FDA removed black box warning for HRT

[Anonymous]

Re heart disease, the most important study is proably Hodis & Mack 2022, because it pulls together data from previous randomized trials, meta-analyses, and observational studies. This paper shows that timing is everything. When initiated in women <60 or <10 years since menopause, HRT reduces coronary heart disease events and all-cause mortality by roughly 30–50%, with no increase in stroke in this age/timing group. When started later, though, HRT shows no benefit and may be associated with increased risks. https://pmc.ncbi.nlm.nih.gov/articles/PMC9178928

There are plenty of other papers on the topic, but Hodis & Mack incorporate and synthesize them.

As with type 2 diabetes, HRT does not have FDA approval for prevention of heart disease.

And, similar to type 2 diabetes, The NAMS 2022 statement does not recommend starting HRT primarily to prevent cardiovascular disease, but they acknowledge that randomized trials, meta-analyses, and observational data suggest fewer cardiovascular events in *appropriately selected* (i.e. younger women who initiate HRT near menopause), and that overall benefits outweigh risks for most healthy symptomatic women <60 or within 10 years of menopause.

[Anonymous]

Anonymous wrote:

Anonymous wrote:

Anonymous wrote:For those who want data and official medical positions, here's some research on HRT and type 2 diabetes. Summarizing, it shows that across multiple large randomized trials and meta-analyses, HRT with estrogen (with or without progestin) reduces the risk of developing type 2 diabetes on the order of 20–30% and improves insulin resistance and glucose control:

Margolis KL et al., Diabetologia 2004 — 15,641 postmenopausal women randomized and placebo controlled: https://link.springer.com/article/10.1007/s00125-004-1448-x

Mauvais-Jarvis et al. 2017 – Endocrine Reviews
https://academic.oup.com/edrv/article/38/3/173/3063786

Note that HRT does not have an FDA-approved prevention indication.

The North American Menopause Society in their 2022 position statement said that they do NOT recommend starting HRT primarily to prevent diabetes, but that a diabetes-preventive effect is a real, evidence-based benefit in appropriate women (younger, early postmenopause): https://pubmed.ncbi.nlm.nih.gov/35797481/

Sure. But since we are being so detailed about the absolute of HRT it is also important to be detailed about the absolute benefits: “The cumulative incidence of treated diabetes was 3.5% in the hormone therapy group and 4.2%”

So there was 0.7% fewer diabetes cases in the HRT group. Hardly a stunning number on an individual level. These findings are probably most important to conclude that a woman with diabetes or at risk of it can take HRT without a negative impact on diabetes.

Oh! Oh! Now do breast cancer risk!!!!! Let’s see those research skillz that clearly pay the bills. That is, if you’re not busy getting a lube-free fk from your devoted DH right now as you stalk this thread all day.

Wow. You truly are not making the case that the HRT discourse is impartial.

Take a step back please.

[Anonymous]

Anonymous wrote:Re heart disease, the most important study is proably Hodis & Mack 2022, because it pulls together data from previous randomized trials, meta-analyses, and observational studies. This paper shows that timing is everything. When initiated in women <60 or <10 years since menopause, HRT reduces coronary heart disease events and all-cause mortality by roughly 30–50%, with no increase in stroke in this age/timing group. When started later, though, HRT shows no benefit and may be associated with increased risks. https://pmc.ncbi.nlm.nih.gov/articles/PMC9178928

There are plenty of other papers on the topic, but Hodis & Mack incorporate and synthesize them.

As with type 2 diabetes, HRT does not have FDA approval for prevention of heart disease.

And, similar to type 2 diabetes, The NAMS 2022 statement does not recommend starting HRT primarily to prevent cardiovascular disease, but they acknowledge that randomized trials, meta-analyses, and observational data suggest fewer cardiovascular events in *appropriately selected* (i.e. younger women who initiate HRT near menopause), and that overall benefits outweigh risks for most healthy symptomatic women <60 or within 10 years of menopause.

Thanks. part of my concern with this research is that it uses (I believe) standardized dosages, types and delivery methods of hormones. Whereas there is much more varied in how HRT is actually prescribed in real life.

[Anonymous]

Anonymous wrote:

Anonymous wrote:

Anonymous wrote:For those who want data and official medical positions, here's some research on HRT and type 2 diabetes. Summarizing, it shows that across multiple large randomized trials and meta-analyses, HRT with estrogen (with or without progestin) reduces the risk of developing type 2 diabetes on the order of 20–30% and improves insulin resistance and glucose control:

Margolis KL et al., Diabetologia 2004 — 15,641 postmenopausal women randomized and placebo controlled: https://link.springer.com/article/10.1007/s00125-004-1448-x

Mauvais-Jarvis et al. 2017 – Endocrine Reviews
https://academic.oup.com/edrv/article/38/3/173/3063786

Note that HRT does not have an FDA-approved prevention indication.

The North American Menopause Society in their 2022 position statement said that they do NOT recommend starting HRT primarily to prevent diabetes, but that a diabetes-preventive effect is a real, evidence-based benefit in appropriate women (younger, early postmenopause): https://pubmed.ncbi.nlm.nih.gov/35797481/

Sure. But since we are being so detailed about the absolute of HRT it is also important to be detailed about the absolute benefits: “The cumulative incidence of treated diabetes was 3.5% in the hormone therapy group and 4.2%”

So there was 0.7% fewer diabetes cases in the HRT group. Hardly a stunning number on an individual level. These findings are probably most important to conclude that a woman with diabetes or at risk of it can take HRT without a negative impact on diabetes.

