Could polycystic ovary syndrome be linked to cognitive decline?

Article written in collaboration with Professor Vittorio Unfer, UniCamillus lecturer and PCOS expert

Are women with polycystic ovary syndrome (PCOS) at risk of early cognitive decline? It can’t be stated with certainty, but according to a study by researchers at the University of California, San Francisco, it seems that this is quite likely.

Heather Huddleston, a specialist in Reproductive Endocrinology, led a longitudinal study lasting for more than 30 years. During this time, 907 women were monitored, 66 of whom suffered from PCOS. At the beginning of the study, they were all between 18 and 30 years old. By the end of the study, they had undergone imaging tests and assessments to measure memory, attention, verbal skills, and cognitive abilities.

The results found a lower score particularly in the tests administered to women suffering from polycystic ovaries, also highlighting a reduced integrity of the white matter in the brain.

What exactly is polycystic ovary syndrome?

What is PCOS?

Polycystic ovary syndrome is a condition that affects some women of childbearing age. It involves the ovaries producing an excessive amount of androgens (hyperandrogenism), male sex hormones that are typically only present in minimal quantities in women.

It is so named because it is characterized by numerous small cysts forming on the ovaries, which produce these androgens (although ovarian cysts are not exclusive to women with PCOS).

These cysts are caused by the absence of ovulation found in people with this condition, accompanied by absent or highly irregular menstrual cycles.

Symptoms of PCOS include:

– irregular, scant, or even absent cycles

– hirsutism

– weight gain, especially around the abdomen

– acne or oily skin

– thinning of hair

– infertility

Without a timely diagnosis there is a risk of developing long-term consequences such as endometrial cancer, endometrial hyperplasia, coronary artery disease, hypertension, and hyperlipidaemia.

The exact causes of PCOS are unclear, although a frequent correlation between PCOS and type II diabetes, or some form of insulin resistance, has been observed. High insulin levels can in turn cause an increase in androgens. Obesity can also raise insulin levels, thereby exacerbating PCOS symptoms.

Heredity in polycystic ovary syndrome has been observed—often, a woman with PCOS has a mother or sister with the same condition.

Insights from our expert

How can an ovarian defect correlate with brain problems? We spoke to Professor Vittorio Unfer, UniCamillus lecturer in Gynaecology and Obstetrics, specialised in the study of PCOS, and the world’s leading advocate for the use of myo-inositol to manage this syndrome.

The University of San Francisco study highlights a coexistence between cognitive decline and PCOS. Is it a matter of causality or ‘mere’ correlation?

“The findings of Huddleston’s study at the University of San Francisco suggest that middle-aged women with PCOS show lower cognitive performance and reduced white matter integrity compared to women of the same age without PCOS. To clarify actual causality, more in-depth research is needed to confirm these results and determine the potential molecular pathways underlying the observed outcome, including modifiable factors.”

How is PCOS related to cardiovascular, cerebral, and cognitive health?

“To easily understand how PCOS can correlate with cardiovascular health, just think that some patients with this syndrome may exhibit alterations in glucose metabolism leading to concurrent conditions such as hyperinsulinaemia, weight gain, development of type 2 diabetes, and insulin resistance, which can impact the patient’s cardiovascular health over the years.

Closely linked to the pathogenesis of PCOS and glucose metabolism are inositol levels, a natural molecule involved in signalling pathways of some hormones, including insulin and follicle-stimulating hormone. Alterations in inositol levels can contribute to the onset of pathological conditions at the reproductive, metabolic, and endocrinological levels, as mentioned above.

Beyond the metabolic-hormonal sphere, recent studies have also identified a link between PCOS and the cerebral sphere, demonstrating that women with PCOS have a greater predisposition to the onset of depression, related to a reduction in cerebral inositol levels, as well as a series of clinical manifestations of the syndrome (acne, infertility, weight gain) that can affect the patient’s mood.”

From this data we understand PCOS can affect health beyond the reproductive aspect. Are there other problems it can cause?

“PCOS is a highly complex syndrome that can coexist with various clinical conditions. As already mentioned, in some types of patients, PCOS correlates with endocrine-metabolic alterations, including weight gain, insulin resistance, type 2 diabetes, hyperandrogenism.

Additionally, women with this syndrome are more predisposed to thyroid issues. Not surprisingly, inositol plays a physiological role as a second messenger of the thyroid-stimulating hormone, and it appears that the incidence of subclinical hypothyroidism is higher in women with PCOS than in those without the syndrome.

Migraine is also very common in women with PCOS. Undoubtedly, genetic factors have profound effects on the causes of migraine, but sexual hormones (oestrogen and progesterone) have been noticed to play a significant role, too. At the same time, some conditions common in women with PCOS, such as sleep apnoea, amenorrhoea, and vascular disease, can cause—or intensify—migraine in women with PCOS.

Interestingly, it’s also possible to identify an iatrogenic origin of PCOS based on the ovarian reduction of inositol. Some medications used in psychiatric clinical practice, like lithium and valproic acid, base their therapeutic action on a reduction of cerebral inositol, elevated in manic phases. However, the reduction of inositol induced by these medications doesn’t only affect the central nervous system but also other tissues collaterally, leading to the onset of a series of adverse reactions, including PCOS, as well as other conditions such as weight gain, hypothyroidism and dysmetabolism.”

Could this study offer interesting insights into the treatment of PCOS? What are, in your opinion, the future research areas to analyse?

“Huddleston et al.’s study suggests a multidisciplinary approach in treating PCOS, offering a crucial perspective to consider, not least, mental health in the management of patients with the disease. Certainly, there are still various, stimulating goals to achieve in clinical research on PCOS, so further insights are needed to complete what has emerged in this study and reach a 360-degree approach for these patients.

Future research areas are now directed towards increasingly personalised therapeutic approaches. Recent evidence has shown how important it is, also in the context of PCOS, to perform a precise and accurate diagnosis that can identify the correct phenotype of the patient and guarantee a personalised and effective therapeutic approach.”

Is there general advice that can be given to women living with PCOS
or to those who suspect they might have it? How can the problems they face be mitigated?

“Changes in lifestyle and proper nutrition are two highly recommended approaches for women living with PCOS, especially those patients showing metabolic-hormonal alterations. Adding physical exercise, in terms of aerobic activity, can have a positive impact on the clinical condition of these patients.

The use of insulin-sensitizing agents, including dietary supplements based on inositol, represents an effective approach in patients with PCOS, finding a therapeutic rationale for use in those patients characterized by endocrine-metabolic alterations. Thanks to scientific research, it’s clear that there are different types of patients with PCOS and that each requires a specific treatment.

The use of oral contraceptives can and should be employed in the management of PCOS when there is a contraceptive request from the patient. However, considering the risk factors involved, such as cardio-metabolic risk, hormonal therapy is effective when it’s combined with lifestyle changes or the intake of insulin sensitizers (metformin, inositol), which have the aim of rebalancing the metabolic parameters at risk of being compromised.

By improving the diagnostic profile of PCOS patients, it’s possible to identify the right therapeutic rationale and ensure an approach that is as personalised and effective as possible, so as to aim for a significant improvement in the quality of life of these patients.”