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How ignorance and gender inequality thwart treatment of a widespread illness

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Doctors pull back curtains on either side of illustration. At centre, two women look up at plants and depiction of female reproductive system

Credit: Chiara Zarmati

On a visit to a woman at home in rural Zambia, community-health worker Janet Chisaila unpacks a bag that contains swabs, sample pots and a 3D-printed model of a vagina and cervix. Using the model, Chisaila explains how to use the swabs to take genital samples. The woman then goes to a private area to do her sampling. Later, she visits the local health clinic, where Chisaila’s colleague Alice Mwale, a nurse, takes digital photographs of the woman’s cervix, which are then uploaded to a secure platform. Thousands of miles away, at the London School of Hygiene & Tropical Medicine, clinician and principal investigator Amaya Bustinduy logs in to the platform to review the images and offer advice.

The woman is one of around 2,500 taking part in a study1 called Zipime Weka Schista! (Do self-testing, sister!), which aims to transform the diagnosis of a little-known neglected tropical disease (NTD) called female genital schistosomiasis (FGS). By combining FGS screening with testing for HIV, human papillomavirus (HPV) and a sexually transmitted disease called trichomoniasis in a single visit, the tests are striking a blow for gender equality and women’s sexual- and reproductive-health rights. “This approach has empowered the women to know about these diseases,” says Chisaila. “They have been given the confidence to talk about some of these health issues and have access to treatment and care.”

FGS is a debilitating gynaecological condition caused by chronic infection with a parasitic disease known as schistosomiasis. Painful and stigmatizing, the disease is associated with reduced fertility and miscarriage. Infection increases the risk of contracting HIV, and probably HPV and cervical cancer as well. Although it was first recorded2 125 years ago, few people — even health-care workers in regions where the condition is thought to be most common — are aware that it exists. “FGS is neglected, under-researched and overlooked in endemic countries,” says Kwame Shanaube, clinical epidemiologist and site coordinator of the Zipime Weka Schista! study at Zambart, a Zambian non-governmental public-health research organization in Lusaka that specializes in public health and grew out of a collaboration between the University of Zambia’s School of Medicine and the London School of Hygiene & Tropical Medicine.

Women and girls are vulnerable to FGS both because of their sex and because of socially determined roles and expectations that increase their exposure to infection and make it difficult for them to access treatment or talk about their symptoms. The social roles of women expose them more often to infection, and make it harder to access prevention and treatment, or even to talk about their symptoms than do those of men. “It’s very hard for women to talk about painful sex and sub-fertility in contexts where it’s hard to access a health-care provider,” says Sally Theobald at the Liverpool School of Tropical Medicine, UK, who studies gender inequity and health systems. “So it is this chronic pain and rights issues that have been going on for decades and decades.”

FGS is a disease of compounded neglect: ignored because it is an illness found mainly in low-income countries; overlooked because of a lack of awareness; stigmatized because it pertains to sexual health; and further neglected because it affects women, especially low-income and marginalized women, whose health is chronically underfunded and under-researched. Tackling it is therefore not merely a biomedical problem, but also one that involves addressing gender inequality and the sexual and reproductive health rights of women and girls.

An insidious disease

Schistosomiasis, also called bilharzia, is caused by parasitic worms known as schistosomes. The species that causes FGS, Schistosoma haematobium, infests freshwater lakes and rivers. The larvae burrow through a person’s skin, making their way to a collection of veins around the bladder and pelvic organs. There, the larvae mature into adults, each the size of a grain of rice, and mate. Each female worm lays hundreds of eggs. These work their way through the bladder wall with the aid of sharp spines and destructive enzymes. Once in the bladder, the eggs are released through urination into the environment to start the cycle anew.

Three children carrying two large buckets of water between them

In some societies, girls are expected to fetch the family’s water.Credit: Simon Townsley/Panos Pictures

Left untreated, the infection becomes chronic. “These worms can live in your bloodstream for 30 or 40 years,” says Evan Secor, a parasitologist at the US Centers for Disease Control and Prevention in Atlanta, Georgia. Between 30% and 75% of women infected with S. haematobium go on to develop FGS, which occurs when schistosome eggs end up trapped in the tissues of the reproductive system, including the cervix, vagina and fallopian tubes. These trapped eggs cause pain and become surrounded by immune cells, forming inflamed nodules called granulomas, which in turn can lead to scarring. Men can also get genital schistosomiasis, particularly those whose occupations put them at increased risk, such as freshwater fishermen.

Only about 15,000 women and girls in endemic areas have been included in study surveys for FGS, so there are no precise figures for the prevalence of the condition, says Bustinduy. Estimates suggest that between 30 million and 56 million women globally have FGS, most of them in sub-Saharan Africa.

Part of the problem lies in the difficulty of diagnosing the disease. Conventional approaches involve inspecting the cervix with an instrument known as a colposcope, or taking a biopsy and sending it to a lab to look for schistosome eggs under a microscope. But these tools are rarely available in endemic areas — colposcopes are expensive and require specialized gynaecological training to use.