Oh! Oh! Now do breast cancer risk!!!!! Let’s see those research skillz that clearly pay the bills. That is, if you’re not busy getting a lube-free fk from your devoted DH right now as you stalk this thread all day.

I did that above.

[Anonymous]

Anonymous wrote:

Anonymous wrote:For those who want data and official medical positions, here's some research on HRT and type 2 diabetes. Summarizing, it shows that across multiple large randomized trials and meta-analyses, HRT with estrogen (with or without progestin) reduces the risk of developing type 2 diabetes on the order of 20–30% and improves insulin resistance and glucose control:

Margolis KL et al., Diabetologia 2004 — 15,641 postmenopausal women randomized and placebo controlled: https://link.springer.com/article/10.1007/s00125-004-1448-x

Mauvais-Jarvis et al. 2017 – Endocrine Reviews
https://academic.oup.com/edrv/article/38/3/173/3063786

Note that HRT does not have an FDA-approved prevention indication.

The North American Menopause Society in their 2022 position statement said that they do NOT recommend starting HRT primarily to prevent diabetes, but that a diabetes-preventive effect is a real, evidence-based benefit in appropriate women (younger, early postmenopause): https://pubmed.ncbi.nlm.nih.gov/35797481/

Sure. But since we are being so detailed about the absolute of HRT it is also important to be detailed about the absolute benefits: “The cumulative incidence of treated diabetes was 3.5% in the hormone therapy group and 4.2%”

So there was 0.7% fewer diabetes cases in the HRT group. Hardly a stunning number on an individual level. These findings are probably most important to conclude that a woman with diabetes or at risk of it can take HRT without a negative impact on diabetes.

Correct, the absolute difference was 0.7%.
That represents a 21% reduction in diabetes risk relative to the placebo -- that's the real effect.

Note that the data were from the WHI, which had an average age of 63, and enrolled many women who were more than 10 years post menopause. The effect would likely be larger among women <60 but we don't have that data.

[Anonymous]

Anonymous wrote:

Anonymous wrote:

Anonymous wrote:

Anonymous wrote:

Anonymous wrote:

Anonymous wrote:To the people who think hormone replacement therapy is just a grift from the wellness industry why aren’t you looking at the other side of the grift? It’s not as if women who don’t choose hormone replacement theory are aging naturally, lol

I’m a healthcare policy walk who can answer any question on Medicare spend and is deep on the data of what happens to aging women in America. Anyone who says women are aging naturally are either deeply delusional or deeply denial and throw in a dose of deeply ignorant.

Do you have any idea of the number of postmenopausal women who are on antidepressants, anti-anxiety meds, prescriptions sleep aids, hypertension drugs, statins, osteoporosis medications, treatments for UTI, treatments for sexual dysfunction, and the list goes on. Not to mention the care that we spend on frailty from hip fractures, chronic pain meds from bone breaks, hospitalizations caused from UTIs in older women and again the list goes on.

Do you know a lot of dentists will not treat women who are on osteoporosis meds beyond basic cleanings because the mortality rate for any kind of dental surgery for women on these meds is so high? Have you thought about what might happen if you need to go on osteoporosis meds, and something happens to your dental health. You probably should.

While I agree that the evidence does not seem to be there to just put every woman on HRT for primary prevention - if women are having symptoms there does seem to be good evidence that it does help prevent the need for some of these other medical conditions.

I’d be very wary of anyone trying to stop any kind of discourse on HRT. It’s just a grift on the other side and frankly, the spend is a lot higher than what we would spend on HRT. Again, I will stress that I do not think every woman should be on HRT, but to not even entertain the need for research and do not even question The bad advice women got 25 years ago from a deeply flawed that has been retracted, there’s something really disturbing going on there.

There’s zero evidence that HRT’s “prevent” all the things you listed. HRTs are very effective for one thing - hot flashes. There is good evidence for osteoporosis. But women are still going to need statins, SSRIs, therapy, blood pressure meds, even when HRT.

It's important to pause here to distinguish between indication (what offical approval does the therapy have) and effectiveness, as well as the standards of evidence for treatment vs. prevention.

HRT is indicated for the *treatment* of hot flashes and other vasomotor symptoms, genitourinary symptoms, osteoporosis, and other issues related to estrogen deficiency. It is also indicated for the *prevention* of osteoporosis in at-risk postmenopausal women. It has both treatment and prevention indication for osteoporosis, because the biological mechanism is direct and clear (and has been confirmed in every major study).

But it's much harder to get preventive indications when biological mechanisms aren't direct, and/or don't apply equally to all populations-- for example, cardiovascular disease and type 2 diabetes. These diseases are complex, and they involve multiple pathways. So it's much, much harder to meet a blanket indication standard. That said, multiple randomized trials and meta analyses do suggest quite strongly that HRT helps prevent type 2 diabetes. And newer trials and re-analysis of the women's health initiative (removing women who had already developed heart disease, for example) offer evidence that women who begin HRT before 60 have lower rates of heart-disease and all-cause mortality. But because the data are more complex and more nuanced, the FDA can’t write a blanket approval for prevention the way it can for treating hot flashes or preserving bone.

