Mental Health Across the Menstrual Cycle in Polycystic Ovary Syndrome: Insights and Implications

Abstract

Purpose of Review

We reviewed a wide body of emerging research highlighting the possibility for premenstrual exacerbations of mood symptoms in polycystic ovary syndrome (PCOS).

Recent Findings

Neuroendocrine dysregulation, sensitivity to ovarian hormone fluctuations as well as higher levels and types of adverse childhood experiences and demographic factors are emerging factors explaining high rates of psychiatric disorders in PCOS. Ovulatory dysfunction, common in PCOS, significantly interferes with one’s identity and quality of life. Results on pharmacologic and non-pharmacologic treatments for mood symptoms are mixed, though improvements in the physical sequalae of PCOS could also improve mood symptoms. However, significant improvements on the methodological quality are needed, particularly the evaluation of mood symptoms across the menstrual cycle.

Summary

Evidence is preliminary on whether there are premenstrual exacerbations of psychiatric symptoms in PCOS. Prospective, longitudinal studies with larger sample sizes are needed to comprehensively understand the psychiatric profile in PCOS.

Introduction

PCOS is a common endocrine condition affecting 8–13% of reproductive aged females in the US [1, 2]. As a multi-system syndrome, PCOS increases risk for multiple medical comorbidities, including infertility, endometrial cancer, obesity, and cardiovascular disease [1, 3, 4]. The phenotypes of PCOS, driven by race and ethnicity (Fig. 1), further complicate symptom presentation and prevalence of medical comorbidities of PCOS [1, 2]. Additionally, people with PCOS show over double the odds for developing depression and anxiety, and over triple the odds for developing any eating disorder, compared to people without PCOS [5, 6]. Prior studies have mostly focused on PCOS-specific psychosocial stressors (e.g., struggles with infertility, long delays to confirm a diagnosis, experiences of weight stigma) to explain the increased rates of psychiatric disorders [7–9]. However, evolving research on menstrual-cycle dependent fluctuations of symptoms offer an alternative hypothesis underlying such significant rates.

Fig. 1.

Diagnostic criteria and PCOS phenotypes. Diagnostic criteria have been redefined three times and recently classified into four separate phenotypes (A-D), according to the three PCOS characteristics. PCOM, polycystic ovarian morphology; NIH, National Institutes of Health; AE-PCOS, Androgen Excess-PCOS Society [1, 2].

In typical menstrual functioning, estradiol and progesterone vary across follicular and luteal phases with lower levels of estradiol and progesterone in the follicular phase, estradiol levels increasing and peaking by ovulation, and then a rapid decrease of both progesterone and estradiol, signaling menstruation. Such fluctuations in ovarian hormones can lead to significant premenstrual mood and affective symptoms (e.g., low mood, irritability, anxiety) in vulnerable individuals, such as those with premenstrual syndrome (PMS) or premenstrual dysphoric disorder (PMDD) [10, 11]. In PCOS, ovulatory dysfunction is a key diagnostic criterion, and abnormal bleeding patterns impact approximately 60–85% of people with PCOS [12, 13]. Menstrual bleeding patterns vary significantly, ranging from monthly to absent entirely [14]. Despite the lack of menstrual regularity, a recent case report suggests that patients with PCOS experience similar premenstrual exacerbations of mood symptoms [15]. Additionally, anecdotal reports from patients with PCOS describe cyclical premenstrual exacerbations of mood symptoms that significantly interfere with their daily functioning similar to people with PMS or PMDD.

In this brief review, we summarized the current state of knowledge that support the potential for premenstrual/menstrual exacerbations of PCOS-related psychiatric symptoms. In doing so, we emphasized a wide body of emerging research in need of further investigation regarding neuroendocrine influences, adverse childhood experiences, and the effects of irregular menses on quality of life. We conclude with pharmacological and non-pharmacological treatments that could improve PCOS mood symptoms over the menstrual cycle for future research and clinical considerations.

