Estradiol (Postmenopausal)
Estradiol, the most potent of the three primary estrogens (estradiol, estrone, and estriol), plays an essential role in maintaining the health of nearly every tissue in the body, in particular the reproductive tissues, brain, skin, bone, liver, and cardiovascular system. Physiological levels of estradiol formed cyclically with natural progesterone throughout a woman’s premenopausal years maintain the health and youthfulness of these tissues.
Menopause results in the loss of ovarian estrogen production and a consequent drop in circulating levels of estradiol. If, during menopause, estradiol drops well below the lower end seen in premenopausal women, this can be associated with adverse effects in the reproductive tissues (incontinence, vaginal dryness), brain (lowered neurotransmitters, increased hot flashes and night sweats), skin (more rapid aging), bone (accelerated loss and greater risk for osteoporosis and fracture), liver (compromised hormone metabolism and reduced synthesis of hormone binding globulins, reducing the circulating half-lives of hormones that are bound to them), and cardiovascular system (increased risk for insulin resistance, diabetes, and cardiovascular disease).
Needless to say, estrogens, and specifically estradiol, are essential for maintaining health in both premenopausal and postmenopausal women.
While estradiol plays this significant role in maintaining health, it can also have the opposite effect when certain catechol metabolites are formed in excess and not eliminated properly. Two separate enzymes are involved in converting estradiol and estrone to their respective 2- and 4-catechol derivatives. 2-catechol estrogens are formed by the interaction of the cytochrome enzyme designated CYP1A1. 4-catechol estrogens are formed from CYP1B1. If methylated, both 2- and 4-catechols are essentially rendered inert (harmless), and are excreted in urine. In a healthy individual the formation of estrogens, their beneficial utilization by tissues, and their subsequent elimination in urine and feces are biochemically well coordinated and balanced. However, estradiol and estrone can turn bad in the same way as beneficial oils can go rancid. In fact, the process is very similar and involves oxidation of the estrogens to highly reactive and potentially dangerous metabolites. If these metabolites are not properly channeled down safe pathways of elimination, this could be damaging to some tissues in a way that may eventually be expressed as cancer, most notably breast cancer.
In the presence of excessive reactive oxygen species (ROS) such as peroxylipids, formed mostly from transfats consumed in the diet, the catechol estrogens are further co-oxidized to highly reactive 2- and 4-estrogen quinones. In fact, the reason for avoiding trans-fats to protect the cardiovascular system against damage is the same reason to avoid them to protect the breasts from damage that may lead to breast cancer. ROS such as peroxylipids are very electrophilic (electron hungry) molecules that, under normal circumstances, are inactivated rapidly by interaction with glutathione (the most abundant nucleophilic molecule in tissues, which donates electrons to reactive electrophiles to inactivate them) and glutathione transferase. However, if ROS are in abundance and glutathione levels are low, the highly reactive catechol quinones can bind to DNA, causing mutations that can lead to cancer. 4-quinone estrogens are considered much more dangerous than 2-quinone estrogens because the former cause DNA damage that leads to more permanent (unfixable) mutations (2) that can produce aberrant cancer cells, and given the right circumstances (e.g., a compromised immune system) eventually a breast tumor.
General guide to interpretation:
Lower levels of estradiol and estrone, and higher relative levels of 16-hydroxyestrone and estriol are associated with lower breast cancer risk in postmenopausal women not supplementing with exogenous estrogens (i.e., estrogen replacement therapy). However, this is also dependent on the level of catechol estrogens present, their relative levels (2 vs 4), and how well they are methylated.
If estrogens (estradiol and estrone) are low, as are the catechol estrogens, this would portend a lower risk for breast cancer, but possibly a higher risk for symptoms (e.g., hot flashes), conditions (e.g., bone loss), and diseases (e.g., cardiovascular disease) associated with estrogen deficiency. When estradiol, estrone, and estriol are low, the methylated estrogens would be expected to be low also because of low levels of precursor catechol estrogens. If, however, catechol estrogens are elevated, regardless of the estradiol or estrone level, and methylated estrogens are low, this could indicate higher risk. Keep in mind that the catechol estrogens are not dangerous per se, unless converted to more reactive quinone estrogens. Whether the quinone estrogens damage DNA, or are rapidly inactivated will depend on many factors that are modifiable through diet and nutritional supplements. Excessive dietary consumption of unhealthy trans-fats oxidizes catechol estrogens to more dangerous quinone estrogens, and if glutathione is not present in adequate amounts the quinone estrogens are more likely to damage DNA, and lead to mutations that could be eventually expressed as breast cancer.
