Your Brain On (And Off) Estrogen
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This is Dr. Lisa Mosconi. She’s a professor of Neuroscience in Neurology and Radiology, and is one of the 1% most influential scientists of the 21st century. That’s not a random number or an exaggeration; it has to do with citation metrics collated over 20 years:
A standardized citation metrics author database annotated for scientific field
What does she want us to know?
Women’s brains age differently from men’s
This is largely, of course, due to menopause, and as such is a generalization, but it’s a statistically safe generalization, because:
- Most women go through menopause—and most women who don’t, avoid it by dying pre-menopause, so the aging also does not occur in those cases
- Menopause is very rarely treated immediately—not least of all because menopause is diagnosed officially when it has been one year since one’s last period, so there’s almost always a year of “probably” first, and often numerous years, in the case of periods slowing down before stopping
- Menopausal HRT is great, but doesn’t completely negate that menopause occurred—because of the delay in starting HRT, some damage can be done already and can take years to reverse.
Medicated and unmedicated menopause proceed very differently from each other, and this fact has historically caused obfuscation of a lot of research into age-related neurodegeneration.
For example, it is well-established that women get Alzheimer’s at nearly twice the rate than men do, and deteriorate more rapidly after onset, too.
Superficially, one might conclude “estrogen is to blame” or maybe “the xx-chromosomal karyotype is to blame”.
The opposite, however, is true with regard to estrogen—estrogen appears to be a protective factor in women’s neurological health, which is why increased neurodegeneration occurs when estrogen levels decline (for example, in menopause).
For a full rundown on this, see:
Alzheimer’s Sex Differences May Not Be What They Appear
It’s not about the extra X
Dr. Mosconi examines this in detail in her book “The XX Brain”. To summarize and oversimplify a little: the XX karyotype by itself makes no difference, or more accurately, the XY karyotype by itself makes no difference (because biologically speaking, female physiological attributes are more “default” than male ones; it is only 12,000ish* years of culture that has flipped the social script on this).
*Why 12,000ish years? It’s because patriarchalism largely began with settled agriculture, for reasons that are fascinating but beyond the scope of this article, which is about health science, not archeology.
The topic of “which is biologically default” is relevant, because the XY karyotype (usually) informs the body “ignore previous instructions about ovaries, and adjust slightly to make them into testes instead”, which in turn (usually) results in a testosterone-driven system instead of an estrogen-driven system. And that is what makes the difference to the brain.
One way we can see that it’s about the hormones not the chromosomes, is in cases of androgen insensitivity syndrome, in which the natal “congratulations, it’s a girl” pronouncement may later be in conflict with the fact it turns out she had XY chromosomes all along, but the androgenic instructions never got delivered successfully, so she popped out with fairly typical female organs. And, relevantly for Dr. Mosconi, a typically female brain that will age in a typically female fashion, because it’s driven by estrogen, regardless of the Y-chromosome.
The good news
The good news from all of this is that while we can’t (with current science, anyway) do much about our chromosomes, we can do plenty about our hormones, and also, the results of changes in same.
Remember, Dr. Mosconi is not an endocrinologist, nor a gynecologist, but a neurologist. As such, she makes the case for how a true interdisciplinary team for treating menopause should not confined to the narrow fields usually associated with “bikini medicine”, but should take into account that a lot of menopause-related changes are neurological in nature.
We recently reviewed another book by Dr. Mosconi:
The Menopause Brain – by Dr. Lisa Mosconi
…and as we noted there, many sources will mention “brain fog” as a symptom of menopause, Dr. Mosconi can (and will) point to a shadowy patch on a brain scan and say “that’s the brain fog, there”.
And so on, for other symptoms that are often dismissed as “all in your head”, as though that’s a perfectly acceptable place for problems to be.
This is critical, because it’s treating real neurological things as the real things they are.
Dr. Mosconi’s advice, beyond HRT
Dr. Mosconi notes that brain health tends to dip during perimenopause but often recovers, showing the brain’s resilience to hormonal shifts. As such, all is not lost if for whatever reason, hormone replacement therapy isn’t a viable option for you.
