911������

Science and Sex: A Bold Agenda for Women’s Health

This commentary is adapted from the keynote speech delivered by Paula A. Johnson, MD, MPH at the 2023 NAM Annual Meeting.��

Since the predecessor of the 911������ Academy of Medicine, the Institute of Medicine (IOM), was founded in 1970, the country has looked to us to shape the way science is done, the way care is delivered, and the ways policies can support the well-being of women.

A little history might help us better understand where we are today. For example, as we are all wrestling with the implications of the Dobbs decision and its negative impacts on women’s health, it’s worth remembering that in 1975, as a relatively new organization, the IOM conducted a study of legalized abortion in response to Roe v. Wade (IOM, 1975). It did not consider abortion as an issue of rights or ethics, but as a public health issue—and found that legal abortion reduced the risk of maternal death, compared to illegal abortion and full-term pregnancy.

Alongside its stellar work over the years on maternal and reproductive health, this body has helped to shine a light on the neglect of women’s overall health in both scientific research and clinical practice.

In 1977, after thalidomide and other drugs prescribed to pregnant women turned out to cause birth defects, the Food and Drug Administration (FDA) not only banned pregnant women from being included in early clinical trials—it banned all women capable of becoming pregnant. Women were routinely excluded from most medical research.��The operative assumption was that what was true for men would generally be true for women. And diseases that were more prevalent in women were largely ignored.

Women might not have been making much progress on the health care front in the 1970s and ‘80s, but we were making progress in national politics. A key voice speaking out against this injustice was someone we recently lost, U.S. Representative Pat Schroeder, who served in Congress for 24 years (Seelye, 2023). She said it was the famous 1980s Physicians’ Health Study—which found that taking aspirin daily would prevent heart attacks—that tipped her off to the problem: every single one of the 22,000 physicians included in the clinical trial was a man (Physicians’ Health Study, 2009). And yet the findings were presented as if they held true for women, too—which we now know is not the case (Ridker et al., 2005).

In 1990, the Congressional Caucus for Women’s Issues asked the Government Accountability Office (Nadel, 1990) to look into the exclusion of women from medical research funded by the 911������ Institutes of Health (NIH; Government Accountability Office, 1990). The GAO found that the NIH was violating its own policies. In response, the NIH established the Office of Research on Women’s Health (NIH, n.d.a.).

By 1993, women in both parties in the House and Senate—led by Pat Schroeder, Olympia Snowe, and Barbara Mikulski—ensured that the NIH Revitalization Act included a mandate that women and minorities be included in clinical research (NIH, 2017).

In 1994, the IOM released a report considering the ethical and legal implications of women’s exclusion from clinical research. It blisteringly described a medical and scientific culture rife with bias that left women’s health unjustly understudied. The report notably put its finger on the deadly “male norm” in medical research. The conclusion was that “these biases . . . produce findings that are not valid for large segments of the population.�� (IOM, 1994).

Then in 2001, the IOM released the landmark report Exploring the Biological Contributions to Human Health: Does Sex Matter? (IOM, 2001). It coined a key phrase: “Every cell has a sex.” The implications of that five-word sentence are vast—all-encompassing—and this body helped the scientific and medical community understand that. Because women and men are different at cellular and molecular levels—thanks to that 23rd pair of chromosomes—�������� it is not just women’s sex organs that develop differently, but their hearts, their lungs, their immune systems, and more (Klein and Flanagan, 2016).

The intersection of these fundamental genetic differences, with the hormonal and reproductive changes across a woman’s life span, have ripple effects on every aspect of her health: Pharmaceuticals can act differently in men and women. Diseases have different prevalences in women and can manifest themselves differently. The report recommended that investigators consider sex as a biological variable in all biomedical and health-related research—a policy that the NIH would only put in place 15 years later.

That said, social factors also have a profound influence on health and deserve study, including gender, race, and other factors. In 2010, with a report titled Women’s Health Research: Progress, Pitfalls, and Promise, this body pointed out that the groups of women generally at highest risk of having or dying from a condition—those of lower socioeconomic status and members of racial and ethnic minorities—are the least represented in biomedical research (IOM, 2010). It takes sufficient data to inform the understanding of vulnerable populations.

In addition to its crucial work in illuminating the scientific, clinical, and public health issues surrounding women’s health, this body has had an important influence on health policy, helping to make sure it is evidence-based.

It was an honor to have served, with several colleagues here today, on the IOM committee that in 2011 recommended which preventative care services for women should be included under the Affordable Care Act (ACA) at no cost (IOM, 2011). For example, we argued successfully that contraception was a preventative service that should be covered without out-of-pocket costs—a critically important evidence-based conclusion—after years during which some insurers paid for Viagra prescriptions, but not for birth control (ABC News, 2002).