Neuroendocrine Influences

In normal ovulatory functioning, the gonadotropin-releasing hormone (GnRH) in the hypothalamic-pituitary-ovarian axis controls the production of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), which then regulate ovarian androgen and estrogen production [16]. The GnRH pulse generator is abnormal in PCOS, resulting in increased LH pulse frequency, LH pulse amplitude, and LH/FSH ratio. This neuroendocrine dysregulation contributes to a greater sensitivity to the fluctuations of estrogen and progesterone, excessive androgen production, and potentially the development of psychiatric disorders [17, 18]. Additionally, PCOS has been considered as low-grade chronic inflammation, associated with an increased circulation of C-reactive protein, interleukin-18, and other inflammatory markers [19]. Cortisol, the primary glucocorticoid hormone of the hypothalamic–pituitary–adrenal (HPA) axis, is essential for regulating physiological homeostasis and mood when exposed to a physical or psychological stressor [20]. In PCOS, the HPA axis is overactive, leading to excessive cortisol production and associated effect of chronic physiologic anxiety and sensitivity to stress [17, 18]. In the only study that examined cortisol levels across the menstrual cycle of participants with PCOS, hair cortisol concentrations collected during the follicular phase were significantly higher in people with PCOS compared to healthy controls (130 vs 63 pg/mg of hair cortisol, p < 0.001) [21], suggesting increased cortisol levels and potentially anxiety during this phase.

Altered gonadal (androgens and their products; progesterone) and neuroactive steroids (NASs) are also implicated in PCOS mood and quality of life (QoL) symptoms [22]. In a sample of 211 Iranian women with PCOS, free androgen index (FAI) was significantly correlated with total QoL scores (r = −0.14; p = 0.042) [23]. In another study, FAI was significantly associated with overall mean PCOS QoL scores (ß = 0.53, p = 0.0002), depression (ß = 0.45, p = 0.01), hirsutism (ß = 0.99, p = 0.0002) and menstrual irregularity (ß = 0.31, p = 0.04), though these associations attenuated after adjusting for age and body mass index [24].

Dysregulated NASs play a significant role in both typical menstrual functioning and menstrual irregularities observed in PCOS [22]. The NAS allopregnanolone (ALLO), a metabolite of progesterone which acts as a positive allosteric modulator of the GABA-A receptor and regulates stress responses, has been implicated in other hormonally mediated mental health conditions (e.g., postpartum depression, PMDD). Given the dysregulated GnRH signaling observed in PCOS, one would assume that downstream production of ALLO would also be dysregulated, which could increase risk for mood symptoms in PCOS. However, results on ALLO levels and relationship with PCOS psychiatric symptoms are inconsistent [22]. For example, out of 11 blood steroid profile levels (e.g., progesterone, androstenedione, testosterone, ALLO), only androstenedione levels were correlated with mood symptoms assessed by the Hospital Anxiety and Depression Scale (HADS) [25] in 25 patients with PCOS compared with 31 patients with regular menstruation; no association was found between ALLO levels and HADS scores in PCOS patients [26], although bloods samples and mood symptoms were assessed at baseline without consideration of menstrual cycle phase.

Adverse Childhood Experiences and Demographic Influences

Adverse childhood experiences (ACEs) are consistently associated with increased risk for depression and anxiety in the general population [27] and linearly associated with premenstrual disorders (e.g., PMS or PMDD) for women who endorse four or more ACEs compared with women without ACEs [28]. Further, ACEs and premenstrual disorders were stronger among women without a history of post-traumatic stress disorder (PTSD), anxiety, or depression, demonstrating the independent effect of ACEs on menstrual cycle dependent mood symptoms [28, 29].

Research on the effect of ACEs on menstrual functioning and/or mood symptoms in PCOS are limited. A cross-sectional analysis from the Australian Longitudinal Study of Women’s Health [30] revealed that a self-reported diagnosis of PCOS was associated with significantly higher prevalence of depression, anxiety, PTSD, and obsessive–compulsive disorder; ACEs were considered the strongest association with these psychiatric disorders (ACEs ≥ 4: adjusted OR 2.9, 95% CI 2.4–3.5), women with PCOS were more likely to report a higher frequency of ACEs compared to women without PCOS (ACEs ≥ 4: 19.3% vs 9.2%). Another study found that childhood maltreatment was independently associated with probable PCOS in women without a history of psychiatric disorders (OR = 5.11, 95% CI 1.87–13.98); physical abuse was also associated but nonsignificant when other maltreatment types were considered [31]. Additional, 4.46% of youth formerly in foster care with complex ACEs (maltreatment, adverse household factors), 10.00% with environmental ACEs (exposure to environmental harm, natural disasters), and 2.15% of those with lower ACEs self-reported a diagnosis of PCOS, highlighting the link between ACEs and risk of chronic health conditions [32].

