Polycystic ovary syndrome (PCOS), a prevalent endocrine-metabolic disease in women of reproductive age, usually appears in adolescence (1). Its prevalence ranges from 5% to 18% in women and 3.4% to 11% in adolescent girls, depending on different diagnostic criteria (2, 3). The primary clinical characteristics encompass irregular menstrual periods, presentation of androgen excess (such as hirsutism, acne, and laboratory hyperandrogenism), and polycystic ovary morphology (PCOM) on ultrasound. According to the commonly used Rotterdam criteria, meeting at least 2 of the above criteria and excluding other diseases can be diagnosed as PCOS (4). However, the diagnosis of PCOS in adolescent girls remains challenging due to the overlap of these features with the presentation in adolescence. Based on the recent 2023 Evidence-Based Guidelines for PCOS, menstrual irregularity and clinical/biochemical hyperandrogenemia are necessary to diagnose PCOS in adolescents, and PCOM is not suggested as a diagnostic criterion for PCOS in adolescence (5).

Women with PCOS are at significant risk of a broad spectrum of complications, including infertility, obesity, insulin resistance, metabolic syndrome, diabetes, and cardiovascular disease (6). In addition to the metabolic and reproductive aspects, PCOS significantly impacts the psychological health of women affected (6). It should be noted that adolescents are vulnerable to mental health problems, given the dramatic changes in hormones, body, brain, social environment, and cognition in this special period (7). For adolescent girls with PCOS, the illness’s underlying pathophysiology and associated physical features may lead to apparent concerns about body image, reduction of self-esteem, depression, and anxiety (8–10). Depression is distinguished by a consistently low mood and a lack of interest or pleasure, with primary symptoms including appetite disorders, sleep disturbances, and concentration deficit, among others (11). In recent years, many cross-sectional studies have investigated the fact that the prevalence of depression has significantly increased in girls with PCOS. Anxiety is an emotional experience of inner nervousness and impending disaster, often manifested as excessive concern, inability to sit still, and autonomic nervous disorders, such as chest tightness, palpitations, sweating, and so on (12). Self-esteem is an individual’s subjective evaluation of self-worth, and mental disorders are related to the decline of self-esteem (13, 14). There is growing evidence that women with PCOS are prone to psychological problems. For these patients, the quality of life (QoL) can be substantially impacted in various aspects of fulfilling life and subjective well-being (15). Besides, adolescent depression and anxiety are linked to elevated odds of adult depression and anxiety disorders, thereby adding to the long-term burden of disease (16, 17). Considering elements like the greater possibility of binge eating, higher sedentary behaviors, and the use of psychiatric medications, these psychological issues are likely to contribute to weight gain and a higher risk of cardiovascular disease (18, 19). In this sense, psychological disorders in adolescence can have multiple, long-term detrimental effects on the well-being of patients.

At present, several researchers have conducted investigations on depression and anxiety in adolescent girls with PCOS. Emeksiz HC. et al. reported that female adolescents with PCOS exhibited higher levels of depression and anxiety compared to healthy controls (20). In a cross-sectional study conducted by Çoban ÖG and colleagues, the rate of psychiatric disorders, including major depressive disorder and anxiety disorder, in the PCOS group was considerably higher than that in the control subjects (21). However, Zachurzok A. et al. had a contradictory result, which showed that no association was discovered between self-esteem, anxiety, depression, and PCOS in adolescent girls (22). Collectively, the findings of studies on this topic are still inconclusive. Furthermore, to our knowledge, no meta-analysis has been performed on anxiety and depression in adolescent girls with PCOS.

Given the numerous adverse impacts of psychological problems and the contrasting conclusions regarding the mental health of adolescent girls with PCOS, it is critical to summarize available evidence in this area. Therefore, we undertook a systematic review and meta-analysis of observational studies that explored depression and anxiety of adolescent females with PCOS. This study aimed to investigate the prevalence and extent of depression and anxiety, as well as the situation of self-esteem and QoL in adolescent girls with PCOS. We anticipate that this research will be helpful for clinicians in timely identifying high-risk populations and promoting the physical and mental well-being of women with PCOS.

This is the first systematic review and meta-analysis to summarize available evidence on the situation of depression and anxiety in adolescent girls (aged 10 - 19 years old) with PCOS. In this meta-analysis, we discovered that adolescent females with PCOS had a higher risk of depression and a higher level of depression scores than controls. However, there were no significant differences in the prevalence and extent of anxiety between the two groups. In addition, self-esteem and QoL, the secondary indices in our study, were also not substantially different between the two groups.

In the current study, PCOS adolescents were 2.21 times more likely to have depression than the control group. In line with our results, the statistically significant association between PCOS and depression was also observed in some previous meta-analyses mainly targeting adults, with elevated odds of depression over two to four times in PCOS participants (36–39). Besides, we found that PCOS adolescents experienced more serious depressive symptoms than controls, which was also in accordance with previous studies (39–42). Even though our effect sizes are lower than those in all of the research mentioned above, which primarily focused on adult PCOS, it is still important to note the significant link between PCOS in adolescents and depression. Based on global estimate, approximately 280 million people are affected by depression, with its prevalence rises significantly during adolescence (43, 44). Extensive evidence has illustrated that early-life depression is linked to several adverse health outcomes, including not only suicidal tendencies, recurrence and co-occurrence of mental disorders, and increased risk of cardiovascular disease but also long-term impairments in education, employment, and social participation (16, 18, 45). As a result, our study highlighted the need to early identify and manage depression in adolescents with PCOS to foster favorable health outcomes.

