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The Medication Reality

If medication didn't really work for you, you are probably right. Large meta-analyses of antidepressant randomized controlled trials show drug-placebo differences are small, with more impact in very severe depression and small to modest mean differences overall. [1] Minimal clinical improvement on global ratings corresponds to an effect size nearer 0.8, and typical antidepressant-placebo differences fall short of that threshold (0.3-0.4).

Irving Kirsch has been particularly vocal in this area, arguing that analyses of both published and unpublished clinical trial data consistently show that most of the benefits of antidepressants in treating depression and anxiety are due to the placebo response. [2]

Some people do have a positive response to antidepressants. For them, the problem is solved and the rest of this newsletter doesn't really apply unless they want a stronger effect, are concerned about a lasting effect, or want to stop medication.

The Numbers for Medication Alone:

If we're targeting 50% symptom reduction, placebo produces results in around 35-40% of people, while medication achieves 40-47% depending on symptoms. [3] For remission (where symptom scores drop below a certain level): placebo works for 20-25% of people, while medication works for 25-28%. [3]

For those who do respond, relapse rates over 6-12 months tell an interesting story: about 40% of people relapse on placebo, compared to 20% continuing medication. [4] The problem is that most medications cause side effects so people usually know if they are on placebo.

Exercise: The Most Robust Intervention

A 2023 meta-analysis of 41 randomized controlled trials involving 2,264 participants found a large effect of exercise versus non-active controls on depressive symptoms, with a difference of about -0.95 and a number needed to treat to get a benefit of approximately 2 (When people start exercising, roughly half of them will likely see a difference in mood). [5] Both aerobic and resistance training showed large effects, especially when supervised and at moderate intensity.

A 2024 network meta-analysis of 218 RCTs with approximately 14,000 participants reported moderate reductions in depression for walking/jogging, yoga, strength training, mixed aerobic exercise, and tai chi/qigong versus active controls, with dose-response relationships by intensity and good tolerability for yoga and strength work. [6]

And think of all the other benefits you get from exercise!

Dance: Movement Plus Connection

Dance-specific interventions have shown significant reductions in depressive symptoms versus no-intervention controls in adults and older adults across multiple randomized controlled trials and meta-analyses. [7] Effect sizes are typically small to moderate, and the group/social components may account for part of the benefit.

Sleep: A Critical Target

A 2024 meta-analysis in major depressive disorder patients with insomnia found that cognitive behavioral therapy for insomnia (CBT-I) increased depression response rates from about 17% in controls to approximately 32% in CBT-I groups, beyond the sleep improvements alone. [8]

Gratitude Practices

A 2023 systematic review of 64 randomized controlled trials found that gratitude interventions—including journaling, letters, and apps—improved gratitude, mental health, and reduced anxiety and depressive symptoms versus controls, with small to moderate effects. [9] Individual RCTs using digital gratitude programs report small to moderate reductions in repetitive negative thinking and depressive symptoms, with effects maintained at follow-up.

EFT (Emotional Freedom Techniques)

A 2024 meta-analysis of randomized controlled trials reported a large pooled effect size of approximately 1.27 for depression reduction, with group formats and moderate baseline depression showing the greatest benefit. [10]

HeartMath and HRV Biofeedback

A meta-analysis of randomized controlled trials with approximately 794 participants reports a medium effect size (0.38) of heart rate variability biofeedback on depressive symptoms across clinical and nonclinical samples. [11] A separate RCT adding HRV biofeedback to psychotherapy for major depressive disorder found greater improvement in heart rate variability and superior depression outcomes compared with psychotherapy alone. [12]

Expressive Writing

In community samples, expressive writing (Pennebaker journaling) has been associated with modest short-term reductions in depressive symptoms and mental/physical complaints, though effects often attenuate by 4-6 months. [13]

Diet Matters

In postmenopausal women, higher dietary glycemic index (too many simple carbs) was prospectively associated with greater odds of developing depression over 3 years, even after adjusting for multiple lifestyle and dietary factors. [14]

A 2025 systematic review and meta-analysis suggests ketogenic diets are associated with modest improvements in depressive symptoms, particularly when biochemical ketosis is confirmed, though the review emphasizes heterogeneity, small samples, and short follow-up, calling for well-powered randomized controlled trials. [15]

Supplements: Selective Benefits

A 2016 meta-analysis restricted to adults with major depressive disorder found an overall difference of approximately 0.40 favoring omega-3 polyunsaturated fatty acids over placebo— comparable in magnitude to effect sizes reported for antidepressants. [16] Higher EPA doses and concurrent antidepressant use showed larger benefits. With the right formulation and context (EPA-heavy, approximately 1 gram per day, as add-on therapy), omega-3 can approximate antidepressant-like effect sizes.

