Benefits of Progesterone

BIOLOGY OF PROGESTERONE

Overview

Progesterone is the Master Hormone in all women. It is the hormone responsible for balancing the activities of a woman’s 27 different estrogens. Once past puberty, the need to balance estrogen by achieving optimal progesterone levels, is foundational for a woman to enjoy good health & wellness.

When a young woman fails to maintain sufficient progesterone, she will experience some of the 150+ symptoms of PMS, migraines, cramps, increased risk for PCOS & endometriosis, uterine fibroids and female-specific cancers. At menopause, a progesterone deficiency has been shown to be the underlying cause of hot flashes, night sweats, insomnia, foggy thinking, unexplained weight-gain, increased cancer risk and osteoporosis.

BioIdentical or Synthetic: the Research

The journal Postgraduate Medicine, 2009 Jan;121(1):73-85, stated, in part:
“Physiological data and clinical outcomes demonstrate that bioidentical hormones are associated with lower risks, including the risk of breast cancer and cardiovascular disease, and are more efficacious than their synthetic and animal-derived counterparts. Until evidence is found to the contrary, bioidentical hormones remain the preferred method of HRT. Of special concern is their relative safety compared with traditional synthetic and animal-derived versions, such as conjugated equine estrogens (CEE), medroxyprogesterone acetate (MPA), and other synthetic progestins. Bioidentical hormones have some distinctly different, potentially opposite, physiological effects compared with their synthetic counterparts, which have different chemical structures. Both physiological and clinical data have indicated that progesterone is associated with a diminished risk for breast cancer, compared with the increased risk associated with synthetic progestins.” link 1The bioidentical hormone debate: are bioidentical hormones (estradiol, estriol, and progesterone) safer or more efficacious than commonly used synthetic versions in hormone replacement therapy?

“Slowing the Aging Process with Natural Progesterone”

John Lee MD – Author
Pioneer in Use of
Natural Progesterone

note: The above article by Dr. John Lee, M.D., is Progesterone 101 (a must-read).
The  references below for progesterone’s supportive role of the central nervous system & the human brain is vital.

