The Women’s Health Gap: 5 Cautionary Tales of Clinical Blunders
By Deborah Borfitz
November 19, 2025 | Progress on women’s health, which was only truly recognized at the federal level when the Food and Drug Administration (FDA) asked for the inclusion of women in clinical trials in 1993, encountered a large obstacle earlier this year when the White House cut off a major funding initiative established by previous administrations intended to right the harms from decades of largely failing to include women in medical research. The move marks a succession of blind spot moments in the history of human research that have had damaging consequences for women, according to Nisha Perez, ScD, MS, MSPM, head of drug metabolism, pharmacokinetics, toxicology, and clinical pharmacology at HotSpot Therapeutics.
As a female scientist with a specialty in drug development, Perez is on a quest to shed light on the importance of ensuring metabolism differences between the sexes are considered when developing a drug and that female-specific disorders are worth funding. This includes her work at HotSpot, a company developing an IRF5 inhibitor for a range of autoimmune diseases including lupus, a disease that significantly disproportionately impacts women (around 80% of patients).
She’ll be making her case with five cautionary tales where female-specific data were inadequately considered at the inaugural Health Executive & Research Summit (HERS) in San Diego next March.
These are chronic issues of neglect that long predate the current administration, she notes, though the recent actions are undeniably damaging, including wiping out the 50-year-old National Women's Health Network, which was the backbone for integrating women's health across the federal research portfolio, and undercutting the continuity of the landmark Women’s Health Initiative study. The financial perils of neglecting women’s health were laid bare in a 2024 report by the World Economic Forum in collaboration with the McKinsey Health Institute. The research effort found women spend an average of nine years in poor health across their lives, 25% more than men, and that closing that gap could allow at least $1 trillion to be pumped into economic productivity annually.
Consider menopause, a natural biological process experienced by all women at some point, which can significantly impact their quality of life as well as elevate their risk of numerous diseases. It is estimated that therapeutics specific to menopause would have a GDP equal to all oncology combined, says Perez. Despite the National Institutes of Health (NIH) recently adding menopause as a research category in 2024, it receives less than 1% of total federal funding.
In industry, people often talk of finding the next "blue ocean,” referring to markets where there is no competitor, she says. The vast, underserved women’s health market has been almost completely overlooked despite significant untapped opportunities for growth and innovation. Money is of course a key motivator for change. But Perez’s real mission is to alleviate the medical burdens specifically for the 51% of the U.S. population who happen to be female.
It won’t be easy, and the effort may be further hampered by recent moves at the federal level, she says. Within weeks of taking office, President Trump made targeted cuts to numerous grants related to diversity, equity, and inclusion (DEI) and minority health, many of which indirectly or directly impacted women's health research. He also ordered federal agencies to remove information from government websites pertaining to “gender ideology” and DEI initiatives that led to the removal or alteration of numerous pages containing female-specific information that included critical health and medical matters.
Focus on Male Animals
Many of the problems in women's health research stem from the historical exclusion of female animals in preclinical studies and underrepresentation of female participants in clinical trials, says Perez, a critical scientific gap given diseases, drug responses, and physiological processes can differ between sexes.
In her personal experiences throughout her two decades of drug research and development, she reflects on times when animal models were run without female mice, even when the disease was female predominant, and muses of the time she had to show where the ovaries were in a rodent to fellow researchers. While late-stage toxicology studies capture both sexes, there are times in earlier stages of research a reminder is needed to include both animal sexes.
Case Study #1: Ambien
The insomnia medication Ambien (zolpidem) hit the U.S. market in 1992, based on studies predominantly in men. But it was more than 20 years later, in 2013, that the FDA required lower recommended starting doses after real-world experience showed that the drug was causing next-morning impairment in activities requiring alertness, notably driving, says Perez. “Now, women tend to go on the 5mg dose and men on the 10mg dose, and doctors can make adjustments based on patient weight.”
The move was based on the revelation that women metabolize the drug more slowly than men, meaning they had higher drug concentrations in their bloodstream, she says. The manufacturer (Sanofi) “had the data; it just hadn’t been parsed out enough during the investigational process.”
Case Study #2: Digoxin
The drug digoxin has been used to treat heart conditions for over 200 years, and it remains a treatment for heart failure and atrial fibrillation, says Perez. A significant portion of its current use is based on approvals in the late 1990s following clinical trials conducted via the Digitalis Investigation Group (DIG).
Post-hoc analyses done by the DIG have found digoxin has “different effects on mortality in women with heart failure versus men,” she says. Analysis in the 2000s revealed that yet again women had metabolism and higher concentration differences that had led to a 20% increase in risk of mortality, leading to doses being refined and lowered for women.
As with Ambien, funding plays a major role in preventable harm, continues Perez. “Sometimes the reason these things take so long to elucidate is because biotech and pharmaceutical companies are trying to get a drug to market as quickly as possible ... Industry sometimes does not prioritize understanding if there are going to be these population nuances.” It is also “hard, especially now, to convince investors to fund post-hoc analyses of something that is already out there.”
Case Study #3: Thalidomide
One of the huge tragedies of the late 1950s and early 1960s was the use of the drug thalidomide, which was marketed as a sedative to treat morning sickness in pregnant women. But because of insufficient testing for safety during pregnancy, thousands of children were born with severe birth defects that included truncated limbs, deafness, and internal organ damage, says Perez.
This led to stricter drug testing regulations—specifically, in the U.S., passing of the Kefauver-Harris Amendment in 1962 laying the groundwork for the FDA’s three-phase clinical trial system that requires drug manufacturers to prove both the safety and effectiveness of new drugs. But even this did not make a huge impact, Perez says, since drugs continued to be poorly studied in women.
