As the bike toppled, he thrust out his left arm to break the fall. It didn’t seem like a serious accident, yet “I couldn’t get up,” he said.

At the emergency room, X-rays showed that he had fractured both his hip, which required surgical repair, and his shoulder. Klein, a dentist, went back to work in three weeks, using a cane. After about six months and plenty of physical therapy, he felt fine.

But he wondered about the damage the fall had caused. “A 52-year-old is not supposed to break a hip and a shoulder,” he said. At a follow-up visit with his orthopedist, “I said, ‘Maybe I should have a bone density scan.’”

As Klein suspected, the test showed he had developed osteoporosis, a progressive condition, increasing sharply with age, that thins and weakens bones and can lead to serious fractures. Klein immediately began a drug regimen and, now 70, remains on one.

Osteoporosis occurs so much more commonly in women, for whom medical guidelines recommend , that a man who was not a health care professional might not have thought about getting a scan. The orthopedist didn’t raise the prospect.

But about will suffer an osteoporotic fracture in their remaining years, and among older adults, about .

When they do, “men have worse outcomes,” said Cathleen Colón-Emeric, a geriatrician at the Durham VA Health Care System and Duke University and the lead author of a recent study of osteoporosis treatment in male veterans.

“Men don’t do as well in recovery as women,” she said, with (25% to 30% within a year), disability and institutionalization. “A 50-year-old man is more likely to die from the complications of a major osteoporotic fracture than from prostate cancer,” she said.

(What’s “major”? Fractures of the wrist, hip, femur, humerus, pelvis or vertebra.)

In her ages 65 to 85, conducted at Veterans Affairs health centers in North Carolina and Virginia, only 2% of those assigned to the control group had undergone bone-density screening.

“Shockingly low,” said Douglas Bauer, a clinical epidemiologist and osteoporosis researcher at the University of California-San Francisco, who published in JAMA Internal Medicine. “Abysmal. And that’s at the VA, where it’s paid for by the government.”

But establishing a bone health service — overseen by a nurse who entered orders, sent frequent appointment reminders and explained results — led to dramatic changes in the intervention group, who had at least one risk factor for the condition.

Forty-nine percent of them said yes to a scan. Half of those tested had osteoporosis or a forerunner condition, osteopenia. Where appropriate, most of them began medications to preserve or rebuild their bones.

“We were pleasantly surprised that so many agreed to be screened and were willing to initiate treatment,” Colón-Emeric said.

After 18 months, bone density had increased modestly for those in the intervention group, who were more likely to stick to their drug regimens than osteoporosis patients of either sex in real-world conditions.

The study didn’t continue long enough to determine whether bone density increased further or fractures declined, but the researchers plan a secondary analysis to track that.

The results revive a longtime question: Given how life-altering, even deadly, such fractures can be, and the availability of effective drugs to slow or reverse bone loss, should older men be screened for osteoporosis, as women are? If so, which men and when?

Such issues mattered less when life spans were shorter, Bauer explained. Men have bigger and thicker bones and tend to develop osteoporosis five to 10 years later than women do. “Until recently, those men died of heart disease and smoking” before osteoporosis could harm them, he said.

“Now, men routinely live into their 70s and 80s, so they have fractures,” he added. By then, they have also accumulated other chronic conditions that impair their ability to recover.

With osteoporosis testing and treatment, “a man could see a clear-cut improvement in mortality and, more importantly, his quality of life,” Bauer said.

Both patients and many doctors still tend to regard osteoporosis as a women’s disease, however. “There’s a bit of a Superman idea,” said Eric Orwoll, an endocrinologist and osteoporosis researcher at Oregon Health & Science University.

“Men would like to believe they’re indestructible, so a fracture doesn’t have the implication that it should,” he added.

One patient, for example, for years resisted entreaties from his wife, a nurse, to “see someone” about his visibly rounded upper back.

Bob Grossman, 74, a retired public school teacher in Portland, blamed poor posture instead and told himself to straighten up. “I thought, ‘It can’t be osteoporosis — I’m a guy,’” he said. But it was.

Another obstacle to screening: “Clinical practice guidelines are all over the place,” Colón-Emeric said.

Professional associations like the Endocrine Society and the American Society for Bone and Mineral Research recommend that men 50 and older who have a risk factor, and all men over 70, .

But the and the have deemed the evidence for screening of men “insufficient.” Clinical trials have found that osteoporosis , as in women, but most male studies have been too small or lacked enough follow-up to show whether fractures also declined.

The task force’s position means that Medicare and many private insurers generally won’t cover screening for men who haven’t had a fracture, though they will cover care for men diagnosed with osteoporosis.

“Things have been stalled for decades,” Orwoll said.

So it may fall to older men themselves to ask their doctors about a DXA (pronounced DECKS-ah) scan, widely available at $100 to $300 out-of-pocket. Otherwise, because osteoporosis is typically asymptomatic, men (and women, who are also undertested and undertreated) don’t know their bones have deteriorated until one breaks.

“If you had a fracture after age 50, you should have a bone scan — that’s one of the key indicators,” Orwoll advised.

Other risk factors: falls, a family history of hip fractures, and a fairly long list of other health conditions including rheumatoid arthritis, hyperthyroidism and Parkinson’s disease. Smoking and excessive alcohol use increase the odds of osteoporosis as well.

“A number of medications also do a number on your bone density,” Colón-Emeric added, notably steroids and prostate cancer drugs.

When a scan reveals osteoporosis, depending on its severity, doctors may prescribe oral medications like Fosamax or Actonel, intravenous formulations like Reclast, daily self-injections of Forteo or Tymlos, or twice-annual injections of Prolia.

Lifestyle changes like exercising, taking calcium and vitamin D supplements, stopping smoking, and drinking only moderately will help but aren’t sufficient to stop or reverse bone loss, Colón-Emeric said.

Although guidelines don’t universally recommend it, at least not yet, she would like to see all men age 70 and up be screened, because the odds of disability after hip fractures are so high — two-thirds of older people will not regain their prior mobility, she noted — and the medications that treat it are effective and often inexpensive.

But that osteoporosis threatens men, too, has progressed “at a snail’s pace,” Orwoll said.

Klein remembers attending a seminar to instruct patients like him in using the drug Forteo. “I was the only male there,” he said.

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“I didn’t know what I was going to do, where I was going to go,” he told me, describing a period of crisis that began in 2017.

Seeking a change of venue, Rousseau moved to the mountains of North Carolina, the start of an extended period of wandering. Soon, a sense of emptiness enveloped him. He had no friends or hobbies — his work as a doctor had been all-consuming. Former colleagues didn’t get in touch, nor did he reach out.

His wife had passed away after a painful illness a decade earlier. Rousseau was estranged from one adult daughter and in only occasional contact with another. His isolation mounted as his three dogs, his most reliable companions, died.

Rousseau was completely alone — without friends, family, or a professional identity — and overcome by a sense of loss.

“I was a somewhat distinguished physician with a 60-page resume,” Rousseau, now 73, wrote in the Journal of the American Geriatrics Society in May. “Now, I’m ‘no one,’ a retired, forgotten old man who dithers away the days.”

In some ways, older men living alone are disadvantaged compared with older women in similar circumstances. Research shows that men tend to have fewer friends than women and be less inclined to make new friends. Often, they’re reluctant to ask for help.

“Men have a harder time being connected and reaching out,” said , a psychiatrist who directs the Harvard Study of Adult Development, which has traced the arc of hundreds of men’s lives over a span of more than eight decades. The men in the study who fared the worst, Waldinger said, “didn’t have friendships and things they were interested in — and couldn’t find them.” He recommends that men invest in their “social fitness” in addition to their physical fitness to ensure they have satisfying social interactions.

Slightly more than 1 in every 5 men ages 65 to 74 live alone, according to . That rises to nearly 1 in 4 for those 75 or older. Nearly 40% of these men are divorced, 31% are widowed, and 21% never married.

That’s a significant change from 2000, when only 1 in 6 older men lived by themselves. Longer life spans for men and rising rates are contributing to the trend. It’s difficult to find information about this group — which is dwarfed by the number of women who live alone — because it hasn’t been studied in depth. But psychologists and psychiatrists say these older men can be quite vulnerable.

When men are widowed, their health and well-being tend to decline more than women’s.

“Older men have a tendency to ruminate, to get into our heads with worries and fears and to feel more lonely and isolated,” said Jed Diamond, 80, a therapist and the author of “” and “.”

Add in the decline of civic institutions where men used to congregate — think of the Elks or the Shriners — and older men’s reduced ability to participate in athletic activities, and the result is a lack of stimulation and the loss of a sense of belonging.

Depression can ensue, fueling excessive alcohol use, accidents, or, in the most extreme cases, suicide. Of all age groups in the United States, men over age 75 have the , by far.

For this column, I spoke at length to several older men who live alone. All but two (who’d been divorced) were widowed. Their experiences don’t represent all men who live alone. But still, they’re revealing.

The first person I called was Art Koff, 88, of Chicago, a longtime marketing executive I’d known for several years. When I reached out in January, I learned that Koff’s wife, Norma, had died the year before, leaving him hobbled by grief. Uninterested in eating and beset by unremitting loneliness, Koff lost 45 pounds.

“I’ve had a long and wonderful life, and I have lots of family and lots of friends who are terrific,” Koff told me. But now, he said, “nothing is of interest to me any longer.”

“I’m not happy living this life,” he said.

Nine days later, I learned that Koff had died. His nephew, Alexander Koff, said he had passed out and was gone within a day. The death certificate cited “end stage protein calorie malnutrition” as the cause.

The transition from being coupled to being single can be profoundly disorienting for older men. Lodovico Balducci, 80, was married to his wife, Claudia, for 52 years before she died in October 2023. Balducci, a renowned physician known as the “patriarch of geriatric oncology,” in the Journal of the American Geriatrics Society, likening Claudia’s death to an “amputation.”

“I find myself talking to her all the time, most of the time in my head,” Balducci told me in a phone conversation. When I asked him whom he confides in, he admitted, “Maybe I don’t have any close friends.”

Disoriented and disorganized since Claudia died, he said his “anxiety has exploded.”

We spoke in late February. Two weeks later, Balducci moved from Tampa to New Orleans, to be near his son and daughter-in-law and their two teenagers.

“I am planning to help as much as possible with my grandchildren,” he said. “Life has to go on.”

Verne Ostrander, a carpenter in the small town of Willits, California, about 140 miles north of San Francisco, was reflective when I spoke with him, also in late February. His second wife, Cindy Morninglight, died four years ago after a long battle with cancer.

“Here I am, almost 80 years old — alone,” Ostrander said. “Who would have guessed?”

When Ostrander isn’t painting watercolors, composing music, or playing guitar, “I fall into this lonely state, and I cry quite a bit,” he told me. “I don’t ignore those feelings. I let myself feel them. It’s like therapy.”

Ostrander has lived in Willits for nearly 50 years and belongs to a men’s group and a couples’ group that’s been meeting for 20 years. He’s in remarkably good health and in close touch with his three adult children, who live within easy driving distance.

“The hard part of living alone is missing Cindy,” he told me. “The good part is the freedom to do whatever I want. My goal is to live another 20 to 30 years and become a better artist and get to know my kids when they get older.”

The Rev. Johnny Walker, 76, lives in a low-income apartment building in a financially challenged neighborhood on Chicago’s West Side. Twice divorced, he’s been on his own for five years. He, too, has close family connections. At least one of his several children and grandchildren checks in on him every day.

Walker says he had a life-changing religious conversion in 1993. Since then, he has depended on his faith and his church for a sense of meaning and community.

“It’s not hard being alone,” Walker said when I asked whether he was lonely. “I accept Christ in my life, and he said that he would never leave us or forsake us. When I wake up in the morning, that’s a new blessing. I just thank God that he has brought me this far.”

Waldinger recommended that men “make an effort every day to be in touch with people. Find what you love — golf, gardening, birdwatching, pickleball, working on a political campaign — and pursue it,” he said. “Put yourself in a situation where you’re going to see the same people over and over again. Because that’s the most natural way conversations get struck up and friendships start to develop.”

Rousseau, the retired South Carolina doctor, said he doesn’t think about the future much. After feeling lost for several years, he moved across the country to Jackson, Wyoming, in the summer of 2023. He embraced solitude, choosing a remarkably isolated spot to live — a 150-square-foot cabin with no running water and no bathroom, surrounded by 25,000 undeveloped acres of public and privately owned land.

“Yes, I’m still lonely, but the nature and the beauty here totally changed me and focused me on what’s really important,” he told me, describing a feeling of redemption in his solitude.

Rousseau realizes that the death of his parents and a very close friend in his childhood left him with a sense of loss that he kept at bay for most of his life. Now, he said, rather than denying his vulnerability, he’s trying to live with it. “There’s only so long you can put off dealing with all the things you’re trying to escape from.”