Looking for schistosome eggs in urine samples is cheap, but misses most FGS cases because the correlation between eggs in urine and FGS is only about 20–30% . Molecular testing to detect schistosome DNA in samples such as urine is much more reliable but requires specialist facilities and expensive reagents. Facilities such as these are also usually found only in hospitals, which can be hard for people with low incomes to travel to. And gynaecological examination of girls and young women before they are sexually active is unacceptable in some cultures.

Diagnostic delays mean that, even after standard treatment with a drug called praziquantel that kills the adult worms, women can have permanent tissue damage. Delphine Pedeboy-Knoetze, who grew up in France but who now lives and works in South Africa, had FGS that went undiagnosed for several months. She still experiences chronic pain six years later. “It’s extremely demoralizing, because nobody can establish what’s wrong,” she says. Consultations with multiple specialists in various countries have yielded no answers. This adds to the mental-health burden of FGS. “It’s the loneliness of it,” she says. “That’s the scariest feeling, because you think, ‘Oh wow, I really am on my own’.”

An array of neglect

The astonishing lack of awareness of FGS among health workers starts with education. FGS is not mentioned in many medical textbooks and rarely forms part of medical training. The classic symptom of urogenital schistosomiasis is blood in the urine, which can be confused with menstruation or ‘spotting’. This means that the disease is assumed to affect men only. “Health professionals do not have FGS in their radar of diagnosis,” says Motto Nganda, a clinician at the Liverpool School of Tropical Medicine who has studied how to integrate FGS management into primary health-care settings in Liberia.

Yellow Schistosoma larva on brown background

Schistosoma larvae can burrow through a person’s skin.Credit: LENNART NILSSON, TT/SCIENCE PHOTO LIBRARY

This means that genital symptoms can be wrongly attributed to sexually-transmitted infections, with the result that women are not only given ineffective treatment, but also stigmatized. Teenage girls report being scolded by clinic nurses who assume that the girls have had premarital sex, while older women (or their partners) have been accused of infidelity. Pedeboy-Knoetze, for example, was told that she had herpes and to be suspicious of her partner.

Larger political decisions have also shaped the neglect of FGS, says Laura Dean, who studies person-centred health-system responses to NTDs at the Liverpool School of Tropical Medicine. Mass drug-administration is the main effort to control NTDs that can be tackled in this way, including schistosomiasis, she says. The approach is designed to prevent and treat these diseases in endemic areas. This is an essential strategy and one that should be continued, Dean says. However, it isn’t a magic bullet that, in isolation, can prevent continuous cycles of reinfection — particularly for a disease such as schistosomiasis that is closely linked to the broader environment and access to clean water, sanitation and hygiene. People who cannot access these programmes, or for whom the drugs don’t work, can develop chronic morbidities. This risk is especially high for diseases such as schistosomiasis in which there is a high risk of reinfection3.

Compounding all of these factors is gender: the social expectations and roles that societies attribute to men and women (and people of other genders). Gender is increasingly being recognized as a key factor that affects an individual’s vulnerability to NTDs, and FGS is a classic example. “Gender norms in many contexts mean that much of the work done by women in households and communities involves a lot of interaction with water,” says Theobald. This includes doing the family’s laundry and fetching water from local rivers and ponds. “So there’s ongoing exposure to schistosomiasis in multiple ways.”

Gender also affects access to treatment and health care. For schistosomiasis, this involves the mass administration of praziquantel in vulnerable populations4. This is often delivered to children in schools, but girls are less likely to attend school than are boys, says Secor. Gender inequality also affects how women experience the disease once they have it. “It brings subfertility, it brings painful sex, it brings discharge, and it’s in a context where there’s so much pressure to conceive,” says Theobald. For example, in some parts of Liberia and Nigeria, a woman’s social status is linked to fertility and her ability to have children. As a result of poor sexual and reproductive health, including pregnancy complications or infertility, women with FGS can be ostracized, accused of witchcraft, and faced with the loss of their homes and partners5.

“The fact that there’s a parasite that’s easily treatable with a dose of praziquantel that costs very little and that can change the outcome of a woman’s life, and we’re not doing that, is absolutely shocking,” says Pedeboy-Knoetze. “Shame on the global-health community and shame on the medical community for this.”

Attack on all fronts

All of this means that programmes to tackle FGS need to build in social, political and cultural factors, as well as biomedical ones. They also need to work with the clinical resources that are available in endemic areas. In the past few years, a number of projects have piloted ways to do this. The Zipime Weka Schista! study, for example, uses culturally appropriate ways to raise awareness of FGS. Drama groups perform songs and dances in areas such as community marketplaces to draw in members of the public and communicate messages about FGS. Community workers then go door to door to offer more information and to recruit study participants.

