Everything You Ever Wanted to Know About Natural Progesterone
(In-depth review of progesterone) by Dr. Lindsey Berkson
Progesterone is now regarded as so breast protective that there’s a scientific call to add it to breast cancer medications like Tamoxifen! It promotes brain and sleep health in both men and women and works with Vitamin D to reduce inflammation in the nervous system and brain.
Part 1 and 2.
Part 1 — Introduction to Progesterone
What is progesterone? Progesterone is a hormone. Its name comes from “pro” — meaning to support, and “gest” — meaning gestation. It triggers pregnancy and keeps it going.
Progesterone initiates birth by helping sperm get attracted to, swim towards, and penetrate into the deeper layer of eggs produced by the female. Once pregnant, the soon-to-be mom’s body secretes increasingly high levels of progesterone (up to 400 mg/day) to help “hold” the pregnancy to full term. Thus, progesterone is mostly thought of as a female pregnancy hormone.
But it’s so much more.
Progesterone is a natural anti-inflammatory agent, a brain protector in both sexes of all ages, a natural Ambien, and new science suggests it is so breast protective that some breast cancer survivors should be taking it!
This is an introduction to the expanding job descriptions of progesterone.
It’s bi-gender. Progesterone is present in young boys and girls as well as men and women, occurring in various amounts. Young and middle-aged healthy Venus and Mars bodies, brains, and nervous systems produce progesterone. Why do we all have it? Progesterone wears diverse “hats” to keep us well. As you will learn, this means that natural progesterone therapy can be a useful additional treatment tool for many conditions.
Brain and nervous system. Progesterone protects your brain. Progesterone is part of a critical group of endogenous (naturally made) steroids (hormones) called neurosteroids. Neurosteroids protect brain and nervous system tissues. Progesterone is produced locally right inside the brain and throughout the mass of nerves inside the spinal cord to do just this. Progesterone production inside our brain and entire nervous system, including the one in our gut, happens in boys, girls, men, and women.
Neuroprotective. In the brain, gut and throughout the spinal cord, progesterone is neuroprotective. This means progesterone protects these tissues from damage from excess inflammation, regulates synaptic conversations, lubes neurotransmitters, and even protects outer nerve sheaths called myelin (one reason why progesterone therapy is helpful in some demyelinating diseases).
Progesterone protects brain volume. A healthy brain has an optimal size or volume. Aging shrinks brain volume, especially in the area where we keep memories and our sense of who we are (the hippocampus). Anything that protects brain volume promotes better thinking and loss of it (cognitive decline).
It could be said that progesterone acts like a brain filler in the way some use cosmetic procedures to fill wrinkles in the skin. It’s all about volume.
It’s been shown that in the middle of the month, when a woman produces a surge of progesterone, her hippocampus enlarges in response. Thus, progesterone helps keep memories and sense-of-self alive and kicking, by helping maintain better “hippocampal volume.” “Hippocampal Shrinkage” (loss of volume) occurs right before onset of cognitive decline diseases manifest, such as Lewy Body Dementia and Alzheimer’s disease, all clearly linked to less brain volume in this specific brain area.
Adjunctive care for brain disorders. Forward-thinking neurologists, based on a growing body of animal and human research, are using progesterone therapy (referred to as replacement) as adjunctive (additional) care in diverse brain diseases, such as Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, attention deficit disorder, anger issues (impulsivity control issues, especially in children), to avoid on-going need for medication in epilepsy, and in various PMS complaints, especially “emotional PMS.”
Progesterone therapy is even used to hasten brain recovery after brain injury or stroke. Progesterone does this by reducing cerebral edema, reducing excessive inflammation, and making the flux of minerals in and out of the brain more Zen-like. Both you body and brain adore ZEN.
Not many practitioners yet appreciate that progesterone wears so many protective nervous system “hats.”
Natural anti-inflammatory agent. Progesterone acts as a natural anti-inflammatory agent to keep neuronal tissue operating more naturally. It can be used orally or even intravenously to tamp down inappropriate molecules of inflammation in conditions such as multiple sclerosis, Parkinson’s disease, epilepsy, depression, as you will soon learn, even inflammatory bowel disease.
Progesterone helps fight inflammatory infections, such as the physiologic fallout from Lyme disease, Coxsackievirus, and Epstein-Barr Virus. Progesterone especially comes to the anti-inflammatory rescue when combined with vitamin D.