Estrogen plays a crucial role in brain energy, and women’s declining estrogen levels during menopause increase the need for antioxidants to protect brain health—something not often talked about.
Specifically, Dr. Mosconi tells us, women need more antioxidants and have different metabolic responses to diets compared to men.*
*Yes, even though men usually have negligible estrogen, because their body (and thus brain, being also part of their body) is running on testosterone instead, which is something that will only happen if either you are producing normal male amounts of testosterone (requires normal male testes) or you are taking normal male amounts of testosterone (requires big bottles of testosterone; this isn’t the kind of thing you can get from a low dose of testogel as sometimes prescribed as part of menopausal HRT to perk your metabolism up).
Note: despite women being a slight majority on Earth, and despite an aging population in wealthy nations, meaning “a perimenopausal woman” is thus the statistically average person in, for example, the US, and despite the biological primacy of femaleness… Medicine still mostly looks to men as the “default person”, which in this case can result in seriously low-balled estimates of what antioxidants are needed.
In terms of supplements, therefore, she recommends:
- Antioxidants: key for brain health, especially in women. Rich sources include fruits (especially berries) and vegetables. Then there’s the world’s most-consumed antioxidant, which is…
- Coffee: Italian-style espresso has the highest antioxidant power. Adding a bit of fat (e.g. oat milk) helps release caffeine more slowly, reducing jitters. Taking it alongside l-theanine also “flattens the curve” and thus improves its overall benefits.
- Flavonoids: important for both men and women but particularly essential for women. Found in many fruits and vegetables.
- Chocolate: dark chocolate is an excellent source of antioxidants and flavonoids!
- Turmeric: a natural neuroprotectant with anti-inflammatory properties, best boosted by taking with black pepper, which improves absorption as well as having many great qualities of its own.
- B Vitamins: B6, B9, and B12 are essential for anti-aging and brain health; deficiency in B6 is rare, while deficiency in B9 (folate) and especially B12 is very common later in life.
- Vitamins C & E: important antioxidants, but caution is needed with fat-soluble vitamins to avoid toxicity.
- Omega-3s: important for brain health; can be consumed in the diet, but supplements may be necessary.
- Caution with zinc: zinc can support immunity and endocrine health (and thus, indirectly, brain health) but may be harmful in excess, particularly for brain health.
- Probiotics & Prebiotics: beneficial for gut health, and in Dr. Mosconi’s opinion, hard to get sufficient amounts from diet alone.
For more pointers, you might want to check out the MIND diet, that is to say, the “Mediterranean-DASH Intervention for Neurodegenerative Delay” upgrade to make the Mediterranean diet even brain-healthier than it is by default:
Four Ways To Upgrade The Mediterranean Diet
Want to know more from Dr. Mosconi?
Here’s her TED talk:
Click Here If The Embedded Video Doesn’t Load Automatically!
Enjoy!
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Can a drug like Ozempic help treat addictions to alcohol, opioids or other substances?
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Semaglutide (sold as Ozempic, Wegovy and Rybelsus) was initially developed to treat diabetes. It works by stimulating the production of insulin to keep blood sugar levels in check.
This type of drug is increasingly being prescribed for weight loss, despite the fact it was initially approved for another purpose. Recently, there has been growing interest in another possible use: to treat addiction.
Anecdotal reports from patients taking semaglutide for weight loss suggest it reduces their appetite and craving for food, but surprisingly, it also may reduce their desire to drink alcohol, smoke cigarettes or take other drugs.
But does the research evidence back this up?
Animal studies show positive results
Semaglutide works on glucagon-like peptide-1 receptors and is known as a “GLP-1 agonist”.
Animal studies in rodents and monkeys have been overwhelmingly positive. Studies suggest GLP-1 agonists can reduce drug consumption and the rewarding value of drugs, including alcohol, nicotine, cocaine and opioids.
Out team has reviewed the evidence and found more than 30 different pre-clinical studies have been conducted. The majority show positive results in reducing drug and alcohol consumption or cravings. More than half of these studies focus specifically on alcohol use.