It’s not the life he envisioned, but it’s one that fits him, Rousseau said. He stays busy with volunteer activities — cleaning tanks and running tours at Jackson’s fish hatchery, serving as a part-time park ranger, and maintaining trails in nearby national forests. Those activities put him in touch with other people, mostly strangers, only intermittently.

What will happen to him when this way of living is no longer possible?

“I wish I had an answer, but I don’t,” Rousseau said. “I don’t see my daughters taking care of me. As far as someone else, I don’t think there’s anyone else who’s going to help me.”

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In ads on Google, Facebook, and elsewhere, testosterone telemedicine websites may promise a quick fix for sluggishness and low libido in men. But evidence for that is lacking, physicians said, and the midlife malaise for which testosterone is being touted as a solution is more likely caused by chronic medical conditions, poor diet, or a sedentary lifestyle. In fact, doctors — and the FDA recommends that all testosterone supplements carry a warning that they may increase the risk of heart attack and stroke.

Valid medical reasons do exist for treating some men with testosterone. The hormone as a medication has existed for decades, and today’s patients include , some transgender men who use it to help transition physically, and, sometimes, . It has also been used for decades by bodybuilders and athletes to .

However, online dispensaries can overplay the idea of what is sometimes called “male menopause,” or even “manopause,” to drive sales of highly profitable testosterone-boosting injectables, often ignoring safety guidelines that should prevent healthy men from using the hormone. Some of the websites target military veterans.

“I have seen ads online that do cross the line,” said , a physician and the chief academic officer for the Heart, Vascular, and Thoracic Institute at the Cleveland Clinic. “For mood and low energy, prescribing testosterone provides little to no benefit. They are promoting testosterone for indications that are not on the label.”

Testosterone telehealth websites almost all cite published in 2002 by New England Research Institutes scientists who found testosterone levels drop 1% a year in men over 40. , director of the Center for Reproductive Medicine and Andrology at the University of Muenster in Germany, said the data behind the statistic included older men in deteriorating health whose levels declined because of illnesses.

“Healthy men do not show a drop,” he said.

That 2002 study led to a flood of “low-T” ads on U.S. television — ads that were later banned in a that accused the pharmaceutical industry of exaggerating the low-T phenomenon to scare men into buying drugs. According to , the market for testosterone supplements stood at $1.85 billion in 2023.

The deluge of ads “has fueled demand for a largely uninsured product, allowing for high markups,” said , director of health policy at the USC Schaeffer Center for Health Policy & Economics and a research associate at the National Bureau of Economic Research. “The primary driver is manufactured demand.”

, a professor of evidence-based pharmaceutical policy at the University of Sydney’s Charles Perkins Centre in Australia, said low testosterone should really be seen as a sign of a condition that needs to be treated. She said diabetes, heart disease, high blood pressure, obesity, exposure to like PFAS, and stress can all reduce testosterone levels.

Several websites reviewed by Â鶹ŮÓÅ Health News brand themselves as news and fitness magazines, with advertisements embedded in articles steering readers toward order forms for testosterone replacement therapy, shorthanded as TRT. The sites’ prices for TRT range from $120 to $135 a month, not including initial mail-back blood tests for around $60. Some sites promise increased libido and reduced stomach fat.

Male Excel’s ads on Google, for example, say TRT “improves mood” and “restores vitality.” And its site says testosterone treatment will provide “muscular definition,” “weight loss,” “explosive drive,” “deeper sleep,” and “restored energy” above a link to a free assessment on its online telehealth platform. Craig Larsen, the company’s CEO, did not reply to several attempts to contact him by phone and email.

Both and are among the sites that pitch to military veterans. Hone Health included a video of a veteran who said he was treatment by a Department of Veterans Affairs hospital.

Saad Alam, CEO and co-founder of Hone, said that his company is what he called a “conservative” player in the market. He said that Hone prescribes only to men who are hypogonadal and tests men every 90 days, unlike other companies that operate telehealth websites as what he called a “cash grab.”

“I agree that patients should be treated by their doctors. But the U.S. medical system isn’t at a point where it can service men who have this problem, and some endocrinologists would rather treat patients who are higher-profit,” Hone said. “That’s why people are coming to us.”

One popular form of TRT is injectable testosterone cypionate. According to the Medicare average sales price database, it costs $0.027 per milligram. Online purveyors who sell the drug directly to consumers in 200 mg/mL vials for an average price of $129 per month are charging the equivalent of $1.55 per mg — a markup of more than 50 times the average Medicare price.

According to a , the TRT telehealth websites create a way to circumvent doctors who refuse to prescribe the hormone. In that study, , a urologist at the Memorial Healthcare System in Florida, posed as an online mystery shopper. He reported an above-normal testosterone level, and stated his desire to start a family, even though such therapy can curb sperm production. But six of the seven unnamed online TRT clinics prescribed him testosterone via a medical professional.

“And that’s concerning,” Dubin said. “Telemedicine helps men with hypogonadism who might be too embarrassed to discuss erectile dysfunction. But we need to do a better job of understanding the appropriateness of care.”

Still, while the FDA doesn’t allow off-label marketing, it does allow such off-label prescriptions.

Off-label use of testosterone replacement has become . And among male service members who received TRT in 2017, fewer than half met the clinical practice guidelines, according to a .

Phil Palmer, a 41-year-old Marine Corps veteran who lives outside Charleston, South Carolina, said he pays out-of-pocket for bloodwork and prescriptions for a pellet skin-implant form of testosterone and for , a drug that can help counter the male infertility that is a side effect of . He said the treatment appeals to him and other veterans dealing with the aftermath of military service.

“The environment we served in and stress levels have a lot to do with it,” Palmer said. “We were exposed to burn pits. The military doesn’t teach you to eat well — we ate a lot of processed food.”

In medical settings, TRT can speed recovery of soldiers who have bone density issues or spinal cord injuries, said , a professor of physical medicine and rehabilitation at the University of Michigan Medical School. But, he said, “for men in the normal-T range, using an online prescription to buy testosterone to reduce stomach fat can be counterproductive.”

Those who use it also risk having to , because TRT can cause the body to cease its own production of the hormone.

Palmer, who that helps veterans heal through exercise, nutrition, and mentorship, said the medication has been helpful for him but urges fellow veterans to seek care from their doctors rather than what he called “bro science” websites touting testosterone.

“It’s not a magic pill,” he said.

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The reasons for the gap are vexing, experts said, but may provide an important window into unique challenges faced by Black men as they try to gain not only good health but also an equal footing in the U.S.

Generally, higher education means better-paying jobs and health insurance, healthier behaviors and longer lives. This is true across many demographic groups. And studies show life expectancy is higher for educated Black men — those with a college degree or higher — compared with those who have not finished high school.

But the increase is not as big as it is for whites. This comes on top of the many health obstacles Black men already face. They are more likely to die from chronic illnesses like cardiovascular disease, diabetes and cancer than white men, and their life expectancy, on average, is lower. Experts point to a variety of factors that might play a role, but many said the most pervasive is racism.

Researchers note that Black women face many of the same challenges as Black men, but Black women generally have a longer life expectancy than Black men. (They also point out that it is hard to draw conclusions about Hispanic residents because of a lack of studies on the issues.) As a result, many experts said that the health problems stem from a persistent devaluation of Black men in U.S. society.

“At every level of income and education, there is still an effect of race,” said David Williams, a professor of public health at Harvard University who developed a scale nearly 30 years ago .

The precise difference in health gains between educated white men and educated Black men is hard to pinpoint because of differences in study designs. Some studies, for example, look at life expectancy, while others look at disease burden or depression.

Experts said, however, that the evidence is strong and convincing that these gaps have persisted over many years. A published in Health Affairs, for example, found that life expectancy for white men with the most education was 12.9 years longer than for white men with the least education. For Black men, the difference was 9.7 years.

In addition, other research shows how that gap plays out. A — years cut off because of health challenges — between the groups. Educated Black men lost 12.09 years, while educated white men lost 8.34 years, according to the study, published in the Journal of Health and Social Behavior.

Racism affects Black men’s health and it is persistent, experts said.

“No matter how far you go in school, no matter what you accomplish, you’re still a Black man,” said Derek Novacek, who has a doctorate in clinical psychology from Emory University and is researching Black-white health disparities at UCLA.

S. Jay Olshansky, a professor of epidemiology and biostatistics at the University of Illinois in Chicago and lead author of the 2012 study, said possible risk factors for various diseases and environmental issues could also play a role: “I’d be very surprised if this wasn’t part of the equation. The risk of diabetes and obesity is much higher among the Black population, even those that are highly educated.”

Among other possible causes that researchers are probing are stress and depression.

“When you follow other groups, with more education depression declines,” said Dr. Shervin Assari, associate professor of medicine at Charles R. Drew University of Medicine and Science in Los Angeles County, California, who studies race, gender and health. “But when you look at Black men — guess what? .”

Depression is often an indicator of physical well-being as well as a contributing factor to many chronic illnesses, such as hypertension, obesity and diabetes.

Isolated at Home and Work

Researchers who study the health of various racial and ethnic groups, as well as the social factors that influence health outcomes, see cause for concern. The findings suggest that the power of discrimination to harm Black men’s lives may be more persistent than previously understood. And they could mean that improving Black men’s health may be more complicated than previously believed.

“What has surprised me is how powerfully and consistently discrimination predicts poor health,” said Williams.

the issue. As early as last April researchers noticed higher death and hospitalization rates for Black people. The patterns have persisted, with Black patients being to die of the virus and Black men have the of covid deaths.

The covid outcomes, Williams and others suggested, helped point out that the health and well-being of middle-class, educated Black men have been overlooked.

Higher education hasn’t brought about the health equity many experts had expected. While Black men have worse health than other groups if they are not educated, they can’t catch up to their white peers even when they are.

“What society has done to Black men is to corner them,” Assari said.

Black men, even with an education, have less of a financial and social safety net than white men. That brings added stress, the experts said. Also, as Black men climb a corporate, academic or managerial ladder, many feel isolated. And social isolation harms health.

Thomas LaVeist, a sociologist and dean of the school of public health at Tulane University, said that in a white-dominated society Black men are less likely to have family members with high incomes or social and business connections who can open doors for them. And once hired into the workplace, they are less likely to have mentors, LaVeist said, and that lack of connections is associated with stress, depression and other factors that can lead to poorer health.

“There needs to be a designated effort to provide an on-ramp” for Black men, he said.

And they may have experienced more cumulative adversity and continued racism.

“Your high socioeconomic status doesn’t protect you from the impact or from the incidence” of racism, said Dr. Adrian Tyndall, associate vice president for strategic and academic affairs at University of Florida Health.

“That is difficult,” added Tyndall, who is Black. “If I were to walk out of this institution and into the community, where people don’t know me, I could be called the N-word. And yeah, that’s pretty depressing.”

The Need to Prove Yourself

The cumulative effect of discrimination takes a toll psychologically and physiologically — but so does the anticipation of it.

“It’s not just the actual exposure in dealing with these kinds of experiences, but it’s ‘What do you do before leaving home?’ You’re careful about your dress, your behavior, the way you look because of the threat of discrimination, and so you react,” said Williams, the Harvard professor.

For example, when Williams, who is Black, first became a professor at Yale University, he wore a coat and tie every day. No one else in his department did that. And yet, he said, he kept up the practice for years.

LaVeist remembers getting onto an elevator at an academic medical center around 1990, shortly after earning his Ph.D., and a passenger wearing a white coat — presumably a doctor — assumed LaVeist worked in housekeeping. The man asked LaVeist, who was dressed in a suit, to clean up a spill on the sixth floor.

“When I told him that I was a professor, he didn’t speak,” said LaVeist. “He simply didn’t speak.”

Greg Pennington, 67, of Atlanta, has a doctorate in clinical psychology from the University of North Carolina and an undergraduate degree from Harvard, owns a professional consulting firm and has worked with hundreds of men individually as well as dozens of Fortune 500 companies. “It’s not so much that [Black men] experience discrimination and depression ‘even after’ they have advanced degrees,” he said. “It’s more descriptive to say ‘throughout the whole process.’”

Despite their academic credentials, Black men said, they often feel they need to prove themselves, which adds another layer of stress.

“It’s almost like I can’t fail; I’m representative of other Black males,” said Woodrow W. Winchester III, director of professional engineering programs at the University of Maryland-Baltimore County. “Your value and your success are around advancing the collective.”

The bottom line, experts agreed, is that discrimination has a lingering effect on health.

Dana Goldman, director of the USC Schaeffer Center for Health Policy and Economics, was co-author of the 2012 Health Affairs study on these chasms. Goldman said he agrees that the underlying cause is racism and added that he thinks one solution is to improve education. He and others suggested that schools, starting in the lower grades, need to provide Black students with more culturally appropriate curricula that bolster their self-image and help build social relationships between white and Black youngsters. Those efforts need to continue as students progress into higher education.

“The policy remedy is not just less racism but to improve the quality of our schools, occupational safety and public health,” Goldman said.