Progesterone and Vitamin D. Numerous studies show that vitamin D and progesterone work in synergy. They “fight” abnormal or dangerously prolonged inflammation, especially in the brain, nervous system, and even the gut wall. Vitamin D deficiency or even insufficiency (you have low normal levels but not enough to protect you) has been demonstrated to cause and worsen progesterone signaling and block the body’s ability to use progesterone, even if it’s in normal levels in the bloodstream.
Vitamin D and progesterone help the immune system “see” cancer cells in the uterus, breast, prostate, and gut wall, so it can then take action to fight them off.
Cutting-edge neurologists use vitamin D added to natural progesterone therapy in cases of chronic infections that attack the nervous system and even in attentional disorders like ADHD or brain disorders like epilepsy.
Progesterone and the gut. Progesterone can be a useful adjunctive (additional) tool for treating some cases of inflammatory bowel disease and ulcerations of the gut lining at any level of the gut (from the esophagus to the small and large intestines).
Why? In essence, the brain and gut are identical twins. Brain and intestinal tissues originally come from the exact same fetal embryonic cells. These cells split in half, with half of the cells going to the brain and the other to the gut. What is good for the brain in our head is also good for our “second brain” in our gut. This means that progesterone replacement can be an extra tool to help heal abnormal inflammation, ulcers, and cell damage in both the brain and the intestinal tract.
Studies show that progesterone acts like a natural anti-acid, soothing the lining of the esophagus and gut. If parietal cells make too much stomach acid, progesterone acts like a natural antacid reversing potential damage.
Progesterone disruptors. Any compounds that block the natural signaling of progesterone are called “anti-progestins”. It’s a little bit confusing as we called natural progesterone by the name progesterone, and synthetic progesterone man-made molecules progestins. But any process or molecules that block progesterone’s right of way are labeled anti-progestins.
We produce less progesterone as we age, so aging is a natural anti-progestin. But modern life is filled with unnatural molecules that can also block healthy progesterone signals and act as synthetic or environmental or toxic anti-progestins. One example is the pain medication family, many found over-the-counter, called NSAID (non-steroidal anti-inflammatory agents. Many studies show that regular daily use of NSAIDs, like Motrin, is linked to an increased risk of gut inflammation and ulcerations. Why? Motrin is an anti-progestin. It blocks the benefits of progesterone. And especially at the gut lining, as this medication is swallowed so it directly exposes the gut lining.
An Italian study in 2015 demonstrated that just a 10-day course of NSAIDs, taking the amount suggested on the label, reduced progesterone’s signal activity so much that most women in the randomized trial can became infertile. The NSAID acting as an anti-progestin action blocked progesterone signaling so significantly and in such a short period of time.
Many endocrine disruptors in today’s environment, like breakdown products of some insecticides, act as powerful anti-progestins. So the progesterone inside your body is potentially under attack. When seeing a doctor for any hormonal issue it is critical they know how to access if endocrine disruptor is part of your health issue. They should also be educated in protocols that could effectively detoxify falter progesterone hormone pathways by clearing out receptors and supplying the nutrients that make the hormone (ligand) and receptor (receiving protein satellite “station”) more able to function healthfully.
Sleep. Many of us sleep better when we are younger. Why? Younger brains make more progesterone. Progesterone promotes deep restorative sleep by helping the brain achieve healthier “sleep architecture”. This means that progesterone signals inside the brain help achieve stages of sleep, such REM, the stage where much of our healing and repair takes place.
We spend one-third of our lives in sleep. Healthy brain progesterone levels are part of making this huge portion of our lives watch our physiologic backs the rest of our day. As we age, brains make less progesterone. Our adrenal glands, if chronically stressed by emotions or poor dietary choices, may also make less. Thus, there is a tendency with normal aging and with chronic stress, to promote insomnia or create a non-restorative sleep. You sleep but you wake up ass though you hadn’t. But appropriate progesterone therapy (right delivery mode and dosage) helps with this.
Where does progesterone come from?
· Corpus luteum. Progesterone is made in a premenopausal woman in the middle of her menstrual cycle from a burst follicle.
· Fat cells also produce progesterone.
· Adrenal glands make progesterone. Cholesterol goes into the adrenal glands to supply the building block material to create other hormones. The adrenals take cholesterol and produce progesterone in a conveyor belt process to ultimately make male hormones and the stress hormone cortisol. The more stressed we are, the more progesterone is stolen (called “progesterone steal”) to create cortisol. Then, less progesterone is available to tamp down inflammation and boost brain and sleep health.
· Progesterone is also produced inside the brains of young males and females to protect brain and sleep health.
· Plant progesterone. Progesterone has been detected in the leaves of the Common Walnut, or English Walnut tree. Five new progesterone-related steroids have been found in plants belonging to the buttercup family. It’s often made in the laboratory from yam, but yam itself does not contain progesterone.
