Science's women's health issue argues sex shapes disease well beyond reproduction

Yevgeniya Nusinovich, a senior editor at Science ^[11], said she considered including cardiovascular and metabolic disease, where sex differences also play a role, "but it didn't seem like there would be enough new biological insights (with mechanisms, not just clinical observations) for entire coherent review articles." ^[12] In my view her line between mechanisms and clinical observations is the line between cause and correlation, since observations only record that women and men differ while mechanisms explain why ^[12].

The issue's introduction claims more than the evidence base its own editor describes. It says "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." ^[2] STAT describes two reviews that take up that claim directly, one on pain and one on sex chromosomes ^[15]. By Nusinovich's account, heart and metabolic disease did not have the mechanistic literature to join them ^[12].

Pain is where the case beyond reproduction is strongest, and even there the review reports a shortfall in efforts to understand female pain ^[7]. The twice-the-rate figure for functional pain ^[6] is a prevalence count; it does not explain the cause. The review's candidate mechanisms are an attempt to answer that question ^[7]. The authors wrote: "Women are desperately waiting for concrete answers that might help eliminate the common 'all in your head' approach to their illnesses." ^[8]

The issue was published Thursday ^[1], and on trials its four editors ^[3] were direct. "The importance of doing clinical trials specifically in women has gained recognition over the years, and it's something that should continue to be elevated, including as research funding cuts are targeted at this and other women-specific research, threatening the quality of women's future healthcare," they said ^[4]. STAT's report does not give a figure for how underrepresented women are in trials, or for the size of the cuts ^[5].

Tiarney Ritchwood, a public health professor at Wake Forest University School of Medicine who studies health equity, said funding already shapes where the field looks. "We tend to focus on women in their reproductive years, and a lot of that I do think is driven by what institutions are willing to fund," she said ^[13]. Nusinovich puts the issue's post-reproductive work in a separate category, "because the focus here is not on improving reproductive success but on considerations for a woman's own health." ^[11]

I think the editors' funding argument holds, on one condition. The money helps only if the studies it pays for measure sex as a variable of interest. Nicole Woitowich, executive director of the Northwestern University Clinical and Translational Sciences Institute, who did not take part in the issue, put that condition this way: "There is still so much we don't know about women's health simply because sex is often considered an extraneous variable." ^[14]