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Why estrogen is not the answer to every midlife health issue
It's time we move beyond estrogen, isn't it?
Over at my midlife strong account on Instagram, I see lots of posts about midlife health. One in particular got me thinking.
This post was about a study on estrogen exposure and risk of dementia. The researchers classify risk based on estrogen exposure, including menopause timing, contraceptive use, and number of pregnancies.
In short, increased estrogen exposure over a woman’s life is associated with a lower risk. Then, the poster went on about how every perimenopausal and menopausal women need to take estrogen or terrible things will happen.
In the comments, some women were distraught, with one saying “I’m screwed” based on her history. Another was a woman who had breast cancer and could not take estrogen, was discouraged for the lack of recommendations for women like her.
This is the story that midlife women hear again and again. Because estrogen eventually declines, it is to blame for everything that goes wrong health-wise. When I first got into midlife health, I thought that too, but I no longer do. In fact, I believe this thinking is a big part of the problem.
Whether or not we take estrogen, women need to understand what changes at midlife and why. After these years of intense research, I have a pretty good idea about why the drop in estrogen can be problematic. But that doesn’t mean is has to be problematic.
The missing developmental stage info
What if, for adolescence, we only discussed puberty and not adolescence as a whole? That would be crazy, right? We understand that the whole stage is adolescence – early, middle, and late–and puberty is a part of that.
Yet we have not taken time to define the developmental stage of midlife for women or men. Because even though we consider development in terms of growth and childhood, our bodies are changing until the day we die.
I’m not the only one to think this. In 2015, in the Research in Human Development Journal, Margie Lachman called for more research at midlife:
It is fair to say that of all the periods in the life course, the middle years, roughly ages 40 to 59, are the most overlooked. There are no journals or professional societies specifically devoted to midlife, yet all age periods, infancy, childhood, adolescence, young adulthood and old age, have dedicated publications and organizations...My wish is for more research devoted directly to the middle years and embedded within the context of the life course
And it’s hurting us as we sort through the effects of menopause with no foundation from which to build upon. Yet based on the research we do have; I’ve come up with some different talking points. One that moves beyond estrogen deficiency scare tactics.
The Midlife Takeover
As women transition through menopause, their risk of chronic disease rises. The dominant theory for helping women— and treatment—has been to replace hormones.
Yet, due to mixed study results, researchers and organizations like the Menopause Society, do not recommend hormone therapy to optimize heart and brain health. The only health outcome we know for sure hormone therapy helps prevent is osteoporosis. A recent study in Endocrinology presents research gaps in the heart health area:
Preclinical studies largely indicate that estrogen has a protective effect within endothelium by increasing production of NO, vascular endothelial growth factor, and other mediators that augment endothelial migration and proliferation. However, it still remains unclear why these estrogen-induced, anti-atherosclerotic effects within the vasculature do not translate to improved CVD outcomes.
In the US, it is no longer called hormone replacement therapy but menopausal hormone therapy because you are not actually replacing hormones. It’s more about giving the right amount to manage symptoms like hot flashes and each woman will be different.
And that’s another key. Taking hormones will never equate to what our cycles were before. And why would we need that? After the reproductive stage, the body no longer prioritizes getting pregnant, and estrogen and progesterone have different roles.
Another important factor often missed is that by 40, the effects of aging have taken place even more hormones decline. The way I look at it is half the story of changing health at midlife is about aging and the other half hormones.
A development perspective would look at a woman’s changing body and ask, what does it need? Instead of always looking to add estrogen back, what if we found ways to take over the jobs of hormones, while also paying special attention to the effects of aging?
I call this “the Midlife Takeover,” because there are many ways to help keep our bodies strong and healthy.
Taming Oxidative Stress
Oxidative stress is the imbalance between the production of reactive oxygen species or reactive nitrogen species (free radicals) and antioxidants that detoxify them. And it increases with aging and menopause.
Elevated oxidative stress depletes nitric oxide, the magic midlife molecule you can read about here. NO helps keep arteries flexible–and plaque from forming — with good blood flow, amongst many other amazing things. When NO gets too low for our endothelium (the cells that line blood vessels) becomes dysfunctional.
Adding estrogen is one way to decrease oxidative stress–especially in younger women — but it’s not the only way and each of us has needs.
For instance, magnesium supplements may help lower oxidative stress. But one woman may not be getting enough from her diet while another gets plenty, so taking magnesium may not have an effect.
Another study found that as women move through menopause, those with high homocysteine have more oxidative stress. So, for another woman, working on decreasing her homocysteine by upping her B vitamins may help.
Getting enough antioxidant micronutrients like vitamins C, E, D, and riboflavin is important to avoid oxidative stress and inflammation, according to a 2021 Frontiers of Neuroscience study.
And maintaining and building muscle can help lower oxidative stress too. In one study, lower muscle mass in early postmenopause was linked to higher oxidative stress markers.
I could go on, but suffice it to say we need to do a variety of things to help keep oxidative stress at bay. The University of Colorado researchers showed that reduced estrogen levels lead to oxidative stress, recommended research:
Future investigations should examine whether maintaining estradiol concentration and/or implementing lifestyle or other preventive strategies that mitigate oxidative stress during the perimenopausal years is effective in preserving or attenuating the decline in endothelial function in women.
