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Why is it important to evaluate the cardiovascular system in patients with polycystic ovary syndrome?
#MedTwitter #medstudenttwitter #Tweetorial #PCOS #Cardiology #Science @USFQ_Ecuador
#MedTwitter #medstudenttwitter #Tweetorial #PCOS #Cardiology #Science @USFQ_Ecuador
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Polycystic ovary syndrome (PCOS) is the most common endocrine-metabolic disorder in reproductive-age women, with a prevalence between 6 and 20%, depending on how it is defined. https://www.nature.com/articles/nrendo.2018.24
Polycystic ovary syndrome (PCOS) is the most common endocrine-metabolic disorder in reproductive-age women, with a prevalence between 6 and 20%, depending on how it is defined. https://www.nature.com/articles/nrendo.2018.24
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The most common definition is Rotterdam Criteria, with 2 out of 3 of the following features:
- Hyperandrogenism
- Ovulatory dysfunction
- Polycystic ovarian morphology
https://www.nejm.org/doi/full/10.1056/NEJMcp1514916
The most common definition is Rotterdam Criteria, with 2 out of 3 of the following features:
- Hyperandrogenism
- Ovulatory dysfunction
- Polycystic ovarian morphology
https://www.nejm.org/doi/full/10.1056/NEJMcp1514916
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However, PCOS is not only acne, hirsutism and menstrual irregularities: it can also double or even triple the rate for the development of metabolic syndrome, type 2 diabetes, and cardiovascular disorders (CVD).
https://www.nature.com/articles/nrendo.2010.217?draft=collection
https://journals.lww.com/greenjournal/Abstract/2018/08000/Polycystic_Ovary_Syndrome.9.aspx
However, PCOS is not only acne, hirsutism and menstrual irregularities: it can also double or even triple the rate for the development of metabolic syndrome, type 2 diabetes, and cardiovascular disorders (CVD).
https://www.nature.com/articles/nrendo.2010.217?draft=collection
https://journals.lww.com/greenjournal/Abstract/2018/08000/Polycystic_Ovary_Syndrome.9.aspx
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PCOS is often associated with
- Insulin resistance (IR)/hyperinsulinemia
- Hypertension
- Dyslipidemia
- Obesity
However, does PCOS represent a real cardiovascular risk in patients?
PCOS is often associated with
- Insulin resistance (IR)/hyperinsulinemia
- Hypertension
- Dyslipidemia
- Obesity
However, does PCOS represent a real cardiovascular risk in patients?
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Evidence of PCOS having a real risk of CVD and mortality is controversial. Nevertheless, some of the markers used suggest that this problem exist, such as:
- Carotid intima-media thickness (CIMT)
- Flow-mediated dilatation (FMD)
- Quantification of coronary artery calcium
Evidence of PCOS having a real risk of CVD and mortality is controversial. Nevertheless, some of the markers used suggest that this problem exist, such as:
- Carotid intima-media thickness (CIMT)
- Flow-mediated dilatation (FMD)
- Quantification of coronary artery calcium
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- FMD predicts occult coronary artery disease and endothelial dysfunction
- CIMT helps to predict CV events
- Quantification of coronary artery calcium shows coronary atherosclerosis. https://pubmed.ncbi.nlm.nih.gov/28457146/
- FMD predicts occult coronary artery disease and endothelial dysfunction
- CIMT helps to predict CV events
- Quantification of coronary artery calcium shows coronary atherosclerosis. https://pubmed.ncbi.nlm.nih.gov/28457146/
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All of these markers have shown, in multiple studies, an increased risk of CVD in older PCOS patients. Endothelial dysfunction is the first step for these outcomes.
https://pubmed.ncbi.nlm.nih.gov/28457146/
All of these markers have shown, in multiple studies, an increased risk of CVD in older PCOS patients. Endothelial dysfunction is the first step for these outcomes.
https://pubmed.ncbi.nlm.nih.gov/28457146/
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So, with this information we can now try to elucidate the possible mechanisms by which PCOS represents a higher CV risk. Which one do you think it is?
So, with this information we can now try to elucidate the possible mechanisms by which PCOS represents a higher CV risk. Which one do you think it is?
