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Meet Sally!
In this video Sally will give you an introduction to the blog about estrogen.
Meet the estrogens
Meet the liver Estrogens
Did you know …
Is the family name and there are many Estrogens
- The main Estrogens
– E1 – Estrone – the lazy Estrogen
– E2 – Estradiol – the powerful Estrogen
– E3 – Estriol – the quiet Estrogen – also known as 16-OH-E2 – 16-hydroxyestradiol
- The pregnancy Estrogen – only found in females
– E4 – Estetrol – the native Estrogen of the foetus
- The liver Estrogens – a very long list of Estrogen metabolites ready for excretion. BUT these hormones can still stimulate Estrogen receptors if they come back into circulation and can be converted back to the main Estrogens
- Estrogens are fat-soluble hormones made from cholesterol
- Estrogens are a type of ‘anabolic steroid’
- Anabolic means tissue builder and Estrogen builds fat, skin, bone, muscle and brain cells, etc.
- Steroid means made from cholesterol
- Estrogen creates changes in cell activity and function through its 2 nuclear receptors ER-alpha and ER-beta
- Estradiol binds equally well to both receptors
- Estrone binds preferentially to the alpha receptor
- Estriol binds to the beta receptor
- ER-αlpha is upregulated in the majority of breast cancers
- ER-beta levels, in contrast, are decreased in tumour cells
- Estrogen creates all that is female, such as body shape, reproduction ability and mood, etc
- Estrogens are produced in both men and women from the day we’re born until the day we die in:
– fat cells
– the Adrenal glands
– the brain
– the liver
- Estrogens are produced in women from puberty to menopause in:
– the Ovaries
- Estrogens are produced in men from puberty until they die in:
– the Testicles
- Science demonstrates that Estrogen is much more than just a fertility hormone, absolutely essential for brain, cardiovascular, skeletal, gut health, and much more
- Measuring Estrogen in the blood is limited to Estradiol
- Measuring all the main Estrogens and some of the liver Estrogens is possible through urine – BUY HERE
- Estrogen levels in fertile women fluctuate throughout the cycle
- When measuring Estrogen levels know which day in your cycle you get tested so you evaluate in the appropriate reference range
- Estrogen supports optimal Insulin function, keeping fat storage under control
- Estrogen balances Cortisol, making women more resilient to stress
- Estrogen supports nitric oxide production increasing vasodilation and thereby optimal blood pressure levels
- Estrogen supports brain cell growth and connections and the production of neurotransmitters such as Serotonin
- Estrogen supports bone density and strength
- As Estrogen levels decline in peri-menopause symptoms like brain fog, poor memory and mood swings, high blood pressure and cardiovascular problems, increased tummy fat and type 2 Diabetes, decreased ability to cope with stressful situations and osteoporosis unfortunately become part of the make-up for women 50+.
Meet The Estrogens
Estrone / E1 – the lazy hormone
- Discovered in 1929
- Is produced in fats cells (breast tissue)
- Is produced in the Adrenals
- Is produced in the Ovaries
- Is produced from Estradiol in liver, uterus and breast
- Is a storage hormone
- Can converts to Estradiol
- Is the dominant Estrogen after menopause
- Is broken down to the Hydroxy-Estrogen’s in the liver
- Previously given as a form of ERT
- High estrone levels may increase the growth of breast cancer and uterine cancer.
Estradiol / E2 – the powerful hormone
- Discovered in 1933
- Is produced primarily in the Ovaries
- Is produced in the Adrenals
- Is produced in the Hypothalamus of the brain
- Is produced in the liver
- Is produced in the testicles
- Is produced in fat cells (breast tissue)
- It makes you a woman in everyway
- Converts to Estrone in liver, uterus and breast
- Is broken down to the Hydroxy-Estrogen’s in the liver
- Is the common form for ERT and contraception and hormone therapy for transgender women
Estriol / E3 – the quiet hormone
- Discovered in 1930
- Is produced in the placenta during pregnancy
- Is produced in the liver from Estradiol
- Is a hydroxy-Estrogen
- Especially important for vaginal health and skin
- Possibly has a controlling effect on Estradiol and Estrone.