Of course if there is a specific deficiency, such as low B12, or iron, or sometimes low methylfolate in a susceptible patient, this should be addressed.

Hormone Therapy for Perimenopausal Depression

Two out of three double-blind randomized controlled trials showed that transdermal 17β-estradiol (about 0.1 mg/day, with cyclic progesterone when uterus intact) can significantly reduce depressive symptoms in women with confirmed perimenopause compared with placebo, even when they meet criteria for major depressive disorder. [17]

For men, low testosterone (also test free testosterone) is a reversible cause of depression.

Thyroid hormone levels should be optimized.

Therapy: All Roads Lead to Rome

A network meta-analysis of 331 randomized controlled trials involving 34,285 patients compared cognitive behavioral therapy, interpersonal therapy, psychodynamic therapy, behavioral activation, problem-solving, third-wave therapies, life-review, and non-directive counseling. [18] All major therapies outperformed care-as-usual and wait-list (standardized mean difference roughly -0.3 to -0.8 versus usual care), with very small differences between active modalities. Non-directive counseling was somewhat less efficacious.

The Power of Integration

One study combined multiple elements: addressing the relationship between cognitive, behavioral, emotional, somatic and environmental factors proposed to maintain the self-perpetuating cycle of symptoms; a focus on psychosomatics (the reciprocity of body and mind); and attention to associations between unhealthy lifestyle behaviors and symptoms/disability. [19] Physical therapists focused mainly on the somatic symptoms and bodily dysfunctions associated with diagnosed mental disorders. This approach led to roughly 2/3 of patients improving—similar to coordinated care models where someone is responsible for keeping track of patients, their interventions, and their ongoing symptoms.

The Healing Depression Project offers a similar type of multi-modal intervention, in addition to a therapeutic diet and functional medicine expertise.



REFERENCES

[1] Pigott HE, Kim T, Xu C, Kirsch I, Amsterdam J. What are the treatment remission, response and extent of improvement rates after up to four trials of antidepressant therapies in real-world depressed patients? A reanalysis of the STAR*D study's patient-level data with fidelity to the original research protocol. BMJ Open. 2023.
https://bmjopen.bmj.com/content/13/7/e063095

[2] Kirsch I. Placebo Effect in the Treatment of Depression and Anxiety. Front Psychiatry. 2019.
https://pubmed.ncbi.nlm.nih.gov/31249537/

[3] Pigott HE, Kim T, Xu C, Kirsch I, Amsterdam J. What are the treatment remission, response and extent of improvement rates after up to four trials of antidepressant therapies in real-world depressed patients? A reanalysis of the STAR*D study's patient-level data with fidelity to the original research protocol. BMJ Open. 2023.
https://bmjopen.bmj.com/content/13/7/e063095

[4] Kato M, Hori H, Inoue T, Iga J, Iwata M, Inagaki T, Shinohara K, Imai H, Murata A, Mishima K, Tajika A. Discontinuation of antidepressants after remission with antidepressant medication in major depressive disorder: a systematic review and meta-analysis. Mol Psychiatry. 2021.
https://www.nature.com/articles/s41380-020-0843-0

[5] Heissel A, Heinen D, Brokmeier LL, Skarabis N, Kangas M, Vancampfort D, Stubbs B, Firth J, Ward PB, Rosenbaum S, Hallgren M, Schuch F. Exercise as medicine for depressive symptoms? A systematic review and meta-analysis with meta-regression. Br J Sports Med. 2023.
https://bjsm.bmj.com/content/57/16/1049