Others agree that the findings suggest a need to reconsider broad policy changes — in education, housing and the justice system — so that Black males feel confident and supported in pursuing better educations and jobs. 

It will be a long-term project, said Williams, the Harvard professor.

“We need a Marshall Plan for all disenfranchised Americans,” he said, but one that especially addresses implicit biases and how American society views and treats Black males.

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But there’s one question she still can’t answer: What makes some patients so much sicker than others?

Advancing age and underlying medical problems explain only part of the phenomenon, said Ranney, who has seen patients of similar age, background and health status follow wildly different trajectories.

“Why does one 40-year-old get really sick and another one not even need to be admitted?” asked Ranney, an associate professor of emergency medicine at Brown University.

In some cases, provocative new research shows, some people — men in particular — succumb because their immune systems are hit by friendly fire. Researchers hope the finding will help them develop targeted therapies for these patients.

In in Science, 10% of nearly 1,000 COVID patients who developed life-threatening pneumonia had antibodies that disable key immune system proteins called interferons. These antibodies — known as autoantibodies because they attack the body itself — were not found at all in 663 people with mild or asymptomatic COVID infections. Only four of 1,227 healthy individuals had the autoantibodies. The study, published on Oct. 23, was led by the COVID Human Genetic Effort, which includes 200 research centers in 40 countries.

“This is one of the most important things we’ve learned about the immune system since the start of the pandemic,” said Dr. Eric Topol, executive vice president for research at Scripps Research in San Diego, who was not involved in the new study. “This is a breakthrough finding.”

In by the same team, authors found that an additional 3.5% of critically ill patients had mutations in genes that control the interferons involved in fighting viruses. Given that the body has 500 to 600 of these genes, it’s possible researchers will find more mutations, said Qian Zhang, lead author of the second study.

serve as the body’s first line of defense against infection, sounding the alarm and activating an army of virus-fighting genes, said virologist Angela Rasmussen, an associate research scientist at the Center of Infection and Immunity at Columbia University’s Mailman School of Public Health.

“Interferons are like a fire alarm and a sprinkler system all in one,” said Rasmussen, who wasn’t involved in the new studies.

show interferons are suppressed in some people with COVID-19, perhaps by the virus itself.

Interferons are particularly important for protecting the body against new viruses, such as the coronavirus, which the body has never encountered, said Zhang, a researcher at Rockefeller University’s St. Giles Laboratory of Human Genetics of Infectious Diseases.

When infected with the novel coronavirus, “your body should have alarms ringing everywhere,” said Zhang. “If you don’t get the alarm out, you could have viruses everywhere in large numbers.”

Significantly, patients didn’t make autoantibodies in response to the virus. Instead, they appeared to have had them before the pandemic even began, said Paul Bastard, the antibody study’s lead author, also a researcher at Rockefeller University.

For reasons that researchers don’t understand, the autoantibodies never caused a problem until patients were infected with COVID-19, Bastard said. Somehow, the novel coronavirus, or the immune response it triggered, appears to have set them in motion.

“Before COVID, their condition was silent,” Bastard said. “Most of them hadn’t gotten sick before.”

Bastard said he now wonders whether autoantibodies against interferon also increase the risk from other viruses, such as influenza. Among patients in his study, “some of them had gotten flu in the past, and we’re looking to see if the autoantibodies could have had an effect on flu.”

Scientists have long known that viruses and the immune system compete in a sort of arms race, with viruses evolving ways to evade the immune system and even suppress its response, said Sabra Klein, a professor of molecular microbiology and immunology at the Johns Hopkins Bloomberg School of Public Health.

Antibodies are usually the heroes of the immune system, defending the body against viruses and other threats. But sometimes, in a phenomenon known as autoimmune disease, the immune system appears confused and creates autoantibodies. This occurs in diseases such as when antibodies attack the joints, and , in which the immune system attacks insulin-producing cells in the pancreas.

Although doctors don’t know the exact causes of autoimmune disease, they’ve observed that the conditions often occur after . Autoimmune diseases are more common as people age.

In yet another unexpected finding, 94% of patients in the study with these autoantibodies were men. About 12.5% of men with life-threatening COVID pneumonia had autoantibodies against interferon, compared with 2.6% of women.

That was unexpected, given that autoimmune disease is far , Klein said.

“I’ve been studying sex differences in viral infections for 22 years, and I don’t think anybody who studies autoantibodies thought this would be a risk factor for COVID-19,” Klein said.

The study might help explain why men are more likely than women to become critically ill with COVID-19 and die, Klein said.

“You see significantly more men dying in their 30s, not just in their 80s,” she said.

Akiko Iwasaki, a professor of immunobiology at the Yale School of Medicine, noted that several genes involved in the immune system’s response to viruses are

Women have two copies of this chromosome — along with two copies of each gene. That gives women a backup in case one copy of a gene becomes defective, Iwasaki said.

Men, however, have only one copy of the X chromosome. So if there is a defect or harmful gene on the X chromosome, they have no other copy of that gene to correct the problem, Iwasaki said.

Bastard noted that one woman in the study who developed autoantibodies has a rare genetic condition in which she has only one X chromosome.

Scientists have struggled to explain why men have a higher risk of hospitalization and death from COVID-19. When the disease first appeared in China, experts speculated that men suffered more from the virus because they are much more likely to smoke than Chinese women.

Researchers quickly noticed that men in Spain were also more likely to die of COVID-19, however, even though men and women there smoke at about the same rate, Klein said.

Experts have hypothesized that men might be put at higher risk by being less likely to wear masks in public than women and more likely to delay seeking medical care, Klein said.

But behavioral differences between men and women provide only part of the answer. Scientists say it’s possible that the hormone estrogen may somehow protect women, while testosterone may put men at greater risk. Interestingly, recent studies have found that obesity poses a with COVID-19 than to women, Klein said.

Yet women have their own form of suffering from COVID-19.

Studies show women are more likely to experience long-term COVID symptoms, lasting weeks or months, including fatigue, weakness and a kind of mental confusion known as “brain fog,” Klein noted.

As women, “maybe we survive it and are less likely to die, but then we have all these long-term complications,” she said.

After reading the studies, Klein said, she would like to learn whether patients who become severely ill from other viruses, such as influenza, also harbor genes or antibodies that disable interferon.

“There’s no evidence for this in flu,” Klein said. “But we haven’t looked. Through COVID-19, we may have uncovered a very novel mechanism of disease, which we could find is present in a number of diseases.”

To be sure, scientists say that the new study solves only part of the mystery of why patient outcomes can vary so greatly.

Researchers say it’s possible that some patients are protected by past exposure to other coronaviruses. Patients who get very sick also may have inhaled higher doses of the virus, such as from repeated exposure to infected co-workers.

Although doctors have looked for links between disease outcomes and blood type, studies have produced .

Screening patients for autoantibodies against interferons could help predict which patients are more likely to become very sick, said Bastard, who is also affiliated with the Necker Hospital for Sick Children in Paris. Testing takes about two days. Hospitals in Paris can now screen patients on request from a doctor, he said.

Although only 10% of patients with life-threatening COVID-19 have autoantibodies, “I think we should give the test to everyone who is admitted,” Bastard said. Otherwise, “we wouldn’t know who is at risk for a severe form of the disease.”

Bastard said he hopes his findings will lead to new therapies that save lives. He notes that the body manufactures many types of interferons. Giving these patients a different type of interferon — one not disabled by their genes or autoantibodies — might help them fight off the virus.

In fact, a pilot study of 98 patients published Thursday in journal found benefits from an inhaled form of interferon. In the industry-funded British study, hospitalized COVID patients randomly assigned to receive interferon beta-1a were more than twice as likely as others to recover enough to resume their regular activities.

Researchers need to confirm these findings in a much larger study, said Dr. Nathan Peiffer-Smadja, a researcher at Imperial College London who was not involved in the study but wrote an accompanying editorial. Future studies should test patients’ blood for genetic mutations and autoantibodies against interferon, to see if they respond differently than others.

Peiffer-Smadja notes that inhaled interferon may work better than an injected form of the drug because it’s delivered directly to the lungs. While injected versions of interferon have been used for years to treat other diseases, the inhaled version is still experimental and not commercially available.

And doctors should be cautious about interferon for now, because a study led by the found no benefit to an injected form of the drug in COVID patients, Peiffer-Smadja said. In fact, there was a trend toward higher mortality rates in patients given interferon, although this finding could have been due to chance. Giving interferon later in the course of disease could encourage a destructive immune overreaction called a cytokine storm, in which the immune system does more damage than the virus.

Around the world, scientists have launched more than 100 clinical trials of interferons, according to , a database of research studies from the National Institutes of Health.

Until larger studies are completed, doctors say, Bastard’s findings are unlikely to change how they treat COVID-19.

Dr. Lewis Kaplan, president of the Society of Critical Care Medicine, said he treats patients according to their symptoms, not their risk factors.

“If you are a little sick, you get treated with a little bit of care,” Kaplan said. “You are really sick, you get a lot of care. But if a COVID patient comes in with hypertension, diabetes and obesity, we don’t say, ‘They have risk factors. Let’s put them in the ICU.’”

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The law, which took effect Jan. 1, mandates that insurers cover vasectomies without requiring patients to pay anything out-of-pocket — just as they must do for more than a dozen birth control methods for women.

But the measure may run afoul of Internal Revenue Service rules that do not include vasectomies among approved preventive services for high-deductible health plans. People with health savings accounts — which are exempt from tax liabilities — tied to those plans could no longer contribute to the savings accounts in that case.

Under the , insurers generally can’t charge patients a copayment or require any other cost sharing for prescription contraceptive drugs or devices approved by the Food and Drug Administration. The 2016 law is similar to what’s required under the federal Affordable Care Act, with a twist: It adds male sterilization — — to the list of services that are free for patients.

“While the ACA made important strides … it completely left men out of the equation,” said Karen Nelson, president and CEO of Planned Parenthood of Maryland, whose organization supported the bill.

Before the law took effect, a vasectomy at the organization’s Baltimore office would cost between $225 and $1,100, depending on someone’s ability to pay, said Nelson. Now the procedure will generally cost nothing for men in insured plans in Maryland.

The state law doesn’t apply to companies that are “self-funded,” meaning they pay their employees’ health care claims directly rather than buying state-regulated insurance policies.

Under IRS rules, consumers making tax-free contributions to health savings accounts (HSAs) that are linked to high-deductible health plans have to pay for all their medical care until they reach their deductible of at least in 2018. The only exception is for preventive services. The hitch for the Maryland law is that vasectomies aren’t on the IRS .

The IRS hasn’t responded to a by Maryland Insurance Commissioner Al Redmer Jr. A this year — after it failed to pass last year — that would exempt these high-deductible plans from the state mandate to cover vasectomies before the deductible is met. Such a move would preserve the tax advantages of the HSAs linked to them.

Maryland is joining a few other states, including , Vermont and, starting next year, , that have expanded contraceptive coverage without cost sharing to include male sterilization.

Vermont’s law includes language to exempt high-deductible plans with health savings accounts. While the issue has raised concerns in Maryland, in Illinois and Oregon it hasn’t appeared to generate much attention to date, legislative analysts say.

Some advocates for extending no-cost coverage to vasectomies noted that the IRS’ list of approved preventive services specifically says that it isn’t exhaustive.

But until the issue is clarified, “the safest thing to do is not make a contribution to your HSA,” said , a Maryland resident and president of HSA Consulting Services. Ramthun helped implement health savings accounts while working for the Treasury Department during the George W. Bush administration. He stressed that the uncertainty applies only to HSA contributions made after the law became effective in 2018, not to earlier contributions. The issue doesn’t affect people’s medical coverage.

Beyond the uncertainty around health savings account contributions, Maryland’s law requiring coverage of vasectomies without cost sharing addresses a gap in men’s preventive coverage.

“There are arguments to be made that male condoms and vasectomies have preventive benefits for both women and men, in terms of [sexually transmitted infection] prevention and preventing pregnancy,” said Mara Gandal-Powers, senior counsel at the National Women’s Law Center.

Seven percent of men ages 18 to 45 have had a vasectomy, according to a by researchers at Northwestern University. The prevalence increased to 16 percent among men ages 36 to 45. Men with higher incomes, higher education and a regular source of health care were more likely to have had the procedure, the study found.

The Maryland law doesn’t apply to the method of birth control that many men use: condoms. A by state Sen. John Astle, a Democrat, would expand the law to include condom coverage.

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A couple of years after his arrival, he broke his foot during a game and afraid of the cost, didn’t seek medical care.

“Some of my family warned me that if I went to the hospital and couldn’t pay the bill, I’d get a bad credit record,” said Uribe, 41, who made about $300 a week and had no health insurance. “I wanted to buy a car or a house someday.” Instead, he hobbled through workdays and stayed off the field for three years; the residual pain is sometimes disabling, even two decades later.