In 2014, my research group at the Connors Center for Women’s Health and Gender Biology��at Brigham and Women’s Hospital partnered with the Kaiser Family Foundation and the Jacob’s Institute for Women’s Health on an evidence-based policy report to identify the remaining gaps in scientific research pertaining to sex (Connors Center��Twenty-one years after the 1993 Revitalization Act, the NIH was still not fully living up to its inclusion policies.

Among the list of problems we flagged, two stand out: first, there was some progress, in that the number of women included in trials increased.��However, even when women were included, the vast majority of federally funded studies still did not report sex-specific findings. Given the biological importance of sex, when you give an average as a result, that’s not good for women—or for men.��The second problem we flagged was that in basic and preclinical research, the vast majority of studies continued to be focused on male animals and male cells. Without sex as a variable, what you have is very poor science.

Here is how Pat Schroeder described the lagging NIH: “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.’” (Rovner, 2015).

In 2016, the NIH finally began expecting that sex be a biological variable factored into the design, collection, analyses, and reporting of all the studies it supports (NIH, n.d.b.). Even asking the question—What does sex mean for this study?—is leading us in important new directions.

Today, we are still wrestling with the issues of representation in research, as the Academies’ 2022 report Improving Representation in Clinical Trials and Research confirms (NASEM, 2022).

That said, we clearly have made some progress. The percentage of participants in NIH-funded trials who are women has increased from 44 percent in 2013 to 52 percent in 2018 (NASEM, 2022). Our understanding of the different course diseases take in women has improved. But there is so much more to do in research, including determining why rates of early onset cancer are rising in women and why there is a mental health crisis among our youth—with teen girls being impacted disproportionately—and more (Koh et al., 2023; CDC, 2023a).

And there is so much more to do in translating the knowledge we gain through research to clinical care. Maternal mortality is getting worse, not better. Although cardiovascular disease is the leading cause of death for women, women presenting with chest pain in an emergency room still wait longer to be seen than men, and women of color wait the longest—and we still don’t understand the underlying biology of the observed sex differences (American Heart Association News, 2022). Women in North America are much more likely to have two or more chronic conditions than in other high-income countries (Gunja et al., 2022).

goal of ensuring that women have equal access to the best evidence-based understanding and treatment remains unrealized.

And on the policy front, we seem to be going backward. In the wake of the Dobbs decision—which reversed decades of progress on women’s reproductive health and which is creating health care deserts for women around the country—it is time for a bold new agenda for women’s health (Weiner, 2023).��

The 911������ Academy of Medicine has the capacity to have significant influence at this critical moment in time. Today, I want to suggest three pillars for any agenda we develop:

First, we need to do the fundamental science right—and admit how much we don’t yet know. Second, the title of this meeting—“From Cells to Society”—should represent the approach to the greatest problems in women’s health, with an effort to understand the biology from the molecule up and then to translate that research into clinical care and public health interventions. Third, we need health policies—and leadership—that support the larger goal of gender equity in our society.

There’s a reason that science comes first on my list: it informs every aspect of our health care system, from individual patient care to federal policy. When the research is inadequate or misleading, it distorts decision-making throughout the system.

The work of applied mathematician Arthur Mirin has shown that when you consider the burden a disease represents, diseases that are male dominant are largely overfunded by the NIH (Smith, 2023). Those that are female dominant are largely underfunded.

But the funding doesn’t have the full desired impact if we don’t design our studies properly. We are still wrestling with a medical and scientific culture where ignorance about the importance of sex remains rampant. A survey of NIH study section members in 2016 and 2017, after the “Sex as a Biological Variable” policy was put in place, found that about a third did not believe it was important for all NIH-funded research to consider sex in experimental design (Woitowich and Woodruff, 2019a; Woitowich and Woodruff, 2019b).

Another survey conducted in 2020 of scientists who conduct biomedical research using vertebrate animals—this is four years after the policy was put in place—found that only about half always analyze their findings by sex (Waltz et al., 2021).

Even at the very frontiers of medical research, sex is not always considered. Last year, Dr. Sarah Mitchell of Princeton’s Ludwig Institute for Cancer Research surveyed the preclinical literature for her subspecialty—anti-aging interventions—focusing on mouse studies of calorie restriction, one of the most investigated interventions (Mitchell and Mitchell, 2022).