· Progesterone replacement. A modified molecule that is like progesterone but not exactly like it is called a progestin. When the laboratory produces an “exact molecular copy” of human natural progesterone, it is called progesterone.
Progesterone replacement, in both men and women, as well as boys and girls, can be given to treat excessive inflammation and inflammatory diseases, anywhere in the body, especially in issues of neural and gut tissue and also to treat insomnia.
Progesterone replacement can be given to men and boys and girls, but it is usually in a reduced dosage compared to adult women.
Progesterone for these purposes is best given orally. This does not mean that topical delivery does not give benefits. But the best brain, nervous system, gut, and sleep benefits come from oral delivery. Individual cases may vary as to who does better with time release versus fast acting.
Why oral? When progesterone is swallowed, it passes from the stomach first to the liver (this is called the first “hepatic pass”). A progesterone derivative or metabolite is formed in the liver, called allopregnanolone. This neurosteroid has been widely studied. It is the main reason that oral progesterone acts like a natural Ambien and also as an natural anti-inflammatory agent.
Oral progesterone, in the right dosage and delivery system (oral, topical, troche, etc.), promotes anti-inflammatory benefits and deeper healthier sleep. It helps various neurodegenerative diseases and even some cases of depression. It has not been shown to help the optic nerve (an extension of the brain) or the retina.
The sleep protective benefits of progesterone are not accomplished by topical dermal delivery as this avoids the first hepatic pass and the sleep metabolite isn’t produced.
Allopregnanolone is so brain protective it is being looked at as adjunctive care for Alzheimer’s disease, Parkinson’s disease, Lewy Body dementia, and MS.
Allopregnanolone protects mitochondria. Mitochondria make energy. They are the energy producing organelles inside cells that have a lot to do with overall health, but especially brain health, focus, memory, and motivation. To drive us health ward, we need large enough populations of highly functional mitochondria. In contrast, if our mitochondria are too few or malfunctioning, we become more open to a wide variety of diseases, Healthy mitochondria require progesterone!
Hormone family. Progesterone is a single sex steroid hormone. It is part of the larger sex steroid hormone family. Other members are estrogens, testosterone, oxytocin and more. If any one member of this family is dysfunctional, this can adversely affect progesterone functioning.
This means that you can have normal progesterone levels on any kind of test (blood, urine, saliva) but, for example, if your thyroid is dysfunctional, if your adrenals or estrogens are not healthy, progesterone may not be able to serve you like it should. Test results may appear normal but behind the scenes you are having less brain, sleep, and anti-inflammatory nervous system protection.
Hormones and aging. Our hormones are at their highest peak in our mid-20’s. It’s downhill from there. It is no coincidence that as we age and our sex steroid hormones decline, our brain is slowly becoming vulnerable to dysfunction. Plasticity is being lost. Rigidity is being gained.
Progesterone replacement slows this down if not reverses this a bit as it is clearly linked to helping maintain healthier brain volume.
Progesterone’s bad rap. Progesterone has two forms: the bio-identical form as found in nature and the synthetic form, called progestins. In the synthetic form, molecules have been changed so they can be patented and sold at a profit as a drug.
Progestins are not progesterone. The human body has never seen progestins before. The human body does not respond uniformly to them. These patentable drugs have been linked with many serious side effects, from clots and heart attacks to breast cancer. The Women’s Health Initiative (WHI, 2002) was stopped early due to an increased risk of breast cancer in the women on hormone replacement. Numerous later re-analyses clearly showed that these adverse issues were mainly due to the addition of progestins to the estrogen medication. The combination drug used was called Prempro (the progestin was medroxyprogesterone acetate added to horse estrogen Premarin).
The fear generated by the early scary headlines of the WHI study still lingers in the brains of many women and doctors, even though so much has come out to show that synthetic progestins were at fault, and, in fact, estrogen was breast protective (in younger non-obese women).
Alas, too many women remain afraid of hormones. They choose to “age gracefully” without hormone replacement. These misunderstandings mean many miss out on progesterone’s benefits.
Natural bio-identical progesterone is the progesterone with the most benefits. Especially on the breast. Even in breast cancer survivors.
Part 2 — Progesterone and Breast Cancer Survivors
New research. (From Nature Reviews Cancer, December 2016) Two international investigative groups teamed up from Australia and Boston (University of Adelaide’s Dame Roma Mitchell Cancer Research Laboratories and the Cancer Research UK Cambridge Institute). Their in-depth research now shows that progesterone protects breast health. It protects breast tissue so much it should be added to breast cancer drugs like Tamoxifen!
