Sex-Based Bias in Medical Research is Dangerous

3/18/2024

Historically, medical research has tended to favor men as clinical trials and testing were only conducted on men for centuries. The primary reasoning for this was the belief that female hormones were too complicated to be included in medical studies. Another major concern was the impact of drugs on a woman’s childbearing ability and fertility. In 1977, the Food and Drug Administration policy recommended excluding women from Phase I and II medical trials. This cautious approach was in response to the side effects of thalidomide, a sedative that caused pregnant women to give birth to children with severe limb deformities.

The FDA’s policy was to be enforced regardless of if a woman was single, used contraception, or if their husband had a vasectomy. Essentially, it did not matter if a woman had no intention of being pregnant, they were excluded from trials regardless. This resulted in a lack of data on how drugs impact women. In 1986, the policy changed to encourage the inclusion of women in clinical trials, and in 1993, the NIH inclusion policy was officially written into law. 

Despite this, women continue to be underrepresented in Phase I and II medical trials. The medical field has long been predominantly composed of men, resulting in the belief that any results obtained from research on men would be able to be extrapolated for women. Of course, women have several biological differences from men, therefore this approach to medical research can have deadly consequences

A research study conducted by Dr. Mariana Martinho of Hospital Garcia de Orta, Almada, Portugal on cardiovascular health in men and women found that women are twice as likely to die of a heart attack than men. Women are twice as likely as men to develop Alzheimer’s, are four times as likely as men to have an autoimmune disease, and twice as likely to have depression or anxiety. Yet, clinical trials conducted on Alzheimer’s disease include eight times more men than women. Trials conducted on autoimmune diseases include twice as many men than women, and trials conducted on depression and anxiety often have a majority of male participants. 

This inequality primarily occurs in the early stages of testing. Women only account for 29 to 34 percent of participants in Phase I medical trials today. A recent study conducted by Marci Cottingham and Jill Fisher concluded that pharmaceutical companies continue to pose restrictions on the participation of women in early clinical trials due to their “childbearing potential”. Phase I trials are vital for determining how a drug interacts with the human body, as well as any potential side effects the drug may have. Although later trial phases such as Phase 3 tend to include a good representation of women, testing for these phases is determined by data collected during Phases I and II, such as the dosage and expected response. 

Dr. Jeff Mogil, a professor of pain studies at McGill University, has been studying sex differences in drugs his entire career. While studying a drug in graduate school, he realized it significantly affected men but had almost no effect on women. When he brought his findings to the graduate student supervising the research, the supervisor responded, “Sex differences are to be enjoyed, not studied.” Not only is this attitude toward women’s health irresponsible, but historically very common. 

Fortunately, Dr. Mogil ignored this advice and dedicated his career to investigating sex differences in pain processes. In 2015, he published a study showing how men and women use completely different cells to process pain in the spinal cord. This is significant because it means that if drugs developed to assist pain target one of these cells, the drug would have no impact on the other sex. 

It is necessary for women’s health that the female sex is included in the early stages of medical and drug testing. Not only do women need to be involved as patients, but they also need to have positions as researchers to prevent sex-related bias in medical research. To ignore the data showing the dangers of only conducting testing on men is immoral and unethical.