This consists of a mixture of estrogens isolated from horse urine (Premarin). The CEE was administered orally. Both studies were randomized, placebo-controlled studies. Half the women were given an inactive placebo rather than hormone(s). Both studies were terminated early because a reduction in cardiovascular disease was not observed for most women and some women had dangerous side-effects. In particular, an increased risk of dangerous blood clotting is associated with oral administration of CEE.

A review of the observational and WHI estrogen trial results describes potential explanations for the conflicting results.In addition, co-administration of MPA (medroxyprogesterone acetate, a type of progestin) with CEE was associated with a slightly increased risk of breast cancer. Some benefits of using an estrogen supplement such as reduced risk of bone fractures were confirmed by these studies. However, for the older postmenopausal women who were recruited for this study, the undesirable side-effects of treatment generally were greater than the health benefits. Based on the results of these studies, CEE and MPA are no longer given to women in order to try to prevent cardiovascular disease in older women. Younger postmenopausal women seeking relief from conditions such as hot flashes, sleep disturbance and urinary/vaginal atrophy are still candidates for hormone replacement therapy. Alternatives to orally administered CEE and MPA are being increasingly used by women since the termination of the WHI studies.

For example, other forms of estrogen (such as esterified estrogens) or topical administration of estradiol may reduce the risk of blood clotting compared to that for oral CEE.Finally, the low fat dietary pattern trial of the WHI yielded conflicting and controversial results. However, the WHI trial has been argued as unnecessary by many scientists, who already knew a full decade ago that total fat intake is not related to cardiovascular risk nor postmenopausal breast cancer risk. Criticisms:;The dietary trial has been criticized by epidemiologists for its lack of validity, both internal (the desired endpoint for fat reduction in diet was not fully achieved) as well as external (a group of post menopausal women is not generalizable to all women). Finally, the mechanism of disease of developing breast cancer may have a significantly longer time course than the duration of the study, and intervention may have been most effective prior to menopause.
 

Women's Health Initiative

The Women's Health Initiative (WHI) was initiated by the National Institutes of Health (NIH) in 1991. The objective of this women's health research initiative was to conduct medical research into some of the major health problems of older women. In particular, clinical trials were designed and funded that address cardiovascular disease, cancer, and osteoporosis. Study components:There are actually 4 different randomized interventions and a separate observational-only cohort in the WHI. All 4 of the randomized components overlap with each other to some extent (and a few even overlap with the observational study). The 4 interventions and their abbreviated terminology are: Estrogen-progestin versus placebo:;;This phase studied estrogen plus progestin compared to placebo (the "WHI-E+P" trial), among healthy postmenopausal women. It was abruptly stopped early in 2002 for exceeding global index of adverse events, and resulted in the worldwide decline in use of hormone replacement therapy.

citation needed Virtually every endpoint was exactly predicted from observational cohort studies, including the major endpoints of breast cancer, stroke, colorectal cancer and bone fracture. The sole exception was coronary heart disease.citation needed Conjugated estrogen versus placebo:Conjugated equine estrogen vs. placebo (“WHI-CEE” trial), among women with prior hysterectomy:The CEE trial was conducted among women with hysterectomy; thus, the women didn’t need progestin to counteract the uterine cancer risk of estrogen. CEE therapy interestingly was not associated with risk of breast cancer When one mentions the “estrogen” results in WHI, one must be very careful which estrogen trial is being referred. ,sdijfoighugyaustdystdfas Calcium and vitamin D versus placebo:Calcium + VitaminD combination vs. placebo (WHI-CalcVitD). This had 2 major papers arise from it in NEJM 2006, and one in May 2007 in the Archives of Internal Medicine :CRC endpoint Fracture endpoint Non-intervention cohort:The non-interventional observational cohort study (WHI-OS) of 93,000 women drawn from the same national clinical coordinating centers (many epidemiology studies conducted within this observational component of the WHI).

The WHI Postmenopausal Hormone Therapy Trials were part of the effort to address the high risk of cardiovascular disease in older women. By the early 1990s, many physicians had come to interpret results from previous clinical trials and studies using experimental animals as indicating that administration of an estrogen supplement to postmenopausal women would lower the incidence of cardiovascular disease. Two hormone clinical trials were designed and conducted:The estrogen that was administered in the WHI studies was conjugated equine estrogen (CEE).