Recent scientific confirmations are beginning to shed light on a long-overlooked aspect of health research: how women's menstrual cycles can influence the effectiveness of medications. This emerging understanding challenges the historical treatment of the menstrual cycle as insignificant background noise in clinical studies and drug development.
Estrogen, a hormone that fluctuates throughout a woman's menstrual cycle, plays a significant role in various bodily functions. When medications are introduced, these hormonal shifts can lead to differing outcomes for women compared to men. This realization comes as researchers re-examine data and conduct new studies, indicating that the sex-based differences in drug response may have been masked by grouping participants together.
COVID-19 Vaccine Efficacy
Following the rollout of COVID-19 vaccines in 2021, anecdotal reports suggested differential effects in women. Subsequent research has confirmed small, temporary alterations in menstrual cycles post-vaccination, with an average cycle length increase of about half a day. More significantly, studies have begun to investigate how the timing of vaccination within the menstrual cycle impacts vaccine effectiveness. One June study found that women vaccinated during the follicular phase, a period starting with menstruation, were 35% more likely to experience side effects than those vaccinated during the luteal phase. Furthermore, individuals vaccinated in the follicular phase experienced protection for approximately 200 days longer than those vaccinated in the luteal phase.
This line of inquiry treats the menstrual cycle as a critical variable rather than a factor to be controlled or disregarded. "We may be sitting on a significant source of unexplained variation in how women respond to treatment and we have simply never looked in that direction," noted Dr. Julia Craggs, a women's health physician, to New Scientist.
Re-evaluation of Alzheimer's Drug Candidate
A decade ago, the drug davenutide, intended to treat progressive supranuclear palsy (PSP), failed to demonstrate efficacy. The drug targets accumulated tau proteins, implicated in conditions like Alzheimer's disease, frontotemporal dementia, and schizophrenia. A re-examination of data in 2023 revealed that women responded to the drug while men did not—a difference that was obscured when data was analyzed collectively. Subsequent research in mice indicated that female mice with higher estrogen levels absorbed more of the nasal spray drug than males. A small human trial involving six women and two men mirrored these findings, with women showing greater drug uptake. Researchers suggest that estrogen's role in regulating blood flow around the brain and its interaction with the blood-brain barrier may explain these differential responses. Davenutide is now back in development.
Broader Implications for Drug Metabolism
A 2025 review indicated that estrogen can affect the metabolism of drugs processed by CYP enzymes, a group of enzymes primarily found in the liver responsible for breaking down medications and toxins. These enzymes metabolize a substantial portion, between 50% and 80%, of commonly prescribed drugs. Medications such as ibuprofen, omeprazole, alprazolam, and sildenafil are among those processed by CYP enzymes. The review suggested that fluctuating estrogen levels could alter how the liver processes these substances. Specifically, estrogen was found to suppress two CYP enzymes, CYP1A2 and CYP2C19, potentially hindering drug metabolism through their pathways.