Due to the phenotypes of PCOS driven by race and ethnicity (see Fig. 1) [1], demographic and associated factors may also elucidate menstrual functioning and psychiatric symptoms in PCOS. While White women with PCOS reported significantly higher prevalence of anxiety than Black women with PCOS (75.9% vs. 61.3%), Black women with PCOS reported significantly lower QoL scores in infertility comparatively [33], potentially serving as a proxy for ovulatory dysfunction. Additionally, women who experienced low socioeconomic status in childhood were at risk for developing later PCOS, although higher education levels were identified as a protective factor [34]. Understanding the effect of ACEs and demographic factors on psychiatric symptoms across the menstrual cycle in PCOS is a rich area for identifying subpopulations at increased risk for PCOS psychiatric disorders.

The Effects of Anovulation and Irregular Menses on Identity and Quality of Life

The experience of anovulation and irregular menses in PCOS profoundly impact mood symptoms and QoL. In a cross-sectional study of 808 Korean adolescent females, self-reported menstrual cycle irregularity appeared to increase as frequency of reported mental health problems increases. Even after adjusting for multiple factors (e.g., age at menarche, sleep duration), high levels of reported stress and depression were associated with increased risk for menstrual irregularities [35]. Similarly, a retrospective longitudinal cohort study of 321 participants with hyperandrogenic PCOS had a higher incidence of depression and subsequently, higher incidence of developing metabolic syndrome, (adjusted hazard ratio 1.56, 95% CI 1.10–2.20, p = 0.01) [36]. These studies highlight the importance of early screening and treatment for mental health concerns and menstrual cycle regularity to potentially prevent onset of PCOS and associated metabolic concerns. Sexual dysfunction and satisfaction in PCOS should also be considered as an important reproductive health indicator and highly dependent on ovulatory status. Compared with a matched control group, women with anovulatory PCOS reported significantly lower scores across all domains of sexual functioning (desire, arousal, lubrication, satisfaction, and total score) [37].

Qualitative analyses also demonstrate the significant impact of anovulatory PCOS and irregular menses on self-perception and identity. Specifically, the experience of menstrual irregularities, and related PCOS symptoms resulted in increased struggles to feel “normal” and perceived to feel less feminine among women from the US and United Kingdom [38]. Further, women in Australia describe feelings of frustration and anger after long struggles with infertility and subsequent diagnosis of PCOS, wishing that ovulatory dysfunction and appropriate treatments were identified sooner in their process to conceive [39].

Treatment Considerations

A range of evidence-based psychotherapies are effective in improving PCOS-related mood symptoms [40, 41]. Currently, there are no medications approved by the US Food and Drug Administration specifically for PCOS. Pharmacologic treatments typically focus on symptom management of menstrual abnormalities, metabolic dysregulation, and androgen excess though use of hormonal contraceptives, insulin sensitizers, and/or anti-androgens [2]. The relationship between pharmacologic management of PCOS and mood is understudied. While some studies suggest PCOS treatment leads to improvement in mood symptoms [42, 43], others do not [44]. These studies have notable limitations, including small sample sizes, lack of control groups, and use of depression screeners with poor sensitivity to detect changes in symptoms.

A recent naturalistic, parallel-group, longitudinal study of 33 patients with PCOS found that pharmacologic treatment of PCOS led to significant improvement in depression and anxiety symptoms compared to healthy controls (Cohen’s d 0.43–0.55, p < 0.05) [45]. Though preliminary in nature due to small sample size, this study is significant for suggesting that pharmacologic management of the physical sequelae of PCOS is a reasonable first-line strategy for addressing mood or anxiety symptoms prior to starting antidepressant medication. However, baseline HADS scores reflected subclinical symptoms, and none of the patients treated in the study had a diagnosed psychiatric disorder. Further evidence is needed to evaluate the effect of pharmacologic management of PCOS to address diagnosed mood or anxiety disorders, prior to treatment of antidepressants in patients with more severe or impairing mood symptoms. Even for subclinical symptoms, it remains unclear if one particular medication class is more beneficial for mood versus others, given the naturalistic, non-randomized study design. The theoretical mechanisms by which PCOS treatment with individual medication classes may impact mood in patients with PCOS are discussed in further detail below.

