Blood fat levels predict diabetes remission following gastric bypass surgery

A newly developed test could help doctors more accurately predict whether individuals who undergo gastric bypass surgery will experience a remission of type 2 diabetes within two years of the procedure, according to University of Utah Health scientists.
The test, which measures blood levels of ceramides, a waxy, fat-like substance similar to cholesterol, can also be used to assess the likelihood that a gastric bypass patient will have a recurrence of type 2 diabetes within a decade.
“These human studies validate our prior findings in rodents that ceramides are major drivers of diabetes. They also reveal a new tool in the physician’s arsenal for managing the health of the increasing number of people undergoing bariatric surgery,” says Scott Summers, Ph.D., corresponding author of the study and co-director of the Diabetes Metabolism Research Center.
The study appears in Med, a Cell Press medical journal.
In previous studies, Summers and his colleagues found that ceramides can reduce the amount of insulin a body can produce or use, increasing the likelihood that a person will develop type 2 diabetes. Intrigued, they decided to examine the association between ceramides, diabetes, and severe obesity.
More than 24 million Americans are severely obese with a body mass index (BMI) of 35 or higher, according to the American Society for Metabolic and Bariatric Surgery (ASMBS). As a result, many of them have a substantial risk of developing type 2 diabetes, heart disease, and other severe conditions. For some of these individuals, gastric bypass surgery is often the best option.

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Lager beer, whether it contains alcohol or not, could help men's gut microbes

Like wine, beer can have health benefits when consumed in moderation. Non-alcoholic beers have become wildly popular recently, but are these drinks also healthful? In a pilot study, researchers in ACS’ Journal of Agricultural and Food Chemistry report that compared to their pre-trial microbiome, men who drank either one alcoholic or non-alcoholic lager daily had a more diverse set of gut microbes, which can reduce the risk for some diseases.
Trillions of microorganisms line human gastrointestinal tracts, directly impacting their host’s well-being. Studies have shown that when more types of bacteria are present, people tend to have a lower chance of developing chronic diseases, such as heart disease and diabetes. And beer contains compounds, such as polyphenols, as well as microorganisms from its fermentation, that could impact the variety of microbes in the human gut. A previously published “cross-over” study showed that when both men and women consumed non-alcoholic lager beer for 30 days, their gut microbiome diversity increased. Many of those same people were also in a second group that drank an alcoholic version of the beer, and it didn’t have the same effect. Few other clinical trials have tested this issue, so Ana Faria and colleagues wanted to see if they would find similar results with men in a different type of study — a parallel, randomized trial design — with two separate groups of participants.
In this double-blind study, 19 healthy men were randomly divided into two groups who drank 11 fluid ounces of either alcoholic or non-alcoholic lager with dinner for 4 weeks. The researchers found that the participants’ weight, body mass index and serum markers for heart health and metabolism didn’t change during the study. But at the end of the 4-week period, both groups had greater bacterial diversity in their gut microbiome and higher levels of fecal alkaline phosphatase, indicating an improvement in intestinal health. The researchers suggest that these results could differ from those of the prior study because of the different designs of the trials, and because the participants were living in different communities. But based on this pilot study, the researchers say that consuming one bottle of beer, regardless of its alcohol content, may be beneficial to the gut microbiome and intestinal health of men. However, they add that because the safest level of alcohol consumption is none, non-alcoholic beer may be the more healthful choice.
The authors acknowledge funding from the Programa Operacional Competitividade e Internacionalização — COMPETE2020, Fundação para a Ciência e a Tecnologia (FCT), the Center for Health and Technology and Services Research (CINTESIS) and the Comprehensive Health Research Center (CHRC).
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New material paves the way for remote-controlled medication and electronic pills

Biomedicines are produced by living cells and are used to treat cancer and autoimmune diseases among other things. One challenge is that the medicines are very expensive to produce, something that limits global access. Now researchers from Chalmers have invented a material that uses electrical signals to capture and release biomolecules. The new and efficient method may have a major impact in the development of biomedicines and pave the way for the development of electronic pills and drug implants.
The new material is a polymer surface* which at an electrical pulse changes state from capturing to releasing biomolecules. This has several possible applications, including use as a tool for the efficient separation of a medicine from the other biomolecules that cells create in the production of biological medicines. The results of the study were recently published in the scientific journal Angewandte Chemie.
Biomedicines are very expensive to produce due to the lack of an efficient separation technique, and new techniques with a higher drug yield are required to reduce production costs and ultimately the cost of treating patients.
“Our polymer surfaces offer a new way of separating proteins by using electrical signals to control how they are bound to and released from a surface, while not affecting the structure of the protein,” says Gustav Ferrand-Drake del Castillo, who publicly defended his doctoral thesis in chemistry at Chalmers and is the lead author of the study.
The conventional separation technique — chromatography — binds biomolecules tightly to the surface and strong chemicals are required to make them release, which leads to losses and a poor yield. Many new medicines have proved to be highly sensitive to strong chemicals, which creates a major production problem for the next generation of biomedicines. The lower consumption of chemicals results in a benefit to the environment, while the fact that the surfaces of the new material can also be reused through several cycles is a key property. The process can be repeated hundreds of times without affecting the surface.
Functions in biological fluids
The material also functions in biological fluids with a buffering capacity, in other words fluids with the ability to counteract changes in the pH value. This property is remarkable since it paves the way for the creation of a new technique for implants and electronic “pills” that release the medicine into the body via electronic activation.

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High-intensity focused ultrasound (HIFU) can control prostate cancer with fewer side effects

In recent years, a new treatment strategy known as focal therapy (partial gland ablation) has emerged for prostate cancer considered to be “intermediate risk” — mostly, small tumors confined to one area of the prostate. At Memorial Sloan Kettering Cancer Center (MSK), researchers have been working closely with an advanced focal therapy approach known as high-intensity focused ultrasound (HIFU), guided by magnetic resonance imaging (MRI).
Now a landmark clinical trial has demonstrated this less-invasive method works well for many patients. The phase 2 trial, led by MSK urologic cancer surgeon Behfar Ehdaie, looked at a particular type of HIFU treatment, also called MR-guided focused ultrasound (MRgFUS), in men with intermediate-risk cancer. The novel approach effectively controlled the disease in patients and greatly reduced adverse side effects of treatment. This suggests many men with intermediate-risk prostate cancer can avoid surgery, chemotherapy, and radiation.
“We believe this novel treatment strategy will improve the lives of many prostate cancer patients,” Dr. Ehdaie says. “To draw a parallel with how breast cancer treatment changed 30 years ago, you could think of focal therapy as a ‘male lumpectomy.’ Instead of removing all the tissue in a breast or prostate, we have learned that it is safe and effective to treat specific areas and greatly reduce the burden on patients.”
Results from the clinical trial, published June 14, 2022, in Lancet Oncology, represent a major step toward having the new HIFU approach become part of widespread prostate cancer treatment.
When the cancer is confined to the prostate gland, the main treatment options have traditionally included active surveillance (close monitoring), surgery, and radiation. But men who needed surgery or radiation often had persistent side effects, such as urinary and sexual problems, that could reduce quality of life.
“Advancements in prostate cancer over the past two decades have been headlined by successes that have benefited all patients, and now focal therapy provides another exciting area that can move the needle in prostate cancer management,” Dr. Ehdaie says.

