Women live longer than men. This fact is conserved in sickness, during famines, during epidemics, and even during starvation. But longevity is not the same as vitality, and the statistics behind this headline tell a much more complicated story.

Despite outliving men in nearly every country, women spend a disproportionately larger share of their lives in poor health. According to a landmark McKinsey Health Institute report, that gap translates to roughly 75 million disability-adjusted life years (DALYs) lost annually. This means losing 7 days of healthy living per woman per year. Imagine that – although for some of you reading this, you don’t have to, because that’s the reality you’re living in.

It is a quiet epidemic, one that rarely makes front pages and barely registers in the budgets of the institutions tasked with solving it. The reasons are structural, scientific, and deeply entrenched. For most of medical history, the male body has been the default: the template against which disease is defined, drugs are dosed, and clinical trials are designed. What we call “standard” medicine may, in fact, be male medicine. And that distinction matters enormously.

I will now walk you through why sex biology is one of the most consequential and underfunded frontiers in modern healthcare and why closing the gap is not just a matter of equity, but of scientific completeness.

I. The Burden of Being a Woman

When people think of women’s health, they tend to think of reproductive health: contraception, pregnancy, menopause. It is an understandable association, but a limiting one. Sexual and reproductive health accounts for roughly 5% of the total women’s health burden. The remaining 95% is split between conditions that affect women disproportionately (47%), including autoimmune disease and depression, and conditions that do not affect women disproportionately (~43%). Of the conditions that do not affect women disproportionately, I started to wonder: is there really no difference at all? Do they manifest differently in female bodies? And by assuming similar cause and mechanism regardless of sex, are we overwriting an important nuance?

Cardiovascular disease (CVD) is a stark example of nuance. Heart disease happens across sexes. In fact, it is the leading cause of death in women globally, with more than 60M women living with CVD. Yet, it remains widely perceived, by patients and physicians alike, as predominantly a male disease. Think Vito Corleone in The Godfather or a reference from this decade – Mr. Big from Sex and the City after that infamous Peloton session. And yet, no female counterpart quickly comes to mind. This perception has consequences.

Heart disease doesn’t look the same in women

Before age 50, men have a higher incidence of coronary artery disease (CAD), a type of CVD characterized by blockage of major blood vessels primarily due to atherosclerosis, a type of plaque buildup. But when women do experience acute coronary events, their prognosis is worse. After menopause, the incidence of CAD in women rises sharply and ultimately surpasses that in men, a transition driven in part by the withdrawal of estrogen’s cardioprotective effects.

The biology of atherosclerosis itself differs by sex. In women, plaques tend to be more stable, richer in smooth muscle cells, and prone to erosion rather than rupture. Women are also significantly more likely to experience atypical symptoms: shortness of breath, fatigue, nausea, or pain in the back and jaw, rather than the canonical crushing chest pressure that medical training centers on (Fig 1).

Pregnancy adds another layer of complexity. Hypertensive disorders of pregnancy, including preeclampsia, affect up to 10% of pregnant women in the United States and account for over 70,000 maternal deathsworldwide each year with lasting cardiovascular fingerprints for both mother and baby.

I would also be incredibly remiss if I didn’t mention that these disparities are not evenly distributed. Women of color face compounding disadvantages: higher rates of hypertension, more aggressive disease courses, and documented disparities in access to care and quality of treatment.

The consequences of this health gap are well-documented: women are 50% more likely to receive an incorrect diagnosis following a cardiac event. This is failure at the systems level. Troponin tests, which measure levels of proteins released into the bloodstream upon heart muscle cell damage, are used as the gold standard for diagnosing acute coronary syndrome. However, historically they have been calibrated against male reference ranges. Women are offered fewer diagnostic tests, referred less frequently to cardiologists, and prescribed cardiovascular medications at lower rates. For cardiac events, time is of the essence, but for women, the clock keeps ticking.

Fig 1. Depiction of cardiovascular disease symptoms in men vs women.

II. X Marks the Spot… Sort Of

To understand why the female body experiences disease differently, you have to start with the genome. Women carry two X chromosomes; men carry one. That difference is not merely a matter of sex determination. It shapes immunity, metabolism, epigenetics, and cardiovascular risk in ways science is only beginning to map.

