The Trusted Pharmacist

What if the estrogen missing from your hormone therapy wasn't left out because it failed, but because no one could build a profitable drug around it?
Your body naturally produces three estrogens: estrone, estradiol, and estriol. Yet most hormone therapy replaces only estradiol. It is easy to assume that estriol was studied, found ineffective, and discarded. But that is not what happened. It didn't necessarily lose a scientific argument; it lost a business one, and over time, we mistook that silence for proof.
That missing conversation matters because estrogen does not produce the same effect everywhere in the body. And this could help explain why some women see their hot flashes disappear on estradiol while continuing to struggle with mood changes, disrupted sleep, brain fog, gut problems, recurrent UTIs, or unexplained inflammation. Their treatment may not be failing; it may simply be addressing only part of the hormonal picture.
In this episode, I talk about why you never hear about estriol, why it's not about effectiveness, and when to consider asking your doctor about it. 
What You'll Discover in This Episode
Why your body produces three estrogens, while most hormone therapy replaces only one

How estriol may have lost a business argument, not a scientific one

Why the absence of an FDA-approved estriol product does not automatically prove that estriol is ineffective

The crucial difference between a hormone binding to a receptor and fully activating it

How estrogen receptor alpha and estrogen receptor beta can produce very different effects throughout the body

Why estradiol can successfully relieve hot flashes while mood, sleep, memory, gut, or inflammatory symptoms remain

What research involving the brain, gut, immune system, and urogenital tissue suggests about receptor beta

What human multiple sclerosis trials may reveal about estriol's potential immune effects, and what those studies cannot yet prove

Why elevated cholesterol and metabolic health may further complicate estrogen receptor signaling

The strongest scientific objections to combination hormone therapy—and why they deserve serious answers

Why estriol being a "weaker" estrogen may be a feature in some formulations, not necessarily a flaw

How poorly timed blood tests can make a compounded hormone cream appear ineffective

What to ask your provider if your current estrogen therapy is helping, but you still do not feel like yourself

 
PS. If you enjoy the show, remember to leave a review on your favorite podcast app! Reviews help the podcast reach a wider audience and help more people.
 
Research Referenced in This Episode
Every study below includes a PubMed ID (PMID), which you can use to find the original paper at PubMed.
This episode discusses hormone therapy for educational purposes only. It is not medical advice or a substitute for a conversation with your healthcare provider about your symptoms, medical history, and treatment.
Estrogen Receptor Biology
Binding affinities of 74 naturally occurring estrogen metabolites at estrogen receptors alpha and beta. Estriol demonstrated preferential binding to ERβ.
Zhu BT, et al. Endocrinology. 2006. PMID: 16728493

Comparative transcriptional activity of estradiol at ERα and ERβ.
Bhavnani BR, et al. Endocrinology. 2008. PMID: 18599548

Crystal structure research examining how estradiol interacts with ERβ.
Souza PCT, et al. Scientific Reports. 2017. PMID: 28615710

27-hydroxycholesterol as a negative allosteric modifier of estradiol binding at ERβ.
Starkey NJE, et al. Endocrinology. 2018. PMID: 29579190

Brain, Mood, and Memory
Effects of an ERβ-selective agonist and estradiol on serotonergic neurons after ovariectomy.
Suzuki H, et al. Molecular Psychiatry. 2013. PMID: 22665260

Antidepressant effects of estradiol and an ERβ-selective agonist after long-term ovarian hormone deprivation.
Hou Y, et al. Journal of Psychiatry & Neuroscience. 2019. PMID: 30565903

Effects of ERβ activation on synaptic proteins, hippocampal signaling, and memory performance.
Liu F, et al. Nature Neuroscience. 2008. PMID: 18297067

Estriol treatment, cortical atrophy, remyelination, and neuronal preservation.
Meyer CE, et al. Laboratory Investigation. 2023. PMID: 37245852

ERβ-mediated neuroprotection independent of peripheral anti-inflammatory effects.
Tiwari-Woodruff S, et al. Proceedings of the National Academy of Sciences. 2007. PMID: 17785421

Gut Health
Effects of ERα- and ERβ-selective agonists and estradiol on intestinal cell proliferation and apoptosis.
Schleipen B, et al. Carcinogenesis. 2011. PMID: 21856997

The role of ERβ in intestinal tight junctions and gut permeability.
Braniste V, et al. American Journal of Physiology—Gastrointestinal and Liver Physiology. 2011. PMID: 21252046

How the gut microbiome and the estrobolome influence circulating estrogen.
Baker JM, et al. Maturitas. 2017. PMID: 28778332

