Sex differences in melatonin suppression: understanding the role of sex hormones
- Carolina Guidolin
- Oct 27
- 4 min read
Research Spotlight Blog No.6
Carolina Guidolin is a PhD student at the Translational Sensory Circadian Neuroscience laboratory (Max Planck Institute) and at the Technical University of Munich in Germany. Her research interest is focused on understanding sex differences in light sensitivity, and the effect of the menstrual cycle and the oral contraceptive pill on melatonin suppression in the evening. Carolina is passionate about contributing to efforts aimed at bridging the gender data gap in chronobiology. Alongside her research, she enjoys making circadian and sleep science accessible to a wider audience by hosting the Light O’Clock podcast.
Sex differences in “non-visual” effects of light
Light doesn’t just help us see the world around us, it also affects how our bodies function. It sets our internal clock (our circadian rhythm), influences how alert we feel, controls the release of the hormone melatonin, and even changes the size of our pupils.
These “non-visual” effects of light are driven by special cells in the eye called ipRGCs (intrinsically photosensitive retinal ganglion cells (check out this previous blog for more information about retinal cells and circadian rhythms)). There is growing evidence that individuals respond to light very differently, with some being more and some less “light sensitive”. One example is when examining the effect of light on the hormone melatonin. In the evening, when melatonin starts to be produced around 5 hours before sleep, exposure to light causes suppression of this hormone, meaning that the amount produced is reduced. However, there is large variability in how this affects people, meaning that if two individuals are exposed to the same light in the evening, one might be suppressing melatonin to a great extent and the other one be only suppressing it a little bit.
Scientists are interested in understanding: which factors contribute to these differences in sensitivity to light? Some studies show that biological sex is might play a role – with females suppressing more melatonin (i.e., being more sensitive) in response to moderate and bright lights compared to males. However, it is not so clear yet if sex steroid hormones as those naturally occurring in the menstrual cycle or those present in the oral contraceptive pill might be influencing this response, and explaining the sex difference observed.
Animal studies do show that sex steroid hormones like estrogen and testosterone influence how light is processed and how it affects circadian rhythms. In humans, however, this question hasn’t been explored much. Most studies don’t track participants’ hormone levels or menstrual cycle phases, and people using hormonal contraceptives (like the pill) are often grouped together without considering how these synthetic hormones might change light sensitivity.
Understanding the role of sex hormones
Our project aims to fill this gap. We want to understand how natural sex hormones (occurring across the menstrual cycle) and synthetic sex hormones (as those in the oral contraceptive pill) affect how our bodies respond to light at night. Specifically, we are asking: Do sex hormones influence the extent to which evening light suppresses melatonin?
To do this, we are recruiting three groups of participants: individuals who are naturally cycling (i.e. have a regular menstrual cycle), individuals who take the oral contraceptive pill, and healthy male participants. Each participants undergoes five experimental sessions to capture hormonal changes across the menstrual and pill cycle, and across an equivalent time for healthy male participants.
This is a very involved study, since the experimental sessions last for up to 8 hours in the evening. When participants arrive to the laboratory, they consume a meal and undergo some pupillometry measurements. These are measurements where we are interested to see how the pupil reacts to light, and we will check if sex hormones affect this response. Later on, participants sit in a private “experimental booth” in dim light and the hormone melatonin is measured throughout the evening using salivary samples. After 2 hours, the participants wear a virtual reality headset that exposes them to light, and we keep measuring melatonin to see how much of it is suppressed during this time. We also take blood samples, as unfortunately measurements of sex hormones in saliva are not as reliable as it is for melatonin.
Since even individuals with a regular menstrual cycle do have a little bit of variation in the cycle length, we need track the participants’ cycle to make sure we invite them to the lab at the right menstrual cycle phase. To do this, we ask them to keep track of the day when their period starts and also to take at-home tests to track the day of their ovulation.
Towards more inclusive circadian and sleep studies
Understanding the effects of sex hormones is important not just because it might explain the sex differences in light sensitivity, it also matters for how we design research. In many areas of biology and medicine, sex hormones are considered as “confounding variables” in biomedical research, – basically, as “noise” that might affect the study results. As a result, studies have historically focused on male participants, leaving us with a limited understanding of how biological rhythms work in females. By studying both women and men, and accounting for hormonal changes, we hope to bring more inclusivity and precision to the science of the non-visual effects of light.
Blog by Carolina Guidolin