Why Women's Health Was Left Out
For decades the first tests of new medicines were run largely without women who could become pregnant, and the gap left a measurable trail in side effects. The new wellness market promises to close it, while selling the kind of expectation that a 1977 experiment showed can produce symptoms of its own.
Answer to the question
Why has women's health been understudied?
Mainly because of protective rules and a male default. A 1977 FDA guideline said women of childbearing potential should not join phase 1 and early phase 2 drug trials, and only the 1993 NIH Revitalization Act required women in NIH-funded clinical research. A 2020 review found women have adverse drug reactions nearly twice as often as men.
Key takeaways
- A 1977 FDA guideline said women of childbearing potential should not be included in phase 1 and early phase 2 drug trials; the FDA revoked that restriction in 1993, the year the NIH Revitalization Act required women in NIH-funded clinical research.
- In Irving Zucker's 2020 analysis of 86 drugs, 76 reached higher blood levels or cleared more slowly in women, and 96 per cent of those were linked to more adverse reactions in women.
- A January 2024 report by the World Economic Forum and the McKinsey Health Institute estimates that women spend 25 per cent more of their lives in poor health than men.
- Diane Ruble's 1977 study showed that believing a period is close raises reported physical symptoms, while a 1998 NIMH study found a real abnormal response to normal hormone changes in women with premenstrual syndrome.
General information on women's health research, not medical advice; see a qualified professional. Medical review:.
In 1977 the researcher Diane Ruble told some women that their period was close and others that it was some way off, whatever their real cycle phase. Those led to believe it was close reported more physical symptoms, such as water retention, than those led to believe they were between periods.
False forecasts and reported symptoms
Ruble's two-page report in Science argued that questionnaires about premenstrual symptoms measure belief as well as the body, so earlier conclusions about the size and physical basis of menstrual changes needed re-examining. Her result raises the question this article answers. Did women's health fall behind because women's symptoms were misread, or because women were left out of the research that decides how medicines are tested? The record of trials, side effects and diagnosis suggests mainly the second.
Chapter 9 of David Robson's The Expectation Effect (2022), "Untapped genius", takes the first possibility seriously. Drawing on the neuroscientist Gina Rippon, it argues that expectations shape the experience of premenstrual syndrome and that gendered expectations shape children's developing brains, part of the book's wider case that the brain works as a prediction machine. The chapter gives Rippon's account without the scientific debate around it. Expectation can inflate a symptom, and the idea of expectation can also be used to explain away a symptom that has a physical cause.
Protective rules, missing women
Ruble's study appeared in the year the US Food and Drug Administration issued "General Considerations for the Clinical Evaluation of Drugs", a guideline developed, in the agency's later words, "within the protective environment brought on by the thalidomide experience a decade earlier". It stated that women of childbearing potential should not be included in phase 1 and early phase 2 trials, the stages that include dose tolerance studies. They could join later trials, but much of the earliest dose and safety work went ahead without them. The FDA revoked the restriction in 1993, one step in a reversal of policy on women's health research that took most of four decades.
1. 1977: FDA guidance keeps women of childbearing potential from early trials.
2. 1986: the NIH urges researchers to include women in human studies.
3. 1990: about a fifth of NIH grant applications omit participants' sex.
4. 1993: the NIH Revitalization Act requires women in NIH-funded clinical research.
5. 2016: NIH policy on sex as a biological variable takes effect.
Laboratory animals stayed mostly male for longer. A 2011 review led by Annaliese Beery, with Irving Zucker, looked at studies of mammals in ten biological fields from 2009 and found a male bias in eight of them, strongest in neuroscience, where single-sex studies of male animals outnumbered those of females by 5.5 to 1. Over the previous half-century, the authors reported, male bias in animal studies had grown while it fell in human studies, and the belief that female animals are too variable for routine use in research was without foundation. Studies of both sexes, they added, frequently failed to analyse results by sex.
Side effects by sex
Withdrawn drugs gave an early sign of the cost. A General Accounting Office report of January 2001 found that 10 prescription drugs had left the American market since the start of 1997, and that eight of them posed greater health risks for women than for men. Four of the eight, the report said, may have led to more adverse events in women because they were prescribed more often to women.
Of 10 prescription drugs that left the American market from 1997, eight posed greater health risks for women than for men.
A 2020 analysis offers one explanation. Searching the published literature for sex differences in how 86 drugs reach and leave the blood, Zucker and Brian Prendergast found that 76 reached higher concentrations or took longer to clear in women. For 59 drugs with clearly identifiable adverse reactions, that difference predicted which sex had more reactions in 88 per cent of cases, and 96 per cent of the drugs with higher levels in women were linked to more reactions in women. Body weight did not explain it. Their paper starts from two facts: women experience adverse drug reactions nearly twice as often as men, and most drugs in use were approved on trials conducted on men.
