Risks Associated with Polycystic Ovary Syndrome

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Risks Associated with Polycystic Ovary Syndrome

Main article: Polycystic Ovary Syndrome Overview

Updated: 18-October-2024

Risks Associated with Polycystic Ovary Syndrome

Women diagnosed with Polycystic Ovary Syndrome are also at higher risk of other disorders and complications.

These risks include:

  • Endocrine disorders
  • Cardiovascular disease
  • Gestational diabetes, Impaired glucose tolerance, Type 2 diabetes
  • Liver disease
  • Kidney stones
  • Endometrial cancer
  • Infection
  • Pregnancy complications
  • Inflammatory disorders
  • Cognitive impairment
  • Mental disorders
  • Eating disorder
  • Obstructive sleep apnea
  • Asthma

Endocrine Disorders

Studies show that women with PCOS are at higher risk of other endocrine disorders, specifically insulin resistance (relative risk = 3.0), hypothyroidism (relative risk = 3.4), hyperprolactinaemia (relative risk = 3.15) and even acromegaly.1,2 However, not all studies support the link between PCOS and hypothyroidism or hyperprolactinaemia.3 Further studies are needed to better understand the contrary findings. Mahboobifard F, et al reported that at least 1 in 4 women with PCOS aged ≤35 years are diagnosed with hyperprolactinaemia.4 While the risk of Hashimoto’s thyroiditis may depend on ethnicity.5,6

Hypothyroidism and hyperprolactinemia, are well known causes of infertility in non-PCOS women.

Subclinical hypothyroidism, defined as TSH levels between 5 and 10 mIU/L and normal FT3 and FT4 levels, was also found to be two times more prevalent in women with PCOS (44% vs. 21%).7 Current evidence suggests that obesity and insulin resistance exacerbate this disorder within an immune compromised environment.8,9 However, there is some debate around this diagnosis given other makers of thyroid dysfunction.10

In fact, women with PCOS and normal thyroid results should check their levels of anti-thyroid peroxidase antibodies (anti-TPO) to detect the onset of autoimmune thyroid disease much earlier.11

Cardiovascular Disease

Women with PCOS also have an elevated risk of cardiovascular disease due to higher incidences of obesity, hypertension (caused by obesity), dyslipidemia, insulin resistance, hyperinsulinaemia and hyperhomocysteinemia.12,13,14,15,16,17,18,19

Inversely some of these studies also suggest that weight loss, particularly among obese women with PCOS, will reduce this risk somewhat.

Interestingly, not all obese women with PCOS are metabolically unhealthy. In fact, 1 in 3 obese women with PCOS were found not to have metabolic syndrome which may be partly related to diet (Mediterranean).20

A recent study reported the intake of saturated fat contributes to dyslipidemia and atherogenesis in women with PCOS, compared to non-PCOS women.21 It also revealed this effect is amplified in obese women, with or without PCOS, highlighting the importance of both diet and weight management among women to control this risk factor.

Even as women with PCOS get older and androgen levels decrease the risk of cardiovascular disease remains the same requiring long-term management.22

Gestational Diabetes, Impaired Glucose Tolerance, Type 2 Diabetes

In women diagnosed with PCOS there is a 3 to 5 fold increased risk of gestational diabetes, impaired glucose tolerance and type 2 diabetes, independent of obesity linked specifically to elevated androgen levels and also Selenoprotein P which is produced by the liver.23,24,25,26,27,28

Interestingly the severity of PCOS is also greater in non-obese women with first-degree relatives (family history) featuring type 2 diabetes mellitus (T2DM), compared to women with only second degree T2DM relatives, adding further evidence to the effect of genes in this condition.29

Liver Disease

Nonalcoholic fatty liver disease (NALFD) is significantly more common in women with PCOS (52% vs. 30%).30 Clinically, higher liver stiffness is positively linked to waist circumference, metabolic syndrome, calcium, DHEAS, testosterone and HOMA-Insulin resistance levels among PCOS women.31,32 In another study, independent predictors of nonalcoholic liver disease, after adjusting for duration of PCOS and insulin resistance, identified hyperandrogenism, elevated BMI and alanine aminotransferase.33 Interestingly, liver fat content increases, when Free Androgen Index (FAI) is less than 41.94, but decreases when FAI is greater than 41.94, confirming the real effect of androgen levels on liver fat content.34 Animal models suggest that under low to medium hyperandrogenism, liver dysfunction is primarily regulated by androgen receptors in the liver.35 However under high hyperandrogenism, androgen receptors in the brain and adipose tissue are the primary regulators of liver dysfunction.