She found that in 2022, a majority of papers did not consider both sexes, and a minority didn’t report sex at all. This hardly makes sense, when important sex differences have been observed. Research by Dr. Mitchell has shown that in one strain of mice, both sexes live longer when their calories are restricted by 20 percent (Mitchell et al., 2016). But when they are fed 40 percent fewer calories, the males live longer, but the females die sooner.

As a general rule, women outlive men, despite generally experiencing worse health, and the diseases of aging have different prevalences in men and women (UN News, 2019). So, as geroscience, or the study of aging across the life span, takes off, and we search for geroprotectors to extend both the life span and the health span, we need to ensure that the differences in the ways women age—and respond to interventions—receive the attention they deserve.

We also clearly need to make better use of the sex-based health data we have accumulated over decades—and to employ the powerful new tools of data science, machine learning, and artificial intelligence to help us find correlations we might have missed.

Within women’s health, we also need the equivalent of the revolution that has taken place in the field of cancer in recent years, thanks to advances in molecular biology, genomics, and immunology. We need to replace our rudimentary disease-by-disease model with a focus on the underlying mechanisms of health and disease, which are essential for us to understand the best strategies for prevention and treatment.

This argues, also, for taking a life-course approach to women’s health, to understand how exposures during fetal development and in girlhood affect outcomes during the reproductive years, and then menopause and aging.

To do good science, we have to admit how much we don’t yet know. And we must be vigilant in making the most out of every dollar spent on research by considering sex and other critical determinants of health.

While we commit to good science and continue exploring the biological impact of sex, it is also clear that social and environmental factors have an important influence on health and well-being—including race, ethnicity, and gender. So let’s not allow what happened to women happen to other gender minorities, in terms of being left out of the research.

We need to expand the study of gender to include gender minorities and to develop strategies to study the health of transgender people across the life span, including the impact of hormonal therapy started at different stages in the life cycle. We must learn how to include the trans population in clinical trials—now.

And as we consider the etiology of disease, we need to look hard at rampant inequities at the intersection of race, ethnicity, and sex. While research is crucial to making health care more equitable, there is no guarantee that it will have an impact. That depends entirely on what we do with it.

Which brings me to my second point: we need to take a cells-to-society approach to the greatest challenges in women’s health. Maternal and infant mortality offer a scorching example of why we need an all-in effort.

The United States has the dubious distinction of having one of the highest maternal mortality rates among high-income countries—largely because Black women fare so badly, dying of pregnancy-related complications at 2.6 times the rate of White women (OECD Stat, 2023; Gunja et al., 2022; Hoyert, 2023). Infant mortality among Black babies is also more than twice that of White babies (CDC, 2023b). And these gaps persist at all levels of education and income (Miller et al., 2023). In Black women, the number one cause of maternal mortality is cardiac and coronary conditions, followed by cardiomyopathy (Trost et al., 2022).

Research into reproductive health and cardiovascular health has told us that discrete conditions experienced many years apart are, in fact, connected—even though these two fields generally exist in their own separate clinical silos. Cardiometabolic disorders of pregnancy—such as preeclampsia and gestational diabetes—are risks for cardiovascular disease as women age.��When you add pre-eclampsia to preterm delivery and low birth weight, the likelihood that a woman will experience a major cardiovascular event in the future quadruples—and the likelihood that she will die of cardiovascular disease doubles (Riise et.al, 2017).

At the same time, these same cardiometabolic factors—including hypertension of pregnancy—can be associated with life-threatening outcomes during and after childbirth. Clearly, general internists, obstetricians, and cardiologists need to pay much more attention to young women at risk. We are doing better but need to do more!

At the molecular level, more than two decades of work on the biomarkers of preeclampsia by Dr. Ravi Thadhani and Dr. S. Ananth Karumanchi has led to a new FDA-approved diagnostic test to flag those women at greatest risk of life-threatening preeclampsia (Thadhani et al., 2022). This is an outstanding advance. But our research means little if we don’t succeed at translating it into clinical care.

Fortunately, Black women’s poor outcomes in childbirth have been getting some long-overdue public attention, in part due to outstanding journalism, including that of Linda Villarosa, and in part due to the terrible first-person stories from celebrities such as Serena Williams and Beyoncé—as well as the tragic death of Olympic sprinter Tori Bowie (Chappell, 2023). Williams said that a day after giving birth, her providers initially dismissed her when she told them that she was having a pulmonary embolism, something she’d experienced before (Haskell, 2018).

In general, women’s health care is weakened by a lack of knowledge about sex-specific issues—and a lack of respect. Women patients are often not trusted as reliable reporters of their own symptoms—especially Black women.

