From the Guidelines
Very low testosterone in men, known as hypogonadism, is often caused by a combination of factors including obesity, diabetes, and other chronic diseases, as well as testicular damage or dysfunction, and pituitary tumors. According to a recent study published in 2024 1, mean levels of testosterone are lower in men with diabetes compared with age-matched men without diabetes, but obesity is a major confounder. The study highlights the importance of evaluating comorbidities, such as diabetes, in men with low testosterone levels.
Some of the key causes of very low testosterone in men include:
- Testicular damage from injuries, infections like mumps orchitis, chemotherapy, or radiation
- Genetic conditions such as Klinefelter syndrome
- Pituitary tumors or other brain-related issues affecting hormone production
- Medications, especially opioids, glucocorticoids, and some psychiatric drugs
- Chronic diseases, including diabetes, obesity, liver or kidney disease
- Excessive alcohol consumption
- Normal aging
- Environmental factors like exposure to endocrine-disrupting chemicals
Diagnosis of low testosterone typically involves measuring testosterone levels, preferably in the morning when levels are highest, using an accurate and reliable assay 1. Further tests, such as luteinizing hormone and follicle-stimulating hormone levels, may be needed to further evaluate the individual. Treatment depends on the underlying cause and may include testosterone replacement therapy, lifestyle modifications like weight loss and exercise, or addressing specific medical conditions or medication issues. Men experiencing symptoms of low testosterone should consult a healthcare provider for proper evaluation and individualized treatment.
From the FDA Drug Label
Testosterone Cypionate Injection is indicated for replacement therapy in the male in conditions associated with symptoms of deficiency or absence of endogenous testosterone. Primary hypogonadism (congenital or acquired)-testicular failure due to cryptorchidism, bilateral torsion, orchitis, vanishing testis syndrome; or orchidectomy. Hypogonadotropic hypogonadism (congenital or acquired)-idiopathic gonadotropin or LHRH deficiency, or pituitary-hypothalamic injury from tumors, trauma, or radiation. The causes of very low testosterone in men include:
- Primary hypogonadism due to:
- Congenital conditions such as cryptorchidism
- Acquired conditions such as testicular failure from bilateral torsion, orchitis, or vanishing testis syndrome
- Orchidectomy
- Hypogonadotropic hypogonadism due to:
- Congenital conditions such as idiopathic gonadotropin or LHRH deficiency
- Acquired conditions such as pituitary-hypothalamic injury from tumors, trauma, or radiation 2
From the Research
Causes of Very Low Testosterone in Men
- Age: Serum testosterone levels decrease with age 3
- Type 2 diabetes: Men with type 2 diabetes have been shown to have significantly lower testosterone levels than men without diabetes 3, 4
- Obesity: The single most significant risk factor for testosterone deficiency in men is obesity, which can cause a functional hypogonadotrophic hypogonadism 5
- Metabolic syndrome: Low testosterone is associated with metabolic syndrome, which includes insulin resistance, obesity, and cardiovascular disease 3, 6
- Cardiovascular disease: Low testosterone is associated with cardiovascular disease 3, 6
- Osteoporosis: Male hypogonadism is associated with low bone mineral density and increased fragility fracture risk 7
Pathophysiological Mechanisms
- Obesity-induced increase in levels of leptin, insulin, proinflammatory cytokines, and oestrogen can cause a functional hypogonadotrophic hypogonadism 5
- Hypogonadism can worsen obesity, creating a self-perpetuating cycle 5
- Low testosterone can mediate dysglycaemia, predicting future diabetic risks and increased mortality 4
Reversibility and Management
- Obesity-induced hypogonadism is reversible with substantial weight loss 5
- Lifestyle measures, such as weight loss and optimization of comorbidities, can improve androgen deficiency symptoms 5, 4
- Testosterone replacement therapy may be a viable option in some men with diabetes and low testosterone, but clinicians must be aware of contraindications and implement appropriate monitoring procedures 3, 4