TLDR: Evidence is not the same thing as approval. I think that's partly what makes this discussion so challenging.

I don’t disagree with what you wrote. I was responding to the PP who seemed to be trying to claim that HRT can replace the medications/therapies/lifestyle interventions for basically all chronic diseases. No. Even if HRT has some protective effect on heart disease, depression, diabetes, joint pain, etc, women will still need to take statins, GLPs, SSRIs, get therapy, etc. it doesn’t cure any of those things, even in the most positive of trials.

But no one wrote that. You’ve misinterpreted that post, per your apparent usual.

Are you a researcher or a physician?

Many people on this thread have implied or stated that HRT is more beneficial than it is. That particular PP seemed to be implying that HRT is so beneficial that it will meaningfully reduce the number of women who need diabetes meds, SSRIs, and osteoporosis meds.

+1

PP didn’t imply at all:
“ if women are having symptoms there does seem to be good evidence that it does help prevent the need for some of these other medical conditions. ”

[Anonymous]

Anonymous wrote:

Anonymous wrote:For those who want data and official medical positions, here's some research on HRT and type 2 diabetes. Summarizing, it shows that across multiple large randomized trials and meta-analyses, HRT with estrogen (with or without progestin) reduces the risk of developing type 2 diabetes on the order of 20–30% and improves insulin resistance and glucose control:

Margolis KL et al., Diabetologia 2004 — 15,641 postmenopausal women randomized and placebo controlled: https://link.springer.com/article/10.1007/s00125-004-1448-x

Mauvais-Jarvis et al. 2017 – Endocrine Reviews
https://academic.oup.com/edrv/article/38/3/173/3063786

Note that HRT does not have an FDA-approved prevention indication.

The North American Menopause Society in their 2022 position statement said that they do NOT recommend starting HRT primarily to prevent diabetes, but that a diabetes-preventive effect is a real, evidence-based benefit in appropriate women (younger, early postmenopause): https://pubmed.ncbi.nlm.nih.gov/35797481/

Sure. But since we are being so detailed about the absolute of HRT it is also important to be detailed about the absolute benefits: “The cumulative incidence of treated diabetes was 3.5% in the hormone therapy group and 4.2%”

So there was 0.7% fewer diabetes cases in the HRT group. Hardly a stunning number on an individual level. These findings are probably most important to conclude that a woman with diabetes or at risk of it can take HRT without a negative impact on diabetes.

This PP doesn't understand statistics. She doesn't know the difference between absolute difference and relative risk, so her post is seriously misleading.

Here's an example: Using seatbelts lowers your risk of death in a serious car crash by 50%. If you don't use a seatbelt and you get in a serious crash, your risk of dying is 43%. If you use a seatbelt, the risk drops to 21%. So by using a seatbelt, you cut your risk in half! Pretty good, right?

But the chances of anyone dying in a serious car crash isn't especially high. So the *absolute* difference between seat belt users and non-users -- 0.0005% -- looks absolutely tiny. That tiny-seeming number = cutting your chance of death in half.

So when PP says, 0.7% (absolute difference) is "hardly a stunning number on an individual level," she's completely misunderstanding what the appropriate "individual" number is. The "individual" number is the decrease in the relative risk an individual might have. That number is 21%, and that is the effect of HRT.

Whether you think a 21% reduction is a compelling number or not is up to you.

[Anonymous]

Anonymous wrote:

Anonymous wrote:

Anonymous wrote:For those who want data and official medical positions, here's some research on HRT and type 2 diabetes. Summarizing, it shows that across multiple large randomized trials and meta-analyses, HRT with estrogen (with or without progestin) reduces the risk of developing type 2 diabetes on the order of 20–30% and improves insulin resistance and glucose control:

Margolis KL et al., Diabetologia 2004 — 15,641 postmenopausal women randomized and placebo controlled: https://link.springer.com/article/10.1007/s00125-004-1448-x

Mauvais-Jarvis et al. 2017 – Endocrine Reviews
https://academic.oup.com/edrv/article/38/3/173/3063786

Note that HRT does not have an FDA-approved prevention indication.

The North American Menopause Society in their 2022 position statement said that they do NOT recommend starting HRT primarily to prevent diabetes, but that a diabetes-preventive effect is a real, evidence-based benefit in appropriate women (younger, early postmenopause): https://pubmed.ncbi.nlm.nih.gov/35797481/

Sure. But since we are being so detailed about the absolute of HRT it is also important to be detailed about the absolute benefits: “The cumulative incidence of treated diabetes was 3.5% in the hormone therapy group and 4.2%”

So there was 0.7% fewer diabetes cases in the HRT group. Hardly a stunning number on an individual level. These findings are probably most important to conclude that a woman with diabetes or at risk of it can take HRT without a negative impact on diabetes.

This PP doesn't understand statistics. She doesn't know the difference between absolute difference and relative risk, so her post is seriously misleading.

Here's an example: Using seatbelts lowers your risk of death in a serious car crash by 50%. If you don't use a seatbelt and you get in a serious crash, your risk of dying is 43%. If you use a seatbelt, the risk drops to 21%. So by using a seatbelt, you cut your risk in half! Pretty good, right?

But the chances of anyone dying in a serious car crash isn't especially high. So the *absolute* difference between seat belt users and non-users -- 0.0005% -- looks absolutely tiny. That tiny-seeming number = cutting your chance of death in half.

