Hormonal Decline and Osteoporosis in Men and Women - Part 2

Hormonal Therapy Men

Another study evaluated an oral low-dose estrogen therapy on bone mineral density in osteopenic postmenopausal women.  This study investigated 120 postmenopausal hysterectomized women.  The change in BMD differed significantly after 24 months.  Women on estrogen therapy showed significant increase in spine and hip Z-scores whereas the placebo control group showed significant decreases in spine and total hip BMD.  The results indicated the positive effect of an oral low-dose estrogen therapy on bone mineral density.

A further study was to reviewed osteopenia and male hypogonadism from primary testicular failure due to a prior lymphoma in addition to osteopenia.  The patient received supplementary calcium, vitamin D and testosterone.  Improvement in serum testosterone level was noted within six weeks along with increased energy, libido, and erectile function.  A dual-energy x-ray absorptiometry (DEXA) scan showed improvement in bone status also.  Therefore, male hypogonadism was associated with increased risk for osteopenia as well as osteoporosis.  It was noted that supplemental testosterone therapy, because of its direct effect and its aromatization to estrogen, could directly improve bone mineral density in patients suffering from hypogonadism.  One of the primary treatment regimens for hypogonadism is testosterone replacement and this helped increase bone mineral density.

According to the third National Health and Nutrition Examination Survey, between 3% and 6% of U.S. men have osteoporosis in the hip while 28% to 47% have osteopenia.  Prior to the age of 50 years, most fractures are traumatic in origin and are not caused by osteoporosis.  Fractures caused by osteoporotic fragility gradually increase in men from 60 to 80 years of age when testosterone levels are significantly reduced.  Osteoporotic fractures commonly occur about the femoral neck and the vertebra of the spine.  Vertebral fractures in men are found along the entire spine however the majority are in the lower thoracic area.  African-American men have significantly less incidents of hip fractures compared to Caucasian men.

More than 95% of circulating testosterone is bound to albumin and sex hormone-binding globulin (SHBG) leaving only a small amount of biologically active free testosterone to mediate androgen effects.  Although total testosterone does not always decrease in all men, there is commonly an increase in concentration of SHBG, resulting in a decline of free, biologically active testosterone.

Furthermore, testosterone is locally converted to dihydrotestosterone which more aggressively binds to the androgen receptors or aromatized to estradiol.  The incidence of osteoporosis in men is directly correlated to the reduction in circulating testosterone.  Because androgens promote an increase in osteoblasts, while inhibiting osteoclastic activity, decreasing bone density may ensue.  When discussing male osteoporosis secondary to hypogonadism, the direct effect of testosterone is likely 25% of its effectiveness, whereas its aromatization to estrogen contributes to the remaining 75%.

One study in question showed how estrogen may have regulatory effects on bone turnover in functional hypogonadal men and women.  In the study in question, endogenous estrogen and testosterone were suppressed.  Exogenous estrogen and testosterone were then administered.  Markers of bone turnover were then measured to determine which sex hormones were dominant in regulating bone resorption.  In patients with suppressed testosterone and estrogen, but no replacement, there was an increase in urinary excretion of particular markers suggesting increased bone turnover in the absence of sex hormones.

When estrogen alone was suppressed, there was still a high level of bone turnover marker excretion but not as significant as when both androgens were suppressed.  The changes seen when testosterone alone was suppressed and estrogen was not replaced, indicate the crucial role of estrogen on BMD.  Estrogen and testosterone were determined to have an additive effect on maintaining BMD.  Estrogen also not only enhanced bone mass but also retarded bone loss.  Furthermore, testosterone therapy was beneficial because of its action on osteoblast proliferation and osteoclast inhibition plus its aromatization to estrogen, resulted in improved bone density.

Furthermore, long-term treatment with testosterone replacement therapy has been shown to be well tolerated in men with osteoporosis.  In one particular study of testosterone treatment in hypogonadal men, it was found that bone mineral density increased approximately 7.5% in the L2 through L4 vertebra of the lumbar spine and by 5% in the femoral trochanter region.

One further study revealed that using testosterone replacement for 18-30 months resulted in a 3.1% increase in BMD.  Mean estrogen levels were also higher after treatment with testosterone.  Serum markers of bone turnover in turn were all decreased.

One further study reviewed the effects of testosterone therapy on the lumbar spine and hip mineral density in elderly men.  The study took place in Mexico and the aim of the study was to analyze the effect of testosterone therapy on bone mineral density in healthy elderly men who had low levels of total testosterone.

In this case, 48 men over 60 years old with decreased testosterone levels, that is levels less than or equal to 320 ng/dL comprised the study.  25 of the 48 received intramuscular injections of Testosterone Enanthate every three weeks for a period of 12 months straight.  The remaining 23 participants formed a control group.  All participants had measurements of bone mineral density of both the lumbar spine and hip before and at the end of the study as well as testosterone and estradiol levels.

The conclusion was that testosterone therapy elicited a positive effect in lumbar BMD in elderly men who otherwise had diminished testosterone serums levels.

One further study made note of the therapeutic role of androgens in the treatment of osteoporosis in men.  The source of the study was the Harvard Medical School, Massachusetts General Hospital, Boston, USA.  The study recognized the interest in the relationship between androgens and bone mineralization in men.  The study recognized that increases in serum androgens during puberty allow for skeletal maturation and the attainment of peak bone mass, and the persistence of normal testosterone secretion during adulthood was important for the maintenance of bone density.

It was stated that testosterone deficiency was associated with heightened bone turnover and was a major risk factor for osteoporosis in men.  The administration of testosterone in androgen-deficient men led to increases in BMD and a reduction in markers of bone turnover suggesting that the androgens did have a dampening effect on bone remodeling.

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