This is an educational challenge for all of us. We need to better understand how to effectively teach the next generation of health care professionals that quick��judgments and implicit bias can undermine the care they give their patients. Although we have known this for years, we are not achieving the behavior changes we need to see. We also need to take a public health approach to the challenge of maternal mortality.

Though it has not succeeded in eliminating the mortality gap for Black mothers, the State of California has succeeded in keeping its pregnancy-related mortality ratio well below the national ratio—with the assistance of the California Maternal Quality Care Collaborative, formed in 2006 (Maternal, Child, and Adolescent Health Division, 2021; Center for Academic Medicine, Neonatology, n.d.).

This partnership among the state Department of Health, Stanford University, and nearly every hospital in the state offers evidence-based toolkits for health care providers and hospitals to better prevent, screen for, prepare for, and address maternal risks (Montagne, 2018). Providers around the country should be adopting these best practices that connect academic medicine with public health and health care delivery.

Of course, even the most advanced health care means nothing to someone who can’t access it. If we are going to improve health outcomes for women, we need health policies—and leadership—that support the larger goal of gender equity in our society.

Without question, the Affordable Care Act has dramatically improved access to health insurance and health care—and it has been particularly important for women (Norris, n.d.). Before the ACA, many individual plans did not even include maternity coverage, and pregnancies could be treated as preexisting conditions used to deny women coverage or increase their premiums.

However, if you follow the news even slightly, you know how tenuous these gains are. While our uninsured rate is the lowest it’s been in history, we still have nearly 8 percent of our population uninsured (Becerra, 2023). The lack of expansion of federally covered Medicaid in so many states and the lack of federally mandated paid leave for new mothers are topics that deserve their own talk (KFF, 2023; OECD Family Database, 2022).

And, after the Dobbs decision, we now live in a fractured country in terms of health policy—one where women’s right to make their own medical decisions is severely limited in many states and where doctors now fear terminating a pregnancy even to save a woman’s life (Guttmacher Institute, 2023).

So what can we do to ensure more equitable policies, better clinical care, and more scientifically sound research?

Clearly, there is a training aspect. We need to do much more, for example, to educate both scientists and health care professionals about the ways that sex differences influence health and disease—not as a single lecture or as an aside, but as a central and integrated component of undergraduate, graduate, and research training.

We also need to recognize that who you are influences what you see—and that inclusiveness breeds excellence, since a variety of perspectives is so essential to progress in all fields. We need more women and minorities in positions of leadership—in medicine, in science, in biotechnology, in the pharmaceutical industry, and in policy and politics. We also need to recognize the ways that the culture of academic science and medicine are hard on women. While women are now percent of U.S. medical school enrollees, they are just 34 percent of academic physician-scientists—and even scarcer in scientific leadership (Association of American Medical Colleges, 2023; Browne, n.d.).

One reason is the fact that women in academic medicine and biomedical scientists encounter bias on all sides.

In 2021, my co-authors and I published a paper that demonstrated that journal article peer reviewers in the medical sciences are biased against studies focused on women (Murrar, et al., 2021). Of course, such studies are much more likely to be conducted by women scientists. Even though the reviewers found the studies focused on women more likely to contribute to medical science, they were nonetheless twice as likely to recommend for publication the same research conducted in men.

Unfortunately, publication bias is far from the only insult experienced by women in STEM [science, technology, engineering, and mathematics] fields. There is the gender gap in pay and promotions, and there is the sexual harassment.��In 2018, I co-chaired a committee of the 911������ Academies of Sciences, Engineering, and Medicine that published the first evidence-based report on the sexual harassment of women in academic science, engineering, and medicine (NASEM, 2018). We found that academic workplaces are second only to the military in rates of sexual harassment—with women of color experiencing the most harassment.

This is shocking only if you consider it hastily: although we are improving, these are environments where men outnumber women, especially in leadership, and where cultures characterized by disrespect and a lack of civility can develop, creating the conditions where sexual harassment, including gender harassment, is more likely to occur.

Frankly, as all of us in higher education work so hard to bring young women into science, engineering, and medicine, it is beyond discouraging to think they are being harassed out of those fields. The 911������ Academies is leading important work in this area as a follow-�������� up to the report.

So where do we go from here? First of all, optimism is in order! We should take heart from the fact that there is a growing understanding that women’s health and the study of sex and gender merit much more attention. The fact that this meeting is devoted to this topic is a major step forward!

Also helping us set a new course is the just-released Women’s Health Innovation Opportunity Map. Sponsored by the [Bill & Melinda] Gates Foundation and the NIH’s Office of Research on Women’s Health, it offers 50 ways to improve women’s health globally—including improving our data collection and disease modeling.

