Good morning,

How is your weekend going? I was out of town for work last week and am happy to be home.

Here’s what I have for you today:

• One big thing. How did one study scare tens of millions of women off hormones? It’s a crazy story with important lessons for women and men. 📉

• You have to check this out. Two articles and three books for additional reading. 📚

Get another cup of coffee and let’s jump in? 🦘

1️⃣ ONE BIG THING

The Gen X guide to hormone replacement therapy for women.

Well, here I go.

I'm a 53-year-old man, and I’m not a doctor.

Today, I am going to talk about menopause.

Quick note to the guys, if you are thinking this one is not for you, I’d encourage you to keep reading. If you have a female partner, sister, friend, etc., you should 100% keep reading.

As a regular reader of my letters, you know I periodically cover health topics relevant to our age group and frequently reference Dr. Peter Attia.

I am writing about menopause today because I just listened to the following short exchange from his podcast The Drive (Episode 358):

Host: You have stated you think the work of the WHI, and as a result, the demonization of HRT, is one of the biggest missteps in modern medical history. Is that still your thinking?

Attia: It is, yeah. It really is. It’s definitely one of the things that frustrates me more than anything else in the last 50 years, as it pertains to medical research.

What is the WHI?

And what is this “biggest misstep in modern medical history”?

Let’s start here:

A 2024 study found that less than 2% of women over 40 took hormone replacement therapy (HRT). A 2020 study found that just 5% of postmenopausal women used HRT.

Now, let's back up 25 years:

In 1999, the estrogen drug “Premarin was consistently the first or second most prescribed drug in the United States, beating out medications for common ailments like high blood pressure and diabetes, with an estimated 40% of women of postmenopausal age taking it or an alternative estrogen formulation,” explained the New Yorker. In 2000, doctors issued 92 million prescriptions for hormone therapy to women.

From 40% to 2% in twenty-five years.

What happened?

The biggest misstep in modern medical history.

The Women’s Health Initiative (WHI) on HRT “was and is one of the largest women's health research projects ever launched in the United States. The WHI clinical trial and observational study enrolled more than 161,000 postmenopausal women between 50 and 79,” explains Dr. Angela De Rose.

What did the WHI conclude?

Even if you have never heard of this study, you probably know the answer:

Hormone replacement for women causes cancer!!

HRT was such a cancer risk that the study was halted early, showing a 26% increase in the risk of developing breast cancer.

Here is a snapshot of the media coverage from the early 2000s:

Pandemonium.

Tens of millions of women stopped taking hormones to treat menopausal symptoms.

And with good cause. A 26% increase in cancer risk is alarming!

Or is it?

If you’re like me, you have probably seen percentages used professionally in wildly misleading ways. But nothing will ever top this WHI bungle.

In that study, the rate of breast cancer for the placebo group was 30 cases per 10,000 women.

In the study group that received hormones, the rate of breast cancer was 38 cases per 10,000 women.

People read the 26% increase stat and heard something akin to 1 in 4. But the reality was a change from a 0.0030 to 0.0038 incidence of cancer.

Believe it or not, it gets worse.

The study group that set off the cancer alarm bells was taking the drug Prempro, which is made up of conjugated estrogens plus medroxyprogesterone acetate (MPA), a progestin.

Later analysis of the WHI data found that tiny increase in cancer risk (from 30 to 38 out of 10,000 women) was specifically tied to the MPA in Prempro (not the estrogen), and only for women starting HRT in their 60s or later (doctors generally recommend starting HRT during perimenopause, which typically begins in the mid-40s).

A separate treatment group in the same WHI study received the drug Premarin, which is just estrogen (without MPA). This group saw a 23% decrease in breast cancer risk, but that was lost in the cacophony of alarm bells (and yes, that 23% was also based on very small baseline numbers).

The current medical consensus.

A 2017 study followed up with 27,347 of the WHI study participants. In short, they looked at who was still alive, and who had died, running statistical analysis to find any connections.

This study found no increase in all-cause mortality, cardiovascular mortality, or cancer mortality in women who used menopausal hormone therapy.