Person sitting at table, wearing white coat, blue gloves and blue face mask, holding pipette in one hand

A health worker at a medical centre in Zimbabwe tests for schistosome parasites.Credit: Xinhua/Shutterstock

Reactions from the communities have been positive, says Rhoda Ndubani, a social scientist and study manager of Zipime Weka Schista! at Zambart. The project is reducing stigma around these diseases and giving women the confidence to talk about them and seek treatment, she adds. It’s also empowering the nurses and community midwives. “It’s really helping us because, before, I did not know that women can actually get schistosomiasis,” says Mwale. Training and handheld colposcopes are already allowing nurses to make FGS diagnoses independently and to administer praziquantel immediately.

Similar messages came out of a study in Liberia. Nganda, Dean and their colleagues piloted a clinical-care package in primary-care settings, which included an FGS symptoms checklist, training in simple gynaecological examinations and treatment guides. Importantly, the package included training traditional midwives, who are trusted in local communities. The study diagnosed and treated 245 women and girls over a period of 6 months, during routine primary health care6. A related study5 in Nigeria returned similar findings. “It’s showing what is possible to do within different under-resourced health systems,” says Theobald.

Making diagnoses in primary-care settings that are accessible to women is key. “We’re trying to steer away from using hospitals as much as possible, because that is really when the bottleneck comes in,” says Bustinduy. The goal, she says, is to instead promote the use of rural clinics staffed with midwives and nurses. It’s also about making the FGS diagnosis less reliant on clinical examinations, which can result in varying diagnoses depending on the physicians, adds Secor, who chairs a World Health Organization diagnostic advisory panel for FGS diagnostics. “We’re really trying to move to something that’s a little bit more objective,” he says.

Taking inspiration from other self-sampling programmes, such as those in place for HPV and HIV, Bustinduy and her colleagues conducted a study of around 600 women to explore the use of self-sampled genital swabs and DNA testing7. The BILHIV (bilharzia and HIV) study showed that participants readily accepted self-sampling, that it was as good as clinical sampling at detecting FGS, and, therefore, that home-based self-sampling could present a scalable way of diagnosing FGS in endemic regions. In further experiments, the BILHIV study investigated a lower cost alternative to the DNA-amplifying technique PCR called recombinase polymerase amplification (RPA). Unlike PCR, RPA works at room temperature, and is rapid and highly portable. The findings suggested that RPA was a viable alternative to PCR, and could form part of a portable laboratory to be used at point of care8.

FGS is associated with other genital infections, such as HIV, HPV (the main cause of cervical cancer) and trichomoniasis. The Zipime Weka Schista! study therefore aims to see whether testing for all four could be integrated into a single home visit. Like the BILHIV study, the approach is getting a positive reaction from women — especially the self-sampling aspect. “For many, it is the first time they have been screened in this way,” says Chisaila.

Scaling up

There are signs that the condition is slowly starting to shed its neglected status: its association with HIV has brought the sexual and reproductive health communities together, and advocacy by FGS researchers is moving the issue up national and international health agendas. In January, for example, a government committee report recommended that FGS be integrated into the UK government’s sexual and reproductive rights aid programmes. Witnesses testifying to the committee advocated moving away from a focus on individual diseases to a patient-centred one — FGS often falls into a gap between NTD and sexual-health programmes. The Joint United Nations Programme on HIV/AIDS has also recognized the need for FGS integration.

Science has its part to play, too. One aspect is in finding ways to help women like Pedeboy-Knoetze who have tissue damage. “We don’t really have a good way to treat that chronic, longer, more severe pathology,” says Secor. Another is finding ways to prevent the disease, such as vaccination. Adding these to mass drug-administration programmes could reduce the risk of reinfection and help to cut the cycle of transmission. Three vaccines are currently undergoing development. Although each targets the Schistosoma mansoni parasite, which causes intestinal schistosomiasis, one of them also protects against S. haematobium. This vaccine, called Sm-p80 (SchistoShield), is in phase I trials.

More diagnostics are also in the works. DNA swabs are thought not to work well in advanced FGS, because the eggs are walled inside scar tissue, so researchers are exploring two other approaches. One is a test for schistosome antigens in the blood that is scheduled to go into field trials in the next few months, says Secor. Another approach, one Secor’s team is taking, is testing for anti-schistosome antibodies. Although these don’t necessarily reveal whether a person has an active infection (antibodies persist for a long time), such tests could be easy to incorporate into routine clinical screening, such as prenatal visits. Tests under development include lateral-flow tests similar to pregnancy tests or those used to rapidly detect COVID-19 (ref. 9). These tests can detect antibodies or schistosome antigens and are easy for users to interpret, and would ideally cost less than US$1 per test, says Secor. “I’m optimistic,” he says, “but we’re not there yet.”

Complicating matters is that any new approaches to diagnosing and treating FGS must be adapted to the realities of living in some of the poorest, most marginalized communities in the world. “If we can do that, it’s a win–win for gender equity, rights and social justice,” says Theobald. “It’s a win–win for responsive, effective, person-centred health systems.”

