The study proposes to examine whether dosage for estrogen replacement therapy should be individualized, as is done for thyroid hormone replacement therapy. We will examine whether estrogen dosage can be optimized based on an individual's bone turnover, anthropometric indices, or serum levels of estrogen metabolites. This question will be addressed in a randomized double-blinded, placebo-controlled study where bone density will be measured sequentially in postmenopausal women randomized to receive either 0.3, 0.6, or 1.2 mg of Premarin daily. We hypothesize that women who take standard doses of Premarin and have elevated biochemical markers of bone resorption that fall after increasing their dose from 0.625 to 1.25 mg/day will derive skeletal benefit from treatment with 1.25 mg/day of Premarin. Similarly, women who take Premarin whose biochemical markers of bone resorption remain suppressed after having their dose reduced from 0.625 to 0.3 mg will still derive maximal skeletal protection at the lower dose. Potential beneficial or adverse effects of unconventional doses of estrogen on cardiovascular risk factors, body composition, clotting factors, mood and sexual function will also be examined. Because the results of this study will help physicians to adjust estrogen dosing for millions of postmenopausal women taking estrogen replacement, this study has tremendous relevance to aging.
Rosen, H N; Parker, R A; Greenspan, S L et al. (2004) Evaluation of ability of biochemical markers of bone turnover to predict a response to increased doses of HRT. Calcif Tissue Int 74:415-23 |