Hrt cancer risks and best time to start

[Multicolouredsequins]

Hi,
think I'm perimenopausal. Looking to start combined hrt patches due to fatigue, brain fog, night sweats, very heavy but short periods (accompanied by digestive issues), feeling very flat and disengaged etc. Have done quite a bit of reading and have been reassured by Dr Louise Newson re cancer risks etc. However, reading the government guidelines from 2019 has frightened me a bit;
www.gov.uk/drug-safety-update/hormone-replacement-therapy-hrt-further-information-on-the-known-increased-risk-of-breast-cancer-with-hrt-and-its-persistence-after-stopping

Is this report based on the Oxford study which Dr Newson talks about (and somewhat discredits), based on older types of hrt etc? The numbers, although low, do concern me, as I'm expecting to take combined hrt for 10 years potentially. The worst symptoms and negative affects of menopause seem to typically be mid-late 40s to 60, in terms of rapid ageing, decreasing bone density etc etc. I'm worried that if I start now in my 40s I'll have to come off it when symptoms are potentially at their worst due to cancer risks.

The government report also states that they only recommend hrt for post menopausal women, which is news to me!! So typically, 52 years plus. I thought there is a lot of benefit from taking it for peri and menopausal symptoms? Confused! I thought the newer plant based hrt was much safer than this?

Davina talks about the bc risks in her first programme, I seem to recall it was very low, about 4 in every thousand.

i don’t think there’s a limit now on length of time hrt can be taken.

I tend to trust Cancer Research U.K. Org for my information. The risks are very low, but real. They have a good chart to put it in perspective compared to cancer risk of obesity or smoking.
www.cancerresearchuk.org/about-cancer/causes-of-cancer/hormones-and-cancer/does-hormone-replacement-therapy-increase-cancer-risk#HRTrefs0

Ive read Dr Newsons webpage and leaflets and I have to admit I find it concerning that

• she is a GP, not an oncologist or even an epidemiologist. So she’s not any more qualified in researching cancer risks than any GP in any surgery. She’s not done any research or studies herself…she seems to have read the studies that have been done and then dismissed the majority of them.


• she never ever includes references to scientific studies to back up her claims that other studies were flawed/wrong or studies that support the claims or statistics in her leaflets, booklets, and other publications on her website (that I have seen). Where do they come from? How does she know that breast cancer risk is exactly 1 in 7 for all women in the U.K. HRT or no HRT? How does she know HRT protects against dementia? If she’s saying this as a fact, why is she not including a scientific reference to show that?


• she gives the exact same advice to patients no matter what their cancer risk is absent HRT, which seems odd to me. She even says it’s perfectly safe to take HRT if you are a breast cancer survivor….again with no scientific reference to a study supporting this rather surprising to me claim.

I like references to the actual science so I can research for myself, which Cancer Research U.K. does do.

Thanks for your replies. I agree with you, Discovereads, Dr Newson is very vague and general and obviously very pro hrt. The Cancer research link is helpful. The pure stats, with supporting details, are hard to come by. The fact that the risk doubles after 5 years is concerning to me. I can see why some GPs are reluctant to prescribe to peri and menopausal women given the government advice to only prescribe for post menopausal women. But I wonder if taking it during the transition can reduce a lot of the damage and symptoms. I read mixed reports on this.

I think consensus is that if your symptoms are bad enough to be affecting your life significantly, that the benefits usually outweigh the risks. Yes breast cancer risk increases the longer you use it, but doubling an already very low risk results in a still very low risk. I will try and find the exact study and figures for you.

It’s hard to know what will happen to you. Whether your peri and menopause symptoms will last less than average, average or more than average. Family history can give you a clue if available as daughters tend to be similar to their mothers.

All I can go by is averages as my mum died before perimenopause and my grandmother died of breast cancer when I was very young. So I have no idea either.

So average age of menopause is 51 in the U.K. Menopause is defined as having gone 12 months with no period. Menopause symptoms last on average 4-5yrs post menopause. So that is age 56. (although the upper limit is 12 years of symptoms post menopause).

