Sleep Apnea May Correlate With Anxiety, Depression in Patients With PCOS

Jake Remaly

November 23, 2020

Among patients with polycystic ovary syndrome (PCOS), those with obstructive sleep apnea (OSA) are more likely to have moderate to severe depression or anxiety, a study suggests.

This finding could have implications for screening and treatment, Diana Xiaojie Zhou, MD, said at the American Society for Reproductive Medicine's 2020 annual meeting, held virtually this year.

"Routine OSA screening in women with PCOS should be considered in the setting of existing depression and anxiety," said Zhou, a reproductive endocrinology and infertility fellow at the University of California, San Francisco. "Referral for OSA diagnosis and treatment in those who screen positive may have added psychological benefits in this population, as has been seen in the general population."

Patients with PCOS experience a range of comorbidities, including higher rates of psychological disorders and OSA, she said.

OSA has been associated with depression and anxiety in the general population, and research indicates that treatment, such as with continuous positive airway pressure (CPAP), may have psychological benefits, such as reduced depression symptoms.

PCOS guidelines recommend screening for OSA to identify and alleviate symptoms such as fatigue that may to contribute to mood disorders. "However, there is a lack of studies assessing the relationship between OSA and depression and anxiety specifically in women with PCOS," Zhou said.

A Cross-Sectional Study

To evaluate whether OSA is associated with depression and anxiety in women with PCOS, Zhou and colleagues conducted a cross-sectional study of all women seen at a multidisciplinary PCOS clinic at university between June 2017 and June 2020.

Participants had a diagnosis of PCOS clinically confirmed by the Rotterdam criteria. Researchers determined OSA risk using the Berlin questionnaire, which is divided into three domains. A positive score in two or more domains indicates a high risk of OSA.

The investigators used the Patient Health Questionnaire-9 (PHQ-9) to assess depression symptoms, and they used the Generalized Anxiety Disorder-7 (GAD-7) to assess anxiety symptoms.

Researchers used two-sided t-test, chi-square test, and Fisher's exact test to evaluate for differences in patient characteristics. They performed multivariate logistic regression analyses to determine the odds of moderate to severe symptoms of depression (that is, a PHQ-9 score of 10 or greater) and anxiety (a GAD-7 score of 10 or greater) among patients with a high risk of OSA, compared with patients with a low risk of OSA. They adjusted for age, body mass index, free testosterone level, and insulin resistance using the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR).

The researchers examined data from 201 patients: 125 with a low risk of OSA and 76 with a high risk of OSA. The average age of the patients was 28 years.

On average, patients in the high-risk OSA group had a greater body mass index (37.9 vs. 26.5), a higher level of free testosterone (6.5 ng/dL vs. 4.5 ng/dL), and a higher HOMA-IR score (7 vs. 3.1), relative to those with a low risk of OSA. In addition, a greater percentage of patients with a high risk of OSA experienced oligomenorrhea (84.9% vs. 70.5%).

The average PHQ-9 score was significantly higher in the high-risk OSA group (12 vs. 8.3), as was the average GAD-7 score (8.9 vs. 6.1).

In univariate analyses, having a high risk of OSA increased the likelihood of moderate or severe depression or anxiety approximately threefold.

In multivariate analyses, a high risk of OSA remained significantly associated with moderate or severe depression or anxiety, with an odds ratio of about 2.5. "Of note, BMI was a statistically significant predictor in the univariate analyses, but not so in the multivariate analyses," Zhou said.

Although the investigators assessed OSA, depression, and anxiety using validated questionnaires, a study with clinically confirmed diagnoses of those conditions would strengthen these findings, she said.

Various Possible Links

Investigators have proposed various links between PCOS, OSA, and depression and anxiety, Zhou noted. Features of PCOS such as insulin resistance, obesity, and hyperandrogenemia increase the risk of OSA. "The sleep loss and fragmentation and hypoxia that define OSA then serve to increase sympathetic tone and oxidative stress, which then potentially can lead to an increase in depression and anxiety," Zhou said.

The results suggests that treating OSA "may have added psychological benefits for women with PCOS and highlights the broad health implications of this condition," Marla Lujan, PhD, chair of the ASRM's androgen excess special interest group, said in a society news release.

"The cause of PCOS is still not well understood, but we do know that 1 in 10 women in their childbearing years suffer from PCOS," said Lujan, of Cornell University, Ithaca, N.Y. "In addition to infertility, PCOS is also associated with type 2 diabetes and cardiovascular complications such as hypertension and abnormal blood lipids."

In a discussion following Zhou's presentation, Alice D. Domar, PhD, said the study was eye opening.

Domar, director of integrative care at Boston IVF and associate professor of obstetrics, gynecology, and reproductive biology at Harvard Medical School, Boston, said that she does not typically discuss sleep apnea with patients. "For those of us who routinely work with PCOS patients, we are always looking for more information."

Although PCOS guidelines mention screening for OSA, Zhou expects that few generalists who see PCOS patients or even subspecialists actually do.

Nevertheless, the potential for intervention is fascinating, she said. And if treating OSA also reduced a patient's need for psychiatric medications, there could be added benefit in PCOS due to the metabolic side effects that accompany some of the drugs.

Zhou and Lujan had no relevant disclosures. Domar is a co-owner of FertiCalm, FertiStrong, and Aliz Health Apps, and a speaker for Ferring, EMD Serono, Merck, and Abbott.

SOURCE: Zhou DX et al. ASRM 2020. Abstract O-146.

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