Prevention Strategies:
1) Prevention strategies begin with reducing the overall burden of excessive estradiol and estrone in the absence of diminished levels of progesterone, which often occurs in the early phases of menopause (perimenopause-ages 35-55). Progesterone supplementation helps reduce the estrogen burden by increasing the conversion of E2 to E1 (activates 17-beta-hydroxysteroid dehydrogenase), and E1 to E1-sulfate (E1-SO4), an inert form of estrogen that will not enter target cells. 2) 2-hydroxy catechol estrogens are safer than 4-hydroxy catechol estrogens; these are created from the cytochrome enzyme CYP1A1, which is activated by phytochemicals found in cruciferous vegetables (cauliflower, broccoli, cabbage), and by iodine, progesterone, and Vitamin D. If 2-hydroxy catechol estrogens are low, or are low relative to the 4-hydroxy catechol estrogens, consider lowering consumption of meats and increasing consumption of green leafy and cruciferous vegetables.
3) 4-hydroxy catechol estrogens are created from the cytochrome enzyme CYP1B1, which is induced by man-made petrochemical toxins (some drugs, oils, plastics, pesticides, household chemicals, etc.) that contaminate our food, water, and air. If 4-hydroxy catechol estrogens are elevated, consider identifying and avoiding exposure to these petrochemical products as much as possible.
4) As the good (2-OH-catechols) and bad (4-OHcatechols) are both rendered inactive by COMTmediated methylation, it is important to maintain adequate substrates for COMT. These include vitamins B6, B12, and folate, as well as betaine. Excessive estrogens tend to deplete these vitamins, so supplementation during times of estrogen excess (often at perimenopause) is vital to clearing catechol estrogens such that they are less likely to spill over into the highly reactive and mutagenic 4-estrogen quinones.
5) Prevent the conversion of the 2- and 4-catechol estrogens into their respective quinones, and provide adequate substrate to inactivate them if they do. The 2- and 4-catechol estrogens are activated to their quinones by oxidized fats and some heavy metals such as arsenic and mercury. Removal of bad (trans) fats from the diet and countering the heavy metals with adequate beneficial elements such as iodine and selenium are important for preventing further oxidation of estrogen catechols to estrogen quinones.
6) Iodine, progesterone (only when estrogens are within normal to high physiological range of a premenopausal woman), and Vitamin D have all been shown to increase formation of 2-hydroxy catechol estrogens, and decrease the relative concentration of the more dangerous 4-hydroxy catechol estrogens. Consider supplementation if any of these is found to be low by testing.
7) Glutathione is important as the last step in detoxification of quinone estrogens. Excessive medications, hormone therapy, and exposure to environmental toxins such as heavy metals, cigarette smoke and excessive industrial air pollution results in high utilization and lower levels of glutathione. Cysteine is the most limiting amino acid as regards glutathione synthesis, and vitamin C is an essential nutrient for reactivation of oxidized glutathione. Selenium also plays an important role in glutathione’s effectiveness as an anti-oxidant, and low levels of selenium have been associated with higher risks for cancers of the breasts and prostate. If quinone estrogens are elevated, particularly if the methylated catechol estrogens are low, consider foods high in sulfur containing amino acids (allium foods like garlic and onions) and/or supplementation with N-acetylcysteine and Vitamin C. Also consider supplementation with selenium, an essential element in many anti-oxidant enzymes, if it is found to be low.
8) Inadequate production of melatonin has been linked with breast cancer. Melatonin has antiestrogenic actions, acting as a selective estrogen receptor modulator in breast tumor cells, and also downregulating aromatase, thus reducing local estrogen synthesis from androgenic precursors.