[6] Noetel M, Sanders T, Gallardo-Gómez D, Taylor P, Del Pozo Cruz B, van den Hoek D, Smith JJ, Mahoney J, Spathis J, Moresi M, Pagano R, Pagano L, Vasconcellos R, Arnott H, Varley B, Parker P, Biddle S, Lonsdale C. Effect of exercise for depression: systematic review and network meta-analysis of randomised controlled trials. BMJ. 2024.
https://www.bmj.com/content/384/bmj-2023-075847

[7] Moratelli JA, Veras G, Lyra VB, Silveira JD, Colombo R, de Azevedo Guimarães AC. Evidence of the Effects of Dance Interventions on Adults Mental Health: A Systematic Review. J Dance Med Sci. 2023.
https://pubmed.ncbi.nlm.nih.gov/37287281/

[8] Furukawa Y, Nagaoka D, Sato S, Toyomoto R, Takashina HN, Kobayashi K, Sakata M, Nakajima S, Ito M, Yamamoto R, Hara S, Sakakibara E, Perlis M, Kasai K. Cognitive behavioral therapy for insomnia to treat major depressive disorder with comorbid insomnia: A systematic review and meta-analysis. J Affect Disord. 2024.
https://pubmed.ncbi.nlm.nih.gov/39242039/

[9] Diniz G, Korkes L, Tristão LS, Pelegrini R, Bellodi PL, Bernardo WM. The effects of gratitude interventions: a systematic review and meta-analysis. Einstein (Sao Paulo). 2023.
https://pubmed.ncbi.nlm.nih.gov/37585888/

[10] Seok JW, Kim JU. The Effectiveness of Emotional Freedom Techniques for Depressive Symptoms: A Meta-Analysis. J Clin Med. 2024.
https://pubmed.ncbi.nlm.nih.gov/39518619/

[11] Schumann A, Helbing N, Rieger K, Suttkus S, Bär KJ. Depressive rumination and heart rate variability: A pilot study on the effect of biofeedback on rumination and its physiological concomitants. Front Psychiatry. 2022.
https://pmc.ncbi.nlm.nih.gov/articles/PMC9452722/

[12] Caldwell YT, Steffen PR. Adding HRV biofeedback to psychotherapy increases heart rate variability and improves the treatment of major depressive disorder. Int J Psychophysiol. 2018.
https://pubmed.ncbi.nlm.nih.gov/29307738/

[13] Sloan DM, Feinstein BA, Marx BP. The durability of beneficial health effects associated with expressive writing. Anxiety Stress Coping. 2009.
https://pmc.ncbi.nlm.nih.gov/articles/PMC4842937/

[14] Gangwisch JE, Hale L, Garcia L, Malaspina D, Opler MG, Payne ME, Rossom RC, Lane D. High glycemic index diet as a risk factor for depression: analyses from the Women's Health Initiative. Am J Clin Nutr. 2015.
https://pmc.ncbi.nlm.nih.gov/articles/PMC4515860/

[15] Janssen-Aguilar R, Vije T, Peera M, Al-Shamali HF, Meshkat S, Lin Q, Lou W, Laviada-Molina H, Phillips ML, Bhat V. Ketogenic Diets and Depression and Anxiety: A Systematic Review and Meta-Analysis. JAMA Psychiatry. 2025.
https://pubmed.ncbi.nlm.nih.gov/41191382/

[16] Mocking RJ, Harmsen I, Assies J, Koeter MW, Ruhé HG, Schene AH. Meta-analysis and meta-regression of omega-3 polyunsaturated fatty acid supplementation for major depressive disorder. Transl Psychiatry. 2016.
https://pubmed.ncbi.nlm.nih.gov/26978738/

[17] Xiang X, Palasuberniam P, Pare R. Exploring the Feasibility of Estrogen Replacement Therapy as a Treatment for Perimenopausal Depression: A Comprehensive Literature Review. Medicina (Kaunas). 2024.
https://pmc.ncbi.nlm.nih.gov/articles/PMC11279181/

[18] Cuijpers P, Quero S, Noma H, Ciharova M, Miguel C, Karyotaki E, Cipriani A, Cristea IA, Furukawa TA. Psychotherapies for depression: a network meta-analysis covering efficacy, acceptability and long-term outcomes of all main treatment types. World Psychiatry. 2021.
https://onlinelibrary.wiley.com/doi/10.1002/wps.20860

[19] Wijnen J, Gordon NL, van 't Hullenaar G, Pont ML, Geijselaers MWH, Van Oosterwijck J, de Jong J. An interdisciplinary multimodal integrative healthcare program for depressive and anxiety disorders. Front Psychiatry. 2023.
https://www.frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2023.1113356/full

Understanding the Source of Blood Glucose Elevation

Insulin resistance is far more than just a blood sugar problem. It's a complex physiological state involving multiple organ systems, what researchers call the "Ominous Octet" - eight interconnected mechanisms that contribute to hyperglycemia. By understanding how these systems work together, we can develop root cause prevention and treatment strategies.