“We made everything harder, but we didn’t exactly make it better,” she says. Understanding drugs in the context of pregnancy, and the effects on children, also remains underfunded. Pregnant women are understandably routinely excluded from clinical trials and are therefore instructed not to take anything for many medical conditions because of the potential harmful effects of the treatment on the developing fetus and the significant lack of safety data for many of the available medications.
New AI and machine learning techniques need to come on the scene to help address potential harms and thereby inform some of the treatment gaps, Perez continues. Funding for building new models for embryo-fetal toxicity or gestation is noticeably lacking.
Case Study #4: Addyi
In 2015, a drug called Addyi (flibanserin) was brought to market for the treatment of sexual desire disorder in women. Interest in the therapeutic area skyrocketed after the highly profitable launch of Viagra (1998) and Cialis (2003) for treating erectile dysfunction in men, says Perez.
Since women have their own arousal issues, companies rushed to get anything out there to capitalize on the commercial opportunity, she continues. But, in her view, Addyi isn’t particularly safe or efficacious and comes with strict precautions. Originally developed by Boehringer Ingelheim for depression, it was repurposed by Sprout Pharmaceuticals for desire, notably not showing an improvement in physiologically based arousal or hydration issues.
As part of the submission process, an alcohol-drug interactions study was required in case a warning was needed on the drug label not to take the medication, Perez explains. Of the 25 participants in that study, only two were women.
The seemingly obvious problem here is that women process alcohol differently than men, she says. “We literally have less alcohol metabolizing enzyme than men do and, on top of that, alcohol is water-soluble and women, being smaller, have a lower volume of water so [men] have more dilution power ... so, we reach intoxication more easily.”
Case Study #5: Seldane and Propulsid
Two drugs are notorious standouts for triggering fatal heart arrhythmias in women—the antihistamine Seldane (terfenadine) and the gastrointestinal drug Propulsid (cisapride). The two drugs appeared in a 2001 FDA audit of drugs withdrawn from the U.S. market in the prior decade, uncovering that 80% of the drugs posed a greater risk to women than men, Perez reports.
Both drugs “hit a specific potassium channel that affects the women’s hearts differently [women have a naturally longer QT interval] than the men’s in that they caused a longer arrhythmia,” she says. This critical distinction wasn’t caught because of the way sponsors ran their clinical trials. “Even though they had the information that this could happen, the bulk of studies were done in men, and it wasn’t until yet again there was real-world patient evidence that the differences between sexes were realized.”
A lot of money goes into drug discovery and development, and repeated blind spots like these cause a lot of waste in dollars, put lives at risk, and harm the reputation of the pharmaceutical industry, Perez points out.
The Long View
The problem is not that scientists don’t want to do the right thing, says Perez, but that they often aren’t given the time and money to do it. Men still hold the lion’s share of decision-making power in terms of who is running companies and occupying board seats. If speed to market and turning a profit is prioritized, precautions may be neglected, and drugs may not be thoroughly explored across all populations.
The FDA, for its part, issued a significant, broad statement in the form of a final rule in 2000, prohibiting the categorical exclusion of women of reproductive potential from early phase clinical research on products intended for life-threatening diseases and conditions. But the agency’s position on the inclusion of women as outlined in guidances and recommendations have generally encouraged voluntary compliance. “It’s up to the discretion of companies to be thoughtful and include more women,” Perez says.
They can opt to do the “quick thing” and de-emphasize the long view, including ones that might make them some real money. Perez has been part of programs that could have expanded into different patient populations; however, that takes time, education, and money. “I’ve been told its easier to kick the can down the road to doctors to figure out and that the most important objective is to get to market ASAP.”
In terms of female trial recruitment, men, she believes, are generally more willing to take risks, while women tend to be more cautious. “It is easier to get young men who are willing to do any sort of clinical trial for like a thousand bucks than it is women ... [who] need to feel like there is going to be a positive outcome,” she says. “There needs to be better strategies to recruit women, but this requires effort and investment.”
Costly Standstill
The political environment is impossible to ignore in all this. A 2024 report by the National Academies found that the level of federal grant funding devoted to women’s health has declined as a share of the overall NIH budget. A strong counter movement and national push for increased funding are needed to get back on track, says Perez.
“If you think about things like endometriosis, it takes an average of seven years to get diagnosed because we have such little information on the disease,” she says. It hasn’t been properly studied due to lack of funding and there are limited non-invasive diagnostics or biomarkers.
When women go to their doctor complaining of severe pain and bleeding, they might suffer for five years before their insurance company will agree to pay for an MRI. By then, the fibrosis could have spread to their bladder and intestines. A definitive diagnosis requires surgery, she says, “which is disheartening.”
Diagnosing endometriosis quicker would translate into less medical spending on treating symptoms and visits to the emergency room. Data on the enormous economic burden of endometriosis exists (Frontiers in Global Women’s Health, DOI: 10.3389/fgwh.2022.902371). “Yet it remains underfunded by investors and understudied by biotech and pharma” says Perez.
“If anything exciting happens, it’s probably going to come from a European or Asian institution,” says Perez. This is evidenced by new financing mechanisms announced by the European Union (EU) and the Bill & Melinda Gates Foundation, the EU’s broader investment in investment in projects focused on women’s health, China’s “Sheconomy” despite its traditionally male-dominated society (BMJ, DOI: 10.1136/bmj.q1774), and improving maternal healthcare in that country (BMJ, DOI: 10.1136/bmj-2023-078640).
“It’s incredibly important that industry is aware of these historical and persisting research gaps,” she says. “Drug developers and regulatory agencies alike need to recognize that women often have subtle differences in metabolism and how hormones effect their bodies. Understanding, appreciating, and prioritizing research on these nuances are essential to ensuring women’s health. These are our wives, these are our daughters, these are our mothers—we are worth the investment.”