The type of trabecular bone remodeling that occurs with aging also differs between the sexes, as males tend to have trabecular thinning and females tend to lose trabecular connectivity . Although the prevalence of osteoporosis amongst males ≥ 50 is significantly lower than the female population, male osteoporosis and osteopenia and its clinical consequences are significant. Regarding male osteoporosis specifically, some organizations, including those in Canada, the USA, and Europe, have adopted the use of gender-specific reference populations 7, 8. They defined osteoporosis as the category in which individuals have a BMD standard deviation (SD) measurement, referred to as the T-score, of 2.5 or less below the norm established from their young adult female Caucasian reference population. Osteoporosis, as described by the World Health Organization (WHO) since 1994, is a condition characterized by low bone mass and microarchitectural bone deterioration that leads to bone fragility and fracture susceptibility . As such, this review will focus on answering key questions regarding male hypogonadism as well as highlighting areas requiring further research and exploration.
Membership in BHOF will help build your practice, keep your team informed, provide CME credits, and allow you access to key osteoporosis experts. Join our community to learn more about osteoporosis, or connect with others near you who are suffering from the disease. While taking steroids, it is especially important to get enough calcium and vitamin D. Talk with your healthcare provider about taking the lowest dose for the shortest period of time for your condition.
Taking steroid medicines as pills in a dose of 5 mg or more for three or more months can increase the chance of bone loss and developing osteoporosis. If you need to take a medicine that causes bone loss, work with your healthcare provider to determine the lowest possible dose you can take to control your symptoms. If you have any of the following diseases or conditions, talk to your doctor or health care provider about what you can do to keep your bones healthy.
We identified a single report using osteoclast-specific androgen receptor knockout mice, which reported no effect on bone mass in either male or female mice; however, full gene knockdown could not be confirmed, leaving these results in question . This suggests that testosterone signaling through the androgen receptor in osteoblasts is important in trabecular but not cortical bone formation. In osteoblasts, the loss of the androgen receptor resulted in decreases in trabecular bone mass, fewer trabeculae, and an increase in trabecular separation with no effect on cortical bone 54–56. Despite their limitations, mouse cell lines have provided insights into the role of testosterone in bone cells by generating cell line-specific knockouts of aromatase and the androgen receptor often by using Cre-Lox recombination technology. Finally, global knockouts in mice of androgen or estrogen receptors lead to impairment of important negative regulation mechanisms outside of the bone itself which can lead to further derangement of hormone levels 52, 53. The levels of free estrogen in mice are also significantly lower when compared to humans which may suggest that localized metabolism of sex hormones in mice contribute more significantly to bone physiology in murine models as compared to humans.
One could speculate that LH or FSH may have protective effects on bone which would be lost in secondary hypogonadism, yet studies have found that FSH stimulates osteoclast activity , and in both women and men, higher FSH levels are correlated with decreased BMD 107–110. Therefore, while useful in suggesting a role of testosterone in BMD and fracture risk, these large observational trials do not directly address the possible role of hypogonadism itself in BMD and fracture risk. In terms of fracture risk, neither testosterone nor estrogen levels were predictive of risk, though patients with both low testosterone and low estrogen were at the greatest risk of fracture overall suggesting a combined role of both hormones . This also suggests an important role of testosterone in contributing to bone strength and fracture risk as trabecular bone is an important determinant to both . Models of primary hypogonadism utilizing orchiectomy also result in the loss of other gonadal-specific hormones such as inhibin A which may also contribute to bone health . Analysis of men discovered to have incidental radiographic fragility fractures has found a convincing link to these individuals having lower bone mass and decreased bone cortical thickness; these correlate with fracture risk independent of BMD .
For simplicity, it has been advocated by the WHO and others to use the traditional standard female-only reference population. Ideally, in order to capture and acknowledge the differences in the peak BMD reference that occurs between males and females, the male peak BMD reference should be higher than that of females. This updated reference standard has been accepted by a number of international organizations and authorities 3–6, yet many recognize that this Caucasian and female-only reference population is less than ideal for different ethnicities and male gender. After a fracture, 60% of surviving men have a higher chance of suffering a second fracture. It is estimated that 2 million men in the United States currently have osteoporosis.
It seems reasonable to anticipate that low bioavailable levels of testosterone in aging men, similar to the decreased estrogen levels in menopause, would correlate to a loss in bone mineral density (BMD) and an increase in fracture risk. 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. 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.
Checking testosterone levels is as easy as having a blood test. Because prostate cancer is so common, doctors tend to be leery of prescribing testosterone to men who may be at higher than average risk of having undiagnosed prostate cancer. Some men and women experience immediate side effects of testosterone treatment, such as acne, disturbed breathing while sleeping, breast swelling or tenderness, or swelling in the ankles. However, the wisdom and effectiveness of testosterone treatment to improve sexual function or cognitive function among postmenopausal women is unclear.
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.

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