So when PP says, 0.7% (absolute difference) is "hardly a stunning number on an individual level," she's completely misunderstanding what the appropriate "individual" number is. The "individual" number is the decrease in the relative risk an individual might have. That number is 21%, and that is the effect of HRT.

Whether you think a 21% reduction is a compelling number or not is up to you.

Great now do the breast cancer and stroke risk.

[Anonymous]

Anonymous wrote:

Anonymous wrote:

Anonymous wrote:

Anonymous wrote:For those who want data and official medical positions, here's some research on HRT and type 2 diabetes. Summarizing, it shows that across multiple large randomized trials and meta-analyses, HRT with estrogen (with or without progestin) reduces the risk of developing type 2 diabetes on the order of 20–30% and improves insulin resistance and glucose control:

Margolis KL et al., Diabetologia 2004 — 15,641 postmenopausal women randomized and placebo controlled: https://link.springer.com/article/10.1007/s00125-004-1448-x

Mauvais-Jarvis et al. 2017 – Endocrine Reviews
https://academic.oup.com/edrv/article/38/3/173/3063786

Note that HRT does not have an FDA-approved prevention indication.

The North American Menopause Society in their 2022 position statement said that they do NOT recommend starting HRT primarily to prevent diabetes, but that a diabetes-preventive effect is a real, evidence-based benefit in appropriate women (younger, early postmenopause): https://pubmed.ncbi.nlm.nih.gov/35797481/

Sure. But since we are being so detailed about the absolute of HRT it is also important to be detailed about the absolute benefits: “The cumulative incidence of treated diabetes was 3.5% in the hormone therapy group and 4.2%”

So there was 0.7% fewer diabetes cases in the HRT group. Hardly a stunning number on an individual level. These findings are probably most important to conclude that a woman with diabetes or at risk of it can take HRT without a negative impact on diabetes.

This PP doesn't understand statistics. She doesn't know the difference between absolute difference and relative risk, so her post is seriously misleading.

Here's an example: Using seatbelts lowers your risk of death in a serious car crash by 50%. If you don't use a seatbelt and you get in a serious crash, your risk of dying is 43%. If you use a seatbelt, the risk drops to 21%. So by using a seatbelt, you cut your risk in half! Pretty good, right?

But the chances of anyone dying in a serious car crash isn't especially high. So the *absolute* difference between seat belt users and non-users -- 0.0005% -- looks absolutely tiny. That tiny-seeming number = cutting your chance of death in half.

So when PP says, 0.7% (absolute difference) is "hardly a stunning number on an individual level," she's completely misunderstanding what the appropriate "individual" number is. The "individual" number is the decrease in the relative risk an individual might have. That number is 21%, and that is the effect of HRT.

Whether you think a 21% reduction is a compelling number or not is up to you.

Great now do the breast cancer and stroke risk.

These were done upthread, but here are the numbers in one place:

Breast cancer (combined HRT): risks increase
Absolute increase: 0.5% over 5 years
Relative risk increase: 20% to 30% over 5 years
This is the equivalent of going from 23 per 1000 (non-HRT baseline) to ~28 per 1000 (with HRT) over 5 years.
Net effect: 5 extra cases per 1000 over 5 years.

Breast cancer (estrogen only HRT)
No increased risk, and WHI actually showed a small reduction of risk. But estrogen-only applies only to women without a uterus.
Net effect: 0 or possibly protective.

Type 2 diabetes: risks decrease
Absolute decrease: ~1% to 3% over 5 years
Relative risk reduction: ~20% to 30%
This is the equivalent of going from 50 cases per 1000 (non-HRT baseline for healthy women) to 35-40 per 1000 (with HRT) over 5 years.
Net effect: 10 to 15 fewer cases over 5 years

Cardiovascular disease: risks decrease*:
Absolute decrease: 0.6% to 2% over 5 years
Relative risk reduction: 30 to 50%
This is the equivalent of going from ~20–40 per 1000 (non-HRT baseline) to ~10–20 events per 1000 over 5 years
Net effect: 10-20 fewer serious coronary heart disease events (heart attacks and cardiac death) per 1,000 over 5 years
*in women who start HRT <60 or are within 10 years of menopause, the "early initiation" window. HRT is generally not recommended to initiate in older women.

But even this doesn't tell the whole story. Cardiovascular disease is the #1 killer of women -- far more common than breast cancer (35% of deaths vs. <3% ). So a risk relative reduction of 30-50% in coronary heart disease among early starters translates into vast population benefits. This is why trials show all-cause mortality falls by ~30-40% in early starters.

Stroke: data show no increased risk for women who begin HRT (transdermal estrogen, micronized progesterone) under 60 years of age or within 10 years of menopause. (There was a small increased stroke risk with the older formulations, and risks increased with age).

MOST IMPORTANT CAVEAT: we do NOT all have the same risks of diseases. Family history, BMI, BP, lifestyle, personal medical history, etc., all matter here. This is why the decision to take or not take HRT should never be one-size-fits all. So even with all the available data on risks and benefits, you really must discuss the decision with a health care provider who knows you, and understands your specific risk profile.

Hope this is helpful to anyone still reading. I'm going to bow out of this thread now, hoping that most readers can discern best-available data from strong opinions. Wishing you all well as we navigate our respective choices.