However, translating research evidence from animal models to people living with addiction is challenging. Although these results are promising, it’s still too early to tell if it will be safe and effective in humans with alcohol use disorder, nicotine addiction or another drug dependence.
What about research in humans?
Research findings are mixed in human studies.
Only one large randomised controlled trial has been conducted so far on alcohol. This study of 127 people found no difference between exenatide (a GLP-1 agonist) and placebo (a sham treatment) in reducing alcohol use or heavy drinking over 26 weeks.
In fact, everyone in the study reduced their drinking, both people on active medication and in the placebo group.
However, the authors conducted further analyses to examine changes in drinking in relation to weight. They found there was a reduction in drinking for people who had both alcohol use problems and obesity.
For people who started at a normal weight (BMI less than 30), despite initial reductions in drinking, they observed a rebound increase in levels of heavy drinking after four weeks of medication, with an overall increase in heavy drinking days relative to those who took the placebo.
There were no differences between groups for other measures of drinking, such as cravings.
Some studies show a rebound increase in levels of heavy drinking. Deman/Shutterstock In another 12-week trial, researchers found the GLP-1 agonist dulaglutide did not help to reduce smoking.
However, people receiving GLP-1 agonist dulaglutide drank 29% less alcohol than those on the placebo. Over 90% of people in this study also had obesity.
Smaller studies have looked at GLP-1 agonists short-term for cocaine and opioids, with mixed results.
There are currently many other clinical studies of GLP-1 agonists and alcohol and other addictive disorders underway.
While we await findings from bigger studies, it’s difficult to interpret the conflicting results. These differences in treatment response may come from individual differences that affect addiction, including physical and mental health problems.
Larger studies in broader populations of people will tell us more about whether GLP-1 agonists will work for addiction, and if so, for whom.
How might these drugs work for addiction?
The exact way GLP-1 agonists act are not yet well understood, however in addition to reducing consumption (of food or drugs), they also may reduce cravings.
Animal studies show GLP-1 agonists reduce craving for cocaine and opioids.
This may involve a key are of the brain reward circuit, the ventral striatum, with experimenters showing if they directly administer GLP-1 agonists into this region, rats show reduced “craving” for oxycodone or cocaine, possibly through reducing drug-induced dopamine release.
Using human brain imaging, experimenters can elicit craving by showing images (cues) associated with alcohol. The GLP-1 agonist exenatide reduced brain activity in response to an alcohol cue. Researchers saw reduced brain activity in the ventral striatum and septal areas of the brain, which connect to regions that regulate emotion, like the amygdala.
In studies in humans, it remains unclear whether GLP-1 agonists act directly to reduce cravings for alcohol or other drugs. This needs to be directly assessed in future research, alongside any reductions in use.
Are these drugs safe to use for addiction?
Overall, GLP-1 agonists have been shown to be relatively safe in healthy adults, and in people with diabetes or obesity. However side effects do include nausea, digestive troubles and headaches.
And while some people are OK with losing weight as a side effect, others aren’t. If someone is already underweight, for example, this drug might not be suitable for them.
In addition, very few studies have been conducted in people with addictive disorders. Yet some side effects may be more of an issue in people with addiction. Recent research, for instance, points to a rare risk of pancreatitis associated with GLP-1 agonists, and people with alcohol use problems already have a higher risk of this disorder.
Other drugs treatments are currently available
Although emerging research on GLP-1 agonists for addiction is an exciting development, much more research needs to be done to know the risks and benefits of these GLP-1 agonists for people living with addiction.
In the meantime, existing effective medications for addiction remain under-prescribed. Only about 3% of Australians with alcohol dependence, for example, are prescribed medication treatments such as like naltrexone, acamprosate or disulfiram. We need to ensure current medication treatments are accessible and health providers know how to prescribe them.
Continued innovation in addiction treatment is also essential. Our team is leading research towards other individualised and effective medications for alcohol dependence, while others are investigating treatments for nicotine addiction and other drug dependence.
