In an interesting article on estrogen in the NYT:
... the Women’s Health Initiative, or W.H.I. It was a federally financed examination of adult women’s health, extraordinary in scale and ambition, that started up in the early 1990s; one of its drug trials enrolled more than 16,000 women for a multiyear comparison of hormone pills versus placebos. On July 9, 2002, W.H.I. investigators announced that they had ended the trial three years early, because they were persuaded that it was dangerous to the hormone-taking participants to let them continue. ...
First of all, ... there are different forms of estrogenic molecules — ... estradiol. It’s [Estradiol] not the estrogen used in the W.H.I. study. Pharmaceutical estradiol like mine comes from plants whose molecules have been tweaked in labs until they are atom for atom identical to human estradiol, the most prominent of the estrogens premenopausal women produce naturally on their own. The W.H.I. estrogen, by contrast, was a concentrated soup of a pill that is manufactured from the urine of pregnant mares. ...
The progesterone he prescribed ... , like the estradiol, is a molecular replica of the progesterone women make naturally. It’s different from the progesteronelike synthetic hormone that was used for the W.H.I. study that ended in 2002. That medication was a formulation whose multisyllabic chemical name shortens to MPA and which has a problematic back story of its own: MPA takes care of the uterine-cancer risk, but there’s reason to suspect it may be a factor in promoting breast cancer. And it’s ingested as a pill, which means that like equine estrogens ... MPA metabolizes through the liver, possibly creating additional complications en route, before going about its business.
The biggest difference between me and the W.H.I. women, though, has to do with age and timing. I started on the patches while my own estrogen, pernicious though its spikes and plummets may have been, was still floating around at more or less full strength. The average age of the W.H.I. women was just over 63, though the study accepted women as young as 50. More significant, though, most of them were many years past their final menstrual period, which is the technical definition of menopause, when they began their trial hormones. The bulk of the group was at least 10 years past; factoring in the oldest women, the average number of years between the volunteers’ menopause and their start on the trial medications was 13.4.
The bottom line:
... one undiplomatic critic sum up the W.H.I. as “the wrong drugs, tested on the wrong population,”
Gelman's blog also discusses another randomized trial that did not fully answer the question on PSA screening. More here.