The Liver Estrogens
- Are Estrogen metabolites on their way to
- BUT these hormones can still stimulate Estrogen receptors if they come back into circulation
- Which type of Estrogen you make in the liver is genetically controlled by CYP-450 enzyme family, but also effected by diet and lifestyle
Two Phases of liver detoxification
- Phase 1 – Estrone and Estradiol are converted to hydroxy version, which are in principle free radicals
- Phase 2 – phase 1 hormones are conjugated (stabilised and made water soluble) in various ways
Phase 1 the Hydroxy Estrogens
- 2-OH-E1 – 2-Hydroxyestrone – less estrogenic and generally considered ‘safe’
- 2-OH-E2 – 2-Hydroxyestradiol – less estrogenic and generally considered ‘safe’
- 4-OH-E1 – 4-Hydroxyestrone – may create DNA damage and mutations and generally considered ‘unsafe’
- 4-OH-E2 – 4-Hydroxyestradiol – may create DNA damage and mutations and generally considered ‘unsafe’
- 16-OH-E1 – 16-Hydroxyestrone – may increase estrogen stimulation in breast tissue and endometrium, creating larger breasts and heavier bleeds
- 16-OH-E2 – Estriol – the 3rd main Estrogen
Phase 2
- In phase 2 Estrogens are made water soluble in various ways, creating many more Estrogens
- The processes are called
- Methylation
- Glutathione conjugation
- Sulfation
- Acetylation
- Glucuronidation
- Amino acid conjugation
An example of some of the ‘new’ Estrogens
Methoxy Estrogens
- 2-ME1- 2-Methoxyestrone
- 2-ME2 – 2-Methoxyestradiol
- 4-ME1 – 4-Methoxyestrone
- 4-ME2 – 4-Methoxyestradiol
- 2-MeO-E3 – 2-Methoxyestriol
Sulfated Estrogens
- E1-3S – Estrone 3-sulfate
- E2-3S – Estradiol 3-sulfate
- E2-17S – Estradiol 17β-sulfate
- E3-3S – Estriol 3-sulfate
- E2DS – Estradiol 3,17β-disulfate
Glucuronidated Estrogens
- E1-G – Estrone 3-glucuronide
- E2 -3G – Estradiol 3-glucuronide
- E2-17G – Estradiol 17β-glucuronide
- E3-3G – Estriol 3-glucuronide
- E3-16G – Estriol 16α-glucuronide
Mixed conjugated Estrogens
- E2-3G-17βS – Estradiol 3-glucuronide 17β-sulfate
- E2-3S-17βG – Estradiol 3-sulfate 17β-glucuronide
- E3-3S-16G – Estriol 3-sulfate 16α-glucuronide.
Testing Estrogen levels
Blood tests
- Estradiol – only Estradiol is measured in blood
- SHBG – sex hormone binding globulin – binds Estrogen and Testosterone making them inactive
- Testosterone – is converted to Estrogen, low Testosterone can cause low Estrogen
- FSH and LH – indicate ovarian function
Urine testing is gold standard for Estrogens
- Estrone
- Estradiol
- Estriol
- Hydroxy-Estrogens
- Glutathione
- Methylation
You also get to see:
- Progesterone
- Testosterone
- DHEA
- Cortisol
DNA testing
- Estrogen production
- Hydroxy-Estrogen preference
- Liver detoxification abilities
Which Hydroxy-Estrogens are you making?
Knowing which hydroxy-Estrogens you make is important.
In principle your DNA dictates and you can test yours here
But so do your lifestyle choices:
- Chronic inflammation increases production of the 4-hydroxy
- Alcohol decreases the 2-hydroxy and increases the 16-hydroxy
- Smoking increases all the hydroxy’s
- BBQ increases all the hydroxy’s
- Environmental toxins, such as PAH’s PBA, phthalates, increases all the hydroxy’s
Supplements that support production of the 2 hydroxy-Estrogens:
- DIM
- Quercetin
- Resveratrol
Estrogen Receptors (ERs)
- Receptors are proteins, that receive and convert chemical signals that cause some form of cellular/tissue response, e.g. a change in gene activity, etc.