Another promising development: in addition to the centers and labs focused on sex and gender differences represented at this conference, Rockefeller University has now launched a new ��—with the support of its vice chair, Marlene Hess—which will explore how sex and gender influence biological processes (Rockefeller University, 2023).

Given that 26 scientists affiliated with Rockefeller have won Nobel Prizes over the years, I have high hopes for the science that will emerge. Rockefeller scientists have already led the way in discovering the biology that contributed to the higher male death rate that we observed early in the COVID-19 pandemic (Bastard et al., 2020).

Second, we need to improve the science we do and make use of the incredible tools in our hands, to move away from a mainly disease-based model of women’s health and to begin understanding the underlying biological mechanisms that protect women or make them vulnerable.

Third, we need an ecosystem-wide approach to issues in women’s health. This includes academic institutions, which are both a producer and an effector arm of science—producing the scientists who serve on study sections, who then decide who gets grants and how this science is performed. Universities and medical schools need to understand that this is a weak spot, and they have a role in promoting the fact that sex is a critical variable in research.

As mentioned earlier, they also need to incorporate this concept into medical education and research training at all levels.

We need private philanthropy, large and small, to incorporate sex and gender in their major initiatives.

We need academic journals to promote a sea change in the way we do both preclinical and clinical research by requiring manuscript data to be disaggregated by sex.

We need the biopharmaceutical industry and device makers to embrace the principles we discussed earlier and to make sex an early consideration in research and development.

We need the venture capital industry to wake up to the fact that women are not a niche market, but rather the majority of the population—and to start investing in start-ups focused on women’s health.

We need to find common ground in this divided country and to determine how and where women’s health is being advanced successfully and then replicate these models.

We need to keep the health of women at the center as we address the grand challenges of our time, including climate change.

We need policymakers to ensure that women’s health research remains a national priority and to fund it accordingly—and to hold funding agencies to task.

Finally, we need the 911������ Academies to lead the way in setting out a bold and evidence-based agenda, as they so often have in the past.

There is a world of opportunity in front of all of us—if we focus on improving women’s health—to improve health for everyone and, by extension, to make this a better, more equitable, prosperous, and healthy world.

 

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Join the conversation!

@DrPaulaJohnson, president of @Wellesley College, explains how more equitable policies, better clinical care, and more scientifically sound research can improve women’s health outcomes. Read the new #NAMPerspectives commentary:

����A new #NAMPerspectives authored by @DrPaulaJohnson explores the history of research on women’s health and offers a bold new agenda for the future:

