Menopause is a neurological transition that reshapes the female brain. At menopause, ovarian estrogen production drops sharply and permanently, one of the most abrupt endocrine shifts in a woman's lifetime, and because estrogen plays a central role in brain function, this transition triggers measurable structural and metabolic changes in the brain. Yet for decades, clinical trials on brain health failed to acknowledge sex as a relevant factor, and some excluded women entirely, with perimenopausal and postmenopausal women particularly overlooked. As a result, treatments have been developed and prescribed with no understanding of how hormonal changes alter drug metabolism or brain health in women. The consequences are huge: nearly 2/3 of all Alzheimer's cases occur in women, and accumulating evidence points to the hormonal shifts of menopause as a critical and potentially modifiable factor.

Miscarriage is staggeringly common. An estimated 23 million pregnancies end in miscarriage annually. Despite this burden, current clinical guidelines do not advise routine examination of pregnancy tissue, leaving over 90% of all miscarriage cases unexplained. This knowledge gap is the direct result of chronic underinvestment in research: NIH has historically underfunded miscarriage research, with limited private funding to fill the gap, and less than 2% of all medical research funding goes to pregnancy, childbirth, and female reproductive health combined. Millions of women are told there is no answer for their pregnancy loss when the truth is that this is not a medical inevitability, it is a funding choice, and it is one we can reverse.

Endometriosis is a chronic inflammatory condition affecting at least 11% of women worldwide (over 190 million people) yet there is no cure, there is no non-invasive diagnostic tool, and surgery is still required to confirm diagnosis, a delay that increases symptom severity, accelerates disease progression, and drives up costs for patients and health systems alike, contributing to an average diagnostic wait of 7-10 years. The funding level for this disease is equally striking. In FY24, NIH only allocated $28 million to endometriosis research compared to $311 million for prostate cancer and $3.1 billion for HIV/AIDS, despite endometriosis affecting more than five times as many Americans as HIV. Current treatments are limited to pain management and hormonal suppression — neither of which addresses the root cause, the infertility it drives, or the elevated cancer risk it carries. This is not a scientific dead end. It is a funding choice.

We know that Adverse Childhood Experiences (ACEs) cause harm. What we don't know is how profoundly that harm differs by sex — and that gap is costing women their health. Sex-specific differences in both the prevalence and long-term consequences of ACEs have rarely been analyzed, especially in the longitudinal studies most needed to understand them. What limited evidence exists is striking: studies rarely explore sex differences in ACE outcomes despite males and females differing meaningfully in their experiences of ACEs, their inflammatory responses, and their depressive symptoms. In women specifically, ACEs have been linked to a dose-response increase in autoimmune disease, including rheumatoid arthritis, lupus, thyroid disease, and Sjögren's syndrome, conditions that already disproportionately affect women and remain poorly understood. In women, ACE exposure has also been linked to endometriosis, fibroids, chronic pain, migraines, and cardiovascular disease, a constellation of female-predominant conditions whose shared roots in early adversity are almost entirely unresearched. We cannot build effective prevention or treatment without understanding who is being harmed, how, and why. Sex is not a subgroup. It is a primary variable — and it is time to treat it as one.

Polyendocrine Metabolic Ovarian Syndrome (PMOS, formerly known as PCOS) affects 1 in 10 women of reproductive age worldwide, making it one of the most common endocrine disorders in existence, yet it remains one of the most underfunded and least understood. PMOS is clinically defined by a cluster of hormonal and metabolic features because the complexity and heterogeneity of PMOS have consistently confounded researchers attempting to understand its causes and long-term consequences. 70% of women with PMOS remain undiagnosed, largely because the science to support consistent diagnosis and treatment simply does not exist. Annual NIH funding for PMOS from 2016-2022 was $32 million — compared to $262 million for rheumatoid arthritis and $66 million for tuberculosis, despite PMOS affecting greater numbers of people with comparable degrees of morbidity. There is no standardized protocol for treating PCOS; current treatments involve lifestyle modification and medications to manage reproductive symptoms and insulin resistance, but there are no treatments that directly target hyperandrogenism — the core hormonal driver of the disease that affects 70% of patients. PMOS is not an unsolvable disease, it is a neglected one, and we’re investing in the foundational research needed to finally understand, diagnose, and treat it.