Biology of Progesterone for Both Genders

  • Differentiating Between Natural Progesterone and Synthetic Progestins: Why Important  link2Progesterone and the Luteal Phase: …Differentiating between natural progesterone and synthetic progestins: clinical implications for premenstrual syndrome and perimenopause management
    link 3In Defense of Progesterone: A Review of the Literature link4Differential regulation of endothelium behavior by progesterone and medroxyprogesterone acetate
  • Progesterone Supports a Healthy Heart link5Protective actions of progesterone in the cardiovascular system
  • Progesterone supports the brain to heal from damage after traumatic brain injury (the Human Brain Has an Inordinately Large Number of Progesterone Receptor Sites) link 6Progesterone and the Nervous System/Brain link7Effect of progesterone traumatic brain injury link8The membrane-associated progesterone-binding protein 25-Dx: expression, cellular localization and up-regulation after brain and spinal cord injuries (2008) link9The membrane-associated progesterone-binding protein 25-Dx is expressed in brain regions involved in water homeostasis and is up-regulated after traumatic brain injury(2005)
  • Progesterone is the precursor for Allopregnanalone (the nervous system has the capacity to bio-convert progesterone into its active metabolite allopregnanolone. The enzymes required for progesterone and allopregnanolone synthesis are widely distributed in brain and spinal cord. Increased local biosynthesis of pregnenolone, progesterone and 5α-dihydroprogesterone may be a part of an endogenous neuroprotective mechanism in response to nervous system injuries. Progesterone and allopregnanolone neuroprotective effects have been widely recognized) link10Progesterone and allopregnanolone in the central nervous system: response to injury and implication for neuroprotection
  • “Progesterone prevented membrane cell damage, motoneuron loss and cell death. Allopregnanolone treatment was also neuroprotective.” link11Neuroprotection by steroids after neurotrauma in organotypic spinal cord cultures: a key role for progesterone receptors and steroidal modulators of GABA(A) receptors
  • Progesterone supports the body to normalize the symptoms of Multiple Sclerosis link12Progesterone and Nestorone promote myelin regeneration in chronic demyelinating lesions of corpus callosum and cerebral cortex
  • Progesterone Supports a Happy Mood, via Allopregnanolone Production link13Allopregnanolone is synthesized from progesterone
  • Progesterone Supports a Healthy Heart link 14 Frequency-dependent Acceleration of Cardiac Repolarization by Progesterone Underlying Its Cardiac Protection Against Drug-Induced Proarrhythmic Effects in Female Rabbits llink15Protective actions of progesterone in the cardiovascular system: potential role of membrane progesterone receptors (mPRs) in mediating rapid effects
  • Facilitates thyroid hormone function and utilization
