Yuan and colleagues recently investigated whether a buildup of adverse life events, such as in relation to family, work, and society, was associated with POI diagnosis. Previous research has shown that adverse life events in early childhood and cumulatively (chronic stress) can trigger an “epigenetic mechanism” called DNA methylation. If genes are compared to light switches, DNA methylation determines when our genes are “switched on or off”, but the gene itself is not affected. This means that while our DNA sequence stays the same, the way our body "reads" those genes can change in response to the environment.

In Shanghai, China, the researchers studied a group of women who had been diagnosed with idiopathic POI (an unknown cause of POI) within months of their diagnosis. They also studied a group of women who did not have POI over a period of several years. The researchers looked at how many significant life events each woman had experienced (measuring positive and negative life events on a scale) and, in some of the women, their “epigenetic age”. This is like a biological clock calculated from DNA, but it is not always the same as someone’s birth age. If someone’s epigenetic age is “accelerated”, it means their body shows signs of being older than their

actual birth age.

The key findings:

- On a standardised scale measuring life events, women with POI had significantly more adverse

life events (a median score of 48.5 on the scale) compared to women without POI (a median score

of 20.0 on the scale). But there were no differences in the number of positive life events

between both groups.

- When looking across all the women, those with adverse life events were over two times more likely to have a POI diagnosis.

- There were specific changes in over 5,000 sites on the DNA of women with POI, compared to

women without POI. These sites would reflect the specific “coordinates” of where the "light switches" mentioned earlier were flipped. These changes affected genes responsible for energy, sleep cycles, and how the brain handles stress.

This new research suggests a strong link between adverse life events and biological changes in women with POI, highlighting a vital need for integrated mental health and psychosocial support.

Overall, the researchers suggest an association between adverse life events and POI, which may be understood on a biological level. But what remains unclear is whether stress (such as from a build up of negative life events) contribute to POI, or does POI change the way the body handles stress? 

The researchers seem to suggest the former and compare this to a rocket metaphor: cumulative life stress acts like fuel and once it reaches a certain threshold, it can trigger the onset of POI (see Figure 1). We already know that stress activates the HPA axis (the brain’s core stress response system), which might suppress the hormones needed for healthy ovary function. But, on the

other hand, low oestrogen levels can make the HPA axis even more sensitive. This might lead women with POI to experience more negative impacts from stress on their health. For example, more severe symptoms of POI during stressful times. More research is needed to understand this further, but this new research begins to shed light on the impact of POI- it is more than changes to reproductive ability.

Turning research into self-advocacy:

- A POI diagnosis can be a distressing life event in its own right, often bringing feelings of grief or

anxiety. It is well-documented that POI is associated with an increased risk of depression

and poorer mental health.

- If you are feeling overwhelmed, share this research with your doctor. Managing your stress

response through counselling, talking therapies, or mindfulness should be a vital part of supporting your long-term physical and mental health.

- If you are feeling that your mental health is struggling, it’s important to seek help.

Samaritans: Confidential emotional support available 24/7. Call 116 123 or visit www.samaritans.org.

Mind: A charity that provides support and information on mental health. Visit www.mind.org.uk or text 86463.

Daisy Network: A charity for women with POI. Visit https://www.daisynetwork.org for more

information and support services relating to POI.

Figure 1: Life stress associated with POI: a rocket metaphor from Yuan et al.

(2026), published in Climacteric. © 2026 The Author(s). Published by Informa UK

Limited, trading as Taylor & Francis Group.

Link to paper: https://www.tandfonline.com/doi/full/10.1080/13697137.2025.2610484