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Hormone replacement therapy

Confused about the safety of hormone replacement therapy? You’re not alone.



Physics Nobel laureate Richard Feynman once described his view of the search for truth in science in a lecture in 1963: “If something is true, really so, [and] you continue observations and improve the effectiveness of the observations, the effects stand out more obviously. Not less obviously. That is, if there is something really there, and you can’t see good because the glass is foggy, and you polish the glass and look clearer, then it’s more obvious that it’s there, not less.”

Which brings us to the subject of hormone replacement therapy (HRT). Despite two decades of studies aimed at assessing the risks and benefits of HRT, specifically in relation to heart disease and breast cancer, things are about as clear as a glass buried in peat bog.

Yes, we can partly blame the media, as they know that headlines like “HRT: nothing to worry about” are not going to attract as many eyeballs as “HRT shrinks women’s brains” (a recent and real headline). You would also blame two decades of conflicting and confounding results. Consider just a few research highlights from the past couple of decades:

1992: The first randomised controlled study of HRT is published, finding that even after 22 years of use, women on HRT don’t have an increase in breast cancer.

1995: The Nurses’ Health Study, which followed 121,700 female nurses from 1976 to 1992, finds no increased risk of breast cancer.

2000: The Nurses’ Health Study reports that HRT reduces the development of cardiovascular disease by 40%.

2002: The World Health Initiative (WHI) study is stopped after women in the study taking oestrogen plus progestin were found to have higher rates of both heart disease and breast cancer.

2003: The Million Women Study shows that combined HRT is more likely to cause breast cancer than oestrogen-only HRT.

2004: The WHI reports there is no increase in the risk of breast cancer associated with the use of oestrogen alone, but an increased risk of stroke.

2006: The WHI reaffirms its findings that oestrogen-only therapy does not increase the risk of breast cancer. It later reports there is also no increased risk shown among women randomised to take oestrogen and progestin combined.

2007: Combined data from two of WHI’s hormone trials suggest that women who start hormone therapy within 10 years of menopause reduce their risk of heart disease whereas those who start later increase their risk. The Nurses’ Health Study reaches the same conclusion.

2009: Women using oestrogen for more than five years are found to double their annual risk of breast cancer.

2011: The WHI releases its seven-year follow-up data, showing that women in their fifties who have had a hysterectomy can take oestrogen-only therapy for up to six years without any significant increased risk of breast cancer. Two months earlier, researchers on the Million Women Study released a report that said HRT had an adverse influence on breast cancer risk – the risks were greater with oestrogen-­progestin than oestrogen-only and if hormonal therapy started at around the time of menopause rather than later.

Confused? The researchers probably are, too. Some experts have blamed the contradictory nature of all these results on the design of the studies. Some of the key ones were observational and some were randomised control trials. Observational studies showed that HRT appeared to protect against coronary heart disease, for instance, whereas randomised trials found it increased the risk.

Which study design is superior depends on who you talk to, and there is still debate about that. Some say a combination of the two is needed to make sense of it all.

More recently it has been argued that it wasn’t the design of the studies but discrepancies in the timing of the start of treatment relative to menopause. Others say it’s to do with the populations being studied. An editorial in this month’s British Medical Journal suggests that as 68% of women were aged 60 when they enrolled in the WHI’s randomised trial, the WHI’s population isn’t the best when trying to reach conclusions about younger women and oestrogen prescription.

In other words, the glass still needs quite a bit of polishing and may never be clear. Which may be more interesting to a scientific researcher than someone whose life has been made miserable by hot flushes, night sweats and demonic mood swings.

The current status seems to be that risks are real, but often exaggerated, and it very much depends on the person. The only sensible advice then is to avoid the internet, ignore the headlines and talk to your doctor.