Hormonal Contraceptives

In the general population, combined hormonal contraceptives (CHCs) variably impact mood symptoms, with adolescents being more vulnerable to negative effects [46, 47]. CHCs are considered an evidence-based treatment option for PMDD [48]. Because mood symptoms in PMDD are secondary to hormonal fluctuations throughout the menstrual cycle [49], earlier studies suggested CHCs improve symptoms through suppression of ovulation and maintenance of steady state hormone levels [50]. The relationship between CHCs, ovulation suppression, and PMDD symptoms is likely more complex as results on the effect of CHC treatment for PMS/PMDD are mixed. Interpretation of CHC studies in PMDD are complicated by large placebo effects, use of different hormone combinations, and variable hormone doses and patterns of use [50–52]. In PCOS, CHCs are used to regulate menstrual cycles and decrease androgen levels [2]. Elevated blood levels of androgens and clinical signs of hyperandrogenism have been connected with higher depression scores [53], so one possible mechanism for antidepressant effect in PCOS could be their direct effect on reducing blood androgen levels.

Few studies have examined the relationship between CHC treatment and mood in PCOS patients. A 2012 prospective study of 36 patients with PCOS showed no difference in depression scores after 6 months of treatment with oral contraceptives pills (OCPs) [44]. In contrast, a randomized controlled trial (RCT) evaluating the effects of preconception interventions (OCPs, lifestyle modification, or combined OCPs/lifestyle modification) administered prior to ovulation induction with clomiphene on live birth rates in 149 patients with PCOS showed significant improvement in prevalence of depression (decreased from 13.3 to 4.4%) for patients randomized to OCPs (OR 0.30, 95% CI 0.09–0.99, p < 0.05) [43]. Additionally, newer anti-androgenic progestins (desogestrel, cyproterone acetate, and drosperinone) had similar improvement in QoL measures compared to levonorgestrel after three months of treatment in 88 patients with PCOS [54]. After 6 months of treatment, use of OCPs with cyproterone acetate, a highly potent anti-androgenic progestin, was associated with significant improvement in QoL compared to use of OCPs with levonorgestrel (p < 0.042). However, no specific depression measures were used to assess the impact of different progestin components on mood and there was significant participation attrition from 200 to 88, increasing risk for type 1 error.

Though CHCs are preferentially used for patients with PCOS due to their effect of lowering elevated androgen levels, systemic progestin only contraceptives, such as the depot medroxyprogesterone acetate, levonorgestrel-releasing intrauterine device, or etonogestrel implant, can also be used for endometrial protection, and/or menstrual cycle control [55]. These agents can suppress ovulation and reproductive hormone production and represent a useful alternative for patients who have medical contraindications, intolerance, or preference to avoid CHCs. Evidence on the association between progestin only contraceptives and mood in the general population are mixed, either demonstrating an increased risk for depression [47, 56] or no association [57]. Though the relationship between mood symptoms and progestin only contraceptives in PCOS patients has not yet been systematically studied, 96 adolescent patients with PCOS found that mood changes (18%) were the third most common reason for discontinuation, following bleeding (41%) and concern for weight gain (23%) [58].

Given the mixed findings and small number of available studies, additional research is needed to clarify the role of hormonal contraceptives in treating mood symptoms in PCOS. In addition to addressing lingering questions on optimal dosing and progestin components in CHCs for PCOS-related mood symptoms, future studies could evaluate how CHC use impacts mood in individuals with more severe depressive symptoms or specific PCOS phenotypes.

Insulin Sensitizers

Insulin sensitizers, such as metformin and thiazolidinediones (TZDs), decrease insulin resistance in PCOS patients, leading to improved ovulatory functioning and lower androgen levels. Pioglitazodone, a TZD, led to significant reductions in Hamilton Depression Rating Scale (HDRS) [59] compared to metformin in patients with PCOS and major depression (38.3% vs 8.3% HDRS reduction, p < 0.001). Notably, the homeostatic model assessment of insulin resistance which uses fasting insulin and fasting blood glucose as key parameters, did not differ between the two groups suggesting that pioglitazone’s antidepressant effect was due to its anti-inflammatory effects and not its insulin-sensitizing action [42].

