PCOS and Metformin #46
How does Metformin work for PCOS?
Hello lovely people,
Let’s review how Metformin works. This is one of the most common treatments offered for PCOS, so it’s important that we know how it works.
This week’s question:
How does Metformin work for PCOS?
In this newsletter:
What is Metformin?
How does it work?
Why is Meformin prescribed to us?
Side effects
What is Metformin?
Metformin (dimethyl biguanide) has been used as a first-line treatment for type 2 diabetes for over 50 years. Its history is linked to Galega officinalis (also known as goat's rue), a traditional herbal medicine in Europe, found to be rich in guanidine, which, in 1918, was shown to lower blood glucose. Metformin was introduced in the USA in 1995. In addition to diagnosed type 2 diabetes, metformin can be prescribed for pre-diabetics and PCOS, making it one of the most widely prescribed drugs.
How does it work?
Metformin lowers blood glucose levels in several ways:
Controls liver glucose production: Metformin helps lower high blood sugar by telling the liver to produce less glucose. It does this by reducing gluconeogenesis, where the liver makes new glucose.
Better uptake of glucose: Metformin also helps cells take in more glucose.
In muscles, it encourages the production of transporters (GLUT4) that pull in more glucose.
Reduces glucose absorption in the intestines: Metformin is believed to make it harder for the intestines to absorb glucose.
Activation of AMPK: The primary way metformin works is by activating something called AMP-activated protein kinase (AMPK) in the liver. Think of AMPK as a regulator that helps balance energy in the body:
In muscles, activated AMPK helps bring in more glucose, especially when insulin isn't working well.
AMPK also helps the body use fats for energy, reducing the liver's glucose production.
Why is Metformin prescribed to us?
Metformin has been studied on PCOS extensively. It has been shown to help lower BMI, insulin levels, and cholesterol and increase the chances of ovulation and pregnancy in several meta-analyses.
Due to the vital link between insulin resistance (poor glucose control) and PCOS symptoms, this is prescribed to us to lower glucose levels. If you want to dive deep into how insulin resistance affects PCOS, please head here. In short, Metformin decreases insulin levels, reducing the amount of androgens (testosterone) circling.
Side Effects
The less severe side effects of metformin include gastrointestinal side effects such as diarrhoea, bloating, fluctuance, and nausea. Up to 25% of patients suffer metformin-associated gastrointestinal (GI) side effects, with approximately 5% unable to tolerate metformin at all. In addition, long-term treatment with metformin can lead to vitamin B12 and folic acid deficiencies as absorption is decreased.
One of the most severe side effects of Metformin is lactic acidosis. Metformin should be avoided in those with severely compromised renal function, acute heart failure, and severe liver disease. Due to the overall decrease in uptake for the liver, metformin decreases liver uptake of lactate, which can lead to dangerous amounts gathering in the blood, leading to severe lactic acidosis.
In conclusion…
Metformin is a good treatment option for PCOS but can only be taken as a prescription from your doctor. I have not yet tried it myself, but I am considering it. One of the most fascinating things about Metformin is that it has shown the potential to increase lifespan. It has been suggested that Metformin can reduce all-cause mortality associated with diseases that accelerate ageing, including cancer and cardiovascular disease. This is one of the things that intrigues me about taking it.
I hope you enjoyed this newsletter.
See you next Sunday,
Francesca
1 Sources
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Thrasher, J.(2017), Pharmacologic Management of Type 2 Diabetes Mellitus: Available Therapies. The American Journal of Medicine, 130(6), pp.S4-S17.
Dumitrescu, R., Mehedintu, C., Briceag, I., Purcărea, V. L., & Hudita, D. (2015). Metformin-clinical pharmacology in PCOs. Journal of Medicine and Life, 8(2), 187.
Melin, J., Forslund, M., Alesi, S., Piltonen, T., Romualdi, D., Spritzer, P. M., Tay, C. T., Pena, A., Witchel, S. F., Mousa, A., & Teede, H. (2023). The impact of metformin with or without lifestyle modification versus placebo on polycystic ovary syndrome: a systematic review and meta-analysis of randomized controlled trials. European Journal of Endocrinology, 189(2), S38–S64. https://doi.org/10.1093/ejendo/lvad098
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