Polycystic Ovary Syndrome (PCOS) affects one in seven reproductive-age women worldwide. PCOS impacts women’s physical and mental health, and it may also have detrimental effects on their social lives, academic achievement and careers. Studies show women with PCOS have higher rates of depression, anxiety, eating disorders, infertility and postpartum depression compared with women without the condition.

The economic burden of PCOS is enormous. Previous studies show PCOS-related economic costs totals billions of dollars. But few studies have examined the costs associated with PCOS-associated mental health care. Learning more about these costs may help policymakers and clinicians allocate resources for mental health care for women with PCOS.

Yadav et al. analyzed the results of 25 studies to assess the mental health impact of PCOS and its costs. The analysis found that women with PCOS are 60% more likely to have depression or anxiety compared to women without the condition. They were also twice as likely to have eating disorders. Caring for these mental health issues in PCOS patients increases US healthcare costs by approximately $4.2 billion yearly. These costs raise the healthcare-related economic burden of treating PCOS and associated conditions to $15 billion in the United States each year.

The analysis suggests that earlier recognition and better treatment of PCOS could reduce associated healthcare costs and improve the quality of life for women with PCOS. The results may help policymakers and clinicians understand the condition's impact and prioritize resources for PCOS care. More research on the condition is necessary to reduce the enormous economic and personal burden caused by it.

Polycystic ovary syndrome (PCOS) is a highly prevalent disorder, highly inherited complex polygenic, multifactorial disorder (Azziz et al., 2016). PCOS is the single most common endocrine-metabolic disorder in reproductive-aged women today, affecting 5–15% of unselected reproductive-aged women (1990 National Institutes of Health criteria), and potentially represents a significant financial burden to our healthcare (Azziz et al., 2005; Riestenberg et al., 2022). Pathophysiological abnormalities in gonadotropin secretion or action, ovarian folliculogenesis, steroidogenesis, insulin secretion or action, and adipose tissue function, among others, have been described in PCOS. Women with PCOS are at increased risk for glucose intolerance and type 2 diabetes mellitus (T2DM), hepatic steatosis and metabolic syndrome, hypertension, dyslipidemia, vascular thrombosis, cerebrovascular accidents, possibly cardiovascular events, subfertility, and obstetric complications, endometrial carcinoma, and mood and psychosexual disorders (Azziz et al., 2016).

Although the physical symptoms of PCOS are increasingly recognized by practicing clinicians, little attention has focused on the psychological correlates of this frequent endocrine disorder (Himelein and Thatcher, 2006; Brutocao et al., 2018). A significant amount of research has been conducted showing the direct causal relationship between PCOS diagnosis and mental health (MH) disorders. PCOS is associated with an increased risk of a diagnosis of depression, anxiety, bipolar disorder, and obsessive–compulsive disorder (OCD) and is associated with worse symptoms of depression, anxiety, OCD, and somatization (Himelein and Thatcher, 2006; Brutocao et al., 2018). Screening for these disorders to allow early intervention may be warranted.

In order to allow for a more accurate prioritization of the disorder as a public health priority, we have pursued a comprehensive estimation of the economic burden of PCOS. In previous studies conducted by our team, we estimated the mean annual cost of the initial evaluation of PCOS to be $93 million, that of hormonally treating menstrual dysfunction/abnormal uterine bleeding to be $1.35 billion, that of providing infertility care to be $533 million, and that of treating hirsutism to be $622 million in 2014 USD (Azziz et al., 2005). In a more recent study, we estimated the mean annual costs of PCOS-associated T2DM and associated stroke to be $1.5 and $2.4 billion in 2020 USD, respectively (Riestenberg et al., 2022). The present study aims to assess the direct healthcare-related economic burden of PCOS-related MH disorders. To do so, we conducted a systematic review and meta-analysis of published studies with human subjects and controls that analyzed the relationship between MH disorders and previous diagnosis of PCOS, and then calculated the related direct economic burden.

A total of 2018 studies were identified during the initial literature review, of which 78 were screened by title and abstract (Figure 1). Forty-three potentially eligible studies were reviewed in detail, of which 18 were excluded due to insufficient information. For example, some studies did not include information on a control group, did not include measures of association, used a continuous outcome instead of dichotomous outcome, or did not provide information about risk/prevalence that was needed to compute the PRs. The general characteristics of the 25 included studies (Alur-Gupta et al., 2019; Tan et al., 2017; Karjula et al., 2017; Tay et al., 2020; Kaur et al., 2019; Asik et al., 2015; Cesta et al., 2016; Hussain et al., 2015; Månsson et al., 2008; Jedel et al., 2010; Li et al., 2017; Damone et al., 2019; Hollinrake et al., 2007; Pastore et al., 2011; Cinar et al., 2011; Adali et al., 2008; Lee et al., 2017; Pirotta et al., 2019; Koric et al., 2021; Joham et al., 2016; Muchanga et al., 2017; March et al., 2018; Tay et al., 2019; Alur-Gupta et al., 2021; Fugal et al., 2022) are detailed in Supplementary file 2a–d.

