The buried mystery of oestrogen effects in post menopausal women

 The cardiovascular protective effect of estrogen in premenopausal women is assumed to be due to improvement in HDL:LDL ratio, diminished atherogenesis and improved vascular health attributed to NO and PgI. These factors formed the basis of their use in postmenopausal women for better cardiovascular outcomes. Indeed, estrogens provide cardiovascular protection in early post menopause but with advancement of age, the protective effects wane. In the year 2002, the findings of the landmark trial, Women's Health Initiative, showed for the first time that the risks associated with HRT outweigh the benefits and henceforth, the popularity of HRT declined rapidly. The real world evidence generated from the trial was enough to overwhelm the popular pharmacological concepts of estrogenic  cardiovascular benefits and ever since the mechanism of estrogenic effect in postmenopausal women has remained a mystery. Perhaps, it will be never be possible to know, because estrogens are no longer given to postmenopausal womem for long years. The use has become restricted for vasomotor symptoms and atrophic vaginitis. They are given for the shortest possible time in the smallest possible dose. At present, we can only speculate the possible reasons for adverse cardiovascular effect of estrogen in post menopausal women. One reason may be that estrogen increase the synthesis of clotting factors in the liver and that may be responsible for increased incidents of deep vein thrombosis, acute myocardial infarction etc. But then, why they don't increase the cardiovascular risk in premenopausal women, no body knows. There are many mysteries of nature which are yet not known to mankind.