    “Estrogen dominance causes the liver to produce high levels of a protein called “thyroid binding globulin”, which, as its name suggests, binds the thyroid hormone and decreases the amount of thyroid hormone that can be assimilated into and utilized by the cells.What does this lead to? Low thyroid function and all of the negative side effects that come along with it.”  link16Progesterone therapy increases free thyroxine levels–data from a randomized placebo-controlled 12-week hot flush triallink17Conclusion: This work provides evidences that progesterone has a direct effect on thyroid cells, through its receptor, upregulating genes involved in thyroid function and growth.link 18Progesterone & Thyroid: A Hormonal Connection Essential for Optimal Women’s Health link19Friends or Foes? Estrogen, Progesterone & Thyroid Hormones
  • Progesterone is Anti-estrogenic (the average 54 year old male in the US, has higher estrogen levels that the average 54 year old female!) link20Progesterone Binds Excess Estrogen and Flushes Them Out of the Body
  • Progesterone Supports Normal, Programmed Cell Replacement in breast, ovarian & prostate tissues link21Progesterone-Mediated Non-Classical Signaling link22Estrogen Biosynthesis, Phase I and Phase II Metabolism, and Action in Endometrial Cancer (Estrogen Dominance) link23Estrogen-induced Loss of Progesterone Receptor Expression in Normal and Malignant Ovarian Surface Epithelial Cells of the Ovary link 24Progesterone Action in Breast, Uterine, and Ovarian Cancers
  • Progesterone Supports the Body’s Natural Process of Inhibiting Tumor Formation in Breast & Prostate Cells link25Progesterone receptor modulates estrogen receptor-α action in breast cancer26 link26 “Three studies involving 86,881 postmenopausal women reported that the use of natural progesterone was associated with a significantly lower risk of breast cancer compared with synthetic progestins. Use of progesterone has been linked to lower rates of uterine and colon cancers and may also be useful in treating other cancers such as ovarian, melanoma, mesothelioma, and prostate.”
  • Progesterone receptor modulates estrogen receptor-α action in breast cancer link27Progesterone Receptor Inhibits Aromatase and Inflammatory Response Pathways in Breast Cancer Cells via Ligand-Dependent and Ligand-Independent Mechanisms link28Roles for estrogen and progesterone in breast cancer prevention link29Antiestrogen Action of Progesterone in Breast Tissue
  • Progesterone Supports the Body’s Ability to Alleviate the underlying cause of Hot Flashes link30Hormone variability and hot flash experience: Results from the midlife women’s health study of 798 midlife women link 31Hot flashes, energy, and aging, Dr. Ray Peat
  • Progesterone Supports the Activity of Osteoblast Cells (in US, women, on average, lose 1.5% bone/year) (bone health) “Progesterone plus estradiol or other anti-resorptive therapies adds 0.68%/year and may be a highly effective osteoporosis treatment. US average is 1.5% bone loss/year” link32Progesterone for the Prevention and Treatment of Osteoporosis in Women
  • Progesterone as a Bone-Trophic Hormone link33Progesterone as a Bone-Trophic Hormone – J C Prior link34Evidence for Progesterone Receptors in Human Osteoblast-Like Cells
  • Progesterone Supports Phase IV sleep (the restorative, restful sleep) link35Progesterone Prevents Sleep Disturbances and Modulates GH, TSH, and Melatonin Secretion in Postmenopausal Women link36Effects of progesterone on sleep link37Progesterone has both sedative and anxiolytic effects, stimulating benzodiazipine receptors, which play an important role in sleep cycle