Read the other articles in The Conversation’s Ozempic series here.
Shalini Arunogiri, Addiction Psychiatrist, Associate Professor, Monash University; Leigh Walker, , Florey Institute of Neuroscience and Mental Health, and Roberta Anversa, , The University of Melbourne
This article is republished from The Conversation under a Creative Commons license. Read the original article.
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If You’re Poor, Fertility Treatment Can Be Out of Reach
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Mary Delgado’s first pregnancy went according to plan, but when she tried to get pregnant again seven years later, nothing happened. After 10 months, Delgado, now 34, and her partner, Joaquin Rodriguez, went to see an OB-GYN. Tests showed she had endometriosis, which was interfering with conception. Delgado’s only option, the doctor said, was in vitro fertilization.
“When she told me that, she broke me inside,” Delgado said, “because I knew it was so expensive.”
Delgado, who lives in New York City, is enrolled in Medicaid, the federal-state health program for low-income and disabled people. The roughly $20,000 price tag for a round of IVF would be a financial stretch for lots of people, but for someone on Medicaid — for which the maximum annual income for a two-person household in New York is just over $26,000 — the treatment can be unattainable.
Expansions of work-based insurance plans to cover fertility treatments, including free egg freezing and unlimited IVF cycles, are often touted by large companies as a boon for their employees. But people with lower incomes, often minorities, are more likely to be covered by Medicaid or skimpier commercial plans with no such coverage. That raises the question of whether medical assistance to create a family is only for the well-to-do or people with generous benefit packages.
“In American health care, they don’t want the poor people to reproduce,” Delgado said. She was caring full-time for their son, who was born with a rare genetic disorder that required several surgeries before he was 5. Her partner, who works for a company that maintains the city’s yellow cabs, has an individual plan through the state insurance marketplace, but it does not include fertility coverage.
Some medical experts whose patients have faced these issues say they can understand why people in Delgado’s situation think the system is stacked against them.
“It feels a little like that,” said Elizabeth Ginsburg, a professor of obstetrics and gynecology at Harvard Medical School who is president-elect of the American Society for Reproductive Medicine, a research and advocacy group.
Whether or not it’s intended, many say the inequity reflects poorly on the U.S.
“This is really sort of standing out as a sore thumb in a nation that would like to claim that it cares for the less fortunate and it seeks to do anything it can for them,” said Eli Adashi, a professor of medical science at Brown University and former president of the Society for Reproductive Endocrinologists.
Yet efforts to add coverage for fertility care to Medicaid face a lot of pushback, Ginsburg said.
Over the years, Barbara Collura, president and CEO of the advocacy group Resolve: The National Infertility Association, has heard many explanations for why it doesn’t make sense to cover fertility treatment for Medicaid recipients. Legislators have asked, “If they can’t pay for fertility treatment, do they have any idea how much it costs to raise a child?” she said.
“So right there, as a country we’re making judgments about who gets to have children,” Collura said.
The legacy of the eugenics movement of the early 20th century, when states passed laws that permitted poor, nonwhite, and disabled people to be sterilized against their will, lingers as well.
“As a reproductive justice person, I believe it’s a human right to have a child, and it’s a larger ethical issue to provide support,” said Regina Davis Moss, president and CEO of In Our Own Voice: National Black Women’s Reproductive Justice Agenda, an advocacy group.
But such coverage decisions — especially when the health care safety net is involved — sometimes require difficult choices, because resources are limited.
Even if state Medicaid programs wanted to cover fertility treatment, for instance, they would have to weigh the benefit against investing in other types of care, including maternity care, said Kate McEvoy, executive director of the National Association of Medicaid Directors. “There is a recognition about the primacy and urgency of maternity care,” she said.
Medicaid pays for about 40% of births in the United States. And since 2022, 46 states and the District of Columbia have elected to extend Medicaid postpartum coverage to 12 months, up from 60 days.
Fertility problems are relatively common, affecting roughly 10% of women and men of childbearing age, according to the National Institute of Child Health and Human Development.
