Estrogens and bone health in men
The roles of estrogen and testosterone. A recent study done at the Mayo Clinic showed that estrogen played a dominant role in regulating the male skeleton. See Calcif Tissue Int 2001 Oct;69(4):189-92, Estrogens and bone health in men. Khosla S and others, PMID: 11730247. Using 59 men with a mean age of 68 who had their endogenous testosterone and estrogen eliminated, the authors sequentially replaced either testosterone, estrogen, or both and assessed the impact on bone. They concluded: "We found that estrogen played the major role in regulating bone resorption in these men, and that both estrogen and testosterone were important in maintaining bone formation. Collectively then, these findings indicate that estrogen plays a dominant role in regulating the male skeleton." (Editor's comment: In men with osteoporosis, the first thought is often whether testosterone replacement is needed, and rarely is estrogen considered. This study showed that estrogen might need to become more of an issue that it has been heretofore.)
The effect of micronized estradiol (E2) in older men receiving hormonal suppression therapy for prostate cancer. This was a complex study involving men who were receiving LH-releasing hormone agonists as a part of prostate cancer therapy. Basically, this shuts down the hypothalamic-pituitary feedback from circulating sex hormones. In the nine-week study, the men were given 1-mg/day of micronized E2 or placebo. At baseline (BL), six weeks, and nine weeks, serum levels of estrone, testosterone, E2, parathyroid hormone, SHBG, and vitamin D were tested as well as markers of bone resorption and bone formation. With E2 treatment, E2 levels rose into the normal male range, and two resorption markers decreased significantly from BL, while bone formation didn't change. The authors conclude: ". . .that E2 inhibits bone resorption in hypogonadal men through a direct skeletal effect that is independent of PTH. Low dose estrogen may be an option for the prevention and/or treatment of bone loss in this population." See J Clin Endocrinol Metab 2002 Nov 1;87(11):4907-4913, The effect of micronized estradiol on bone turnover and calciotropic hormones in older men receiving hormonal suppression therapy for prostate cancer. Taxel P and others. PMID: 12414849.
Estradiol and androgens in men on glucocorticoids. See Metabolism 2002 Nov;51(11):1458-62, Low circulating estradiol and adrenal androgens concentrations in men on glucocorticoids: A potential contributory factor in steroid-induced osteoporosis. Hampson G and others, PMID: 12404198. There were 38 men in group A with idiopathic osteoporosis (IOP) and 39 men with steroid-induced osteoporosis (SIOP) in group B, all of whom had serum E2 and adrenal androgens tested to see the relationship between bone mineral density (BMD) and the circulating hormones. The findings included: With SIOP there was a higher prevalence of low serum testosterone concentrations (<9.0 nmol/L)(P=.0052) which was significantly correlated with steroid dosage (r=-0.42, P=.0089) and E2 concentrations (r=0.42, P=.012). There was a significant positive association between BMD at the lumbar spine and E2 (P=.004) in men with SIOP. A high proportion of subjects in both groups had low E2 (<48 pmol/l), group A had 44.7% and group B had 36%. Serum adrenal androgens concentrations were also significantly suppressed in group B. The authors state, "In conclusion, the data show that adrenal androgens synthesis is markedly suppressed in men with SIOP. The clinical relevance of this finding remains to be determined. This study also shows a positive association between serum estradiol and BMD and high prevalence of low serum estradiol in men with SIOP. Low serum estradiol may contribute to bone loss in men with SIOP." (Editor's comment: Since serum E2 was low in both groups, that appears to be a possible factor in either IOP or SIOP, and the testing of E2 concentrations appears to be warranted, especially for men with IOP. If they are found to be low, E2 therapy may be indicated.)
Using the male rat model to test the effect of E2. See J Bone Miner Res 2002 Nov;17(11):2080-6, Evidence from the aged orchidectomized male rat model that 17 beta-estradiol is a more effective bone-sparing and anabolic agent that 5 alpha-dihydrotestosterone. Vandenput L and Others, PMID 12412816. This study was done to evaluate the effect of E2 versus androgen on orchidectomy (ORX)-induced bone loss and associated changes in body composition. ORX rats were treated with either E2, 0.75 microgram/day, or different doses of nonaromatizable androgen (DHT), 45, 75, and 150 microgram/day. Low doses of DHT and E2 inhibited the ORX-induced rise of bone turnover markers similarly. High-dose DHT prevented the ORX-induced decrease of trabecular bone density but had no significant effect on cortical thinning. This bone-sparing effect occurred at the expense of hypertrophy of the ventral prostate and seminal vesicles. However, E2 restored both the trabecular bone density and cortical thickness in ORX rats and prevented age-related bone loss. In contrast to DHT, E2 increased lean body mass and inhibited the ORX-associated increase of fat mass. The authors note, "We conclude that, in the aged ORX rat model, E2 is more effective in preventing ORX-induced bone loss than DHT. Additionally, E2 has anabolic effects on muscle tissue and prevents the ORX-related increase in fat mass. Overall, these data suggest that anabolic action on bone and body composition is dependent on stimulation of both androgen receptors and estrogen receptors. "
Estrogen's effect on bone turnover in young men. This is an interesting study by Leder BZ and others reported in J Clin Endocrinol Metab 2003 Jan;88(1):204-10. The study points out that testosterone and estrogen are "independent mediators of bone resorption in young adult men." This study agrees with the above studies in that estrogen is a significant factor in bone health in men. It is apparent that both estrogen and testosterone levels should be evaluated when men have osteoporosis.
Editor's summary. Researchers are developing more and more evidence that E2 levels can be an important part of the picture for men with osteoporosis. I suggest that men ask to have their E2 levels tested and, if found to be low, discuss E2 supplements with their care provider via some form of 17 beta-estradiol. With this type of therapy, serum E2 levels can be monitored periodically to see that they are brought to and remain at the normal male level. It appears that this therapy can improve not only BMD, but may positively effect muscle and fat body masses.