You are experiencing perimenopause now at age 40 something. It’s up to you how badly you are affected. I would, based on averages, think you’d have a good chance of potentially needing HRT until age 56.

Ok
The appendix to the Lancet study referenced on the Cancer Reasearch U.K. webpage I linked has tables showing risk by age starting HRT (called MHT or Menopause Hormone Therapy in the study)

Supplementary appendix
This appendix formed part of the original submission and has been peer reviewed. We post it as supplied by the authors.
Supplement to: Collaborative Group on Hormonal Factors in Breast Cancer. Type and timing of menopausal hormone therapy and breast cancer risk: individual participant meta-analysis of the worldwide epidemiological evidence. Lancet 2019; published online Aug 29. dx.doi.org/10.1016/S0140-6736(19)31709-X.

www.thelancet.com/cms/10.1016/S0140-6736(19)31709-X/attachment/be2ed261-4ada-4ee7-9350-d3d9c072a859/mmc1.pdf

I took a few screen shots.

The Oxford studies one was the Million Women Study- have been criticised and discredited. They do not take into account the use of micronised progesterone. Some of the researchers seem to have a bias and decide on the results they want beforehand. Nick Panay- eminent UK HRT researcher and meno consultant- is on record in an online paper saying this.

The risk if there is one is tiny. It's around 4 extra cases per 1000 women over 5 years. And remember that this is based on the synthetic progestogens not Utrogestan. There is research from Denmark and France showing no increase in BC over many years using Utrogestan.

It has been known for years (I was told this by my consultant 15 years ago) that it's not estrogen that 'causes^ BC, but the type of progestin used. (women using estrogen-only HRT have fewer cases of BC than women never using HRT.)

@Discovereads You are doing Dr Newson a bit of a disservice! She may be 'just' a GP but she talks to and meets all the experts. She's not working in a bubble. She rates highly my own consultant who was a main speaker at the British Menopause Society annual conference a few years ago.

@Multicolouredsequins If you are in your 40s, the risks (whatever they are) do not start until you reach the age of menopause- 51. So you only start' counting' risks then.

You need to weigh up the benefits and quality of life.
When I discuss risks with my dr (as I'm a long-term user ) I am asked to think about the risks of NOT using HRT (which for me are a factor.)

It's all about your individual situation, your lifestyle, (which could be working, looking after ageing parents, having risk factors for heart disease, or osteoporosis, or even bowel cancer - HRT protects against these.)

Consultants will tell you that they have women in their 80s and 90s on HRT. Despite what people say, for some women the flushes and insomnia never stop. They need a small dose of estrogen for ever.

HRT may have risks, but they are very small. NOT using HRT has risks too. It's easy to forget that.

It's worth knowing that the article in the Lancet- the meta analysis - included ALL research some of which should never have been included.

It included studies that were not peer reviewed, studies that were observational, (based on what women answered on forms, known to be unreliable) and studies that were done on women with BC (so a bias already in place.) And of all the thousands of women it did include, the number using Utrogestan was under 50.

Not saying that study has no place, or that there are no risks, but if you care to research a bit more, you will find a lot of researchers pointing out its limitations.

Many thanks ladies for your intelligent and informed answers, they're really helpful. I need to spend some time studying the Lancet report, but those screen shots are really useful, Discovereads, thank you. The risk does seem pretty low overall. Some of the newer forms of hrt haven't been around long enough to have a great deal of research on them I suppose, but the general consensus seems to be that they're generally less risky than older types. I didn't think about counting user time from menopause, but the risks do seem very low for those taking it in their 40s or certainly not significantly higher than starting in the 50s instead. I'm sorry to hear about your mum and grandma, Discovereads. My mum went through it without hrt, and seems to think she wasn't too bad, but I still think her behaviour was dreadful at the time and was quite damaging to our relationship. She sleeps with a summer duvet all year round with an open window, although I've started doing this over the last year myself! She definitely had completely unreasonable rages. My gran suffered with overheating into her 80s, I never realized it was probably menopausal at the time. She had very brittle bones too. I'm sure she would have benefitted. Thank you for your help, it's much appreciated x

The Oxford studies one was the Million Women Study- have been criticised and discredited. That study was on breast cancer mortality so was not the Oxford study used in the collaboration to do a meta-analysis of breast cancer risk.