Figure 1

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Excess prevalence of anxiety in women with PCOS

Twelve studies, all assessed as ‘high quality’ (Supplementary file 2e), were initially identified, measuring an association between anxiety and PCOS (Alur-Gupta et al., 2019; Tan et al., 2017; Karjula et al., 2017; Tay et al., 2020; Kaur et al., 2019; Asik et al., 2015; Cesta et al., 2016; Hussain et al., 2015; Månsson et al., 2008; Jedel et al., 2010; Li et al., 2017; Damone et al., 2019). However, only ten studies were included in the meta-analysis, as two studies were excluded due to the lack of prevalence data (Jedel et al., 2010; Li et al., 2017). Compared to age-matched women without PCOS, those with PCOS had a higher prevalence of anxiety in the meta-analysis (random effects PR: 1.42; 95% CI: 1.32, 1.52; I² 43.82%; Figure 2A). For our economic burden calculations, we considered PCOS patients as having a 1.42-fold greater risk of anxiety compared to those without PCOS.

Figure 2 with 3 supplements see all

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Considering that comparably aged women of the general population have a prevalence of anxiety of 9.15%, the overall prevalence of anxiety in women with PCOS can be estimated to be 1.42 × 9.15% = 12.99%. The excess prevalence of anxiety due to PCOS is therefore 12.99–9.15% = 3.84%; the excess number of anxiety cases due to PCOS is 5,631,459 × 3.84% = 216,248 individuals.

In the U.S., the additional direct healthcare costs associated with MH disorders in PCOS were estimated to be $1.939 billion/yr., $1.678 billion/yr., and $0.644 in 2021 USD for anxiety, depression, and eating disorders, respectively. The combined additional direct healthcare costs associated with depression and anxiety in PCOS was estimated to be $4.261 billion/yr. in 2021 USD, of which 45% can be attributable to anxiety, 40% to depression, and the remainder to eating disorders. While the prevalence of postpartum depression appeared to be increased in PCOS, the difference did not reach significance on meta-analysis and this outcome was not included in our economic burden calculations.

Taken together, including our prior economic burden assessments (Azziz et al., 2005; Riestenberg et al., 2022), the total excess economic burden estimated for PCOS exceeds $15 billion annually in 2021 USD (Table 2). Of this cost, approximately 28% will be accounted for the cost of treating PCOS-related MH disorders, including anxiety, depression, and eating disorders; 29.5% will be accounted for the cost of treating reproductive endocrine morbidities (menstrual dysfunction/abnormal uterine bleeding, hirsutism, and infertility); 15.1% is attributable to obstetrical and pregnancy related disorders; and 10.1% and 16.1% is attributable to T2DM and strokes, respectively. The cost of the initial diagnostic evaluation of PCOS is very low ($166 million annually in 2021 USD; Table 2), accounting for only 1.1% of the total economic burden attributable to direct healthcare costs of the disorder estimated so far. These data strongly suggest that ensuring quality diagnosis and evaluation for all patients with PCOS is a cost-effective approach to ameliorating the complications and costs associated with the disorder.

For perspective, the estimated direct healthcare costs attributable to ovarian cancer, lung cancer, prostate cancer, and breast cancer, in the U.S. are $7.8, $16.8, $26.7, and $20.5 billion in 2021 USD, respectively (Waters and Graf, 2018), compared to $15.2 billion for PCOS so far. Furthermore, the included costs are only for those morbidities that to date have been confirmed as increased in PCOS relative to controls after careful meta-analyses considering the quality of the studies. As further studies are undertaken it is likely that the economic burden of PCOS related to direct healthcare costs will continue to rise.