Biology of Progesterone for Women

  • Differentiating Between Natural Progesterone and Synthetic Progestins: Why Important  link38Progesterone and the Luteal Phase: …Differentiating between natural progesterone and synthetic progestins: clinical implications for premenstrual syndrome and perimenopause management
  • Progesterone vs. synthetic progestins: a systematic review and meta-analysis (a study involving 86,881 postmenopausal women) link39Progesterone vs. synthetic progestins and the risk of breast cancer: a systematic review and meta-analysis
  • Progesterone Supports Fertility, Conception, Full-Term Pregnancy link40Luteal phase deficiency (LPD) is a condition of insufficient progesterone exposure to maintain a normal secretory endometrium and allow for normal embryo implantation and growth link41Progestogen for treating threatened miscarriagelink42The significance of the human corpus luteum in pregnancy maintenancelink43Assessment of the luteal phase in stimulated and substituted cycles
  • High Levels of Progesterone During Pregnancy link44Hormones in pregnancy
  • Progesterone Supports the body’s ability to correct the underlying cause of most of the 150 different symptoms of PMS/PMDD link45Lowered Plasma Steady-State Levels of Progesterone Combined With Declining Progesterone Levels During the Luteal Phase Predict Peri-Menstrual Syndrome and Its Major Subdomains
  • Progesterone Facilitates thyroid hormone function and utilization
    “Estrogen dominance causes the liver to produce high levels of a protein called “thyroid binding globulin”, which, as its name suggests, binds the thyroid hormone and decreases the amount of thyroid hormone that can be assimilated into and utilized by the cells.What does this lead to? Low thyroid function and all of the negative side effects that come along with it.”  link46Progesterone therapy increases free thyroxine levels–data from a randomized placebo-controlled 12-week hot flush triallink47Conclusion: This work provides evidences that progesterone has a direct effect on thyroid cells, through its receptor, upregulating genes involved in thyroid function and growth.link 48Progesterone & Thyroid: A Hormonal Connection Essential for Optimal Women’s Healthlink 49Friends or Foes? Estrogen, Progesterone & Thyroid Hormones
  • Progesterone Supports a Woman’s Normal Libido (Progesterone is the Precursor for Testosterone,source of libido in women)link50Within-cycle Fluctuations in Progesterone Negatively Predict Changes in Both In-Pair and Extra-Pair Desire Among Partnered Women link51Within-cycle Fluctuations in Progesterone Negatively Predict Changes in Both In-Pair and Extra-Pair Desire Among Partnered Women link52Menstrual cycle phase predicts women’s hormonal responses to sexual stimuli link53General sexual desire, but not desire for uncommitted sexual relationships, tracks changes in women’s hormonal status
  • Progesterone Supports Healthy, Happy Ovaries (lol) link54Effects of Progesterone on Ovarian Tumorigenesis in Xenografted Mice link55Progesterone Reduces Cell Survival in Primary Cultures of Endometrioid Ovarian Cancer link 56Progesterone Acts via the Progesterone Receptor to Induce Adamts Proteases in Ovarian Cancer Cells link57Progesterone Action in Breast, Uterine, and Ovarian Cancers
  • Progesterone Supports Normal, Programmed Cell Replacement in breast & ovarian tissues link 58Progesterone inhibits growth and induces apoptosis in breast cancer cells link59Progesterone-Mediated Non-Classical Signaling link60Estrogen Biosynthesis, Phase I and Phase II Metabolism, and Action in Endometrial Cancer (Estrogen Dominance) link 61Estrogen-induced Loss of Progesterone Receptor Expression in Normal and Malignant Ovarian Surface Epithelial Cells of the Ovary link62Progesterone Action in Breast, Uterine, and Ovarian Cancers
  • Progesterone Supports a Healthy Endometrium link63Altered Expression of Genes Involved in Progesterone Biosynthesis, Metabolism and Action in Endometrial Cancer link 64Estrogen Biosynthesis, Phase I and Phase II Metabolism, and Action in Endometrial Cancer (Estrogen Dominance)
  • Progesterone Supports Inhibition of Tumor Formation in Breast Cells link65Progesterone inhibits growth and induces apoptosis in breast cancer cells link66Progesterone receptor modulates estrogen receptor-α action in breast cancer link67Progesterone Receptor Inhibits Aromatase and Inflammatory Response Pathways in Breast Cancer Cells link68Roles for estrogen and progesterone in breast cancer prevention link69Antiestrogen Action of Progesterone in Breast Tissue
  • Progesterone Supports women in Menopause link70Progesterone for treatment of symptomatic menopausal women
  • Progesterone Alleviates the underlying cause of Hot Flashes link71Hormone variability and hot flash experience: Results from the midlife women’s health study of 798 midlife women link72Hot flashes, energy, and aging, Dr. Ray Peat
  • Supports Osteoblast Function (bone health) “Progesterone plus estradiol or other anti-resorptive therapies adds 0.68%/year and may be a highly effective osteoporosis treatment. US average is 1.5% loss/year” link73Progesterone for the Prevention and Treatment of Osteoporosis in Women
  • Progesterone as a Bone-Trophic Hormone link74Progesterone as a Bone-Trophic Hormone – J C Prior link75Evidence for Progesterone Receptors in Human Osteoblast-Like Cells
  • Progesterone Supports Phase IV sleep (the restorative, restful sleep) link76Progesterone Prevents Sleep Disturbances and Modulates GH, TSH, and Melatonin Secretion in Postmenopausal Women link 77Effects of progesterone on sleep link78Progesterone has both sedative and anxiolytic effects, stimulating benzodiazipine receptors, which play an important role in sleep cycle
  • Progesterone protects the brain from damage after traumatic brain injury link79Progesterone and the Nervous System/Brain link80Effect of progesterone traumatic brain injury
  • Progesterone is the Precursor to Allopregnanolone Supports a Happy Mood link 81Allopregnanolone is synthesized from progesterone