- Agonists
– Activate the receptor
- Antagonists
– Bind to receptors but do not activate them
– Blocking the receptor
ERs
- Two types of Estrogen receptor:
– Nuclear Estrogen receptors – ERα and Erβ
– Various Membrane Estrogen receptors
- Once activated by Estrogen, the ERa and ERβ are able to transport the message into the nucleus binding to DNA and thereby regulate the activity of different genes
- Estradiol binds equally well to both receptors
- Estrone binds preferentially to the ERa
- Estriol binds to the ERβ
- ERa was discovered in 1958
- ERβ was discovered in 1996
- ERa speeds up the effects of Estrogen
- ERβ slows down or calms the effects of Estrogen
ER Agonists and Antagonists
- Agonists
– Endogenous Estrogens – estradiol, estrone, estriol,
– Natural Estrogens – ERT, conjugated estrogens
– Synthetic Estrogens – Ethinylestradiol, Diethylstilbestrol
- Mixed agonist and antagonist
– Phytoestrogens
– Selective Estrogen receptor modulators – tamoxifen
- Antagonists
– Anti-Estrogens – letrozole.
Symptoms of low Estrogen
- Irregular periods
- Infertility
- Weak bones
- Painful intercourse
- Hot flashes
- Depression
- Increase in urinary tract infections
- Problems with memory
- Lost interest and passion
- Suddenly sad for no reason
- Can’t hold focus and concentration as before
- Emotionally sensitive / fragile / tears come at the drop of a hat for the strangest of things / mini breakdowns
- Poor sleep – wake a lot during the night
- Lack of reserve, more tired than usual
- Breast tissue shrinking
- Increased tummy fat
- Suddenly high cholesterol
- Problems with blood sugar regulation and insulin resistance
- Reduced sensation in your vagina, sex not as pleasurable as before
- Pain during intercourse
- Low libido
- Light bleeds
- Dryness in eyes, nose and mouth
- Skin is dry
- Vaginal dryness and thinning of the vaginal lining
- Stiff, painful joints and muscles
- Increased need to urinate, can’t hold yourself for longer periods at a time
- Difficulty holding yourself when you sneeze, jump, etc.
Why do I have symptoms of low Estrogen?
- Often the natural result of menopause which shouldn’t occur before 45 years of age
- Hysterectomy
- Excessive training
- Eating disorders such as anorexia
- Very low fat %
- Thyroid disorders
- Pituitary disorders.
Symptoms of Excess Estrogen
- Mood swings
- Increased fat storage especially hips, buttocks, thighs and breasts
- Heavy and/or long bleeds
- Problems with uterine fibroids
- Endometriosis / exaggerated growth of the uterine wall
- Uterine fibroids
- PMS symptoms before your period, such as, nervous, tense, sad
- PCO
- Menstrual headaches or migraines
- Tender and/or lumpy breast tissue, maybe worse up to your period
- History of breast cancer in the family or self
- Swollen feet and hands, especially up to your period
- Pigmental changes in your face (dark areas)
- Facial flushing and/or Rosacea
- Gall stones or your gall bladder has been removed
- Varicose veins or spider veins (face and legs)
- Thyroid nodules or a history of Thyroid cancer.
Why do I have Symptoms of excess Estrogen
High Estrogen symptoms can occur if:
- Progesterone levels are low – known as Estrogen dominance
- Too much Estrogen from ERT or contraceptive pills
- High fat % / obesity
- Exposure to endogenous xeno Estrogens in personal care products, plastics, pesticides, textiles, etc.
- Exposure to endogenous xeno Estrogens from plant Estrogens from soy, legumes and seeds, etc.
- Ovarian tumours
- Reduced liver detoxification – think nutrients, alcohol, fatty liver
- Gut dysbiosis – unpacking conjugated Estrogens
- Certain antibiotics and other medication
- certain herbal or natural remedies, such as red clover, black cohosh that may increase Estrogen.