Estriol and the Immune System
Immune markers in postmenopausal women receiving oral estradiol.
Itaborahy RM, de Medeiros SF. Climacteric. 2016. PMID: 27593223

Estriol treatment and changes in inflammatory and anti-inflammatory immune signals in women with multiple sclerosis.
Soldan SS, et al. Journal of Immunology. 2003. PMID: 14634144

Estriol-generated tolerogenic dendritic cells in an autoimmune model.
Papenfuss TL, et al. Journal of Immunology. 2011. PMID: 21317386

Estriol and pulmonary inflammatory gene expression during influenza infection.
Vermillion MS, Ursin RL, Klein SL, et al. Endocrinology. 2018. PMID: 30032246

Estriol regulation of TNF and IL-6 responses in a murine endotoxemia model.
Zuckerman SH, et al. Inflammation. 1996. PMID: 8979148

Review of estriol's immunomodulatory role across multiple sclerosis and other immune-mediated conditions.
Ali E, Mangold C, Peiris AN. Menopause. 2017. PMID: 28375935

Human Clinical Trials of Estriol
Phase I trial of oral estriol in women with relapsing-remitting multiple sclerosis. Inflammatory brain lesions decreased during treatment, returned after withdrawal, and decreased again when treatment resumed.
Sicotte NL, et al. Annals of Neurology. 2002. PMID: 12436153

Phase II randomized, placebo-controlled trial of estriol added to standard therapy in 164 women with relapsing-remitting multiple sclerosis.
Voskuhl RR, et al. The Lancet Neurology. 2016. PMID: 26621682

Estriol Physiology and Ovarian Function
Ovarian transplantation and immune function in post-reproductive mice.
King A, et al. Frontiers in Endocrinology. 2023. PMID: 36755910

Route of Administration and Inflammation
Changes in C-reactive protein among postmenopausal women using different hormone preparations in the PEPI trial.
Circulation. 1999. PMID: 10500035

Effects of oral and transdermal estradiol on C-reactive protein and other inflammatory markers.
Zegura B, et al. Atherosclerosis. 2003. PMID: 12732395

An Important Note About the Evidence
This research includes receptor pharmacology, animal studies, and human clinical trials conducted in specific patient populations, most notably women with multiple sclerosis. These different forms of evidence cannot automatically establish that estriol will produce the same benefits for every woman using menopausal hormone therapy.
There is currently no large randomized controlled trial directly comparing estradiol alone with combined estradiol-and-estriol therapy in postmenopausal women. There is also no equivalent trial establishing that estradiol alone replaces everything women may lose when natural production of all three estrogens declines.
The purpose of sharing this research is not to present estriol as a miracle or to suggest that women who are doing well on estradiol should change their treatment. It is to show why the scientific conversation remains open—and to give women and their healthcare providers the sources they need to examine the evidence for themselves.
 
About Your Host
Steve Hoffart is an award-winning pharmacist, entrepreneur, speaker and podcaster. As the visionary founder of Magnolia Pharmacy, Steve saw a need for a more personal pharmacy that could make a bigger impact. Today, Steve and his team of experts deliver on that promise, working with patients and their physicians to solve medication problems and offer personalized solutions to achieve better health and wellness. As host of The Trusted Pharmacist podcast and through his combined reach of over 1M on social media, Steve shares actionable advice on nutrition, supplements, and wellness strategies while advocating for meaningful change in healthcare.
 
Stay Ahead with Steve the Pharmacist!
Loving the show? Want more insights into how your body works? Head over to TheTrustedPharmacist.com and sign up with your email! You'll get the latest episodes, plus exclusive health tips to help you take charge of your wellness. Don't miss out – join me today!

What if your go-to sleep aid was keeping you from deep, restorative sleep?
People come into the pharmacy every day looking for over-the-counter sleep aids or sleep supplements, so I reached out to neurologist and sleep expert Dr Stasha Gominak. 
She has a very different view on what's disrupting our sleep, and practical steps we can take to transform our sleep.
 