 

Biology of Progesterone for Men

  • Progesterone is the Precursor for Testosterone link82Progesterone in turn is the precursor of the mineralocorticoid aldosterone, which is converted to testosterone, highlighting the critical role of progesterone is testosterone synthesis link83Progesterone increases ex vivo testosterone production
  • Testosterone Supports Improved Muscle Mass link84Effects of Testosterone Supplementation for 3 Years on Muscle Performance and Physical Function in Older Men
  • Testosterone Supports Weight Loss link85Testosterone and weight loss: the evidence
  • Testosterone Strengthens Bones link86Testosterone treatment substantially increased BMD
  • Testosterone Supports a Healthy Heart link87Normalization of testosterone level is associated with reduced incidence of myocardial infarction and mortality in men
  • Testosterone Fuels Libido link88Sex, Energy, Well-Being and Low Testosterone: An Exploratory Survey of U.S. Men’s Experiences on Prescription Testosterone
  • Testosterone Supports an E.D.-Free Life! link89Testosterone therapy in erectile dysfunction link 90The effect of testosterone on androgen receptors and human penile growth link 91Update on corpus cavernosum smooth muscle contractile pathways in erectile function: a role for testosterone? link 92Effects of testosterone supplementation on depressive symptoms and sexual dysfunction
  • Testosterone Supports a Decrease Alzheimer’s Risk & Improves Cognitive Function link 93The Effects of Testosterone Supplementation on Cognitive Functioning in Older Men link 94Effects of Testosterone Therapy on Cognitive Function in Aging: A Systematic Review
  • Testosterone Supports Increased Athletic Performance link 95Conclusions: Circulating testosterone of adults explains most, if not all, the sex differences in sporting performance
  • Testosterone Supports Increased Hemoglobin (low hemoglobin=anemia) link 96Testosterone substantially increased hemoglobin and corrected mild anemia in both men who had unexplained anemia and men who had anemia of known cause
  • Testosterone Supports Male Magnetism Toward Women link 97Men with elevated testosterone levels show more affiliative behaviours during interactions with women
  • Progesterone Supports Normal Breast Size in Men (links coming soon)
  • Progesterone Blocks 5AR, the Enzyme that Converts a Man’s Valuable Testosterone to DHT (normal consequence of aging). DHT is Implicated in an Elevated PSA Count (links coming soon)
  • Progesterone Is a Proven, Successful Treatment for Traumatic Brain Injury (links coming soon)
  • The Human Brain Has an Inordinately Large Number of Progesterone Receptor Sites, Ergo, Progesterone Supports a Balanced Brain Chemistry (links coming soon)
  • RepeatProgesterone is the Precursor for Testosterone link98Progesterone in turn is the precursor of the mineralocorticoid aldosterone, which is converted to testosterone, highlighting the critical role of progesterone is testosterone synthesis link99Progesterone increases ex vivo testosterone production

 

Clarification of a Long-Standing Misconception

It is important to note, there are two progesterones, one made by the body and one that is molecularly altered and patentable.

It is a common practice for health care professionals to say “progesterone” when referring to the synthetic “progestin”.

This is an important distinction, as “progestins” have a litany of side-effects. Conversely, “biologically identical progesterone” has a 40+ year history of safe, effective use, when administered in a safe cream formula.

An Article by Anna Rushton

ACKNOWLEDGEMENTS

TWO LEGENDARY MENTORS

To those who came before us:

 We would like to take a moment to honor and appreciate your dedication and service to the world. Among them, two very important people must be mentioned. These devoted men pioneered the study of women’s health and the use of bio identical hormones.

First, our primary personal Mentor and Friend was Dr. John R. Lee, M.D.

Dr. Lee, was internationally acknowledged as a pioneer and expert in the study and use of the hormone progesterone, and on the subject of hormone replacement therapy for women. He used transdermal progesterone extensively in his clinical practice for 20 years, doing research which showed that it can reverse osteoporosis. Dr. Lee also famously coined the term “estrogen dominance,” meaning a relative lack of progesterone compared to estrogen, which causes a list of symptoms familiar to millions of women.

Dr. Lee had a distinguished medical career, including graduating from Harvard and the University of Minnesota Medical School. After he retired from a 30-year family practice in Northern California he began writing and traveling around the world speaking to doctors, scientists and lay people about progesterone. Dr. Lee also taught a very popular course on “Optimal Health,” at the College of Marin for 15 years, for which he wrote the book Optimal Health Guidelines. His second self-published book, written for doctors, was Natural Progesterone: The Multiple Roles of a Remarkable Hormone. He then teamed up with Virginia Hopkins and others to write the best-selling books:

WHAT YOUR DOCTOR MAY NOT TELL YOU ABOUT MENOPAUSE: The Breakthrough Book on Natural Progesterone (Warner Books, 1996)

WHAT YOUR DOCTOR MAY NOT TELL YOU ABOUT PREMENOPAUSE: Balance Your Hormones and Your Life from Thirty to Fifty (Warner Books, 1999)

WHAT YOUR DOCTOR MAY NOT TELL YOU ABOUT BREAST CANCER: How Hormone Balance Can Help Save Your Life, (Warner Books, 2002)

Second, we’d like to take a moment to thank Dr. Ray Peat PhD.