The risk if there is one is tiny. It's around 4 extra cases per 1000 women over 5 years.. Source for this? The Lancet paper I linked above reports “The absolute increase would be about 2.0 per 100 women (one in every 50 users) for oestrogen-plus-daily-progestagen MHT, 1.4 per 10 women (one in 70 users) for oestrogen-plus-intermittent-progestagen MHT, and 0.5 per 100 women (one in 200 users) for oestrogen-only MHT.”

If you are in your 40s, the risks (whatever they are) do not start until you reach the age of menopause- 51.. Source? The Lancet paper states that “Few women had started MHT at ages 30–39 years, but among those who were still current users 15 years later, there were significant risks with oestrogen-progestagen and oestrogen-only preparations (appendix p 40). Substantial numbers of women, however, had started MHT in each of the age groups 40–44, 45–49, 50–54, and 55–59 years, and for each group the RRs were similar” and “There was extensive information in the prospective studies on the effects of starting MHT use at various ages throughout the range 40–59 years. For women who had started anywhere in this age range the RRs among current users were similar, and were all highly significant.” and the tables I posted showed the increased risk by age and HRT type. Your statement makes no sense either because there are no risks if you take it due to premature menopause, as in before you would naturally start menopause. But natural menopause is not the same age for everyone. So you can’t take the average age of menopause and claim everyone is safe taking it before then when their age of menopause is going to be in a range, not exactly age 51.

This is not true. The Data Collection section details the criteria for inclusion in the meta-analysis. This was peer reviewed.

“Ineligible studies
Epidemiological studies that had collected information on MHT use and breast cancer risk, but not on the type or timing of MHT used, were ineligible for this meta-analysis. Principal investigators from 31 such studies have contributed to this collaboration but, while their data had been included in the Collaborative Group’s 1997 report70 on breast cancer risk associated with use of any type of MHT, they are not eligible to be included here. Studies with no controls were also ineligible, for example if expected breast cancer cases were calculated from national statistics71, as were studies that selectively recruited women with screen-detected breast cancer72 (as MHT reduces the sensitivity and specificity of mammographic screening, so restricting analyses to screen-detected tumours could attenuate the magnitude of any association73).”

”Data collection and definitions
For every participating study anonymised information was sought from principal investigators for every case (women with incident invasive breast cancer) and control (women without breast cancer) on socio-demographic, reproductive, anthropometric, and other potential confounding factors. The individual participant datasets contributed by principal investigators were checked and collated centrally so that the present analyses used definitions that were as similar as possible across studies. Apparent inconsistencies were rectified, where possible, by correspondence with the investigators. After the records had been checked and corrected, investigators were sent summary tables and listings of the variables from their study that were to be used in analyses, for final confirmation.
Prospective and retrospective studies
Studies contributing data to this meta-analysis were defined as “prospective” if information on MHT use and other factors was recorded before the diagnosis of breast cancer (and sensitivity analyses explored the effects of excluding from the prospective studies cases with onset less than 1 year after the last report about MHT use; Appendix p21). Prospective studies were included using a nested case-control design: cases were postmenopausal women with incident invasive breast cancer and up to 4 controls were selected for each case, matched by age, year of birth, and broad geographical region, as appropriate. Information on MHT use and other factors relates to that recorded up to the index date, ie the date of diagnosis for cases or the equivalent date for controls. Every prospective study contributed information on the cases and controls, but not on the populations at risk from which the cases and controls were drawn.
Studies were defined as “retrospective” if information on MHT use and other factors was recorded after the diagnosis of breast cancer. In the retrospective studies exposure information was recorded at a time when the cases would have known that they had been diagnosed with breast cancer and the controls would have known that they did not have breast cancer. In some retrospective studies the information on MHT use was not objectively verified (or not objectively verified in comparable ways). Hence, in some retrospective studies there is the potential not only for differential participation but also for differential recording of MHT exposure or of confounding factors between women already diagnosed with breast cancer and unaffected controls.”

And of all the thousands of women it did include, the number using Utrogestan was under 50.

