Tag: PCOS

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Immune Dysfunction as a Possible Aspect of PCOS Pathology

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The study “Androgens Modulate the Immune Profile in a Mouse Model of Polycystic Ovary Syndrome” sheds light on immune dysfunction as a possible aspect of PCOS pathology, which could constitute a novel target for therapies.

The study shows that hyperandrogenism, a key characteristic of polycystic ovary syndrome (PCOS), affects immune cell populations in reproductive, metabolic, and immunological tissues in a PCOS-like mouse model. These findings are of great importance as it is known that immune dysfunction is an essential part of reproductive complications and metabolic disease, which are very common among women with PCOS. 

However, as the study shows that hyperandrogenism affects different tissues in unique ways, any possible treatments would have to be carefully tailored to target specific tissue dysfunctions. Since concurrent treatment with an androgen receptor antagonist prevented many changes in the mouse model we used in our study, combination therapies that include both anti-androgens and other drugs that target specific altered immune pathways could be explored.

Alteration of immune cells in adipose tissue

One of the most fascinating findings was the clear alterations of immune cells in adipose tissue, despite an unaltered fat mass of the androgen exposed mice. It is well known that immune cells in adipose tissue contribute to insulin resistance in overweight and obese individuals, but here we have an insulin resistant mouse model that mimics normal weight women with PCOS. The impact of androgens on immune cells in adipose tissue is therefore very interesting considering the high prevalence of insulin resistance and type-2 diabetes among normal weight women with PCOS. Another rather surprising finding was the drastic decrease of eosinophils in the uterus, as these don’t express the androgen receptor. This shows that androgens play a broader and more complex role in modulating the immune environment than only through direct androgen receptor activation on immune cells. 

The next step will be to dissect the underlying mechanisms of the immune alterations, and to assess if these do contribute to the reproductive complications and metabolic comorbidities of PCOS. This will include further characterisation of immune cell changes to understand how their function could be affected and link these to reproductive and metabolic mechanisms. We also want to understand how the effect of androgens on eosinophils and mature NK cells is mediated, since neither of them expresses the androgen receptor. 

Source: Karolinska Institutet

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Polycystic Ovary Syndrome Tied to Cognitive Problems

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Those with polycystic ovary syndrome (PCOS) may be more likely to have memory and thinking problems in middle age, according to a study involving over 900 women, 66 of whom had PCOS. The study, published in Neurology, followed the women for 30 years.

PCOS is a hormonal disorder that is defined by irregular menstruation and elevated levels of androgen. Other symptoms may include excess hair growth, acne, infertility and poor metabolic health.

“Polycystic ovary syndrome is a common reproductive disorder that impacts up to 10% of women,” said study author Heather G. Huddleston, MD, of the University of California, San Francisco.

“While it has been linked to metabolic diseases like obesity and diabetes that can lead to heart problems, less is known about how this condition affects brain health. Our results suggest that people with this condition have lower memory and thinking skills and subtle brain changes at midlife. This could impact a person on many levels, including quality of life, career success and financial security.”

The study involved 907 female participants who were 18 to 30 years old at the start of the study.

They were followed for 30 years, at which time they completed tests to measure memory, verbal abilities, processing speed and attention. At the time of testing, 66 participants had polycystic ovary syndrome.

In a test measuring attention, participants looked at a list of words in different colours and were asked to state the colour of the ink rather than read the actual word. For example, the word “blue” could be displayed in red, so the correct response would be red.

Researchers found for this test, people with PCOS had an average score that was approximately 11% lower compared to people without the condition.

After adjusting for age, race and education, researchers found that people with polycystic ovary syndrome had lower scores on three of the five tests that were given, specifically in areas of memory, attention and verbal abilities, when compared to those without this condition.

At years 25 and 30 of the study, a smaller group of 291 participants had brain scans.

Of those, 25 had PCOS. With the scans, researchers looked at the integrity of the white matter pathways in the brain by looking at movement of water molecules in the brain tissue.

Researchers found that people with PCOS had lower white matter integrity, which may indicate early evidence of brain aging.

“Additional research is needed to confirm these findings and to determine how this change occurs, including looking at changes that people can make to reduce their chances of thinking and memory problems,” Huddleston said.

“Making changes like incorporating more cardiovascular exercise and improving mental health may serve to also improve brain aging for this population.”

A limitation of the study was that PCOS diagnosis was not made by a doctor but was based on androgen levels and self-reported symptoms, so participants may not have remembered all the information accurately.

The study was funded by the University of California, San Francisco.

Source: American Academy of Neurology 

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A Keto Diet may Improve Fertility in Women with PCOS

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The ketogenic (keto) diet may lower testosterone levels in women with polycystic ovary syndrome (PCOS), according to a new paper published in the Journal of the Endocrine Society. The diet also appeared to lower follicle-stimulating hormone (FSH) levels, which may thereby improve the chances of ovulating. These improvements in hormonal balance could help alleviate fertility problems.

