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SEX STEROIDS
Dehydroepiandosterone (DHEA)
Dehydroepiandosterone (DHEA)
is a precursor for androgen and estrogen formation in peripheral tissue. The
levels of DHEA and its sulfated prohormone dehydroepiandosterone (DHEA-S) decreases
with age.10
Investigators
have correlated these low levels with bone loss, particularly in the very old.
A very small study investigated the effects of 10% DHEA vaginal cream. Over
a 12 month period bone density was increased and bone turnover decreased without
apparent endometrial stimulation.10
These changes in BMD also showed a significant decrease in plasma alkaline phosphatase
and urinary hydroxyproline/creatinine ratio. Moreover, serum osteocalcin, a
marker for bone formation, increased two-fold over baseline values. Data from
these small studies are promising, but long-term studies are needed to investigate
the possible role of DHEA in osteoporosis prevention in men and women.
Testosterone
Hypogonadism is a risk factor for osteoporosis in men. The prevalence of hypogonadism is increased fivefold in elderly men with hip fractures. There is increasing evidence which suggests that androgen replacement therapy could prevent bone loss in elderly hypogonadal men.10, 11
Testosterone replacement therapy for 6 to 8 months increased spinal BMD in all patients in one study. Another study reported an increase in spine and trabecular BMD in hypogonadal men treated with testosterone.Bone-specific alkaline phosphatase and urinary hydroxyproline levels were reduced in this study. It has also been shown that testosterone reduces the risk of glucocorticoid-induced osteoporosis in men of all ages on long term prednisone treatment. Transdermally administered testosterone also seems to increase BMD in elderly hypogonadal men.
The major side effect of the hormone is increase in hematocrit levels. Other side effects include increase in prostate-specific antigen, gynecomastia and water retention. Long-term placebo-controlled trials are needed to examine the effects of testosterone treatment on the incidence of hip fracture and to better define the risk-benefit ratio of treatment in older men before this treatment can be recommended widely.
Tibolone
Tibolone is a synthetic steroid having weak estrogenic, androgenic, and progestogenic activity.12 It behaves as a tissue-specific receptor and intracrine mediator (TRIM). Because of its estrogenic properties, it relieves menopausal symptoms and decreases bone resorption. It has a reduced effect on endometrial proliferation due to its progestogenic and androgenic properties. A prospective, placebo-controlled trial demonstrated that Tibolone was effective in preventing bone loss 10 although there were incidences of vaginal bleeding (18%) and breast tenderness (15%) with Tibolone therapy.The effect of Tibolone on fractures is yet to be determined.
Tibolone is currently approved for use in several European countries and is presently undergoing review by the FDA in the United States.
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