BRAIN INSULIN RESISTANCE
Many experts now believe insulin resistance begins in the brain. Toxins, processed foods, and chronic stress disrupt normal hunger and satiety signals, setting the stage for metabolic dysfunction throughout the body (Sears & Perry, 2015). Environmental endocrine-disrupting chemicals can alter insulin signaling not just in peripheral tissues but through central mechanisms that affect global glucose regulation (Schulz & Sargis, 2021).
How to test: Unfortunately, brain insulin resistance is difficult to measure directly outside research settings, but symptoms like constant hunger, food cravings (especially for carbohydrates), and difficulty feeling satisfied after eating may indicate central regulation issues.
How to address: Reducing exposure to environmental toxins, minimizing ultra-processed foods, managing stress, and ensuring adequate sleep can all help restore normal brain signaling patterns. Practicing mindful eating can reconnect you with natural hunger and fullness cues.


FAT CELL DYSFUNCTION
Adipose tissue isn't just for energy storage - it's an active endocrine organ affecting whole-body insulin sensitivity. Initially, fat cells help manage glucose loads, but as they become insulin resistant, they not only fail to take up glucose but actively release free fatty acids that cause further problems throughout the body. These elevated free fatty acids impair insulin secretion and disrupt insulin signaling pathways, creating a vicious cycle (Sears & Perry, 2015).
Interestingly, even lean individuals with prediabetes often show elevated fasting free fatty acids (Pfeiffer & Kabisch, 2021).
How to test: Serum free fatty acids can be measured in both fasting state and after dextrose consumption during an oral glucose tolerance test (OGTT). Elevated levels, especially when they don't drop appropriately after dextrose consumption, suggest adipose tissue insulin resistance.
How to address: Omega-3 fatty acids help adipose tissue by promoting the formation of smaller, more insulin-sensitive fat cells capable of storing more fat without becoming dysfunctional. Regular physical activity, especially strength training and high-intensity interval training, can improve adipose tissue function and insulin sensitivity. Fat tissue is also disrupted by a variety of environmental toxins.


LIVER INSULIN RESISTANCE
The liver plays a crucial role in glucose regulation through storage of glucose as glycogen, glucose production, and adjusting insulin levels. When adipose tissue becomes insulin resistant, the free fatty acids released travel directly to the liver, promoting fatty liver development and liver insulin resistance (Sears & Perry, 2015).
How to test: Indexes derived from fasting glucose and insulin measurements, such as HOMA-IR, primarily reflect liver insulin resistance rather than whole-body insulin sensitivity (Abdul-Ghani et al., 2007). Elevated liver enzymes (ALT, AST) and imaging studies showing fatty infiltration also suggest hepatic insulin resistance.
How to address: Omega-3 fatty acids (again) improve liver function and protect against non-alcoholic fatty liver disease (Aziz et al., 2024). Reducing refined carbohydrates and added sugars, and especially alcohol intake, helps decrease the liver's fat production, while intermittent fasting (eating earlier in the day is preferable) may improve hepatic insulin sensitivity.


MUSCLE INSULIN RESISTANCE
Skeletal muscle is the primary site of glucose disposal, accounting for approximately 70-80% of whole-body glucose uptake after a meal. Muscle becomes insulin resistant largely due to fatty acids from fat cells, and due to inflammatory cytokines released from several organs (Sears & Perry, 2015).
How to test: During an oral glucose tolerance test, the decline in plasma glucose between the 1 hour and the 2 hour marks primarily reflects muscle glucose uptake (Abdul-Ghani et al., 2007). This can provide insight into muscle insulin sensitivity.
How to address: Regular exercise is the most powerful intervention for muscle insulin resistance. Both aerobic exercise and resistance training improve muscle glucose uptake through both insulin-dependent and insulin-independent pathways. Omega-3 fatty acids have demonstrated protective effects against muscle insulin resistance as well (Sinha et al., 2023). Adequate vitamin D and magnesium are also important for optimal muscle insulin sensitivity. Air pollution from PM2.5 particles impact muscle insulin resistance, and can be mitigated at home using an air purifier.