Liu et al. assessed the current burden of PCOS at the global, regional, and country-specific levels in 194 countries and territories according to age and sociodemographic index (SDI) (Liu et al., 2021). The investigators used data from the Global Burden of Diseases, Injuries and Risk Factors Study (GBD) 2017 to estimate the total and age-standard PCOS incidence rates and the associated disability-adjusted life-years (DALYs) rates among women of reproductive age in both 2007 and 2017, and the trends in these parameters from 2007 to 2017. The data sources used in GBD take many forms, including census data, vital registrations, disease registries, survey data, and published and unpublished scientific literature, among other sources (https://www.healthdata.org/acting-data/what-data-sources-go-gbd). These investigators concluded that PCOS accounted for 0.43 million associated DALYs. They also noted slight increases in the age-standardized incidence of PCOS and DALYs among women of reproductive age (15–49 years) from 2007 to 2017 at the global level, and in most regions and countries. Safiri et al. also used the GDB Study 2017 database to determine the global, regional, and national burden of PCOS, by age and SDI, over the period 1990–2019 (Safiri et al., 2022). These investigators reported that in 2019 the global age-standardized point prevalence and annual incidence rates for PCOS were 1677 (1.7%) and 59 (0.06%) per 100,000, respectively.

Neither one of these studies estimated the economic cost of the burden observed. Furthermore, we should note that (Liu et al., 2021) reported only on global age-standardized PCOS incidence rates (i.e., the occurrence of new cases of PCOS over a specified period of time), not prevalence rates (i.e., the total proportion of persons in the population who have PCOS at a specified point in time or over a specified period of time), among women of reproductive age. While Safiri et al., 2022 present an estimate of prevalence, we should note that the estimate is significantly lower than that reported when populations are assessed directly for the prevalence of PCOS (1.7% vs. 6.6% or greater), likely reflecting the chronic underdiagnosis of PCOS.

Ding et al. estimated the burden of disease attributable to type 2 DM in women with PCOS using individual patient data from a UK primary care database between 2004 and 2014 and aggregate data from the literature to obtain conversion rates through disease progression (Ding et al., 2018). A simulation approach was applied to model the population dynamics of PCOS over a follow-up period of 25 years in using Bayesian modeling. The investigators estimated that the associated annual healthcare burden of T2DM in PCOS was at least £237 million in 2014 pounds in the UK. Taking into account the relative populations of reproductive-aged women (15–49 years) of the UK and the U.S. (14.7 vs. 76.5 million) (United Nations, Department of Economic and Social Affairs, Population Division, 2022), the healthcare inflation rate since 2014 (19.2%), and the conversion rate of pounds to dollars in mid-2021 (0.72 USD to 1 pound), the economic burden for PCOS-associated T2DM estimated by Ding et al., 2018 is equivalent to $2.04 billion 2021 USD, somewhat higher than the $1.527 2021 USD that we previously estimated (Table 2; Riestenberg et al., 2022).

The strength of this study lies in the exclusive inclusion of peer-reviewed and controlled studies. However, our analysis encountered limitations due to the restricted number of studies that satisfied the inclusion criteria. This could be due to the fact that PCOS diagnosis creates an umbrella effect that encompasses physical as well as MH disease which creates a false belief in patients that they cannot be treated or diagnosed with a disease other than PCOS due to the misconception that their symptoms stem solely from the PCOS diagnosis. Other limitations of this study include the fact that while the cost estimates were conducted for the U.S., the meta-analysis used some studies from other countries.

Additional possible limitations stem from the inclusion of studies that relied on self-reported PCOS, which could introduce recall and reporting bias, potentially affecting the reported PRs of MH-related conditions. However, we should note that the point estimates changed little when excluding studies that used self-reported PCOS. In our calculations, we used inflation-adjusted estimates from previous studies to account for the changing value of currency over time. While this method provides a useful approximation, we acknowledge that it does not account for changes in treatment practices, healthcare policies, or the overall structure of healthcare costs that might have occurred since the original estimates were made. Finally, while other MH disorders have been shown to be associated with PCOS, such as bipolar disorder and OCD, we focused our study solely on the four most common disorders found in the literature (Himelein and Thatcher, 2006; Brutocao et al., 2018).

In conclusion, our current study suggests that the additional direct healthcare costs due to PCOS-related anxiety, depression, and eating disorders exceeds $4 billion annually in 2021 USD in the U.S. So far, the total direct economic burden of PCOS exceeds $15 billion annually in 2021 USD, and MH disorders account for almost one-third of these costs. Notably, these estimates are solely for the U.S. and PCOS is a global disease. As PCOS is clinically most apparent during the reproductive age, we should note that the number of women between the ages of 15 and 49 worldwide is estimated to be about 1.9 billion (United Nations, Department of Economic and Social Affairs, Population Division, 2022). Taking into account that most studies assessing the prevalence of PCOS report a minimum rate similar to what was used on the present study (i.e., 6.6% based on the NIH criteria) (Bozdag et al., 2016), we can estimate that there are at least 125.4 million women affected with PCOS worldwide. Consequently, the worldwide economic burden for PCOS can be assumed to be enormous.

