29 August, 2016

New scare about hormone replacement therapy and breast cancer

HRT is very beneficial to many women as they cease menstruation.  It relieves the many physical problems they experience at that time. So, as with anything popular,  the elites had to find something wrong with it.  And there was a big scare around the beginning of this century saying that it caused breast cancer. Subsequent research, however, largely cleared the HRT pill of that danger and official guidance these days is that there is little to worry about.

A new study just out (summary and journal abstract below), however, has renewed the scare. And the new study is methodologically strong.  It takes careful account of things not well considered in previous studies.  There are a couple of reasons not to be too bothered by the findings, however.  The first is that, as with most medical research, only the relative risk is reported, not the absolute risk.  I had to scratch fairly deeply to find the absolute risk behind the current results.  It was about 40 in 1,000.  Out of 1,000 old ladies, 40 will get cancer from taking the HRT pill. That is not negligible but it is not a great risk either.  Most of us do more risky things with some regularity -- like driving a car.

The second thing to note is that not all HRT pills are the same.  What is most lacking in old ladies is the female hormone estrogen.  Those old ladies who get around in masculine haircuts have lost most of their female hormones so are in a sense post-female.  So replacing the estrogen is all that should be required to restore the old  balance in the woman's life.  And that is what most HRT pills do.

For women whom the estrogen doesn't help much, however, there is another sort of pill: estrogen plus progestogen. And that is inherently risky.  Progestogens produce progesterone, which is a major pregnancy hormone.  Worldly-wise men know why their women  get irritable once a month (PMT).  It is when her ovaries are producing progesterone to prepare the womb for conception.  So progesterone is vital for conception but it is also the bad-mood hormone. I once saw a rather spectacular example of progesterone-induced rage myself. The woman concerned was deeply embarrassed afterwards. That increased progesterone levels  might have other problems is therefore easily understood.

And it appears that it does.  The research below found absolutely no problem with the estrogen-only pill but did find problems with the combined pill. The progestogen-containing pill does slightly elevate the risk of breast cancer.  Giving old ladies a pregnancy hormone is pretty wild to start with so it is no surprise that it might have some ill effects.

But there is a BIG problem with the causal arrow here.  As is deplorably common in the medical literature, the authors assume that correlation is causation, which is a gross statistical fallacy.

What they have not done is ask WHY the women concerned were put on the combined pill in the first place?  Were they less healthy in various ways from the beginning?  Would they have got more cancer anyway, with or without the pill?   So being put on the combined pill may be an  indicator that the old ladies were from the beginning more likely to get cancer rather than the pill causing the cancer.

So this research is not conclusive at all.  Only a before-and-after experimental design could answer questions about cause.  Even the combined pill could be completely harmless.

Nonetheless, I agree with the most common medical advice, that women should by and large stick to the estrogen-only pill.  We KNOW that it is harmless


HRT raises the risk more than threefold for women who had taken it for 15 years, the Institute of Cancer research found Credit: Press Association

Hormone replacement therapy can triple the risk of breast cancer, the biggest ever study has found, following more than a decade of controversy.

Last year the National Institute of Health and Care Excellence (Nice) changed guidance to encourage more doctors to prescribe HRT claiming too many menopausal women had been left suffering in silence.

HRT is used to treat uncomfortable symptoms of the menopause - such as hot flushes, migraines, disrupted sleep, mood changes and depression - by topping up the decreased levels of hormones produced by the body.

But doctors were reluctant to prescribe it after a study in 2002 suggested it could raise the risk of cancer, a claim later widely disputed.

Now new findings by the Institute of Cancer Research and Breast Cancer Now suggest the original risk had actually been underestimated.

A study of 100,000 women over 40 years found those who took the combined oestrogen and progestogen pill for around five years were 2.7 times more likely to develop cancer compared to women who took nothing, or only the oestrogen pill.

The risk rose to 3.3 times for women who took the drugs for 15 years or more.

Around 14 in 1,000 women in their 50s are expected to develop breast cancer, but that rises to 34 in 1000 for women taking the combined pill, the study suggests.

"Our research shows that some previous studies are likely to have underestimated the risk of breast cancer with combined oestrogen-progestogen HRT," said study leader Professor Anthony Swerdlow, of The Institute of Cancer Research.