Dr Peat has a Ph.D. in Biology from the University of Oregon, with specialization in physiology. The schools where he has taught include: the University of Oregon, Urbana College, Montana State University, National College of Naturopathic Medicine, Universidad Veracruzana, the Universidad Autónoma del Estado de México, and Blake College. He also conducts private nutritional counseling.

Dr. Peat started his work with progesterone and related hormones in 1968. In his papers on Physiological Chemistry and Physics (1971 & 1972) and in his dissertation (University of Oregon, 1972), he outlined his findings regarding progesterone, and the hormones closely related to it, as protectors of the body’s structure and energy against the harmful effects of estrogen, radiation, stress, and lack of oxygen.

The key idea was that energy and structure are interdependent, at every level.

We resonate greatly with many of the statements Dr. Peat makes:

“”Marketing” of these as products, without understanding just what they do and why they do it, seems to be adding confusion, rather than understanding, as hundreds of people sell their misconceptions with their products. The very concept of “marketing” is at odds with the real nature of these materials, which has to do with the protection and expansion of our nature and potential. A distorted idea of human nature is sold when people are treated as “the market.”

It seems that all of the problems of development and degeneration can be alleviated by the appropriate use of the energy-protective materials. When we realize that our human nature is problematic, we can begin to explore our best potentials.”

We feel very privileged to have role models like Dr. Lee and Dr. Peat who pioneered the pathway of empowering the lives of women and beyond, with the safe use of bio identical progesterone. The education and research they’ve provided has been founded on integrity and a commitment to improving the lives of others. We’ve worked with and seen first hand for more than two decades, the value these men have brought to the lives of millions.

It is our Mission to continue the Legacy!

 

REFERENCES

Stein DG. The case for progesterone. Ann NY Acad Sci. 2005 Jun;1052:152-69.

Hotze SF. Hormones, Health, and Happiness. Houston, TX: Forrest Publishing; 2005.

Syst Rev. 2016; 5: 121. Published online 2016 Jul 26. doi: 10.1186/s13643-016-0294-5 PMCID: PMC4960754 PMID: 27456847. Progesterone vs. synthetic progestins and the risk of breast cancer: a systematic review and meta-analysis. Noor Asi,corresponding author1,7 Khaled Mohammed,1 Qusay Haydour,1,2 Michael R. Gionfriddo,3 Oscar L. Morey Vargas,4 Larry J. Prokop,5 Stephanie S. Faubion,6 and Mohammad Hassan Murad1

Files JA, Ko MG, Pruthi S. Bioidentical hormone therapy. Mayo Clin Proc. 2011;86:673–680. doi: 10.4065/mcp.2010.0714. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Stanczyk FZ, Hapgood JP, Winer S, Mishell DR., Jr. Progestogens used in postmenopausal hormone therapy: differences in their pharmacological properties, intracellular actions, and clinical effects. Endocr Rev. 2013;34:171–208. doi: 10.1210/er.2012-1008. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Progestins. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-. 2019 Jun 6. PMID: 31643562

Chitturi S, Farrell GC. Adverse effects of hormones and hormone antagonists on the liver. In, Kaplowitz N, DeLeve LD, eds. Drug-induced liver disease. 2nd ed. New York: Informa Healthcare USA, 2007, pp. 707-22. (Review of hepatotoxicity of female sex hormones published in 2007 states that progestin-only contraceptives or high dose progestin regimens used in breast cancer may rarely produce cholestasis).

Adlercreutz H, Tenhunen R. Some aspects of the interaction between natural and synthetic female sex hormones and the liver. Am J Med 1970; 49: 630-48. [PubMed] (Review of the hepatic effects of synthetic estrogens and progestins states that “intrahepatic cholestasis and jaundice… have been reported only for progestogens with the 19-norsteroid configuration”).

Reproductive Hormone Market Predicts Steady Growth Till 2027

Top Leading Companies: Pfizer, Allergan, Bayer, MERCK Groups, Jenapharm, ABBVIE, Xianju Pharma,Mayne Pharma