How to evaluate the risk-benefit ratio of the low-dose hormone replacement therapy?

Since the results of the women health initiative study showing an overall negative risk-benefit ratio with 0.625 mg of conjugated estrogens plus 2.5mg of medroxyprogesterone acetate, the use of the lowest effective dose of steroids in hormone replacement therapy (HRT) is recommended. A low-dose regimen appears to induce less side effects such as breast tenderness or leg pain than do higher dose preparations. The decrease in hot flashes with low-dose estrogens, range 60-70%, is less than the 80-90% reduction with standard dosing. But this mean that 60-70% of menopausal women do not need higher doses. The same applies to bone preservation which is dose dependent: the number of non-respondant women will be higher than with standard doses. However, randomized double-blind, placebo controls trials have defined positive effects on bone of low doses of HRT with adequate calcium and Vitamin D in elderly women. The use of bone densitometry and of biochemical markers of bone turnover is mandatory in women using low or ultra-low-dose preparations. In spite of the lack of trials conducted with low-dose HRT, this treatment seems to be safer: Beside the low-dose HRT, one must consider some other facts: In the future, it is conceivable that more comprehensive pharmacogenomic studies will lead to effective algorithms for individualizing the right dose of steroids to be used in HRT.