A gap counted in years
In 2024 the McKinsey Health Institute described the habit behind this bluntly, writing that women have been treated by the scientific and medical communities "as though they are small men". Its report with the World Economic Forum, published on 17 January 2024, tried to put a size on women's health as a whole. It estimates that women spend 25 per cent more of their lives in poor health than men, even though they live longer. On its modelling, closing the gap would add an average of seven healthy days for every woman each year, more than 500 days over a lifetime, and up to $1 trillion a year to the global economy by 2040.
The report also argues that women's health is often simplified to sexual and reproductive health, which it says "meaningfully underrepresents women's health burden". Conditions inside that definition go unrecognised too. The World Health Organization's fact sheet on polycystic ovary syndrome, dated 22 January 2026, estimates that it affects 10 to 13 per cent of women of reproductive age, and that up to 70 per cent of those affected worldwide do not know they have it.
A gap expressed in healthy days and dollars comes from disease-burden models, and an undiagnosed share is hard to count. The 2001 report tied half of the excess risk partly to prescribing, and in the 2020 analysis higher drug levels in men predicted more reactions in men in only 29 per cent of cases. Even so, women entered trials late, and a common condition still goes unrecognised in many of the women who have it.
Wellness sold as expectation
Five days after that WHO update, the Global Wellness Summit released its trends for 2026, one headed "Women Get Their Own Lane in Longevity", with the ovary described as "command central" for women's health. Marketing works partly by setting expectations, and a market that sells hormonal explanations for everyday feelings is in the business of creating the expectation Ruble found in 1977. The 2013 Canadian study described below began from that point, noting that the common belief in premenstrual mood symptoms is shaped by social expectations about gender, emotionality and hormonal influences.
Hormones still matter for some women. When researchers at the US National Institute of Mental Health suppressed ovarian function in women with premenstrual syndrome, in a 1998 study with Peter Schmidt as first author, symptoms fell compared with placebo. Ten women whose symptoms improved were then given estradiol and progesterone in turn, each for four weeks, in a double-blind crossover design, and their symptoms came back, while 15 women without the syndrome showed no change in mood on the same regimen. The team concluded that "the occurrence of symptoms represents an abnormal response to normal hormonal changes".
In the general population, daily circumstances seem to count for more. Sarah Romans and colleagues asked a random sample of Canadian women aged 18 to 40 to record their mood every day for six months, giving 395 complete cycles, in a study published in 2013. Only half the mood items showed any link with cycle phase, mostly with menstruation itself rather than the days before it, and physical health, perceived stress and social support predicted mood much better. The authors wrote that the results did not support the widespread idea of a specific premenstrual low mood.
Only half the mood items showed any link with cycle phase, and physical health, perceived stress and social support predicted mood much better.
The answer to the opening question is mostly the second. Expectation shapes how women report how they feel, and hormone sensitivity is real for some, but the larger shortfall lies in who was tested and who gets diagnosed, and a wellness market built on hormonal explanations changes neither. The FDA's 1993 guideline did more than lift its restriction: it encouraged women of childbearing potential to take part in early trials.
Common questions
Why has women's health been understudied?
Mainly because of protective rules and a male default. A 1977 FDA guideline kept women of childbearing potential out of phase 1 and early phase 2 drug trials, and only in 1993 did the NIH Revitalization Act require women in NIH-funded clinical research. Animal studies stayed mostly male for longer, with single-sex studies of males outnumbering those of females 5.5 to 1 in 2009 neuroscience.
Do women get more side effects from medicines?
Women experience adverse drug reactions nearly twice as often as men, as the 2020 analysis by Irving Zucker notes. Of 86 drugs, 76 reached higher blood levels or cleared more slowly in women, and that predicted more reactions in women. A 2001 government report found eight of ten withdrawn drugs posed greater risks for women.
Is premenstrual syndrome caused by expectation?
Partly, for some reported symptoms. Diane Ruble's 1977 study found that women led to believe their period was close reported more physical symptoms. A 1998 National Institute of Mental Health study found that women with the syndrome reacted abnormally to normal hormone changes, so for them the symptoms have a hormonal trigger.
Sources
Ruble, D. N. (1977). 'Premenstrual symptoms: a reinterpretation.' Science, 197(4300), 291-292. doi:10.1126/science.560058. Abstract read: women's perceived cycle phase was separated experimentally from actual phase; those led to believe they were premenstrual reported significantly more physical symptoms, such as water retention, than those led to believe they were intermenstrual.
Robson, D. (2022). The Expectation Effect: How Your Mindset Can Transform Your Life. Canongate. Read in full by this publication, with a reliability audit. Ch. 9, 'Untapped genius' (Gina Rippon on gendered expectations and premenstrual syndrome).
