We Are All Zebras Now

“I’d rather not renew your prescription for hormone replacement therapy because it increases the risk of stroke,” said my doctor.

Which was ironic, given what happened next.

But even during that phone call I was not convinced. “From the literature, it looks like overall mortality is the same with or without HRT, and quality of life is higher with HRT.”

“You might be more likely to break a bone without estrogen. But a stroke is a devastating event.” My doctor was not wrong. In their 2022 position statement, the North American Menopause Society (NAMS) reviewed hundreds of medical studies and concluded that on average there is a real risk of stroke for women over 60 using HRT. But that is not all they said.

All humans, doctors included, find simplifying assumptions useful. “Look for horses not zebras” they are taught in medical school. The problem is that the effects of estrogen are not simple.

If you were born a woman, you have estrogen receptors all over your body: in your skin, your brain, your bones, your liver, your colon—not just in your reproductive organs. The decrease in estrogen after menopause affects the whole body. No surprise that the NAMS report identifies effects of hormone replacement therapy in many body systems and on multiple conditions. Adding to the complexity, the studies of these effects enrolled various numbers of patients and have different levels of statistical significance. They used varied formulations and dosage levels, and any one of three different routes of administration: oral medication, transdermal patches, and local application. Each route of administration has a different safety and efficacy profile. For example, the increased risk of stroke is based on a study of oral administration and may be lower for transdermal application. In addition, some studies looked at estrogen plus progesterone therapy (for women with a uterus) while others looked at estrogen alone (for women post-hysterectomy). That’s a lot of variables to conflate. No wonder that many of the studies give contradictory results (for example, some show positive effects on heart health where others indicate increased risk).

 

Positive Effects of HRT Per the 2022 NAMS Report Include:

Negative Effects of HRT Per the 2022 NAMS Report Include:

·      Lower incidence of vasomotor symptoms (hot flashes, night sweats, and insomnia (which can lead to cardiovascular issues) ·      Reduces risk of colorectal cancer ·      Lower risk of developing Type 2 Diabetes ·      Prevents bone loss due to osteoporosis ·      Controls symptoms of Genitourinary Syndrome of Menopause (includes effects on vaginal tissues, urinary issues such as urgency and UTIs) ·      Lowers risk of fractures ·      Improves synthesis of collagen ·      Improves some aspects of sexual function ·      Decreases risk of macular degeneration ·      Decreases dizziness and vertigo ·      Protects joint health and reduces joint pain ·      Enhances mood and may prevent depression

·      Higher risk of stroke ·      Higher risk of venous thromboembolism ·      Higher risk of gallbladder disease ·      Higher risk of urinary incontinence ·      Higher risk of ovarian cancer ·      Higher risk of coronary heart disease

 

Consider how these risk and benefit tradeoffs might look for different women. A woman with a family history of ovarian cancer, for example, might evaluate these effects of HRT much differently than a woman with a predisposition to diabetes. The levels of risk are quite different too. For example, the risk of gallbladder disease, while higher for women on HRT, is extremely low either with or without HRT.

To focus on the risk of stroke alone is like the fable where the visually impaired man holds the tail of an elephant and declares that an elephant is like a rope. It’s not wrong, but it’s not the whole story.

Even the NAMS report is not the whole story. Over the course of its twenty pages, the report points out that inadequate or no studies exist regarding the effects of HRT on conditions including cataracts, dry eye disease, olfactory changes, muscle tissue, cognition, heart disease and liver disease. In addition, data are lacking regarding optimal dosage, route of administration, and long term effects, even for those conditions where some studies were conducted. All told, phrases such as “no data were available,” “data are insufficient,” and “randomized trials are needed” appear in the NAMS report more than fifty times.

The pharmaceutical industry continues to justify high prices in the United States with unfounded claims that their profits support research. As I pointed out in another essay, sixty years ago a US Senate investigation identified a 2500% markup in one formulation of HRT. Women who were not yet born when that investigation occurred are post-menopausal now, and sixty years of windfall profits have not produced adequate research.

Despite the complexity, the NAMS report boils down to a one-sentence recommendation for women my age:

“For women who are aged older than 60 years, the benefit-risk ratio appears less favorable due to the greater absolute risks of coronary heart disease, stroke, venous thromboembolism, and dementia.”

The upshot of that phone call with my doctor was that I came off the estrogen transdermal patch three months ago.

Six weeks later I saw a different doctor for a skin problem.

“Is it bacterial or fungal?” I asked.

“Neither”, he said  “it’s not an infection. It’s eczema.”

“What? I’ve never had eczema.”

“Then the question is: Why now?”

I had no idea. I’m 69 and always thought eczema was a problem that started in childhood. For example, my daughter developed eczema in her teens. When I told her about my new diagnosis, she said, “My eczema went away when I was pregnant, and it never came back.”

That was a lightbulb moment. Pregnancy means lots of hormone changes. I looked up eczema and low estrogen. Even though the NAMS report does not mention eczema, the link with low estrogen was clear.

Meanwhile, the vasomotor symptoms that prompted me to choose HRT in the first place came back: hot flashes, night sweats, insomnia. No surprise there.

Then one night as I was going to sleep my heart rate suddenly went way up. Not only fast, but bumpy and fast, like a car going seventy with a flat tire. My watch has a built-in health monitor. I put it on and called the advice nurse. The ECG setting on the watch said I was in AFIB, or atrial fibrillation, meaning one of the upper heart chambers was misfiring. Plus my heart rate was rising.