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19 Best Sex Toys (2024): Gender Inclusive, Couples, Solo

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Sex tech has come a long way in the past 10 years—not only in terms of cultural acceptance and awareness but also technology. Gone are the days of clunky, pink, plastic rabbit vibrators and sex toys that feel like knockoff action figures. Today’s toys are designed by sex educators, medical professionals, and some of the world’s greatest sexperts. They feature ultra-premium, medical-grade silicone, robust Bluetooth connectivity, programmable vibration patterns, and multiple motors all designed to help you have a good time.

There’s never a bad time to invest in a little extra self-care. These are the best sex toys, vibrators, smart vibrators, personal wand massagers, and accessories, all of which we’ve personally tested. There’s something here for everyone, every gender, and every body. The language on these products isn’t always gender-inclusive, but we approached testing with a gender-inclusive mindset, testing these with a variety of different genitals, bodies, and partners.

Be sure to check out our other bedroom-related guides, including the Best Vibrators, Best Clitoral Suction Toys, Best Lubes, Best Mattresses, and Best Sound Machines.

Updated May 2024: We’ve added the Coconu Wave and Le Wand vibrators.

Special offer for Gear readers: Get WIRED for just $5 ($25 off). This includes unlimited access to WIRED.com, full Gear coverage, and subscriber-only newsletters. Subscriptions help fund the work we do every day.

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Collection of different types of sex toys on a blue and pink background

Photograph: MyroslavaPavlyk/Getty Images

Which Toys Are for My Body?

The sex tech industry has conditioned us to think of toys in terms of male and female, penis and vagina, but that’s reductive and inaccurate, and it contributes to a larger narrative about the relationship between genitals and gender. It’s unhelpful, and I have a lot of feelings about it. We opt to be as specific as possible and use anatomical terms to describe individual erogenous zones—and there are way more than just P and V.

The vulva is the exterior part of the vagina. It includes the labia majora, labia minora, the urethra, and the clitoris. The clitoris is the center of erogenous nerves in the vulva, and it’s much larger than just the exterior portion. Its internal structures extend down to either side of the vagina, which is where you’ll find the G-spot—the area stimulated by toys that curve toward the front of your body.

The phallus is what’s commonly referred to as the shaft of the penis, and it includes a couple of erogenous zones. The glans is the top of the phallus, usually referred to as the “head,” and the frenulum is a thin strip of connective tissue on the underside of the glans that can be particularly sensitive to targeted stimulation. Last but not least, the anus is, well … it’s the butthole. The rectum is the interior portion that attaches to the anus. Both of these areas can be sensitive to internal and external stimulation.

For people born with phalluses, there’s an additional erogenous zone here: the prostate or P-spot. This is a walnut-sized gland that lives between the internal structures of the penis and the rectum, and it can be reached by toys that curve toward the front of your body.


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Why it’s essential to study sex and gender, even as tensions rise

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Person in a black t-shirt holding a sign protests outside the school districts educational support complex in Katy.

In 2023, students protested against a new policy in Texas, where parents would be notified if their child asks to be identified as transgender.Credit: Brett Coomer/Houston Chronicle/Getty

This week, Nature is launching a collection of opinion articles on sex and gender in research. Further articles will be published in the coming months. The series will highlight the necessity and challenges of studying a topic that is both hugely under-researched and, increasingly, the focus of arguments worldwide — many of which are neither healthy nor constructive.

Some scientists have been warned off studying sex differences by colleagues. Others, who are already working on sex or gender-related topics, are hesitant to publish their views. Such a climate of fear and reticence serves no one. To find a way forward we need more knowledge, not less.

Nearly 20 researchers from diverse fields, including neuroscience, psychology, immunology and cancer, have contributed to the series, which provides a snapshot of where scholars studying sex and gender are aligned — and where they are not. In time, we hope this collection will help to shape research, and provide a reference point for moderating often-intemperate debates.

In practice, people use sex and gender to mean different things. But researchers studying animals typically use sex to refer to male and female individuals, as defined by various anatomical and other biological features. In studies involving humans, participants are generally asked to identify their own sex and/or gender category. Here, gender usually encompasses social and environmental factors, including gender roles, expectations and identity.

For as long as scientific inquiry has existed, people have mainly studied men or male animals. Even as recently as 2009, only 26% of studies using animals included both female and male individuals, according to a review of 10 fields in the biological sciences1. This bias has had serious consequences. Between 1997 and 2000, for instance, eight prescription drugs were removed from the US market, because clinical testing had not revealed women’s greater risk of developing health problems after taking the drugs.

The tide, however, is turning. Many journals, including those in the Nature Portfolio, and funders, such as the US National Institutes of Health, have developed guidelines and mandates to encourage scientists to consider sex and, where appropriate, gender in their work.

These efforts are reaping benefits2. Studies, for example, are showing that a person’s sex and/or gender can influence their risk of disease and chances of survival when it comes to many common causes of death — including cardiovascular conditions and cancer.