GASTROINTESTINAL/INCRETIN EFFECT ABNORMALITIES
The gut plays a crucial role in glucose metabolism through the secretion of incretin hormones that stimulate insulin release. Approximately 65-70% of insulin response following oral glucose comes from incretin effects that don't occur when glucose is administered intravenously.
The key incretins are GIP from K-cells (in the duodenum and small intestine) and GLP-1 from L-cells, with GLP-1 being one of the most potent insulin-releasing substances known (Holst & Orskov, 2004). In type 2 diabetes, incretins are released but the pancreas fails to respond.
How to test: Incretin effects are difficult to measure outside research settings, which typically compare insulin responses to oral versus intravenous glucose administration.
How to address: Plant polyphenols show glucose lowering effects, sometimes stimulating GLP-1 secretion by modulating gut microbiota and inhibiting DPP-IV activity so incretin levels can rise (Wang et al., 2021). Dietary approaches that support a healthy gut microbiome may improve incretin function.


PANCREATIC BETA CELL DYSFUNCTION
Pancreatic beta cells make insulin. These cells may fail to respond adequately to the signals causing insulin release. These insulin-producing cells require proper redox signaling balance - neither too little nor too much oxidative capacity is optimal for insulin secretion (Ježek et al., 2021). Beta cells are particularly vulnerable to inflammatory mediators, which can impair function long before cell death occurs (Sears & Perry, 2015).
How to test: The C-peptide is the best way to measure beta cell function. The C-peptide to glucose ratio at 1 hour during an OGTT (called C-peptide index or CPI) serves as a predictive marker. Patients who later develop diabetes show average CPI values of 2.5, compared to 6.56 in those who don't develop diabetes (Zhang et al., 2017).
How to address: Reducing overall inflammation and oxidative stress helps protect beta cell function. Dietary approaches rich in antioxidants, omega-3 fatty acids, and polyphenols provide beta-cell protection. Managing blood glucose levels within normal ranges prevents glucotoxicity that damages beta cells over time.



ALPHA CELL DYSFUNCTION
Alpha cells in the pancreatic islets contribute to hyperglycemia through dysregulated glucagon secretion. Glucagon, a type of stress hormone, normally raises blood glucose, but in diabetes, its secretion becomes excessive and poorly regulated.
GLP-1 normally inhibits glucagon release from alpha cells, a function that may be impaired as glucose regulation becomes impaired (Wang et al., 2021).
How to test: Glucagon can be measured as part of an oral glucose tolerance test. In healthy individuals, glucagon levels decline after glucose consumption, but this suppression may be impaired in prediabetes.
How to address: GLP-1 receptor agonist medications help normalize glucagon secretion. Dietary approaches that minimize blood sugar spikes and reduce overall inflammation may help restore normal alpha cell function. Stress reduction techniques are important since glucagon is a type of stress hormone.


KIDNEY GLUCOSE REABSORPTION
The kidneys play an underappreciated role in glucose balance. Normally, they reduce blood glucose by allowing excess to spill into the urine when levels get too high. But in diabetes, they paradoxically increase glucose reabsorption, worsening hyperglycemia.
How to test: Glucose in the urine can be easily tested, but more sophisticated measurements of kidney function and glucose handling require specialized tests not routinely available.
How to address: There are many interventions to optimize kidney health if this is starting to become a problem. They may involve avoiding foods with added phosphates, measuring and addressing blood CO2 levels, and other approaches.