The X chromosome and cardiovascular risk

The influence of the X chromosome on cardiovascular health is something we’re only starting to appreciate. Studies in the four-core genotypes (FCG) mouse model delineate contributions from sex chromosome complement (XX vs. XY) and sex organs, revealing the interactive effects between the two. Mice with two X chromosomes, regardless of whether they have ovaries or testes, accumulate more fat than XY mice, demonstrating that X chromosome dosage is a meaningful determinant of fat storage — particularly under conditions of high-fat diet or reduced gonadal hormones. The extra X promotes fat accumulation in ways that may independently elevate cardiovascular risk.

Having two X’s also means that to balance out the dosage of X chromosome genes between XX and XY cells, transcriptional inactivation of one X chromosome occurs during development. Of course, nothing is perfect and some genes escape inactivation (~20% of X chromosome genes). One gene of special interest is KDM5C, an epigenetic regulator responsible for DNA methylation, thereby controlling expression of thousands of genes. Ongoing studies aim to further explore the effect of DNA-methylation on cardiometabolic health.

Yet, saying the presence of an additional X explains the whole picture is like the blind man touching the elephant’s trunk and yelling “Snake!” Human evidence adds texture, if not clarity. Women with Turner syndrome (XO) have a higher prevalence of cardiovascular disease and men with Klinefelter syndrome (XXY) show elevated rates of cardiovascular mortality. Interpreting these signals is complicated by co-existing conditions (anatomical cardiovascular abnormalities, hypogonadism, and metabolic susceptibilities) that make isolating the independent contribution of the sex chromosomes genuinely difficult.

Research in transgender individuals receiving hormone therapy adds another level of nuance: trans women have an increased risk of myocardial infarction compared to age-adjusted cisgender peers — a finding that, while still being characterized, suggests the hormonal and chromosomal axes of cardiovascular risk interact in ways that remain underexplored.

The X chromosome picture is, in short, real but partial. It illuminates mechanisms without fully resolving them. Which may itself be the most important takeaway: CVD is an example to illuminate the incompleteness of sex-specific science. This is not a feature unique to cardiology. It is both a warning sign and hopefully a preview of the trove of knowledge left to be discovered. Any indication with deep mechanistic complexity — autoimmunity, neurodegeneration, metabolic disease — stands to be better understood when researchers stop treating “male” as the default and start asking what female biology specifically does. The field doesn’t just owe women better science. It stands to gain from it.

III. Bridging the Gap

Despite women making approximately 80% of household healthcare decisions, only 5-6% of healthcare R&D investment is directed at women’s health. This asymmetry is an equity problem but could also be the catalyst for change.

The data problem

Before solutions can scale, the evidence base (e.g. data and science) needs to exist. Much of it doesn’t. Our mechanistic understanding of how common diseases manifest differently in female bodies remains fragmentary. The definitions and measurement scales used for symptoms predominantly affecting women, from chronic pain to fatigue to perimenopause, lack standardization, making it hard to aggregate findings or design meaningful trials.

Fig 2. Plot showing PubMed search results for keywords including “sex-specific”, “sex differences”, “biological sex”, and “sex-stratified”, as plotted by field (neuroscience, cardiology, immunology) from the years 1995 to 2023 as absolute counts (left) or as proportion of total papers published in that field that year (right) with dotted line showing the year SABV went into effect.  

The NIH mandated in 2016 that sex be treated as a biological variable in preclinical research (the SABV policy). While over the last 10 years, there has been a general increase in papers highlighting sex-specific differences, of the total number of papers published in a given field, sex-specific research consistently remains under 1% (Fig 2). Compliance has been inconsistent, enforcement limited, and the cultural inertia of male-default science is not undone by a single mandate.

The tools problem

To mine for gold, you need a good axe. Technology has come a long way, with the development of high-throughput sequencing and single-cell analyses. But to go mining in the ovary, we are dangerously lacking in tools. This was explained to me by Mariko Foecke, PhD, a former PhD student in Dr. Diana Laird’s lab at UCSF who is now a scientist at Vitra Labs, a start-up developing hormone-free in vitro fertilization (IVF). Long story short: she knows ovaries. And what she tells me is that conventional tools used in fields like immunology, such as flow cytometry, are much harder to apply in reproductive biology due in part to something seemingly so trivial: a lack of validated antibodies. (That’s before you account for the fact that grown oocytes exceed the theoretical size limits of most microfluidic devices). Additionally, a key limitation of tamoxifen-based induction systems is that tamoxifen functions as a selective estrogen receptor modulator, which disrupts pregnancy and precludes its use in pregnant mice. Investigators in this field are forging ahead with one hand tied behind their backs.

