Weighing the relative risks: estradiol, osteoporosis, breast cancer

#1

This is partly a rant, and may be of no interest if you’re not a woman thinking about these issues. But I would certainly appreciate inputs.

My osteoporosis is severe: my T score at the right hip is negative 4.0. FRAX says that my risk of a hip fracture in the next five years exceeds 50% and my risk of a major osteoporotic fracture – spine, wrist, foot – exceeds 65%. I have already had fragility fractures.

Doing all I can think of – resistance training, vibration, diet, protein, creatine, supplements, ralosifene, including DHEA, and about to start LDN and teraparatide. But teraparatide will not get me where I need to be, given where I am now.

I want to add estradiol (patch). No doctor will prescribe because: 6 years ago I had a very tiny, very indolent estrogen/progesterone sensitive breast cancer. The three “tumors” were under 2 mm. The Ki67 was 1%. (Ki67 is a protein that manifests on the surface of the cell when it is about to divide. So it is a measure of whether the cancer is active or indolent. Anything under 14% is considered indolent. Mine was 1%. Should add that you have to ask for this (Ki67)–or you won’t get it.) I actually believe that the many needle biopsies knocked some DCIS cells out of their membranes – and “caused” the cancer. But, be that as it may, the cancer was about as much of a nothingburger as a cancer can be.

OK I understand that doctors have to follow guidelines. But I don’t. In fact I used estradiol and progesterone for 26 years, ordering it from Canada, after my obgyn decided I had been on it long enough.

So, now I know, because more recent research has shown, that estradiol has a miniscule to zero effect on stimulating breast cancer. Now it is known that progesterone is the culprit, the hormone that actually stimulates the breast cancer. And, I am taking raloxifene, which prevents the sensors in the breast cells from being able to take up whatever circulating estrogen there may be. (Raloxifene is a SERM-- selective estrogen reuptake modulator).

If I were to have a recurrence it would be treatable. But I feel that the probability, given the initial episode, is truly miniscule.

If I break a hip, my life as I live it now would be over (greater than 50% probability) or I would be dead (30% probability).

It seems so clear to me that I should throw everything at the osteoporosis that I possibly can. It is by far the greatest threat. But the doctors do not see it that way. This is all so frustrating but I am so grateful that I can get around this –

So many women have now decided to use estradiol that the patches are stocked out. Maulik can’t get them. But I will stay in touch so that I can grab some when they get restocked.

Anyone here who is taking rapamycin has gone through a version of this – weighing the potential benefits and risks and making a decision about whether it is a good intervention for you personally. This is just a version of this – having to decide for yourself what’s best for you. You all have empowered me to decide things for myself, even though this has nothing to do with rapamycin.

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#2

Does it mean both did not prevent your osteoporosis?

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#3

The estradiol and progesterone did not prevent the osteoporosis but I do believe it slowed the progression. The osteoporosis has gotten much worse since I stopped using the estradiol and progesterone six years ago. I believe I should have gone back on it a few years ago, and also started teriparatide a few years ago. The best I can hope for now, I believe, is halting the progression.

I have so many risk factors for osteoporosis – genetics, early menopause, small body, and I did not do much about building muscle as a young person.

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#4

I’ve been lifting weights regularly since college (my favorite workout), but at 52 was diagnosed with osteopenia anyway. At about the same time I started BHRT for menopause. Fast forward 8 yrs and I was dreading a new dexa scan. To my huge surprise, my bones were fine - according to my doc, I have bones of a 30 yr old woman. So yeah, I really think the estrogen (I use cream, combo of estradiol, estriol, testosterone and progesterone) did the trick.

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#5

I find the topic confusing. On one hand, we hear to couple estrogens with progesterone to reduce cancer risk… on the other hand, a doc I consulted with suggested I add more progesterone to use as a sleep aide… ffwd, my regular doc said ‘you know more progesterone increases your cancer risk, right? ‘ (Needless to say, I stopped taking extra).

My cousin just told me her doctor prescribed her Bio-est (not just estradiol, but also estriol). Apparently this is not the ideal combo for bones, but it potentially might lower the slight cancer risk. I only learned about this yesterday, so I’m just sharing it as something to investigate due to your past cancer. I have no idea why her doc suggested this vs good ol tried and true estrodial gel.