For reasons both economic and cultural, Hispanic men are loath to interact with the health system. Women across all races are more likely to seek care than men. But the gender gap in the Hispanic community is especially troubling to health care providers. Studies show that Latino men are than Latinas to get treatment.

That is true even though Hispanic men are more likely than non-Hispanic whites to be , have or have . tend to do so heavily, contributing to the group’s higher rates of and deaths from . Many take risky jobs such as construction workers and laborers, and are more likely to die from on-the-job injuries than other workers, show.

Hispanics’ share of the population is expected to widen from nearly a fifth now to a quarter by 2045. As that number grows, researchers worry that the nation could face costly consequences as long-ignored conditions lead to serious illness and disability.

“It could literally break the health care system,” said José Arévalo, board chairman of Latino Physicians of California, which represents Hispanic doctors and others who treat Latinos.

And now, some medical professionals fear the effects of President Donald Trump’s crackdown on illegal immigrants.

“When the community faces this kind of stress, I worry that people will do unhealthy things, like abuse alcohol, to deal with it,” said Kathleen Page, co-director of Centro SOL, a health center at Johns Hopkins Bayview Medical Center, and founder of the city’s Latino HIV Outreach Program. “That means they may not work as much,” she added. “They’ll have less money, which means they’re less likely to seek care.”

Welcomed by Baltimore officials, immigrants have driven the city’s Hispanic population, tripling it to 30,000 since 2000.

Here, as elsewhere, evidence suggests that for many Hispanic men, seeking health care is an extraordinary event. Hospital data show they are more likely than Hispanic women, white women and white men to go to the emergency room as their primary source of treatment — a sign that they wait until they’ve no choice but to get help.

Some care providers say medical institutions haven’t done enough to keep Hispanic men healthy, or to persuade them to get regular exams.

“There’s been an ongoing need for institutions to become more culturally attuned and aware of bias,” said Elena Rios, president of the National Hispanic Medical Association, which represents the nation’s 50,000 Latino physicians.

There are some significant differences in health risk and illness rates among Hispanic subgroups — Puerto Ricans are more likely to be smokers, for example. Compared with Hispanics born in the U.S., those born elsewhere have much lower rates of cancer, heart disease and high blood pressure. Overall, Hispanics live longer than whites.

But these advantages may be dissipating as Latinos and adopt unhealthy habits such as and diets high in fatty, processed foods.

“I tell people we live longer and suffer,” said Jane Delgado, a clinical psychologist and Cuban-American who serves as president of the National Alliance for Hispanic Health.

Researchers who investigate gaps in cancer testing have found that all ethnic groups and genders have seen a decrease in late-stage colon cancer diagnoses and deaths in recent years — except Hispanic men, who get screened at the lowest rates of any race or ethnic group.

Often, health problems arise after immigrants come up against an insurance barrier. A few years after Jose Cedillo came to Baltimore from Honduras, the 41-year-old cook noticed his legs were often numb or painful. Worried about finances, he eschewed treatment and continued to work, before finally going to a clinic where he was diagnosed with diabetes.

In the seven years since, his health has so deteriorated he can’t work, is frequently homeless and spends long stints in the hospital. As an immigrant who came to the U.S. illegally, he is not eligible for government-paid insurance or disability payments. And he can’t afford medicine. Instead, he said, “I’ll drink alcohol to numb the pain.”

Part of the problem is that Spanish speakers are underrepresented among medical professionals. After arriving here, Uribe’s family members frequently brought along an English-speaking nephew or niece when they could afford to see doctors. Otherwise, “we’d travel a long ways to find a doctor who spoke Spanish,” he said.

Hospitals frequently lack cultural understanding and bilingual staffing, administrators admit. Though Latinos make up nearly 20 percent of the population, only 5 percent of physicians and 7 percent of registered are Hispanic. That gap has widened as more Hispanics have come to this country during the past three decades, according to a UCLA study released in 2015.

“Too often, people don’t understand what you’re saying, they don’t know what you’re going to charge them, what dietary restrictions you might place upon them,” said James Page, vice president for diversity at Johns Hopkins Medicine. “It creates a trust issue for Hispanics. We’ve got to get better at serving them.”

That is particularly true in mental health. Only 1 percent of psychologists in the U.S. are Hispanic, meaning that Spanish-speaking men who do seek therapy will probably struggle to find it.

In Baltimore, there is only one Spanish-language support group for men who suffer from anxiety and depression, local psychologists and Latino advocates say. The city employs one Spanish-speaking substance abuse counselor. A small handful of bilingual social workers citywide offer reduced-rate counseling sessions, and only three psychiatrists offer therapy sessions conducted in Spanish.

For Peter Uribe, the key to maintaining his family’s health is getting help paying for care. His wife and brother both suffer from epileptic seizures, and his brother’s despondency caused Uribe to become depressed, he said. In 2015, he obtained insurance for his family through a charity program. With the help of now-affordable medicines, his wife’s seizures waned, and he sought help for chronic depression. Since he now speaks English, finding counseling help is easier.

In January, after intervention from a Latino advocacy group, the charity renewed the Uribes’ policy for two years. Peter Uribe calls it a godsend:

“I honestly have no idea what we’d do without it.”

Michael Anft is a Baltimore-based journalist and writer whose work regularly appears in AARP: The Magazine, The Chronicle of Higher Education and other publications. Daniel Trielli, a data journalist at Capital News Service at the Philip Merrill College of Journalism, contributed to this report.

supports KHN’s coverage of health disparities in East Baltimore.

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I keep seeing featuring young people asking their parents why they didn’t get the vaccine to protect against the human papillomavirus — HPV. If you’re unfamiliar with HPV, it’s a sexually transmitted infection that has been linked to various cancers, including cervical cancer in women.

I didn’t get vaccinated. So lately I’ve been wondering: Now that I’m 29, is it too late for me to get the vaccine?

I found out about HPV eight years ago when a college girlfriend got immunized. Back then, the Centers for Disease Control and Prevention only recommended the vaccine for girls and young women between the ages of 11 and 26. , they said, to try to reach girls before they become sexually active. The vaccine is also more effective at a younger age.

At the time, I remember thinking that limiting it to females was strange — after all, males still spread HPV, right? But with my partner vaccinated, I let it go. I didn’t know HPV could cause health problems for men.

But HPV absolutely affects men. It causes genital warts and is as a leading cause of cancers in the back of the mouth and throat, the area called the oropharynx. The CDC now estimates about 70 percent of all may be caused by HPV, including roughly 12,600 cases in men each year.

“There are now more oropharynx cancers in men in the United States each year than there are cervical cancers in women,” said , a surgeon and researcher at the University of Texas MD Anderson Cancer Center in Houston.

And there’s no way to screen for oropharyngeal cancer, so Sturgis says most people catch it late.

“Typically it’s a man, while he’s shaving,” said Sturgis. “He notices a lump in his neck. That means it’s already a cancer that has spread.”

HPV also puts men at risk for cancers of the anus and penis. Those are rare, but still make me anxious.

So, for men like me who missed the vaccine, is it still worth it?

The answer is complicated. In 2011, the CDC began recommending the vaccine for males ages 11 through 21 years old (26 for some high-risk groups).

Despite my age, researchers I talked to said that the vaccine could still help — if I haven’t already been exposed.

But therein lies a complication. An estimated of sexually active people will be exposed to HPV by age 45. In most people, the virus goes away on its own after two years. For men, there’s no commercially available test to find out if you have been exposed. Women can be checked for HPV exposure as part of a Pap test.

To have 80 percent of sexually active young adults exposed sounds bleak. But there’s a caveat: “There are several dozen types of HPV that infect the genital region,” said psychologist , who co-directs the Center for HPV Research in Indianapolis. Only a fraction of those cause cancer or warts, and the latest version of the vaccine Gardasil protects against nine of those HPV types — the ones responsible for a vast majority of HPV-related problems.

So let’s say — hypothetically — you’re kind of shy and haven’t had that many partners. Is it possible you’ve been spared?

“The chances you’ve been exposed to all nine types are actually vanishingly small,” said , a microbiologist who studies HPV and HPV vaccines at the National Cancer Institute.

Schiller said the vaccine might not be a bad idea for someone outside the CDC’s recommended age range. Still, it’s not cheap.

“You’re past the age where your health insurance is going to pay for it,” said Schiller, so getting the vaccine isn’t imperative — it’s a personal decision.

“Peace of mind for you may be worth more than it is for some other people,” he told me.

So, I got the vaccine. It’s costing $130 out of pocket per dose, and the CDC recommends three shots. But it could help me, even if it just calms my anxious inner voice. And it might keep me from spreading the virus to someone else.

This story is part of a partnership that includes , and Kaiser Health News.

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That’s the good news. Unfortunately, according to from the Government Accountability Office, NIH can’t tell whether researchers are also examining outcomes by sex to see whether men and women are affected differently by what’s being tested.

That’s important because, for example, a drug or dosage appropriate for a man might be less effective or even lead to harm when taken by a woman.

But NIH does not make available usable information on which studies have separated results by sex and what those results are. NIH “does not maintain, analyze or report summary data to oversee whether analysis of outcomes by sex are planned or conducted,” the report found.

This is not the first time the GAO has criticized NIH for its implementation of the requirement to include women in research trials. In 2000, the agency needed to do a better job ensuring “that certain clinical trials be designed and carried out to permit valid analysis by sex.” Once again, NIH officials are promising to do better. The agency has 60 days to formally respond to the new report.

Meanwhile, those who fought to require parity in clinical trials have been left sputtering.

“It’s just very frustrating,” said former Rep. Patricia Schroeder of Colorado. “It reminds me of when you ask your children to move the clothes from the washer to the dryer. Then you go back and the clothes are still wet and they say, ‘Well you didn’t tell me to turn the dryer on.’”

Schroeder said she got interested in the subject in the early 1990s when studies came out showing that a daily aspirin could prevent heart attacks — and when she learned that all the test subjects had been men. “They didn’t even use female rats,” she said.

In fact, under  from the Food and Drug Administration that were not changed until 1993, women of childbearing age were not even allowed to participate in drug trials, largely in response to serious birth defects that arose after drugs like thalidomide and DES were used by women.

Pushed by a group of women members of Congress, including Schroeder, the requirement to include women in clinical trials was written into law as part of a signed by President Bill Clinton.

But even as more women are being included in clinical trials, there is growing scientific evidence of just how biologically different men and women are, and how differently they sometimes react to drugs and other medical interventions.

“We’re finally able to include women well enough to understand that they express disease differently, that certain risk for disease was different and certain outcomes for disease were different,” said Paula Johnson, a professor at Harvard Medical School and head of the Connors Center for Women’s Health and Gender Biology at Brigham and Women’s Hospital in Boston.

Heart disease, Alzheimer’s and lung cancer are examples of how are affected in different ways, she said. “But they’re just examples; these differences occur across all diseases where we’ve asked the question.”

Indeed, in 2013 the for the popular sleeping pill Ambien after it became clear that the drug took longer to leave women’s systems and could pose a danger the next morning.

Other research has shown that biological differences go to the most basic level.

“The truth of the matter is men and women are very different at the cellular level, at the molecular level, at the systemic level,” said Doris Taylor, director of regenerative medicine research at Texas Heart Institute.

Taylor, who has been studying the use of stem cells to treat heart disease, said that “we got very different results if you gave male cells or female cells.”

Given the significant differences recently discovered, it’s actually dangerous not to stratify research results by sex, experts say.

“If you’re mixing those results [from men and women], there will be more noise in the system,” Taylor said. “And you’re going to miss what you might otherwise see as an effect or lack of effect. That is the danger.”

Leaders at the NIH say they agree with the GAO’s recommendations and will try to do better. But, as usual in science, it’s complicated.

“It’s a problem because we don’t get to understand whether treatments work as well in women as they do in men, and when things are not reported separately by sex, we also don’t get to see whether there might be some indication of differences in toxicity or adverse events,” said Dr. Janine Clayton, head of the NIH .

One big problem, said Clayton, is the lack of information on differences by sex reported in leading medical journals. Of the large clinical trials described in journals, she said, “fewer than one-third had any sex-specific information in the publication.”

Often that’s because the numbers are so small that the results may not be statistically significant, “and it’s difficult to publish non-statistically significant results,” Taylor said.

But if those results are somehow made available, researchers could combine them together into what’s called a . “We’ve been trying to work with the journal editors for many years on this,” Clayton said.

Another problem is that NIH is not the only funder of medical research. Private industry, including pharmaceutical companies, pays for many — if not most — later-stage clinical studies. Privately funded studies also do not follow all NIH rules.

Meanwhile, in light of recent discoveries about biological differences by sex, Clayton says NIH is moving to require more basic, pre-clinical studies to , in an effort “to make sure that sex as a biological variable is accounted for in the design, analysis and reporting” of all research funded by the agency. That requirement takes effect in January.

Clayton, however, said she cannot discuss exactly what the agency will do to ensure better reporting by sex of the results of later trials involving humans. She said that will be included in the agency’s formal response to the GAO report.

