Historically, medical research has relied heavily on male participants, with findings often generalized to women and children. If women’s health is discussed at all, it’s largely framed around reproduction. In this Special Issue of Science, four Reviews and a Perspective highlight the research that is seeking to close the critical gaps in women’s health. “Overall, it is becoming increasingly clear that women’s health and sex-dependent biological differences go well beyond reproduction and affect people throughout their lifespan and across different medical conditions,” write Science Senior Editor, Yevgenia Nusinovich and colleagues.
It has long been recognized that millions of women, especially younger women, are disproportionately affected by pain disorders; women experience functional pain disorders at roughly twice the rate of men, with some conditions showing an even greater disparity. Persistent pain can be especially debilitating when it affects the pelvis, where disorders involving the gut, bladder, and reproductive organs, including IBS, endometriosis, and vulvodynia, can produce unpredictable symptoms. In this Review, Archana Venkataraman and colleagues synthesize recent advances in understanding these conditions, focusing on the roles of sex hormones, immune-neural interactions, the gut microbiome, and endogenous analgesic pathways; fluctuations in ovarian hormones beginning at puberty appear to be a major contributor, they say. While a growing body of research is beginning to illuminate how hormonal signals interact in women’s bodies to produce sex differences, major gaps remain between the widespread burden of pain among women and the scientific efforts to understand and treat it. “Women are desperately waiting for concrete answers that might help eliminate the common ‘all in your head’ approach to their illnesses, shorten the long wait between symptoms and diagnosis/treatment, and ultimately provide mechanism-based strategies for disease treatment,” write the authors.
Menopause research has historically been underfunded and understudied, despite its enormous impact on half of the human population and nearly 40% of a woman’s lifespan. In a second Review, Larua Gravelsins and colleagues argue that menopause research needs a major rethink, shifting from a one-size-fits-all view of the transition to a precision-medicine approach that accounts for differences in symptoms, timing, genetics and hormone treatments. The authors say this shift could help address the persistent gaps in understanding menopause and menopause hormone therapy. “Diminishing menopause to ’just aging’ is a disservice to women,” write Gravelsins et al. “Menopause is a full-body, hormonally driven change that, like other endogenous hormonal transitions, affects individuals differently based on their individual biology and life experience.”
In a third Review, Dan Corral and Yasmine Belkaid highlight the emerging research surrounding the immune system’s role in preparing a mother’s body for pregnancy. Pregnancy triggers one of the most extensive periods of physiological remodeling in adult life, requiring coordinated changes across nearly every maternal organ. While these changes have traditionally been attributed largely to hormones, new research shows that the immune system actively directs this remodeling, reprogramming maternal tissues in ways that may influence health well beyond pregnancy. Yet despite its profound biological importance, the mechanisms underlying this transformation remain incompletely understood and have historically been understudied.
The final Review by Dena Dubal and colleagues examines how XX and XY chromosomes influence aging and diseases, including neurological, immune, cancer, and cardiometabolic disorders. According to the authors, the collective findings from these studies emphasize the importance of integrating sex chromosome biology into precision medicine and have important implications for future therapeutics and clinical trial design.
In a Perspective, Michael Stout and Francesca Duncan discuss how the ovaries influence health after menopause. The postmenopausal ovary has long been viewed as a largely dormant organ once its reproductive function ends, but growing evidence suggests it remains biologically active for decades after menopause. Determining the ovary’s postmenopausal functions, and whether removing it after menopause affects long-term health, will require further research.