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Cancer clinical trials bounce back after significant COVID-19 disruption: Data from two large US cancer centers

Data from two large cancer centres in the United States have shown that the COVID-19 pandemic caused substantial disruption to clinical trials for cancer treatment and care.
The research, published in the leading cancer journal Annals of Oncology today (Wednesday), shows that, compared to the immediate pre-pandemic period, there was a 46% decrease in new patient accruals, and a 24% decrease in newly activated trials between March and May 2020.
In particular, a pronounced decrease in the numbers of new patients recruited to trials at Dana-Farber Cancer Institute (Boston, Massachusetts) and the Tisch Cancer Institute at Mount Sinai Medical School (New York) occurred in academically sponsored trials as opposed to industry sponsored trials.
The research also shows that non-White patients were one and a half times more likely than White patients to be taken off trials during the pandemic.
Co-author, Dr Chris Labaki, a postdoctoral research fellow, at Dana-Farber, said: “Oncology clinical trials experienced a significant disruption during the early phase of the COVID-19 pandemic, with fewer new patients enrolled to trials and fewer trials started. This major decline probably reflects the strain imposed on the healthcare system during the pandemic as resources were diverted towards immediate hospital and patient needs.
“However, the good news is that both patient accruals and trial activations gradually recovered during the subsequent periods of the pandemic and have now returned to higher-than-normal levels, despite the ongoing nature of the pandemic. This shows that cancer centres are able to adapt to the COVID-19-related disruptions in clinical trial activities, which is crucial if we are to achieve better and novel therapeutic options for patients with cancer.”
Compared to the immediate pre-pandemic period (December 2019 to March 2020), by March to May 2021 the numbers of patients recruited to trials had increased by nearly 3%, and the numbers of newly activated trials had increased by 30%.

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Nordic walking improves functional capacity in people with heart disease

Researchers identified a greater increase in functional capacity, the ability to perform activities of daily living, as a result of Nordic walking in patients with coronary heart disease compared to standard high-intensity interval training and moderate-to-vigorous intensity continuous training. The results of their randomized clinical trial are published in the Canadian Journal of Cardiology.
Cardiovascular rehabilitation and exercise training programs following major cardiovascular events are associated with considerable improvements in functional capacity and cardiorespiratory fitness, as well as mental health. However, some individuals do not enjoy monotonous forms of exercise, such as walking and stationary cycling, and therefore may stop exercising once their cardiovascular rehabilitation program is completed. Researchers explored more diverse exercise options that might appeal to more people to determine whether they could get more individuals to continue to exercise and what benefits might be achieved.
Growing evidence suggests that non-conventional exercise interventions, such as high-intensity interval training and Nordic walking are more effective than traditional exercise approaches in improving functional capacity measured by a six-minute walk test — an important predictor of cardiovascular events in patients with coronary artery disease. Nordic walking is an enhanced form of walking exercise that uses specifically designed poles to further engage both the upper and lower body muscles.
“Patients with coronary artery disease frequently demonstrate diminished functional capacity, low quality of life and increased the risk of subsequent cardiovascular events and mortality,” explained lead investigator Jennifer L. Reed, PhD, Exercise Physiology and Cardiovascular Health Lab, Division of Cardiac Prevention and Rehabilitation, University of Ottawa Heart Institute; Faculty of Medicine; and School of Human Kinetics, Faculty of Health Sciences, University of Ottawa, Ottawa, ON, Canada.
Investigators compared the prolonged effects of 12-week rehabilitation with 1) high-intensity interval training; 2) moderate-to-vigorous intensity continuous training; and 3) Nordic walking, on functional capacity, quality of life and depression symptoms in patients with coronary artery disease. One hundred and thirty patients were randomized to a 12-week training in one of these three groups followed by a 14-week observation phase.
While all exercise programs improved depression symptoms and quality of life, the improvement in functional capacity was greatest after Nordic walking (+19%) when compared to high-intensity interval training (+13%) and moderate-to-vigorous intensity continuous training (+12%).
“This is a key finding because lower functional capacity predicts higher risk of future cardiovascular events in people with coronary artery disease,” noted Dr. Reed. “Nordic walking engages core, upper and lower body muscles while reducing loading stress at the knee, which may have resulted in greater improvements in functional capacity.”
“No previous study has directly compared the long-term effects of high-intensity interval training, moderate-to-vigorous intensity continuous training and Nordic walking,” commented Tasuku Terada, PhD, Exercise Physiology and Cardiovascular Health Lab, Division of Cardiac Prevention and Rehabilitation, University of Ottawa Heart Institute, Ottawa, ON, Canada.
“This study is novel in that it simultaneously compared the sustained effects (i.e., 14 weeks after the completion of cardiovascular rehabilitation) of different exercise programs that can readily be incorporated into daily exercise. When prescribing exercise for patients with coronary artery disease, patients’ preference should be considered. Our findings can impact patient care by providing alternative exercise options based on their interests and needs,” he concluded.
In an accompanying editorial, Carl J. Lavie, MD, Department of Cardiovascular Diseases, John Ochsner Heart and Vascular Institute, Ochsner Clinical School, the University of Queensland School of Medicine, New Orleans, LA, USA, and colleagues noted that the addition of Nordic walking to a cardiovascular rehabilitation program could provide an ideal progression from standard moderate intensity continuous training or traditional walking, especially for deconditioned patients who may not tolerate high intensity exercise, or for patients in whom high-intensity interval training may be contraindicated.
“The addition of Nordic poles to moderate to vigorous intensity walking is a simple, accessible option to enhance improvements in walking capacity, increase energy expenditure, engage upper body musculature, and improve other functional parameters such as posture, gait, and balance,” commented Dr. Lavie.
“Providing a variety of exercise options enhances patient enjoyment and progression, which is important for adherence and maintenance. Exercise modalities should be prescribed with consideration of patient goals, preferences, and capabilities,” he advised.

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Cholesterol-lowering gene changes may increase the risk of cataracts