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References

1. ABC News. 2002. Erections get insurance; why not the pill? June 19. https://abcnews.go.com/US/story?id=91538 (accessed December 5, 2023).
2. American Heart Association News. 2022. Women and Black adults wait longer to be seen in the ER for chest pain. https://www.heart.org/en/news/2022/05/04/women-and-black-adults-wait-longer-to-be-seen-in-the-er-for-chest-pain (accessed December 5, 2023).
3. Association of American Medical Colleges. 2023. 2023 facts: Enrollment, graduates, and MD-PhD data by institution. https://www.aamc.org/data-reports/students-residents/data/2023-facts-enrollment-graduates-and-md-phd-data (accessed December 5, 2023).
4. Bastard P. et al. 2020. Autoantibodies against type I IFNs in patients with life-threatening COVID-19.Science. https://www.science.org/doi/10.1126/science.abd4585.
5. Becerra, X. 2023. New HHS Report shows national uninsured rate reached all-time low in 2023 after record-breaking ACA enrollment period. https://www.hhs.gov/about/news/2023/08/03/new-hhs-report-shows-national-uninsured-rate-reached-all-time-low-2023-after-record-breaking-aca-enrollment-period.html (accessed December 5, 2023).
6. Browne, A. n.d. Demographic characteristics and work experiences of physician scientists in the U.S.: Analysis of the 2022 911������ Sample Survey of Physicians (NSSP). Washington, DC: Association of American Medical Colleges.
7. CDC (Centers for Disease Control and Prevention). 2023a. S. teen girls experiencing increased sadness and violence. https://www.cdc.gov/media/releases/2023/p0213-yrbs.html#:~:text=According%20to%20new%20CDC%20data,reported%20over%20the%20past%20decade (accessed December 5, 2023).
8. CDC. 2023a. Infant Mortality. https://www.cdc.gov/reproductivehealth/maternalinfanthealth/infantmortality.htm (accessed December 5, 2023).
9. Center for Academic Medicine, Neonatology. n.d. California Maternal Quality Care Collaborative. https://www.cmqcc.org/ (accessed December 5, 2023 ).
10. Chappell, B. 2023. Tori Bowie, an elite Olympic athlete, died of complications from childbirth. NPR, June 13. https://www.npr.org/2023/06/13/1181971448/tori-bowie-an-elite-olympic-athlete-died-of-complications-from-childbirth#:~:text=Hangst%2FGetty%20Images-,Tori%20Bowie%2C%20who%20captured%20gold%20as%20a%20sprinter%20in%20the,according%20to%20an%20autopsy%20report.&text=She%20was%20once%20the%20fastest%20woman%20in%20the%20world (accessed December 5, 2023 ).
11. Connors Center (Mary Horrigan Connors Center for Women’s Health and Gender Biology). Sex-Specific Medical Research: Why Women’s Health Can’t Wait. . ��https://www.brighamandwomens.org/assets/bwh/womens-health/pdfs/connorsreportfinal.pdf (accessed December 5, 2023).
12. Gunja, M. Z., E. D. Gumas, and R. D. Williams III. 2022. The U.S. maternal mortality crisis continues to worsen: An international comparison. The Commonwealth Fund, December 1. https://www.commonwealthfund.org/blog/2022/us-maternal-mortality-crisis-continues-worsen-international-comparison (accessed December 5, 2023).
13. Gunja, M. Z., S. Seervai, L. C. Zephyrin, and R. D. Williams II. 2022. Health and health care for women of reproductive age: How the United States compares with other high-income countries. Washington, DC: The 911������ Academies Press. https://www.commonwealthfund.org/publications/issue-briefs/2022/apr/health-and-health-care-women-reproductive-age (accessed December 5, 2023).
14. Guttmacher Institute. 2023. Interactive map: US abortion policies and access after https://states.guttmacher.org/policies/ (accessed December 5, 2023).
15. Haskell, R. 2018. Serena Williams on motherhood, marriage, and making her comeback. Vogue, January 10. https://www.vogue.com/article/serena-williams-vogue-cover-interview-february-2018 (accessed December 5, 2023).
16. Hoyert, D. L. 2023. Maternal mortality rates in the United States, 2021. Hyattsville, MD: 911������ Center for Health Statistics. https://dx.doi.org/10.15620/cdc:124678.
17. IOM (Institute of Medicine). 2011. Clinical preventive services for women: Closing the gaps. Washington, DC: The 911������ Academies Press. https://doi.org/10.17226/13181.
18. IOM. 2010. Women’s health research: Progress, pitfalls, and promise. Washington, DC: The 911������ Academies Press. https://doi.org/10.17226/12908.
19. IOM. 2001. Exploring the biological contributions to human health: Does sex matter? Washington, DC: The 911������ Academies Press. .
20. IOM. 1994. Women and Health Research: Ethical and Legal Issues of Including Women in Clinical Studies, Volume 1. https://doi.org/10.17226/2304.
