In response to your great suggestions, we’ve decided to address the most frequently mentioned common thread: Hormone Replacement Therapy and Alzheimer’s, Both At and After Menopause. This is a huge topic, we’ll piece apart a few threads, pertinent to some recent news and your questions.

“Is it Too Late for Me?”

A bright and engaging 63-year-old woman (I’ll call her Beverly) visited my office recently, concerned about the health of her brain. Her mother had died with Alzheimer’s Disease and in sharing that information with a friend of hers had first learned about the connection between hormone replacement and brain health. Her mother had undergone a surgical menopause at the age of 45, so lost her usual female hormones earlier than the age of normal menopause (about 52).Beverly’s menopause was normally timed, but she had never taken hormone replacement—her physician had counseled against considering hormones,even though her menopausal symptoms were significant.  “Don’t worry,” HE told her, “those hot flashes will go away in a year or two. Better than getting breast cancer or a stroke.”

At this point, I nearly jumped out of my chair, for many reasons.

1. FIRST of all, how would that physician like to suffer through hot flashes, night sweats, and sleep loss for “a year or two”? Recent evidence tallies the range as from one to 7-10 years, or more in some women.

2. Secondly, the idea that HRT causes either breast cancer or a stroke is horribly outdated, relying on research over 20 years old (and massively corrected since then). At that time, docs were prescribing forms of HRT that should be committed to the garbage heap, having been replaced by safer and even beneficial forms.

3. Thirdly, HRT is about a lot more than reversing hot flashes, as those 20+years of research have shown benefits such as:

• • Improved cognition

  • Better gum health, enabling better food consumption

  • REDUCED breast cancer risk

  • Improved “metabolism,” less tendency to gain weight or have high blood sugar

  • Lower adverse cholesterol numbers

  • Reduced cardiovascular inflammation

  • AND blood pressure

  • Better bone strength

  • Less colon cancer

  • …. And more, but those are the highlights.

Beverly stopped me briefly on gum health—why do I care about that? Because better gums help us keep our teeth for chewing and chewing is good for the brain and for our overall nutrient intake—and interrupted me completely before I’d reached the end of the list. Her question is a salient one, “Is it too late for me?”

Let’s spend a little more time on all the HRT benefits before we get to that very important question of hers.

OUT WITH THE OLD, IN WITH THE NEW

In 2002 a massive study was interrupted mid-stream: the Women’s Health Initiative study was well underway to evaluate what the effects of hormone replacement therapy.Older women (past the age of menopause) were recruited for a massive comparison of hormone therapy, comparing

First Group: No hormones

Second Group: “Estrogen” only, using Premarin® which is horse urine estrogen…!

• NOT biologically identical and only available orally

• Oral estrogen in any form markedly increases the risk of blood clots

Third Group: “Estrogen” (Premarin®) and “progesterone” in which the “progesterone” was actually Provera® medroxy-progesterone,a patent-able synthetic analogue of progesterone, similar to the ingredients in birth control pills.

• NOT biologically identical to progesterone, in fact…it shares only ONE effect with biological progesterone…and in every other way has an OPPOSITE effect. (For instance, CAUSES cognitive impairment rather than helping to RELIEVE it.)

The WHI study was initiated because it seemed from common practice that women were benefiting from hormones: happier, less menopausal symptoms and seemingly with less problems with their brains, bones, and hearts. The FORMS of the hormone replacing drugs I would consider primitive, but they were the common practice at the time: synthetic versions of natural hormones, only partially overlapping but largely DIRECTLY OPPOSITE to the effects of the now-recommended forms. CURRENTLY, best practices suggest that women’s hormones be replaced with

• Biologically identical estradiol(estrogen) applied topically through a transdermal patch

• Biologically identical progesterone (conventionally available as an oral preparation)

• Considered an alternative would be to use compounded versions of the above

WHAT ABOUT EVEN OLDER WOMEN?

When women are more than 5-10 years past menopause, their Primary Care providers and GYNs generally advise them that HRT is now dangerous for them. Is there really a basis for this? I submit that the known physiological effects of topical estradiol and real progesterone have significant benefits that far outweigh risks for most women of any age.

All of the studies that show problems with HRT in older women are based on looking back at records of women prescribed the wrong hormones (Premarin and Provera, combined in PremPro) as described above. Hopefully very few physicians are prescribing those anymore. 

The most recent dire and alarming study was specifically about brain health, appearing first in the British Medical Journal (BMJ) and reported by CNN.  Outrageously, “the study only looked at people who used a certain type of HRT — a combination of estrogen and progestin that was widely prescribed at that time” according to CNN.  How on earth did the BMJ Editorial Board run an article on an antiquated form of HRT as if it claimed anything useful!?  If it had been titled, “Yet Another Cautionary Lesson on the Old Ways,” I think it could have been helpful!

“NOT SO HELPFUL FOR OLDER WOMEN”

…should be the title of any study of HRT applied to older women. Indeed, it is true: it is BETTER to start HRT as soon as those same hormones have disappeared from an aging woman’s body.  The benefit is definitely LESS if initiated later in life, but it can still be significantly helpful.  Our practice is to review the risks, benefits and options: happy to start proper HRT even later in life, and see how the woman feels and how her labs and other tests verify that feeling, or not!

ARE THERE NATURAL ALTERNATIVES?

There are indeed supplements that can help with many of the above symptoms. For example, soy- or pomegranate-derived isoflavones can help particularly with the brain- and bone-building features of HRT. 

Taking prescribed hormones, I would suggest, is now a “natural” option, replacing lost hormones with prescriptions that boost blood levels of our own previous hormones.

Did you know that only 3 mammalian species actually go through menopause?  Can you guess the other two? Only humans, pilot and Orca whales cease cyclic fertility with age.  Never in evolution, however, has any species ceased hormone production with more than a third of life remaining.  My mature body was quite happy with hormones for 40 years, and I plan to test out my guess that it will continue happy for another 40 or more past that! 

Each woman requires her own unique evaluation for HRT and there is no one size fits all solution. However, the known science of topical estradiol and real progesterone support the high likelihood of benefit outweighing risk for most women no matter their age.

******

Some of my favorite relevant papers are listed below.  

Wharton, Asthana. et al., Potential role of estrogen in the pathobiology and prevention of Alzheimer’s disease. Amer J Transl Res 2009;1(2):131-147

Gersh FL, et al. Postmenopausal hormone therapy for cardiovascular health: the evolving data. Heart 2021;0:1–8. doi:10.1136/heartjnl-2019-316323

Irwin RW, Brinton RD., Medroxyprogesterone acetate antagonizes estrogen up-regulation of brain mitochondrial function. Endocrinology 2011 152:556 –567.

Stanczyk F., et al, Progestogens Used in Postmenopausal Hormone Therapy: Differences in Their Pharmacological Properties, Intracellular Actions, and Clinical Effects. Endocrine Reviews, April 2013, 34(2):171–208

* Nevzati E, Shafighi M, Bakhtian KD, Treiber H,Fandino J, Fathi AR. Estrogen induces nitric oxide production via nitric oxide synthase activation in endothelial cells. Acta Neurochir Suppl. 2015;120:141-5.

*And* Walker, et a., The phytoestrogen Genistein Produces Acute Nitric Oxide-Dependent dilation of Human Forearm Vasculature With Similar Potency to 17b-Estradiol.  Circulation 2001; 103:258-262.