People who have genetic variations associated with lowering LDL-cholesterol similar to statin medications appear to have an increased risk of developing cataracts and having cataract surgery, according to new research published today in the Journal of the American Heart Association (JAHA). JAHA is an open access, peer-reviewed journal of the American Heart Association.
Previous research has found some evidence that statin medications may increase the risk of cataracts. In this study, researchers explored whether certain genes that mimic the activity of statins may also independently increase the risk of developing cataracts.
Statin medications reduce levels of LDL-cholesterol by inhibiting an enzyme called HMG-CoA-reductase (HMGCR). Previous research efforts have confirmed that variants in the HMGCR gene region of the human genome affect how people metabolize cholesterol.
“We were able to establish a link between genetic variants that mimic inhibition of HMGCR and the development of cataracts,” said lead study author Jonas Ghouse, M.D., Ph.D., a fellow in the cardiac genetics group, Laboratory for Molecular Cardiology in the department of biomedical sciences at the University of Copenhagen in Denmark. “We were not able to find any association between newer non-statin, lipid-lowering medications and cataract risk, so this effect is likely specific to statins. However, it’s important to stress that the benefits of statins for lowering levels of low-density lipoproteins in people who have high blood cholesterol levels completely outweighs the small risk of cataracts, and cataract surgery is effective and safe.”
Using the UK Biobank, a large database of UK residents that tracks serious health and medical conditions of nearly half a million adults, researchers analyzed genetic data for more than 402,000 people. The researchers focused on five common previously identified genetic variants that lower the level of LDL cholesterol. They then calculated genetic scores based on each variant’s previously identified impact on LDL cholesterol. Genetic coding data was examined to identify carriers of a rare mutation in the HMGCR gene called a predicted loss-of-function mutation.
“When we carry a loss-of-function mutation, the gene is less likely to work,” Ghouse said. “If that gene doesn’t work, the body can’t produce that protein. Simply put, the loss-of-function mutation in the HMGCR gene equals taking a statin medication.”
The study found: The HMGCR genetic risk score identified people with a higher risk of cataracts and cataract surgery. Each 38.7 mg/dL reduction in LDL cholesterol by the genetic score was associated with a 14% higher risk of cataracts and a 25% higher risk of cataract surgery. Among 169,172 with HMGCR sequencing data, 32 (0.02%) carried one of 17 rare HMGCR predicted loss-of-function mutations. Compared with non-carriers, carriers of these rare mutations were more than four-and-a-half times as likely to develop cataracts and over five times as likely to have cataract surgery.Ghouse said he was surprised by the magnitude of the association. “The main difference between the two analyses is that loss-of-function mutations are really more detrimental than common variants, meaning they mimic change that is often induced by medications,” he said. “We believe that the true effect lies closer to the loss-of-function mutation association than the common variant association. When taking statins, you have an almost-complete inhibition of that protein, and when you have a loss-of-function mutation you also have a significantly reduced ability to produce that protein.”
According to the authors, one major limitation of the study is that while carrying these genetic variants constitutes a lifelong risk for the development of cataracts, that risk should not be evaluated the same for people who begin taking statins later in life given the positive impact statins may have by lowering blood cholesterol levels. Further evaluation of this association in more clinical trials is needed to confirm these findings.
“Our associations reflect lifelong treatment, whereas statin treatment typically occurs later in life,” Ghouse said. “However, there is a specific group of patients who are diagnosed with high cholesterol in childhood and start statin treatment at a young age, so they could be identified and followed up more closely for cataracts.”
The study was funded by BRIDGE — Translational Excellence Programme, The John and Birthe Meyer Foundation, The Innovation Fund Denmark (PM Heart), NordForsk and the Hallas-Møller Emerging Investigator grant.
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Genetic discovery could spell mosquitoes' death knell

A UC Riverside genetic discovery could turn disease-carrying mosquitoes into insect Peter Pans, preventing them from ever maturing or multiplying.
In 2018, UCR entomologist Naoki Yamanaka found, contrary to accepted scientific wisdom, that an important steroid hormone requires transporter proteins to enter or exit fruit fly cells. The hormone, ecdysone, is called the “molting hormone.” Without it, flies will never mature, or reproduce.
Before his discovery, textbooks taught that ecdysone travels freely across cell membranes, slipping past them with ease. “We now know that’s not true,” Yamanaka said.
Every insect species requires ecdysone for some aspect of their journey from egg to offspring-producing adult. And every insect that Yamanaka has tested also possesses the ecdysone transporter that he found in 2018, plus a few more found in a new study. But in this new study, he found mosquitoes to be different.
Mosquitoes have only three of the four transporter proteins that fruit flies possess. They lack the most important, primary ecdysone transporter.
“This primary one is somehow, mysteriously, missing in mosquitoes,” Yamanaka said.

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The Battle Over Gender Therapy