US Food and Drug Administration (1997). 'Investigational New Drug Applications; Proposed Amendment to Clinical Hold Regulations for Products Intended for Life-Threatening Diseases.' Federal Register, 62(185), 24 September 1997, Docket No. 97N-0030. Full text read: describes the 1977 guideline 'General Considerations for the Clinical Evaluation of Drugs', developed 'within the protective environment brought on by the thalidomide experience a decade earlier', which stated that women of childbearing potential should not be included in phase 1 and early phase 2 trials; and the 1993 guideline (58 FR 39406, 22 July 1993) that revoked the restriction.
US Food and Drug Administration (2025). 'Evaluation of Sex Differences in Clinical Investigations: Guidance for Industry.' Final guidance, January 2025, Docket No. FDA-2013-S-0610. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/evaluation-sex-differences-clinical-investigations. Full text read: describes the FDA guideline of 22 July 1993 as lifting a restriction on most women with childbearing potential entering Phase 1 and early Phase 2 trials and as now encouraging their participation.
NIH Office of Research on Women's Health. 'ORWH timeline' (institutional page). Full text read: 1986 NIH inclusion policy urging applicants to include women and minorities; 1990 General Accounting Office study finding about 20 per cent of NIH grant applications gave no information on the sex of the study population; 1993 NIH Revitalization Act requiring inclusion of women and minorities in NIH-funded clinical research; 2016 NIH Policy on Sex as a Biological Variable took effect.
Beery, A. K., & Zucker, I. (2011). 'Sex bias in neuroscience and biomedical research.' Neuroscience and Biobehavioral Reviews, 35(3), 565-572. doi:10.1016/j.neubiorev.2010.07.002. Abstract read: 10 biological fields for 2009; male bias in 8; neuroscience single-sex male studies outnumbered female 5.5 to 1; male bias in non-human studies increased over the past half-century while declining in human studies; belief that female animals are intrinsically more variable is without foundation.
US General Accounting Office (2001). 'Drug Safety: Most Drugs Withdrawn in Recent Years Had Greater Health Risks for Women.' GAO-01-286R, 19 January 2001. Full text read: 10 prescription drugs withdrawn since 1 January 1997; 8 posed greater health risks for women; 4 of these may have led to more adverse events in women because they were prescribed more often to women.
Zucker, I., & Prendergast, B. J. (2020). 'Sex differences in pharmacokinetics predict adverse drug reactions in women.' Biology of Sex Differences, 11, 32. doi:10.1186/s13293-020-00308-5. Abstract read: women experience ADRs nearly twice as often as men; of 86 drugs, 76 had higher PK values in women; for 59 drugs with clinically identifiable ADRs, sex-biased PKs predicted the direction of sex-biased ADRs in 88 per cent of cases; 96 per cent of female-biased PK drugs associated with more ADRs in women; only 29 per cent of male-biased PKs predicted male-biased ADRs; not explained by body weight; authors recommend evidence-based dose reductions for women.
World Economic Forum and McKinsey Health Institute (2024). 'Closing the Women's Health Gap: A $1 Trillion Opportunity to Improve Lives and Economies.' Published 17 January 2024. Full text read of the publication page and the McKinsey Health Institute release: women spend 25 per cent more of their lives in poor health than men; closing the gap could add seven healthy days per woman per year, more than 500 days over a lifetime, and up to $1 trillion a year to the economy by 2040; women treated 'as though they are small men'; women's health often simplified to sexual and reproductive health, which 'meaningfully underrepresents women's health burden'.
World Health Organization (2026). 'Polycystic ovary syndrome' fact sheet, dated 22 January 2026. Full text read: PCOS affects an estimated 10 to 13 per cent of reproductive-aged women; up to 70 per cent of affected women worldwide do not know they have it.
Global Wellness Summit (2026). 'Global Wellness Summit releases 10 wellness trends for 2026', press release, 27 January 2026. Full text read: trend titled 'Women Get Their Own Lane in Longevity', describing the ovary as 'command central' for women's health.
Schmidt, P. J., Nieman, L. K., Danaceau, M. A., Adams, L. F., & Rubinow, D. R. (1998). 'Differential behavioral effects of gonadal steroids in women with and in those without premenstrual syndrome.' New England Journal of Medicine, 338(4), 209-216. doi:10.1056/NEJM199801223380401. Abstract read: leuprolide ovarian suppression reduced symptoms in 10 women with PMS compared with 10 given placebo; estradiol or progesterone add-back brought symptoms back in women with PMS but not in 15 women without it.
Romans, S. E., Kreindler, D., Asllani, E., Einstein, G., Laredo, S., Levitt, A., Morgan, K., Petrovic, M., Toner, B., & Stewart, D. E. (2013). 'Mood and the menstrual cycle.' Psychotherapy and Psychosomatics, 82(1), 53-60. doi:10.1159/000339370. Abstract read: random sample of Canadian women aged 18 to 40, daily mood for six months, 395 complete cycles; only half of mood items showed any cycle-phase association, mostly with menses; physical health, perceived stress and social support were much stronger predictors of mood; results do not support the widespread idea of specific premenstrual dysphoria.