Because of the oncostatic effects of melatonin, breast cancer risk can be reduced by getting adequate sleep and/ or reducing exposure to light at night.
References:
Lee JR, Zava D, Hopkins V. What your doctor may not tell you about breast cancer. How hormone balance may save your life. Warner Books, Inc., New York, NY, 2002. Chapter 6.
Cavalieri EL, Rogan EG, Chakravarti D. Initiation of cancer and other diseases by catechol orthoquinones: a unifying mechanism. Cell Mol Life Sci. 2002;59:665-81.
Huang J, Sun J, Chen Y, Song Y, Dong L, Zhan Q, Zhang R, Abliz Z. Analysis of multiplex endogenous estrogen metabolites in human urine using ultra-fast liquid chromatography-tandem mass spectrometry: a case study for breast cancer. Anal Chim Acta. 2012;711:60-8.
Getoff N, Gerschpacher M, Hartmann J, Huber JC, Schittl H, Quint RM. The 4-hydroxyestrone: Electron emission, formation of secondary metabolites and mechanisms of carcinogenesis. J Photochem Photobiol B. 2010 Jan 21;98(1):20-4.
Arslan AA, Shore RE, Afanasyeva Y, Koenig KL, Toniolo P, Zeleniuch-Jacquotte A. Circulating estrogen metabolites and risk for breast cancer in premenopausal women. Cancer Epidemiol Biomarkers Prev. 2009;18:2273-9.
Obi N, Vrieling A, Heinz J, Chang-Claude J. Estrogen metabolite ratio: Is the 2-hydroxyestrone to 16α-hydroxyestrone ratio predictive for breast cancer? Int J Womens Health. 2011;3:37-51.
Falk RT, Brinton LA, Dorgan JF, Fuhrman BJ, Veenstra TD, Xu X, Gierach GL. Relationship of serum estrogens and estrogen metabolites to postmenopausal breast cancer risk: a nested casecontrol study. Breast Cancer Res. 2013;15:R34.
Fuhrman BJ, Schairer C, Gail MH, Boyd-Morin J, Xu X, Sue LY, Buys SS, Isaacs C, Keefer LK, Veenstra TD, Berg CD, Hoover RN, Ziegler RG. Estrogen metabolism and risk of breast cancer in postmenopausal women. J Natl Cancer Inst. 2012;104:326-39.
Cos S, Gonzalez A, Martínez-Campa C, et al. Estrogen-signaling pathway: a link between breast cancer and melatonin oncostatic actions. Cancer Detect Prev. 2006;30:118-28.
What does it mean if your Estradiol (Postmenopausal) result is too high?
High estradiol in premenopausal women is usually caused by excessive production of androgens (testosterone and DHEA) by the ovaries and adrenal glands, which are converted to estrogens by the ‘aromatase’ enzyme found in adipose (fat) tissue. When estrogen levels are high in postmenopausal women, this is usually due to estrogen supplementation or slow clearance from the body (sluggish liver function). Excess estrogen levels, especially in combination with low progesterone, may lead to the symptoms of “estrogen dominance,” including: mood swings, irritability, anxiety, water retention, fibrocystic breasts, weight gain in the hips, bleeding changes (due to overgrowth of the uterine lining and uterine fibroids) and thyroid deficiency. Estradiol, even at normal, premenopausal levels, can cause estrogen dominance symptoms if not balanced by adequate progesterone. Diet, exercise, nutritional supplements, cruciferous vegetable extracts, herbs and foods that are natural aromatase inhibitors and bioidentical progesterone can help to reduce the estrogen burden and symptoms, naturally.
All Your Lab Results.
One Simple Dashboard.
Import, Track, and Share Your Lab Results Easily
Import, Track, and Share Your Lab Results
Import lab results from multiple providers, track changes over time, customize your reference ranges, and get clear explanations for each result. Everything is stored securely, exportable in one organized file, and shareable with your doctor—or anyone you choose.
Cancel or upgrade anytime
What does it mean if your Estradiol (Postmenopausal) result is too low?