Scott Leibowitz is a pioneer in the field of transgender health care. He has directed or worked at three gender clinics on the East Coast and the Midwest, where he provides gender-affirming care, the approach the medical community has largely adopted for embracing children and teenagers who come out as transgender. He also helps shape policy on L.G.B.T. issues for the American Academy of Child and Adolescent Psychiatry. As a child and adolescent psychiatrist who is gay, he found it felt natural to work under the L.G.B.T. “umbrella,” as he put it, aware of the overlap as well as the differences between gay and trans identity.It was for all these reasons that Leibowitz was selected, in 2017, to be a leader of a working group of seven clinicians and researchers drafting a chapter on adolescents for a new version of guidelines called the Standards of Care to be issued by the World Professional Association for Transgender Health (WPATH). The guidelines are meant to set a gold standard for the field of transgender health care, and this would be the first update since 2012. What Leibowitz and his co-authors didn’t foresee, when they began, was that their work would be engulfed by two intersecting forces: a significant rise in the number of teenagers openly identifying as transgender and seeking gender care, and a right-wing backlash in the United States against allowing them to medically transition, including state-by-state efforts to ban it.During the last decade, the field of transgender care for youth has greatly shifted. A decade ago, there were a handful of pediatric gender clinics in the United States and a dozen or so more in other countries. The few doctors and therapists who worked in them knew one another, and the big debate was whether kids in preschool or elementary school should be allowed to live fully as the gender they identified as when they strongly and consistently asserted their wishes.Now there are more than 60 comprehensive gender clinics in the United States, along with countless therapists and doctors in private practice who are also seeing young patients with gender-identity issues. The number of young people who identify as transgender nationally is about 300,000, according to a new report by the Williams Institute, a research center at U.C.L.A.’s law school, which is much higher than previous estimates. In countries that collect national data, like the Netherlands and Britain, the number of 13-to-17-year-olds seeking treatment for gender-identity issues has also increased, from dozens to hundreds or thousands a year.Just as striking, the types of cases have changed. Many of the current group of teenagers haven’t told their families, from a young age, that they feel they are a different gender, though they often say they internalized such feelings for years. The average age when a young person first comes to a clinic tends to be around 14 or 15, according to some clinicians I talked to. Cases of teenagers coming out as trans aren’t new. But their prevalence is. In addition, the current caseload is around two-thirds youths who were “assigned female at birth,” in the current parlance of the field, and identify as trans boys — or as nonbinary, in a smaller but growing number of cases. In the past, by contrast, most patients at gender clinics were trans girls who were “assigned male at birth.”As they worked on a draft of the adolescent chapter of the Standards of Care, the big debate among clinicians was how they should respond to the thousands of teenagers who are arriving at their doors. Some are asking about medication that suppresses puberty or about hormone-replacement treatments. Leibowitz and his co-authors thought that the timing of the rise in trans-identified teenagers, as well as research from Britain and Australia, suggested that the increased visibility of trans people in entertainment and the media had played a major — and positive — role in reducing stigma and helping many kids express themselves in ways they would have previously kept buried. At the same time, the authors acknowledged that they weren’t sure that visibility was the only factor at play.As they wrote in their December draft chapter, part of the rise in trans identification among teenagers could be a result of what they called “social influence,” absorbed online or peer to peer. The draft mentioned the very small group of people who detransition (stop identifying as transgender), saying that some of them “have described how social influence was relevant in their experience of their gender during adolescence.” In adolescence, peers and culture often affect how kids see themselves and who they want to be. Their sense of self can consolidate, or they can try on a way of being that doesn’t prove right in the long run as the brain further develops the capacity for thinking long-term. To make matters more complicated, as a group, the young people coming to gender clinics have high rates of autism, depression, anxiety and eating or attention-deficit disorders. Many of them are also transgender, but these other issues can complicate determining a clear course of treatment.Without stating them outright, the draft raises tricky questions: Could some of the teenagers coming out as trans today be different from the adults who transitioned in previous generations? For them the benefits are well established and the rate of regret is very low. How many young people, especially those struggling with serious mental-health issues, might be trying to shed aspects of themselves they dislike?Leibowitz and his colleagues knew these were delicate issues. They were deeply troubled when right-wing politicians grasped the unsettled nature of these matters — which barely registered for most Americans 10 years ago — and turned them into political dynamite. In 2019, right-wing groups, the Heritage Foundation and Family Policy Alliance, which fought for many years against same-sex marriage, held a meeting on “Protecting Children From Sexualization” that covered “controversial medical treatments to treat gender dysphoria,” which is defined as a form of distress and is also a psychiatric diagnosis. Model legislation followed. Organizations like Family Policy Alliance helped state legislators draft a ban on gender-related medical treatment for anyone under age 18. Arkansas passed the first such ban in April 2021, and over the next months, similar bills were introduced in 18 other Republican-led state legislatures.WPATH is a 3,300-member international organization, mostly made up of health care professionals. It came into existence in 1979, the year it issued its first Standards of Care. These standards influence the positions taken by major medical groups, including the American Academy of Pediatrics and the American Psychological Association, and the coverage offered by health insurers and national health services around the world. Trans and nonbinary practitioners are helping to write and oversee the new guidelines, called the SOC8 because it’s the eighth edition.Over the eight months I reported on this story, I talked to more than 60 clinicians, researchers, activists and historians, as well as more than two dozen young people and about the same number of parents. WPATH gave me exclusive access to the final SOC8 (which is divided into 18 chapters, most of which address treatment for transgender adults) and lifted some of the confidentiality agreements the authors signed. Now the final version of the new Standards of Care is scheduled to come out this summer — in the midst of a raging political battle.When I started talking to Leibowitz last December, he was watching the political attacks unfold with growing alarm. In his own state, Ohio, there was a bill afoot to ban the care he himself provides to trans young people and sees as essential to their well-being. His group’s job for the SOC8 was to be “as rigorous and scientific as possible,” he said, about how to translate the evidence about gender care into clinical practice. But they were acutely aware that any unknowns that the working group acknowledged — any uncertainties in the research — could be read as undermining the field’s credibility and feed the right-wing effort to outlaw gender-related care.Scott Leibowitz, a child and adolescent psychiatrist, helped lead the working group writing a chapter on adolescents for the Standards of Care, a set of guidelines from the World Professional Association for Transgender Health (WPATH).Maggie McGarvey for The New York TimesThe group was stocked with experts, including Leibowitz’s co-leader for the adolescent chapter, the Dutch child psychiatrist Annelou de Vries, who for 19 years has worked at what was the first transgender pediatric clinic in the world, and the clinical psychologist Ren Massey, who is a former president of the Georgia Psychological Association and is transgender. When WPATH released the draft of the SOC8 for public comment, Leibowitz and his co-authors braced for the inevitable conservative attack. For teenagers who have parental consent, the draft adolescent chapter lowered to 14 (from 16 in the previous guidelines) the recommended minimum age for hormone treatments, which can permanently alter, in a matter of months, voice depth and facial and body hair growth and, later, other features like breast development. It set a minimum recommended age of 15, for breast removal or augmentation, also called top surgery. (The previous standards didn’t set a minimum age.)Opponents of gender-related care did, indeed, denounce all of this. But Leibowitz and his co-authors also faced fury from providers and activists within the transgender world. This response hit them harder, as criticism from your colleagues and allies often does. It arose from two of the conditions the draft chapter established in order for young people to start taking puberty suppressants and hormones. First, the draft said, preteens and teenagers should provide evidence of “several years” of persistently identifying as, or behaving typically like, another gender, to distinguish kids with a long history from those whose stated identification is recent. And second, they should undergo a comprehensive diagnostic assessment, for the purpose of understanding the psychological and social context of their gender identity and how it might intersect with other mental-health conditions.Assessments for children and adolescents have long been integral to the Standards of Care. But this time, the guard rails were anathema to some members of a community that has often been failed by health care providers. “The adolescent chapter is the worst,” Colt St. Amand, a clinical psychologist and family-medicine physician at the Mayo Clinic, posted on the Facebook page of International Transgender Health, which has thousands of members and functions as a bulletin board for the field. (St. Amand is on the working group for another chapter in the SOC8 on hormone