Here is a fairly tidy summary from Dr DeRosa: “Hormones do not cause cancer.”

And yet, as I noted above, very few women currently eligible for HRT are using it—2-5% in the U.S. The number is closer to 15% in the UK. Nothing like the 40% from just 25 years ago.

Assessing health risk-reward in silos.

The WHI mess illustrates another common flaw in assessing risk and reward.

Not only were the WHI conclusions based on a grave misuse of percentages, but they also overlooked the substantial benefits of HRT for women.

Risks should be judged in context, not in isolation. Seat belts are known to cause bruising, abrasions, and rib fractures during accidents, but they also prevent your skull from cracking your windshield.

The list of HRT benefits for women entering menopause is substantial.

Topping this list are the cryptically named vasomotor symptoms (VMS), better known as hot flashes, night sweats, brain fog, mood shifts, insomnia, and more. Plus, symptoms charmingly called the genitourinary syndrome of menopause (GSM) involve vaginal dryness, irritation, and urinary problems.

“Hormone therapy remains the most effective treatment for vasomotor symptoms (VMS) and the genitourinary syndrome of menopause,” says the 2022 position statement of The North American Menopause Society.

This is what was buried by the WHI hysteria—a very effective treatment for major, overwhelming symptoms impacting half the population over a certain age.

“Going on hormone therapy wasn’t a silver bullet for every last issue I had, but it did provide instant, massive relief. I no longer woke up sweating in the middle of the night, convinced my blankets were trying to kill me,” says the actress Naomi Watts in her book Dare I Say It: Everything I Wish I'd Known About Menopause.

Other commonly linked HRT benefits include:

1. Improvements in bone density and reductions in bone fractures. Consider how many people get debilitating hip fractures late in life.

2. Reductions in heart disease. Ttiming matters: when started <60 or <10 years from menopause, HRT lowers heart disease risk and mortality; when started after that, it can increase risk.

3. Reduction/elimination of urinary tract infections. When estrogen levels drop, the tissues in the vagina and urinary tract change a lot. But most doctors treat the symptoms with antibiotics, not the root problem, so infections keep coming back. “One of the most effective treatments is topical estrogen therapy,” says Stacy A. Henigsman. Read here for more, and watch the YouTube link below with Peter Attia / Rachel Rubin for more.

WHI’s collateral damage.

Researching this letter has been educational for me in many ways. I hope it has been helpful for you, too.

Please forward this information to women in your life who are in or approaching perimenopause or menopause.

Unfortunately, the WHI disaster impacted more than patients—it also meant HRT for women was not taught in medical school or residency for two decades.

“That’s the collateral damage of this women’s health initiative, we now have not just a generation of women who have not been treated, but the corollary of that is we have a generation of doctors who have never been trained to do it,” Peter Attia said.

Finding qualified doctors to properly prescribe the right HRT approach may be challenging. Rachel Rubin’s website seems like one place to start.

There is a massive difference between female and male hormone patterns over a lifetime.

I’ll leave you today with the nugget of information from my research that I found most revelatory.

The following graphic may help people better understand and/or explain what’s going on for family members and friends going through the phases of menopause.

For men, testosterone production slowly declines over their lifetime—see the dark green line below.

But for women, hormone production goes from normal to highly erratic (which is perimenopause) to zero (which is postmenopause)—see the red line below.

Reviewing recent books on menopause in The New Yorker, Rebecca Mead said:

“Frostrup writes that between the ages of forty-nine and fifty-one, she ‘barely slept, raged at my husband and kids, and was swamped by levels of anxiety that were as debilitating as they were irrational.’

“Going on hormone therapy restored her well-being, she says, and ‘contributed to maintaining my state of health, hope, and (mostly) happiness ever since.’

“Frostrup avows that she will take hormones for the rest of her life. ‘My estrogen gel will have to be prised from my cold dead hands,” she writes.”

Here is the full discussion on today’s topics (and more), if you would like to dive deeper:

Thanks for reading today, my friend.

Kevin

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