Editor’s Note: This post by Ejura Salihu is the third in our Pharmaceutical Inequalities series. Ejura’s experience of a disrupted menstrual cycle post-COVID19 vaccination prompted her to write a much-needed commentary on why medical trials repeatedly overlook women’s needs and health. The Pharmaceutical Inequalities series is funded by the Holtz Center and the Evjue Foundation.
Like many people worldwide, I was elated when the Covid-19 vaccine became available, so I quickly scheduled an appointment for my first shot. I scoured the internet, especially the Center for Disease Control website, for side effects to look out for. Everything was pretty standard: fever, chills, soreness. Nothing unusual for a vaccine. In fact, I was pretty confident that, like most people, I would experience mild side effects, if any. I had a fever and chills, which I expected, but the change in my monthly cycle was shocking. I had not read anything about that on any official websites, so I was not expecting that side effect. As weeks rolled by, more women started to speak out on social media platforms about the possible impact of the vaccine on their menstrual cycle. The symptoms were similar: longer or skipped periods and heavier periods. Although this would not have influenced my decision to take the vaccine, would it have been helpful to know exactly what to expect? Absolutely! Admittedly, the Covid-19 vaccine was innovative, and we were in the middle of the pandemic, so it can be argued that there was only so much the researchers and pharmaceutical companies could know about side effects, especially long-term side effects. This would be excusable if these side effects appeared months or even years after taking the vaccine since there has not been enough time to examine long-term effects. However, women worldwide reported these menstruation-related side effects within days or weeks. Is it possible that these side effects were missed by multiple pharmaceutical companies during clinical trials? Why would that happen?
It turns out that this is a common issue where women’s health is concerned. In 2019 the Center for Disease Control conducted a study that examined rates of adverse events from vaccines reported from 1990 to 2016. The study results found that 80 percent of people with severe allergic reactions (anaphylaxis), among adults were women (Su et al., 2019). Recently, a study funded by NIH analyzed data on menstrual cycles from about 4,000 women aged 18 to 45. Data were compared for three menstrual cycles before the first vaccine dose to the subsequent cycles. Women who received a COVID-19 vaccine had an average increase in cycle length of nearly one day for each dose. Women who received two vaccine doses within the same menstrual cycle reported an even longer cycle (Edelman et al., 2022). Considering that menstrual cycle length varies from woman to woman, with some women living with Polycystic ovary syndrome (PCOS) or other conditions that impact their menstruation, this is essential information that should be on the Center’s website for women seeking information before getting a vaccine. Yet, the Centre’s website still retains generic details on side effects to date. There is still no mention of sex-specific side effects or additional information for women.
In the largely androcentric healthcare system in the United States (and really, everywhere else in the world), men’s health needs are prioritized. In contrast, women’s health needs are either under-addressed or over-medicalized. There is no middle ground in medical thinking and research about women’s needs and preferences. This has led to a continuous cycle whereby women are considered collateral damage in medical research and practice (Demos, Segal & Kronenfeld, 2009; Block, 2019).
Image credit: Madla et al. (2021)
The dismissal of women’s concerns in healthcare is not unique to vaccine information and distribution but also in how drugs are generally prescribed to men and women. Recent research from the University of California, Berkeley, and the University of Chicago showed that women suffer adverse side effects of prescription medications twice as much as men. Again, this is not the first time that biological sex has been noted as a significant factor in drug metabolism or how people report side effects. Out of the 668 drugs included in the 20 most frequent treatment regimens in the United States, 307 (46%) note significant sex differences in adverse drug effects reports (Yu et al., 2016).
Why does this constant dismissal persist?
Like vaccine formulation, drug dosages have historically been based on clinical trials conducted on men. The issue raised so much criticism that in 1994, the National Institute of Health (NIH) issued guidelines in the Revitalization Act, which mandated that clinical researchers funded by the institute must include women in their studies (Mazure & Jones, 2015).
This was supposed to correct sex imbalance in research subjects’ enrollment. Still, because most clinical trials are conducted by pharmaceutical industries, not the NIH, they are not mandated to follow these guidelines, so men have continued to be the benchmark for medical research and drug safety. Within the NIH, nothing has really changed either. A 2018 review of 107 NIH-funded studies that enrolled both men and women found that 72% of the studies did not include sex in their analyses (Geller et al., 2018). The apparent consequence is that men and women are routinely given the same drugs/dosages when men were the benchmark for the drug’s efficacy and safety in the first place.
There is an urgent need for NIH to enforce the guidelines in their funded studies and then expand the jurisdiction of the guidelines to include privately owned pharmaceutical companies. This would ensure that women are equally involved in clinical trials and that women’s unique health needs are prioritized and met. There is also a need for physicians to re-evaluate drug prescriptions and consider sex-specific adjustments when needed. The current status quo that neglects biological sex differences in pharmacokinetics is harmful to women because it leads to overmedicalization and increased adverse drug reactions among women (Zucker & Prendergast, 2020).
References
Edelman A, Boniface ER, Benhar E, Han L, Matteson KA, Favaro C, Pearson JT, Darney BG (2022). Association Between Menstrual Cycle Length and Coronavirus Disease 2019 (COVID-19) Vaccination: A U.S. Cohort. Obstetrics Gynaecology, 10, 1097
Geller SE, Koch AR, Roesch P, Filut A, Hallgren E, Carnes M. The more things change, the more they stay the same: a study to evaluate compliance with inclusion and assessment of women and minorities in randomized controlled trials. Acad. Med. 2018;93(4):630–635
Madla C.M., Gavins F.K.H., Hamid A.M., Orlu M., Murdan S., Basit A.W. (2021). Let’s talk about sex: Differences in drug therapy in males and females, Advanced Drug Delivery Reviews, 175.
Mazure, C.M., Jones, D.P. Twenty years and still counting: including women as participants and studying sex and gender in biomedical research. BMC Women’s Health 15, 94 (2015).
Su, J. R., Moro, P. L., Ng, C. S., Lewis, P. W., Said, M. A., & Cano, M. V. (2019). Anaphylaxis after vaccination reported to the Vaccine Adverse Event Reporting System, 1990-2016. The Journal of allergy and clinical immunology, 143(4), 1465–1473.
Yu, Y., Chen, J., Li, D., Wang, L., Wang, W., & Liu, H. (2016). Systematic Analysis of Adverse Event Reports for Sex Differences in Adverse Drug Events. Scientific reports, 6, 24955.
Zucker, I., Prendergast, B.J. (2020). Sex differences in pharmacokinetics predict adverse drug reactions in women. Biol Sex Differ., 11,32.