Traditionally, a couple is considered infertile if they’ve been trying to get pregnant unsuccessfully for 12 months. Last year, the ASRM broadened the definition of infertility to incorporate would-be parents beyond heterosexual couples, including people who can’t get pregnant for medical, sexual, or other reasons, as well as those who need medical interventions such as donor eggs or sperm to get pregnant.
The World Health Organization defined infertility as a disease of the reproductive system characterized by failing to get pregnant after a year of unprotected intercourse. It terms the high cost of fertility treatment a major equity issue and has called for better policies and public financing to improve access.
No matter how the condition is defined, private health plans often decline to cover fertility treatments because they don’t consider them “medically necessary.” Twenty states and Washington, D.C., have laws requiring health plans to provide some fertility coverage, but those laws vary greatly and apply only to companies whose plans are regulated by the state.
In recent years, many companies have begun offering fertility treatment in a bid to recruit and retain top-notch talent. In 2023, 45% of companies with 500 or more workers covered IVF and/or drug therapy, according to the benefits consultant Mercer.
But that doesn’t help people on Medicaid. Only two states’ Medicaid programs provide any fertility treatment: New York covers some oral ovulation-enhancing medications, and Illinois covers costs for fertility preservation, to freeze the eggs or sperm of people who need medical treatment that will likely make them infertile, such as for cancer. Several other states also are considering adding fertility preservation services.
In Delgado’s case, Medicaid covered the tests to diagnose her endometriosis, but nothing more. She was searching the internet for fertility treatment options when she came upon a clinic group called CNY Fertility that seemed significantly less expensive than other clinics, and also offered in-house financing. Based in Syracuse, New York, the company has a handful of clinics in upstate New York cities and four other U.S. locations.
Though Delgado and her partner had to travel more than 300 miles round trip to Albany for the procedures, the savings made it worthwhile. They were able do an entire IVF cycle, including medications, egg retrieval, genetic testing, and transferring the egg to her uterus, for $14,000. To pay for it, they took $7,000 of the cash they’d been saving to buy a home and financed the other half through the fertility clinic.
She got pregnant on the first try, and their daughter, Emiliana, is now almost a year old.
Delgado doesn’t resent people with more resources or better insurance coverage, but she wishes the system were more equitable.
“I have a medical problem,” she said. “It’s not like I did IVF because I wanted to choose the gender.”
One reason CNY is less expensive than other clinics is simply that the privately owned company chooses to charge less, said William Kiltz, its vice president of marketing and business development. Since the company’s beginning in 1997, it has become a large practice with a large volume of IVF cycles, which helps keep prices low.
At this point, more than half its clients come from out of state, and many earn significantly less than a typical patient at another clinic. Twenty percent earn less than $50,000, and “we treat a good number who are on Medicaid,” Kiltz said.
Now that their son, Joaquin, is settled in a good school, Delgado has started working for an agency that provides home health services. After putting in 30 hours a week for 90 days, she’ll be eligible for health insurance.
One of the benefits: fertility coverage.
KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF—an independent source of health policy research, polling, and journalism. Learn more about KFF.
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The Pain-Free Mindset – by Dr. Deepak Ravindran
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First: please ignore the terrible title. This is not the medical equivalent of “think and grow rich”. A better title would have been something like “The Pain-Free Plan”.
Attentive subscribers may notice that this author was our featured expert yesterday, so you can learn about his “seven steps” described in our article there, without us repeating that in our review here.
This book’s greatest strength is also potentially its greatest weakness, depending on the reader: it contains a lot of detailed medical information.
This is good or bad depending on whether you like lots of detailed medical information. Dr. Ravindran doesn’t assume prior knowledge, so everything is explained as we go. However, this means that after his well-referenced clinical explanations, high quality medical diagrams, etc, you may come out of this book feeling like you’ve just done a semester at medical school.
Knowledge is power, though, so understanding the underlying processes of pain and pain management really does help the reader become a more informed expert on your own pain—and options for reducing that pain.
