Q: I treat at least 12 young, muscular, active men with low free and total testosterone (100-225 ng/dL) who complain of fatigue. These men work out regularly and deny any supplement use — oral or injectable. They are otherwise healthy. In all cases, follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin, and thyroid-stimulating hormone levels are normal. Why is their testosterone so low?
A: Low testosterone is the hallmark of hypogonadism. Hypogonadism results from dysfunction anywhere along the hypothalamic-pituitary-testis axis and is referred to as primary when the defect is at the level of the testes, secondary when abnormal pituitary function results in inadequate gonadotropic stimulation of the testes, and tertiary if the defect is at the level of the hypothalamus. Through a complex feedback loop, primary hypogonadism should result in elevated levels of LH and FSH. Similarly, tertiary hypogonadism leads to low levels of LH and FSH. If the LH and FSH are truly normal, both primary and tertiary hypogonadism are very unlikely. In contrast, secondary hypogonadism can frequently manifest with low testosterone levels and “inappropriately normal” LH and FSH levels. You have already ruled out hyperprolactinemia and thyroid disease, but if you think the onset was postpubertal (normal testes size), you should consider hemochromatosis, pituitary macroadenomas, and medication effect as well. Despite your patients' insistence that they don't use supplements, I would not rule out the possibility of occult use of anabolic steroids, especially in otherwise healthy, muscular young men. If workup remains unrevealing, I would consider enlisting the help of an endocrinologist.