What You'll Discover In This Episode 
How moving indoors wrecked the brain chemical our body needs

How common sleep aids disrupt our body's natural sleep process

The link between Vitamin D and sleep 

Sleep Trackers: The only metric that might actually be correct

The dosing mistake that might push you into Vitamin D deficiency

Practical dosing and timing for key vitamins 

 
About the Guest
Dr Stasha Gominak is a former practicing neurologist and the creator of RightSleep®, dividing her time between helping individuals, through virtual coaching sessions and teaching clinicians and coaches how to use RightSleep concepts to improve their patients' health and well being.
Dr Gominak completed a Neurology residency in 1989 at the Harvard-affiliated, Massachusetts General Hospital. In 2004 Dr. Gominak began to concentrate on treating neurological illness by improving sleep. She published a pivotal article in 2012 proposing that the global struggle with worsening sleep was linked to reduced sun exposure.
In 2016 she followed with a second article linking the change in the intestinal microbiome to the epidemic of poor sleep, and described a simple process for normalizing sleep and the intestinal bacterial population, called RightSleep®. 
Learn more about RightSleep® at https://drgominak.com/
 
About Your Host
Steve Hoffart is an award-winning pharmacist, entrepreneur, speaker and podcaster. As the visionary founder of Magnolia Pharmacy, Steve saw a need for a more personal pharmacy that could make a bigger impact. Today, Steve and his team of experts deliver on that promise, working with patients and their physicians to solve medication problems and offer personalized solutions to achieve better health and wellness. As host of The Trusted Pharmacist podcast and through his combined reach of over 1M on social media, Steve shares actionable advice on nutrition, supplements, and wellness strategies while advocating for meaningful change in healthcare.
 
Stay Ahead with Steve the Pharmacist!
Loving the show? Want more insights into how your body works? Head over to TheTrustedPharmacist.com and sign up with your email! You'll get the latest episodes, plus exclusive health tips to help you take charge of your wellness. Don't miss out – join me today!

Why do mitochondria come up so often in conversations about energy and longevity, but rarely when women are trying to understand what is happening to their bodies in menopause?
Most people have heard mitochondria described as the "powerhouse of the cell." But they also play a role in muscle function, recovery, cellular communication, and hormone production. As we age, damaged mitochondria can build up while the body becomes less efficient at clearing them away.
Could some of the fatigue, brain fog, reduced strength, and poor recovery women are told to accept as part of menopause or aging also be connected to declining mitochondrial health?
Perimenopause dietitian-nutritionist, Jen Scheinman, explains why mitochondria deserve a bigger place in the menopause conversation. 
We explore the connection between estrogen and mitochondrial function, how mitophagy helps remove damaged mitochondria, and how urolithin A may support that process.
What You'll Discover In This Episode 
Why mitochondria are often overlooked in menopause conversations

What mitochondria do beyond producing energy

How mitochondrial decline may contribute to fatigue and poor recovery

The connection between estrogen and mitochondrial function

What mitophagy is and why it slows with age

How urolithin A supports mitochondrial cleanup

How urolithin A differs from CoQ10 and NAD boosters

What the research suggests about strength, endurance, and recovery

Why mitochondrial support cannot replace sleep, exercise, and nutrition

PS. If you enjoy the show, remember to leave a review on your favorite podcast app! Reviews help the podcast reach a wider audience and help more people.
 
About the Guest
Jen Scheinman is a perimenopause dietitian-nutritionist, longevity and healthy aging expert, and women's health advocate. She holds a master's degree in integrative and functional nutrition and is the founder of Next Jen Health.
Jen also serves as Director of Science Communication at Timeline, where she helps translate emerging research on mitochondrial health, nutrition, and aging into practical guidance people can use to support their health and longevity.
Her expertise has been featured in publications including Vogue, Glamour, Mindbodygreen, and Eat This, Not That! To learn more, visit timeline.com and follow Jennifer on Instagram.
 
About Your Host
Steve Hoffart is an award-winning pharmacist, entrepreneur, speaker and podcaster. As the visionary founder of Magnolia Pharmacy, Steve saw a need for a more personal pharmacy that could make a bigger impact. Today, Steve and his team of experts deliver on that promise, working with patients and their physicians to solve medication problems and offer personalized solutions to achieve better health and wellness. As host of The Trusted Pharmacist podcast and through his combined reach of over 1M on social media, Steve shares actionable advice on nutrition, supplements, and wellness strategies while advocating for meaningful change in healthcare.
 
Stay Ahead with Steve the Pharmacist!
Loving the show? Want more insights into how your body works? Head over to TheTrustedPharmacist.com and sign up with your email! You'll get the latest episodes, plus exclusive health tips to help you take charge of your wellness. Don't miss out – join me today!

