Benefits and risks of sex hormone replacement in postmenopausal women

Because cardiovascular disease (CVD), which is far less common in young women than in men, but increases in prevalence in the postmenopausal years to that of men, estrogen repletion therapy (ERT) or combined hormone replacement therapy (HRT), has been widely used to protect against development of both CVD and osteoporosis, and possibly to delay or prevent cognitive loss or Alzheimer's disease (AD). To test the validity of favorable findings in many small-scale studies, and in clinical practice, a large-scale trial: the Women's Health Initiative (WHI) was undertaken by the National Institutes of Health (NIH), a trial that was prematurely ended because of increased CVD complications, despite some lessening of hip fractures. This paper suggests that the customary high intake of calcium (Ca)-advised to protect against osteoporosis, and the marginal magnesium (Mg) intake in the USA, might well be contributory to the adverse CV effects, that were all thromboembolic in nature. The procoagulant effect of estrogen is intensified by Ca; Mg-which counteracts many steps in the coagulation cascade and inhibits platelet aggregation and adhesion-is commonly consumed in sub-optimal amounts. The high American dietary Ca/Mg ratio might also be contributory to the WHI failure to confirm ERT's favorable mental effects. Discussed are mechanisms by which Mg enhances estrogen's central nervous system protective effects. Mg's improvement of cerebral blood flow, which improves brain metabolism, can also enhance removal of the beta amyloid peptide, accumulation of which is implicated in AD.