Re: Meta analyses and misleading claims about HRT mortality
Another example of a meta-analysis coming up with a wrong result is
the Salpeter meta-analysis on HRT mortality.1 After 40 years of
unjustified claims of health benefits major randomised, double-blind
trials of HRT including the US WHI studies of combined and oestrogen-only
HRT, the Million Women Study, and the HABITS and Stockholm studies of HRT
in breast cancer patients, were terminated early. Increased health risks
include breast and endometrial cancer, myocardial infarction, stroke,
venous thrombosis, and dementia and no overall improvement in the quality
of life. How then has Salpeter managed to claim HRT reduces mortality?
Not one of the 30 short-term randomised controlled trials pooled for
the meta-analysis produced a statistically significant effect of HRT on
mortality. The claimed reduction in mortality for women with a mean age
under 60 was achieved by statistical manipulations. Trials of sick women
with most deaths during the study follow-up were given disproportionate
weighting. For example one small open-label study of 68 controls / 62 HRT
treated ovarian cancer “survivors” was allocated a weight of 41% because
the majority of the women, 41 and 32 women respectively, died during the
study follow-up period. The fact that many studies have found HRT
increases in the risk of fatal ovarian cancer was not mentioned. In
contrast, the largest study of 701 previously healthy women found a 75%
increased mortality risk with HRT use but was weighted at only 2.3%
If only double-blind randomised controls studies with more than a
hundred HRT- treated younger women had been pooled, a completely different
result would be achieved as seven of the deaths occurred in 1450 treated
women and none in 479 control women.
This seems to be an attempt to validate the myth that hormones are
safer for younger women. Breast cancer incidence increases match the
changes, mostly huge increases, in hormone use in hormone-taking countries
since the 1960s. Women diagnosed with breast cancer are still likely to
die of the disease 20 years after diagnosis. Most modern epidemiological
studies fail to clarify which women have never taken hormones, and
therefore underestimate the real mortality risks.
1 Salpeter SR, Walsh JME, Greyber E, Ormiston TM, Salpeter EE.
Mortality associated with hormone replacement therapy in younger and older
women. A meta-analysis. J Gen Intern Med 2004; 19: 791-804.
Competing interests: No competing interests