Estrogen production through the Ages
Infancy
- In infants, the pituitary–gonadal hormone axis is activated for a brief period of time often referred to as “mini-puberty” in baby girls increasing E2 levels briefly
Childhood
- Detectable E2 concentrations in more than half of the prepubertal girls aged 1 to 7 years
- Girls had significantly higher E2 concentrations than boys.
Puberty
- E2 concentrations raises significantly in girls with increasing age, even before physical signs of puberty were evident
- Individual variation in the circulating total E2 levels may reflect varying Estrogen receptor sensitivity or differences in circulating free E2 concentrations influenced not only by total E2 concentrations, but also by SHBG, albumin and E2 clearance.
Menstrual cycle and oral contraceptive use
- Concentrations of E1, E2 and E1-Sulafte change according to menstrual cycle day
- Low levels of E1, E2, and E1-Sulfate in the early follicular phase, which increased in the late follicular phase as expected.
- Significantly higher E1, E2, and E1-Sulfate levels were maintained in the luteal phase.
- Use of oral contraceptives in healthy teenage girls markedly suppressed serum concentrations of total and free E2
Postmenopausal women
- Detectable E2 concentrations in 94% of the 55- to 61-year-old women ranging between 7 and 80 pmol/L,
- E2 levels were significantly lower than E1 concentrations.
- In postmenopausal women, DHEA and its derivative androstenedione are considered major sources of circulating E1 from aromatization in non-gonadal tissues, such as fat tissue and adrenal glands, whereas residual E2 secretion primarily originates from the ovaries.
E1 concentrations increase with age in 70 to 85+ years old women
- Some postmenopausal women have very high E1 levels.
Men
- Assessment of circulating E2 concentrations in men could be useful in various clinical situations including gynecomastia aka man boobs, hypogonadism, and osteoporosis.
- E2 concentrations ranged from 50 to 150 pmol/L, with no changes across adult ages.
- E1 concentrations did not significantly vary with age in 30- to 60-year-old men but were higher than E2 concentrations.
Estrogen and Heart health
Estrogen’s known effects on the cardiovascular system include a mix of positive and negative:
- Increases HDL cholesterol (the good kind)
- Decreases LDL cholesterol (the bad kind)
- Promotes blood clot formation, which could be negative
- Relaxes, smooths and dilates blood vessels so blood flow increases
- Increasing nitric oxide (NO) causing vasodilation and inhibiting platelet aggregation, both of which may be important in protection against stroke.
- Soaks up free radicals, naturally occurring particles in the blood that can damage the arteries and other tissues.
- Probably affects the cardiovascular system in other ways that are as yet undiscovered.
Low Estrogen levels
- May cause your heart and blood vessels to become stiffer and less elastic.
- This can increase your blood pressure
- High blood pressure can damage your blood vessels and increase your risk for stroke, heart disease, and heart failure.
Estrogen and Uterine fibroids
- Also called leiomyomas or myomas, are noncancerous muscle tumours that appear as growths either inside, within the walls of, or on the uterus.
- They are swirls of muscle fibres that can be as small as a pea or as large as a basketball.
- Depending on their location, can cause a lot of problems for women.
- Everything from pain to increased bleeding to infertility.
- If they are small and don’t cause a problem, they can be left alone.
- Are present in 75 to 80% of women, and often require surgery to remove them, though there are some medications that can shrink them.
Estrogen and the brain
Estrogen is produced in the area in the brain called the Hypothalamus which is the Commander in Chief of the hormonal system.
Estrogen is involved in:
- Estrogen facilitates higher cognitive functions
- Exerts effects on brain regions such as the prefrontal cortex and hippocampus.
- Estrogen increases the ability to form neural networks
- All key Estrogen receptors present throughout the body are also present in synapses of the hippocampus and prefrontal cortex especially but also throughout the brain
- This enables Estrogen to initiates signalling pathways which regulates
– Learning
– Memory
– Mood
– Motor coordination
– Pain sensitivity
– Cognition
– Neuroprotection after strokes and injuries as well as Parkinson’s and Alzheimer’s diseases.