ENVIRONMENTAL FACTORS & THERAPEUTIC INTERVENTIONS
Environmental factors significantly impact insulin sensitivity across all organ systems. Air pollution exposure, particularly to fine particulate matter (PM2.5), worsens insulin resistance (Hectors et al., 2013). A quality air purifier can reduce PM2.5 in your home, providing hours of cleaner air daily.
Heavy metal exposure causes persistent disruptions in gut microbiota that don't self-correct after exposure ends (Jin et al., 2023). These metals cause shifts in microbiome composition that affect metabolism and insulin sensitivity. Intriguingly, animal studies suggest fecal microbiome transplantation may help treat heavy metal-induced dysbiosis (Jin et al., 2023). Approaches involving probiotics and prebiotics, and the fasting-mimicking diet improve metabolism.
Plant compounds offer some of the most promising natural interventions. Epicatechin (found in cocoa), epicatechin-containing foods, and anthocyanins show particular promise for improving insulin resistance (Williamson & Sheedy, 2020). Cocoa flavanols improve insulin sensitivity in both healthy and hypertensive populations and enhance blood vessel function in people with type 2 diabetes (Bapir et al., 2022).
A systematic review of 19 randomized controlled trials found anthocyanin supplementation improved HOMA-IR (Daneshzad et al., 2019). These colored compounds found in berries and other vibrant foods work through multiple mechanisms.
Polyphenols (plant substances present in many plant-based foods, including olive oil) undergo processing by intestinal enzymes and gut microbiota, with high concentrations remaining in the digestive tract. Several polyphenols stimulate GLP-1 secretion by acting on specific receptors, activating taste receptors, and regulating cellular signaling. They also indirectly boost GLP-1 by altering gut microbiota composition, particularly increasing bacteria that produce short-chain fatty acids that stimulate GLP-1 release (Wang et al., 2021).


CONCLUSION
Insulin resistance is a whole-body condition involving an intricate dance between the brain, fat tissue, liver, muscle, gut, pancreatic beta and alpha cells, and kidneys. By understanding each component of this interconnected system, we can develop personalized approaches that target each individual's unique pattern of dysfunction.
Future research and clinical practice should focus on identifying which components of the "ominous octet" predominate in individual patients, allowing for more precisely tailored intervention strategies. Addressing as many aspects as possible offers the best chance for meaningful improvement.

Many Systems Go Wrong As Metabolic Health Declines
Modern research reveals an increasingly complex picture leading to metabolic dysfunction. We're familiar with insulin resistance as the inability of muscles to properly take up glucose from the bloodstream. However, muscle insulin resistance is only one of several disruptions that occur as glucose regulation deteriorates.


PANCREAS
If insulin resistance were the only issue, the pancreas would simply produce more insulin to control blood glucose. Unfortunately, the pancreas itself can become affected in two critical ways:

1. It produces more insulin, but is not able to keep up with the demand for insulin
   
2. It begins to produce excessive amounts of glucagon - a hormone normally released when we eat protein and actually raises blood glucose
   

This pancreatic dysfunction typically occurs because the organ is inflamed, and/or affected by oxidative stress.


LIVER
The liver represents a third major factor in this metabolic cascade. Normally, the liver stores glucose as glycogen, releasing it only when blood glucose drops or during stress responses. In metabolic dysfunction, the liver inappropriately releases glucose into the bloodstream when it's not needed. While high insulin should signal the liver to retain glucose, as the body becomes insulin resistant, so does the liver.
The real tragedy unfolds as additional organs join this metabolic disruption:


FAT CELLS
Fat cells, which normally respond to insulin by storing fat after meals, become insulin resistant and inappropriately release free fatty acids. These fatty acids travel to the liver, pancreas, muscles, and kidneys, causing inflammation and damage, and further dysfunction.


BRAIN
The brain becomes affected by the spreading inflammation. Normally, insulin should help suppress appetite after adequate food intake. However, food cravings may arise despite high insulin levels: they represent an abnormal response. This includes disrupted responses to gut hormones like incretins, which normally interact with GLP-1 receptors. These receptors have recently gained fame through GLP-1 agonist medications that help people lose significant weight partly by improving the brain's satiety response.


KIDNEYS
Finally, the kidneys show abnormal glucose handling. Instead of efficiently removing excess glucose from the body, kidneys affected by insulin resistance and metabolic dysfunction reabsorb more glucose than they should. This dysfunction stems from toxicity, inflammation, and poor vascular health.


SOLUTIONSAddressing this complex metabolic disruption requires a multifaceted approach. Toxicity can play a role in all 8 of these systems. This highlights the importance of strategies such as:

• Avoiding heavy metals, industrial chemicals, pesticides, microplastics, etc.
  