“If your pulse goes over 140 you should go to the Emergency Room,” said the nurse on the phone.

“It just hit 145,” I said.

On the way to the hospital my heart rate topped 160. When we arrived I held up my watch so the ER clerk could see the AFIB reading. She ushered me into the back like a celebrity, ahead of all the folks sitting in plastic waiting room chairs. A smiling woman connected me to an EKG machine. “You’re in AFIB all right.” She sounded so cheerful. “I’ve recorded the big bumps.”

They moved me to a room with a monitor, hooked me to an IV, and then, like magic, it was over. Heart rate down, normal rhythm, start to finish in about two hours. The ER doctor prescribed a beta blocker and referred me to cardiology.

At the AFIB clinic that week, I asked whether all this—the eczema and the AFIB—could be related to stopping HRT. They were not sure. What they were sure about is that AFIB causes a fivefold increase in the risk of—you guessed it—stroke.

One morning three weeks later I started on my daily walk and my heart rate took off. It instantly passed 150. I took a beta blocker and another at 30 minutes as directed. The AFIB clinic had said not to go to the ER unless the episode lasted over 24 hours. Although I sat still and tried to relax, my pulse topped 160 and stayed over 140 for six hours.

Was this about hormones? I found a country-wide Danish study online that showed that older women taking HRT had a significantly lower rate of AFIB than women who did not use HRT. In trying to lower my risk of stroke, my doctor might actually have raised that very risk.

I sent the readouts from the watch to my doctor. Her assistant called and asked me to come in. The doctor sat with me and looked at the readings. “AFIB is bad for your heart,” she said. “Two events in one month is a lot. If this happens again, let’s consider cardiac ablation.” In that procedure, long tubes are threaded through blood vessels into the heart so that the nodes that trigger AFIB can be frozen or burned. It doesn’t always work.

I had a different idea: Why not treat low estrogen rather than play whack-a-mole with its sequelae?

“Remember when we decided to take me off HRT?”

“Yes,” she said.

“Since then, my vasomotor symptoms have returned, I’ve developed late onset eczema, and now AFIB. All those are linked to low estrogen. I know the NAMS report is cautious about HRT after sixty. But that recommendation is based on averages, and everyone is different.”

“That’s true.” She wrote the prescription, I filled it, and was back on HRT the same day.

Weeks later, the eczema has disappeared and the hot flashes are fading. Best of all, my heart is rock steady, so far. According to my watch, I’ve gone from spending 6% of my time in AFIB to 0-2%.

NAMS is not the only group that publishes HRT recommendations. The day after I resumed HRT, the US Preventive Services Task Force published a new set of recommendations on HRT. For women like me who had a hysterectomy and use estrogen without progesterone, the report listed benefits such as reduced risk of fractures and reduced risk of dying of invasive breast cancer, along with suppressing vasomotor symptoms. It listed these risks:

• Increased risk of stroke
• Increased risk of venous thromboembolism
• Increased risk of gallbladder disease
• Increased risk of urinary incontinence

The report also says that “estrogen use does not have a beneficial effect on risk of coronary heart disease.”

In sum, “The USPSTF concludes with moderate certainty that the use of estrogen alone has no net benefit for the primary prevention of chronic conditions in postmenopausal persons who have had a hysterectomy.” The report also says, “the USPSTF reviewed additional studies that reported on outcomes such as atrial fibrillation… these did not affect the overall assessment of the benefits and harms of hormone therapy.”

Those studies did not affect the “overall assessment.” But just how useful is that “overall assessment?” The known positive and negative effects of HRT are many and complex. The bottom line for women of my age: “There are no data to support routine discontinuation in women aged 65 years.”

We Are All Zebras Now

I’m telling this story not because your experience will be like mine, but for the opposite reason: Because after menopause, every woman is different.

Medical students are taught to look for horses, not zebras. Look for the common diagnoses not the exceptions. Base decisions on the typical cases, not the outliers. Even though the NAMS report and the USPSTF report recommend working with the patient to decide about HRT based on each woman’s individual needs, and even though the reports point out the lack of studies for so many aspects of older women’s health, a busy physician under pressure to see many patients in one day may take the one-size-fits-all approach and see all those patients as horses. But given the pluses and minuses of HRT combined with the varied medical situations of women over sixty, and given how much remains unknown, it’s clear that after menopause we are all zebras. No wonder physicians are more likely to prescribe HRT for themselves than for their patients. After all, they know their own bodies.

I can’t prove that stopping HRT caused my health issues, nor can I prove that resuming HRT improved them. I have no crystal ball to say whether ten years from now going back on HRT will look like a good decision. But it seems like the best decision now, despite my doctor’s initial concerns. With no net impact on mortality and a positive impact on quality of life, I’ll take my chances.

If you get a one-size-fits-all recommendation on HRT, please think deeply (and encourage your doctor to think deeply) about what is best for you—for your heart, your bones, your skin, your brain, your muscles. Not anyone else’s, yours. Studies show potential benefits of HRT for women with conditions as varied as diabetes, osteoporosis, colorectal cancer, and cardiovascular issues. You have lived in your body for a long time, and you know it best. There is only one you, and you have a lot of life to live.