Despite this, many researchers remain unconvinced that the inclusion of sex and gender information is important in their field. Others, who are already doing so, have told Nature that they’re afraid of how their work is perceived and of how it could be misunderstood, or misused.

Because researchers who are exploring the effects of sex and gender come from many disciplines, there will be disagreements. An often-raised and valid concern, for example, is that when researchers compare responses between female and male animals, or between men and women, they exclude those whose sex and/or gender doesn’t fall into a binary categorization scheme. Another is that variability between individuals of the same sex could be more important than that between sexes.

Sometimes sense does seem to get lost in the debates. That the term sex refers to a lot of interacting factors, which are not fully understood, does not invalidate its usefulness as a concept3. That some people misinterpret and misuse findings concerning differences between sexes, particularly in relation to the human brain, should not mean denying that any differences exist.

Tempering the debate

Many of the questions being raised, however, are important to ask, especially given concerns about how best to investigate biological differences between groups of humans, and the continued — and, in some regions, worsening — marginalization of people whose sex and/or gender identity doesn’t fall into narrowly defined norms. Often, such questions and concerns can be addressed through research. For example, studies might find that variability between individuals of the same sex in diet, or body weight, say, are more important predictors of how likely they are to develop anaemia than whether they are male or female.

The problem, then is not the discussions alone: science exists to examine and interrogate disagreements. Rather, the problem is that debates — and work on sex and gender, in general — are being used to polarize opinions about gender identity. As Arthur Arnold, a biologist at the University of California, Los Angeles, and his colleagues describe in their Comment article, last September, legislation banning gender-affirming medical care for people under 18 years old was introduced in Texas on the basis of claims that everyone belongs to one of two gender groups, and that this reality is settled by science. It isn’t. Scientists are reluctant to study sex and gender, not just because of concerns about the complexity and costs of the research, but also because of current tensions.

But it is crucial that scholars do not refrain from considering the effects of sex and gender if such analyses are relevant to their field. Improved knowledge will help to resolve concerns and allow a scholarly consensus to be reached, where possible. Where disagreements persist, our hope is that Nature’s collection of opinion articles will equip researchers with the tools needed to help them persuade others that going back to assuming that male individuals represent everyone is no longer an option.

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We need more-nuanced approaches to exploring sex and gender in research

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Over the past decade, intense and polarizing debates about transgender rights and women’s bodies have escalated worldwide — from politicians being grilled on the definition of a woman to scientific journals being critiqued for the language they use in discussions of women’s health. Meanwhile, studies have accumulated showing that the impacts of sex and gender on human health and behaviour are both far-reaching and complex. This is in part the result of major funding agencies, such as the Canadian Institutes of Health Research and the US National Institutes of Health, as well as various scientific journals1, developing guidelines and mandates to encourage scientists to consider sex and gender in their research (see Nature 605, 396 (2022); Nature Commun. 13, 2845; 2022).

Given the heightened sociopolitical tensions and a widespread perception that considering sex and gender (terms we define below) will ramp up the complexity and costs of research, many scientists might feel it is prudent to avoid examining them in their work. However, studies that engage critically with sex and gender are urgently needed, both to increase understanding of humans across diverse contexts, and to provide insights for societal discussions — whether on health and disease, education or other topics.

Clinicians and regulatory agencies still lack knowledge about how factors related to sex and gender, and their interactions, affect the likelihood of being prescribed a drug, of experiencing severe side effects or of receiving an incorrect dose2. Similarly, in relation to disaster relief, organizations providing aid to those in need could increase the effectiveness of their efforts if they better understood how sex and gender affect people’s ability to access health services, food or water — in the context of sexualized or gender-based violence, say, or because of gendered stereotypes and roles3. To make future products more useful to everyone, many engineering and design fields, from artificial intelligence to robotics, need sex- and gender-informed research. The design of commonly used products, such as seat belts and airbags, needs to take into account factors related to sex and gender to address women’s increased risk of injury and fatality in vehicle crashes4. We urge scientists to engage with the concepts and issues surrounding sex and gender, and to consider the relevance of them to their own field. We also entreat them to embrace complexity, and develop deeper, more-nuanced approaches to interrogating sex and gender than are most commonly used today. This means, among other things, engaging deeply with the mechanisms and factors that underlie apparent differences between groups5.

Causes of confusion

For most research that considers sex and/or gender, limited information is collected for either attribute. For studies involving humans, participants are typically asked to identify their sex and/or gender category; for those involving non-human animals, individuals are usually assigned to a sex category depending on the appearance of their genital anatomy.

Meanwhile, when it comes to promoting understanding of the concepts of sex and gender and the distinctions between them, a starting point frequently offered — including by major research funders — is that sex is biological and gender is social. In other words, sex is meant to refer to various anatomical and other biological features, whereas gender is associated with social and cultural attributes, opportunities and roles.