"We found that current use of combined HRT increases the risk of breast cancer by up to threefold, depending on how long HRT has been used.

"Our findings provide further information to allow women to make informed decisions about the potential risks and benefits of HRT use."

Women taking the oestrogen-only pill have no greater risk

HRT was first developed in the 1940s and was first made available to women in Britain in 1965.

However in 2002 the British Millennium Women Study published findings claiming that HRT raised the risk of cancer. Many doctors immediately withdrew prescriptions while the Medical Healthcare and Regulatory Agency (MHRA) issued new guidance recommending all women be given the "lowest effective dose should be used for the shortest time."

Since then the number of women taking HRT has more than halved with around one in 10 eligible patients now using the drugs, approximately 150,000 women.

More recently a review by Imperial College and a 10-year study by New York University found no evidence of a link, adding further to the confusion and last year the National Institute for Health and Care Excellence (Nice) changed its guidance to encourage doctors to offer HRT claiming one million women were suffering in silence.

At the time Nice said that the cancer risk was 27 in 1,000 so the new research, which followed 100,000 women for 40 years, increases that risk by 54 per cent.

The health watchdog said that the new study should not change how doctors prescribed HRT.

We found that current use of combined HRT increases the risk of breast cancer by up to three fold, depending on how long HRT has been usedProfessor Anthony Swerdlow, Institute of Cancer Research

Professor Mark Baker, director of the Centre for Guidelines at NICE, said: "As with Nice guidance this study recognises there is no increased risk of breast cancer with oestrogen-only HRT but the combined HRT can be associated with an increased risk of breast cancer.

"The guideline makes clear that menopausal women should be informed that the impact of HRT on the risk of breast cancer varies with the type of HRT used.

"The message from our guidance to women is clear - talk about the menopause with your clinician if you need advice on your symptoms - it's very important to discuss the options to find what might help you."

The new study also found that the risk declined when women stopped taking HRT and there was no danger at all for women only taking oestrogen, which accounts for half of all prescriptions.

Baroness Delyth Morgan, chief executive at Breast Cancer Now, said: "Whether to use HRT is an entirely personal choice, which is why it's so important that women fully understand the risks and benefits and discuss them with their GP. We hope these findings will help anyone considering the treatment to make an even more informed decision.

"On balance, some women will feel HRT to be a necessity. But in order to minimise the risk of breast cancer during treatment, it is recommended that the lowest effective dose is used for the shortest possible time.

"The good news is that the increased risk of breast cancer begins to fall once you stop using HRT."

SOURCE

Menopausal hormone therapy and breast cancer: what is the true size of the increased risk?

Michael E Jones et al.

Abstract

Background:  Menopausal hormone therapy (MHT) increases breast cancer risk; however, most cohort studies omit MHT use after enrolment and many infer menopausal age.

Methods: We used information from serial questionnaires from the UK Generations Study cohort to estimate hazard ratios (HRs) for breast cancer among post-menopausal women with known menopausal age, and examined biases induced when not updating data on MHT use and including women with inferred menopausal age.

Results:  Among women recruited in 2003-2009, at 6 years of follow-up, 58?148 had reached menopause and 96% had completed a follow-up questionnaire. Among 39,183 women with known menopausal age, 775 developed breast cancer, and the HR in relation to current oestrogen plus progestogen MHT use (based on 52 current oestrogen plus progestogen MHT users in breast cancer cases) relative to those with no previous MHT use was 2.74 (95% confidence interval (CI): 2.05-3.65) for a median duration of 5.4 years of current use, reaching 3.27 (95% CI: 1.53-6.99) at 15+ years of use. The excess HR was underestimated by 53% if oestrogen plus progestogen MHT use was not updated after recruitment, 13% if women with uncertain menopausal age were included, and 59% if both applied. The HR for oestrogen-only MHT was not increased (HR=1.00; 95% CI: 0.66-1.54).

Conclusions:  Lack of updating MHT status through follow-up and inclusion of women with inferred menopausal age is likely to result in substantial underestimation of the excess relative risks for oestrogen plus progestogen MHT use in studies with long follow-up, limited updating of exposures, and changing or short durations of use.

British Journal of Cancer (2016) 115, 607-615. doi:10.1038/bjc.2016.231





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