I’m about to present a story about women’s health that I find disturbing. I’m upset by the men and women who either did not ask the right questions and those that hid or obscured science for the last 70 years. It seems the defaults we find ourselves unconsciously embracing from convention are sometimes quite sinister. The story feels large, so I’m aiming to break it into three distinct parts. Firstly, the evolutionary norms of women in terms of hormones and births were and are dramatically different from what we currently consider normal. It’s worth learning about the existing situation in contrast to the situation from which we evolved. Secondly, contraceptives are dramatically impactful to women’s physical and psychological health. The momentum of use continues while we are only beginning to tabulate the long term effects of birth control on its first generations. The risks, or really known side effects are under-emphasized. Thirdly, our physical environment is full of xenoestrogens that make all the problems from one and two worse and are contributing significantly to fertility declines and hormonal dysregulation in the global population.
Many far fetched stories are wrong, but a few important ones turn out to be uncomfortably and unavoidably true. For environmental carcinogens like lead, asbestos and smoking we’ve finally more or less embraced change and policy in the direction of health. In the case of obesity, the culture at large seems to acknowledge the state of affairs while essentially only a handful of people are avoiding it. A full 73% of US adults over 20 years old are overweight and if the CDC data is to be believed the category is accelerating its growth. In any case, obesity is a problem that is empirically and observationally validated. The effects of reproductive hormone dysregulation, contraception and exogenous endocrine disruptors on women’s health and psychology on the other hand are not much discussed or even hinted at, except by a very small cadre of authors. I appreciate those authors and believe the implications are immense.
Part 1. A lifetime of exposure
Hormonal exposure was very different in the ancestral environment. Calories were more scarce and less calories meant less insulin to drive the production of sex steroids. This results in modern western women having about 4 times the frequency of menstruation as their forebears living prior to the 1900s. Foraging cultures experience approximately 160 menstruation events in their life, some as low as 100 and modern women experience around 450. The amplitude of hormones has also changed. The hormonal peaks of estrogen and progesterone are on average 50-60% higher for women in modern cultures. As with insulin’s role in diabetes these increases in exposure are not benign.
Modern women are also missing a great deal of oxytocin. Foraging women will spend about three years per child with 12 to 15 total years while modern women will spend about half a year total breastfeeding. That is a 30 fold exposure difference for the mother and child. Oxytocin is one of the only substances that will repair tissues by increasing temperature and vasodilation, and it does so while reducing appetite and creating a sense of relaxation. For a description of the wide benefits of oxytocin please see my article here. Even the lesser period of breastfeeding by western women has been shown to have significant effects on the long term stress reactivity of both participants. The cardiovascular benefits and sense of calm for both mother and child have a long lasting effect. This will be commensurate with the return of insulin and insulin sensitivity to healthy low levels. As to the child’s health, both reduced childhood oxytocin and early menarche are associated with negative lifetime health and behavioral outcomes.
The absolute levels of progesterone can be higher in modern women than foragers, but the relative ratios of estrogen and progesterone are often significantly out of balance due to the relationship between progesterone and sympathetic nervous system activation. Progesterone is a gamma-aminobutyric acid (GABA) agonist and will oppose stress and sympathetic activation, but the system works both ways with sympathetic activation and stress lowering progesterone. Most doctors will recommend getting a contraceptive pill or changing a pill to deal with symptoms facilitated by too little progesterone and too much estrogen.
Women in foraging cultures will get pregnant at low hormone levels, low enough that similar levels in the US would indicate infertility. This is probably because tissue exposed to chronically high hormones will down-regulate receptors. The specific driver of estrogen insensitivity might be insulin rather than estrogen itself. In either case, the foragers are more sensitive while we moderns are not. This situation is called hypothalamic-pituitary estrogen insensitivity, and is essentially like having a kind of diabetes, but with sex steroids instead of insulin.
As in diabetes, where increased insulin drives many downstream pathologies we find many downstream problems with increased estrogen unopposed by progesterone. Cancer of all types, but especially breast and cervical types, are known to be associated with or driven by excess estrogen. Data suggests that modern women are at 100 times more risk of breast cancer than foraging populations (WT). Beyond cancer, estrogen is implicated in a large majority of health conditions through tissue hypoxia, blood clotting, elevated insulin, histamine increases, overactive and inappropriate immune activation and immune degradation. Those system malfunctions result in women having more: alzheimers, autoimmune, chronic pain, depression, mood disturbances, psychiatric conditions and various nervous system issues including migraine headaches. It is very difficult to disentangle the effects of insulin and obesity with those of estrogen, but starting in 2016 and continuing through 2019 life expectancy was flat to declining, even prior to the significant drop in 2020 from COVID.
Relatedly, low progesterone is associated with high estrogen and the pathologies listed above. Increased progesterone opposes adrenaline, cortisol, aldosterone and estrogen and all their deleterious effects. For those like me that might not have known, aldosterone in excess causes high blood pressure and low potassium which will further increase the risk of diabetes, vascular disease and stroke. Progesterone is a relax and repair hormone that reduces sympathetic tone and triggers apoptosis in many cancerous tissues. It increases peripheral temperature and is supportive of an overall higher thyroid, which helps repair and protect the periphery. It makes both muscle and fat less insulin sensitive, so glucose is preferentially delivered to other tissues. Progesterone is also a precursor to allopregnenolone which is a critical neurosteroid related to positive affect, and it turns out endogenous progesterone is also released when we spend time connecting socially.
