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Abstract
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.
Key teaching points:
Part 1
Failure of large test (Women’s Health Initiative: WHI) to confirm cardiovascular (CV) benefit of estrogen repletion therapy (ERT) can be attributed in large part to high dietary Ca/Mg.
The increased CV adverse reactions in WHI participants were due predominantly to thromboembolic complications: cardiac and brain infarctions, pulmonary emboli, and venous thromboses.
Thromboembolic phenomena are known to have been increased by use of estrogen—as oral contraceptives in women and to suppress prostatic cancer in men.
The current high dietary Ca/Mg ratio in the USA, Ca increasing coagulation cascade steps, and Mg inhibiting them and decreasing platelet aggregation, might well have intensified pro-coagulant effects caused by estrogen.
The results of the WHI confirmed the benefit of estrogen and high Ca intake—commonly advised to counteract postmenopausal osteoporosis—in decreasing hip fracture prevalence.
Part 2
A subgroup of the WHI study (WHIM) tested the controversy as to whether estrogen, with and without a progestogen can delay postmenopausal loss of cognition and development of Alzheimer’s disease (AD).
The results, particularly with combined hormone replacement therapy (HRT), were not conclusive, although the HRT group showed more decline of mental scores, and twice as many developed dementia as did women on placebo.
The possibility was considered that some of the dementia might have stemmed from silent brain infarcta—contributed to by increased blood coagulability.
The better results in mental status reported by smaller studies with ERT: estrogen replacement therapy, can be attributed to neurotrophic and neuroprotective effects of estrogen, which has beneficial effects on neurotransmission, as well as to its cerebral arterial vasodilatory effect that counteracts ischemia.
Evidence is presented that correcting the marginal Mg intake of most American women could protect against, not only vulnerability to CV complications of use of HRT, but—by several cited mechanisms—can improve the mental benefit of ERT in postmenopausal women.
Key teaching points:
Part 1
Failure of large test (Women’s Health Initiative: WHI) to confirm cardiovascular (CV) benefit of estrogen repletion therapy (ERT) can be attributed in large part to high dietary Ca/Mg.
The increased CV adverse reactions in WHI participants were due predominantly to thromboembolic complications: cardiac and brain infarctions, pulmonary emboli, and venous thromboses.
Thromboembolic phenomena are known to have been increased by use of estrogen—as oral contraceptives in women and to suppress prostatic cancer in men.
The current high dietary Ca/Mg ratio in the USA, Ca increasing coagulation cascade steps, and Mg inhibiting them and decreasing platelet aggregation, might well have intensified pro-coagulant effects caused by estrogen.
The results of the WHI confirmed the benefit of estrogen and high Ca intake—commonly advised to counteract postmenopausal osteoporosis—in decreasing hip fracture prevalence.
Part 2
A subgroup of the WHI study (WHIM) tested the controversy as to whether estrogen, with and without a progestogen can delay postmenopausal loss of cognition and development of Alzheimer’s disease (AD).
The results, particularly with combined hormone replacement therapy (HRT), were not conclusive, although the HRT group showed more decline of mental scores, and twice as many developed dementia as did women on placebo.
The possibility was considered that some of the dementia might have stemmed from silent brain infarcta—contributed to by increased blood coagulability.
The better results in mental status reported by smaller studies with ERT: estrogen replacement therapy, can be attributed to neurotrophic and neuroprotective effects of estrogen, which has beneficial effects on neurotransmission, as well as to its cerebral arterial vasodilatory effect that counteracts ischemia.
Evidence is presented that correcting the marginal Mg intake of most American women could protect against, not only vulnerability to CV complications of use of HRT, but—by several cited mechanisms—can improve the mental benefit of ERT in postmenopausal women.