While we have examined the direct economic burden related to the medical or health-related costs of the disorder, we should note that a complete understanding of the economic burden of the disorder requires that we also assess the indirect (those attributable to loss of work productivity) and intangible (those related to the pain and sufferings of patients because of a disorder, usually measured by using the reduction in quality of life) costs of the disorder. Our data suggest that improved detection of PCOS and more significant clinical awareness and interventions for PCOS and its associated disorders is a cost-effective approach to ameliorating the economic, health, and quality of life impact of PCOS. Finally, our findings further highlight the need to increase investment in PCOS research, which is currently severely underfunded relative to the economic burden of the disorder (Brakta et al., 2017).

The data is available at Zenodo: https://doi.org/10.5281/zenodo.8122261.

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Author details

1. Surabhi Yadav

   School of Global Public Health, New York University, New York, United States

   Contribution

   Conceptualization, Data curation, Software, Formal analysis, Validation, Writing - original draft

   Competing interests

   No competing interests declared

2. Olivia Delau

   School of Global Public Health, New York University, New York, United States

   Contribution

   Data curation, Software, Formal analysis, Validation, Investigation, Methodology, Writing - original draft

   Competing interests

   No competing interests declared

3. Adam J Bonner

   Department of Obstetrics and Gynecology, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, United States

   Contribution

   Data curation, Formal analysis, Validation, Investigation, Writing – review and editing

   Competing interests

   No competing interests declared

4. Daniela Markovic

   Division of General Internal Medicine and Health Services Research, University of California, Los Angeles, Los Angeles, United States

   Contribution

   Software, Formal analysis, Validation, Methodology, Writing – review and editing

   Competing interests

   No competing interests declared

5. William Patterson

   PCOS Challenge: The National Polycystic Ovary Syndrome, Atlanta, United States

   Contribution

   Conceptualization, Resources, Methodology, Project administration, Writing – review and editing

   Competing interests

   is a Director of Public Affairs, Study Recruitment and Patient Registry Manager, and Intern Preceptor for PCOS Challenge: The National Polycystic Ovary Syndrome Association. The author has no other competing interests to declare

6. Sasha Ottey

   PCOS Challenge: The National Polycystic Ovary Syndrome, Atlanta, United States

   Contribution

   Conceptualization, Resources, Supervision, Investigation, Writing – review and editing

   Competing interests

   received honoraria from Institute for Family Centeredness; has received travel support for attendance at Women's Health Innovation Summit; and is Executive Director for PCOS Challenge: The National Polycystic Ovary Executive Director Syndrome Association. The author has no other competing interests to declare

7. Richard P Buyalos

   Department of Obstetrics and Gynecology, University of California, Los Angeles, Los Angeles, United States

   Contribution

   Conceptualization, Resources, Funding acquisition, Project administration, Writing – review and editing

   Competing interests

   No competing interests declared

8. Ricardo Azziz

   1. Department of Obstetrics and Gynecology, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, United States
   2. Department of Health Policy, Management and Behavior, University at Albany, State University of New York, Rensselaer, United States
   3. Department of Medicine, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, United States
   4. Department of Healthcare Organization and Policy, School of Public Health, University of Alabama at Birmingham, Birmingham, United States

   Contribution

   Conceptualization, Resources, Data curation, Formal analysis, Supervision, Validation, Investigation, Methodology, Project administration, Writing – review and editing

   For correspondence

   razziz67@gmail.com

   Competing interests

   received a grant from Ferring Pharmaceuticals; has received royalties from Wolters Kluwer Health, Johns Hopkins University Press, Springer, and McGraw Hill; has received honoraria from Davidson-Mestman course; has participated on a data safety monitoring board for University of Michigan and Guangzhou Medical University; has held a leadership or fiduciary role at American Society for Reproductive Medicine; holds stock at Martin Imaging and Arora Forge; has received consulting fees from Spruce Biosciences, Fortress Biotech, Rani Therapeutics, Core Access Surgical for PCOS, female reproduction and gynecologic surgery; and serves as Senior Editor at eLife. The author has no other competing interests to declare

   "This ORCID iD identifies the author of this article:" 0000-0002-3917-0483

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