- 3 out 5 of those who develop Alzheimer’s are women
Hormone treatments thus far for women
- Concentrate largely on circulating Estrogen and progesterone levels rather than on receptor dynamics and synaptic regulation
- The focus must shift to develop more successful treatments.
- Cyclical Estrogen is more effective than constant levels of Estrogen as seen in ERT.
Estrogen and Skin
Estrogens are known to have protective and favourable influences on skin health.
Estrogen talks with the fibroblast cells in the Dermis layer of the skin telling them to produce Collagen, Elastin and Hyaluronic Acid.
Estrogen talks to the melanocytes in the Epidermis telling them to produce melanin, the skin pigment.
The loss of Estrogens with aging contributes to diminished dermal health, whereas ERT restores skin health.
Several reports suggest positive correlations between the levels of Estrogens in women and:
- perceived age
- attractiveness
- enhanced skin health
- facial coloration
Low Estrogen
- Weak skin
- Dry skin
- Permanent wrinkles
- Sagging skin
- Weakened skin microbiome and barrier control
High Estrogen
- Hyperpigmentation.
Estrogen and Fat Storing
Estrogen and Fat Storing
- Estrogen supports Insulin the major fat storing hormone
- After menopause when Estrogen levels radically drop women become more Insulin resistant and carbohydrate sensitive which increases visceral fat storage and the risk for Type 2 Diabetes which previously was called age onset Diabetes
- Both high and low levels of estrogen can lead to weight gain
Excess Estrogen
- Extra fat storage predominantly hips, thighs – the pear shape
- Extra fat storage on breasts if more 16 hdyroxy-E1 Estrogen is produced in the liver
Estrogen Deficiency
- fat storage shifts to visceral fat / tummy fat – the apple shape.
Estrogen and your gut
Woman – This is why your bowel movements aren’t irregular
- Estrogen inhibits muscle contraction of muscles in the GI tract
- Estrogen is known to cause GI motility disorders
- Women with IBS often have low Estrogen
- Estrogen affects the production of serotonin and 90 % is produced in the gut
- Serotonin affects how fast food moves through your gut ie. the motility and how sensitive your gut is to sensations like pain and fullness from eating
- Due to the varying levels of sex hormones ie. menstrual cycles, pregnancy and menopause GI symptoms and discomforts can come and go
- Various GI disorders, including reflux, nausea, vomiting, bloating, constipation, gall bladder dysfunction have a higher prevalence in women than in men.
Estrogen and your Uterus and Ovaries
2 main jobs both to do reproduction
- Egg development and maturity
- Thickens the lining of the uterus ie. creates blood
Too High Estrogen
- Development of many eggs at one time – PCO- Poly Cystic Ovaries, which is not necessarily a problem and not the same as PCOS where S stands for syndrome
- Over activation of the uterine lining which can lead to an array of problems from Heavy Bleeds to Uterine fibroids, Endometriosis, and Uterine Cancer.
Too Low Estrogen
- No egg development
- No activation of the uterine wall.
Estrogen and Your Vagina
An area many ladies are uncomfortable talking about and know very little about. So, let’s delve into The Universe of your Vagina (and Vulva).
- Your vagina is a muscular tube approx. 6 – 8cm / 3 – 6 inches long
- Reaching from the vulva to the cervix of the uterus
- Lengthens during arousal and intercourse to accommodate the length of the penis or sex toy
- BTW your vulva is the tissue surrounding the opening to the vagina which is often compared with a flower just before it blooms. What a beautiful description.
Estrogen keeps your vagina and vulva youthful and dynamic
- Strong tube
- Elastic and flexible tube
- Lubricated tube
- Strong pelvic floor
- Bladder control
- Good sensitivity so intercourse is exciting
- Protects by lowering the pH levels and increasing lactobacillus. (if you’re not menopausal and have vaginal infections, consider bacterial imbalances as the cause. Focus on diet and gut health, supplement with topic lactobacillus gel)
Low Estrogen, such as after menopause your vagina becomes
- Thinner
- Weaker
- Dryer
- Painful intercourse
- Low sensitivity so intercourse becomes boring
- Increases the risk of vaginal inflammation
- Increases infections – such as cystitis
- Increases stress incontinence.