21. IOM. 1975. Legalized abortion and the public health: Report of a study. Washington, DC: The 911������ Academies Press. .
22. KFF. 2023. Status of state Medicaid expansion decisions: Interactive map. https://www.kff.org/medicaid/issue-brief/status-of-state-medicaid-expansion-decisions-interactive-map/ (accessed December 5, 2023).
23. Klein, S. L., and K. L. Flanagan. 2016. Sex differences in immune responses. Nature Reviews Immunology 16:626–638. https://www.nature.com/articles/nri.2016.90 (accessed December 5, 2023).
24. Koh, B., D. J. Hao Tan, C. H. Ng, C. E. Fu, W. H. Lim, R. Wenling Zeng, J. N. Yong, J. Hong Koh, N. Syn, W. Meng, K. Wijarnpreecha, K. Liu, C. Seng Chong, M. Muthiah, H. N. Luu, A. Vogel, S. Singh, K. Guan Yeoh, R. Loomba, and D. Q. Huang. 2023. Patterns in cancer incidence among people younger than 50 years in the US, 2010 to 2019. JAMA Network Open 6(8):e2338171. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2808381 (accessed December 5, 2023).
25. Maternal, Child, and Adolescent Health Division. 2021. CA-PMSS surveillance report: Pregnancy-related deaths in California, 20082016. Sacramento, CA: California Department of Public Health.
26. 26. Miller, C. C., S. Kliff, and L. Buchanan. 2023. Childbirth is deadlier for Black families even when they’re rich, expansive study finds. The New York Times, February 12. https://www.nytimes.com/interactive/2023/02/12/upshot/child-maternal-mortality-rich-poor.html (accessed December 5, 2023).
27. Mitchell, S. J., J. Madrigal-Matute, M. Scheibye-Knudsen, E. Fang, M. Aon, J. A. González-Reyes, S. Cortassa, S. Kaushik, M. Gonzalez-Freire, B. Patel, D. Wahl, A. Ali, M. Calvo-Rubio, M. I. Burón, V. Guiterrez, T. M. Ward, H. H. Palacios, H. Cai, D. W. Frederick, C. Hine, F. Broeskamp, L. Habering, J. Dawson, T. M. Beasley, J. Wan, Y. Ikeno, G. Hubbard, K. G. Becker, Y. Zhang, V. A. Bohr, D. L. Longo, P. Navas, L. Ferrucci, D. A. Sinclair, P. Cohen, J. M. Egan, J. R. Mitchell, J. A. Baur, D. B. Allison, R. M. Anson, J. M. Villalba, F. Madeo, A. M. Cuervo, K. J. Pearson, D. K. Ingram, M. Bernier, and R. deCabo. 2016. Effects of Sex, Strain, and Energy Intake on Hallmarks of Aging in Mice. Cell Metabolism 23(6):P1093–P1112. https://doi.org/10.1016/j.cmet.2016.05.027.
28. Mitchell, S., and J. R. Mitchell. 2022. Sexual dimorphism in the response to dietary restriction in mice: A systematic review of the literature. Nutrition and Healthy Aging 7(3–4):87–120. https://content.iospress.com/articles/nutrition-and-healthy-aging/nha220162 (accessed December 5, 2023).
29. Montagne, R. 2018. To keep women from dying in childbirth, look to California. NPR, July 29. https://www.npr.org/2018/07/29/632702896/to-keep-women-from-dying-in-childbirth-look-to-california#:~:text=The%20state%20is%20leading%20the,wasn’t%20always%20that%20way. (accessed December 5, 2023).
30. Murrar, S., P. A. Johnson, Y.-G. Lee, and M. Carnes. 2021. Research conducted in women was deemed more impactful but less publishable than the same research conducted in men. Journal of Women’s Health 30(9). https://doi.org/10.1089/jwh.2020.8666.
31. Nadel, M. V. 1990. 911������ Institutes of Health: Problems in implementing policy on women in study populations, before the Comm. on Energy and Commerce, House of Representatives (statement, Associate Director of 911������ and Public Health Issues, Human Resources Division, General Accounting Office). https://www.gao.gov/products/t-hrd-90-38 (accessed December 5, 2023).
32. NASEM. 2022. Improving representation in clinical trials and research: Building research equity for women and underrepresented groups. Washington, DC: The 911������ Academies Press. https://doi.org/10.17226/26479.
33. NASEM. 2018. Sexual harassment of women: Climate, culture, and consequences in academic sciences, engineering, and medicine. Washington, DC: The 911������ Academies Press. https://doi.org/10.17226/24994.
34. NIH (911������ Institutes of Health). 2017. NIH policy and guidelines on the inclusion of women and minorities as subjects in clinical research. https://grants.nih.gov/policy/inclusion/women-and-minorities/guidelines.htm (accessed December 5, 2023).
35. NIH. n.d.a. The Office of Research on Women’s Health: A history of fostering diversity and inclusion in biomedical research. https://orwh.od.nih.gov/about/mission-history/office-research-womens-health-history-fostering-diversity-and-inclusion#:~:text=The%20Office%20of%20Research%20on%20Women’s%20Health%20(ORWH)%20was%20the,Raub%2C%20Ph (accessed December 5, 2023).