The culprits to lowering progesterone or creating an estrogen imbalance are many. Outside of xenoestrogens and contraceptives, most are related to the stress response. Short term stresses which we properly adapt to are required, healthy and part of the richness of life. Progesterone would increase and follow on from short term stressors. Chronic stressors, implying no period of repair and adaptation, are unfortunately not consistent with robust health.
While I think many people are experiencing too much stress in comprehensible places like their jobs, there are a variety of other stressors easily omitted from typical consideration. Circadian disruption from modern lighting and lifestyles is my guess as to the largest contributor. Shift workers suffer many more health problems than their peers, including significant increases of breast cancer and cardiovascular events.
Another two broad categories involve our relationship with food. First, eating in a way that signals winter or famine is arriving are the common way humans, especially North American humans, eat these days. Diets heavy on omega 6s along with foods high in anti-metabolic compounds let mammals know that winter is approaching and we should reduce our metabolic rates, increase inflammation, increase blood sugar and store more body fat. Secondly, the ingestion of digestive irritants, and anything that causes abdominal pain, inflammation, or malabsorption will work against metabolism and reduce progesterone production. Relatedly an irritant many of us adore and do not want to hear evidence about is alcohol, but the research clearly shows alcohol consumption increases estrogen and reduces progesterone. Perversely, reduced progesterone is related to reduced thyroid which relates to increased sensitivity of the gastrointestinal tract, and the potential to get trapped in a spiral of reduced nutrient intake and further increased stress response.
While the landscape factors described are significantly at odds with women’s well being, we have yet to discuss the effects of contraceptives, or the myriad of xenoestrogens everywhere in our lives and supply chains.
Stay tuned for part 2. Deceptive Contraceptives (working title).
References and Further Reading:
Slowing the Aging Process with Natural Progesterone (A 12 page pdf document)
Ancient Bodies, Modern Lives: How Evolution Has Shaped Women's Health
Count Down: How Our Modern World Is Threatening Sperm Counts, Altering Male and Female Reproductive Development, and Imperiling the Future of the Human Race
How The Pill Changes Everything: The Surprising Science of Women, Hormones, and the Law of Unintended Consequences
Sex, Lies, and Menopause: The Shocking Truth About Synthetic Hormones and the Benefits of Natural Alternatives
Progesterone in Orthomolecular Medicine
Progesterone and Friendship
Social Closeness Increases Salivary Progesterone
Progesterone Vs Stress
Cortisol Blockade of Progesterone
Adrenaline Dominance (Summary Article) - Also relates to the “adrenaline junkie personality”
Progesterone and (reduced) Hypertension
Hypertension in Women the Role of Progesterone and Aldosterone
Progesterone Reduces Sympathetic Tone Without Changing Blood Pressure
Influence of Progesterone on Serotonin Metabolism
Progesterone Resistance in Endometriosis Linked to Failure to Metabolize Estradiol
*This is a terrible title and a perfect example of the researchers conflating progesterone with a progestin
“Progesterone and progestins may relieve pain by limiting growth and inflammation in endometriosis but a portion of patients with endometriosis and pelvic pain do not respond to treatment with progestins.”
***The treatment of endometriosis can usually be done with actual progesterone, it seems like the medical GPs and much of the research community do not realize progesterone separate from progestins exists.
Hypothalamic pituitary insensitivity to estrogen including feedback
“Decreased sensitivity in later life may simply be a continuation of the same pattern of progressive age-related estrogen insensitivity. Levels of LH are higher in perimenopausal women than in younger women, even in the presence of estrogen concentrations that result in lower LH levels in younger women.” “the perimenopausal transition is a time when circulating estrogen levels are equivalent or higher than levels observed in younger women.14 Additionally, exogenous estrogen is therapeutic in perimenopausal women.20 These observations are consistent with the hypothesis that a decrease in estrogen sensitivity occurs as women age through the menopausal transition.”
*Much of the research on hormone replacement must be confused by not realizing the estrogen resistance that has accumulated after a lifetime of ‘hyper-estrogenemia.’ I’m a fan of HRT, but returning estrogen sensitivity makes much more sense to me than continuing to increment estrogen.
Progestins Suppress LH/Progesterone and thus pregnenolone, DHEA, and testosterone too
https://pubmed.ncbi.nlm.nih.gov/33016316/
https://pubmed.ncbi.nlm.nih.gov/12080007/
Medical Conditions with Female Asymmetry
https://www.hopkinsmedicine.org/womans_path_wellness/for_women/disease_more_prevalent.html
*I’m assuming these are Estrogen related and I feel fairly comfortable with that assumption
Expected Life Span Gap Decreasing
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6015620/
Progesterone vs Estrogen
http://raypeat.com/articles/articles/progesterone-summaries.shtml
Lead - Some might have been ignorant but many were knowledgeable and complicit
Breast Feeding
Breast Feeding and the Reduction of Stress
https://pubmed.ncbi.nlm.nih.gov/25768266/
https://www.infantjournal.co.uk/pdf/inf_054_ers.pdf
https://pubmed.ncbi.nlm.nih.gov/15917038/
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(15)01024-7/fulltext
Estrogen and the Thymus:
https://pubmed.ncbi.nlm.nih.gov/16751381/
https://grantome.com/grant/NIH/R03-HD046717-01A1
https://onlinelibrary.wiley.com/doi/full/10.1002/eji.201646309
Menstruation in Dogon Women