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70% of PCOS patients have:
- Low HDL
- High triglyceride
- High total cholesterol and LDL
All of the above are known for being independent risk factors for CVD, specially for atherosclerosis.
https://www.nature.com/articles/nrendo.2010.217?draft=collection
https://www.sciencedirect.com/science/article/pii/S102845591930107X
70% of PCOS patients have:
- Low HDL
- High triglyceride
- High total cholesterol and LDL
All of the above are known for being independent risk factors for CVD, specially for atherosclerosis.
https://www.nature.com/articles/nrendo.2010.217?draft=collection
https://www.sciencedirect.com/science/article/pii/S102845591930107X
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Prevalence of obesity in PCOS ranges between 30 and 60%, this seems to be related to hyperandrogenism’s major role on abdominal visceral adiposity and hyperlipidemia
https://www.nature.com/articles/nrendo.2018.24
https://journals.lww.com/greenjournal/Abstract/2018/08000/Polycystic_Ovary_Syndrome.9.aspx
Prevalence of obesity in PCOS ranges between 30 and 60%, this seems to be related to hyperandrogenism’s major role on abdominal visceral adiposity and hyperlipidemia
https://www.nature.com/articles/nrendo.2018.24
https://journals.lww.com/greenjournal/Abstract/2018/08000/Polycystic_Ovary_Syndrome.9.aspx
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Hyperandrogenism can be clinical (hirsutism, acne, baldness in male pattern), biochemical (high androgens in labs) or both.
Hyperandrogenism can be clinical (hirsutism, acne, baldness in male pattern), biochemical (high androgens in labs) or both.
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80% of PCOS cases present increased androgen levels
PCOS with hyperandrogenism have worst CV outcomes than PCOS without it.
https://www.sciencedirect.com/science/article/pii/B9780128131978000014#:~:text=Importantly%2C%20excess%20androgens%20in%20women,fatty%20liver%20and%20cardiac%20hypertrophy.
80% of PCOS cases present increased androgen levels
PCOS with hyperandrogenism have worst CV outcomes than PCOS without it.
https://www.sciencedirect.com/science/article/pii/B9780128131978000014#:~:text=Importantly%2C%20excess%20androgens%20in%20women,fatty%20liver%20and%20cardiac%20hypertrophy.
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A positive correlation has been shown between hyperandrogenism with “blood pressure (BP), obesity, hyperinsulinemia, and endothelial dysfunction”.
These are major risk factors for CVD.
https://www.sciencedirect.com/science/article/pii/B9780128131978000014#:~:text=Importantly%2C%20excess%20androgens%20in%20women,fatty%20liver%20and%20cardiac%20hypertrophy.
A positive correlation has been shown between hyperandrogenism with “blood pressure (BP), obesity, hyperinsulinemia, and endothelial dysfunction”.
These are major risk factors for CVD.
https://www.sciencedirect.com/science/article/pii/B9780128131978000014#:~:text=Importantly%2C%20excess%20androgens%20in%20women,fatty%20liver%20and%20cardiac%20hypertrophy.
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Studies in animals have revealed that high testosterone levels seemed to be associated with accelerated atheromatous plaque formation. https://www.sciencedirect.com/science/article/abs/pii/S0889852905700797
Studies in animals have revealed that high testosterone levels seemed to be associated with accelerated atheromatous plaque formation. https://www.sciencedirect.com/science/article/abs/pii/S0889852905700797
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Besides, it’s been observed in rats that:
- testosterone stimulates renal angiotensinogen expression
- dihydrotestosterone (DHT) stimulates renin expression in adrenal glands
Both of these phenomena can lead to a rise in BP.
https://www.sciencedirect.com/science/article/pii/B9780128131978000014#:~:text=Importantly%2C%20excess%20androgens%20in%20women,fatty%20liver%20and%20cardiac%20hypertrophy.
Besides, it’s been observed in rats that:
- testosterone stimulates renal angiotensinogen expression
- dihydrotestosterone (DHT) stimulates renin expression in adrenal glands
Both of these phenomena can lead to a rise in BP.
https://www.sciencedirect.com/science/article/pii/B9780128131978000014#:~:text=Importantly%2C%20excess%20androgens%20in%20women,fatty%20liver%20and%20cardiac%20hypertrophy.
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Similarly, increased angiotensinogen is due to high androgens levels
This can increase angiotensin II, that itself increases endothelin, leading to hypertension and a higher CV risk.
https://www.sciencedirect.com/science/article/pii/B9780128131978000014#:~:text=Importantly%2C%20excess%20androgens%20in%20women,fatty%20liver%20and%20cardiac%20hypertrophy.
Similarly, increased angiotensinogen is due to high androgens levels
This can increase angiotensin II, that itself increases endothelin, leading to hypertension and a higher CV risk.
https://www.sciencedirect.com/science/article/pii/B9780128131978000014#:~:text=Importantly%2C%20excess%20androgens%20in%20women,fatty%20liver%20and%20cardiac%20hypertrophy.