Bottom line: this, disguised by its cover as a “think healing thoughts” book, is actually a science-centric, information-dense, well-sourced, comprehensive guide to pain management from one of the leading lights in the field.
Click here to check out The Pain-Free Mindset, and manage yours more comfortably!
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Immunity – by Dr. William Paul
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This book gives a very person-centric (i.e., focuses on the contributions of named individuals) overview of advances in the field of immunology—up to its publication date in 2015. So, it’s not cutting edge, but it is very good at laying the groundwork for understanding more recent advances that occur as time goes by. After all, immunology is a field that never stands still.
We get a good grounding in how our immune system works (and how it doesn’t), the constant arms race between pathogens and immune responses, and the complexities of autoimmune disorders and—which is functionally in an overlapping category of disease—cancer. And, what advances we can expect soon to address those things.
Given the book was published 8 years ago, how did it measure up? Did we get those advances? Well, for the mostpart yes, we have! Some are still works in progress. But, we’ve also had obvious extra immunological threats in years since, which have also resulted in other advances along the way!
If the book has a downside, it’s that sometimes the author can be a little too person-centric. It’s engaging to focus on human characters, and helps us bring information to life; name-dropping to excess, along with awards won, can sometimes feel a little like the book was co-authored by Tahani Al-Jamil.
Nevertheless, it certainly does keep the book from getting too dry!
Bottom line: this book is a great overview of immunology and immunological research, for anyone who wants to understand these things better.
Click here to check out Immunity, and boost your knowledge of yours!
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Millet vs Rye – Which is Healthier?
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Our Verdict
When comparing millet to rye, we picked the rye.
Why?
In terms of macros, they’re about equal on protein, and rye has more carbs and fiber, the ratio of which give it the lower glycemic index, so we say rye wins this category.
In the category of vitamins, millet has more of vitamins B1, B2, B6, and B9, while rye has more of vitamins A, B5, E, and K. Notionally, that’s a 4:4 tie, though rye’s margins of difference are an order of magnitude greater, so we say rye takes a marginal victory on this one.
When it comes to minerals, there’s nothing to debate here: millet has more copper, while rye has more calcium, manganese, phosphorus, potassium, selenium, and zinc. An easy win for rye on this one.
Adding up the sections gives the overall win to rye, but there is one other thing worth mentioning: millet is naturally gluten-free, but rye is not, so if you are avoiding gluten for any reason, you’ll want to pick the millet in this case.
See also: Gluten: What’s The Truth?
Aside from that, by all means enjoy either or both, in moderation! Diversity is good.
Want to learn more?
You might like to read:
Grains: Bread Of Life, Or Cereal Killer?
Enjoy!
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High-Protein Plant-Based Diet for Beginners – by Maya Howard with Ariel Warren
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Seasoned vegans (well-seasoned vegans?) will know that getting enough protein from a plant-based diet is really not the challenge that many think it is, but for those just embarking on cutting out the meat, it’s not useful to say “it’s easy!”; it’s useful to show how.
That’s what this book does. And not just by saying “these foods” and leaving people to wonder if they need to eat a pound of tofu each day to get their protein in. Instead, recipes. Enough for a 4-week meal plan, and the idea is that after a month of eating that way, it won’t be nearly so mysterious.
The recipes are very easy to execute, while still having plenty of flavor (which is what happens when one uses a lot of flavorsome main ingredients and then seasons them well too). The ingredients are not obscure, and you should be able to find everything easily in any medium-sized supermarket.
As for the well-roundedness of the diet, we’ll mention that the “with Ariel Warren” in the by-line means that while the book was principally authored by Maya Howard (who is, at time of writing, a nutritionist-in-training), she had input throughout from Ariel Warren (a Registered Dietician Nutritionist) to ensure she didn’t go off-piste anyway and it gets the professional stamp of approval.
Bottom line: if you’d like to cook plant based while still prioritizing protein and you’re not sure how to make that exciting and fun instead of a chore, then this book will show you how to please your taste buds and improve your body composition at the same time.
Click here to check out High-Protein Plant-Based Diet for Beginners, and dig in!
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