Overdosing in women, medication that stops working before our period, and a research system that thinks we’re too complicated
For most of modern medicine, the drugs you’re prescribed were designed, dosed and tested on men. Female bodies are expected to respond identically. They don’t.
There has been a failure of the pharmaceutical industry to show up for women and their individual differences. This has resulted in us overdosing on commonly prescribed drugs, and prescriptions that don’t account for how our menstrual cycle can influence a drug’s effectiveness (e.g. SSRIs, ADHD medication) - right when we need it to work most, as we’ll get onto later.
The Beginning of How Women Were Written Out
In the late 1950s and early 1960s, thalidomide, prescribed for morning sickness, caused severe birth defects in thousands of babies. In 1977, the FDA recommended excluding women of childbearing potential from early-phase clinical trials as we were too risky and complicated (1). Meant to be protective, it instead erased women from research altogether for nearly two decades.
That changed on paper in 1993, when the NIH Revitalization Act required women and minority groups to be included in federally funded research (1). Trials were to be large enough to analyse results by subgroup, and cost could no longer be an excuse to leave us out (1). The right to be included was restored, but women were still routinely left out of important research.
Women are Still Missing From the Trials that Shape Your Care
Decades later, the gap persists. Let's take a look at the year 2017. In trials of ischaemic heart disease, women make up a median of just 22% of participants - despite heart disease affecting women differently to men (2). Across 300 trials published in that year, women's enrolment fell below 50% in every single disease category studied except one, immune disease (68%).
Age made it worse: overall enrollment fell from 47% in trials of young or middle-aged adults → to 33% in trials in the elderly (2) - meaning the women taking the most medication are the ones missing most from the research behind it. Trials of invasive, higher-risk interventions enrolled only 31% women (2). That immune disease field, at 68%, is proof this isn't an unsolvable problem - just one nobody's bothered to solve everywhere else.
The reasons given for lack of representation? Our menstrual cycle adds variables to the data (we say - it’s hardly an impossible hurdle to overcome), and it’s feared postmenopausal women’s dementia rates complicate being able consent (screening out a dementia diagnosis, rather than an entire demographic, would solve that!).
The patterns start earlier. Before a drug even reaches human trials, it has to clear preclinical research. Male-only studies dominate 8 of 10 biological disciplines. In pharmacology, for every 5 male studies, there's just 1 female one (3). Even when females are included, results are rarely broken down by sex, so differences go unseen.
This means preclinical data doesn't reflect real-world disease patterns, even though it's what determines which drugs move forward to human trials.
Are we overdosing women? Yes, and not just because of our “size”
We can’t just take a smaller dose to women, or assume a drug works in the same way in their bodies, especially given the influence of the menstrual cycle and key life changes such as menopause and pregnancy.
A 2020 analysis looked at 86 drugs known to have sex differences in pharmacokinetics - meaning how the body absorbs, distributes, and clears a drug. For 76 out of 86 drugs, women showed higher blood concentrations and/or slower clearance than men taking the same dose (4). In other words, the standard dose frequently leaves more drug in a woman's body, for longer.
Of those drugs, 59 also had clearly documented adverse reactions, which let the researchers test something important: did that buildup actually translate into more side effects? It did, and consistently: whichever sex accumulated more of a drug was more likely to experience its side effects 88% of the time.
Specifically, 96% of drugs that built up more in women were linked to higher rates of adverse reactions in women, while the same pattern held for men only 29% of the time. This effect persisted even after accounting for body weight, so it isn't simply a matter of size (4).
This is clear evidence that a one-size-fits-all drug dose for men and women ignores real, measurable differences in how their bodies process medication.
Do Your Meds Stop Working Before Your Period? Your cycle changes how your drugs work.
ADHD: Many women report their medication stops working in the days before their period. This is because the drop in oestrogen pulls down dopamine, the system stimulant medication relies on. At this point in the cycle, there is more of a dopamine deficit that the usual ADHD medication dose cannot keep up with.
Yet we only have a single small study (of just nine women) that wisely trialled increasing the ADHD medication dose temporarily for that “bad” premenstrual week. Women reported positive effects of a dose adjustment cyclically - it improved their ADHD and mood symptoms in a way that equalised with their “good” weeks the rest of the month (5). While this could be life changing for women who struggle more with ADHD before their period, no further research has been done. As a result, it’s still far from being listed in clinical guidelines - it remains overlooked.
Schizophrenia: The dopamine system is central to schizophrenia, and oestrogen fluctuations across the cycle and the sharp decline at menopause can alter how well medication works, strengthening the case for dosing that accounts for cycle phase and life stage (6). Researchers have even proposed formal frameworks to test this: establishing a woman's symptom pattern across several cycles first, then trialling an added dose during the vulnerable premenstrual week against a placebo (7).
