In the previous chapters of this series, we revealed how the historic exclusion of women from research, along with long-standing gaps in addressing female-specific health issues continues to have far-reaching consequences for diagnostics, treatment options and outcomes. Decades of underrepresentation within clinical trials, gaps in provider training, the legacy of the WHI 2002 report on HRT and unreasonable delays in diagnoses have left many women feeling unheard and dismissed when they seek treatment. While the challenges might seem insurmountable, there are reasons for hope. Awareness of these significant gender gaps in healthcare is growing, and concrete steps are being taken to address the issues.

In recent years, organizations such as the NIH in the United States and the Tri-Council in Canada have emphasized the importance of including both sexes in preclinical animal studies, unless scientifically justified otherwise. This approach has also extended to clinical trials, with regulations requiring gender and age stratification to ensure diverse representation. Despite these advances, protections for pregnant and lactating women remain a priority in regions like the EU and Canada, though recent policy changes in the U.S. have raised concerns among researchers. These measures aim to enhance our understanding of sex differences in health and disease; however, their effective implementation and enforcement remain challenging, particularly in light of recent political shifts that have impacted NIH policies on granting and funding.

If we don’t want it to take decades to achieve parity in women’s health, there are changes that could be made now to make up for lost time and set the stage for closing the gap. There are actionable steps in clinical trials, research funding, infrastructure, and continuing medical education that could accelerate our progress and move us toward health equity for women much sooner.

Clinical Trials and Product Development

• Include sex-disaggregated analyses in phase-II/III trials and dose–exposure curves for women. This would include the publication of safety and efficacy data by sex in publicly accessible open repositories to support guideline updates.
• Include sex-specific guidance on product labels when side effects are different for women or sex differences in pharmacokinetics exceed a defined threshold (e.g. 25%).
• Create a fast-track review system for products and treatments that address diseases and conditions that disproportionately affect women (similar to the U.S. priority-review system for neglected diseases).

Research Funding and Infrastructure

• Designate a portion of government research grants for pharmacokinetics of existing approved drugs in diverse female cohorts (pregnancy, perimenopause, menopause, polypharmacy), where this information is currently not available.
• Designate research grant funding for research into diseases, disorders, and conditions that predominantly affect women.
• Leverage the Genomic Data Sharing (GDS) Policy framework from the Human Genome project and tie research funding to immediate sharing of female-specific health data (such as pharmacokinetics, genetics and longitudinal drug-response data), in a central, publicly funded repository (similar to GenBank and EMBL-bank). Data submission to a global biobank of this nature would reduce redundancies and dramatically accelerate research and the development of treatments that directly support women’s health. This should be part of a larger initiative to develop national and international biobanks that link hormonal status, genetics, and longitudinal drug-response data to support validation of sex-specific biomarkers.
• Endow “Women’s Health Translational Hubs” within academic medical centers to pair companies developing diagnostics and treatments with medical teams and hospital pharmacies.
• Offer tax credits for companies that develop diagnostics and therapeutics for women-dominant diseases (e.g., endometriosis, osteoporosis, menopause, lupus, fibromyalgia).
• Publish annual scorecards and metrics on grants, product approvals, data sharing, publication of funded research, and women’s health innovation uptake.

• Update existing systems with mechanisms to streamline the integration of the latest research findings, ensuring the timely updating and implementation of prescribing information. Though mechanisms are in place in both Canada and the US for updating prescribing information based on post-market data and voluntary reports, prescribing updates can incur long delays. For example, vaginal estrogen products can provide significant benefits in treating genitourinary symptoms of menopause, yet they still contain “black box” warnings about risk of cancers, dementia and cardiovascular disease (that stemmed from the WHI 2002 study on systemic estrogen), despite a large cohort study over 18 years showing vaginal estrogen posed no added risks for cardiovascular disease or cancer (they did not assess dementia) [1]. The North American Menopause Society has been fighting to get the labeling changed for years, and a recent FDA panel may have brought us closer to making this happen.
• Enact policies that require provincial health care systems (and in the US, private insurers) to cover the cost of companion diagnostics that can have a significant impact on medication choice, dosing and treatment outcomes (e.g., hormone-level or enzyme-genotyping assays).

Continuing Medical Education (CME)

Medical education is another vital area in need of reform. We cannot have true “patient-centered care” if the needs of women are not specifically addressed, and this means eliminating the unconscious biases that leave women underserved. Many US states have already implemented mandatory implicit bias training on specific clinical areas and populations [2], and this needs to be extended to all healthcare providers as part of a broader institutional strategy targeting behaviours and not just concepts. Research suggests that one-time conceptual training does not produce sustained change [3].

We need to open up the conversation, train and equip doctors with the tools to recognize and counteract their own biases and focus on patient-centered care. This isn’t about blame; it’s about identifying and deconstructing our natural unconscious associations to improve care and deliver on the promise of precision medicine for all patients. We need to have women and members of marginalized communities, who are in science and medicine, participate in the design of implicit bias training programs that both educate the perpetrators and equip victims and bystanders with tools to counteract instances when they occur [4,5].

