Putting gender on the agenda

Journal name:
Nature
Volume:
465,
Page:
665
Date published:
DOI:
doi:10.1038/465665a
Published online

Biomedical research continues to use many more male subjects than females in both animal studies and human clinical trials. The unintended effect is to short-change women's health care.

Differences in the physiology of males and females, and in their response to disease, have been recognized for decades in many species — not least Homo sapiens. The literature on these differences now encompasses everything from variations in gene expression between male and female mice, to a higher susceptibility to adverse drug reactions in women compared with men. Moreover, hormones made by the ovaries are known to influence symptoms in human diseases ranging from multiple sclerosis to epilepsy.

And yet, despite the obvious relevance of these sex differences to experimental outcomes, three articles in this issue (see pages 688, 689 and 690) document that male research subjects continue to dominate biomedical studies. Some 5.5 male animal models are used for every female in neuroscience, for example. And apart from a few large, all-female projects, such as the Women's Health Study on how aspirin and vitamin E affect cardiovascular disease and cancer, women subjects remain seriously under-represented in clinical cohorts. This is despite reforms undertaken in the 1990s, when sex discrimination in human trials was first widely recognized as a problem.

Admittedly, there can be legitimate reasons to skew the ratios. For instance, researchers may use male models to minimize the variability due to the oestrous cycle, or because males allow them to study the Y chromosome as well as the X. And in studies of conditions such as heart disease, from which female mice are thought to be somewhat protected by their hormones, scientists may choose to concentrate on male mice to maximize the outcome under study.

“Medicine as it is currently applied to women is less evidence-based than that being applied to men.”

However justifiable these imbalances may be on a case-by-case basis, their cumulative effect is pernicious: medicine as it is currently applied to women is less evidence-based than that being applied to men.

The research community can take a number of steps to address this problem. Journals can insist that authors document the sex of animals in published papers — the Nature journals are at present considering whether to require the inclusion of such information. Funding agencies should demand that researchers justify sex inequities in grant proposals and, other factors being equal, should favour studies that are more equitable.

Funding agencies and researchers alike should also start thinking seriously about how to deal with the most fundamental sex difference: pregnancy. Pregnant women get ill, and sick women get pregnant. They need therapies, too, even though they are carrying a highly vulnerable fetus and their bodies are undergoing massive changes in hormonal balance, immune function and much else besides. Entering pregnant women in clinical trials is problematic in the extreme, for a host of ethical reasons. But ignoring the problem is not an answer either — the result is that physicians will prescribe drugs whose effects during pregnancy are poorly known. One possible solution is systematic retrospective data collection from women who have had no choice but to take an unproven drug while they were pregnant.

More generally, drug regulators should ensure that physicians and the public alike are aware of sex-based differences in drug reactions and dosages. And medical-school accrediting bodies should impress on their member institutions the importance of training twenty-first-century physicians in how disease symptoms and drug responses can differ by sex. Finally, speeding more women into the senior ranks of science, which they still struggle to reach (see page 832), could well have a salutary effect in creating an environment in which all such efforts can thrive.

These may be the first steps in the direction of truly personalized medicine — what, after all, is more personal than sex. But they are urgently necessary ones.

Comments

  1. Report this comment #10960

    Anurag Chaurasia said:

    Lower house of Indian parliament has recently passed a law to reserve 33% parliamentary seats for females. World scientific bodies should follow this & implement a law that at least 33% scientific projects, experimental animals/human trails, lab experiments etc should be conducted on female in order to remove gender differences in science. Anurag chaurasia, ICAR,India, anurag@nbaim.org, anurag_vns1@yahoo.co.in, +919452196686(M)

  2. Report this comment #10965

    Dolores Bentham said:

    " to shortchange women's heath care"? Or to save their lives.

  3. Report this comment #10966

    Dolores Bentham said:

    I meant the "OR" Not "AND". The conjunction makes a big difference.

  4. Report this comment #11720

    Elizabeth Pollitzer said:

    Science leaders' consensus on gender in science. An FP7 funded project, genSET, www.genderinscience.org, convened a series of consensus seminars where 14 European science leaders deliberated over a wider range of gender issues in science. They have identified 4 target areas for institutional action on the gender dimension: science knowledge making; human capital; practices and processes; and regulation and compliance. They have also identified 13 specific recommendation for action across these four areas. These recommendations have been informed by over 120 recent research studies and consultation with high-ranking gender research experts. All of this is available in genSET website.

  5. Report this comment #11728

    Norma Swenson said:

    When I first read this piece in Nature I didn't know whether to laugh or cry. It is clear that those who wrote it are quite sincere but ahistoric and did not know or refer to what came before. They can be forgiven for not knowing there was and is a global women's health movement, or something once called feminism, within recent decades. But if they did a literature search of just the so-called scientific literature, they surely would have come across the important article in Science, featuring Barbara Seaman but also several others, dated Science 11 August 1995 269: 766-770 [DOI: 10.1126/science.7638586] (in Articles) by C. Mann.

    But more important than that is the fact that the NIH, National Institutes of Health of US gov, established the Office of Women's Health Research in 1990 precisely because women were not represented or grossly underrepresented in gov't funded clinical trails, thus distorting research results and their application, for exactly the reasons given in this Nature article. It is very hard to believe that the editors of NATURE were unaware of this fact. Judy Norsigian & The Boston Women's Health Book Collective, now Our Bodies, Ourselves ourbodiesourselves.org, played a central role in assisting with the original testimony to establish this office, which is still very influential in US medical and public health education and training, and funded by the US government .

    ODORWH-research@mail.nih.gov

    So it seems nobody reading the article thus far knew any of this either, or in any case did not offer this information to readers. Amazing.

  6. Report this comment #35724

    Leah Kimple said:

    "Differences in the physiology of males and females, and in their response to disease, have been recognized for decades in many species ? not least Homo sapiens. The literature on these differences now encompasses everything from variations in gene expression between male and female mice, to a higher susceptibility to adverse drug reactions in women compared with men. Moreover, hormones made by the ovaries are known to influence symptoms in human diseases ranging from multiple sclerosis to epilepsy." Makes sense to me!
    http://eyeonjesus.com":http://eyeonjesus.com/ | Legal Shield | Easytether

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