[Anonymous]

Anonymous wrote:

Anonymous wrote:

Anonymous wrote:

Anonymous wrote:

Anonymous wrote:For those who want data and official medical positions, here's some research on HRT and type 2 diabetes. Summarizing, it shows that across multiple large randomized trials and meta-analyses, HRT with estrogen (with or without progestin) reduces the risk of developing type 2 diabetes on the order of 20–30% and improves insulin resistance and glucose control:

Margolis KL et al., Diabetologia 2004 — 15,641 postmenopausal women randomized and placebo controlled: https://link.springer.com/article/10.1007/s00125-004-1448-x

Mauvais-Jarvis et al. 2017 – Endocrine Reviews
https://academic.oup.com/edrv/article/38/3/173/3063786

Note that HRT does not have an FDA-approved prevention indication.

The North American Menopause Society in their 2022 position statement said that they do NOT recommend starting HRT primarily to prevent diabetes, but that a diabetes-preventive effect is a real, evidence-based benefit in appropriate women (younger, early postmenopause): https://pubmed.ncbi.nlm.nih.gov/35797481/

Sure. But since we are being so detailed about the absolute of HRT it is also important to be detailed about the absolute benefits: “The cumulative incidence of treated diabetes was 3.5% in the hormone therapy group and 4.2%”

So there was 0.7% fewer diabetes cases in the HRT group. Hardly a stunning number on an individual level. These findings are probably most important to conclude that a woman with diabetes or at risk of it can take HRT without a negative impact on diabetes.

This PP doesn't understand statistics. She doesn't know the difference between absolute difference and relative risk, so her post is seriously misleading.

Here's an example: Using seatbelts lowers your risk of death in a serious car crash by 50%. If you don't use a seatbelt and you get in a serious crash, your risk of dying is 43%. If you use a seatbelt, the risk drops to 21%. So by using a seatbelt, you cut your risk in half! Pretty good, right?

But the chances of anyone dying in a serious car crash isn't especially high. So the *absolute* difference between seat belt users and non-users -- 0.0005% -- looks absolutely tiny. That tiny-seeming number = cutting your chance of death in half.

So when PP says, 0.7% (absolute difference) is "hardly a stunning number on an individual level," she's completely misunderstanding what the appropriate "individual" number is. The "individual" number is the decrease in the relative risk an individual might have. That number is 21%, and that is the effect of HRT.

Whether you think a 21% reduction is a compelling number or not is up to you.

Great now do the breast cancer and stroke risk.

These were done upthread, but here are the numbers in one place:

Breast cancer (combined HRT): risks increase
Absolute increase: 0.5% over 5 years
Relative risk increase: 20% to 30% over 5 years
This is the equivalent of going from 23 per 1000 (non-HRT baseline) to ~28 per 1000 (with HRT) over 5 years.
Net effect: 5 extra cases per 1000 over 5 years.

Breast cancer (estrogen only HRT)
No increased risk, and WHI actually showed a small reduction of risk. But estrogen-only applies only to women without a uterus.
Net effect: 0 or possibly protective.

Type 2 diabetes: risks decrease
Absolute decrease: ~1% to 3% over 5 years
Relative risk reduction: ~20% to 30%
This is the equivalent of going from 50 cases per 1000 (non-HRT baseline for healthy women) to 35-40 per 1000 (with HRT) over 5 years.
Net effect: 10 to 15 fewer cases over 5 years

Cardiovascular disease: risks decrease*:
Absolute decrease: 0.6% to 2% over 5 years
Relative risk reduction: 30 to 50%
This is the equivalent of going from ~20–40 per 1000 (non-HRT baseline) to ~10–20 events per 1000 over 5 years
Net effect: 10-20 fewer serious coronary heart disease events (heart attacks and cardiac death) per 1,000 over 5 years
*in women who start HRT <60 or are within 10 years of menopause, the "early initiation" window. HRT is generally not recommended to initiate in older women.

But even this doesn't tell the whole story. Cardiovascular disease is the #1 killer of women -- far more common than breast cancer (35% of deaths vs. <3% ). So a risk relative reduction of 30-50% in coronary heart disease among early starters translates into vast population benefits. This is why trials show all-cause mortality falls by ~30-40% in early starters.

Stroke: data show no increased risk for women who begin HRT (transdermal estrogen, micronized progesterone) under 60 years of age or within 10 years of menopause. (There was a small increased stroke risk with the older formulations, and risks increased with age).

MOST IMPORTANT CAVEAT: we do NOT all have the same risks of diseases. Family history, BMI, BP, lifestyle, personal medical history, etc., all matter here. This is why the decision to take or not take HRT should never be one-size-fits all. So even with all the available data on risks and benefits, you really must discuss the decision with a health care provider who knows you, and understands your specific risk profile.

Hope this is helpful to anyone still reading. I'm going to bow out of this thread now, hoping that most readers can discern best-available data from strong opinions. Wishing you all well as we navigate our respective choices.

Right - so the absolute risks AND absolute benefits are small. And we won’t get into how you are cherry picking studies, the limits of observational studies, and the fact that there are so many possible combinations of dosages and types of hormones administered that are not studied in detail.

