Obesity is associated with lower levels of negative emotions in polycystic ovary syndrome in clinical and animal studies

Abstract

Background: Polycystic ovary syndrome (PCOS) is one of the most common endocrine and metabolic disorders in women of reproductive age. It is frequently comorbid with obesity and negative emotions. Currently, there are few reports on the relationship between obesity and negative emotions in patients with PCOS. Here we performed both basic and clinical studies to study the relationship between obesity and negative emotions in PCOS.

Methods: We performed a cross-sectional study including 608 patients with PCOS and 184 healthy participants to assess the mental health status of people with different body mass indices (BMI). Self-rated anxiety, depression, and perceived stress scales were used for subjective mood evaluations. Rat PCOS models fed 45 and 60% high-fat diets were used to confirm the results of the clinical study. Elevated plus maze and open field tests were used to assess anxiety- and depression-like behaviors in rats.

Results: We observed overweight/obesity, increased depression, anxiety, and perceived stress in women with PCOS, and found that anxiety and depression were negatively correlated with BMI in patients with severe obesity and PCOS. Similar results were confirmed in the animal study; the elevated plus maze test and open field test demonstrated that only 60% of high fat diet-induced obesity partly reversed anxiety- and depression-like behaviors in PCOS rats. A high-fat diet also modulated rat hypothalamic and hippocampal luteinizing hormone and testosterone levels.

Conclusion: These results reveal a potential relationship between obesity and negative emotions in PCOS and prompt further investigation. The interactions between various symptoms of PCOS may be targeted to improve the overall well-being of patients.

Keywords: Obesity; luteinizing hormone; negative emotion; polycystic ovary syndrome; testosterone.

Figure 1.

Boxplots of emotional scales for PCOS patients with different symptoms. (A) Hirsutism vs. no hirsutism. (B) Menstrual irregularity vs. menstrual regularity. These groups were compared by Wilcoxon rank sum test, *p < 0.05, **p < 0.01,***p < 0.001 as indicated. Borders of box represent 25th and 75th percentiles; internal line within large shaded box represents median; Central dot represents mean; and external whisker lines represent 1.5× interquartile range.

Figure 2.

Restricted cubic spline analysis of the non-linear relationship between BMI and negative emotions for PCOS and control groups. (A) Relationship between BMI and SDS. (B) Relationship between BMI and SAS. The vertical line is the WHO Asian classification standard of BMI. Residuals are represented by shadows.

Figure 3.

Boxplots of negative emotions and LH level of PCOS patients in different BMI groups. (A) SAS scores in different BMI groups. (B) SDS score in different BMI groups. (C) LH level in different BMI groups. (D) LH/FSH ratio in different BMI groups. A one-way ANOVA was conducted to compare the differences among these groups, followed by post-hoc tests using the Tukey method, *p < 0.05 as indicated. Borders of box represent 25th and 75th percentiles; internal line within large shaded box represents median; Central dot represents mean; and external whisker lines represent 1.5× interquartile range.

Figure 4.

Effect of high-fat diet on anxiety- and depressive-like behaviors in DHEA-induced PCOS rats. (A) Representative activity traces of rats in the elevated plus maze test. (B) Frequency of entries into open arm. (C) Frequency of entries into close arm. (D) Entries into open-to-close arm ratio. (E) Time spent in open arm. (F) Time spent in close arm. (G) Time spent in open-to-close arm ratio. (H) Total distance moved. (I) Time spent in the center zone. (J) Frequency of entries into the center zone. *p < 0.05, **p < 0.01, compared as indicated. ns: not statistically significant.

Figure 5.

Effect of high-fat diet on mRNA levels in DHEA-induced PCOS rats. (A–F) The mRNA levels of glucocorticoid receptor, androgen receptor, LH receptor, LHβ, β-endorphin, and interleukin-6 in hypothalamus. (G–L) The mRNA levels of glucocorticoid receptor, androgen receptor, LH receptor, LHβ, β-endorphin, and interleukin-6 in hippocampus. *p < 0.05, **p < 0.01, compared as indicated. ns: not statistically significant.

Figure 6.

Effect of high-fat diet on protein levels in DHEA-induced PCOS rats. (A,B) Hypothalamic protein levels of LH and testosterone. (C,D) Hippocampal protein levels of LH and testosterone. (E,F) Serum protein levels of LH and testosterone. *p < 0.05, **p < 0.01, compared as indicated. ns: not statistically significant.