So what are we waiting for??
Vitamins and minerals
If you’ve been reading this newsletter long enough, you know that I believe nutrition needs change at midlife for women. I recently did a recap of key micronutrients that are affected by estrogen you can read about there.
That other half of the midlife puzzle–aging–also affects micronutrient status. Hypochlorhydria, the decrease in stomach acid that happens as we age, affects the absorption of iron, vitamin B12, calcium, magnesium, zinc, and vitamin C. Then, when you add on certain medications that impact nutrient absorption, you have a double whammy.
In fact, the second most prescribed drug, the antihypertensive drug ace inhibitors, has been shown to decrease zinc status. Metformin frequently prescribed for diabetes increases the risk of calcium, vitamin D, and vitamin B12 deficiencies. According to a U.S. services study, 22% of outpatient diabetes patients had vitamin B12 deficiency.
The seventh most prescribed medication, proton pump inhibitors (PPIs), interferes with the absorption of aforementioned nutrients due to neutralizing stomach acid. In fact, chronic use of PPIs is linked to increased bone fractures in post-menopausal women. Research also shows these drugs can induce magnesium deficiency, resulting in muscle cramps and abnormal heart rhythms.
By the way, drugs like PPIs are not meant to be taken long-term!! Yet 50% of the time they are prescribed inappropriately, according to a large UK study.
A higher Ph in the stomach increases the risk of ulcers (Helicobacter pylori) and small intestinal bacterial overgrowth (SIBO). That’s because strong stomach acid is a defense against pathogens.
It’s not clear exactly what causes the decline in stomach acid. According to a WebMD article, we need iron, zinc and B vitamins to maintain stomach acid, but I couldn’t find the original research to support this.
If you’re having stomach issues, talk to your healthcare provider about getting the right tests to determine if you have hypochlorhydria. It could be due to inflammation from oxidative stress or other factors, we really just don’t know.
Just another gap in the research for midlife women.
A broader view of exercise and bone health
Estrogen is FDA approved to maintain bone mass. But this does not mean those of us who don't take estrogen are doomed.
There’s also strength training. According to a 2007 study, resistance training prevented bone loss in early post-menopause just as much as menopausal hormone therapy. A recent meta-analysis shows exercise as a promising strategy to combat osteoporosis, but the quality of evidence is low.
We need to do more high-quality studies. And why on earth do most insurance companies only cover bone density screening after 65, when midlife is over?
I share the results of my DEXA bone screening here.
The Vagina problem
When estrogen declines, so does vaginal health. More than half of midlife women have the genitourinary syndrome of menopause (vaginal atrophy or atrophic vaginitis) and this number jumps to 84% six years after menopause.
In 2014, the name was changed from vaginal atrophy to genitourinary syndrome of menopause (GSM) to better describe the symptoms that include the entire female genitourinary tract, including the vagina, labia, urethra, and bladder.
The primary culprit to GSM is declining estrogen levels that decrease lubrication, increase the ph, and alter the microbiome of the vagina. As I’ve looked at the research, I’ve found that without estrogen, there’s a vagina problem.
Symptoms can range from dryness, burning, and irritation; urinary symptoms and conditions of dysuria, urgency, and recurrent urinary tract infections (UTIs); and sexual symptoms of pain and dryness. Physical changes and signs are varied.
Women can have all or some of these symptoms. In the Vaginal Health Insights, Views & Attitudes (VIVA) online survey of 3,520 postmenopausal women 80% said GSM negatively affected their life, 75% said it affected sexual intimacy, and 36% said it made them feel old.
Additionally, the recurrent UTIs and bladder issues can adversely affect health and quality of life. It’s important to note that any symptoms should be checked out with a medical professional as they can be caused by other, more rare conditions. Never assume it’s just hormones.
Basically, estrogen increases glycogen in the vagina, which increases good bacteria, including different strains of lactobacillus. More of this good bacterium keeps the pH in check.
When you have more good bacteria, you’re less likely to get infections and that includes UTIs. You’re also less likely to get annoying symptoms that come on as you transition to menopause, which can lead to more serious symptoms with your bladder.
The best news is vaginal estrogen is safe and non-systemic, meaning it’s not (or minimally) absorbed in the bloodstream. This means many women who can’t take hormone therapy, often quality for vaginal estrogen. But there are other options too, such as vaginal DHEA and a medication called Ospemifene. Check with your healthcare provider.
I’m intrigued with the emerging research shows, taking probiotics with the right bacteria can help increase it in the vagina. According to a 2022 review on the subject:
The use of probiotics can improve vaginal flora, increase beneficial bacteria, reduce the number of harmful bacteria, and further maintain the stability of vaginal flora environment
You can take it vaginally, but oral preparations work too. There’s a probiotic for women’s health from Culturelle that includes all the strains found to be good for vaginal health. There’s also one called Clairevee that I’ll keep an eye on. Maybe with more research, probiotics alone could do the trick to help with The Vagina Problem.
Looking beyond estrogen
I’m happy when women find relief taking estrogen and progesterone and I’m sure it enhances the health of some women. Yet we need to look beyond estrogen if we are to help midlife women build strong robust heath.
There’s so much work to be done to help define the new needs of midlife women. I often wonder what we are waiting for.
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