treatments.) In a publicly streamed discussion on YouTube on Dec. 5, activists and experts criticized the adolescent chapter, with the emotion born of decades of discrimination and barriers to care. “This statement sucks,” Kelley Winters, a moderator of International Transgender Health who is an interdisciplinary scholar and community advocate in the field, said of the assessment. “This is talking about singling out trans kids, and specifically with a mental-health provider, not medical staff, to interrogate, to go down this comprehensive inquisition of their gender.” The requirement for evidence of several years of gender incongruity before medical treatment is “harmful and destructive and abusive and unethical and immoral,” said Antonia D’orsay, another moderator of the group who is a sociologist and psychologist. In January, in a public comment to WPATH, International Transgender Health blasted the adolescent chapter for “harmful assertion of psychogatekeeping” that “undermines patient autonomy.”And just like that, after four years of painstaking work, Leibowitz, de Vries and the rest of their group were being called out as traitors by peers and the community they sought to care for. “We understood the enormity of the need for these standards from the beginning,” Leibowitz told me. “I’m not sure we recognized the enormity of the controversy. It’s a result of the fact that our world, the world of gender care, has exploded.”In the 1950s and ’60s, a small cadre of doctors in Europe and the United States started to talk about how to evaluate adults who wanted to medically transition. Harry Benjamin, the endocrinologist for whom WPATH was originally named, embraced the idea that the people he agreed to treat (mostly trans women) were “born in the wrong body.” Fearing lawsuits from dissatisfied patients, the doctors were quick to exclude patients for reasons of mental stability. And, arbitrarily, they only included those who they believed would go on to pass as the gender they identified with, as Beans Velocci, a historian at the University of Pennsylvania, wrote in an article last year in TSQ: Transgender Studies Quarterly. Some doctors made trans adults promise to live as heterosexuals after they transitioned.The small group of clinicians who wrote the first Standards of Care were all cisgender. After WPATH was created in 1979, transgender advocates increasingly gained influence in the organization, but many transgender people viewed subsequent versions of the standards as imposing paternalistic and demeaning barriers to treatment. For some genital surgery, the standards required adults to live for a year as the gender they identified with and to provide referrals from two mental-health professionals. The SOC8 is the first version to dispense with these requirements, adopting a model of “shared decision-making” between adult patient and surgeon.The leap toward medical transition for young people occurred in the Netherlands in the 1980s. Peggy Cohen-Kettenis, a Dutch clinical psychologist specializing in children, began receiving referrals of teenagers who were experiencing gender dysphoria (then called gender identity disorder). But therapy wasn’t the primary answer, Cohen-Kettenis, who is retired, told me over the phone this spring. “We can sit and talk forever, but they really needed medical treatment.” As their bodies developed in ways they didn’t want, “they only did worse because of that.” She decided to help a few of her patients start hormone treatments at 16 rather than waiting until 18, the practice in the Netherlands and elsewhere at the time. She monitored them weekly, then monthly. “To my surprise, the first couple were doing much better than when they first came,” she said. “That encouraged me to continue.”Cohen-Kettenis helped establish a treatment protocol that proved revolutionary. Patient Zero, known as F.G., was referred around 1987 to Henriette A. Delemarre-van de Waal, a pediatric endocrinologist who went on to found the gender clinic in Amsterdam with Cohen-Kettenis. At 13, F.G. was in despair about going through female puberty, and Delemarre-van de Waal put him on puberty suppressants, with Cohen-Kettenis later monitoring him. The medication would pause development of secondary sex characteristics, sparing F.G. the experience of feeling that his body was betraying him, buying time and making it easier for him to go through male puberty later, if he then decided to take testosterone. Transgender adults, whom Cohen-Kettenis also treated, sometimes said they wished they could have transitioned earlier in life, when they might have attained the masculine or feminine ideal they envisioned. “Of course, I wanted that,” F.G. said of puberty suppressants, in an interview in “The Dutch Approach,” a 2020 book about the Amsterdam clinic by the historian Alex Bakker. “Later I realized that I had been the first, the guinea pig. But I didn’t care.”Over the next decade, Cohen-Kettenis and Delemarre-van de Waal designed an assessment for young people who seemed like candidates for medical treatment. In questionnaires and sessions with families, Cohen-Kettenis explored the reasons for a young person’s gender dysphoria, considering whether it might be better addressed by therapy or medication or both. The policy was to delay treatment for those with issues like attention-deficit and eating disorders or who lacked stable, supportive families, in order to eliminate factors that might interfere with the treatment. “We did a lot of other work before letting them start, which created a lot of frustration for them,” Cohen-Kettenis said. “Maybe we were too selective in the early stages.” In retrospect, she says, she thinks young people who might have benefited were excluded.The stringent screenings seemed critical, however, given the opposition they faced. Other doctors, in the Netherlands and outside it, publicly accused them of recklessness. At a low moment, at a medical conference in the late 1990s, she said, they were likened to Nazis experimenting on children.Cohen-Kettenis stressed that she and her growing team at the Amsterdam clinic were not channeling children toward a particular outcome. The Dutch advised what they called “watchful waiting.” Throughout his childhood, with his parents’ support, F.G. lived as a boy, with short hair and a gender-neutral nickname. But Cohen-Kettenis counseled parents to “keep the door open, as much as possible, for children to be able to change back.” Among the adolescents who came to the clinic beginning at the age of puberty, 41 percent went on puberty suppressants, and more than 70 percent received hormone treatments and went on to surgery.The Amsterdam clinic attracted international interest. Norman Spack, an endocrinologist at Boston Children’s Hospital who began treating transgender adults in the 1980s, and Laura Edwards-Leeper, then a child psychologist there, visited Amsterdam in 2007 for a gathering of clinicians from countries including Canada, Britain, Norway and Belgium. Spack and Edwards-Leeper went back to Boston, where they and another doctor were opening the first dedicated gender clinic for kids in the United States that provided medical treatment based on the fundamentals of the Dutch approach — a comprehensive assessment before patients could begin puberty suppressants or hormone treatments and close consultation between a clinic’s mental-health professionals and medical doctors.Scott Leibowitz joined the Boston clinic as a psychiatrist in training a year later. In the early days, families traveled long distances for appointments. The waiting list grew. Edwards-Leeper and Spack eventually shortened the period a child had to be in therapy before the clinic did its own assessment, from a year to between three and six months. “If a child was on the cusp of puberty, and anxious about how their body was about to change, we tried to squeeze them in faster, which I still think is really important,” Edwards-Leeper says.Tori (a nickname), who is 13 and lives outside Atlanta: “With gender, it has been more and more, wanting more things to happen. And luckily I have parents who are willing to let me describe myself and be whoever I want.”Anne Vetter for The New York TimesIn 2011, de Vries and her colleagues published the first of two landmark studies about medical interventions in adolescence. Among the first 70 patients who received puberty suppressants at the Amsterdam clinic after their initial assessment at the mean age of about 13½, the researchers found “a significant decrease in behavioral and emotional problems over time.” A second study published in the journal Pediatrics in 2014, of about 55 of those who went from puberty suppressants to hormone treatments at the mean age of about 16½, showed that five years after starting hormone treatments and at least one year after surgery, they had the same or better levels of well-being as a control group of cisgender adults their age. None of the 55 regretted their treatment. (The 15 of the original 70 who were not included in the follow-up study did not take part mainly because of the timing of their surgery.)For the first time, a long-term, peer-reviewed study showed positive outcomes after medical treatment in adolescent patients who’d gone through Cohen-Kettenis and Delemarre-van de Waal’s protocol. They had all been through a version of the type of assessment the December draft of the SOC8 adolescent chapter would recommend years later. They had experienced gender dysphoria since childhood (according to their families), lived in supportive environments and had no interfering mental-health conditions. As is often the case in medicine, the question for those drafting the SOC8 would be how to apply the findings of a particular cohort to the growing numbers of teenagers lining up at clinics in a host of countries.In the United States and Canada, meanwhile, two dueling approaches to therapy for young children, before they reached puberty, were vying for supremacy. At what is now called the Child and Adolescent Gender Center at the University of California, San Francisco, Diane Ehrensaft, a developmental and clinical psychologist, was counseling families to take what she and others called a “gender affirming” approach, which included a social transition: adopting a new name and pronouns for a child who expressed such a preference, along with letting kids dress and play as they pleased.For years, Ehrensaft’s intellectual foil was Ken Zucker, a psychologist and prominent researcher who directed a gender clinic in Toronto. Between 1975 and 2009, Zucker’s research showed that most young children who came to his clinic stopped identifying as another gender as they got older. Many of them would go on to come out as gay or lesbian or bisexual, suggesting previous discomfort with their sexuality, or lack of acceptance, for them or their families. Based on this research, in some cases