Direct economic burden of mental health disorders associated with polycystic ovary syndrome: Systematic review and meta-analysis

  1. Surabhi Yadav
  2. Olivia Delau
  3. Adam J Bonner
  4. Daniela Markovic
  5. William Patterson
  6. Sasha Ottey
  7. Richard P Buyalos
  8. Ricardo Azziz

  • Curated by eLife

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    This important paper describes a valuable systematic review and meta-analysis of mental health problems in polycystic ovary syndrome (PCOS) that drive the excess economic burden associated with this common endocrine disorder. Interestingly, the cost of the diagnostic evaluation is only a relatively minor part of the total costs, but mental health disorders were identified as a significant component of the economic burden. These solid findings could not have been anticipated intuitively and are of considerable value for public health prioritization of PCOS.

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Abstract

Polycystic ovary syndrome (PCOS) is the most common hormone disorder affecting about one in seven reproductive-aged women worldwide and approximately 6 million women in the United States (U.S.). PCOS can be a significant burden to those affected and is associated with an increased prevalence of mental health (MH) disorders such as depression, anxiety, eating disorders, and postpartum depression. We undertook this study to determine the excess economic burden associated with MH disorders in women with PCOS in order to allow for a more accurate prioritization of the disorder as a public health priority.

Methods:

Following PRISMA reporting guidelines for systematic review, we searched PubMed, Web of Science, EBSCO, Medline, Scopus, and PsycINFO through July 16, 2021, for studies on MH disorders in PCOS. Excluded were studies not in humans, without controls, without original data, or not peer reviewed. As anxiety, depression, eating disorders, and postpartum depression were by far the most common MH disorders assessed by the studies, we performed our meta-analysis on these disorders. Meta-analyses were performed using the DerSimonian–Laird random effects model to compute pooled estimates of prevalence ratios (PRs) for the associations between PCOS and these MH disorders and then calculated the excess direct costs related to these disorders in U.S. dollars (USD) for women suffering from PCOS in the U.S. alone. The quality of selected studies was assessed using the Newcastle-Ottawa Scale.

Results:

We screened 78 articles by title/abstract, assessed 43 articles in full text, and included 25 articles. Pooled PRs were 1.42 (95% confidence interval [CI]: 1.32–1.52) for anxiety, 1.65 (95% CI: 1.44–1.89) for depression, 1.48 (95% CI: PR: 1.06–2.05) for eating disorders, and 1.20 (95% CI: 0.96–1.50) for postpartum depression, for PCOS relative to controls. In the U.S., the additional direct healthcare costs associated with anxiety, depression, and eating disorders in PCOS were estimated to be $1.939 billion/yr, $1.678 billion/yr, and $0.644 billion/yr in 2021 USD, respectively. Postpartum depression was excluded from the cost analyses due to the non-significant meta-analysis result. Taken together, the additional direct healthcare costs associated with anxiety, depression, and eating disorders in PCOS were estimated to be $4.261 billion/yr in 2021 USD.

Conclusions:

Overall, the direct healthcare annual costs for the most common MH disorders in PCOS, namely anxiety, depression, and eating disorders, exceeds $4 billion in 2021 USD for the U.S. population alone. Taken together with our prior work, these data suggest that the healthcare-related economic burden of PCOS exceeds $15 billion yearly, considering the costs of PCOS diagnosis, and costs related to PCOS-associated MH, reproductive, vascular, and metabolic disorders. As PCOS has much the same prevalence across the world, the excess economic burden attributable to PCOS globally is enormous, mandating that the scientific and policy community increase its focus on this important disorder.

Funding:

The study was supported, in part, by PCOS Challenge: The National Polycystic Ovary Syndrome Association and by the Foundation for Research and Education Excellence

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  1. Version published to 10.7554/elife.85338 on eLife
  2. eLife

    Author Response

    Reviewer #2 (Public review):

    1. The systematic review includes data from some studies where PCOS is self-reported. While self-reported PCOS information has been found to be largely sensitive and specific, it would be of interest to know if prevalence ratios of mental health-related were impacted by self-reporting.

    Thank you for your insightful comment regarding the potential impact of self-reporting on the prevalence ratios of mental health-related outcomes in women with PCOS. We agree that this is an important factor to consider.

    In response, we have revisited all the studies included in our review. We have updated Supplemental Tables 2-4 to provide greater transparency and understanding. These revised tables now include a new column specifying the mental health assessment method used in each study. This update should allow for a more nuanced interpretation of the results, taking into account the potential impact of self-reporting.