This is a valid point as Utrogestan is relatively new so there’s not much on it yet. But what there is is very reassuring.

In the appendix, the Lancet paper I linked actually found that the breast cancer relative risk for <5 years use of oestrogen + micronised natural progesterone (Utrogestan) was 0.91, i.e. 9% lower than for never-users of HRT. Of course sample size was only 50 so could not be included in the main paper itself as a requirement was to have a sample size of at least 1000.

There is growing evidence that Utrogestan (micronised natural/bio-identical progesterone) is a far safer choice than synthetic progestins.

A large French study which assessed and compared the association between different HRTs and breast cancer risk, followed up 80,377 women for an average of 8.1 post-menopausal years, and found that compared with HRT never-use, there was no increased risk of breast cancer for oestrogen-progesterone (relative risk 1.00), whereas those using oestrogen plus progestins had a relative risk of 1.16-1.69 (depending on the progestin used).
Source: Risk of breast cancer by type of menopausal hormone therapy: a case-control study among post-menopausal women in France. PLoS ONE, 2013; 8(11): e78016. doi:10.1371/journal.pone.0078016

A meta-analysis of studies of postmenopausal women using progesterone vs. synthetic progestins in combination with oestrogen found that progesterone-oestrogen was associated with a lower risk of breast cancer compared with synthetic progestins (relative risk 0.67).
Source: progesterone vs. synthetic progestins and the risk of breast cancer: a systematic review and meta-analysis. Systematic Reviews, 2016; 5:121; DOI 10.1186/s13643-016-0294-5

Sorry for the masses of cut and pastes. I should have just said @JinglingHellsBells is correct in that the Lancet study is looking at both current and older forms of HRT. So you do have to take that into consideration that risks will be averaged across the decades and so would be higher than the risk today.

Some of the newer forms of hrt haven't been around long enough to have a great deal of research on them I suppose, but the general consensus seems to be that they're generally less risky than older types. Yes the evidence is growing that they are less risk to even no risk. But there hasn’t been time for very long term studies yet.

I can’t use utrogestan and have a mirena for progesterone, so slightly riskier. I decided to pretty well give up alcohol during the week, as my original HRT doctor, one of Dr Newson’s colleagues, said that drinking more than a small amount was a known BC risk which I could reduce if I wanted to help balance out the (small) progesterone risk. She also urged me to retain my healthy weight and keep up my exercise regime as other ways of helping reduce overall risk.

Many women on MN admit to drinking far more than the recommended level of alcohol per week, but are concerned about the HRT- related risk of BC (this point is not directed at you, OP). That white wine bottle in the fridge is probably our real enemy, sad to say.

I believe there’s research somewhere that shows that women on HRT are less likely to die of BC, if very slightly more likely to develop it.

I believe there’s research somewhere that shows that women on HRT are less likely to die of BC, if very slightly more likely to develop it.

There is an observational study…so not something to rely on
”Further reassuring evidence has been reported from Finland, studying 489,105 women using HRT in 1994 to 2009 and comparing breast cancer mortality rate with that in women not using HRT.

The study showed that the risk of dying from breast cancer was reduced in all users of HRT, regardless of duration of HRT use, age or whether the HRT was estrogen only or estrogen plus progestogen. For age, the largest reduction in risk was in the 50-59 age group, and for type of HRT, estrogen only users showed a larger risk reduction than estrogen plus progestogen.

Overall, in this Finnish population, 1 in 10 women with breast cancer will die from the disease, while 1 in 20 women with breast cancer who use HRT will do so.

While this is an observational study rather than a gold standard randomised controlled trial, these findings add more evidence to the understanding of association of breast cancer risk and of breast cancer mortality in women who use HRT.”
thebms.org.uk/2016/07/breast-cancer-mortality-use-hrt/

Thank you!

Blimey @Discovereads I don't have time to read everything you have posted!
But it is very contradictory to what I have read.

I suggest you read this about the Lancet paper. It's by Prof Michael Baum, a leading breast surgeon and who is regarded as an expert.