PCOS is the most common hormone disorder in women, affecting 7–10% of women of childbearing age. It can cause infertility and raises the risk of developing diabetes, obesity and other metabolic health problems.

Women with PCOS have at least two of these signs:

  • Elevated levels of testosterone and other androgen hormones associated with male reproduction,
  • Irregular periods, and
  • Large ovaries with many small follicles.

The keto diet is a high fat, low carbohydrate diet that has shown promising effects in women with PCOS. Studies have shown that it may help women lose weight and maintain weight loss, improve their fertility, optimise their cholesterol levels and normalise their menstrual cycles.

“We found an association between the ketogenic diet and an improvement in reproductive hormone levels, which influence fertility, in women with PCOS,” said study author Karniza Khalid, MBBS, MMedSc, of the Ministry of Health Malaysia in Kuala Lumpur, Malaysia. “These findings have important clinical implications, especially for endocrinologists, gynaecologists and dieticians who, in addition to medical treatment, should carefully plan and customise individual diet recommendations for women with PCOS.”

The researchers conducted a meta-analysis of clinical trials in women with PCOS on the keto diet and examined the diet’s effects on their reproductive hormones (FSH, testosterone and progesterone) and weight change.

They found women with PCOS who were on the keto diet for at least 45 days saw significant weight loss and an improvement in their reproductive hormone levels. Their FSH ratio was lower, which means they may have a better chance of ovulating. The women also had lower testosterone levels, which could help with excess hair growth and other symptoms of excess male sex hormones.

Source: The Endocrine Society

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B Cells Are Elevated in PCOS – But Are not The Cause

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While previous research have shown that while more B cells are present in women in polycystic ovary syndrome (PCOS), a new study by researchers at Karolinska Institutet has ruled out B cells as the cause of this common syndrome. The study is published in eLife.

Affecting 10–15% of women of fertile age, PCOS is linked to irregular ovulation and menstruation, pregnancy complications, and insulin resistance, all of which are worsened by being overweight. PCOS increases with rising body mass index, and in women with severe obesity, it is around 25%. While the root cause of the condition is unknown, a driver is a surplus of androgens.  

A recent study has shown that women with PCOS have a higher number of B cells in their blood and proposed that these contribute to the development of PCOS through the production of autoimmune antibodies.

“We’ve now examined how B cells affect the development of PCOS with the goal to find new ways of treating the conditions,” says the study’s last author Elisabet Stener-Victorin, research group leader for reproductive endocrinology and metabolism at the Department of Physiology and Pharmacology at Karolinska Institutet.

First, blood from women with PCOS was examined and showed abnormal variations in the frequency of different populations of B cells compared to healthy women. Among these were the so called double negative B cells, a heterogeneous cluster, where some have been described as poised to develop autoimmune functions.

To study whether B cells may cause PCOS, the researchers transferred antibodies from women with PCOS to mice to see if they developed the syndrome. While this proved not to be the case, they did put on weight.

Mice unaffected by B cells

The next step was to transfer B cells from PCOS-like mice (induced by continuous exposure to androgens) to mice lacking B cells to test the hypothesis that B cells drive the development of the disease. However, the recipient mice were unaffected by this transfer.

To see if B cells play an essential role in the development of PCOS, mice lacking B cells were exposed to androgens. These mice were not protected as expected, but developed the same characteristics as normal mice acquire when exposed to androgens.

Finally, androgen exposed PCOS-like mice displayed altered B cell frequencies, as women with PCOS, and simultaneous treatment with a drug that blocks androgen receptors, prevents these alterations of B cells in both blood and tissues, such as ovaries and endometrium.

The researchers conclude that androgens are necessary for the condition to form, but not B cells, the role of which remains unclear.

“B cells are clearly affected in the syndrome, which could contribute to a higher susceptibility to some comorbidities, but they don’t cause PCOS,” says Sara Torstensson, PhD student at Institutet and shared first author.

“We are now studying how other immune cells are affected and how this influences reproductive and metabolic function in PCOS,” says Angelo Ascani, guest PhD student at Graz University, Austria and also first author.

Source: Karolinska Institutet

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Sons Born to Women with PCOS Can Also Encounter Health Problems

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Sons of women with polycystic ovary syndrome (PCOS) have a twofold increased risk to develop obesity, according to a study published in Cell Reports Medicine. The findings highlight a previously unknown risk of passing PCOS-related health problems across generations through the male side of a family, say the the researchers from Karolinska Institutet.

PCOS is caused by overproduction of testosterone by the ovaries and affects around 15% of women of childbearing age worldwide, impacting fertility. In addition, the disease is associated with various health problems such as diabetes, obesity, and mental illness. 

Daughters of women with PCOS have a fivefold risk of developing the same disease. Although it is not yet clear how sons of women with PCOS are affected, research suggests that they are more likely to have weight and hormone problems

The researchers used both registry data and mouse models in the newly published study to determine if and how PCOS-like traits are passed from mothers to their sons. Just over 460 000 sons born in Sweden between July 2006 and December 2015 were included in the registry study. Of these, roughly 9000 had mothers with PCOS. The researchers then identified which of the children were obese. 