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As the bike toppled, he thrust out his left arm to break the fall. It didn’t seem like a serious accident, yet “I couldn’t get up,” he said.

At the emergency room, X-rays showed that he had fractured both his hip, which required surgical repair, and his shoulder. Klein, a dentist, went back to work in three weeks, using a cane. After about six months and plenty of physical therapy, he felt fine.

But he wondered about the damage the fall had caused. “A 52-year-old is not supposed to break a hip and a shoulder,” he said. At a follow-up visit with his orthopedist, “I said, ‘Maybe I should have a bone density scan.’”

As Klein suspected, the test showed he had developed osteoporosis, a progressive condition, increasing sharply with age, that thins and weakens bones and can lead to serious fractures. Klein immediately began a drug regimen and, now 70, remains on one.

Osteoporosis occurs so much more commonly in women, for whom medical guidelines recommend , that a man who was not a health care professional might not have thought about getting a scan. The orthopedist didn’t raise the prospect.

But about will suffer an osteoporotic fracture in their remaining years, and among older adults, about .

When they do, “men have worse outcomes,” said Cathleen Colón-Emeric, a geriatrician at the Durham VA Health Care System and Duke University and the lead author of a recent study of osteoporosis treatment in male veterans.

“Men don’t do as well in recovery as women,” she said, with (25% to 30% within a year), disability and institutionalization. “A 50-year-old man is more likely to die from the complications of a major osteoporotic fracture than from prostate cancer,” she said.

(What’s “major”? Fractures of the wrist, hip, femur, humerus, pelvis or vertebra.)

In her ages 65 to 85, conducted at Veterans Affairs health centers in North Carolina and Virginia, only 2% of those assigned to the control group had undergone bone-density screening.

“Shockingly low,” said Douglas Bauer, a clinical epidemiologist and osteoporosis researcher at the University of California-San Francisco, who published in JAMA Internal Medicine. “Abysmal. And that’s at the VA, where it’s paid for by the government.”

But establishing a bone health service — overseen by a nurse who entered orders, sent frequent appointment reminders and explained results — led to dramatic changes in the intervention group, who had at least one risk factor for the condition.

Forty-nine percent of them said yes to a scan. Half of those tested had osteoporosis or a forerunner condition, osteopenia. Where appropriate, most of them began medications to preserve or rebuild their bones.

“We were pleasantly surprised that so many agreed to be screened and were willing to initiate treatment,” Colón-Emeric said.

After 18 months, bone density had increased modestly for those in the intervention group, who were more likely to stick to their drug regimens than osteoporosis patients of either sex in real-world conditions.

The study didn’t continue long enough to determine whether bone density increased further or fractures declined, but the researchers plan a secondary analysis to track that.

The results revive a longtime question: Given how life-altering, even deadly, such fractures can be, and the availability of effective drugs to slow or reverse bone loss, should older men be screened for osteoporosis, as women are? If so, which men and when?

Such issues mattered less when life spans were shorter, Bauer explained. Men have bigger and thicker bones and tend to develop osteoporosis five to 10 years later than women do. “Until recently, those men died of heart disease and smoking” before osteoporosis could harm them, he said.

“Now, men routinely live into their 70s and 80s, so they have fractures,” he added. By then, they have also accumulated other chronic conditions that impair their ability to recover.

With osteoporosis testing and treatment, “a man could see a clear-cut improvement in mortality and, more importantly, his quality of life,” Bauer said.

Both patients and many doctors still tend to regard osteoporosis as a women’s disease, however. “There’s a bit of a Superman idea,” said Eric Orwoll, an endocrinologist and osteoporosis researcher at Oregon Health & Science University.

“Men would like to believe they’re indestructible, so a fracture doesn’t have the implication that it should,” he added.

One patient, for example, for years resisted entreaties from his wife, a nurse, to “see someone” about his visibly rounded upper back.

Bob Grossman, 74, a retired public school teacher in Portland, blamed poor posture instead and told himself to straighten up. “I thought, ‘It can’t be osteoporosis — I’m a guy,’” he said. But it was.

Another obstacle to screening: “Clinical practice guidelines are all over the place,” Colón-Emeric said.

Professional associations like the Endocrine Society and the American Society for Bone and Mineral Research recommend that men 50 and older who have a risk factor, and all men over 70, .

But the and the have deemed the evidence for screening of men “insufficient.” Clinical trials have found that osteoporosis , as in women, but most male studies have been too small or lacked enough follow-up to show whether fractures also declined.

The task force’s position means that Medicare and many private insurers generally won’t cover screening for men who haven’t had a fracture, though they will cover care for men diagnosed with osteoporosis.

“Things have been stalled for decades,” Orwoll said.

So it may fall to older men themselves to ask their doctors about a DXA (pronounced DECKS-ah) scan, widely available at $100 to $300 out-of-pocket. Otherwise, because osteoporosis is typically asymptomatic, men (and women, who are also undertested and undertreated) don’t know their bones have deteriorated until one breaks.

“If you had a fracture after age 50, you should have a bone scan — that’s one of the key indicators,” Orwoll advised.

Other risk factors: falls, a family history of hip fractures, and a fairly long list of other health conditions including rheumatoid arthritis, hyperthyroidism and Parkinson’s disease. Smoking and excessive alcohol use increase the odds of osteoporosis as well.

“A number of medications also do a number on your bone density,” Colón-Emeric added, notably steroids and prostate cancer drugs.

When a scan reveals osteoporosis, depending on its severity, doctors may prescribe oral medications like Fosamax or Actonel, intravenous formulations like Reclast, daily self-injections of Forteo or Tymlos, or twice-annual injections of Prolia.

Lifestyle changes like exercising, taking calcium and vitamin D supplements, stopping smoking, and drinking only moderately will help but aren’t sufficient to stop or reverse bone loss, Colón-Emeric said.

Although guidelines don’t universally recommend it, at least not yet, she would like to see all men age 70 and up be screened, because the odds of disability after hip fractures are so high — two-thirds of older people will not regain their prior mobility, she noted — and the medications that treat it are effective and often inexpensive.

But that osteoporosis threatens men, too, has progressed “at a snail’s pace,” Orwoll said.

Klein remembers attending a seminar to instruct patients like him in using the drug Forteo. “I was the only male there,” he said.

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“I didn’t know what I was going to do, where I was going to go,” he told me, describing a period of crisis that began in 2017.

Seeking a change of venue, Rousseau moved to the mountains of North Carolina, the start of an extended period of wandering. Soon, a sense of emptiness enveloped him. He had no friends or hobbies — his work as a doctor had been all-consuming. Former colleagues didn’t get in touch, nor did he reach out.

His wife had passed away after a painful illness a decade earlier. Rousseau was estranged from one adult daughter and in only occasional contact with another. His isolation mounted as his three dogs, his most reliable companions, died.

Rousseau was completely alone — without friends, family, or a professional identity — and overcome by a sense of loss.

“I was a somewhat distinguished physician with a 60-page resume,” Rousseau, now 73, wrote in the Journal of the American Geriatrics Society in May. “Now, I’m ‘no one,’ a retired, forgotten old man who dithers away the days.”

In some ways, older men living alone are disadvantaged compared with older women in similar circumstances. Research shows that men tend to have fewer friends than women and be less inclined to make new friends. Often, they’re reluctant to ask for help.

“Men have a harder time being connected and reaching out,” said , a psychiatrist who directs the Harvard Study of Adult Development, which has traced the arc of hundreds of men’s lives over a span of more than eight decades. The men in the study who fared the worst, Waldinger said, “didn’t have friendships and things they were interested in — and couldn’t find them.” He recommends that men invest in their “social fitness” in addition to their physical fitness to ensure they have satisfying social interactions.

Slightly more than 1 in every 5 men ages 65 to 74 live alone, according to . That rises to nearly 1 in 4 for those 75 or older. Nearly 40% of these men are divorced, 31% are widowed, and 21% never married.

That’s a significant change from 2000, when only 1 in 6 older men lived by themselves. Longer life spans for men and rising rates are contributing to the trend. It’s difficult to find information about this group — which is dwarfed by the number of women who live alone — because it hasn’t been studied in depth. But psychologists and psychiatrists say these older men can be quite vulnerable.

When men are widowed, their health and well-being tend to decline more than women’s.

“Older men have a tendency to ruminate, to get into our heads with worries and fears and to feel more lonely and isolated,” said Jed Diamond, 80, a therapist and the author of “” and “.”

Add in the decline of civic institutions where men used to congregate — think of the Elks or the Shriners — and older men’s reduced ability to participate in athletic activities, and the result is a lack of stimulation and the loss of a sense of belonging.

Depression can ensue, fueling excessive alcohol use, accidents, or, in the most extreme cases, suicide. Of all age groups in the United States, men over age 75 have the , by far.

For this column, I spoke at length to several older men who live alone. All but two (who’d been divorced) were widowed. Their experiences don’t represent all men who live alone. But still, they’re revealing.

The first person I called was Art Koff, 88, of Chicago, a longtime marketing executive I’d known for several years. When I reached out in January, I learned that Koff’s wife, Norma, had died the year before, leaving him hobbled by grief. Uninterested in eating and beset by unremitting loneliness, Koff lost 45 pounds.

“I’ve had a long and wonderful life, and I have lots of family and lots of friends who are terrific,” Koff told me. But now, he said, “nothing is of interest to me any longer.”

“I’m not happy living this life,” he said.

Nine days later, I learned that Koff had died. His nephew, Alexander Koff, said he had passed out and was gone within a day. The death certificate cited “end stage protein calorie malnutrition” as the cause.

The transition from being coupled to being single can be profoundly disorienting for older men. Lodovico Balducci, 80, was married to his wife, Claudia, for 52 years before she died in October 2023. Balducci, a renowned physician known as the “patriarch of geriatric oncology,” in the Journal of the American Geriatrics Society, likening Claudia’s death to an “amputation.”

“I find myself talking to her all the time, most of the time in my head,” Balducci told me in a phone conversation. When I asked him whom he confides in, he admitted, “Maybe I don’t have any close friends.”

Disoriented and disorganized since Claudia died, he said his “anxiety has exploded.”

We spoke in late February. Two weeks later, Balducci moved from Tampa to New Orleans, to be near his son and daughter-in-law and their two teenagers.

“I am planning to help as much as possible with my grandchildren,” he said. “Life has to go on.”

Verne Ostrander, a carpenter in the small town of Willits, California, about 140 miles north of San Francisco, was reflective when I spoke with him, also in late February. His second wife, Cindy Morninglight, died four years ago after a long battle with cancer.

“Here I am, almost 80 years old — alone,” Ostrander said. “Who would have guessed?”

When Ostrander isn’t painting watercolors, composing music, or playing guitar, “I fall into this lonely state, and I cry quite a bit,” he told me. “I don’t ignore those feelings. I let myself feel them. It’s like therapy.”

Ostrander has lived in Willits for nearly 50 years and belongs to a men’s group and a couples’ group that’s been meeting for 20 years. He’s in remarkably good health and in close touch with his three adult children, who live within easy driving distance.

“The hard part of living alone is missing Cindy,” he told me. “The good part is the freedom to do whatever I want. My goal is to live another 20 to 30 years and become a better artist and get to know my kids when they get older.”

The Rev. Johnny Walker, 76, lives in a low-income apartment building in a financially challenged neighborhood on Chicago’s West Side. Twice divorced, he’s been on his own for five years. He, too, has close family connections. At least one of his several children and grandchildren checks in on him every day.

Walker says he had a life-changing religious conversion in 1993. Since then, he has depended on his faith and his church for a sense of meaning and community.

“It’s not hard being alone,” Walker said when I asked whether he was lonely. “I accept Christ in my life, and he said that he would never leave us or forsake us. When I wake up in the morning, that’s a new blessing. I just thank God that he has brought me this far.”

Waldinger recommended that men “make an effort every day to be in touch with people. Find what you love — golf, gardening, birdwatching, pickleball, working on a political campaign — and pursue it,” he said. “Put yourself in a situation where you’re going to see the same people over and over again. Because that’s the most natural way conversations get struck up and friendships start to develop.”

Rousseau, the retired South Carolina doctor, said he doesn’t think about the future much. After feeling lost for several years, he moved across the country to Jackson, Wyoming, in the summer of 2023. He embraced solitude, choosing a remarkably isolated spot to live — a 150-square-foot cabin with no running water and no bathroom, surrounded by 25,000 undeveloped acres of public and privately owned land.

“Yes, I’m still lonely, but the nature and the beauty here totally changed me and focused me on what’s really important,” he told me, describing a feeling of redemption in his solitude.

Rousseau realizes that the death of his parents and a very close friend in his childhood left him with a sense of loss that he kept at bay for most of his life. Now, he said, rather than denying his vulnerability, he’s trying to live with it. “There’s only so long you can put off dealing with all the things you’re trying to escape from.”

