Cancer & HRT: What’s Safe?

For many people, hormone replacement therapy (HRT) is a very straightforward choice. Many benefits, few risks, and the few risks that do stand are fewer and lesser than the risks of untreated menopause.

See for example: What You Should Have Been Told About The Menopause Beforehand

And with regard to the risks of untreated menopause that many don’t pay as much attention to as ideally they might, see:

• What Menopause Does To The Heart
• Menopause, & When Not To Let Your Guard Down
• Alzheimer’s Sex Differences May Not Be What They Appear

…alongside other more well-known risks, such as osteoporosis (something heavily driven by untreated menopause, and greatly reduced by appropriate HRT)

But what about cancer?

First, know that most of the scaremongering about cancer is due to one (1) incredibly flawed study, which has been well-refuted by a huge weight of counterevidence in the decades since.

The (deeply flawed) Women’s Health Initiative (WHI) study, conducted in the 90s and published in 2002, linked HRT to breast cancer, causing fear, but it turned out that this was quite bad science in several ways and the reporting was even worse (even the flawed data did not really support the conclusion, much less the exaggerations and outright fabrications in the headlines).

Its most egregious mistakes included:

• It was based on conjugated equine estrogens (CEE) derived from horse urine, not modern bioidentical estrogen made in a lab and molecularly identical to the estradiol that humans produce naturally—estradiol is one of several estrogens that humans produce and can easily metabolize, and it is functionally “better” than the others (such as estrone), as the body can use it more readily. Surprising nobody, human estrogens work better in humans than horse estrogens do.
• It was also based on hormone analogs, such as medroxyprogesterone acetate (MPA), which is a progestin and not the same thing as progesterone (which latter is often prescribed nowadays under names such as utrogestan or cyclogest, which deliver actual progesterone—if you have a choice between those two, this writer has used both and recommends cyclogest for its better absorption rates). Anyway, back to MPA: after the usual animal testing of MPA, the US tested it in third-world countries, where it was found to cause various kinds of cancer (breast, cervical, ovarian, uterine), before rolling it out in the US anyway. You may be wondering why it still got rolled out in the US, and we can’t say for sure, but a likely reason is that somebody crunched the numbers and found that the profits from the sales would exceed the costs of out-of-court settlements.
• It also had major methodological design flaws, including an unaddressed 40% dropout rate (which meant that a lot of data was from participants who were nominally in the CEE+MPA group, but dropped out early, and then got recorded as having seen no benefits despite having been on HRT. The blinding was also weak, and to top it all off, MPA-mediated cancer was recklessly attributed to the CEE in the analysis. In other words “these people took MPA, which we know causes cancer, but since they also took CEE, we will consider that to have been equally to blame”.

Unclear whether the WHI study authors also believe that ice cream sales increase shark attacks.

As we say, it has since been refuted (here’s one example paper out of many) and in fact, HRT can even be a protective factor, depending on the HRT regimen, but fearmongering headlines made it to mainstream news, whereas “oopsies, never mind, we take that back” didn’t.

The short version of the current state of the science is: breast cancer risk varies depending on age, HRT type, and dosage; some kinds of HRT can increase the risk marginally in those older than 60, but absolute risk is low compared to placebo, and taking estrogen alone can reduce risk at any age in the event of not having a uterus (almost always because of having had a hysterectomy; as a quirk, it is possible to be born without, though).

It’s worth noting that even in the cases where HRT marginally increased the risk of breast cancer, it significantly decreased the risk of cancers in total, as well fractures and all-cause-mortality compared to the placebo group.

In other words, it might be worth having a 0.12% risk of breast cancer, to avoid the >30% risk of osteoporosis, which can ultimately be just as fatal (without even looking at the other things the HRT is protective against).

However! In the case of those who already have (or have had) breast cancer, increasing estrogen levels can indeed make that worse/return, and it becomes more complicated in cases where you haven’t had it, but there is a family history of it, or you otherwise know you have the gene for it.

In such cases, you might consider: The Hormone Therapy That Reduces Breast Cancer Risk & More

And now for HRT and gynecologic cancers

More recently… You know what, we often cite recent research here, and often it’s just a few days post-publication because, well, we keep our eyes on things. Today, this one’s special, because this paper’s publication date is 4 months from now, at time of writing! But we have an advance copy, so we’ll share its findings with you.

Anyway, researchers (Dr. Jamie McDowell et al.) investigated estrogen therapy in patients with gynecologic cancers (including endometrial cancer and ovarian cancer), and found that many gynecologic cancer patients (about 40%) are pre- or perimenopausal at diagnosis; treatments like surgery, chemotherapy, and radiotherapy often trigger ovarian insufficiency and early menopause.

In other words, the cancer precedes the drop in hormones that may then be replaced with HRT.

In terms of what specialist doctors consider safe, Dr. McDowell and her team asked 293 members of the Society of Gynecologic Oncology and the American College of Obstetricians and Gynecologists, who reported:

• 63.8% prescribe estrogen therapy for endometrial cancer patients
• 65.2% prescribe estrogen therapy for epithelial ovarian cancer patients
• 96.8% prescribe estrogen therapy for cervical cancer patients

Of those who responded in the negative, the most common reason for withholding estrogen therapy was the incorrect belief that risks outweigh benefits, despite evidence that this is not true for most cancers.

As for that evidence, the paper itself cites a stack of sources, so rather than list them all, we’ll just mention that you can see them at the bottom of:

Estrogen therapy in patients with gynecologic cancer: a survey of gynecologists and oncologists in the United States

Want to learn more?

Most women’s biggest concern in this regard, unless having a personal history of one of the other cancers, is breast cancer. Which is reasonable, given its very high prevalence rates with or without HRT.

While we’ve given some pointers above on how one might proceed to get maximum benefits with minimal risks, for a truly deep dive, we recommend this excellent book that we reviewed a little while ago:

The Smart Woman’s Guide to Breast Cancer – by Dr. Jenn Simmons

Take care!