[Anonymous]

Anonymous wrote:

Anonymous wrote:

Anonymous wrote:

Anonymous wrote:

Anonymous wrote:

Anonymous wrote:For those who want data and official medical positions, here's some research on HRT and type 2 diabetes. Summarizing, it shows that across multiple large randomized trials and meta-analyses, HRT with estrogen (with or without progestin) reduces the risk of developing type 2 diabetes on the order of 20–30% and improves insulin resistance and glucose control:

Margolis KL et al., Diabetologia 2004 — 15,641 postmenopausal women randomized and placebo controlled: https://link.springer.com/article/10.1007/s00125-004-1448-x

Mauvais-Jarvis et al. 2017 – Endocrine Reviews
https://academic.oup.com/edrv/article/38/3/173/3063786

Note that HRT does not have an FDA-approved prevention indication.

The North American Menopause Society in their 2022 position statement said that they do NOT recommend starting HRT primarily to prevent diabetes, but that a diabetes-preventive effect is a real, evidence-based benefit in appropriate women (younger, early postmenopause): https://pubmed.ncbi.nlm.nih.gov/35797481/

Sure. But since we are being so detailed about the absolute of HRT it is also important to be detailed about the absolute benefits: “The cumulative incidence of treated diabetes was 3.5% in the hormone therapy group and 4.2%”

So there was 0.7% fewer diabetes cases in the HRT group. Hardly a stunning number on an individual level. These findings are probably most important to conclude that a woman with diabetes or at risk of it can take HRT without a negative impact on diabetes.

This PP doesn't understand statistics. She doesn't know the difference between absolute difference and relative risk, so her post is seriously misleading.

Here's an example: Using seatbelts lowers your risk of death in a serious car crash by 50%. If you don't use a seatbelt and you get in a serious crash, your risk of dying is 43%. If you use a seatbelt, the risk drops to 21%. So by using a seatbelt, you cut your risk in half! Pretty good, right?

But the chances of anyone dying in a serious car crash isn't especially high. So the *absolute* difference between seat belt users and non-users -- 0.0005% -- looks absolutely tiny. That tiny-seeming number = cutting your chance of death in half.

So when PP says, 0.7% (absolute difference) is "hardly a stunning number on an individual level," she's completely misunderstanding what the appropriate "individual" number is. The "individual" number is the decrease in the relative risk an individual might have. That number is 21%, and that is the effect of HRT.

Whether you think a 21% reduction is a compelling number or not is up to you.

Great now do the breast cancer and stroke risk.

These were done upthread, but here are the numbers in one place:

Breast cancer (combined HRT): risks increase
Absolute increase: 0.5% over 5 years
Relative risk increase: 20% to 30% over 5 years
This is the equivalent of going from 23 per 1000 (non-HRT baseline) to ~28 per 1000 (with HRT) over 5 years.
Net effect: 5 extra cases per 1000 over 5 years.

Breast cancer (estrogen only HRT)
No increased risk, and WHI actually showed a small reduction of risk. But estrogen-only applies only to women without a uterus.
Net effect: 0 or possibly protective.

Type 2 diabetes: risks decrease
Absolute decrease: ~1% to 3% over 5 years
Relative risk reduction: ~20% to 30%
This is the equivalent of going from 50 cases per 1000 (non-HRT baseline for healthy women) to 35-40 per 1000 (with HRT) over 5 years.
Net effect: 10 to 15 fewer cases over 5 years

Cardiovascular disease: risks decrease*:
Absolute decrease: 0.6% to 2% over 5 years
Relative risk reduction: 30 to 50%
This is the equivalent of going from ~20–40 per 1000 (non-HRT baseline) to ~10–20 events per 1000 over 5 years
Net effect: 10-20 fewer serious coronary heart disease events (heart attacks and cardiac death) per 1,000 over 5 years
*in women who start HRT <60 or are within 10 years of menopause, the "early initiation" window. HRT is generally not recommended to initiate in older women.

But even this doesn't tell the whole story. Cardiovascular disease is the #1 killer of women -- far more common than breast cancer (35% of deaths vs. <3% ). So a risk relative reduction of 30-50% in coronary heart disease among early starters translates into vast population benefits. This is why trials show all-cause mortality falls by ~30-40% in early starters.

Stroke: data show no increased risk for women who begin HRT (transdermal estrogen, micronized progesterone) under 60 years of age or within 10 years of menopause. (There was a small increased stroke risk with the older formulations, and risks increased with age).

MOST IMPORTANT CAVEAT: we do NOT all have the same risks of diseases. Family history, BMI, BP, lifestyle, personal medical history, etc., all matter here. This is why the decision to take or not take HRT should never be one-size-fits all. So even with all the available data on risks and benefits, you really must discuss the decision with a health care provider who knows you, and understands your specific risk profile.

Hope this is helpful to anyone still reading. I'm going to bow out of this thread now, hoping that most readers can discern best-available data from strong opinions. Wishing you all well as we navigate our respective choices.

Right - so the absolute risks AND absolute benefits are small. And we won’t get into how you are cherry picking studies, the limits of observational studies, and the fact that there are so many possible combinations of dosages and types of hormones administered that are not studied in detail.

How is 30% drop in all cause mortality a small absolute benefit? What is your background to take this tack?