Splitting data by sex or gender category can be a useful starting point to help identify sex- and gender-related differences and disparities. Similarly, the ‘sex is biological and gender is social’ framing can offer a valuable initial toehold, because it serves as a reminder that not every difference observed between sex or gender groups is rooted in biology: social and environmental factors are often important, too.

Ultimately, however, both the approaches commonly used to categorize individuals and the way in which many researchers think about sex and gender do not necessarily lead to studies that can adequately address the complexities and diversity of humans. They can even be misleading.

For a start, sex is not a fixed thing. Neither is gender.

For us, the term sex is best understood as both a categorization scheme (in which individuals are typically classed as male, female or intersex) and a complex constellation of traits and factors across several levels of biological organization that show considerable variability between and within individuals. Sex-related factors and traits include anatomical features, hormones, levels of gene expression and physiological, reproductive, metabolic or neurological processes — but no single trait comprehensively defines an individual’s sex. In all animals, including humans, developmental processes that occur during sexual differentiation (during fetal development and after birth) are not determined by single genes. Instead, sex phenotypes emerge from the complex interplay of numerous molecular pathways that can be influenced by environmental experiences through epigenetic, endocrine, neurological and other mechanisms across people’s lifespan6.

Similarly, the term gender encompasses much more than people’s sense of self as a gendered individual, or their ‘gender identity’. Gender can be understood as a categorization scheme, in which a person can identify as a man or woman (whether cisgender or trans), as non-binary or with one or more other evolving terms. Gender also encompasses roles, norms, relations and opportunities that vary between cultures and over time, and which affect people’s income, autonomy, domestic and public roles, and their access to power and resources.

Furthermore, sex and gender are not neatly separable.

Various studies have shown that environmental and social factors can affect people’s biology in numerous ways. Gendered dressing patterns affect people’s exposure to sunlight7, for instance, affecting their levels of vitamin D, which can in turn influence bone density8,9. In other words, although bone density is affected by levels of oestrogen or testosterone, it should not be understood as solely a sex-related trait, but as something that is shaped by social and environmental factors rooted in gender, too. Similarly, patterns of gendered socialization related to dress, types of play (for example, indoor or outdoor) and vigilance about cleanliness might result in boys and girls having distinct patterns of exposure to microorganisms — which could, in turn, have implications for the maturation of their immune system and susceptibility to developing conditions such as an allergy or autoimmune disorder10. Some scholars focusing on issues around sex and gender use the hybrid terms gender/sex or sex/gender in recognition of such entanglement11,12.

To add to the difficulties, many scientific organizations, journals and researchers fail to clarify what exactly they mean by sex and gender, or they conflate the terms or use them interchangeably. Moreover, patterns of use can differ according to people’s language, discipline or country. For example, the term gender medicine has been used to describe at least three distinct things: a branch of medicine focused on disease-related differences between men and women13; the study of how sex and gender influence an individual’s health14,15; and the provision of care for children with differences in sexual development16. To help address this confusion, we have mapped the relationships between various areas of science concerned with sex and gender, and policies linked to equity, diversity and inclusion17.

Embracing complexity

In our view, continued dialogue between scholars and journal editors will help to clarify and refine terminologies. However, putting aside the problems with how the terms are used and understood, when sex and gender are considered in research at all, the standard approach is to compare female and male individuals. Such comparisons can be useful for flagging characteristics that warrant further investigation. However, in making such comparisons, researchers often overlook the fact that there is substantial heterogeneity in sex/gender categories and substantial overlap between them for many traits. Ultimately, relying too heavily on a binary comparison approach risks describing the realities incorrectly for everyone, not just for women or non-binary people. It also contributes to the marginalization of those with variations in sexual development and people with diverse gender identities.

Take, for example, research on blood donation. In 2017, researchers in Canada published findings that among frequent blood donors, women had low levels of ferritin (a marker of iron levels) more often than did men18. The study prompted Canadian Blood Services — the organization that manages most of the country’s blood supply — to alter its policy on donation intervals: for all female donors, it has extended the time between donations from 8 to 12 weeks. (Since January 2023, Canadian Blood Services has also been intermittently testing ferritin levels in donors’ blood, but only in women.)

Indian villagers carrying babies wade through flood waters after collecting relief food

Gendered roles and behaviours affect people’s health and well-being.Credit: Diptendu Dutta/AFP/Getty

By focusing the policy on the sex category of the donor, the organization effectively treats all women as being at the same risk of low iron levels, which is higher than that of men, without attending to the specific factors that are most likely to be mechanistically related to that risk: body size, amount of menstrual blood loss and dietary iron intake. The change to donation interval for women — based on a binary analysis — also glosses over the heterogeneous and overlapping nature of the data, including the fact that the frequent donors also included women who did not have low iron levels, and men who did. A more nuanced interpretation of the findings, along with further research that probed the specific sex- and gender-related factors that increase people’s risk of developing low iron levels, could allow policies to be refined in ways that are better oriented to the mechanistic factors that matter most.