“We discovered that sons of women with PCOS have a twofold increased risk of obesity and of having high levels of “bad” cholesterol, which increases the risk of developing insulin resistance and type 2 diabetes later in life”, says study leader Elisabet Stener-Victorin, professor at Karolinska Institutet. 

These findings were confirmed in the mouse study, where the researchers examined male offspring of female mice that before and during pregnancy were fed either a standard diet or a diet rich in fat and sugar, and were exposed to high levels of the male sex hormone dihydrotestosterone during pregnancy to mimic the pregnancy of normal weight individuals and obese women with PCOS. 

The male mice were then fed a standard diet until adulthood when their fat distribution and metabolism were examined. 

“We could see that these male mice had more fat tissue, larger fat cells, and a disordered basal metabolism, despite eating a healthy diet”, says Elisabet Stener-Victorin.

To investigate the reproductive function of the offspring and whether physiological characteristics can be passed on from generation to generation, the first-generation male mice were mated with healthy female mice that were not exposed to male sex hormones or a diet rich in fat and sugar. The whole process was repeated in the second generation to reach the third generation which is the first generation that was not affected by the mother condition.  
 
“Through these experiments, we can show that obesity and high levels of male hormones in the woman during pregnancy can cause long-term health problems in the male offspring. Their fat tissue function, metabolism, and reproductive function deteriorate, which in turn affects future generations”, says Qiaolin Deng, associate professor at the same department and one of the researchers behind the study.
 
“These findings are important because they highlight the risk of passing health problems down through the male side of a family, highlight the risk of passing this kind of health problem, and they may help us in the future to find ways to identify, treat and prevent reproductive and metabolic diseases at an early stage,” says Elisabet Stener-Victorin.

Source: Karolinska Institutet

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Choice of Words Matters for PCOS Patients’ Wellbeing

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The choice of words that doctors doctors use when diagnosing female patients with polycystic ovary syndrome (PCOS) can negatively impact their wellbeing and how they view their condition later on in life, according to new research published in the British Journal of General Practice.  

PCOS can result in a range of physical symptoms, such as dysmenorrhoea or amenorrhoea, and metabolic issues. University of Surrey researchers found that the use of the word ‘raised’ by practitioners when discussing test results can lead to higher levels of body dissatisfaction and dieting behaviour amongst women, whilst the use of the word ‘irregular’ can result in concerns about fertility. 

Jane Ogden, Professor of Health Psychology at the University of Surrey, said: “Diagnostic consultations may take a few minutes, yet how these minutes are managed, what words are used and how this makes a patient feel may change how they make sense of their condition and influence their wellbeing in the longer term. It is important that doctors have an awareness of the words they use and think about how they could be perceived by patients.”  

In one of the first studies of its kind, researchers investigated the impact of PCOS diagnostic consultations and whether the language used impacted the subsequent wellbeing of patients.

To assess the impact, researchers surveyed 147 females with PCOS and asked about their satisfaction with their consultation, the language used during it and their overall wellbeing.  

Researchers found that those who had felt uncomfortable with the consultation process were more likely to report poorer body esteem, reduced quality of life and greater concerns about health in later life. Over a quarter of those surveyed were dissatisfied with how doctors managed their distress and were unhappy with the lack of rapport they had with their practitioners.  

Prof Ogden added: “Words matter, as patients often replay conversations that they have had with doctors in a bid to make sense of situations. Although words such as ‘raised’ and ‘irregular’ are simple words they are vague which can cause women to worry, as they automatically think the worst, as they have not been provided with all the facts. Such anxiety at the time of diagnosis, can negatively impact how they feel about themselves as their life progresses.” 

Source: University of Surrey

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Comorbidities are Common in Polycystic Ovary Syndrome

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Polycystic ovary syndrome (PCOS) is the most common hormonal disorder in reproductive-age women. In a study published in Acta Obstetricia et Gynecologica Scandinavica, women with PCOS were more likely to also have migraine, hypertension, tendinitis, osteoarthritis, and endometriosis.  Affected women were also using medications more often and reported their own health to be poorer than women without PCOS.  

Few studies have systematically assessed the overall comorbidity in women with PCOS, which should be of greater importance given the high costs of PCOS-related comorbidity. For example, PCOS-related type 2 diabetes alone has been estimated to carry an annual cost of $310 million in the UK and $1.77 billion in the USA. The syndrome often remains underdiagnosed despite being so common, and therefore is less represented in national databases, making it harder to assess comorbidities.

The present study included 246 women with PCOS symptoms or diagnoses and 1573 controls who were surveyed during their late reproductive years at age 46.  

“PCOS is often labelled as a reproductive concern; however, in most cases this is well managed with fertility treatments. Our study underscores the need for health professionals to acknowledge the risk for several comorbidities and increased health burden related to this common syndrome,” said senior author professor Terhi T. Piltonen, MD, PhD, of the University of Oulu, in Finland. “Women should also be aware of this risk, and they should be supported by early diagnosis and treatment.”  

Source: Wiley