Zucker advised parents to box up the dolls or princess dresses, so a child who was being raised as a boy (a majority then) wouldn’t have those things to play with.In 2012, the last version of WPATH’s Standards of Care, with Cohen-Kettenis and Zucker among the authors, cited his work 15 times and called social transition in early childhood “controversial.” The American Psychological Association said in 2015 guidelines that there was no consensus about a best practice for children before puberty, describing both accepting children’s “expressed gender identity” (citing de Vries and Cohen-Kettenis, Ehrensaft, Edwards-Leeper and Spack, among others) and, alternatively, encouraging them to “align with their assigned gender roles” (citing Zucker, among others).At the end of 2015, the Canadian medical center that ran Zucker’s clinic in Toronto shut it down because of complaints from activists and a parents’ group about his method. (Zucker sued the center for defamation and later received an apology and a settlement of $450,000.) In February 2017, protesters interrupted and picketed a panel featuring Zucker at the inaugural conference of USPATH (the U.S. affiliate of WPATH) in Los Angeles. That evening, at a meeting with the conference leaders, a group of advocates led by transgender women of color read aloud a statement in which they said the “entire institution of WPATH” was “violently exclusionary” because it “remains grounded in ‘cis-normativity and trans exclusion.’” The group asked for cancellation of Zucker’s appearance on a second upcoming panel. Jamison Green, a trans rights activist and former president of WPATH, said the board agreed to the demand. “We are very, very sorry,” he said.After that controversy, other providers were on notice that Zucker’s methods were no longer acceptable. His approach was likened to conversion therapy, which treats being gay or trans as a mental illness to be cured, and which many states and localities have made illegal.The Amsterdam clinic shifted, too. Some Dutch families socially transitioned kids on their own, which de Vries and her colleagues accepted; they began counseling other families about social transition too. Though the Amsterdam researchers’ previous results, like Zucker’s, showed that most kids who came to the clinic in elementary school later realigned with the genders of their birth, and often came out as gay, lesbian or bisexual, de Vries and her colleagues now see those findings as a product of their time, when the children whom parents brought to the clinic included many boys with an interest in wearing feminine clothing and playing with dolls that didn’t turn out to be gender dysphoria. Today many Dutch parents are more accepting of this behavior, and the Amsterdam clinicians think that as a result, most of the children who come to the clinic are asserting a strong and persistent gender preference. It’s more likely that such children will stay the course of being transgender, research shows. One long-term study, published in 2021, of 148 kids in the United States who socially transitioned with their families’ support between the ages of 8 and 14, found that five years later their psychological well-being was on par with their siblings and a control group of cisgender peers.There is a separate chapter in the SOC8 that focuses on young children and that recommends that health care professionals and parents support social transition when it originates with the child while also recognizing that for some kids, gender is fluid. An outstanding question, asked by gay commentators like the author Andrew Sullivan, is whether some kids who socially transition today, and remain trans, would have grown up to be gay or lesbian in previous generations. “I know there are worries that effeminate males can be assumed to be female or masculine girls can be assumed to be male,” says Amy Tishelman, the lead author of the SOC8 chapter on children and a child psychologist who is the former director of clinical research at the gender clinic at Boston Children’s Hospital. “That’s not what we’re advocating. Support for trans people should not be a way of limiting what a girl or a boy or a woman or a man or a person can be.”Marci Bowers, a gynecologic and reconstructive surgeon, is slated to be the next president of WPATH.Ryan Young for The New York TimesA few months before the release of the December draft of the SOC8, WPATH had a preview of the firestorm to come. In October 2021, the journalist Abigail Shrier published a post called “Top Trans Doctors Blow the Whistle on ‘Sloppy’ Care” on the Substack of Bari Weiss, a former opinion editor and writer for The New York Times.” The word “sloppy” was a quote from Erica Anderson, a clinical psychologist who was a past president of USPATH and who worked at the U.C.S.F. gender center for years before leaving in October (for unrelated reasons). She told Shrier she expected more regret among young people because some providers were rushing them toward medication without sufficient mental-health evaluations.Shrier also quoted Marci Bowers, a gynecologic and reconstructive surgeon who is slated to be the next president of WPATH, who voiced a separate concern about blocking puberty too early. Though there is no published data on this question, over hundreds of surgeries, Bowers has found that trans girls who don’t go through male puberty may find it difficult to have an orgasm after they have genital surgery as adults. They also could have less penile tissue with which to create a vagina, which can lead to more complications from surgery, according to Bowers. These concerns apply in a small percentage of cases in the United States, as most teenagers come to gender clinics at 14 or older, after puberty. But for the younger kids, Bowers advocated delaying puberty suppressants to a later stage of development.Anderson and Bowers are transgender women, which brought more attention to their critique and to their decision to talk to Shrier, who is the author of a 2020 book, “Irreversible Damage: The Transgender Craze Seducing Our Daughters,” which many trans people and their allies abhor. Many trans health providers were furious. “I was like, Whoa, what is this? And then I texted Erica,” says Maddie Deutsch, the president of USPATH and a professor at U.C.S.F. as well as the medical director of the Gender Affirming Health Program there, who is also transgender. “We were all broadsided.” She worries about the political fallout. “States like Texas and Florida are looking to these articles to fan the flames.”About a week after Shrier’s post appeared, USPATH and WPATH issued a statement opposing “the use of the lay press” for scientific debate about gender-related medical treatment. Anderson disagreed with the directive. “Some of our colleagues would have us shut up,” she told me in the fall. “No. It’s not OK to ignore the problems.” In late November, she and the child psychologist Laura Edwards-Leeper published an opinion essay in The Washington Post. They said they were “disgusted” by the proposed state bans on gender-related medical treatment for minors, but they warned that some providers in the United States were “hastily dispensing medicine” and skipping comprehensive assessments.‘Young people are quite capable of understanding themselves, but not all of them will.’The following week, news broke in Texas that the only gender clinic for adolescents that provides hormone therapy in the Dallas region, Genecis, was being disbanded, a result of political pressure from Gov. Greg Abbott. “We have wolves at the door,” says Ehrensaft, who worked with Anderson at U.C.S.F. and is an author on the SOC8 chapter on children with Edwards-Leeper. “Conversations among us get aired as controversy and confusion. You end up eating your own instead of making the wolves go away.” Others were scathing about placing blame. “Every time a law passes blocking trans youth from getting care, I hope it’s called an Edwards-Leeper law,” Andrew Cronyn, a pediatrician and a former adviser on policy about L.G.B.T. health for the American Academy of Pediatrics, wrote on a professional email list with more than 500 recipients. “And I hope that every time one of the youth who is blocked from affirmative care dies, she gets sent a copy of the obituary.” He subsequently apologized and the post was removed at his request.When I spoke to Bowers in December, she distanced herself from Anderson and Edwards-Leeper. “The most important thing is access to care,” she said. “And that is a much bigger problem than the issue of how the medical community and transition is failing people.” But she remained intent on drawing attention to her concerns about the early suppression of puberty. “Sexual satisfaction is a huge thing,” she said. “You’ve got to talk about it.”Partly in response to Bowers’s concerns, the December draft of the SOC8 adolescent chapter suggested that health care providers discuss “future unknowns related to sexual health” when families consider puberty suppressants. The Amsterdam clinic often waits to prescribe suppressants until later in puberty.In the United States, waiting would be a major shift for the relatively small group of younger kids at gender clinics. For them, families weigh the relief the medications can provide against the health implications. Taking puberty suppressants (or hormones) for gender affirmation is “off-label,” meaning this specific use of the medications is not approved by the Food and Drug Administration. Off-label prescriptions are common and don’t imply anything improper, but there may be less research about the drug’s effects. If young people continue on to hormone treatments, puberty suppressants “probably” compromise fertility, especially for trans girls, Stephen M. Rosenthal, a pediatric endocrinologist at the gender center at U.C.S.F. who is on the group for the SOC8 chapter on hormone treatments, explained in a review last year for Nature Reviews Endocrinology. The medication can also prevent bone density from increasing as it typically would, and while levels returned to normal in trans boys who went on to hormone therapy, they remained low in trans girls who did the same, according to a 2020 study from the Amsterdam clinic. Little is known about the impact on brain development. “The relative paucity of outcomes data raises notable concerns,” Rosenthal wrote in his review. But he has no hesitation about prescribing puberty suppressants to kids who are deemed ready for them at his clinic. “The observed benefits greatly outweigh the potential adverse effects,” he said.As winter approached, criticism of Anderson and Edwards-Leeper by their peers mounted as right-wing attacks on medical care for minors grew louder. In early November, the board of USPATH privately censured Anderson, who served as a board member. In December, the board imposed a 30-day moratorium on speaking to the press for all board members. That