It’s not the life he envisioned, but it’s one that fits him, Rousseau said. He stays busy with volunteer activities — cleaning tanks and running tours at Jackson’s fish hatchery, serving as a part-time park ranger, and maintaining trails in nearby national forests. Those activities put him in touch with other people, mostly strangers, only intermittently.

What will happen to him when this way of living is no longer possible?

“I wish I had an answer, but I don’t,” Rousseau said. “I don’t see my daughters taking care of me. As far as someone else, I don’t think there’s anyone else who’s going to help me.”

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In ads on Google, Facebook, and elsewhere, testosterone telemedicine websites may promise a quick fix for sluggishness and low libido in men. But evidence for that is lacking, physicians said, and the midlife malaise for which testosterone is being touted as a solution is more likely caused by chronic medical conditions, poor diet, or a sedentary lifestyle. In fact, doctors — and the FDA recommends that all testosterone supplements carry a warning that they may increase the risk of heart attack and stroke.

Valid medical reasons do exist for treating some men with testosterone. The hormone as a medication has existed for decades, and today’s patients include , some transgender men who use it to help transition physically, and, sometimes, . It has also been used for decades by bodybuilders and athletes to .

However, online dispensaries can overplay the idea of what is sometimes called “male menopause,” or even “manopause,” to drive sales of highly profitable testosterone-boosting injectables, often ignoring safety guidelines that should prevent healthy men from using the hormone. Some of the websites target military veterans.

“I have seen ads online that do cross the line,” said , a physician and the chief academic officer for the Heart, Vascular, and Thoracic Institute at the Cleveland Clinic. “For mood and low energy, prescribing testosterone provides little to no benefit. They are promoting testosterone for indications that are not on the label.”

Testosterone telehealth websites almost all cite published in 2002 by New England Research Institutes scientists who found testosterone levels drop 1% a year in men over 40. , director of the Center for Reproductive Medicine and Andrology at the University of Muenster in Germany, said the data behind the statistic included older men in deteriorating health whose levels declined because of illnesses.

“Healthy men do not show a drop,” he said.

That 2002 study led to a flood of “low-T” ads on U.S. television — ads that were later banned in a that accused the pharmaceutical industry of exaggerating the low-T phenomenon to scare men into buying drugs. According to , the market for testosterone supplements stood at $1.85 billion in 2023.

The deluge of ads “has fueled demand for a largely uninsured product, allowing for high markups,” said , director of health policy at the USC Schaeffer Center for Health Policy & Economics and a research associate at the National Bureau of Economic Research. “The primary driver is manufactured demand.”

, a professor of evidence-based pharmaceutical policy at the University of Sydney’s Charles Perkins Centre in Australia, said low testosterone should really be seen as a sign of a condition that needs to be treated. She said diabetes, heart disease, high blood pressure, obesity, exposure to like PFAS, and stress can all reduce testosterone levels.

Several websites reviewed by Â鶹ŮÓÅ Health News brand themselves as news and fitness magazines, with advertisements embedded in articles steering readers toward order forms for testosterone replacement therapy, shorthanded as TRT. The sites’ prices for TRT range from $120 to $135 a month, not including initial mail-back blood tests for around $60. Some sites promise increased libido and reduced stomach fat.

Male Excel’s ads on Google, for example, say TRT “improves mood” and “restores vitality.” And its site says testosterone treatment will provide “muscular definition,” “weight loss,” “explosive drive,” “deeper sleep,” and “restored energy” above a link to a free assessment on its online telehealth platform. Craig Larsen, the company’s CEO, did not reply to several attempts to contact him by phone and email.

Both and are among the sites that pitch to military veterans. Hone Health included a video of a veteran who said he was treatment by a Department of Veterans Affairs hospital.

Saad Alam, CEO and co-founder of Hone, said that his company is what he called a “conservative” player in the market. He said that Hone prescribes only to men who are hypogonadal and tests men every 90 days, unlike other companies that operate telehealth websites as what he called a “cash grab.”

“I agree that patients should be treated by their doctors. But the U.S. medical system isn’t at a point where it can service men who have this problem, and some endocrinologists would rather treat patients who are higher-profit,” Hone said. “That’s why people are coming to us.”

One popular form of TRT is injectable testosterone cypionate. According to the Medicare average sales price database, it costs $0.027 per milligram. Online purveyors who sell the drug directly to consumers in 200 mg/mL vials for an average price of $129 per month are charging the equivalent of $1.55 per mg — a markup of more than 50 times the average Medicare price.

According to a , the TRT telehealth websites create a way to circumvent doctors who refuse to prescribe the hormone. In that study, , a urologist at the Memorial Healthcare System in Florida, posed as an online mystery shopper. He reported an above-normal testosterone level, and stated his desire to start a family, even though such therapy can curb sperm production. But six of the seven unnamed online TRT clinics prescribed him testosterone via a medical professional.

“And that’s concerning,” Dubin said. “Telemedicine helps men with hypogonadism who might be too embarrassed to discuss erectile dysfunction. But we need to do a better job of understanding the appropriateness of care.”

Still, while the FDA doesn’t allow off-label marketing, it does allow such off-label prescriptions.

Off-label use of testosterone replacement has become . And among male service members who received TRT in 2017, fewer than half met the clinical practice guidelines, according to a .

Phil Palmer, a 41-year-old Marine Corps veteran who lives outside Charleston, South Carolina, said he pays out-of-pocket for bloodwork and prescriptions for a pellet skin-implant form of testosterone and for , a drug that can help counter the male infertility that is a side effect of . He said the treatment appeals to him and other veterans dealing with the aftermath of military service.

“The environment we served in and stress levels have a lot to do with it,” Palmer said. “We were exposed to burn pits. The military doesn’t teach you to eat well — we ate a lot of processed food.”

In medical settings, TRT can speed recovery of soldiers who have bone density issues or spinal cord injuries, said , a professor of physical medicine and rehabilitation at the University of Michigan Medical School. But, he said, “for men in the normal-T range, using an online prescription to buy testosterone to reduce stomach fat can be counterproductive.”

Those who use it also risk having to , because TRT can cause the body to cease its own production of the hormone.

Palmer, who that helps veterans heal through exercise, nutrition, and mentorship, said the medication has been helpful for him but urges fellow veterans to seek care from their doctors rather than what he called “bro science” websites touting testosterone.

“It’s not a magic pill,” he said.

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The reasons for the gap are vexing, experts said, but may provide an important window into unique challenges faced by Black men as they try to gain not only good health but also an equal footing in the U.S.

Generally, higher education means better-paying jobs and health insurance, healthier behaviors and longer lives. This is true across many demographic groups. And studies show life expectancy is higher for educated Black men — those with a college degree or higher — compared with those who have not finished high school.

But the increase is not as big as it is for whites. This comes on top of the many health obstacles Black men already face. They are more likely to die from chronic illnesses like cardiovascular disease, diabetes and cancer than white men, and their life expectancy, on average, is lower. Experts point to a variety of factors that might play a role, but many said the most pervasive is racism.

Researchers note that Black women face many of the same challenges as Black men, but Black women generally have a longer life expectancy than Black men. (They also point out that it is hard to draw conclusions about Hispanic residents because of a lack of studies on the issues.) As a result, many experts said that the health problems stem from a persistent devaluation of Black men in U.S. society.

“At every level of income and education, there is still an effect of race,” said David Williams, a professor of public health at Harvard University who developed a scale nearly 30 years ago .

The precise difference in health gains between educated white men and educated Black men is hard to pinpoint because of differences in study designs. Some studies, for example, look at life expectancy, while others look at disease burden or depression.

Experts said, however, that the evidence is strong and convincing that these gaps have persisted over many years. A published in Health Affairs, for example, found that life expectancy for white men with the most education was 12.9 years longer than for white men with the least education. For Black men, the difference was 9.7 years.

In addition, other research shows how that gap plays out. A — years cut off because of health challenges — between the groups. Educated Black men lost 12.09 years, while educated white men lost 8.34 years, according to the study, published in the Journal of Health and Social Behavior.

Racism affects Black men’s health and it is persistent, experts said.

“No matter how far you go in school, no matter what you accomplish, you’re still a Black man,” said Derek Novacek, who has a doctorate in clinical psychology from Emory University and is researching Black-white health disparities at UCLA.

S. Jay Olshansky, a professor of epidemiology and biostatistics at the University of Illinois in Chicago and lead author of the 2012 study, said possible risk factors for various diseases and environmental issues could also play a role: “I’d be very surprised if this wasn’t part of the equation. The risk of diabetes and obesity is much higher among the Black population, even those that are highly educated.”

Among other possible causes that researchers are probing are stress and depression.

“When you follow other groups, with more education depression declines,” said Dr. Shervin Assari, associate professor of medicine at Charles R. Drew University of Medicine and Science in Los Angeles County, California, who studies race, gender and health. “But when you look at Black men — guess what? .”

Depression is often an indicator of physical well-being as well as a contributing factor to many chronic illnesses, such as hypertension, obesity and diabetes.

Isolated at Home and Work

Researchers who study the health of various racial and ethnic groups, as well as the social factors that influence health outcomes, see cause for concern. The findings suggest that the power of discrimination to harm Black men’s lives may be more persistent than previously understood. And they could mean that improving Black men’s health may be more complicated than previously believed.

“What has surprised me is how powerfully and consistently discrimination predicts poor health,” said Williams.

the issue. As early as last April researchers noticed higher death and hospitalization rates for Black people. The patterns have persisted, with Black patients being to die of the virus and Black men have the of covid deaths.

The covid outcomes, Williams and others suggested, helped point out that the health and well-being of middle-class, educated Black men have been overlooked.

Higher education hasn’t brought about the health equity many experts had expected. While Black men have worse health than other groups if they are not educated, they can’t catch up to their white peers even when they are.

“What society has done to Black men is to corner them,” Assari said.

Black men, even with an education, have less of a financial and social safety net than white men. That brings added stress, the experts said. Also, as Black men climb a corporate, academic or managerial ladder, many feel isolated. And social isolation harms health.

Thomas LaVeist, a sociologist and dean of the school of public health at Tulane University, said that in a white-dominated society Black men are less likely to have family members with high incomes or social and business connections who can open doors for them. And once hired into the workplace, they are less likely to have mentors, LaVeist said, and that lack of connections is associated with stress, depression and other factors that can lead to poorer health.

“There needs to be a designated effort to provide an on-ramp” for Black men, he said.

And they may have experienced more cumulative adversity and continued racism.

“Your high socioeconomic status doesn’t protect you from the impact or from the incidence” of racism, said Dr. Adrian Tyndall, associate vice president for strategic and academic affairs at University of Florida Health.

“That is difficult,” added Tyndall, who is Black. “If I were to walk out of this institution and into the community, where people don’t know me, I could be called the N-word. And yeah, that’s pretty depressing.”

The Need to Prove Yourself

The cumulative effect of discrimination takes a toll psychologically and physiologically — but so does the anticipation of it.

“It’s not just the actual exposure in dealing with these kinds of experiences, but it’s ‘What do you do before leaving home?’ You’re careful about your dress, your behavior, the way you look because of the threat of discrimination, and so you react,” said Williams, the Harvard professor.

For example, when Williams, who is Black, first became a professor at Yale University, he wore a coat and tie every day. No one else in his department did that. And yet, he said, he kept up the practice for years.

LaVeist remembers getting onto an elevator at an academic medical center around 1990, shortly after earning his Ph.D., and a passenger wearing a white coat — presumably a doctor — assumed LaVeist worked in housekeeping. The man asked LaVeist, who was dressed in a suit, to clean up a spill on the sixth floor.

“When I told him that I was a professor, he didn’t speak,” said LaVeist. “He simply didn’t speak.”

Greg Pennington, 67, of Atlanta, has a doctorate in clinical psychology from the University of North Carolina and an undergraduate degree from Harvard, owns a professional consulting firm and has worked with hundreds of men individually as well as dozens of Fortune 500 companies. “It’s not so much that [Black men] experience discrimination and depression ‘even after’ they have advanced degrees,” he said. “It’s more descriptive to say ‘throughout the whole process.’”

Despite their academic credentials, Black men said, they often feel they need to prove themselves, which adds another layer of stress.

“It’s almost like I can’t fail; I’m representative of other Black males,” said Woodrow W. Winchester III, director of professional engineering programs at the University of Maryland-Baltimore County. “Your value and your success are around advancing the collective.”

The bottom line, experts agreed, is that discrimination has a lingering effect on health.

Dana Goldman, director of the USC Schaeffer Center for Health Policy and Economics, was co-author of the 2012 Health Affairs study on these chasms. Goldman said he agrees that the underlying cause is racism and added that he thinks one solution is to improve education. He and others suggested that schools, starting in the lower grades, need to provide Black students with more culturally appropriate curricula that bolster their self-image and help build social relationships between white and Black youngsters. Those efforts need to continue as students progress into higher education.

“The policy remedy is not just less racism but to improve the quality of our schools, occupational safety and public health,” Goldman said.