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#6

Yes, the whole subject of osteoporosis is confusing.

I was all set to start teriparatide – and still may – but –

I went back into Promethease to revisit the narrative around my “weak bones”. This time, I read the supporting research too. Promethease showed that I am homozygous on several SNP’s for the risk allele having to do with how the WNT16 processes --sclerostin. So, seeing that, I asked AI whether romosozumab (Evinity) or teriparatide (generic Forteo) would be a better drug. It said that Evinity would be signficantly better! (It was developed to treat a rare bone disorder that arises from an over abundance of sclerostin.)

After testing parathyroid hormone and calcium, my endocrinologist was all set to prescribe teriparatide. But now I asked him (sent all the info) to prescribe romosuzumab instead. I don’t have answer yet.

Romusuzumab would cost me a lot, lot more given my medicare advantage plan deductible. It is administered as an injection once a month in the doctor’s office. So it is billed as a procedure, not a drug. Ouch! (the pocketbook, not the needle). And would probably have to wait another eternity to get scheduled. But, it does seem clear that, despite the cardio warnings, it would be a better option for me personally.

Anyone taking or considering Evinity? I felt so strongly that I would not take it, but am grateful for the combination of genetic information and AI, which has shown me that I should change my mind. I hope my doctor and insurance will agree.

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#7

I would definitely take the minimal risk of taking estradiol & progesterone. Breaking hips will end quality of life. I’ve lost friends that way.

I’ve been over weight most of 75 years that I’ve lived, so osteoporosis is not a concern. That’s about the only benefit to being fat. Thankfully with the GLP-1 agonists, my weight is under control & my bones are strong. 9 months ago ago, I started HRT, long past the “recommended” window of within 10 years of post menopause. It has helped with urogenital issues.

If you travel, estradiol is very cheap in Thailand & does not require a prescription.

Good luck. I like your thoroughness.

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#8

This paper (which is one of my favourite papers)
https://www.nature.com/articles/s43587-021-00105-8

Implies citrate would assist with osteoporosis

I am not aware of anyone trying it and it would be interesting to find out what effect it has.

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#9

Hi I belong to a FB forum of women over 60 who are using BHRT for first time some in their 70s. Many are using it for OP and seeing good results. I know this is anecdotal accounts but happy to share the FB link for you to explore? This is also true for my Inspire OP group out of interest. Of course many battle to get BHRT even prescribed but persistence pays off. I just want to add they are all microdosing and transdermal not oral.

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#10

Michele, thanks for reminding me about Inspire. It has been a while since I looked at the site.

#11

John,

Reminder: I’m taking your citrate protocol. My osteoperios has not gotten worse.

Does this paper suggest I should consider adding acetate?

#12

The problem is that the ACSS2 enzyme can be self inhibited so although some acetate in some way (not as acid) might be helpful it may not actually increase nuclear levels of acetyl-CoA.

ACLY, however, when acetylated translocates to the nucleus. That is the enzyme that converts citrate to acetyl-CoA.

I am glad to hear your osteoporosis has not got worse. In many ways that is the first step and hopefully there can be a step to improve.

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#13

John, just looked at your protocol. So much in-depth information: thank you.

I’m certain there is some magnesium citrate in my big tub of supplements – will dig it out and rejigger with the threonate/glycinate –

#14

Potassium citrate might do double duty here as potassium has its own benefits. Of course dosage matters to not overdo it.

#15

I’d personally keep magnesium glycinate and add potassium citrate on top. I actually do do it though right now I’m in de facto washout out of laziness to refill my potassium citrate pills. It’s useful for kidney stones too, to which I’m prone.

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#16

Among a group of healthy elderly persons without osteoporosis, treatment with K-citrate for 24 months resulted in a significant increase in aBMD and volumetric BMD at several sites tested, while also improving bone microarchitecture. Based on the effect on fracture prediction, an effect on future fractures by K-citrate is possible.

try it

#17

That’s quite a small dose. It is true that citrate has an alkanising effect, but it does other things as well (not least changing acetylation levels).

#18

I think it is important to balance out the cations.

#19

What do you mean by that? I can only think of high school chemistry and balancing both sides of a chemical reaction which I’m sure isn’t to the purpose.

#20

Balance between K Mg and Na