These teams showed that 75% of breast cancers are fed or driven by estrogens. Women are then treated with drugs that block estrogen activity. But many women ultimately become resistant to these drugs and/or can suffer diverse serious issues from them, such as cognitive decline, fractures, blood clots, thick blood (polycythemia), and just aging faster.
This new research says that instead of using anti-estrogen drugs with their adverse issues, women can be given natural bio-identical progesterone to help treat and prevent further cancers!
How? Well-run studies have shown for years that progesterone polices estrogen. It keeps estrogen acting more nice than naughty by blocking estrogen’s possible excessive growth signals. That’s why many functional practitioners have added progesterone to hormone replacement for many years.
But these Australian and Bostonian researchers show that progesterone also does this in breasts that have had cancer. This is a paradigm shit.
Bio-identical progesterone “re-programs” estrogen. It gives breast tissue estrogen “upgrades.” These progesterone-upgraded estrogens then act better, safer, and healthier.
There is a natural “cross-talk” between estrogen and natural progesterone. This natural dialogue helps switch “off” the growth of cancer cells. Even in women who have had breast cancer!
This is not the case with most synthetic progestins.
One trial in collaboration with a UK group at the University of Liverpool is suggesting adding progesterone to Tamoxifen to protect premenopausal breast cancer patients better than by using Tamoxifen alone.
This is the tip of the hormonal iceberg. Hormones are the major emails in our bodies computer. Their signals are the emails of life, keeping life vibrant. When hormone signals wan, this correlates with aging. If hormone therapy is prescribed strategically and individualized, you often have less risk of getting cancer on replacement than you would if you didn’t take it!
If you have low thyroid functioning (hypothyroidism), you might take thyroid replacement. If you have insufficient insulin, you are given insulin replacement. Why not with sex hormones, especially since they are so brain, gut, and breast protective?
Hormones are crucial. Hormones are the major signaling molecules of the body. They keep the brain at a healthier volume so it functions better. They protect lung tissue against lung disease. They protect kidney health, which directs our cardiovascular health. They protect our blood vessels and heart. They even keep our vocal cords strong and youthful sounding.
We are living longer but we do not want to outlive our hormone signals.
And we especially don’t want to miss out on great anti-inflammatory, restorative sleep and breast tissue protection.
But modern progesterone is under modern attack from various factors:
Toxic pollutants. Modern life can threaten our progesterone and all its benefits. Environmental pollutants, such as plastics (phthalates, heavy metals, and pesticides) can act as progesterone hijackers. They block progesterone function at diverse levels of metabolism.
Birth control pills and NSAIDS (non-steroidal anti-inflammatory over-the-counter pain meds) tamp down progesterone levels.
Nutrient insufficiencies and deficiencies. Toxic pollutants can block nutrients and processes (like methylation) that allow receptors (satellite receiving stations that accept hormone signals and deliver them to your genes) and cause receptor resistance. In this case, it is called progesterone resistance. Poor diets can create nutrient deficiencies that also can contribute to progesterone resistance.
Adrenal stress. The more stressed we are, the more the adrenals steal from progesterone to make cortisol. Thus, chronic stress can cause lower levels of progesterone, leaving a woman more prone to infertility and both men and women more prone to cognitive dysfunction and neurologic disease, and even severe chronic infection.
What helps besides taking bioidentical hormone therapy?
· Exercise. It appears that regular robust exercise helps maintain healthy genes to receive hormone signals. And that may be one mechanism, among many, whereby exercise is protective against cancer. Healthy regular exercise boosts progesterone genes and progesterone protective functions.
· Strategic detoxes to keep receptors free of toxins.
· And healthy digestion, food choices and nutrient programs all play a role in various segments involved in how hormone deliver their signals ultimately to our genes.
Moral of this story. Do not be closed-minded to hormone replacement because you are fearful of hormones; or you think aging gracefully without them makes more natural sense; or you are a high risk or cancer survivor. You might be missing out.
But you must work with practitioners that know this science.
I hear too many OBGYNs and even endocrinologists say they don’t believe in hormone replacement.
Hormones are not a religion. They are a science that can hold protective treatment answers for you or your loved ones.
This means that if you had breast cancer and were told you are never again a candidate for any kind of hormone replacement, you may be getting the wrong information. You actually may be worse off by NOT taking hormone replacement.
Stay hormonally open-minded.
Find practitioners that are, too.
It does no good to ask a provider if you are a candidate for hormone replacement if that provider doesn’t know this science. Which means, many, many docs out there. But the memo is being circulated.