The existing NAFLD definition was recently revised to become metabolic dysfunction-associated fatty liver disease (MAFLD). This new definition requires two markers of metabolic dysfunction in addition to steatosis be present to confirm MALFD. In normal weight women with PCOS, a C reactive protein (CRP) >2.0mg/L, Homeostasis Model Assessment-Insulin Resistance (HOMA-IR) value ≥2.5 and steatosis would confirm MAFLD.36

Kidney Stones

Hyperuricemia and kidney stones is a recently reported risk associated with PCOS.37,38 Experts always suspected this given other studies linking male androgen hormones to the formation of kidney stones.39,40 According to Dovom et al. women with PCOS are 2 to 3 times more likely to develop kidney stones (especially those with irregular cycles and polycystic ovaries).41

Endometrial Cancer

In women with irregular or absent periods there is an 2 to 6 fold increased risk of developing endometrial cancer (womb lining) caused by a lack of menstruation, although the overall risk is still low.42,43 An endometrial thickness less than 7 mm is considered unlikely to develop into cancer, which can be checked by ultrasound. However, induction of menstrual flow is recommended whenever duration of cycle is greater than 3 months.

Women with PCOS require extra attention during pregnancy.

Infection

Bacterial vaginosis, a bacterial infection associated with inflammation and hormone disorders is significantly more prevalent in women with PCOS.44 However further research is needed to better understand the underlying cause and effects.

Especially since an earlier study reported bacterial vaginosis as a potential cause of subfertility, among women with PCOD or unexplained infertility, with antibiotic treatment more than doubling the cumulative pregnancy rates after 6 months.45

Pregnancy Complications

A retrospective cohort study comparing 42,391 women with PCOS and 795,480 women without PCOS found that women with PCOS had a higher prevalence of gestational diabetes (24% vs 13%), gestational hypertension (14% vs 8%) and preeclampsia (5% vs 3%) during pregnancy.46 Crucially, poor sperm quality also increases the risk of preeclampsia.47,48

Early pregnancy loss is also more prevalent in women with PCOS.49,50 This is currently associated with an impaired endometrium and is being investigated further.51

In a PGD FET (Fresh Embryo Transfer) study, comparing lean PCOS women and non-PCOS women, reported similar clinical pregnancy rates (50% vs. 55%) but significantly higher rates of early pregnancy loss in women with PCOS (27% vs. 10%).

Source: Luo L, et al. (2017)

Interestingly, blastocyst formation rates for PCOS embryos was also lower (54% vs 62%) than non-PCOS embryos, although this needs to be confirmed in a larger study.52 They concluded that women with PCOS, independent of BMI and karyotype, have an increased risk of early miscarriage.

To understand the possible reason for this, a recent meta-analysis of 22 studies, featuring 11,182 women with PCOS, identified both BMI and insulin-resistance as independent risk factors associated with an increased risk of spontaneous abortion in ART cycles,53 which may or may not apply to women with PCOS who fall pregnant naturally.

Source: Sun Y, et al. (2020)

However, several PCOS animal studies show that hyperandrogenism and insulin resistance induced foetal loss is the result of uterine and placental defects.54,55,56,57,58 In fact, human studies show abnormalities of the uterine cavity is more prevalent among women with PCOS.59 These abnormalities are likely a result of elevated AMH levels in utero.60,61

Analysis of the Swedish Medical Birth Register, also showed that women with PCOS experience a higher rate of preterm births (6.7% vs. 4.8%) and stillbirth (0.6% vs. 0.3%) compared to those without PCOS.62,63 Although, a matched cohort study in England only found an association between PCOS and preterm births.64 Nevertheless, a retrospective study of 1755 live births in subfertile women with PCOS following FET shows a clear link between endometrial thickness and neonatal complications.65 Abdelsalam et al. suggests women with PCOS and elevated AMH levels are at particular risk of preterm delivery.66