A spokesperson for Canadian Blood Services said that it recognizes that blood donors are a heterogeneous population and that it uses standardized, simple criteria to divide donors into accepted and deferred groups.

In practice, each investigator is best placed to work out which sex- and gender-related factors will be most important to assess on the basis of their study system, goals, tools, methods and resources19, and — crucially — best placed to justify these decisions. Not every possible variable relating to sex and gender needs to be interrogated in all contexts, and there is no one-size-fits-all approach.

Someone studying a new T-cell therapy for colon cancer, for example, might propose that gonadal hormones could modify the efficacy of the treatment, because T cells possess receptors for both oestrogens and androgens. If that researcher was conducting a study in people with colon cancer, they could evaluate whether correlations exist between the efficacy of the drug and serum concentrations of the relevant hormones (which can be affected by biological, social and environmental factors). If they were working with a mouse model of colon cancer, they might use antagonists or agonists of the relevant hormone receptors or give the animals hormone supplements. A different approach would be needed if the researcher was interested in whether the sex of the T-cell donor changes the efficacy of the treatment depending on the sex of the recipient.

These kinds of analysis could have resource implications: in some cases, different reagents, extra measurements or more animals or participants would be required. In our view, considerable resources should be invested in addressing long-standing gender inequities. Furthermore, researchers do not necessarily need to consider sex and gender in every experiment or study. More important is that they build sufficient skills and understanding to be able to consider the potential impacts of sex and gender and justify their research designs accordingly.

Implicit bias

In addition to considering sex and gender in their work and taking more-nuanced approaches to studying both, it is crucial that researchers explore how the influences of sex and/or gender shape their own research.

Many phenomena in diverse fields, including medicine, archaeology and history, show that science has never been insulated from social and cultural biases, or from stereotypes and mythologies about sex and gender. Funders and regulators are still trying to remedy the lack of inclusion or under-representation of women in clinical trials of drugs or devices. Such biases lead to common mislabelling such as ‘the male hormone testosterone’ or ‘the female X chromosome’ even though testosterone and X chromosomes are important for normal physiological function in all human bodies. Likewise, many studies assess the effects of androgens in only male participants, for instance, or analyse only women’s child-care responsibilities.

Truly understanding the impacts of sex and gender on human life will require a mix of transdisciplinary, quantitative, qualitative and intersectional analyses — which strive to assess how people’s experiences are shaped by interacting social processes, such as racism, sexism, homophobia, transphobia, ableism and colonialism.

Given the enormous untapped opportunities for developing insights concerning sex and gender across many contexts, it is essential that more scientists lean in with courage and creativity to interrogate the fascinating complexity of sex- and gender-related impacts — to the benefit of all.

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Life Style

Take these steps to accelerate the path to gender equity in health sciences

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Diversity in science is instrumental in achieving major breakthroughs. Without further accelerating gender parity and other types of diversity — including focusing on the needs of those in and working towards leadership roles — we will continue to lose valuable ground. At a time when academia faces some of its greatest workforce gaps in history, some of our brightest scholars are leaving institutions before reaching their full potential due to a lack of recognition.

Portrait image of Christina Mangurian

Christina MangurianCredit: UCSF

We applaud changes that have been made for early-career researchers, with more women and historically excluded scholars entering research-training institutions now than ever before. But too often, we lose out on investments made by government funders and institutions in early-career researchers because the system was not built to increase the diversity of leaders as they move up the career ladder.

For 25 years, women have made up more than 40% of the medical student body in the United States, but less than 20% of department chairs in academic medicine. Without a major policy shift to accelerate the rate of diversification among leaders in the country, it will take 50 years for academic medicine to reach gender parity1. That’s way too long.

We must address this with urgency, as women’s perspectives and leadership are key in developing new therapies and improving representation in clinical trials. We need more role models for trainees and junior faculty. All of this leads to pipeline retention and more innovative discovery.

Portrait image of Claire D. Brindis

Claire D. BrindisCredit: Marco Sanchez, UCSF Documents and Media

So, what do we do? We must re-evaluate the way the entire scientific academic enterprise is set up to directly, and indirectly, create challenging climates for women, especially for women of colour. Below, we focus on the policies and procedures that would offer the highest yield in the context of the United States, but that have global relevance.

Elevate the status of gender equity on campus

Public policy value statements. Commitments by academic leaders to diversity measures must be backed by strong policies, protocols and actions directed at all career stages, but particularly focused on supporting emerging and senior women leaders. Organizations must hold leaders accountable for incidents of bias, discrimination and bullying and institute formal, tailored training to promote allyship for some, and active rehabilitation for others.

Confidential reporting. We need better reporting systems to ensure that researchers can highlight gender disparities without fear of retaliation. Ombudsman and whistleblower offices can be helpful, but in the United States, many of these are understaffed to meet the demand. There is also an urgent need to test which approaches are most effective at correcting behaviour.

