The continued struggle for female representation in drug trials  

The exclusion of women from drug trials undermines efforts to ensure equitable and effective healthcare for all individuals.

In 2002, the Women’s Health Initiative (WHI) was forced to pause its study on hormone therapy’s effect on menopause symptoms due to results showing it increased the risk for breast cancer, stroke and heart disease, and thrombotic events like pulmonary emboli.

Over 20 years later, in May of this year, JAMA published a review of this study and determined that, given current available hormone therapy formulations as well as risk/benefit analysis, younger menopausal women may actually derive significant benefits from menopausal symptom relief with appropriately prescribed hormone therapies.

The initial study had looked at women who were older and typically years post-menopause – the average age of the study participants was 63.3 years – and the age-related changing of blood vessels, among other things, may be the key to shifting from greater risk to greater benefit with hormone therapy.

I wish this more measured summary of the study’s findings and recommendations had been headlined back in 2002 – and I imagine thousands of my OB/GYN colleagues and billions of menopausal women over the years feel the same.

Yet, due to these 2002 over-generalised published findings, doctors and patients shied away from hormone therapy, which led to unnecessary suffering for many symptomatic menopausal women.

The irony of the WHI study is that after decades of women being excluded from clinical research, Congress finally passed an act in 1993 requiring that the National Institute of Health (NIH) enrol women and persons of colour in clinical trials.

On the heels of this landmark decision, the intentions of the WHI study were excellent – a first of its kind for women – but may have unintentionally set back women’s health innovation.

The reality

If you’re wondering why we are just now reevaluating and reinterpreting findings made in a 2002 women’s health study you may (or may not) be shocked to learn that while there is growing inclusion of women into research trials, they are still underrepresented in key therapeutic research areas, such as cancer and cardiovascular disease.

Excluding women from drug trials can have several harmful consequences. First, it can lead to a lack of understanding about how medications affect women differently than men, as their physiological responses may vary due to hormonal and metabolic differences, among other factors.

This can result in ineffective or potentially harmful treatments for women. It can also hinder progress in medical research by preventing the development of sex-specific treatment approaches.

Additionally, while the amount of research conducted on the behalf of women has grown in the past two decades, research involving pregnant women has been restricted.

This leads to a limited understanding of how best to medically care for pregnant women: for example, less than 10 per cent  of prescription medications have been studied enough to understand the impact in pregnancy on both the woman and her foetus.

While the NIH and American College of Obstetricians and Gynecologists (ACOG) both acknowledge pregnancy as a “medically complex” state that can alter metabolism of medications, and the course of various diseases, increased pregnancy-specific data needs to be collected to optimise the care of women in pregnancy.

Another recent, glaring case study: initial COVID vaccination trials did not include pregnant women, which led to restrictions on the availability of the vaccines as well as restrictions of the use in pregnant women with dire consequences – as unvaccinated pregnant women are more likely to develop severe COVID infections requiring ICU admissions and are more likely to develop other pregnancy-related complications like preeclampsia and preterm birth.

How do we move forward?

The exclusion of women from drug trials undermines efforts to ensure equitable and effective healthcare for all individuals.

It’s crucial for the government and pharmaceutical companies to put more resources and funding into women’s health so we can have a deeper understanding of how to treat diseases that impact over half of the population, for more female and diverse talent to enter the medical field – either as doctors, researchers, healthcare executives – and to incorporate how biological sex can affect medical treatment into provider education.

And, for pregnant women, the answer was proposed by ACOG back in 2015: “A more careful examination…points to the need for evidence-based consideration of pregnancy exposure in research rather than broad exclusion of all pregnant women”.

If evidence demonstrates minimal risk to the foetus as well as potential benefit to the pregnant woman, why should she be denied the right to give informed consent to enrol in a clinical trial?