madman
Super Moderator
TESTOSTERONE AND OSTEOPOROSIS (2023)
J.-M. Kaufman
Department of Endocrinology, UZ Gent, Gent, Belgium
Skeletal effects of testosterone are exerted in part via the androgen receptor and for a substantial part via the estrogen receptors following the aromatization of testosterone to estradiol. Androgen receptor-mediated effects of testosterone, and its 5α-reduced active metabolite dihydrotestosterone, can be exerted both directly on the bone cells and indirectly through effects on striated muscles and mechanical loading on the bones. Sex steroids, both testosterone and estradiol, play an important role in bone maturation and acquisition of peak bone mass during growth as well as in the regulation of bone homeostasis and preservation of skeletal integrity in adult life. Hypogonadism is a well-recognized secondary cause of osteoporosis in men. Acquired profound hypogonadism such as in men receiving androgen deprivation therapy for prostate cancer, induces high bone turnover, accelerated bone loss, and increased fracture risk. The much more progressive and only modest age-related decline of serum testosterone and its biologically active serum-free fraction has been found to be associated with some skeletal changes. However, the main effects of sex steroids to help preserve skeletal health in aging men by limiting bone turnover, bone loss, deterioration of trabecular microarchitecture, and cortical porosity appears to be mediated by estradiol acting on the estrogen receptor-α. Low serum estradiol is associated with increased fracture risk with indications for the existence of a critical threshold level. Notwithstanding these found associations, in a large US-based prospective study, the measurement of serum testosterone and estradiol did not contribute significantly to the prediction of fracture risk above the predictive power of bone densitometry by DXA and clinical risk factors. Presently, the role of testosterone measurements in the work-up of osteoporosis in men is limited to the exclusion of hypogonadism. In postmenopausal women aromatization of androgens from the adrenal origin, and in the first years after menopause also originating in part from the ovary, plays an important role as the only source of circulating estrogen. It has indeed been shown that lower postmenopausal estrogen levels adversely affect bone health and high endogenous testosterone levels have also been associated with decreased fracture risk in postmenopausal women. Potential meaningful clinical implementation of testosterone and estradiol measurements in the context of bone health is presently still hampered by analytical issues and by ill-defined reference ranges for postmenopausal women.
J.-M. Kaufman
Department of Endocrinology, UZ Gent, Gent, Belgium
Skeletal effects of testosterone are exerted in part via the androgen receptor and for a substantial part via the estrogen receptors following the aromatization of testosterone to estradiol. Androgen receptor-mediated effects of testosterone, and its 5α-reduced active metabolite dihydrotestosterone, can be exerted both directly on the bone cells and indirectly through effects on striated muscles and mechanical loading on the bones. Sex steroids, both testosterone and estradiol, play an important role in bone maturation and acquisition of peak bone mass during growth as well as in the regulation of bone homeostasis and preservation of skeletal integrity in adult life. Hypogonadism is a well-recognized secondary cause of osteoporosis in men. Acquired profound hypogonadism such as in men receiving androgen deprivation therapy for prostate cancer, induces high bone turnover, accelerated bone loss, and increased fracture risk. The much more progressive and only modest age-related decline of serum testosterone and its biologically active serum-free fraction has been found to be associated with some skeletal changes. However, the main effects of sex steroids to help preserve skeletal health in aging men by limiting bone turnover, bone loss, deterioration of trabecular microarchitecture, and cortical porosity appears to be mediated by estradiol acting on the estrogen receptor-α. Low serum estradiol is associated with increased fracture risk with indications for the existence of a critical threshold level. Notwithstanding these found associations, in a large US-based prospective study, the measurement of serum testosterone and estradiol did not contribute significantly to the prediction of fracture risk above the predictive power of bone densitometry by DXA and clinical risk factors. Presently, the role of testosterone measurements in the work-up of osteoporosis in men is limited to the exclusion of hypogonadism. In postmenopausal women aromatization of androgens from the adrenal origin, and in the first years after menopause also originating in part from the ovary, plays an important role as the only source of circulating estrogen. It has indeed been shown that lower postmenopausal estrogen levels adversely affect bone health and high endogenous testosterone levels have also been associated with decreased fracture risk in postmenopausal women. Potential meaningful clinical implementation of testosterone and estradiol measurements in the context of bone health is presently still hampered by analytical issues and by ill-defined reference ranges for postmenopausal women.