Low estradiol in premenopausal women is unusual unless they experience an anovulatory cycle (no ovulation) or are supplementing with birth control pills, which can suppress endogenous (made in the body) production of estrogens by the ovaries. A low estradiol level is much more common in postmenopausal women or in women of any age who have had their ovaries surgically removed (oophorectomy) and/or those who have not been treated with hormone replacement. Symptoms and conditions commonly associated with estrogen deficiency include hot flashes, night sweats, sleep disturbances, foggy thinking, vaginal dryness, incontinence, thinning skin, bone loss, and heart palpitations.
Laboratories
Bring All Your Lab Results Together — In One Place
We accept reports from any lab, so you can easily collect and organize all your health information in one secure spot.
Pricing Table
Gather Your Lab History — and Finally Make Sense of It
Finally, Your Lab Results Organized and Clear
Personal plans
$79/ year
Advanced Plan
Access your lab reports, explanations, and tracking tools.
- Import lab results from any provider
- Track all results with visual tools
- Customize your reference ranges
- Export your full lab history anytime
- Share results securely with anyone
- Receive 5 reports entered for you
- Cancel or upgrade anytime
$250/ once
Unlimited Account
Pay once, access everything—no monthly fees, no limits.
- Import lab results from any provider
- Track all results with visual tools
- Customize your reference ranges
- Export your full lab history anytime
- Share results securely with anyone
- Receive 10 reports entered for you
- No subscriptions. No extra fees.
$45/ month
Pro Monthly
Designed for professionals managing their clients' lab reports
- Import lab results from any provider
- Track lab results for multiple clients
- Customize reference ranges per client
- Export lab histories and reports
- Begin with first report entered by us
- Cancel or upgrade anytime
About membership
What's included in a Healthmatters membership
Import Lab Results from Any Source
See Your Health Timeline
Understand What Your Results Mean
Visualize Your Results
Data Entry Service for Your Reports
Securely Share With Anyone You Trust
Let Your Lab Results Tell the Full Story
Once your results are in one place, see the bigger picture — track trends over time, compare data side by side, export your full history, and share securely with anyone you trust.
Bring all your results together to compare, track progress, export your history, and share securely.
What Healthmatters Members Are Saying
Frequently asked questions
Healthmatters is a personal health dashboard that helps you organize and understand your lab results. It collects and displays your medical test data from any lab in one secure, easy-to-use platform.
- Individuals who want to track and understand their health over time.
- Health professionals, such as doctors, nutritionists, and wellness coaches, need to manage and interpret lab data for their clients.
With a Healthmatters account, you can:
- Upload lab reports from any lab
- View your data in interactive graphs, tables, and timelines
- Track trends and monitor changes over time
- Customize your reference ranges
- Export and share your full lab history
- Access your results anytime, from any device
Professionals can also analyze client data more efficiently and save time managing lab reports.
Healthmatters.io personal account provides in-depth research on 10000+ biomarkers, including information and suggestions for test panels such as, but not limited to:
- The GI Effects® Comprehensive Stool Profile,
- GI-MAP,
- The NutrEval FMV®,
- The ION Profile,
- Amino Acids Profile,
- Dried Urine Test for Comprehensive Hormones (DUTCH),
- Organic Acids Test,
- Organix Comprehensive Profile,
- Toxic Metals,
- Complete Blood Count (CBC),
- Metabolic panel,
- Thyroid panel,
- Lipid Panel,
- Urinalysis,
- And many, many more.
You can combine all test reports inside your Healthmatters account and keep them in one place. It gives you an excellent overview of all your health data. Once you retest, you can add new results and compare them.
If you are still determining whether Healthmatters support your lab results, the rule is that if you can test it, you can upload it to Healthmatters.
We implement proven measures to keep your data safe.
At HealthMatters, we're committed to maintaining the security and confidentiality of your personal information. We've put industry-leading security standards in place to help protect against the loss, misuse, or alteration of the information under our control. We use procedural, physical, and electronic security methods designed to prevent unauthorized people from getting access to this information. Our internal code of conduct adds additional privacy protection. All data is backed up multiple times a day and encrypted using SSL certificates. See our Privacy Policy for more details.