To highlight a new Special Issue devoted to women’s health, Science Advances will host a press briefing on Tuesday, March 4, at 11am US ET. Five panelists will each discuss one piece from the issue, including one Focus, one Review, and three Research Articles. Journalists may register to attend the briefing here: https://aaas.zoom.us/webinar/register/WN_N8ujjbcBTk-4Me2WcWX_7A  Nine other pieces from the issue are summarized elsewhere in this press package.

Medicine has historically overlooked the impact of sex and gender, but in a new Focus, Bronwyn Graham and colleagues argue that inclusion is only the first step in repairing this knowledge gap. Although inclusion is important, it still operates within a scientific system in which research focuses on the male body. “Consideration, by definition, requires deeper thought about how sex- and gender-specific variables may influence the outcomes measured,” Graham et al. write.

In a Review, Caspar Kaiser and colleagues examine a long-reported phenomenon called the global gender gap in wellbeing. Although women today self-report higher happiness and satisfaction than men, research has documented an increase in negative affect (experiencing negative emotions and a poor sense of self-worth) in the mental health of women. Kaiser et al. assessed data collected in Europe and the United States from the 1970s to the present, alongside global data gathered from 2006 to 2023. Their analyses uncovered that the gender gap is not as globally universal as thought and revealed an ongoing global decline in women’s wellbeing, especially seen through negative affect.

In one study, Gillian Coughlan and colleagues investigate the effects of menopausal hormone therapy on women’s Alzheimer’s disease (AD) risk and occurrence across age. They examined 146 women between 51 and 89 years old with clinical baseline levels of cognition. Of the participants, 73 took hormone therapy and 73 did not. Coughlan et al. monitored tau expansion over 3.5 years (and β-amyloid expansion over 4.5 years) through PET neuroimaging. Women over 70 years old on hormone therapy showed increased tau accumulation in three regions of the temporal lobe, while women in this demographic who were not on hormone therapy did not show the same increase in tau accumulation. However, this relationship was insignificant in women under 70 taking hormone therapy.

In another study, Madeline Wood Alexander and colleagues consider how age at menopause and history of hormone therapy interact with biomarkers of synaptic health (β-amyloid and tau) to contribute to AD and dementia in women. Wood Alexander et al. examined clinical and autopsy data from 268 Rush Memory and Aging Project participants who entered spontaneous menopause at an average of 49.2 years old. Earlier menopause onset significantly corresponded with more tau tangle buildup and faster cognitive decline. There was no association with β-amyloid levels. Notably, women who entered menopause earlier but then took hormone therapy did not exhibit this association strongly.

In a third study, Margaret Gadek and colleagues examine how aging-driven reactivation of genes in the silent X chromosome affects cognitive decline in female mice. Using RNA sequencing, they observed that transcription of silent X genes, such as Plp1, increased in aging female mice, amplifying existing activity in the active X chromosome. Plp1 facilitates memory-related activities in the hippocampus’s dentate gyrus. Gadek et al. then upregulated Plp1 in hippocampal cells in both aging female and male mice, and saw that it improved their cognition. They corroborated these findings by tracking expression of silent X Plp1 in the parahippocampi of aging women in the Mount Sinai Brain Cohort.

Journalists may download a recording and transcript of the briefing here: https://aaas.zoom.us/rec/share/u7igvloXfFIWQprB-I9KB3RJP4sB7LZ5z-IGekbfM0nSu_Cg0oLq9V8JAhleSIEv.FMtx4wSd696HcyYh, Passcode: s#!6Qcek.

In this Women’s Health-focused Special Issue of Science Advances, 2 Research Articles, 1 Review, and 1 Focus enumerate the impacts of sex differences on genetics, aging, and hormones. In her Introduction, Tali Sharot, Section Editor for Neuroscience at the journal, explains the impetus for the special issue and how such research can rectify current women’s health disparities. “The science of women’s health is at a crossroads,” Sharot writes. “For decades, it has been limited by an underrepresentation of women in clinical trials and research, resulting in diagnostic blind spots, treatment gaps, and inequities in health outcomes.” As part of the Special Issue, a Review by Anna Bonkhoff and colleagues summarizes recent work investigating sex differences related to hormones, genes, and aging in Alzheimer’s disease (AD) and stroke. One study by Monika Haoui and colleagues describes how progesterone and progestins target the Kir7.1 channel to regulate the uterus and support placental function in mid- and late pregnancy, by leveraging experiments with mice and data from human postpartum placental tissues. Another study in mice by Jessica Minder and colleagues details how oxytocin can limit embryonic development during nursing. In a Focus, Jellina Prinsen and colleagues spotlight how research into the menstrual cycle can enhance knowledge about how sex hormones impact the brain and heart, with benefits for female-centered medicine.

A new study from Mass General Brigham researchers has found faster accumulation of tau—a key indicator of Alzheimer’s disease—in the brains of women over the age of 70 who took menopausal hormone therapy (HT) more than a decade before. Results, which are published in Science Advances, could help inform discussions between patients and clinicians about Alzheimer’s disease risk and HT treatment.