SCIENCE MAGAZINE: The latest issue features ‘WOMEN’S HEALTH’….

A Lifelong Focus on Women’s Health

Historically, most human studies have involved male participants, and their findings were assumed to apply to women and children as well. Meanwhile, women’s health typically came up in the context of reproduction and childbearing, if at all. However, biomedical science has come a long way over the years, and it has become increasingly clear that there are sex-dependent differences in many diseases that do not involve reproduction and that occur at all ages. Across all areas of women’s health, including both reproductive and nonreproductive conditions, much remains to be learned about the underlying biology, effects of hormones and genetics, and potential therapeutic interventions.

X and Y chromosomes as determinants of aging and disease

Sex differences have traditionally been attributed to gonadal hormones, but accumulating evidence shows that sex chromosomes exert distinct, cell-autonomous effects on health, aging, and disease. XX and XY complements alter gene dosage, epigenetic programming, immune signaling, metabolism, and cellular stress responses, which shape aging and disease trajectories in women and men. This Review integrates mechanistic advances in sex chromosome biology—including escape from X chromosome inactivation, X reactivation, parent-of-X-origin, X-skew, X- and Y-linked gene functions, and Y loss—with aging, neurologic disease, immunity, cancer, and cardiometabolic disease. We highlight insights from mouse models, human studies, and emerging technologies that disentangle hormone-driven effects from chromosome-mediated effects and discuss translational implications for diagnostics, biomarkers, therapeutics, and clinical trial design, emphasizing the integration of sex chromosome biology into precision medicine.

Reframing menopause and menopause hormone therapy as opportunities for healthy aging

Menopause is an important biological transition with up to 72 symptoms that shapes aging trajectories across organs and encompasses ~40% of the female lifespan. Although menopause awareness is increasing, research on strategies for menopause symptom management and optimizing health in the postmenopausal period is lacking. This Review highlights that menopause characteristics, such as type, timing, and symptom burden, influence health outcomes and later-life disease risk. Similarly, menopause hormone therapy comes in >200 varieties that differ by dose, formulation of estrogens and progestogens, and timing, each with their own distinct risk-benefit profiles. These distinctions are often missed in the literature but have considerable repercussions for outcomes. Optimized menopause care necessitates a precision medicine approach that considers menopause symptoms, genetics, and previous hormone exposures.