The Repercussions of Being Left Out: Unmanaged Conditions, Side Effects, Faster Addiction
In practice, this is why medication for your own conditions can sometimes just not work as expected, or come with side effects that feel disproportionate to what you were warned about - you are not imagining it
Because women are more likely to be left with more drugs than their bodies can clear, and more likely to be prescribed medications never properly tested on them, they carry more of medicine's unmeasured risk, from adverse reactions to dependence.
Addiction is one of the clearest examples of this. Women move from first use of a drug to a full substance use disorder faster than men, and reach out for treatment sooner. This is called the telescoping effect - seen with alcohol, opioids, stimulants, and nicotine (8). The role of ovarian hormones is crucial: estrogen heightens the rewarding effects of drugs during early use, likely through its interaction with dopamine, while progesterone dampens them, so risk shifts across the cycle. Women also transition faster from this dopamine-driven stage into glutamatergic addiction, a later stage where drug use becomes more compulsive and harder to control.
The takeaway
It's a self-perpetuating cycle: conditions that affect women disproportionately, or differently, are rarely studied - so we never learn how to properly account for them in trials, and their absence keeps getting used to justify leaving women out.
Research and clinical care are moving toward greater inclusion, but decades of exclusion still shape the health and treatment women receive today.
Going forward, preclinical and clinical research alike need to include women as a default, and treat the menstrual cycle and hormonal life stages as variables worth studying, not as reasons to look away (and frankly, we think that's the interesting part). Nuance and complexity in trial design should never again be an excuse to leave women without proper care.
References:
1. Liu KA, Mager NA. Women's involvement in clinical trials: historical perspective and future implications. Pharm Pract (Granada). 2016 Jan-Mar;14(1):708. doi: 10.18549/PharmPract.2016.01.708. Epub 2016 Mar 15. PMID: 27011778; PMCID: PMC4800017.
2. Daitch V, Turjeman A, Poran I, Tau N, Ayalon-Dangur I, Nashashibi J, Yahav D, Paul M, Leibovici L. Underrepresentation of women in randomized controlled trials: a systematic review and meta-analysis. Trials. 2022 Dec 21;23(1):1038. doi: 10.1186/s13063-022-07004-2. PMID: 36539814; PMCID: PMC9768985.
3. Beery AK, Zucker I. Sex bias in neuroscience and biomedical research. Neurosci Biobehav Rev. 2011 Jan;35(3):565-72. doi: 10.1016/j.neubiorev.2010.07.002. Epub 2010 Jul 8. PMID: 20620164; PMCID: PMC3008499.
4. Zucker I, Prendergast BJ. Sex differences in pharmacokinetics predict adverse drug reactions in women. Biol Sex Differ. 2020 Jun 5;11(1):32. doi: 10.1186/s13293-020-00308-5. PMID: 32503637; PMCID: PMC7275616.
5. de Jong M, Wynchank DSMR, van Andel E, Beekman ATF and Kooij JJS (2023) Female-specific pharmacotherapy in ADHD: premenstrual adjustment of psychostimulant dosage. Front. Psychiatry 14:1306194. doi: 10.3389/fpsyt.2023.1306194
6. Brand BA, Haveman YRA, de Beer F, de Boer JN, Dazzan P, Sommer IEC. Antipsychotic medication for women with schizophrenia spectrum disorders. Psychol Med. 2022 Mar;52(4):649-663. doi: 10.1017/S0033291721004591. Epub 2021 Nov 12. Erratum in: Psychol Med. 2023 Jul;53(10):4832. doi: 10.1017/S0033291723001344. PMID: 34763737; PMCID: PMC8961338.
7. Yum SK, Yum SY, Kim T. The problem of medicating women like the men: conceptual discussion of menstrual cycle-dependent psychopharmacology. Transl Clin Pharmacol. 2019 Dec;27(4):127-133. doi: 10.12793/tcp.2019.27.4.127. Epub 2019 Dec 31. PMID: 32095480; PMCID: PMC7032965.
8. Towers EB, Williams IL, Qillawala EI, Rissman EF, Lynch WJ. Sex/Gender Differences in the Time-Course for the Development of Substance Use Disorder: A Focus on the Telescoping Effect. Pharmacol Rev. 2023 Mar;75(2):217-249. doi: 10.1124/pharmrev.121.000361. Epub 2022 Dec 12. PMID: 36781217; PMCID: PMC9969523.