36. NIH. n.d.b. NIH policy on sex as a biological variable. https://orwh.od.nih.gov/sex-gender/nih-policy-sex-biological-variable (accessed December 5, 2023).
37. Norris, L. n.d. How Obamacare changed maternity coverage. HealthInsurance.org. https://www.healthinsurance.org/obamacare/how-obamacare-changed-maternity-coverage/ (accessed December 5, 2023 ).
38. OECD Family Database (Organisation for Economic Co-operation and Development Family Database). 2022. 1. parental leave systems. https://www.oecd.org/els/soc/PF2_1_Parental_leave_systems.pdf (accessed December 5, 2023).
39. OECD Stat (Organisation for Economic Co-operation and Development Stat). 2023. Healthcare Quality Indicators. https://stats.oecd.org/Index.aspx?DataSetCode=HEALTH_HCQI (accessed December 5, 2023).
40. Physicians’ Health Study. 2009. Physicians’ Health Study I. https://phs.bwh.harvard.edu/phs1.htm (accessed December 5, 2023).
41. Ridker, P. M., N. R. Cook, I.-M. Lee, D. Gordon, J. M. Gaziano, J. E. Manson, C. H. Hennekens, and J. E. Buring. 2005. A randomized trial of low-dose aspirin in the primary prevention of cardiovascular disease in women. The New England Journal of Medicine 352(13):1293–1304. https://www.nejm.org/doi/full/10.1056/NEJMoa050613 (accessed December 5, 2023).
42. Riise, H.K.R., Sulo G., et al. 2017. Incident Coronary Heart Disease After Preeclampsia: Role of Reduced Fetal Growth, Preterm Delivery, and Parity. Journal of the America Heart Association. https://www.ahajournals.org/doi/full/10.1161/jaha.116.004158.
43. Rockefeller University. 2023. 2022 The Rockefeller University annual financial report. New York.
44. Rovner, J. 2015. GAO: NIH needs to do more to ensure research evaluates gender differences. The Washington Post, November 28. https://www.washingtonpost.com/national/health-science/gao-nih-needs-to-do-more-to-ensure-research-evaluates-gender-differences/2015/11/28/902ed502-9524-11e5-8aa0-5d0946560a97_story.html (accessed December 5, 2023 ).
45. Seelye, K. Q. 2023. Patricia Schroeder, feminist force in Congress, dies at 82. The New York Times, March 14. https://www.nytimes.com/2023/03/14/obituaries/pat-schroeder-dead.html (accessed December 5, 2023).
46. Smith, K. 2023. Women’s health research lacks funding—these charts show how. Nature, May 3. https://www.nature.com/immersive/d41586-023-01475-2/index.html?utm_source=linkedin&utm_medium=social&utm_content=organic&utm_campaign=CONR_JRNLS_AWA1_GL_SCON_SMEDA_NATUREPORTFOLIO (accessed December 5, 2023).
47. Thadhani, R., E. Lemoine, S. Rana, M. M. Costantine, V. F. Calsavara, K. Boggess, B. J. Wylie, T. A. Moore Simas, J. M. Louis, J. Espinoza, S. L. Gaw, A. Murtha, S. Wiegand, Y. Gollin, D. Singh, R. M. Silver, D. E. Durie, B. Panda, E. R. Norwitz, I. Burd, B. Plunkett, R. K. Scott, A. Gaden, M. Bautista, Y. Chang, M. A. Diniz, S. Ananth Karumanchi, and S. Kilpatrick. 2022. Circulating angiogenic factor levels in hypertensive disorders of pregnancy. New England Journal of Medicine Evidence 1(12). https://evidence.nejm.org/doi/full/10.1056/EVIDoa2200161 (accessed December 5, 2023).
48. Trost, S. L., J. Beauregard, G. Chandra, F. Njie, J. Berry, A. Harvey, and D. A. Goodman. 2022. Pregnancy-related deaths: Data from Maternal Mortality Review Committees in 36 US States, 2017-2019. Atlanta, GA: Centers for Disease Control and Prevention. https://www.cdc.gov/reproductivehealth/maternal-mortality/erase-mm/data-mmrc.html.
49. UN News. 2019. Women outliving men ‘everywhere’, new UN health agency statistics report shows. April 4. https://news.un.org/en/story/2019/04/1036091 (accessed December 5, 2023).
50. Waltz, M., K. W. Saylor, J. A. Fisher, and R. L. Walker. 2021. Biomedical researchers’ perceptions of the NIH’s sex as a biological variable policy for animal research: Results from a U.S. national survey. Journal of Women’s Health 30(10):1395–1405. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8590154/ (accessed December 5, 2023).
51. Weiner, S. 2023. The fallout of Dobbs on the field of OB-GYN. AAMC News, August 23. https://www.aamc.org/news/fallout-dobbs-field-ob-gyn#:~:text=The%20historic%20June%202022%20Dobbs,put%20them%20in%20legal%20peril (accessed December 5, 2023 ).
52. Woitowich, N. C., and T. K. Woodruff. 2019a. Research community needs to better appreciate the value of sex-based research. Proceedings of the 911������ of the United States of America 116(15):7154–7156. https://doi.org/10.1073/pnas.1903586116.
53. Woitowich, N. C and T. K. Woodruff. 2019b. Implementation of the NIH sex-inclusion policy: Attitudes and opinions of study section members. Journal of Women’s Health 28(1):9–16. https://pubmed.ncbi.nlm.nih.gov/30539677/ (accessed December 5, 2023).