Can HRT cause cancer?

Two studies: one ‘split study’ from the US called the Women’s Health Initiative (WHI), which looked at the effects of both combined and estrogen-only HRT, and one from the UK called The Million Women Study (MWS), changed perceptions of HRT for decades to come. The WHI studies ran from 1993 to 2002/2004 (the study on combined HRT was stopped two years earlier than the estrogen-only one), and the MWS ran from 1996 to 2001.

Both studies seemed to find increased health risks from HRT at early stages, including slight associations with breast cancer, heart disease, stroke and blood clots. It now seemed that the risks of HRT outweighed the benefits. These preliminary findings were published and widely circulated, leading to a lot of negative press, fear and ‘health scare’ headlines.

Following this, doctors stopped prescribing it (or became more wary of doing so), and women stopped taking it. The result of which can still be seen today — HRT use declined by a dramatic 46% in the five months following the early pause of the WHI trial in the USA. And following the results of the MWS, the number of postmenopausal women in the UK using HRT dropped from 29% in 2001/02, to less than 11% by 2005.

The estrogen-only arm of the WHI trial continued until 2004, when its preliminary findings were also published. Like the combined HRT trial, it stopped prematurely – this time because of a small increased risk of stroke, despite finding significant other benefits (like a reduction in cardiovascular disease and osteoporosis) and no increased risk of breast cancer. The overall message surrounding HRT remained negative.

In the years since these trials, their limitations have become increasingly apparent, and new evidence has been found that goes against much of the original findings. The WHI trial, for example, mainly involved women who had their last period more than a decade before, at a dose we now know to be too high for older women. It also only tested one specific form of HRT (conjugated equine estrogen and medroxyprogesterone acetate). Basically, it didn’t account for how well the right dose and form of HRT could benefit women in order to outweigh or reduce the risks.

There was an issue with the MWS too: the women in the trial were ‘self-selecting’ (they were surveyed during a breast screening) rather than randomized, which often skews results. It could be, for example, that the women attending their breast screening had already found a lump, meaning that those enrolling in the trial were already more likely to have breast cancer than the general population.

But despite growing knowledge within the scientific community that the risks of HRT found by these studies did not reflect the general population, the reputation stuck for much of the world.