Health scare 'clouded views on HRT'

"Thousands of women have had a ‘wasted decade’ of suffering since the HRT scare, according to an international panel of experts,” the Daily Mail has reported.

The news is based on a major re-evaluation of the Women’s Health Initiative (WHI) study, the results of which prompted safety fears in 2002. The re-analysis comes in a series of journal reports which were highly critical of the way the results of the WHI were presented and the media’s interpretation of them. The reports said this led to panic based on scant real-life evidence, which may have caused a change in prescribing practice to the potential detriment of the wellbeing of thousands of women worldwide.

The authors of one review concluded: “While HRT is certainly not appropriate for every woman, it may be for those with symptoms or other indications. In that setting, with initiation near menopause, the weight of evidence supports benefits over risks.”

What is HRT?

Hormone replacement therapy (HRT) is a treatment used to relieve the symptoms of menopause. It replaces the female sex hormones that women’s bodies stop producing after menopause. Reduced production of the hormone oestrogen is associated with many of the symptoms of menopause, including:

hot flushes
night sweats
vaginal dryness
loss of sex drive
stress incontinence
osteoporosis

HRT replaces this hormone, reducing these symptoms. HRT comes in different forms – some are taken continuously and some are taken with breaks in between – as a tablet, patch, implant, gel or cream. Most HRT preparations contain an oestrogen in combination with a progestogen. The kind of HRT a woman is prescribed will be based on her individual circumstances. For more information, see the NHS Choices information on HRT.

Why did HRT fall out of favour?

Safety concerns over long-term use of HRT significantly altered medical thinking on prescribing it, prompted by the initial results of two large trials. These were the US Women’s Health Initiative (WHI) study (published in 2002), part of which was halted early because women using HRT were seen to be at higher risk of breast cancer, and the UK Million Women Study (published in 2003), which also showed a higher rate of breast cancer in women on HRT.

The authors of the new re-analysis said that the scare, which led to a significant drop in prescribing HRT, was not helped by how the science was portrayed worldwide in the media. They were especially critical of the reporting of relative risks (a 26% increase in breast cancer risk) rather than “excess” or “attributable” risk of four extra breast cancer cases per 1,000 women taking HRT over a five-year period. The authors also criticised the dramatic nature of the press releases about the research issued by the Journal of the American Medical Association and the US National Heart, Lung and Blood Institute. They argued that this gave rise to the health scare that sparked the widespread avoidance of HRT.

What have new studies looked at?

A decade after the release of the results of the WHI study, the peer-reviewed journal Climacteric has published an entire issue re-appraising the evidence from the WHI study and other evidence published in the last 10 years.

One of the Climacteric articles stated that the WHI study was designed to address whether older women (much older than the average age for menopause, which in the UK is 52) who mostly did not have symptoms of menopause, benefitted from HRT. However, they authors said the results were generalised to all women, and this in combination with the fact that a 26% relative risk increase in breast cancer was reported (rather than a modest increase in absolute risk) led to the HRT scare.

Other aspects of HRT’s effect on women’s health were examined, including:

quality of life
gynaecological and sexual health
cost-effectiveness
stroke
blood clots
colorectal cancer
dementia
fractures caused by osteoporosis
overall effects of the drop in HRT use

In the new study looking at breast cancer and HRT, the authors concluded that the benefits of HRT in women with low initial risk of breast cancer and significant menopausal symptoms will outweigh the harms, because their absolute risk of cancer is low.

The link between breast cancer and HRT seen in the Million Women Survey has also been disputed by later studies, including in early 2012 a study that criticised the study design of many of the HRT studies.

The reviews concluded that HRT is associated with:

improved quality of life in women going through the menopause
reduced risk of coronary heart disease and death (if taken before the age of 60 or within 10 years of menopause)
modestly increased risk of stroke, venous thromboembolism and breast cancer
reduced risk of colorectal cancer
reduced risk of dementia for those starting HRT early (but later use may increase risk)
decreased risk of fracture

What impact did the scare have?

One analysis that looked at the rates of HRT use found that it had dropped by between 40% and 80%. The positive or negative effects of this decline on disease and death rates have not yet been assessed. A 2011 statement from the International Menopause Society, quoted in the re-analysis, said that the media presentation of the WHI results in 2002 engendered “excessive conservatism” that “has disadvantaged nearly a decade of women who may have unnecessarily suffered severe menopausal symptoms and who may have missed the potential therapeutic window to reduce their future cardiovascular, fracture and dementia risk”.

An analysis of the media’s role in the HRT scare found that the common perception of HRT as risky continued until July 2007, when the trial revised its findings on cardiovascular risk. However, they reported that the media portrayed this revision as a “U-turn” by experts (including on the front page of the Daily Mail), reinforcing the media’s “confused interpretation” of the safety and benefits of HRT. However, the authors said that the “melodramatic presentation” of the WHI results explained the media response.

So, is HRT safe?

Like any drug or treatment, HRT is associated with both risks and benefits. However, according to NICE in 2009, the overall balance of benefits and side effects suggests that HRT is acceptably safe and beneficial enough to justify its use for certain women experiencing severe problems during menopause. This is not to say it is risk-free or suitable for the majority of women, but it does have justified uses.

The Medicines and Healthcare Products Regulatory Agency also provide a useful summary of the evidence regarding both the benefits and the risks of HRT.

In the report in question, the authors stated that the International Menopause Society recommends individualised treatment, with age being taken into account as a safety issue. HRT shows the most benefits for women with symptoms who start HRT within a few years of menopause, and therefore as women get older the potential risks of HRT may outweigh the diminishing benefit offered.

Doctors would assess whether or not HRT was an appropriate treatment on a case-by-case basis. They would take into account factors such as the severity of a woman’s symptoms and whether she has a history of breast cancer (certain types of breast tumour can be encouraged by female hormones).

The findings of this new research do not in themselves suggest that HRT should be offered more widely, but they certainly raise some interesting points over the need for a clear, evidence-based approach to assessing HRT and also in the way perceptions of danger have affected its use. They open the door to further robust research re-evaluating HRT, which needs to be performed and judged in as objective a manner as possible.