Meanwhile, an IVF study reported women with PCOS and amenorrhea were at higher risk of adverse pregnancy outcomes (such as gestational diabetes, hypertensive disorders, premature rupture of membranes, macrosomia) compared to those with oligomenorrhea.67 This finding is supported by an earlier study which suggests adverse pregnancy outcomes in women with PCOS is somehow related to menstrual patterns (and endometrial development).68 Although, this could also be related to coexisting disorders such as endometriosis.69 

However the risk of pregnancy complications in women with PCOS and normal ovulation is practically no different to that of normal women.70

DOES PCOS CAUSE BLOCKED FALLOPIAN TUBES

PCOS does not directly cause blocked fallopian tubes. Instead, the risk of blocked fallopian tubes in women with PCOS appears to vary significantly according to phenotype. Specifically, women with PCOS phenotype A are at significantly higher risk of blocked fallopian tubes (and possibly ectopic pregnancy).71,72 Related studies suggest elevated testosterone levels (hyperandrogenism) causes tubal dysfunction.73,74

Inflammatory Disorders

In a first study of its kind, exploring the link between hormonal imbalance and systemic autoimmune diseases, women with PCOS were compared to age and BMI matched women without PCOS. The prevalence of rheumatoid arthritis (2.3 vs. 1.3 %), systemic sclerosis (0.4 vs. 0.0 %), undifferentiated connective tissue disease (0.5 vs. 0.0 %) and osteoarthritis (5.4 vs. 2.9 %), was higher among women with PCOS, adding further reasons for long term management of PCOS.75,76,77 A similar finding was reported in women with PCOS and inflammatory bowel disease (IBS), with IBS found to be almost twice as prevalent (10.7 vs. 5.8 %).78

Cognitive Impairment

Insulin resistance and excess androgen levels is associated with impaired verbal, motor and visual-spatial cognitive abilities.79,80,81 However studies also show that anti-androgenic treatment in women with PCOS eliminate any significant difference in tests results compared to controls.82 This inherent difference was confirmed recently via magnetic resonance imaging, of 41 women with PCOS, with significant differences observed in the cognitive and emotional regions of the brain compared to controls.83,84

Mental Disorders

In various tests for both personality and psychological disorders, the mean scores comparing women with PCOS, to women without PCOS, are consistently different.85,86 This finding remains true even when both groups of women tested are infertile. Although the mean score is statistically significant, the standard deviation of the scores shows that not all women with PCOS are psychologically affected by this condition. This difference may be explained by obesity, which negatively impacts the quality of life and mental health of infertile women with or without PCOS similarly.87 A postpartum study also observed that women with PCOS are at higher risk of postpartum depressed moods and anhedonia.88 However further analysis found this was most likely related to prenatal depression and anxiety in the women featuring PCOS.

Interestingly a recent study of 200 women with PCOS, found 38% at high-risk for obstructive sleep apnea (OSA).89 Using various questionnaires and statistical analysis, this subgroup of women also showed a 306% increased risk for moderate/severe depression, and 239% increased risk of moderate/severe anxiety, compared to women with PCOS minus OSA.

Treating obstructive sleep apnea may improve psychological well being and decrease the severity of PCOS.

Eating Disorder

Food addiction, an eating disorder, is a newly reported risk associated with PCOS.90 Research suggests this is linked to insulin resistance. Insulin resistance dysregulates appetite hormone levels which play a role in food cravings and reward-based eating. This in turn increases the consumption of ultra-processed foods high in refined carbohydrates and fats which further exacerbates insulin resistance.

Obstructive Sleep Apnea

The prevalence of obstructive sleep apnea (OSA) is as high as 40% in women (and adolescents) with PCOS.91,92,93 Unsurprisingly women with PCOS and OSA have significantly altered endocrine and metabolic characteristics, compared to women with PCOS minus OSA. This included higher blood pressure, BMI, levels of testosterone, fasting plasma glucose and insulin with decreased AMH and HDL cholesterol levels. Coincidentally variations in melatonin production is directly related to menstrual cycles.94 Improvements in menstrual cycle regularity may potentially coincide with increased sleep quality (and decreased OSA).

Obstructive sleep apnea impairs female fertility over and above PCOS.

Source: Zhang Q, et al. (2023)

Asthma

Women with PCOS are at significantly higher risk of asthma and lower lung function.95 This may be related to the myo-inositol imbalance common among women with PCOS but further studies are necessary.96

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