month, Anderson resigned.In February, Governor Abbott ordered child-abuse investigations of parents and providers in Texas who give gender-related medical treatments to kids, generating national headlines and causing fear and anguish for families. In March, Arizona became the second state to ban gender medical care for minors. (The law, which applies to surgery, not medications, is scheduled to go into effect in 2023.)The next month, four doctoral students in psychology asked to drop Edwards-Leeper from their dissertation committees at Pacific University, where she is an emeritus professor. And yet in the same week, she presented on the SOC8 adolescent chapter at the annual pediatric conference of the American Psychology Association, where the moderator of one of her panels praised her for her bravery in voicing her concerns about her field. The roller coaster of reaction, at the same time kids were losing access to care altogether in red states, shook Edwards-Leeper and her co-authors of the SOC8 chapters on adolescents and children. They didn’t want to be blamed for the right-wing backlash — neither by activists nor their own peers.Watching the waves of conflict break, Leibowitz worried. He respected Bowers, Anderson and Edwards-Leeper for raising difficult issues but could see their views being mischaracterized to justify banning gender-related care. For people who don’t know much about the issues, “banning the care probably sounds more enticing than the idea that kids are dictating what treatment they should get,” he says. “Our guidelines are the voice from the middle.”Kat (a nickname), who is 18 and lives in the Midwest: “When I was younger, I tried to wear girls’ clothes, but it hurt. I still can’t quite explain why. But I don’t focus on gender that much now. It’s just one aspect of myself.”Anne Vetter for The New York TimesOne morning over the phone, Leibowitz explained to me the elements of the mental-health assessments he saw as essential. His starting point, when a child presents as transgender, is obtaining a complete diagnostic profile. This means understanding the relationship between gender dysphoria and any other conditions (like depression or an eating disorder) or another factor that might be causing discomfort (like trauma or feeling confined by gender stereotypes) before coming up with a treatment plan. “It’s about understanding how the issues that might make someone experience gender dysphoria are connected,” he said.As Leibowitz and his co-authors discussed revisions over video calls and email, colleagues who were critical of the draft chapter were also working together. Colt St. Amand, the psychologist and physician who disparaged the adolescent chapter on the Facebook page of International Transgender Health, brought together a collective of 16 mental-health professionals who are either transgender (as he is) or nonbinary, or have a close family member who is, to talk about how the assessment guidelines in the adolescent chapter fit with their lived experience and professional knowledge.St. Amand thinks the purpose of an assessment is not to determine the basis of a kid’s gender identity. “That just reeks of some old kind of conversion-therapy-type things,” he told me over the phone in April. “I think what we’ve seen historically in trans care is an overfocus on assessing identity.” He continued: “People are who they say they are, and they may develop and change, and all are normal and OK. So I am less concerned with certainty around identity, and more concerned with hearing the person’s embodiment goals. Do you want to have a deep voice? Do you want to have breasts? You know, what do you want for your body?”The draft of the adolescent chapter suggests that “extended assessments” may be useful for young people who are autistic or have some characteristics of autism without a full diagnosis. “One of the key accommodations for autistic youth is providing more time and structure to support the young person’s self-advocacy and communication capacity,” said John Strang, the specialist on the intersection of autism and gender identity on the SOC8 adolescent and child chapters and a neuropsychologist at Children’s National Hospital in Washington, D.C. But St. Amand calls a standard of extended assessments a “gross generalization” and “discriminatory.”The priority for the collective St. Amand organized, which is working on a series of articles and training materials, is to ensure that transgender and nonbinary youth get the care they need rather than to shield teenagers from taking medication with effects they might later decide they didn’t want. St. Amand’s focus is on a young person’s response after beginning puberty suppression or hormone therapy. “If that is the right thing for them, then the response over time will tell me,” he says. “Once we start those interventions, we are checking in with the patient to see how they’re doing.” If the drugs don’t suit them, in his view, they can simply stop.Colt St. Amand, a clinical psychologist and family-medicine physician at the Mayo Clinic, is in the working group for a chapter on hormone treatments in WPATH’s new Standards of Care.Ben Innes for The New York TimesOther providers, however, see an ethical dilemma stemming from the principle of justice — which promotes access to care for trans youth — and the principle of doing no harm. “I wouldn’t recommend just initiating testosterone straight away,” says Nathaniel Sharon, a child psychiatrist in New Mexico who has helped shape mental-health policy that affects transgender young people for the American Academy of Child & Adolescent Psychiatry. “Their voice gets permanently low. They’re hairy. Their clitoris is enlarged. And what do you do now? I just find that inappropriate and unsafe.”The differences among gender-affirming providers over assessments and medical intervention don’t break down along cisgender-transgender lines. Some transgender practitioners, like Sharon and Ren Massey, a psychologist on the SOC8 adolescent chapter, support the chapter’s approach to assessments. “We need to understand that the reality is that adolescents go through a lot of developmental changes and have a lot of internal and external influences on their development,” Massey says. And some transgender activists also support a cautious approach. “It is life changing,” Jamison Green, the former president of WPATH, says of transitioning. “It is all encompassing. If it’s right for you, then it’s really important. It’s very easy to get interested in a new idea, get excited and not think it through all the way. Young people are quite capable of understanding themselves, but not all of them will. That’s why I think prudence is useful.”Leibowitz had a related concern. For young people who have yearned for puberty suppressants or hormone treatments, reversing course can be difficult, he says. “Some people, once they make the decision, they’re not going to go against it, because they feel internal pressure to continue. They might be susceptible to feeling ashamed.”Research is just beginning about why young people halt medical treatment and what it means for them. Some continue to identify as trans or nonbinary, like Nova West, a 27-year-old filmmaker I spoke to, who was happy with top surgery and the way testosterone lowered their voice and helped them build muscle — and then stopped the treatment because they didn’t want to go bald (which sometimes happens) and felt they’d reached their “optimal gender expression.”Others decide they want to fully detransition and return to their cis identities. Grace Lidinsky-Smith, who is 28, has written about her regret over taking testosterone and having her breasts removed in her early 20s. She told me that she wished she’d had the comprehensive assessment the Standards of Care endorsed for adolescents. “That would have been really good for me,” she said.St. Amand and the collective argue that as no study has directly compared different types of assessment, there’s no evidence that the Amsterdam clinic’s approach is better. They point to research from clinics in the United States, which shows small-to-moderate improvements in depression and anxiety and large improvements in body-related dysphoria for young patients six months or a year after beginning medication. One of those studies is by the clinical child psychologist Laura Kuper, based on a sample of young patients, some of who went through a streamlined assessment process that Kuper helped design at the Genecis program in Dallas. “In medicine in general, if you find a new treatment and it seems overwhelmingly helpful, you start to roll it out before you have a 10-year follow up,” says Kuper, who helped start the collective with St. Amand and is one of the authors of a SOC8 chapter on nonbinary individuals. “You continually reflect on new research and clinical findings as you go.”It’s not yet known how well improvement in the short term predicts how teenagers today will feel as older adults about the changes they made to their bodies. In their draft chapter, Leibowitz, de Vries, Massey and their co-authors note that to date, only the Amsterdam clinic, with its comprehensive assessments, has results showing strong psychological benefits later in life for people who medically transitioned in their teens. Today, the Amsterdam clinic usually requires at least six monthly sessions (following a longer period on a waiting list) to begin medical treatment. “We’ve always said, Do it in a careful way,” de Vries says.Most of the young people today who come to clinics for treatment are affluent and white, live in progressive metropolitan areas and have health insurance. For them, gender-related care has become more accessible since 2016, when the Obama administration included gender identity in a rule against denying health care benefits on the basis of sex. If a provider deems the care medically necessary, it’s possible to get insurance coverage for puberty suppressants, which can be injected or implanted under the skin, and hormone treatments, which can be taken orally, injected or applied as a gel or a patch. Each can cost thousands of dollars a year.But in other parts of the country, there is often no gender clinic and sometimes no therapist or doctor to help transgender kids — who often still face bullying and harassment — navigate the process of coming out. “I have a patient in rural Mississippi who tried to find mental-health support, but it was traumatic,” says Izzy Lowell, a family-practice doctor and the founder of QueerMed, which treats patients mostly via telemedicine (without in-person visits) in about a dozen states covering the Southeast. In effect, states like Arkansas are banning care where it is already rare.‘I say to parents, “I have no idea if your child is trans or not — they need an open field to explore.” ’The Push to Restrict Rights for Young Transgender PeopleCard 1 of 8A growing trend.