[Anonymous]

Anonymous wrote:

Anonymous wrote:Re heart disease, the most important study is proably Hodis & Mack 2022, because it pulls together data from previous randomized trials, meta-analyses, and observational studies. This paper shows that timing is everything. When initiated in women <60 or <10 years since menopause, HRT reduces coronary heart disease events and all-cause mortality by roughly 30–50%, with no increase in stroke in this age/timing group. When started later, though, HRT shows no benefit and may be associated with increased risks. https://pmc.ncbi.nlm.nih.gov/articles/PMC9178928

There are plenty of other papers on the topic, but Hodis & Mack incorporate and synthesize them.

As with type 2 diabetes, HRT does not have FDA approval for prevention of heart disease.

And, similar to type 2 diabetes, The NAMS 2022 statement does not recommend starting HRT primarily to prevent cardiovascular disease, but they acknowledge that randomized trials, meta-analyses, and observational data suggest fewer cardiovascular events in *appropriately selected* (i.e. younger women who initiate HRT near menopause), and that overall benefits outweigh risks for most healthy symptomatic women <60 or within 10 years of menopause.

Thanks. part of my concern with this research is that it uses (I believe) standardized dosages, types and delivery methods of hormones. Whereas there is much more varied in how HRT is actually prescribed in real life.

The variability issue definitely affects FDA approval (a preventive indication requires a specific therapy, in a single dose/range, in a well-defined population). And it's likely why NAMS is so cautious about their language, even as they acknowledge the preventive benefits of HRT. But to your specific question, the studies linked to here -- which are the current gold standard (I hope we get more!) -- have included a range of HRT therapies, doses, and populations. The results are consistent across this variability, which actually strengthens rather than diminishes the case for HRT impact on prevention of these conditions.

[Anonymous]

Anonymous wrote:

Anonymous wrote:

Anonymous wrote:

Anonymous wrote:

Anonymous wrote:

Anonymous wrote:

Anonymous wrote:For those who want data and official medical positions, here's some research on HRT and type 2 diabetes. Summarizing, it shows that across multiple large randomized trials and meta-analyses, HRT with estrogen (with or without progestin) reduces the risk of developing type 2 diabetes on the order of 20–30% and improves insulin resistance and glucose control:

Margolis KL et al., Diabetologia 2004 — 15,641 postmenopausal women randomized and placebo controlled: https://link.springer.com/article/10.1007/s00125-004-1448-x

Mauvais-Jarvis et al. 2017 – Endocrine Reviews
https://academic.oup.com/edrv/article/38/3/173/3063786

Note that HRT does not have an FDA-approved prevention indication.

The North American Menopause Society in their 2022 position statement said that they do NOT recommend starting HRT primarily to prevent diabetes, but that a diabetes-preventive effect is a real, evidence-based benefit in appropriate women (younger, early postmenopause): https://pubmed.ncbi.nlm.nih.gov/35797481/

Sure. But since we are being so detailed about the absolute of HRT it is also important to be detailed about the absolute benefits: “The cumulative incidence of treated diabetes was 3.5% in the hormone therapy group and 4.2%”

So there was 0.7% fewer diabetes cases in the HRT group. Hardly a stunning number on an individual level. These findings are probably most important to conclude that a woman with diabetes or at risk of it can take HRT without a negative impact on diabetes.

This PP doesn't understand statistics. She doesn't know the difference between absolute difference and relative risk, so her post is seriously misleading.

Here's an example: Using seatbelts lowers your risk of death in a serious car crash by 50%. If you don't use a seatbelt and you get in a serious crash, your risk of dying is 43%. If you use a seatbelt, the risk drops to 21%. So by using a seatbelt, you cut your risk in half! Pretty good, right?

But the chances of anyone dying in a serious car crash isn't especially high. So the *absolute* difference between seat belt users and non-users -- 0.0005% -- looks absolutely tiny. That tiny-seeming number = cutting your chance of death in half.

So when PP says, 0.7% (absolute difference) is "hardly a stunning number on an individual level," she's completely misunderstanding what the appropriate "individual" number is. The "individual" number is the decrease in the relative risk an individual might have. That number is 21%, and that is the effect of HRT.

Whether you think a 21% reduction is a compelling number or not is up to you.

Great now do the breast cancer and stroke risk.

These were done upthread, but here are the numbers in one place:

Breast cancer (combined HRT): risks increase
Absolute increase: 0.5% over 5 years
Relative risk increase: 20% to 30% over 5 years
This is the equivalent of going from 23 per 1000 (non-HRT baseline) to ~28 per 1000 (with HRT) over 5 years.
Net effect: 5 extra cases per 1000 over 5 years.

Breast cancer (estrogen only HRT)
No increased risk, and WHI actually showed a small reduction of risk. But estrogen-only applies only to women without a uterus.
Net effect: 0 or possibly protective.

Type 2 diabetes: risks decrease
Absolute decrease: ~1% to 3% over 5 years
Relative risk reduction: ~20% to 30%
This is the equivalent of going from 50 cases per 1000 (non-HRT baseline for healthy women) to 35-40 per 1000 (with HRT) over 5 years.
Net effect: 10 to 15 fewer cases over 5 years

Cardiovascular disease: risks decrease*:
Absolute decrease: 0.6% to 2% over 5 years
Relative risk reduction: 30 to 50%
This is the equivalent of going from ~20–40 per 1000 (non-HRT baseline) to ~10–20 events per 1000 over 5 years
Net effect: 10-20 fewer serious coronary heart disease events (heart attacks and cardiac death) per 1,000 over 5 years
*in women who start HRT <60 or are within 10 years of menopause, the "early initiation" window. HRT is generally not recommended to initiate in older women.