Growth Hormone & IGF Research. June 2004. 14 Suppl A: S18–33. Local synthesis and dual actions of progesterone in the nervous system: neuroprotection and myelination. Schumacher M, Guennoun R, Robert F, Carelli C, Gago N, Ghoumari A, Gonzalez Deniselle MC, Gonzalez SL, Ibanez C, Labombarda F, Coirini H, Baulieu EE, De Nicola AF
Int Immunopharmacol. 2016 Apr;33:83–9. Epub 2016 Feb 12, Progesterone exerts neuroprotective effects against Aβ-induced neuroinflammation by attenuating ER stress in astrocytes. Hong Y, Wang X, Sun S, Xue G, Li J, Hou Y.
Journal of Natural Products, 2010; 100128124334075 . Occurrence of Progesterone and Related Animal Steroids in Two Higher Plants. Pauili, et. al.
Afr Health Sci. 2012 Jun;12(2):153–9. doi: 10.4314/ahs.v12i2.12. Progesterone, selected heavy metals and micronutrients in pregnant Nigerian women with a history of recurrent spontaneous abortion. Ajayi OO, Charles-Davies MA, Arinola OG.
Oxford Journals, Medicine & Health, Human Reproduction. Volume 17, Issue 4. Pp. 933–939. Progesterone serum levels during the follicular phase of the menstrual cycle originate from the crosstalk between the ovaries and the adrenal cortex.
Neuroimage. 2015 Sep;118:154–62. Epub 2015 Jun 6. Hippocampal volume and functional connectivity changes during the female menstrual cycle. Lisofsky N, Mårtensson J, Eckert A, Lindenberger U, Gallinat J, Kühn S.
Arch Toxicol. 2016 Jul 12. [Epub ahead of print] Di (2-ethylhexyl) phthalate impairs steroidogenesis in ovarian follicular cells of prepuberal mice. Lai FN, Liu JC, Li L, Ma JY, Liu XL, Liu YP4, Zhang XF, Chen H, De Felici M, Dyce PW, Shen W.
Nature Reviews Cancer, 2016; Deciphering the divergent roles of progestogens in breast cancer. Jason S. Carroll, Theresa E. Hickey, Gerard A. Tarulli, Michael Williams, Wayne D. Tilley.
European League Against Rheumatism (EULAR) Congress 2015: Abstract OP0131, Presented June 11, 2015.
Gastroenterology. 2008 Jul;135(1):72–81. Epub 2008 Mar 25.Effects of estrogen with and without progestin and obesity on symptomatic gastroesophageal reflux. Zheng Z, Margolis KL, Liu S, Tinker LF, Ye W; Women’s Health Initiative Investigators.
Arch Intern Med. 2008 Sep 8;168(16):1798–804. Postmenopausal hormone use and symptoms of gastroesophageal reflux.
J Clin Pharmacol. 2006 Aug;46(8):925–32. Bata MS, Al-Ramahi M, Salhab AS, Gharaibeh MN, Schwartz J. Delay of ovulation by meloxicam in healthy cycling volunteers: A placebo-controlled, double-blind, crossover study.
Brain Inj. 2016;30(8):960–8. Epub 2016 May 16. A review of the neuroprotective role of vitamin D in traumatic brain injury with implications for supplementation post-concussion. Lawrence DW, Sharma B.
Horm Behav. 2013 Aug;64(3):527–38. Epub 2013 Jul 27. Vitamin D in traumatic brain injury with implications for supplementation post-concussion. Tang H, Hua F, Wang J, Sayeed I, Wang X, Chen Z, Yousuf S, Atif F, Stein DG.
J Biomed Res. 2016 May;30(3):203–8. Epub 2016 May 20.Effect of vitamin D3 on production of progesterone in porcine granulosa cells by regulation of steroidogenic enzymes.
Restor Neurol Neurosci. 2016 Nov 22;34(6):947–963. Progesterone treatment shows greater protection in brain vs. retina in a rat model of middle cerebral artery occlusion: Progesterone receptor levels may play an important role. Allen RS,, Sayeed I, Oumarbaeva Y, Morrison KC, Choi PH, Pardue MT, Stein DG.
Physiol Behav. 2016 Nov 21;169:52–58. [Epub ahead of print] Physical activity induced protection against breast cancer risk associated with delayed parity. Sturgeon KM, Schweitzer A, Leonard JJ, Tobias DK, Liu Y, Cespedes Feliciano E, Malik VS, Joshi A, Rosner B, De Jonghe BC.