The mechanisms underlying the connection between PCOS and vulnerability to depression are not fully clarified, and several potential factors have been explored ( Figure 6 ). Women with PCOS may be distressed about the changes in physical appearance caused by obesity and hirsutism, which become a possible source of PCOS women’s depressed emotion (9, 36). Additionally, their subjective perceptions of symptoms play a more critical role than objective assessment (46). Besides, some PCOS patients’ concerns regarding infertility place a specific psychological strain on them (47). From the point of view of pathophysiology, the potential contribution of hormonal imbalance has also been investigated. Hypercortisolemia caused by chronic stress and hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis plays a crucial role in the development of depression (48). It has been shown that women with PCOS experience a more significant increase in cortisol levels after exposure to stress compared to controls (49). Persistently high cortisol levels will lead to desensitization of cortisol receptors and failure of negative feedback regulation, resulting in persistent hyperfunction of the HPA axis and a vicious cycle (50). Insulin resistance may be associated with depression in PCOS, serving as a physiologic mediator (51). In a randomized controlled trial, the increase of the homeostatic model of insulin resistance (HOMA-IR) elevated the odds of depression by 2.32 (51). One possible explanation is that insulin resistance makes the brain less adaptable, which can lead to changes in the structure or function of key brain regions to influence emotion regulation (52). In addition, in an experiment, dehydroepiandrosterone-induced PCOS mice exhibited depression-like behavior, possibly by down-regulating monoamines and/or their metabolites in brain (53). Hyperandrogenemia may be related to depression in PCOS, which needs to be further explored in human studies. Moreover, several relevant mechanisms have been discussed: inflammation (54), vitamin D insufficiency (55), and change of neurotransmitter (54, 56), which may also be involved in the development of depression in PCOS. Several studies have confirmed the link between potential factors mentioned above [such as BMI (20), hirsutism (26), acne (26), and free testosterone levels (35)] and depression in the adolescent PCOS population.

In our study, no association was observed between PCOS and anxiety in adolescent populations. Although none of the previous meta-analyses on this topic focused entirely on adolescents, the results of subgroup analyses based on age in several studies provided relevant evidence. A meta-analysis conducted by Veltman-Verhulst SM and colleagues suggested that there was no significant difference in anxiety scores within the subgroup of PCOS women who were 24 years old or younger (40). Brutocao C. et al. found that mixed adult/pediatric populations with PCOS had a 1.70-fold risk of anxiety disorder compared to controls, which was lower than in the adult group (OR= 5.22) (39). Taking our results together with previous evidence, we speculate that PCOS has not yet had a notable effect on the situation of anxiety in adolescent girls. This may be because adolescents are still in the early stage of PCOS, and the duration of symptoms is relatively short. What’s more, some symptoms of PCOS, such as irregular menstruation, are likely to be considered normal in adolescence and not enough to attract the attention of adolescents (57). Nonetheless, it should be noted that a lack of included studies constrains the existing evidence. Therefore, our conjecture needs further verification.

In the present study, no substantial differences remained in the domains of self-esteem and QoL between the adolescent PCOS group and the control group. Self-esteem comes from a positive evaluation of self-worth; for teenagers, appearance is an important factor affecting self-esteem (58, 59). Although PCOS may be accompanied by some physical changes, no significant effect of the illness on adolescent girls’ self-esteem was observed in our study. In terms of QoL, only one study has conducted a review targeting adolescents with PCOS, and most of the studies in this review showed impaired QoL in PCOS subjects, which is inconsistent with our results (60). However, it is worth noting that its inclusion criteria differ from ours. Besides, our findings should be cautiously explained due to the limited evidence.

The strengths of our analysis are that it was the first to look into the prevalence and severity of depression and anxiety targeting adolescent girls with PCOS, considering that adolescence is both an early-onset stage of these disorders and a critical period of personal development. We conducted a comprehensive literature search and included studies from multiple regions worldwide, which enhanced our results’ generalizability. Several limitations of our study should be considered. Firstly, the number of studies included was relatively small, and we didn’t delve deeper into the relationship between depression, anxiety, and potential factors. Second, most subjects were Caucasian, implying that more relevant studies should be conducted in more countries. Thirdly, according to the funnel plots ( Supplementary Figure S3 ), it was suggested that there may be some publication bias. In addition, our study still had considerable heterogeneity despite employing appropriate statistical models. Finally, most of the studies we included were cross-sectional, which made it hard to clarify causality.

In conclusion, based on the available evidence, there was a significant association between PCOS and depression among adolescent girls in our study. More large-scale, well-designed studies are needed in the future to draw a more robust conclusion and to clarify the mechanisms linking PCOS and psychological distress. Clinicians should also pay more attention to the mental health status of PCOS patients to facilitate early recognition and timely intervention.