What if the medication that's helping one health problem is quietly contributing to another? 
Many of the most commonly prescribed medications for cholesterol, diabetes, acid reflux, allergies, anxiety, and pain can affect nutrient levels, hormones, sleep, memory, and energy over time. But common doesn't mean the medication is harmless. 
In this episode, I explain why medications should never be put on autopilot. From statins and metformin to acid blockers and antidepressants, I share the questions every patient should be asking to better understand the long-term effects of the medications they take every day.
What You'll Discover In This Episode
Why "normal" blood work doesn't always tell the whole story

How common diabetes medications may contribute to fatigue, brain fog, and nerve problems

The hidden nutrient deficiencies linked to acid reflux medications

What statins can (and can't) tell you about your heart health and cholesterol

Why some allergy and sleep medications may affect memory as you get older

How certain antidepressants, pain medications, and anti-anxiety drugs can impact mood, balance, and cognition

The questions every patient should ask before automatically refilling a prescription

Why medications should be monitored just as carefully as the conditions they're treating

 
PS. If you enjoy the show, remember to leave a review on your favorite podcast app! Reviews help the podcast reach a wider audience and help more people.
 
About Your Host
Steve Hoffart is an award-winning pharmacist, entrepreneur, speaker and podcaster. As the visionary founder of Magnolia Pharmacy, Steve saw a need for a more personal pharmacy that could make a bigger impact. Today, Steve and his team of experts deliver on that promise, working with patients and their physicians to solve medication problems and offer personalized solutions to achieve better health and wellness. As host of The Trusted Pharmacist podcast and through his combined reach of over 1M on social media, Steve shares actionable advice on nutrition, supplements, and wellness strategies while advocating for meaningful change in healthcare.
 
Stay Ahead with Steve the Pharmacist!
Loving the show? Want more insights into how your body works? Head over to TheTrustedPharmacist.com and sign up with your email! You'll get the latest episodes, plus exclusive health tips to help you take charge of your wellness. Don't miss out – join me today!

What happens if the thyroid medication that finally helped you feel like yourself becomes harder to access?
Natural desiccated thyroid has been used for decades, and many women prefer it because it provides both T4 and active T3. Proposed FDA changes have raised questions about its future, but they also bring a much bigger issue into focus. 
Why do so many women still struggle with fatigue, brain fog, weight changes, cold intolerance, and low energy even when they are taking thyroid medication and their lab results are considered "normal"?
Pharmacist and compounding expert Nat Jones explains what more complete thyroid care can look like for women in perimenopause and menopause. We explore why T4 alone may not be enough for every woman, how stress and cortisol can interfere with thyroid function, and how compounded T4/T3 therapy can offer a more individualized approach.
 
What You'll Discover In This Episode 
Why some patients prefer natural desiccated thyroid to levothyroxine

T4 vs. T3: why having both can make a meaningful difference

What your options are if desiccated thyroid becomes harder to access

Why women still feel hypothyroid when their TSH is "normal"

How compounded T4 and T3 can be customized to the individual patient

Why standard thyroid ratios do not work equally well for everyone

The overlooked role of cortisol and chronic stress in thyroid treatment

The additional thyroid markers that may reveal what TSH misses

How ferritin and nutrient deficiencies can affect thyroid function

Why Hashimoto's requires more than simply replacing thyroid hormone

 
PS. If you enjoy the show, remember to leave a review on your favorite podcast app! Reviews help the podcast reach a wider audience and help more people.
 
About the Guest
Nat Jones is a pharmacist and internationally recognized expert in pharmaceutical compounding. After more than 20 years as a compounding pharmacy owner, he joined Professional Compounding Centers of America (PCCA) in Houston, Texas, in 2014, where he serves in the Pharmacy Clinical Services Department.
Dermatology is Nat's primary specialty, with additional expertise in wound and scar care, autoimmune disease, endocrinology, pain management, low-dose naltrexone, GLP-1 therapies, methylene blue, ENT, urology, and men's health. He has spent decades delivering continuing education lectures at medical seminars and webinars around the world and is known for translating complex compounding science into practical strategies healthcare providers can use.
Nat was awarded Fellowship status by the International Academy of Compounding Pharmacists in 2010. He has authored numerous professional articles, e-books, case studies, and consumer publications, and has helped develop hundreds of innovative compounding formulations used by practitioners across the United States.
 
About Your Host
Steve Hoffart is an award-winning pharmacist, entrepreneur, speaker and podcaster. As the visionary founder of Magnolia Pharmacy, Steve saw a need for a more personal pharmacy that could make a bigger impact. Today, Steve and his team of experts deliver on that promise, working with patients and their physicians to solve medication problems and offer personalized solutions to achieve better health and wellness. As host of The Trusted Pharmacist podcast and through his combined reach of over 1M on social media, Steve shares actionable advice on nutrition, supplements, and wellness strategies while advocating for meaningful change in healthcare.
 
Stay Ahead with Steve the Pharmacist!
Loving the show? Want more insights into how your body works? Head over to TheTrustedPharmacist.com and sign up with your email! You'll get the latest episodes, plus exclusive health tips to help you take charge of your wellness. Don't miss out – join me today!