• Reducing the body’s inflammation to improve its detoxification capacity;
  
• Hydrating well to eliminate toxins that exit through the urine;
  
• Following a nutrient-dense diet rich in protective compounds;
  
• Implementing stress reduction practices;
  
• Cultivating a healthy gut ecology, which plays an important role in removing toxins, and in "speaking" directly to the liver to improve glucose regulation.
  

This systems-based understanding of glucose dysregulation explains why comprehensive lifestyle approaches often succeed where single interventions fail. By addressing multiple components of the "ominous octet" simultaneously, we can work toward restoring metabolic harmony.

Summary: How well women feel during menopause depends less on their symptoms and more on their belief that they can manage those symptoms—thus it matters a lot whether doctors help or hurt that belief. Doctors fail women in two ways: using old, outdated information or distrusting good science. Both result in women getting the wrong advice. The fix: women need to build confidence in managing their health and spot good medical care, while doctors need to learn how to tell solid research from weak research. Right now, the system creates a difficult situation, where poor care impairs women's confidence, women’s symptoms get more severe, and leave women with fewer options in life, which makes it harder to design a satisfying life after menopause.Why Informed Consent Fails at Menopause

Quick Takes

#1: The Self-Efficacy MultiplierWomen with high self-efficacy (confidence that they can successfully manage a specific challenge) cope better with menopausal symptoms regardless of severity. But this means that women who struggle the most with self-efficacy will often find themselves seeking help. When they encounter poor medical care, two harms occur: self-efficacy erodes further AND symptoms constrain life more (work, relationships, functioning). Both worsen symptoms. Physicians aren’t just failing to help—they may cause harm by weakening the resource women need most.

#2: Two Paths to Wrong InformationPhysicians fail women by: (1) getting stuck on outdated warnings from old hormone formulations, OR (2) rejecting rigorous trials as untrustworthy while focusing on observational studies and animal models as equally valid. Both betray trust. Example: observational studies suggest MHT clearly protects heart and brain, but randomized trials (which remove selection bias) only prove bone benefits. Being "pro-woman" requires engaging with best science, not abandoning rigor.

#3: Informed Consent Needs BothTrue informed consent requires scientific accuracy AND respect for autonomy. 

• Accuracy without respect = paternalism = no informed consent. 
• Respect without accuracy = informed consent also becomes impossible. 

Women must build self-efficacy and learn to spot quality care. Physicians must develop research literacy, update knowledge regularly, and individualize recommendations. We have work to do.

Favorite Finds

Building Self-Efficacy

There are evidence‑based ways to increase self‑efficacy, including in peri‑ and postmenopausal women. Some interventions have used counseling (Karimlou et al, 2017) or educational sessions (Khandehroo et al, 2025) (Magistro et al, 2025).

Bandura (1977) postulated the existence of 4 sources of self-efficacy, including mastery experiences (choosing a small goal and succeeding), vicarious experiences, verbal persuasion with concrete support, and managing physiological and emotional arousal.

Programs are available in many communities, for example in the Bay Area through Stanford Medicine and Kaiser Permanente’s virtual Navigating Menopause program, and on the more integrative side, Oakland’s Menopause Wellness Circle, and the Menopausitive Workshop. I am not familiar with the details of these programs but they may be worth exploring.

Science Literacy
Anyone can learn research literacy, for example by taking this beginner “massive open online course” from Coursera: Science Literacy.
Getting what you need from a physician visit (or other provider)

• What Patients Say, What Doctors Hear – Danielle Ofri’s book gets 4/5 stars on GoodReads.​
• Doctors Talking with Patients/Patients Talking with Doctors – A classic text on medical communication written mainly for clinicians.
• SHE+ Patient Advocacy guide — A totally free, very useful toolkit especially addressed to patientswho have experienced dismissal
• Self‑Advocacy Guide for Women’s Health (Ms.Medicine) – A free (they request your email) women‑specific downloadable guide
• My Menoplan: menopause‑focused resource that coaches women to set an agenda, prepare a symptom and question list, state visit goals clearly, and use decision tools to guide the discussion
• Healthline has some good free advice as well.

