Estrogens have had a bad rap for a long time but they are major signaling molecules in the body that have many beneficial and complex activities. There are actually over 60 estrogenic-acting estrogens in the human body, though 3 are the most famous Charlie’s Angel estrogens:

  1. Estradiol (the strongest “purest estrogen” that delivers signals to most estrogen receptors),
  2. Estriol (a gentler estrogen that sends anti-cancer signals) and,
  3. Estrone (known as the bad sister estrogens like the bad sisters in Cinderella, that is more predominantly produced in menopause and is often regarded as a pro-carcinogenic (cancer-causing) estrogen.
Are all estrone type estrogens nasty?

Maria wrote and asked me this question yesterday, which is why I put this blog together. The answer is NO.

We need all our estrogens.

Nature never does anything without a good reason. She has robust and helpful job descriptions for all of estrogens. They work together. They are manufactured, travel to tissues that long to “hear” from them, do their job of sending signals to genes inside these tissues, acting like signaling emails. Then the hormones are metabolized (broken down) into smaller pieces, called metabolites. Even these metabolites and their ratios to each other have actions that affect us. All the while estrogens keep morphing in and out of each other, affecting each other as well as distant and diverse tissues.

The main estrogens—estrone (E1), estradiol (E2), and estriol (E3)—fluctuate throughout our life stages, in both males and females, and throughout each month in premenopausal women. They affect diverse healthy biological as well as unhealthy disease processes.

Estrogens protect. Many diseases (such as Parkinson’s, Alzheimer’s, Tourette’s, attention deficit hyperactivity disorder, osteoporosis, and heart disease) are more apt to occur or get worse in women after menopause (when estrogens go down). Some diseases get better during pregnancy when unique estrogens (like estriol) go up. Partum-related depression can occur when these high pregnancy hormone levels plummet after giving birth or make the thyroid dysfunctional for a period of time. This demonstrates an overall protective and greatly influential effect of changing levels and ratios of estrogens to how we feel, our vulnerability to diseases and our health or lack of it.

Estrogens have robust roles in health. In both males and females. So do their breakdown products, metabolites.

Estradiol is the estrogen more often linked to delivering the most powerful estrogenic signals that protect and direct reproduction, heart, bone, vocal and digestive health and more.

The other estrogens have explicit job descriptions, too.

Estrone (E1) is a significant estrogenic hormone contributor in BOTH pre and postmenopausal women and in men, too. It is heart and brain protective.

Estriol (E3) levels are significantly higher in pregnant women than in non-pregnant women and are being appreciated more and more for anti-inflammatory and gut healing effects. This is one reason why many women with inflammatory conditions (like MS and inflammatory bowel diseases) go into remission during pregnancy.

Endocrinology is the production of hormones from their primary glands. The ovaries produce the majority of estrogens. The adrenal glands secrete some estrogens, too. As we age, endocrinologic production of hormones wans. Enter center-stage, the production of hormones by other means.

Intracrinology is the production of hormones in local non-reproductive (glandular) tissues by the action of enzymes. This type of hormone production is active throughout our lives, but especially ramps up as we get older and our ovaries and prostate retire. Intracrinologic production of hormones in local tissues requires converting enzymes. Converting enzymes take “precursor” molecules such as testosterone or DHEA (dehydroepiandrosterone) and morph them into estrogens (and sometimes into male hormones, too). This estrogen alchemy takes place throughout the body, in non-reproductive tissues such as inside your brain, liver, and fat cells and even inside your stomach!

Intracrinology is how much of our hormones are produced in the second half of life for both men and women. It is highly dependent on the pro-hormone DHEA which is the main parent molecule waiting to be morphed into estrogens (and testosterone). DHEA enters tissues, and in the presence of converting enzymes, transforms into estrone, which then converts into estradiol.

This local hormonal production company in various tissues (such as fat, liver, and brain cells) keeps us stronger as we age. Local estrogens (as well as the DHEA itself) help make us less prone to cancer, dementia and heart disease. DHEA and the critical local production of estrone and estriol are closely linked to helping up live longer and do a better healthier job of it.

Why? Many tissues need estrogen. Even estrone.

The effects of estrogens go beyond reproductive functions. Estrone (E1) in mature humans has many beneficial actions. Estrone protects the endothelial lining of blood vessels. The endothelium is the term for the lining of your blood vessels. Your heart is as healthy as you’re the health of the lining of your blood vessels. Estrone helps prevent this endothelium from shrinking and becoming excessively rigid and unhealthy. Rarely in nature is something all good or bad. One reason that women have more estrone when they are older is that their older blood vessels and heart need it. Estrone promotes the production of nitric oxide. This acts like a yogic molecule on the blood vessels keeping them dilated, relaxed and Zen. Estrone and estradiol both help produce healthier blood vessels and thus healthier heart function.

Estriol (E3) is so anti-inflammatory it is used clinically (given by intramuscular injection) in MS patients to reduce brain plaques and symptoms. E3 has pain protective effects against the development of arthritis in experimental animal models. I have been using estriol successfully to treat long-standing cases of interstitial cystitis and various inflammatory bowel diseases as it tamps down inflammation and pain.

