Early 2000s
Approximately 6 million US women were using prescription estrogens in 1992; in the next decade the number grew to 15 million using estrogen therapy, with or without progestins.

2001
Published results from the first year of the Women's HOPE Study, concerning menopausal symptoms, amenorrhea, and metabolism, show significant improvement in vasomotor symptoms (hot flashes, night sweats) and vaginal atrophy in postmenopausal women with intact uteri taking HT as compared with similar women not taking HT (50).

2002
Results from extended, open-label evaluation of the HERS (Heart Estrogen/progestin Replacement Study) indicate no cardiovascular benefit of HT in postmenopausal women with previous history of cardiovascular disease (51, 52).

The National Institutes of Health (NIH) halts the estrogen plus progestin part of the Women's Health Initiative study, the largest randomized prospective trial evaluating the effects of estrogen plus progestin and estrogen alone versus placebo (no hormone). Originally the study was to continue to 2005 but was brought to an early end because the risks of this treatment were found to outweigh the benefits. At the start of the study, a method to weigh all benefits and risk of therapy under a global score index, or a composite score, was designed. It was decided in the beginning that the study would be stopped if the risks exceeded the benefits based on this composite (global) score. The composite score involved comparison of placebo with estrogen plus progestin on the risks of invasive breast cancer, coronary heart disease, stroke, and blood clots and benefits on the prevention of hip fractures in the women taking estrogen plus progestin. If one looked at all causes of death in women taking or not taking hormones, there was no difference between those on hormones and those not taking them. (53).

There was a sharp drop in the use of HT following the publication of the preliminary findings of the WHI estrogen plus progestin trial.

2003
Results from the WHI Memory Study (WHIMS) show that women aged 65 or older who took estrogen plus progestin had twice the rate of dementia, including Alzheimer’s disease, as those taking placebo. Estrogen plus progestin did not protect against mild cognitive impairment (e.g., trouble paying attention and remembering) (54, 55).

2004
The NIH halts the estrogen-alone portion of the WHI because of increased risk of stroke and blood clots. No heart benefits were seen for postmenopausal women with hysterectomies who were taking estrogen alone (56). But surprisingly there was no increased risk of breast cancer. The results from the WHIMS show that women aged 65 years and older taking estrogen alone had an increased risk of mild cognitive impairment (57, 58).

2005
Analysis of data from the WHI study shows that use of up to two years of estrogen plus progestin is associated with increases in the amount of dense tissue seen on mammograms. The increased density reduces the sensitivity of screening mammography and is associated with increased risk of breast cancer (59).

Proponents of “natural” or “bioidentical” HT for menopausal symptoms claim that these products are safer than manufactured forms of HT. The bioidentical hormones used to treat these symptoms are formulated (made in a laboratory) to have the same chemical structure as the estrogen hormones made by your body. However, there is no evidence that custom-made products have better effects than pharmaceutical products. The association between excessive estrogen in the bloodstream and the risk of breast or uterine cancer is the same whether the estrogen is made by the body or in a laboratory (60, 61).

2006
A follow-up study of the postmenopausal women with hysterectomies who took estrogen alone in the WHI reveals no increase in breast cancer over a five year period. Because there was an increased in density of the breast associated with taking estrogen, women were more frequently asked to come back for additional testing because of the suspicion of abnormalities on the mammogram (62).