Deep Dive

The Problem
FACT: Women couldn't vote in the US until 1920 or get credit cards in their own name until 1974. Medical research has systematically neglected women's health. These patterns of dismissing women's importance, autonomy, and concerns persist in clinical practice today.
SOLUTION: Physicians must actively recognize this historical baggage and counteract it with validation, respect, and commitment to filling knowledge gaps.


FACT: Menopause requires of women that they redefine their roles, meaning, relationships, and ways of being in the world. Women who struggle more with this transition experience more disruptive symptoms—and may find themselves needing to seek medical care.
SOLUTION: Recognize menopause as a profound life transition, not just a medical problem. The women in your office are already vulnerable and deserve support.


The Self-Efficacy Connection
FACT: Self-efficacy is your confidence that you can organize and execute a plan to reduce the impact of symptoms on your life. Women with high self-efficacy report better life satisfaction in spite of menopausal symptoms, regardless of symptom severity.
SOLUTION: Build health self-efficacy anytime—even before menopause—the belief that "what I do matters" for health outcomes changes these outcomes.


FACT: When women with lower self-efficacy encounter dismissive or poorly informed physicians, two harms occur: their self-efficacy erodes further AND their symptoms constrain their lives more (work, relationships, sexuality, functioning). Both consequences worsen symptom disruptiveness, creating a downward spiral that can be interrupted by supportive accurate care.
SOLUTION: Physicians must understand they run the risk of worsening one of the root causes of their patients’ distress—they are not just failing to help, but actively damaging women's ability to cope.


The Science Literacy Crisis
FACT: Physicians may fail women in two ways: (1) getting stuck on outdated warnings based on old hormone formulations without knowing current research, OR (2) rejecting rigorous science as untrustworthy while giving undue weight to weaker evidence like observational studies and animal models, or basic petri dish research.
SOLUTION: Real advocacy requires engaging with the best available science. Demand more rigorous research—don't abandon rigor itself. Update knowledge regularly.


FACT: Observational studies show that women who choose hormone therapy (MHT) have better outcomes—but these women also exercise more, eat better, have better healthcare access. This could be the "healthy user effect.” Randomized trials, which remove selection bias, tell a different story: MHT reliably benefits bone health, but cardiovascular and cognitive benefits aren't clearly proven. Also, for breast cancer, while bioidenticals are preferable, if MHT is started within 3 years of menopause and continued past five years, risk increases.
SOLUTION: Understand what research shows so you can be accurate with patients. Promise bone protection, not heart or brain protection. Individualize breast cancer risk assessment. Don't oversell benefits or ignore nuance. Remember to discuss the increased chance of autoimmune disease in women on MHT, and the risks of postmenopausal bleeding. Also be in a position to discuss possible benefits to oral health, skin, hair, and all the other issues MHT can affect.


What Informed Consent Requires
FACT: True informed consent requires both scientific accuracy AND respect for women's autonomy.
SOLUTION: Physicians must weigh multiple factors for each patient: age at menopause, exercise habits, bone health, breast cancer risk, family history, individual goals. Learn to read studies critically, acknowledge uncertainty, and resist oversimplification.


FACT: Most physicians lack training in drawing accurate conclusions from observational studies (selection bias) vs. randomized controlled trials (removes bias), or in clearly defining and evaluating forms of evidence.
SOLUTION: Medical education must include robust research literacy training. Physicians need to understand the consequences of study design.


Action Steps
FOR ALL PATIENTS:

• Build health self-efficacy anytime
• Learn what respectful care looks like: listening, validation, evidence-based recommendations
• Know the red flags: outdated warnings, dismissiveness, inability to explain evidence

FOR PHYSICIANS:

• Get training in research literacy—understand study design, bias, limitations
• Examine your biases and update your knowledge regularly
• Learn to weigh multiple factors for individualized care
• Apply rigorous evidence evaluation to ALL treatments: hormones, antidepressants, osteoporosis medications

FOR HEALTHCARE SYSTEMS:

• Stop making overly broad guideline statements
• Develop better tools for individualized risk assessment
• Support physician education in research literacy

The Bottom Line
​FACT: Women deserve physicians who listen AND know how to read studies. They deserve respect AND accuracy. They deserve real empowerment—grounded in the best evidence, honestly interpreted, with uncertainty acknowledged.
SOLUTION: This is informed consent. Anything less is failing women while claiming to help them.