You will see that most of the points I raised are covered in his statement.

www.lattelounge.co.uk/professor-michael-baums-response-to-the-lancets-publication-of-a-report-on-hrt/

I think the press release put out by the Lancet is irresponsible and will undoubtedly lead to a drop in the use of HRT/ERT plunging thousands of women into a life of misery and for all we know shorten the lives of millions around the world. Remember there are more important threats to women’s lives than breast cancer, which is now only 7th in the league whilst those higher up the league might increase as a result of the withdrawal of oestrogen replacement therapy

“Statistical significance” does not always translate into “clinical significance”.

• Two principles in the practice of medicine – improve length of life (LOL) and quality of life (QOL). [HRT DOES BOTH. PLENTY OF STATS ON WOMEN USING HRT WHO LIVE LONGER.]

• In the modern era paternalism of the profession has been replaced by the principle of partnership whereby patients are helped to make informed decisions.

• The paper in today’s Lancet and its press release is alarmist and will frighten off thousands of women from taking HRT and is of no help for women in making informed choices.

• This paper is extremely difficult to understand even by an expert like me, and I would need many hours to ingest it all.
• Finally, the whole edifice might crumble if we correct the data for the numbers of “over diagnosed” cases from XS use of mammograms amongst women on HRT/ERT who are frightened of developing breast cancer. It thus becomes a self-fulfilling prophecy.

Also, to my knowledge, I don't know if these stats included lifestyle factors such as BMI, exercise, amount of alcohol drunk, family history, smoking, etc.

Thanks for the information and opinions, goes to show that stats can be presented in very different ways. I think it'll be interesting to see another study in 10 + years time based on current forms of hrt, but will realistically be longer until we have a true picture. What I've certainly taken away from my reading so far is the importance of keeping weight in check and avoiding alcohol. Its funny how scared we are of medication when many of us are risking our health daily in other, bigger ways which can be mostly controlled. Food for thought....

I have been shocked at some of the pseudo science and studies I've found online. There is often an undercurrent of misogyny with many. The worst I've read so far was a study from the US, about BC risk, basically using anecdotes to claim that the reason for most women using hrt was vanity. It was dressed up as a scientific study, but was really just women-bashing and talking about the importance of ageing naturally. Shocking really.

I think it'll be interesting to see another study in 10 + years time based on current forms of hrt, but will realistically be longer until we have a true picture.

My meno consultant said they think it is unlikely there will be any new major studies any time soon. (I've asked often is any are taking place.) Partly it's down to cost/ profit. HRT is dirt cheap and there is no real profit in it for the pharma companies. Also, it would need a trial of many 1000s of women, over many years, both for the trial and the long term outcomes.

Sadly, we all have to make a decision based on what is out there now. The only alternatives which are evidently in the pipeline are drugs that relieve flushes etc but don't stimulate the breasts.

'I think it'll be interesting to see another study in 10 + years time based on current forms of hrt'

Yes further information is essential, look at the confusion we have with current papers and interpretation.

I find it incredible that there aren't any studies in the pipeline apparently. If it really did protect against dementia and osteoporosis then you'd think it would be a public health issue. You would think the relevant departments would be very keen to prove the claims thus saving the nhs billions in the treatment of dementia and osteoporosis related fractures, yet its all a bit tumbleweedy on the current and planned research front.

The best we have is utrogestan is probably better than synthetic versions.

My GP said drinking 7 units of alcohol a week increased my risk of breast cancer more than hrt patches.

Really we should be talking about alcohol and weight as problematic rather than hrt

Is HRT cheap? Why are we paying double prescription charges for oestrogen/progesterone patches then? Surely someone is profiting from that?

You don’t have to pay that if you’re in England. If you even get only 1 prescription per month, it is cheaper to buy a prepaid prescription certificate from the NHS.
www.gov.uk/get-a-ppc

Re prescription charges, if you can only get monthly prescriptions, the yearly prescription payment is cheaper. However, if you can get 3 or 6 monthly prescriptions and don’t need any other prescription items, you’re better just paying 2x2 or 4x2 prescrition charges.

Thanks both. I get 4 boxes in each prescription. So 3 prescriptions a year at £18 each.

Any idea why 4 and not 6?! No me neither