Male hypogonadism – Classical vs. non-classical


A debated issue is whether the specific cause of hypogonadism is of importance when deciding whether to treat a man with low testosterone. According to the FDA and Endocrine Society guidelines, only classical hypogonadism should be treated with testosterone therapy. This is a major point of contention.

Classical hypogonadism (also referred to as “organic” hypogonadism) is caused by a congenital, structural, or destructive disorder that results in permanent hypothalamic, pituitary, or testicular dysfunction (primary or secondary hypogonadism). Classical causes of hypogonadism include Klinefelter syndrome (KS), cryptorchidism, some types of cancer chemotherapy, radiation to the testes, trauma, torsion, infectious orchitis, HIV infection, anorchia syndrome, and myotonic dystrophy. The prevalence of classical causes of hypogonadism is very low, around 6% of men with low testosterone.

In contrast, non-classical hypogonadism (also referred to as “functional hypogonadism”) is caused by conditions that suppress gonadotropin and testosterone levels but that are potentially reversible with treatment of the underlying etiology. Non-classical causes of hypogonadism include obesity, type 2 diabetes, metabolic syndrome, opioids, renal failure, COPD, HIV/AIDS. With the epidemic of obesity, type 2 diabetes, metabolic syndrome it is not surprising that the vast majority of men with low testosterone – 94% - have functional hypogonadism.

Considering the wide-ranging benefits of testosterone therapy in men with low testosterone, hypogonadism should be treated regardless of the underlying cause.



Prof. Dr. med. Marija Pfeifer

Paresh Dandona, M.D., PhD
SUNY Distinguished Professor of Medicine
Head, Division of Endocrinology Diabetes and Metabolism
State University of New York at Buffalo


  • Groti K, Zuran I, Antonic B, Forsnaric L, Pfeifer M. The impact of testosterone replacement therapy on glycemic control, vascular function, and components of the metabolic syndrome in obese hypogonadal men with type 2 diabetes. The aging male : the official journal of the International Society for the Study of the Aging Male. 2018;21(3):158-169. Return to content