Others agree that the findings suggest a need to reconsider broad policy changes — in education, housing and the justice system — so that Black males feel confident and supported in pursuing better educations and jobs. 

It will be a long-term project, said Williams, the Harvard professor.

“We need a Marshall Plan for all disenfranchised Americans,” he said, but one that especially addresses implicit biases and how American society views and treats Black males.

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But there’s one question she still can’t answer: What makes some patients so much sicker than others?

Advancing age and underlying medical problems explain only part of the phenomenon, said Ranney, who has seen patients of similar age, background and health status follow wildly different trajectories.

“Why does one 40-year-old get really sick and another one not even need to be admitted?” asked Ranney, an associate professor of emergency medicine at Brown University.

In some cases, provocative new research shows, some people — men in particular — succumb because their immune systems are hit by friendly fire. Researchers hope the finding will help them develop targeted therapies for these patients.

In in Science, 10% of nearly 1,000 COVID patients who developed life-threatening pneumonia had antibodies that disable key immune system proteins called interferons. These antibodies — known as autoantibodies because they attack the body itself — were not found at all in 663 people with mild or asymptomatic COVID infections. Only four of 1,227 healthy individuals had the autoantibodies. The study, published on Oct. 23, was led by the COVID Human Genetic Effort, which includes 200 research centers in 40 countries.

“This is one of the most important things we’ve learned about the immune system since the start of the pandemic,” said Dr. Eric Topol, executive vice president for research at Scripps Research in San Diego, who was not involved in the new study. “This is a breakthrough finding.”

In by the same team, authors found that an additional 3.5% of critically ill patients had mutations in genes that control the interferons involved in fighting viruses. Given that the body has 500 to 600 of these genes, it’s possible researchers will find more mutations, said Qian Zhang, lead author of the second study.

serve as the body’s first line of defense against infection, sounding the alarm and activating an army of virus-fighting genes, said virologist Angela Rasmussen, an associate research scientist at the Center of Infection and Immunity at Columbia University’s Mailman School of Public Health.

“Interferons are like a fire alarm and a sprinkler system all in one,” said Rasmussen, who wasn’t involved in the new studies.

show interferons are suppressed in some people with COVID-19, perhaps by the virus itself.

Interferons are particularly important for protecting the body against new viruses, such as the coronavirus, which the body has never encountered, said Zhang, a researcher at Rockefeller University’s St. Giles Laboratory of Human Genetics of Infectious Diseases.

When infected with the novel coronavirus, “your body should have alarms ringing everywhere,” said Zhang. “If you don’t get the alarm out, you could have viruses everywhere in large numbers.”

Significantly, patients didn’t make autoantibodies in response to the virus. Instead, they appeared to have had them before the pandemic even began, said Paul Bastard, the antibody study’s lead author, also a researcher at Rockefeller University.

For reasons that researchers don’t understand, the autoantibodies never caused a problem until patients were infected with COVID-19, Bastard said. Somehow, the novel coronavirus, or the immune response it triggered, appears to have set them in motion.

“Before COVID, their condition was silent,” Bastard said. “Most of them hadn’t gotten sick before.”

Bastard said he now wonders whether autoantibodies against interferon also increase the risk from other viruses, such as influenza. Among patients in his study, “some of them had gotten flu in the past, and we’re looking to see if the autoantibodies could have had an effect on flu.”

Scientists have long known that viruses and the immune system compete in a sort of arms race, with viruses evolving ways to evade the immune system and even suppress its response, said Sabra Klein, a professor of molecular microbiology and immunology at the Johns Hopkins Bloomberg School of Public Health.

Antibodies are usually the heroes of the immune system, defending the body against viruses and other threats. But sometimes, in a phenomenon known as autoimmune disease, the immune system appears confused and creates autoantibodies. This occurs in diseases such as when antibodies attack the joints, and , in which the immune system attacks insulin-producing cells in the pancreas.

Although doctors don’t know the exact causes of autoimmune disease, they’ve observed that the conditions often occur after . Autoimmune diseases are more common as people age.

In yet another unexpected finding, 94% of patients in the study with these autoantibodies were men. About 12.5% of men with life-threatening COVID pneumonia had autoantibodies against interferon, compared with 2.6% of women.

That was unexpected, given that autoimmune disease is far , Klein said.

“I’ve been studying sex differences in viral infections for 22 years, and I don’t think anybody who studies autoantibodies thought this would be a risk factor for COVID-19,” Klein said.

The study might help explain why men are more likely than women to become critically ill with COVID-19 and die, Klein said.

“You see significantly more men dying in their 30s, not just in their 80s,” she said.

Akiko Iwasaki, a professor of immunobiology at the Yale School of Medicine, noted that several genes involved in the immune system’s response to viruses are

Women have two copies of this chromosome — along with two copies of each gene. That gives women a backup in case one copy of a gene becomes defective, Iwasaki said.

Men, however, have only one copy of the X chromosome. So if there is a defect or harmful gene on the X chromosome, they have no other copy of that gene to correct the problem, Iwasaki said.

Bastard noted that one woman in the study who developed autoantibodies has a rare genetic condition in which she has only one X chromosome.

Scientists have struggled to explain why men have a higher risk of hospitalization and death from COVID-19. When the disease first appeared in China, experts speculated that men suffered more from the virus because they are much more likely to smoke than Chinese women.

Researchers quickly noticed that men in Spain were also more likely to die of COVID-19, however, even though men and women there smoke at about the same rate, Klein said.

Experts have hypothesized that men might be put at higher risk by being less likely to wear masks in public than women and more likely to delay seeking medical care, Klein said.

But behavioral differences between men and women provide only part of the answer. Scientists say it’s possible that the hormone estrogen may somehow protect women, while testosterone may put men at greater risk. Interestingly, recent studies have found that obesity poses a with COVID-19 than to women, Klein said.

Yet women have their own form of suffering from COVID-19.

Studies show women are more likely to experience long-term COVID symptoms, lasting weeks or months, including fatigue, weakness and a kind of mental confusion known as “brain fog,” Klein noted.

As women, “maybe we survive it and are less likely to die, but then we have all these long-term complications,” she said.

After reading the studies, Klein said, she would like to learn whether patients who become severely ill from other viruses, such as influenza, also harbor genes or antibodies that disable interferon.

“There’s no evidence for this in flu,” Klein said. “But we haven’t looked. Through COVID-19, we may have uncovered a very novel mechanism of disease, which we could find is present in a number of diseases.”

To be sure, scientists say that the new study solves only part of the mystery of why patient outcomes can vary so greatly.

Researchers say it’s possible that some patients are protected by past exposure to other coronaviruses. Patients who get very sick also may have inhaled higher doses of the virus, such as from repeated exposure to infected co-workers.

Although doctors have looked for links between disease outcomes and blood type, studies have produced .

Screening patients for autoantibodies against interferons could help predict which patients are more likely to become very sick, said Bastard, who is also affiliated with the Necker Hospital for Sick Children in Paris. Testing takes about two days. Hospitals in Paris can now screen patients on request from a doctor, he said.

Although only 10% of patients with life-threatening COVID-19 have autoantibodies, “I think we should give the test to everyone who is admitted,” Bastard said. Otherwise, “we wouldn’t know who is at risk for a severe form of the disease.”

Bastard said he hopes his findings will lead to new therapies that save lives. He notes that the body manufactures many types of interferons. Giving these patients a different type of interferon — one not disabled by their genes or autoantibodies — might help them fight off the virus.

In fact, a pilot study of 98 patients published Thursday in journal found benefits from an inhaled form of interferon. In the industry-funded British study, hospitalized COVID patients randomly assigned to receive interferon beta-1a were more than twice as likely as others to recover enough to resume their regular activities.

Researchers need to confirm these findings in a much larger study, said Dr. Nathan Peiffer-Smadja, a researcher at Imperial College London who was not involved in the study but wrote an accompanying editorial. Future studies should test patients’ blood for genetic mutations and autoantibodies against interferon, to see if they respond differently than others.

Peiffer-Smadja notes that inhaled interferon may work better than an injected form of the drug because it’s delivered directly to the lungs. While injected versions of interferon have been used for years to treat other diseases, the inhaled version is still experimental and not commercially available.

And doctors should be cautious about interferon for now, because a study led by the found no benefit to an injected form of the drug in COVID patients, Peiffer-Smadja said. In fact, there was a trend toward higher mortality rates in patients given interferon, although this finding could have been due to chance. Giving interferon later in the course of disease could encourage a destructive immune overreaction called a cytokine storm, in which the immune system does more damage than the virus.

Around the world, scientists have launched more than 100 clinical trials of interferons, according to , a database of research studies from the National Institutes of Health.

Until larger studies are completed, doctors say, Bastard’s findings are unlikely to change how they treat COVID-19.

Dr. Lewis Kaplan, president of the Society of Critical Care Medicine, said he treats patients according to their symptoms, not their risk factors.

“If you are a little sick, you get treated with a little bit of care,” Kaplan said. “You are really sick, you get a lot of care. But if a COVID patient comes in with hypertension, diabetes and obesity, we don’t say, ‘They have risk factors. Let’s put them in the ICU.’”

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The law, which took effect Jan. 1, mandates that insurers cover vasectomies without requiring patients to pay anything out-of-pocket — just as they must do for more than a dozen birth control methods for women.

But the measure may run afoul of Internal Revenue Service rules that do not include vasectomies among approved preventive services for high-deductible health plans. People with health savings accounts — which are exempt from tax liabilities — tied to those plans could no longer contribute to the savings accounts in that case.

Under the , insurers generally can’t charge patients a copayment or require any other cost sharing for prescription contraceptive drugs or devices approved by the Food and Drug Administration. The 2016 law is similar to what’s required under the federal Affordable Care Act, with a twist: It adds male sterilization — — to the list of services that are free for patients.

“While the ACA made important strides … it completely left men out of the equation,” said Karen Nelson, president and CEO of Planned Parenthood of Maryland, whose organization supported the bill.

Before the law took effect, a vasectomy at the organization’s Baltimore office would cost between $225 and $1,100, depending on someone’s ability to pay, said Nelson. Now the procedure will generally cost nothing for men in insured plans in Maryland.

The state law doesn’t apply to companies that are “self-funded,” meaning they pay their employees’ health care claims directly rather than buying state-regulated insurance policies.

Under IRS rules, consumers making tax-free contributions to health savings accounts (HSAs) that are linked to high-deductible health plans have to pay for all their medical care until they reach their deductible of at least in 2018. The only exception is for preventive services. The hitch for the Maryland law is that vasectomies aren’t on the IRS .

The IRS hasn’t responded to a by Maryland Insurance Commissioner Al Redmer Jr. A this year — after it failed to pass last year — that would exempt these high-deductible plans from the state mandate to cover vasectomies before the deductible is met. Such a move would preserve the tax advantages of the HSAs linked to them.

Maryland is joining a few other states, including , Vermont and, starting next year, , that have expanded contraceptive coverage without cost sharing to include male sterilization.

Vermont’s law includes language to exempt high-deductible plans with health savings accounts. While the issue has raised concerns in Maryland, in Illinois and Oregon it hasn’t appeared to generate much attention to date, legislative analysts say.

Some advocates for extending no-cost coverage to vasectomies noted that the IRS’ list of approved preventive services specifically says that it isn’t exhaustive.

But until the issue is clarified, “the safest thing to do is not make a contribution to your HSA,” said , a Maryland resident and president of HSA Consulting Services. Ramthun helped implement health savings accounts while working for the Treasury Department during the George W. Bush administration. He stressed that the uncertainty applies only to HSA contributions made after the law became effective in 2018, not to earlier contributions. The issue doesn’t affect people’s medical coverage.

Beyond the uncertainty around health savings account contributions, Maryland’s law requiring coverage of vasectomies without cost sharing addresses a gap in men’s preventive coverage.

“There are arguments to be made that male condoms and vasectomies have preventive benefits for both women and men, in terms of [sexually transmitted infection] prevention and preventing pregnancy,” said Mara Gandal-Powers, senior counsel at the National Women’s Law Center.

Seven percent of men ages 18 to 45 have had a vasectomy, according to a by researchers at Northwestern University. The prevalence increased to 16 percent among men ages 36 to 45. Men with higher incomes, higher education and a regular source of health care were more likely to have had the procedure, the study found.

The Maryland law doesn’t apply to the method of birth control that many men use: condoms. A by state Sen. John Astle, a Democrat, would expand the law to include condom coverage.

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A couple of years after his arrival, he broke his foot during a game and afraid of the cost, didn’t seek medical care.

“Some of my family warned me that if I went to the hospital and couldn’t pay the bill, I’d get a bad credit record,” said Uribe, 41, who made about $300 a week and had no health insurance. “I wanted to buy a car or a house someday.” Instead, he hobbled through workdays and stayed off the field for three years; the residual pain is sometimes disabling, even two decades later.

