However, many men with normal testosterone levels have similar symptoms, so a direct connection between testosterone levels and symptoms is not always clear. Women with high testosterone levels, due to either disease or drug use, may experience a decrease in breast size and deepening of the voice, in addition to many of the problems men may have. Part of this may be due to the difficulty defining "normal" testosterone levels and "normal" behavior.
As testosterone levels decline, men may experience decreased muscle function, leading to reduced physical activity. However, a few studies failed to demonstrate its effects, and no evidence supporting the hypothesis that TRT can prevent bone fracture incidence exists. Several recent studies demonstrated the benefit of TRT on BMD, especially in hypogonadal men with osteopenia and osteoporosis. Testosterone plays an important role in maintaining BMD and bone health among men. Three studies targeting hypogonadal men with osteopenia or osteoporosis demonstrated that TRT could significantly increase their BMD 76,78,83. Moreover, testosterone plays some potential roles in maintaining BMD among men, and TRT is expected to be useful for preventing and managing osteoporosis and improving BMD among hypogonadal men.
Although testosterone may make prostate cancer grow, it is not clear that testosterone treatment actually causes cancer. Affected women may experience low libido, reduced bone strength, poor concentration or depression. As surprising as it may be, women can also be bothered by symptoms of testosterone deficiency. One treatment available for many of these problems is spironolactone, a special type of diuretic (water pill) that blocks the action of male sex hormones. Among women, perhaps the most common cause of a high testosterone level is polycystic ovary syndrome (PCOS). Blood levels of testosterone vary dramatically over time and even during the course of a day.
However, epidemiological information on male osteoporosis attributed to hypogonadism, especially in elderly men, has been less available. Furthermore, ADT can increase the risk of proximal femur fractures by 1.5- to 1.8-fold 14,15. The incidence frequency of femoral neck fracture is fourfold more in men than in women with osteoporosis . In particular, osteoporosis often causes compression spine fractures and femoral neck fractures in elderly men, resulting in a decrease of activities of daily living (ADL) and QOL. Many recent studies support the benefit of TRT on BMD, especially in hypogonadal men with osteopenia and osteoporosis, although a few studies failed to demonstrate its effects.
A final study by Rodriguez-Tolra et al. is a two-year prospective treatment study involving testosterone therapy in 50 hypogonadal males aged ≥50. Hoppéa et al. reviewed 14 of these randomized controlled trials (RCT) of testosterone treatment in males, all of which looked at BMD at the lumbar spine and femoral head, without fracture risk outcomes. There have been a number of small, randomized controlled studies evaluating the effect in men of testosterone treatment on the bone, regardless of underlying testosterone levels, which generally demonstrated improvements to BMD. Other studies looking for correlations between the development of male osteoporosis and testosterone levels give conflicting results.
For example, a man with osteoporosis and low testosterone can increase bone strength and reduce his fracture risk with testosterone replacement. Drinking too much alcohol impacts negatively on bone health and can also lead to frequent falls, which increases the risk of fractures. Following an approach similar to that advocated for women with osteoporosis, we recommend the use of oral anti-resorptive agents as first-line agents in men at a high risk of fracture and the use of bone-forming agents followed sequentially by anti-resorptive agents in men at a very high risk of fracture." The Working Group recommendations cover disease burden; approaches to fracture risk assessment in men, including appropriate interpretation of bone densitometry and absolute fracture risk; thresholds for treatment; and interventions that can be used therapeutically together with their health economic evaluation. By addressing testosterone levels and implementing a comprehensive approach, men can enhance their bone health and overall well-being.
Significant BMD increases were detected the earliest (12 months) and over dispersed body sites (lumbar spine, total hip, trochanter, and intertrochanteric) only for the highest testosterone doses. Vertebrae are comprised of approximately 75% trabecular bone, whereas the femoral head is only 50% trabecular bone . This difference between changes in the femoral neck and spine may be explained by the different contribution of cortical and trabecular bone in these two regions. These participants were treated with intramuscular testosterone injections for 5 to 8 years, the longest study to date. Regarding the lumbar spine BMD, only 5 of the 14 showed significant increases, with the remaining showing nonsignificant (6 of 14) or no (3 of 14) differences after therapy.
Currently, there is a limited amount of data on the effects of different types of hypogonadism on BMD and fracture risk. The differences in BMD between primary hypogonadism and secondary hypogonadism suggest that the type of hypogonadism may affect the overall risk of osteoporosis and fragility fracture. These studies demonstrate decreased BMD in hypogonadal males of all ages, particularly in the lumbar spine 91–100. Additionally, the few subjects that would meet the criteria for hypogonadism likely had late onset hypogonadism related to age-related testosterone decline, which is a distinct entity from primary or secondary hypogonadism in younger males 88–90. For example, in the MrOS study, only men in the lowest testosterone quartile examined would possibly have testosterone levels low enough to meet a clinical diagnosis of hypogonadism.
Thus, testosterone replacement therapy (TRT) is expected to be one of the tools for improving these clinical conditions and QOL in men with LOH syndrome. Currently, TRT should be considered as one of the treatment options to improve hypogonadal symptoms and BMD simultaneously in symptomatic hypogonadal men with osteopenia. However, no evidence supporting the hypothesis that TRT can prevent the incidence of bone fracture exists.

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