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Also, it’s been seen that BP is increased by “supraphysiological concentrations of DHT that stimulate aldosterone secretion in adrenal glands via calmodulin/calmodulin-dependent protein kinase and protein kinase C”, contributing to elevated BP.
https://www.sciencedirect.com/science/article/pii/B9780128131978000014#:~:text=Importantly%2C%20excess%20androgens%20in%20women,fatty%20liver%20and%20cardiac%20hypertrophy.
Also, it’s been seen that BP is increased by “supraphysiological concentrations of DHT that stimulate aldosterone secretion in adrenal glands via calmodulin/calmodulin-dependent protein kinase and protein kinase C”, contributing to elevated BP.
https://www.sciencedirect.com/science/article/pii/B9780128131978000014#:~:text=Importantly%2C%20excess%20androgens%20in%20women,fatty%20liver%20and%20cardiac%20hypertrophy.
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Worth mentioning that hyperinsulinemia contributes to hyperandrogenism by stimulating theca cells in the ovary, which stimulates testosterone production.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3693634/#:~:text=PCOS%20patients%20clearly%20present%20a,%2C%20dyslipidemia%2C%20and%20inflammatory%20state.
Worth mentioning that hyperinsulinemia contributes to hyperandrogenism by stimulating theca cells in the ovary, which stimulates testosterone production.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3693634/#:~:text=PCOS%20patients%20clearly%20present%20a,%2C%20dyslipidemia%2C%20and%20inflammatory%20state.
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Hyperinsulinemia has other effects apart from hyperandrogenism. It can evolve into type 2 diabetes, a disease known for its CV risk.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3693634/#:~:text=PCOS%20patients%20clearly%20present%20a,%2C%20dyslipidemia%2C%20and%20inflammatory%20state.
Hyperinsulinemia has other effects apart from hyperandrogenism. It can evolve into type 2 diabetes, a disease known for its CV risk.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3693634/#:~:text=PCOS%20patients%20clearly%20present%20a,%2C%20dyslipidemia%2C%20and%20inflammatory%20state.
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This IR leads to:
- Rise of proinflammatory mediators
- Impaired endothelial function
- Reduction in vasoreactivity
- Subclinical atherosclerosis https://www.nature.com/articles/nrendo.2018.24
This IR leads to:
- Rise of proinflammatory mediators
- Impaired endothelial function
- Reduction in vasoreactivity
- Subclinical atherosclerosis https://www.nature.com/articles/nrendo.2018.24
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Hyperinsulinemia also generates:
- Hypertrophy of vascular smooth muscle with reduced compliance
- Abnormalities in endothelium-dependent vasodilatation mechanisms
- Interference with the activation of the RAA system and Na retention.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3693634/#:~:text=PCOS%20patients%20clearly%20present%20a,%2C%20dyslipidemia%2C%20and%20inflammatory%20state.
Hyperinsulinemia also generates:
- Hypertrophy of vascular smooth muscle with reduced compliance
- Abnormalities in endothelium-dependent vasodilatation mechanisms
- Interference with the activation of the RAA system and Na retention.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3693634/#:~:text=PCOS%20patients%20clearly%20present%20a,%2C%20dyslipidemia%2C%20and%20inflammatory%20state.
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This leads to a chronic inflammation that is linked to hyperglycemia as this generates an elevation in reactive oxygen species (ROS) concentration.
ROS activates NFkB and this stimulates the synthesis of inflammatory factors; which enhances IR and results in hyperandrogenism
This leads to a chronic inflammation that is linked to hyperglycemia as this generates an elevation in reactive oxygen species (ROS) concentration.
ROS activates NFkB and this stimulates the synthesis of inflammatory factors; which enhances IR and results in hyperandrogenism
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As it is shown, PCOS has a direct connection at the cardiovascular system by different mechanisms, hence why its profound study and prevention is important as more than just a hormonal abnormality.
As it is shown, PCOS has a direct connection at the cardiovascular system by different mechanisms, hence why its profound study and prevention is important as more than just a hormonal abnormality.
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Teaching points:
- PCOS has a abnormal lipid profile
- Hyperandrogenism and IR contribute to CVD by enhancing each other but also by other mechanisms
- There is a chronic inflammatory state
- CV study in PCOS is very important and further studies need to be done
Thank you!
Teaching points:
- PCOS has a abnormal lipid profile
- Hyperandrogenism and IR contribute to CVD by enhancing each other but also by other mechanisms
- There is a chronic inflammatory state
- CV study in PCOS is very important and further studies need to be done
Thank you!