For reasons both economic and cultural, Hispanic men are loath to interact with the health system. Women across all races are more likely to seek care than men. But the gender gap in the Hispanic community is especially troubling to health care providers. Studies show that Latino men are than Latinas to get treatment.

That is true even though Hispanic men are more likely than non-Hispanic whites to be , have or have . tend to do so heavily, contributing to the group’s higher rates of and deaths from . Many take risky jobs such as construction workers and laborers, and are more likely to die from on-the-job injuries than other workers, show.

Hispanics’ share of the population is expected to widen from nearly a fifth now to a quarter by 2045. As that number grows, researchers worry that the nation could face costly consequences as long-ignored conditions lead to serious illness and disability.

“It could literally break the health care system,” said José Arévalo, board chairman of Latino Physicians of California, which represents Hispanic doctors and others who treat Latinos.

And now, some medical professionals fear the effects of President Donald Trump’s crackdown on illegal immigrants.

“When the community faces this kind of stress, I worry that people will do unhealthy things, like abuse alcohol, to deal with it,” said Kathleen Page, co-director of Centro SOL, a health center at Johns Hopkins Bayview Medical Center, and founder of the city’s Latino HIV Outreach Program. “That means they may not work as much,” she added. “They’ll have less money, which means they’re less likely to seek care.”

Welcomed by Baltimore officials, immigrants have driven the city’s Hispanic population, tripling it to 30,000 since 2000.

Here, as elsewhere, evidence suggests that for many Hispanic men, seeking health care is an extraordinary event. Hospital data show they are more likely than Hispanic women, white women and white men to go to the emergency room as their primary source of treatment — a sign that they wait until they’ve no choice but to get help.

Some care providers say medical institutions haven’t done enough to keep Hispanic men healthy, or to persuade them to get regular exams.

“There’s been an ongoing need for institutions to become more culturally attuned and aware of bias,” said Elena Rios, president of the National Hispanic Medical Association, which represents the nation’s 50,000 Latino physicians.

There are some significant differences in health risk and illness rates among Hispanic subgroups — Puerto Ricans are more likely to be smokers, for example. Compared with Hispanics born in the U.S., those born elsewhere have much lower rates of cancer, heart disease and high blood pressure. Overall, Hispanics live longer than whites.

But these advantages may be dissipating as Latinos and adopt unhealthy habits such as and diets high in fatty, processed foods.

“I tell people we live longer and suffer,” said Jane Delgado, a clinical psychologist and Cuban-American who serves as president of the National Alliance for Hispanic Health.

Researchers who investigate gaps in cancer testing have found that all ethnic groups and genders have seen a decrease in late-stage colon cancer diagnoses and deaths in recent years — except Hispanic men, who get screened at the lowest rates of any race or ethnic group.

Often, health problems arise after immigrants come up against an insurance barrier. A few years after Jose Cedillo came to Baltimore from Honduras, the 41-year-old cook noticed his legs were often numb or painful. Worried about finances, he eschewed treatment and continued to work, before finally going to a clinic where he was diagnosed with diabetes.

In the seven years since, his health has so deteriorated he can’t work, is frequently homeless and spends long stints in the hospital. As an immigrant who came to the U.S. illegally, he is not eligible for government-paid insurance or disability payments. And he can’t afford medicine. Instead, he said, “I’ll drink alcohol to numb the pain.”

Part of the problem is that Spanish speakers are underrepresented among medical professionals. After arriving here, Uribe’s family members frequently brought along an English-speaking nephew or niece when they could afford to see doctors. Otherwise, “we’d travel a long ways to find a doctor who spoke Spanish,” he said.

Hospitals frequently lack cultural understanding and bilingual staffing, administrators admit. Though Latinos make up nearly 20 percent of the population, only 5 percent of physicians and 7 percent of registered are Hispanic. That gap has widened as more Hispanics have come to this country during the past three decades, according to a UCLA study released in 2015.

“Too often, people don’t understand what you’re saying, they don’t know what you’re going to charge them, what dietary restrictions you might place upon them,” said James Page, vice president for diversity at Johns Hopkins Medicine. “It creates a trust issue for Hispanics. We’ve got to get better at serving them.”

That is particularly true in mental health. Only 1 percent of psychologists in the U.S. are Hispanic, meaning that Spanish-speaking men who do seek therapy will probably struggle to find it.

In Baltimore, there is only one Spanish-language support group for men who suffer from anxiety and depression, local psychologists and Latino advocates say. The city employs one Spanish-speaking substance abuse counselor. A small handful of bilingual social workers citywide offer reduced-rate counseling sessions, and only three psychiatrists offer therapy sessions conducted in Spanish.

For Peter Uribe, the key to maintaining his family’s health is getting help paying for care. His wife and brother both suffer from epileptic seizures, and his brother’s despondency caused Uribe to become depressed, he said. In 2015, he obtained insurance for his family through a charity program. With the help of now-affordable medicines, his wife’s seizures waned, and he sought help for chronic depression. Since he now speaks English, finding counseling help is easier.

In January, after intervention from a Latino advocacy group, the charity renewed the Uribes’ policy for two years. Peter Uribe calls it a godsend:

“I honestly have no idea what we’d do without it.”

Michael Anft is a Baltimore-based journalist and writer whose work regularly appears in AARP: The Magazine, The Chronicle of Higher Education and other publications. Daniel Trielli, a data journalist at Capital News Service at the Philip Merrill College of Journalism, contributed to this report.

supports KHN’s coverage of health disparities in East Baltimore.

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I keep seeing featuring young people asking their parents why they didn’t get the vaccine to protect against the human papillomavirus — HPV. If you’re unfamiliar with HPV, it’s a sexually transmitted infection that has been linked to various cancers, including cervical cancer in women.

I didn’t get vaccinated. So lately I’ve been wondering: Now that I’m 29, is it too late for me to get the vaccine?

I found out about HPV eight years ago when a college girlfriend got immunized. Back then, the Centers for Disease Control and Prevention only recommended the vaccine for girls and young women between the ages of 11 and 26. , they said, to try to reach girls before they become sexually active. The vaccine is also more effective at a younger age.

At the time, I remember thinking that limiting it to females was strange — after all, males still spread HPV, right? But with my partner vaccinated, I let it go. I didn’t know HPV could cause health problems for men.

But HPV absolutely affects men. It causes genital warts and is as a leading cause of cancers in the back of the mouth and throat, the area called the oropharynx. The CDC now estimates about 70 percent of all may be caused by HPV, including roughly 12,600 cases in men each year.

“There are now more oropharynx cancers in men in the United States each year than there are cervical cancers in women,” said , a surgeon and researcher at the University of Texas MD Anderson Cancer Center in Houston.

And there’s no way to screen for oropharyngeal cancer, so Sturgis says most people catch it late.

“Typically it’s a man, while he’s shaving,” said Sturgis. “He notices a lump in his neck. That means it’s already a cancer that has spread.”

HPV also puts men at risk for cancers of the anus and penis. Those are rare, but still make me anxious.

So, for men like me who missed the vaccine, is it still worth it?

The answer is complicated. In 2011, the CDC began recommending the vaccine for males ages 11 through 21 years old (26 for some high-risk groups).

Despite my age, researchers I talked to said that the vaccine could still help — if I haven’t already been exposed.

But therein lies a complication. An estimated of sexually active people will be exposed to HPV by age 45. In most people, the virus goes away on its own after two years. For men, there’s no commercially available test to find out if you have been exposed. Women can be checked for HPV exposure as part of a Pap test.

To have 80 percent of sexually active young adults exposed sounds bleak. But there’s a caveat: “There are several dozen types of HPV that infect the genital region,” said psychologist , who co-directs the Center for HPV Research in Indianapolis. Only a fraction of those cause cancer or warts, and the latest version of the vaccine Gardasil protects against nine of those HPV types — the ones responsible for a vast majority of HPV-related problems.

So let’s say — hypothetically — you’re kind of shy and haven’t had that many partners. Is it possible you’ve been spared?

“The chances you’ve been exposed to all nine types are actually vanishingly small,” said , a microbiologist who studies HPV and HPV vaccines at the National Cancer Institute.

Schiller said the vaccine might not be a bad idea for someone outside the CDC’s recommended age range. Still, it’s not cheap.

“You’re past the age where your health insurance is going to pay for it,” said Schiller, so getting the vaccine isn’t imperative — it’s a personal decision.

“Peace of mind for you may be worth more than it is for some other people,” he told me.

So, I got the vaccine. It’s costing $130 out of pocket per dose, and the CDC recommends three shots. But it could help me, even if it just calms my anxious inner voice. And it might keep me from spreading the virus to someone else.

This story is part of a partnership that includes , and Kaiser Health News.

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That’s the good news. Unfortunately, according to from the Government Accountability Office, NIH can’t tell whether researchers are also examining outcomes by sex to see whether men and women are affected differently by what’s being tested.

That’s important because, for example, a drug or dosage appropriate for a man might be less effective or even lead to harm when taken by a woman.

But NIH does not make available usable information on which studies have separated results by sex and what those results are. NIH “does not maintain, analyze or report summary data to oversee whether analysis of outcomes by sex are planned or conducted,” the report found.

This is not the first time the GAO has criticized NIH for its implementation of the requirement to include women in research trials. In 2000, the agency needed to do a better job ensuring “that certain clinical trials be designed and carried out to permit valid analysis by sex.” Once again, NIH officials are promising to do better. The agency has 60 days to formally respond to the new report.

Meanwhile, those who fought to require parity in clinical trials have been left sputtering.

“It’s just very frustrating,” said former Rep. Patricia Schroeder of Colorado. “It reminds me of when you ask your children to move the clothes from the washer to the dryer. Then you go back and the clothes are still wet and they say, ‘Well you didn’t tell me to turn the dryer on.’”

Schroeder said she got interested in the subject in the early 1990s when studies came out showing that a daily aspirin could prevent heart attacks — and when she learned that all the test subjects had been men. “They didn’t even use female rats,” she said.

In fact, under  from the Food and Drug Administration that were not changed until 1993, women of childbearing age were not even allowed to participate in drug trials, largely in response to serious birth defects that arose after drugs like thalidomide and DES were used by women.

Pushed by a group of women members of Congress, including Schroeder, the requirement to include women in clinical trials was written into law as part of a signed by President Bill Clinton.

But even as more women are being included in clinical trials, there is growing scientific evidence of just how biologically different men and women are, and how differently they sometimes react to drugs and other medical interventions.

“We’re finally able to include women well enough to understand that they express disease differently, that certain risk for disease was different and certain outcomes for disease were different,” said Paula Johnson, a professor at Harvard Medical School and head of the Connors Center for Women’s Health and Gender Biology at Brigham and Women’s Hospital in Boston.

Heart disease, Alzheimer’s and lung cancer are examples of how are affected in different ways, she said. “But they’re just examples; these differences occur across all diseases where we’ve asked the question.”

Indeed, in 2013 the for the popular sleeping pill Ambien after it became clear that the drug took longer to leave women’s systems and could pose a danger the next morning.

Other research has shown that biological differences go to the most basic level.

“The truth of the matter is men and women are very different at the cellular level, at the molecular level, at the systemic level,” said Doris Taylor, director of regenerative medicine research at Texas Heart Institute.

Taylor, who has been studying the use of stem cells to treat heart disease, said that “we got very different results if you gave male cells or female cells.”

Given the significant differences recently discovered, it’s actually dangerous not to stratify research results by sex, experts say.

“If you’re mixing those results [from men and women], there will be more noise in the system,” Taylor said. “And you’re going to miss what you might otherwise see as an effect or lack of effect. That is the danger.”

Leaders at the NIH say they agree with the GAO’s recommendations and will try to do better. But, as usual in science, it’s complicated.

“It’s a problem because we don’t get to understand whether treatments work as well in women as they do in men, and when things are not reported separately by sex, we also don’t get to see whether there might be some indication of differences in toxicity or adverse events,” said Dr. Janine Clayton, head of the NIH .

One big problem, said Clayton, is the lack of information on differences by sex reported in leading medical journals. Of the large clinical trials described in journals, she said, “fewer than one-third had any sex-specific information in the publication.”

Often that’s because the numbers are so small that the results may not be statistically significant, “and it’s difficult to publish non-statistically significant results,” Taylor said.

But if those results are somehow made available, researchers could combine them together into what’s called a . “We’ve been trying to work with the journal editors for many years on this,” Clayton said.

Another problem is that NIH is not the only funder of medical research. Private industry, including pharmaceutical companies, pays for many — if not most — later-stage clinical studies. Privately funded studies also do not follow all NIH rules.

Meanwhile, in light of recent discoveries about biological differences by sex, Clayton says NIH is moving to require more basic, pre-clinical studies to , in an effort “to make sure that sex as a biological variable is accounted for in the design, analysis and reporting” of all research funded by the agency. That requirement takes effect in January.

Clayton, however, said she cannot discuss exactly what the agency will do to ensure better reporting by sex of the results of later trials involving humans. She said that will be included in the agency’s formal response to the GAO report.

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