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The PCOS Newsletter is a weekly publication answering one PCOS question at the time so we can be empowered by knowledge.

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The cause of PCOS

Updated: Mar 28, 2023

Hello all,


I hope you are having a lovely weekend. This is Francesca from The PCOS Newsletter.


Today’s newsletter discusses a critical and big topic: the cause of PCOS. We are covering whether weight causes PCOS, our microbiome, and how our mother’s womb might have influenced PCOS.


This week’s question

Did I cause my PCOS?

These are some hypothesis of why PCOS might have developed:

  1. Your mum's womb and the exposure to excess androgens and insulin

  2. Low birth weight

  3. Genetics

  4. Excess insulin during adolescence

  5. Alternations in the microbiome

  6. Nutrient Deficiencies

Keep reading to find out details about each.


If you'd like to get to know your body better and understand PCOS, subscribe to our weekly newsletter. We are a community who loves science. 1 question, 1 answer, each Sunday: https://thepcosnewsletter.substack.com/subscribe




I have heard this question countless times from women with PCOS. I have certainly asked myself this on numerous occasions. I often felt somehow guilty for not having a fully functional body. Did I eat too many sweets in my childhood? Did I somehow create this problem in my teenage years?


When something doesn’t have a clear cause, it is easy to believe it might be something we have done. I have no intention of creating fear or guilt, so I will tell you now that with what we know so far, it is unlikely that you have done something specifically to cause your PCOS. However, some fascinating possible causes are worth knowing and exploring.


It is well-established that genetic and environmental factors contribute to developing PCOS. Nevertheless, the exact cause is unknown.


This is what we know so far:


🏋️ Weight alone doesn’t cause PCOS.

One of the most important things to get out of the way is whether weight gain causes PCOS.


It is reasonably well established that obesity doesn’t cause PCOS independently. In a study looking at normal-weight, overweight, moderately obese, and severely obese, the prevalence of PCOS was 9.8%, 9.9%, 12.4%, and 11.5%, respectively. This shows us a pretty stable % across different weight categories. If weight was the primary cause, the numbers would look different for those with excess weight. It would also mean that all women who are overweight would have PCOS.


However, we know that the severity of symptoms increases as the excess fat level rises. This is due to insulin resistance worsening and impacting the overproduction of androgens. Weight doesn’t cause PCOS but can be the driver that sets things in motion and makes the situation worse. This is the reason why weight loss helps manage PCOS.


😵‍💫 Insulin resistance is unclear to be causative of PCOS.

Insulin resistance is a key feature of both overweight and lean PCOS. It can occur in up to 95% of people with overweight PCOS and up to 75% with lean PCOS. Whether insulin resistance comes first and causes PCOS or PCOS causes insulin resistance is a mystery. My logical self thinks that if insulin resistance caused PCOS, all women with type 2 diabetes should, by default, have PCOS. This is not true, and the prevalence of PCOS in women with type 2 diabetes is 21%.


🤰🏼It can start as early as in our mum’s womb.

One of the leading hypotheses is that the baby's exposure to androgen or excess insulin in the uterus alters genes related to our reproductive system and metabolic health.


In addition, maternal psychological distress and/or poor nutrition during pregnancy may have long-term detrimental effects on babies, predisposing them to cardiovascular and metabolic diseases later in life.

In particular, they have found that children of women with PCOS have lower birth weights. This seems to correlate with increased adipose tissue (fat storage) at a young age and higher BMI values.


The above is not to blame our mothers; I am sure they have done their best. However, this is to note that our genetic makeup can be influenced as early as our development in the womb.


🧬 It is primarily genetic.

Approximately 60% to 70% of daughters born to women with PCOS manifest their own PCOS phenotype during adolescence and as young adults. The condition is highly hereditary and is proven in twin studies. A large-scale genome meta-analysis looking at 10,074 PCOS cases found variants in multiple genes involved in the reproductive and metabolic manifestations of PCOS. To name a few, genetic variations in the ovaries have shown an increase in androgen production, and variations in insulin secretion showed the development of insulin resistance.

Fun fact: they found the same genetic variations when analysing women's genes from China and Europe. This suggests that PCOS is an ancient disorder originating before humans migrated out of Africa. However, Stein and Leventhal first reported it in modern medical literature in 1935.


👯‍♀️ It gets activated in the adolescent years.

The moment PCOS manifests itself is when the hypothalamus-pituitary-ovarian axis is activated (aka when puberty and our period start). An increase in insulin levels naturally characterises this time of a woman’s life to support the development of our reproductive system. However, for women predisposed to PCOS, this increase in insulin might mean increased fat storage and androgens, giving a start to PCOS symptoms. The quality of diet at this time can also influence insulin levels. Knowing what we know about the impact of diet on insulin resistance and weight, I was surprised to find very little data on the impact of childhood nutrition on the development of PCOS. In my case, I believe my diet, which was pretty high in sugar and saturated fat at this age, might have influenced the development of my PCOS.