Estrogen’s Role in Breast Cancer
There are 2 ways that Estrogen can be involved in breast cancer:
- Liver detoxification pathways through cytochrome P450-1B1-and the activation of the 4-OH Estrogens
- Stimulation of tumour cell proliferation through receptor-mediated hormonal activity
- Estrogen can create DNA mutations and feed tumour cells.
The statistics – according to Cancer UK
- 5 – 2 % of breast cancer cases in the UK are linked to use of HRT.
- 9 % of breast cancer cases are linked to obesity
- 8 % of breast cancer cases are linked to alcohol consumption (more than 1 unit per day)
- 8% of breast cancer cases are linked to smoking
- 5 % of breast cancer cases are linked to physical inactivity
So why is all the focus on how HRT increases the risk for breast cancer when it is crystal clear that, changing any of the above lifestyle habits will radically decrease your risk for breast cancer?
Other important facts about breast cancer you should consider
Fact
5% of UK women get breast cancer
Question
All women have breasts and we all produce Estrogen, so why don’t all women get breast cancer?
Fact
Developing breast cancer is greatest in women over 60
Question
How can that be, Estrogen levels are much less in women 60+, so why is the risk increased?
Answers
It’s not Estrone/E1, Estradiol/E2 or Estriol/E3 that instigate the cancer it’s the hydroxy-Estrogens produced in the liver which create the DNA mutations that instigate the cancer process.
Metabolism changes with the drop in Estrogen, cells become more resistant to Insulin which increases the risk for metabolic changes in the way the cell makes energy, now thought to be the cause of cancer development
Solutions
- Look after your liver
- Increase the production of the 2-OH Estrogens with:
– Resveratrol
– DIM
– Quercetin
- Optimise making the fat soluble hydroxy-Estrogens water soluble with:
– Glutathione
– Methyl
– Sulphur
– Glucuronic acid
– Acetyl
- Optimise blood sugar and insulin with:
– TRE
– Lower carb intake
- Reduce cortisol with
– Reduce stress
– Focus on Cortisol’s Circadian rhythm.
Estradiol (E2) as Medication
- Used mainly in menopausal hormone therapy and to treat low sex hormone levels in women
- Also used in hormonal birth control for women
- Also used in hormone therapy for transgender women
- Also used in the treatment of hormone-sensitive cancers like prostate cancer in men and breast cancer in women,
- Estradiol can be taken by mouth, held and dissolved under the tongue, as a gel or patch that is applied to the skin, in through the vagina, by injection into muscle or fat, or through the use of an implant that is placed into fat, among other routes
- Side effects in women include:
– breast tenderness
– breast enlargement
– headache
– fluid retention
– nausea
– Men and children who are exposed to Estradiol may develop symptoms of feminization, such as breast development and a feminine pattern of fat distribution, and men may also experience low testosterone levels and infertility.
– may increase the risk of endometrial hyperplasia and endometrial cancer in women with intact uteruses if it is not taken together with a progestogen such as progesterone
– the combination of Estradiol with a progestin, (not with oral progesterone), may increase the risk of breast cancer.
- Estradiol should not be used in women who are pregnant or breastfeeding or who have breast cancer
- Estradiol differs from non-bioidentical estrogens like conjugated estrogens and ethinylestradiol
- Estradiol was discovered in 1933.
- It became available as a medication that same year, in an injectable form known as estradiol benzoate.
- Forms that were more useful by mouth, estradiol valerate and micronized estradiol, were introduced in the 1960s and 1970s and increased its popularity by this route.
- Ethinylestradiol, is the most common Estrogen in birth control pills
- Conjugated Estrogens (brand name Premarin), is used in menopausal hormone therapy
- In 2020, it was the 59th most commonly prescribed medication in the United States, with more than 11 million prescriptions.
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