But even this doesn't tell the whole story. Cardiovascular disease is the #1 killer of women -- far more common than breast cancer (35% of deaths vs. <3% ). So a risk relative reduction of 30-50% in coronary heart disease among early starters translates into vast population benefits. This is why trials show all-cause mortality falls by ~30-40% in early starters.

Stroke: data show no increased risk for women who begin HRT (transdermal estrogen, micronized progesterone) under 60 years of age or within 10 years of menopause. (There was a small increased stroke risk with the older formulations, and risks increased with age).

MOST IMPORTANT CAVEAT: we do NOT all have the same risks of diseases. Family history, BMI, BP, lifestyle, personal medical history, etc., all matter here. This is why the decision to take or not take HRT should never be one-size-fits all. So even with all the available data on risks and benefits, you really must discuss the decision with a health care provider who knows you, and understands your specific risk profile.

Hope this is helpful to anyone still reading. I'm going to bow out of this thread now, hoping that most readers can discern best-available data from strong opinions. Wishing you all well as we navigate our respective choices.

Right - so the absolute risks AND absolute benefits are small. And we won’t get into how you are cherry picking studies, the limits of observational studies, and the fact that there are so many possible combinations of dosages and types of hormones administered that are not studied in detail.

How is 30% drop in all cause mortality a small absolute benefit? What is your background to take this tack?

Where are you getting that from? Also yes, it is likely small in absolute terms (because it’s not like 50% of women between 50-60 die).

[Anonymous]

Anonymous wrote:

Anonymous wrote:

Anonymous wrote:Re heart disease, the most important study is proably Hodis & Mack 2022, because it pulls together data from previous randomized trials, meta-analyses, and observational studies. This paper shows that timing is everything. When initiated in women <60 or <10 years since menopause, HRT reduces coronary heart disease events and all-cause mortality by roughly 30–50%, with no increase in stroke in this age/timing group. When started later, though, HRT shows no benefit and may be associated with increased risks. https://pmc.ncbi.nlm.nih.gov/articles/PMC9178928

There are plenty of other papers on the topic, but Hodis & Mack incorporate and synthesize them.

As with type 2 diabetes, HRT does not have FDA approval for prevention of heart disease.

And, similar to type 2 diabetes, The NAMS 2022 statement does not recommend starting HRT primarily to prevent cardiovascular disease, but they acknowledge that randomized trials, meta-analyses, and observational data suggest fewer cardiovascular events in *appropriately selected* (i.e. younger women who initiate HRT near menopause), and that overall benefits outweigh risks for most healthy symptomatic women <60 or within 10 years of menopause.

Thanks. part of my concern with this research is that it uses (I believe) standardized dosages, types and delivery methods of hormones. Whereas there is much more varied in how HRT is actually prescribed in real life.

The variability issue definitely affects FDA approval (a preventive indication requires a specific therapy, in a single dose/range, in a well-defined population). And it's likely why NAMS is so cautious about their language, even as they acknowledge the preventive benefits of HRT. But to your specific question, the studies linked to here -- which are the current gold standard (I hope we get more!) -- have included a range of HRT therapies, doses, and populations. The results are consistent across this variability, which actually strengthens rather than diminishes the case for HRT impact on prevention of these conditions.

Yeah I’m going to need to see more than that.

[Anonymous]

Anonymous wrote:

Anonymous wrote:

Anonymous wrote:

Anonymous wrote:Re heart disease, the most important study is proably Hodis & Mack 2022, because it pulls together data from previous randomized trials, meta-analyses, and observational studies. This paper shows that timing is everything. When initiated in women <60 or <10 years since menopause, HRT reduces coronary heart disease events and all-cause mortality by roughly 30–50%, with no increase in stroke in this age/timing group. When started later, though, HRT shows no benefit and may be associated with increased risks. https://pmc.ncbi.nlm.nih.gov/articles/PMC9178928

There are plenty of other papers on the topic, but Hodis & Mack incorporate and synthesize them.

As with type 2 diabetes, HRT does not have FDA approval for prevention of heart disease.

And, similar to type 2 diabetes, The NAMS 2022 statement does not recommend starting HRT primarily to prevent cardiovascular disease, but they acknowledge that randomized trials, meta-analyses, and observational data suggest fewer cardiovascular events in *appropriately selected* (i.e. younger women who initiate HRT near menopause), and that overall benefits outweigh risks for most healthy symptomatic women <60 or within 10 years of menopause.

Thanks. part of my concern with this research is that it uses (I believe) standardized dosages, types and delivery methods of hormones. Whereas there is much more varied in how HRT is actually prescribed in real life.

The variability issue definitely affects FDA approval (a preventive indication requires a specific therapy, in a single dose/range, in a well-defined population). And it's likely why NAMS is so cautious about their language, even as they acknowledge the preventive benefits of HRT. But to your specific question, the studies linked to here -- which are the current gold standard (I hope we get more!) -- have included a range of HRT therapies, doses, and populations. The results are consistent across this variability, which actually strengthens rather than diminishes the case for HRT impact on prevention of these conditions.

Yeah I’m going to need to see more than that.

What specifically?