Male Hypogonadism and Osteoporosis: The Effects, Clinical Consequences, and Treatment of Testosterone Deficiency in Bone Health

Abstract

It is well recognized that bone loss accelerates in hypogonadal states, with female menopause being the classic example of sex hormones affecting the regulation of bone metabolism. Underrepresented is our knowledge of the clinical and metabolic consequences of overt male hypogonadism, as well as the more subtle age-related decline in testosterone on bone quality. While menopause and estrogen deficiency are well-known risk factors for osteoporosis in women, the effects of age-related testosterone decline in men on bone health are less well known. Much of our knowledge comes from observational studies and retrospective analysis on small groups of men with variable causes of primary or secondary hypogonadism and mild to overt testosterone deficiencies. This review aims to present the current knowledge of the consequences of adult male hypogonadism on bone metabolism. The direct and indirect effects of testosterone on bone cells will be explored as well as the important differences in male osteoporosis and assessment as compared to that in females. The clinical consequence of both primary and secondary hypogonadism, as well as testosterone decline in older males, on bone density and fracture risk in men will be summarized. Finally, the therapeutic options and their efficacy in male osteoporosis and hypogonadism will be discussed.

The CATCH checklist to investigate adult‐onset hypogonadism

“…Various disorders are commonly associated with hypogonadism, including osteoporosis (Golds et al ., ), type 2 diabetes (T2D), and metabolic syndrome (MetS). To this regard, Association of Clinical Endocrinologists and the American College of Endocrinology recognized that all men who have an increased waist circumference or who have obesity should be assessed for hypogonadism (Garvey et al ., ) and, when diagnosis is confirmed, testosterone replacement therapy (TRT) in addition to lifestyle intervention may be considered.…”

“…However, not all of these defined the age‐group or range of T values required for diagnosis. Furthermore, hypogonadism needs to be checked to prevent its different effects on reproductive and sexual health, on metabolism, and on cardiovascular and bone balance (Corona et al ., ,b; Golds et al ., ; Pastuszak et al ., ). The discrepancies, together with other features linked to clinical evidence of hypogonadism and the importance to prevent worsening of comorbidities, could lead to a definitive checklist that might be useful to fill the gap of being overlooked.…”

Effect of Dose and 5α‐Reductase Inhibition on the Circulating Testosterone Metabolite Profile of Men Administered Oral Testosterone

“…Low concentrations of testosterone can occur for a variety of reasons. Men with low testosterone experience fatigue, depression, diminished libido, loss of muscle strength,2 osteoporosis,3 visceral obesity, and insulin resistance 4. Testosterone replacement therapy (TRT) is the first‐line treatment for testosterone deficiency and has been shown to improve bone density, alleviate depression, and maintain sexual function 5.…”

A Case of Male Osteoporosis: A 37-Year-Old Man with Multiple Vertebral Compression Fractures

“…Hypogonadism is a common cause of osteoporosis in men (rates ranging from 16 to 30% as the attributable cause) [reviewed in [ 5 ]]. It is classified either as hypergonadotropic (primary gonadal failure) or hypogonadotropic (secondary to a defect in the hypothalamic-pituitary axis) hypogonadism [ 6 , 7 ], with the latter being due to congenital (defects in gonadotropin releasing hormone (GnRH) neurons, GnRH regulating neurons, and LH and FSH secreting cells) or acquired etiologies (structural defects or reversible causes).…”