Implement institutional family-friendly policies

Childbearing/rearing leave. In the United States, there have been gains for faculty members at some institutions and major gains nationally for trainees. But there is room to improve, such as provision of affordable, on-site childcare.

Lactation policies. Only 8% of US medical schools provide financial incentives to make up for clinical time lost while lactating in the first 12 months post-birth. Institutions should be leading the way in establishing policies that recognize the biological factors impacting careers.

Elder care and other informal care. A 2023 study2 found that close to half of female faculty are informal caregivers, and close to half are providing elder care as they reach mid-career. Given that institutions are competing to attract mid- or senior-level women, expansion of paid leave policies to include elder care is warranted.

Formalize equitable distribution of resources and access to opportunities

Compensation. Institutions should regularly perform salary reviews as a means of correcting disparities, especially as it pertains to women of colour. Leaders should also regularly review starting salaries, distribution of endowed chairs, salary increases that are far above the norm and recruitment and retention packages.

Sponsorship. Mentoring and sponsorship roles are increasingly recognized, but more oversight is needed. Behind closed doors is where decisions are made as to who gains access to crucial leadership opportunities; making the invisible visible is key to assuring greater institutional equity.

Focus on faculty promotion and retention

Resources. Offering equitable start-up packages and discretionary funds for new faculty members as well as compensation for dedicated mentors for historically excluded early career researchers can create a supportive professional environment. Such resources are important to offset the time requirements placed on excluded groups who are frequently asked to serve on campus and department committees to meet diversity metrics.

Peer support. Community affinity groups facilitate knowledge exchange needed for career advancement, as well as ‘real time’ support for faculty members. They are easy to set up and yield high returns for participants.

A multi-pronged approach is needed to accelerate gender parity in academic medicine leadership. Rather than continue to attribute disparities to individual ‘failures’, institutions must recognize that structural and organizational interventions can make transformational change.

Competing Interests

The authors declare no competing interests.

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Computers

Stop Misunderstanding the Gender Health Gap

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Well, if weight here is being used as a proxy for sex or gender, a larger woman would need the higher dose; a smaller man a lower dose. So why would you just not use weight as the measure for what dose a person should get? That would be a much more effective way of deciding. But because we collect data along certain lines and not others, then guidelines get written along certain lines and not others.

To give another example, sometimes women’s pain is not fully appreciated when they come forward. Women are statistically more likely to go to a doctor when in pain compared to a man. But then common myths and assumptions start to emerge: “It’s not that serious.” “She’s being hysterical.”

So there are lots of things to pick apart here. It’s the picking apart that we often don’t bother with. We just see a difference, and then that gets ascribed to something without us really knowing what the root cause is.

So how can we get better at picking apart sex differences and sexism to reduce the gender health gap?

For me, it’s about taking medicine to the next level of investigation, which is at the level of the social determinants of health. Many of the things that kill most of us have a huge social or environmental component. Things like diet, stress, the way that we are treated in society.

It’s only relatively recently that research started to be done into the impact of sexism and racism on health, and the impact of other social factors. The job that you do, your status as a married person or not, these can also have health outcomes.

So there’s all these little pieces where research is needed, and it’s an ongoing project. It’s not as though you’ll only do a study once into the effects of being married or being a stay-at-home wife on your health. Because those social factors are always changing.

Sex and gender is an aspect of this social story. But it’s important to understand where it can be appropriately invoked. Sometimes gender is relevant, sometimes it’s not. Sometimes sex matters, sometimes it doesn’t.

What’s standing in the way of things getting better?

Well, research funding agencies are much more interested in looking inside our bodies for explanations for why things are as they are. The outside world is much more difficult to study, because social circumstances are always changing. They can be very different between households, even within households. It’s much harder to collect data on social circumstances.

But we’re at the stage where we can learn so much from people’s mobile phones tracking their activity. Data is being collected on what people are eating, their movements, how active they are. Eventually we’ll be able to build personalized pictures of people, and stop generalizing about people in groups and assuming that they’re typical of that group, and then understand them as a complex individual.

Who is making progress on understanding and closing the gender health gap?

Sarah Richardson’s team at Harvard University—she runs the GenderSci Lab—has done incredible work breaking down the causes of gender health disparities. They’re getting medical researchers to think very carefully about the context of the conditions that they’re investigating.

The team did brilliant work during the pandemic. At the beginning there were all these very wild claims about gender differences with the virus—for instance, that women were protected because on average they have a stronger immune system. They showed that if you looked at the data this didn’t really hold up. They helped dispel this very pseudoscientific assumption that the virus was hitting all populations uniformly, and helped end the neglect of demographic patterns as a factor in Covid, the kind of jobs that people were doing, who were frontline workers, and so on.

This work around sex contextualism, as Richardson calls it, is a really compelling model for how to think about sex and gender in research.

Hear Angela Saini speak at the 10th anniversary of WIRED Health on March 19 at Kings Place, London. Get tickets at health.wired.com.

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