Diagnostic tools for women’s health are also very much lagging. Katarina Klett, PhD, the Director of Research Translation at QB3-Central who recently organized a symposium around ovarian health, took time to chat with me on where she sees the biggest gaps and opportunities. She talked to me about her north star: how do we improve patient lives and therefore quality of life for women. There’s a lot of hype currently around wearables, which could be helpful in documenting data around menstrual cycles, sleep, heart health, but “[ultimately], we won’t treat menopause or endometriosis with an app.” Where she sees a major unmet need is in diagnostics for conditions like endometriosis because “1/2 the population has ovaries; 10% of that half anticipate having endometriosis.” These metrics highlight a huge untapped market.

Positive signals

There are reasons for measured optimism. Philanthropic investment from organizations like the Gates Foundation (note: Melinda Gates recently pledged $215M to focus on women’s reproductive and midlife health) and the Novartis Foundation has directed funding toward women-specific research that industry incentives haven’t historically prioritized. The volume of sex-specific research indexed on PubMed has been trending upwards over the past decade (Fig 2). While not a headliner, it’s at least in the lineup; and researchers and investors alike are taking notice.

AI and computational tools may accelerate the catch-up. Sex-balanced stratification in study design, synthetic control arms, and post-hoc sex-disaggregated analysis of existing trial data are all areas where machine learning can reduce the cost and time required to generate sex-specific evidence. And these efforts can start now: data is all around us, as exemplified by Irene Chen’s work, a professor at UC Berkeley and UCSF who mined electronic health records to characterize menopause onset at scale and diversity.

From research to clinic

Translating research into clinical tools and therapies is where the rubber meets the road. On the diagnostics side, companies like Lighthearted AI are developing AI-powered, point-of-care devices designed to detect heart valve and vascular conditions across all skin tones, helping to expand equitable access to care.

In therapeutics, non-hormonal alternatives to address menopause symptoms, like Bayer’s elinzanetant, represent optionality in a space where the current treatment is hormone replacement therapy. Clinical trial design is also evolving: Veradermics, a start-up developing a non-hormonal pill for pattern hair loss, is pursuing dedicated studies in both men and women with the first-ever phase 3 trial for female pattern hair loss currently undergoing active enrollment.

Perhaps most importantly, the framing of women’s health is beginning to shift from episodic to longitudinal. Companies like Midi Health, which raised $150M across two rounds in 2025 and recently surpassed $1B in valuation, are building virtual care models that treat women’s health across the midlife continuum: perimenopause, menopause, and beyond, across all 50 states. The insight underlying this model is deceptively simple: a woman’s biology is not static, and her healthcare shouldn’t be either.

IV. The Next Frontier

Women’s health is the next frontier in medicine, not because the problem is new, but because the confluence of real, documented sex-driven disparities, a still-nascent mechanistic understanding, and an accelerating research base has created conditions for transformative change. The opportunity runs the full length of the translational pipeline: from basic science that has barely begun to characterize sex-specific biology, to the systematic re-examination of existing standards of care, to a future in which treatments for conditions well beyond reproductive health are purpose-built for women. But the stakes here are larger than patient outcomes alone. The deeper problem is that science has been impoverished by the exclusion of women. Correcting such exclusion is not a matter of adding women to existing frameworks; it requires rebuilding parts of those frameworks entirely, such as tool-building and better infrastructure to enable generation of more (and better) data. The publication trends documented here suggest that scientific attention is finally, meaningfully shifting. The question now is whether investment, institutions, and clinical culture will move with the same urgency — because women’s health is not a niche. It is half of medicine.

Written By: Wendy Hung (PhD student in the Department of Immunology, University of California, San Francisco)

Edited By:  Xingyu (Jasmine) Hu (PhD student in the Department of Biomedical Engineering, Boston University)