0.0008g vs. 0.0129 ± 0.0007g controls, p<0.05) and reduced gWAT (0.643 ± 0.107g vs. 1.36 ± 0.31g, p<0.05). Nesting experiments showed that andropausal mice developed impairment of cognitive-behavioral abilities (score: 2.37 ± 0.33 vs. 3.67 ± 0.37 controls, p<0.05). Strikingly, we found that while andropausal mice developed arterial stiffness as early as 7 weeks post-surgery (icPWV: 3.65 ± 0.50m/s vs. 2.17 ± 0.26m/s controls, p<0.05), no differences in fractional shortening, ejection fraction, cardiac output, and stroke volume were observed. Conclusion: Surgically induced andropause in middle-aged mice demonstrated significant weight loss associated with muscle and gWAT reduction, and impairment in cognitive behavior, mirroring the human experience of andropause. Furthermore, our findings indicate that arterial stiffness is an earlier cardiovascular complication that precedes cardiac changes associated with andropause. NIH-NHLBI This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.