🦠 The microbiome might be involved.

The microbiome is made out of trillions of bacteria in our large intestine. These bacteria do more than just form our 💩. Significant research has emerged in the last years showing the power of these bacteria on numerous functions in the body. Mainly they can influence our metabolic health, hormonal health and, most importantly, our immune system.


Guess what? They have found differences in microbiomes for women with PCOS. Compared to healthy individuals, we seem to have a lower diversity of good bacteria and an increase in some non-so-nice bacteria. Bacteria such as Bacteroidetes and Firmicutes are increased for us. They are involved in the altered production of short-chain fatty acids, negatively impacting metabolism, gut barrier integrity, and immunity. The beneficial bacteria, such as Lactobacilli and Bifidobacteria, which enhance immunity and nutrient absorption, are significantly reduced in PCOS patients. How great!


Diet choices influence this diversity. However, I hypothesise that using antibiotics at early ages, lack of breastfeeding or a cesarian birth might influence the makeup of our microbiome early on and lead to the activation of specific genes associated with PCOS. (Is anyone keen to fund this study?)


In addition to the gut microbiome, vaginal microbiome analysis found a significant difference in both vaginal and cervical canal microbiomes on a total of 194 microbial samples. The incidence of BV (Bacterial vaginosis) could be linked to this imbalance. I doubt this is enough to be causative of PCOS. However, it is an interesting data point on the map to consider when examining your medical history.


🍎 Specific nutrient deficiencies might interfere.

A new area of research called Nutrigenomics is looking at SNPs (variations in the genetic makeup) and their impact on different processes in the body. A genetic test can show which areas might not have an optimal function. Nutritionists use this to tailor diets specifically in line with your genetic makeup. As an example, I have higher needs for Omega-3 and Magnesium. These micronutrients are vital for our health and reproductive system. This is another hypothesis of my own: Could it be that not processing these well from a young age has in time, developed suboptimal processes in my body related to PCOS? (another study up for grabs for future research?)


Deficiencies in Vitamin D, Vitamin B12, Folate, Magnesium, Calcium, and Zinc have been found in women with PCOS and supplementation with these has been shown to improve symptoms. I regularly ask myself how a suboptimal level of these micronutrients affects a child’s development, particularly their reproductive system.


Did I cause my PCOS?

To tie this up, I don’t think you have done anything to cause your PCOS. However, I believe in the world of epigenetics (the power of the environment on genes). I think our actions, either now or early on, can influence how we experience PCOS. This is the reason why I write this weekly newsletter because knowing things empowers us to take action. When we have lemons, we make lemonade 🍋. We might complain a bit on the way, but we do the work to live the life we deserve.


I hope you enjoyed this newsletter issue.


Thank you so much to those who replied to my research survey. If you haven’t done so already and would like to help build the roadmap for the newsletter, you can fill out this survey.


See you next Sunday,


Francesca



Sources

De Leo, V., Musacchio, M. C., Cappelli, V., Massaro, M. G., Morgante, G., & Petraglia, F. (2016). Genetic, hormonal and metabolic aspects of PCOS: an update. Reproductive Biology and Endocrinology: RB&E, 14(1), 38. https://doi.org/10.1186/s12958-016-0173-x


Giampaolino, P., Foreste, V., Di Filippo, C., Gallo, A., Mercorio, A., Serafino, P., Improda, F. P., Verrazzo, P., Zara, G., Buonfantino, C., Borgo, M., Riemma, G., Angelis, C. D., Zizolfi, B., Bifulco, G., & Della Corte, L. (2021). Microbiome and PCOS: State-of-art and future aspects. International Journal of Molecular Sciences, 22(4), 2048. https://doi.org/10.3390/ijms22042048


Sirmans, S. M., & Pate, K. A. (2013). Epidemiology, diagnosis, and management of polycystic ovary syndrome. Clinical Epidemiology, 6, 1–13. https://doi.org/10.2147/CLEP.S37559


Steegers-Theunissen, R. P. M., Wiegel, R. E., Jansen, P. W., Laven, J. S. E., & Sinclair, K. D. (2020). Polycystic ovary syndrome: A brain disorder characterized by eating problems originating during puberty and adolescence. International Journal of Molecular Sciences, 21(21), 8211. https://doi.org/10.3390/ijms21218211


Disclaimer: We are all so unique in our own ways so this information is for education purposes only. Please further consult your healthcare provider about your health needs.



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