For medical practitioners in the field, enhanced CME can be leveraged to not only deliver on implicit bias training but also to raise awareness of recent advances in women-specific health issues, including diagnostics and treatments. This could include steps like integrating compulsory sex-based pharmacology modules into CME requirements for physicians, pharmacists, and nurse practitioners.

Closing The Research Gap

On a positive closing note, the last couple of years have seen progress in research targeting women’s health. A “Femtech” industry sector* that focuses on healthcare research, product development, and solutions for women, is gaining ground. Aneira Health in the UK has launched a new platform focused on precision medicine to enhance the health span of women. Medicines360, led by CEO Dr. Andrea Olariu, is a non-profit focused on bringing accessible women’s health solutions to market. Their unique approach to clinical trials resulted in 1.8 million women obtaining access to their low-cost hormonal IUD, Liletta. This successful strategy has evolved into an “innovation hub” with a three-pronged approach to bring affordable women’s health products into clinical trials through internal development, small biotech firms, and industry partnerships. As we mentioned in Chapter 5, more pharmaceuticals are now targeting women’s health. These developments are encouraging, but we need significantly more public and private sector investment in basic and translational research. Organizations like FemTech Canada are petitioning the federal government to properly fund women’s health research.

Ultimately, eliminating the gender gap in healthcare will require broad and systemic changes. We need institutional reforms that incentivize research protocols to not only include females but actually study the role of sex. We need more research into women’s health specifically, with a focus on neglected areas like postpartum care and endometriosis. We need more women included in clinical trials. We need to do a better job of eliminating implicit bias and harassment in medical education and medical environments, and to include this training as a mandatory annual component of CME to ensure it is reinforced and updated. We need CME that updates physicians on advances in women’s health so we can bridge the treatment gap.

We also need to restructure compensation systems in research institutions to create environments that support work-life balance so that women aren’t penalized for having a family. Honestly, changing the publish-or-perish grind and unrealistic expectations of time commitments in academic research would benefit EVERYONE – not just women. We also need more women in leadership positions, as they can have a significant influence on developing innovative treatments for women. These kinds of changes must be made to ensure women are fairly represented in research and medicine and are receiving treatments that target their unique physiology.

This isn’t just about fairness. It’s about saving lives and improving health outcomes for half the world’s population. And those improved health outcomes can have a significant financial impact, translating to reduced overall healthcare costs and improved productivity, with the potential to contribute an additional $1 trillion annually into the global economy by 2040.

As we reach the conclusion of our series on women’s health, we hope it has expanded awareness, stimulated conversations, and inspired a sense of urgency for change. By confronting and closing these gaps in women’s health research, medical care and treatment, we have the opportunity to create healthcare systems that truly serve everyone, irrespective of their sex. It’s a huge undertaking, but we know what needs to be done and we have to do better – for the sake of our mothers, sisters, daughters, and all women who deserve equitable, compassionate and timely healthcare.

*Disclaimer: The mention of specific companies, products, or organizations in this article is for informational purposes only and does not imply endorsement. The companies referenced were not consulted, involved in the preparation of this content, nor did they provide any funding or compensation.

References

[1]        S. N. Bhupathiraju et al., “Vaginal estrogen use and chronic disease risk in the Nurses’ Health Study.,” Menopause, vol. 26, no. 6, pp. 603–610, Dec. 2018, doi: 10.1097/GME.0000000000001284.

[2]        L. A. Cooper, S. Saha, and M. van Ryn, “Mandated Implicit Bias Training for Health Professionals—A Step Toward Equity in Health Care,” JAMA Heal. Forum, vol. 3, no. 8, pp. e223250–e223250, Aug. 2022, doi: 10.1001/jamahealthforum.2022.3250.

[3]        C. O. for S. W. D. (COSWD National Institutes of Health (US), Office of the Director (OD), “Is Implicit Bias Training Effective?,” in Scientific Workforce Diversity Seminar Series (SWDSS), National Institutes of Health (NIH), 2021. [Online]. Available: https://www.ncbi.nlm.nih.gov/books/NBK603840/

[4]        V. S. Periyakoil, L. Chaudron, E. V Hill, V. Pellegrini, E. Neri, and H. C. Kraemer, “Common Types of Gender-Based Microaggressions in Medicine,” Acad. Med., vol. 95, no. 3, 2020, [Online]. Available: https://journals.lww.com/academicmedicine/fulltext/2020/03000/common_types_of_gender_based_microaggressions_in.37.aspx

[5]        A. Llorens et al., “Gender bias in academia: A lifetime problem that needs solutions.,” Neuron, vol. 109, no. 13, pp. 2047–2074, Jul. 2021, doi: 10.1016/j.neuron.2021.06.002.