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What if This Wasn’t Menopause After All?

The patient had the full suite of symptoms — and a jaw that somehow moved out of alignment. That was the clue something was wrong.The 53-year-old woman bit into her salad, enjoying the crispness. But as she swallowed, a chunk of lettuce stuck in her throat. She coughed, and it loosened and came back up. It was a problem she had frequently these days. Her teeth on the right side of her jaw didn’t touch anymore. It was hard to chew her food well. What was really upsetting was that she’d had this problem before — for most of the previous year. When she couldn’t put up with it anymore, she’d gone to her dentist, Dr. Robert Souferian, in Bay Ridge, Brooklyn, who confirmed that her bite had shifted a little. He was reassuring, said that it happened sometimes and offered to file her teeth a little to make the fit better. That worked beautifully — for a few months. But it was now clear that her jaw had shifted again.The woman studied her face in the bathroom mirror. She ate a good diet and did yoga at least once a day. She did everything she could to stay healthy and keep in shape, but she could see that, somehow, she wasn’t aging well. And she wasn’t the only one who noticed. On a recent Zoom call, her mother, with her loving but brutal maternal honesty, said, “Your eyes look awful.” She then joked that maybe the two of them should get “a little work done” together once the pandemic was over. She knew what her mother meant. She had bags under her eyes, and the skin around them was puffy. Her face shone with sweat from near-constant hot flashes. She hardly recognized the face that looked back at her.She returned to Souferian’s office and asked if he could file her teeth once more. This time the dentist looked worried. “That doesn’t make sense,” he told her. Why would her teeth move again? He examined her mouth and jaw carefully. He could see that her bite had shifted, but he couldn’t see why. He was concerned that she could have a growth or tumor inside one of her temporomandibular joints. She wasn’t tender there, and he couldn’t feel anything. Still, it was a possibility he couldn’t ignore. He referred her to a colleague who could do a 360-degree X-ray to look for a mass. When the X-ray didn’t show anything, that dentist sent her for an M.R.I. of the jaw.Her jaw was normal, she was told a few days later. There was no tumor there. However, the dentist continued, the radiologist saw something else she needed to know about. He saw a lesion on her pituitary gland. She should see a neurologist to get that checked out.A Closer Look at the Master GlandThe pituitary gland is just below the middle of the brain, at the level of the eyes. It used to be called the “master gland” because it secretes the hormones that run many of the body’s functions: growth, metabolism, lactation, sex drive and reproduction. She wasn’t sure what it meant to have a lesion there, but she immediately took the dentist’s advice and made an appointment with a neurologist. The doctor was a middle-aged man with a tidy gray beard and a warm, slightly accented voice. He heard her story and reviewed the M.R.I. of her jaw. He agreed that she needed an M.R.I. of the brain so they could see all the surrounding structures and get a better look at the lesion.After the scan she got a call from the neurologist. He confirmed that she did have a lesion on her pituitary. The good news: It wasn’t cancerous. The bad news was that it was large. It would have to be removed. When she heard the word cancer, the woman’s heart began to race. She never even considered the possibility of cancer. She was relieved it wasn’t that. But what did he mean, she would have to get it removed? Did she need brain surgery? “You don’t have to get this done tomorrow,” he answered gently, “but it should be removed within the year.” She would need to see three more doctors, he continued: an ophthalmologist, because the gland and its growth were just above the optic nerves and could affect her vision. She would also need an endocrinologist, and finally she would certainly need a neurosurgeon.She saw the ophthalmologist first. No problem there. That was a relief. She hadn’t felt as if there was anything wrong with her vision, but she hadn’t felt there was anything wrong with her brain either. Then it was back to the internet to find an endocrinologist. She found one who had good reviews and was covered by her insurance. Amazingly, she was able to make an appointment for the next day.Dr. Joan Cantero, the endocrinologist she found, spoke with an air of quiet confidence. The mass was big, Cantero noted, about the size of a marble, which made it twice the size of the gland it was affecting. It would definitely have to be removed.Before her appointment, the patient had done some investigating. She read about pituitary tumors on the internet and asked all her doctor friends. It wasn’t the kind of brain surgery often shown on TV where the head is shaved, the skull cut open with a saw and the surgeon cuts into the puddinglike tissue of the brain itself. This type of brain surgery was done with a scope inserted into the nose, removing the tumor from below. By the time she saw Cantero, the woman was eager to do whatever was needed. As awful as the idea of surgery was, the thought of something growing back there was scary and creepy.Photo illustration by Ina JangChecking an Old PhotoNot so fast, Cantero warned. First, they needed to see if the tumor was making any of the pituitary’s hormones. The doctor suspected the patient had an excess of one of these hormones — an overproduction of growth hormone will cause unregulated enlargement of the soft tissues throughout the body, a disorder called acromegaly. The patient was a small woman, but, the doctor noticed, her hands and feet were huge. Can you take your mask down? Cantero asked. And show me an old photo? The difference in the two faces added to Cantero’s clinical suspicion. But a diagnosis like this requires more than suspicion. Cantero sent the patient to the lab, where a half dozen tubes of blood were drawn and sent off. She returned to the endocrinologist’s office two weeks later. Her growth-hormone levels were nearly five times what they should be: She had acromegaly. The woman had surgery two weeks later.Acromegaly is rare. It is most extreme when the oversecretion of the hormone starts before puberty, when bones can still grow. André Roussimoff, more familiarly known as André the Giant, was 7-foot-4 when he finally stopped growing taller. After puberty, when bone growth stops, only soft tissues will enlarge. That can still cause serious changes in appearance and in health. Untreated, patients with acromegaly will often have obstructive sleep apnea from enlarging tissues in the mouth and throat, high blood pressure, joint breakdown and sometimes an enlarged but weakened heart. This patient, it turned out, had everything except the enlarged heart.After getting this diagnosis, the patient immediately started reading up on the disease. If asked before her diagnosis was made, the only symptom she would have identified was the crooked jaw. Reading about other people’s experiences, she realized how many of the irritations and medical issues she’d been through were from this excess of growth hormone and not, as she had assumed, from the effects of menopause on an active life and an aging body. She’d seen changes in her face. Her hands were so big she couldn’t wear rings. Her feet were enormous. For most of her adult life, she wore a size 8½ shoe. By the time she had her surgery, her feet were so wide she wore a men’s size 9½. Her tongue was so large that she often bit it, and she had sleep apnea. She also had high blood pressure.She was thin for her entire life but needed a knee replacement at 49. She was hot all the time and sweated like crazy. Menopause, she figured — until she read about this tumor.Two days after leaving the hospital, she could fit into her mother’s shoes, a woman’s size 8½. She’s no longer hot and sweaty all the time. It sounds minor, she told me, but that was one of the worst parts of the whole ordeal. And a year after her surgery, she tells me that she looks at least five years younger. Her acquaintances suspect a face lift. Her friends know it was a different kind of surgery. Best of all, she has watched as her face has slowly reverted back to the one she knew so well.Lisa Sanders, M.D., is a contributing writer for the magazine. Her latest book is “Diagnosis: Solving the Most Baffling Medical Mysteries.” If you have a solved case to share, write her at Lisa.Sandersmdnyt@gmail.com.

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