The 3 estrogens do diverse tasks. Estriol protects against cancer. Men have more estriol receptors (estrogen receptor beta) in their lungs than women. That is one reason women are more at risk of lung cancer from smoking (primary, secondary or tertiary exposures) compared to men. The brain, bone, the cardiovascular (heart) system and many other tissues, even kidney and vocal chords, can all be affected differently at different times of life by these 3 Charlie’s Angel estrogens.

Estriol protects breast, lung and gut wall tissue. But in the blood vessels you don’t want too much estriol. You rather have estrone and estradiol. Each estrogen oversees diverse actions for diverse tissues. The ratios of the local estrogens exert various physiologic results.

Estradiol protects the lungs from aging and disease, it protects the vocal chords from old lady or man voice, and it protects the hippocampus, the physiologic soul deep inside your brain.

Estrone is too often regarded as a dangerous pro-cancer hormone. But here are just a few examples of benefits from estrone:

  • Protects blood vessels and heart tissue
  • Is neuroprotective (helps nerves in the spine and brain stay well especially after injuries such as trauma, stroke, etc.)
  • Researchers at the Center for Resuscitation Research, Department of Surgery, University of Texas Southwestern Medical Center, Dallas, Texas reported, “Estrone, the predominant estrogen in postmenopausal women, has been shown to be a promising neuroprotective agent.”
  • In animal models estrone reduces nerve death after injury.
  • Estrone, in the aging woman, helps protect her brain.

Our fat cells make estrone. Usually estrogen replacement is recommended as giving estradiol and estriol together, called bi-est, due to the combination of two—bi—estrogens. Tri-est used to be recommended more often. But as estrone in excess (like estradiol) can promote growth out of control and since most women have enough fat cells, which produce estrone, mostly bi-est formulas are now prescribed. Once in a while a woman is so thin, she may benefit from some Tri-est. This is yet another reminder that all hormone recommendations must be individualized.

It is said that a woman with higher estrogens in menopause has a higher risk of hormonally driven cancers like breast cancer. And that this is especially true for the levels of estrone. But is it “elevated” estrogens or hormones out of balance? If we have enough of the minerals that keep hormones acting safer than not, and if the estrogen ratio to each other is more harmonious than not, and if we have the protective hormones to balance out the estrogens, and if our gut flora correctly chit chats with all the hormonal conversations going on, then is cancer risk really an isolated estrogen phenomenon? I think not.

  • We need hormones, all of them.
  • It’s about balance.
  • And not having a “weakest link” that is silently snagging your health back. For example, hormone health depends on local nutrient robustness, which itself depends on multiple digestive functions. Even hormone health comes back to the gut.

It ‘s never just a “this” for “that” as we have come to think in modern medicine—we have a symptom so we give a drug. That is a binary system of medicine.

I am into the community perspective of medicine. Are all our citizens well and happy making for a healthier community? This includes our community of estrogen.

And, remember we do not live on an isolated island. We live in a chemical soup. Diverse potentially hormone disruptive pollutants gain entry into our bodies from that cheese that was shrunk wrapped in plastic, or your laminate floors, or your new car phthalate dashboard or your perfumes, or the pesticides in your crackers. These can act synergistically as powerful estrogen mimics that disrupt normal estrogenic signaling, no matter the ratio of estrogens inside our body.

Another way estrogen can be hijacked by our polluted planet is not very well known. Estrone is made into a storage form so when we need it, we have reserves, and we don’t have too much active estrone floating around when we don’t need it. This storage form of estrogen is made by converting estrone into a sulfated form called estrone sulfate. But this conversion is blocked by environmental estrogens such as Bisphenol A, which is found in the lining of food cans and also found in the white dental fillings in your mouth and in many other contemporary items such as various plastics. So the “outside” is getting in on our “inside” and affecting our hormones, such as estrone. Just running blood or saliva or urine levels of hormones is not necessarily telling your practitioner the whole story of your internal hormonal dynamics. The story of hormones, and estrones, just keeps getting more intricate. I love the name of the movie with Meryl Streep and Alec Baldwin, which says it all… “It’s complicated!” So if you want to have a practitioner tend your hormones well, you better know someone that has a good handle on the much bigger picture!

Thanks for asking me this question Maria.

Dr. Lindsey Berkson

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References

FASEB J. 2008 Sep; 22(9): 3328–3336. Nongenomic actions of estradiol compared with estrone and estriol in pituitary tumor cell signaling and proliferation

Mol Cell Endocrinol. 2011 Jun 6;339(1-2):136-43. Cellular and molecular actions displayed by estrone on vascular endothelium.

Life Sciences 82(1-2):115-23 · January 2008 The direct action of estrone on vascular tissue involves genomic and non-genomic actions

Steroids. 2014 Mar;81:36-42. doi: 10.1016/j.steroids.2013.11.006. Epub 2013 Nov 20.Rapid actions of xenoestrogens disrupt normal estrogenic signaling.

J Neurotrauma. 2012 Aug 10; 29(12): 2209–2219. Estrone Is Neuroprotective in Rats after Traumatic Brain Injury

Biol Lett. 2015 Apr; 11(4): 20140946. The in ovo conversion of oestrone to oestrone sulfate is rapid and subject to inhibition by Bisphenol A