    Furthermore, we conducted a sensitivity analysis by rerunning the meta-analysis to discern the potential influence of self-reported PCOS on our results, excluding the studies that relied solely on self-reported PCOS diagnosis. After we excluded studies where PCOS was self-reported, the point estimate for anxiety was similar whereas point estimates for depression and eating disorder were slightly higher but none of the estimates were different beyond chance compared to the original analysis. We believe these steps significantly strengthen the clarity and robustness of our findings (Line 314; Supplemental Tables 7 and 8).

    1. Likewise, the screening vs self-reported nature of the mental health disorders is not clear from the information included in the characteristics table.

    We have modified our Supplemental Tables 2-5 to include a column detailing the method of ‘Mental Health Assessment’. We should note that the majority of the studies directly assessed mental health using a variety of validated questionnaires. We have also included in the Discussion a section emphasizing that some of the studies included in the review relied on self-reported PCOS diagnosis and its potential impact. We also highlighted that while self-reported information is generally reliable, it is subject to potential bias that could impact the prevalence ratios of mental health-related conditions (Line 460).

    1. Calculated prevalence ratios were compared with prevalence values for the general population to determine the excess prevalence. However, the source of these general population statistics (i.e., whether these figures come from the control data in the included studies or other sources) is not clear.

    Thank you for raising this important point. We have now clarified in our Methods section that the general population statistics used for determining excess prevalence were derived from the control data in the included studies. We hope this provides the necessary transparency for our approach in calculating and interpreting the prevalence ratios (Line 210).

    1. The estimated costs for anxiety-, depression- and eating disorder-related care are accessed in published papers and used to calculate the excess costs. Conclusions would be strengthened by a defence of these figures, particularly for anxiety where the source paper is from 1999.

    Thank you for your insightful comment. We agree that providing a justification for our choice of cost estimates, especially for the anxiety care cost from a 1999 study, would strengthen our conclusions. The 1999 source was selected because it is a seminal study that offers a comprehensive breakdown of anxiety-related care costs. Despite its age, this paper is often cited in contemporary research due to its rigorous methodology and the granularity of its cost analysis. Adjusted for inflation, its findings still provide an insightful comparison point for current data. To ensure that these figures accurately represent present-day costs, we have adjusted them for inflation using the medical care inflation calculator. Our choice of these specific studies was based on their rigorous methodology, the detailed breakdown of costs, and their relevance to our targeted age groups. The aforementioned adjustments and justifications ensure that these figures aptly represent the present-day costs of treating these conditions.

    Similarly, the 2021 papers on depression and eating disorders present comprehensive and up-to-date analyses of the economic burdens associated with these conditions. These papers were selected for their rigorous methodologies, comprehensive cost breakdowns, and alignment with our age-specific focus. The Greenberg et al. (2021) paper, for example, is an authoritative source that provides detailed analysis on the economic burden of adults with major depressive disorder. Likewise, the paper by Streatfeild et al. (2021) offers a meticulous investigation into the socio-economic cost of eating disorders in the U.S., making it an apt choice for our study. We recognize the necessity of providing a robust justification for our choice of these particular papers, and we have endeavored to do so in our Methods section, thus reinforcing the transparency of our approach. We have clarified this in our Methods section to make our approach more transparent to readers (Line 225).

    1. An inflation tool is used to adjust the figure, but this does not take into account changes in treatment or practice since this estimate was made. The accuracy of these estimated figures is central to the final conclusions.

    Thank you for your valuable comment. We do note that the inflation figures used are a healthcare-specific inflation factor, as healthcare inflation differs from general consumer inflation. However, we agree that the inflation-adjusted figures do not necessarily account for changes in treatment practices since the original estimate was made, assuming these changes would alter the cost of care. We have added a discussion of this limitation in our manuscript and proposed future studies to validate these estimates using more recent data (Line 473).

  3. eLife

    eLife assessment

    This important paper describes a valuable systematic review and meta-analysis of mental health problems in polycystic ovary syndrome (PCOS) that drive the excess economic burden associated with this common endocrine disorder. Interestingly, the cost of the diagnostic evaluation is only a relatively minor part of the total costs, but mental health disorders were identified as a significant component of the economic burden. These solid findings could not have been anticipated intuitively and are of considerable value for public health prioritization of PCOS.

  4. eLife

    Reviewer #1 (Public Review):

    The aim of this study was to evaluate the increased prevalence of mental health (MH) disorders such as depression, anxiety, eating disorders, and postpartum depression in patients with polycystic ovary syndrome (PCOS) the most common reproductive disorder affecting about one in seven reproductive-aged women worldwide. The consequences of excess economic burden were estimated.

