Beyond Replacement: The Evolving Role of Testosterone

How to cite: Pearlman AM. “Beyond Replacement: The Evolving Role of Testosterone.” Grand Rounds in Urology. October 2025. Accessed Jan 2026. https://grandroundsinurology.com/beyond-replacement-the-evolving-role-of-testosterone/

Summary

Amy M. Pearlman, MD, Co-Founder, Prime Institute, Coral Gables, Florida, discusses the evolving role of testosteroneShe centers the intersection of testosterone therapy and glucagon-like peptide-1 (GLP-1) medications, highlighting clinical considerations increasingly relevant to urology practice beyond traditional replacement, focusing on muscle preservation, metabolic health, and aging in the context of modern weight-loss therapies. She centers the intersection of testosterone therapy and glucagon-like peptide-1 (GLP-1) medications, highlighting clinical considerations increasingly relevant to urology practice.

Dr. Pearlman begins with observations from a multidisciplinary practice treating patients with obesity and metabolic disease. She notes that patients achieving the greatest functional and lifestyle improvements are often those combining weight-loss pharmacotherapy with hormone optimization. The widespread use of GLP-1 agonists is contextualized by concerns regarding loss of lean muscle mass during significant weight reduction.

Dr. Pearlman explains that up to a quarter of weight loss may be attributable to lean mass reduction regardless of the weight-loss method, including diet, surgery, or pharmacologic therapy. She frames muscle as a critical metabolic and endocrine organ, influencing inflammation, glucose metabolism, frailty, and long-term independence. She positions preservation of muscle mass as a central strategy for promoting healthy aging and reducing disability.

Dr. Pearlman reviews the anabolic effects of testosterone, including evidence demonstrating increases in fat-free mass and strength across testosterone formulations. While intramuscular therapy produces the greatest gains, benefits are observed across delivery methods in older men. Dr. Pearlman acknowledges the absence of formal studies evaluating combined GLP-1 therapy and testosterone replacement, using clinical experience to illustrate potential benefits.

A representative patient case demonstrates improvements in body composition, including reduced fat mass, decreased waist circumference, and preservation or gain of skeletal muscle despite substantial weight loss. Dr. Pearlman emphasizes that testosterone alone is insufficient without adequate protein intake and resistance training.

Dr. Pearlman concludes with practical guidance for urologists, encouraging engagement in discussions about nutrition, muscle health, and referral for testosterone management when appropriate, positioning testosterone therapy as part of a broader strategy to support metabolic health and aging.

About The 12th Urology Today Conference:

Presented by chair Ryan P. Terlecki, MD, FACS, the 12th Urology Today conference was designed to keep urologists, urologic oncologists, and other healthcare providers educated on the most pertinent issues in urology practices. Areas of focus included urologic oncology, men’s health and reconstruction, female urology, pediatric urology, kidney stones and related conditions, and methods of providing the best care amidst the required logistics of the business side of medicine.