    Meta-analyses were performed using the Der Simonian-Laird random-effects model to compute pooled estimates of prevalence ratios for the associations between PCOS and these MH disorders, and then the excess direct costs in U.S. dollars (USD) for women suffering from PCOS were estimated.

    After screening the articles by title/abstract, 25 articles were selected for their quality according to the Newcastle-Ottawa scale. These studies included a control group. The data showed an increase in the prevalence ratios for each of the selected mental health disorder items: anxiety 1.42, depression 1.65, and eating disorders 1.48. The additional direct health care costs associated with these disorders were estimated to be $4.261 billion per year in 2021 USD.

    The authors extended their previous report that the total cost of evaluating and providing care to reproductive-aged PCOS women in the United States was $4.36 billion. Interestingly, the cost for diagnostic evaluation including laboratory accounted for a relatively minor part of the total costs (approximately 2%). In the present study, mental health disorders were clearly identified as a part of the excess economic burden. Their cost is estimated at $4.261 billion/year. These results were not anticipated intuitively and are of value for prioritization of the disorder as a public health priority.

    Provided that the study is validated for extraction of a meta-analysis, the data are of great interest not only for economic issues but also for early consideration of the mental distress of PCOS patients that has long been underestimated. Several studies have expressed patient resentment of delayed diagnosis and imperfect management, including the physical damage of hyperandrogenism and the associated metabolic syndrome. This medico-economic approach to chronic diseases with a strong impact on quality of life contributes to the global management of PCOS, which is a primary demand of patients.

  5. eLife

    Reviewer #2 (Public Review):

    Yadav et al have performed a careful systematic review and meta-analysis of mental health disorder prevalence ratios in PCOS to estimate the mental health-related excess economic burden associated with this common endocrine disorder. Using random effect modelling of prevalence ratios from quality-assessed, peer-reviewed publications, they determine the excess PCOS-related prevalence and healthcare costs associated with anxiety, depression, and eating disorders to be greater than $4 billion USD per year. In conjunction with previously reported direct economic burden estimates for PCOS, they determine that PCOS healthcare costs exceed $15 billion USD per year (in the US alone) and that mental health disorder-related costs account for nearly one-third of these costs. The findings of this paper will be impactful for a broad field of clinical and bench scientists investigating PCOS, endocrinologists, general practitioners, health economists, and policymakers. The findings of this paper demonstrate the significant contribution that mental health-related pathology makes to the total economic burden associated with PCOS and present a strong case for additional research and policy investment into this underfunded area.

    The important findings and claims presented in this paper are mostly clearly presented and well supported by strong evidence and careful analysis. However, some additional clarity and rationalisation of referenced healthcare cost input to the model would strengthen the conclusions.

    Strengths:
    This paper clearly describes the inclusion criteria and characteristics of the included studies. The papers included were quality assessed using a well-regarded assessment tool and only those with high-quality information were included in subsequent meta-analyses. Publication bias was assessed by multiple methods and data were interpreted accordingly.

    The authors combine their mental health-related findings with previously reported economic burden estimates for specific PCOS-related care and treatment to provide a comprehensive estimation of PCOS-related healthcare costs in the US. They discuss these findings in relation to healthcare-related costs reported for other prevalent disorders and make a compelling case for prioritising research and investment into PCOS.

    An important observation made by the authors is the relatively small contribution to PCOS economic burden made by diagnostic evaluation, supporting quality diagnosis and evaluation as a cost-effective measure to improve PCOS patient treatment.

    Weaknesses:
    The systematic review includes data from some studies where PCOS is self-reported. While self-reported PCOS information has been found to be largely sensitive and specific, it would be of interest to know if prevalence ratios of mental health-related were impacted by self-reporting. Likewise, the screening vs self-reported nature of the mental health disorders is not clear from the information included in the characteristics table.

    Calculated prevalence ratios were compared with prevalence values for the general population to determine the excess prevalence. However, the source of these general population statistics (i.e., whether these figures come from the control data in the included studies or other sources) is not clear. The estimated costs for anxiety-, depression- and eating disorder-related care are accessed in published papers and used to calculate the excess costs. Conclusions would be strengthened by a defence of these figures, particularly for anxiety where the source paper is from 1999. An inflation tool is used to adjust the figure, but this does not take into account changes in treatment or practice since this estimate was made. The accuracy of these estimated figures is central to the final conclusions.

  6. Version published to 10.1101/2023.01.05.23284220v1 on medRxiv