Despite the lesser effect on mood observed in this study, metformin has been associated with antidepressant effects in other trials. A 2019 single-arm, pilot trial of metformin in adolescent and adults with PCOS observed significant reductions in depression and anxiety scores after 3 months of treatment [60]. Similarly, a 2020 prospective, multicenter, cohort study of PCOS participants showed that metformin use in conjunction with lifestyle modifications led to significantly decreased Patient Health Questionnaire-9 scores (−2.75 ± 6.16, p = 0.002 for combined group) whereas lifestyle modifications alone did not lead to significant changes in depression scores after 3 months of treatment [61]. In contrast, there was no effect of myoinositol or metformin on changes in depression scores after 6 months of treatment in an open-label RCT of 45 patients with PCOS [62].

Anti-androgens

Medications such as spironolactone, flutamine, and finasteride reduce systemic levels of androgens, leading to improvement in clinical symptoms such as hirsutism and acne. Spironolactone, the most commonly used anti-androgen, is rarely used as monotherapy in PCOS as it can cause menstrual irregularities and under-virilization of male fetuses [63]. Spironolactone may impact mood through its direct effect on lowering androgen levels or through its antagonism of the mineralocorticoid receptor, which has been implicated in the pathogenesis of depression [64]. However, since these agents are typically used in combination with CHCs, no studies have directly assessed the impact of anti-androgen agents on PCOS-related mood.

Antidepressants

Antidepressants, including selective serotonin reuptake inhibitors (SSRIs), selective serotonin and norepinephrine reuptake inhibitors (SNRIs), and atypical antidepressants, are not routinely used for PCOS because they do not address underlying anovulation, hyperandrogenism, or insulin resistance. However, SSRIs have been linked with modulation of NASs and are considered first line for hormonally driven psychiatric disorders (e.g., PMDD, postpartum depression) [65, 66]. Given the recent evidence of NASs abnormalities in patients with PCOS [22], patients with PCOS could benefit from similar treatment approaches used in PMDD, including preferential use of serotonergic antidepressants, which have been shown to modulate NASs levels.

Given the limited research in this area, the optimal medication approach for PCOS patients with mood symptoms remain unclear. If a patient has not received dedicated PCOS treatment to address the underlying somatic symptoms, it may be reasonable to prioritize pharmacologic treatment of core PCOS symptoms first-line, particularly if mood symptoms are mild. For patients with more severe or persistent mood symptoms, antidepressants should be considered [2]. To date, only one randomized controlled trial has evaluated the use of antidepressants in individuals with PCOS. In 64 participants with PCOS, use of sertraline 50 mg daily led to significantly lower HDRS scores compared with placebo (p < 0.001) and did not alter prolactin levels in patients with both high and low baseline prolactin levels [67]. Though this study establishes sertraline as an effective treatment for mood symptoms in PCOS, there is insufficient evidence to recommend sertraline over other agents. Additional studies are needed to determine if certain antidepressants should be preferentially used, whether metabolism of antidepressants differs compared to the general population, and if there are unique dosing considerations for this population (e.g. do patients with PCOS respond to low dose antidepressants, similar to patients with PMDD? [68]). Whenever possible, clinicians should use antidepressants with lower risk of metabolic side effects, given the significant metabolic comorbidities of PCOS. Future research should explore to what extent the combination of antidepressants with pharmacologic treatment of PCOS improves depression symptoms compared to antidepressants alone.

Dietary and Lifestyle Considerations

Due to the complex nature of PCOS and differential treatment response of pharmacologic agents, people with PCOS often explore non-pharmacologic interventions including nutritional supplements, dietary patterns, and alternative medicine treatments. Recently conducted RCTs provide preliminary evidence on the benefit of these non-pharmacologic interventions on PCOS physical and mood symptoms and warrant additional investigation with larger samples, matched comparison group, and evaluation with typical pharmacological treatments for PCOS.

Nutritional Supplements

As described, metformin is frequently utilized to improve insulin resistance and regulate ovulation. Myoinositol, an insulin sensitizer, can be utilized as an adjunct or alternative to metformin for patients who report difficulty tolerating metformin [2], although recent evidence suggests inconsistent results. While menstrual regularity improved in participants who received either metformin only or metformin combined with myoinositol following 6-months of treatment, menstrual regularity improvements were greater and earlier in the metformin combined with myoinositol group. PCOS QoL scores were also significantly greater in the combination group [69]. In contrast, a 6-month parallel RCT found no significant differences between metformin and myoinositol treatment on body composition, hormonal profile, or metabolic characteristics of PCOS [70].

Other nutritional supplements demonstrate beneficial improvements on a variety of PCOS symptoms and comorbidities. For example, among 34 women with PCOS-related oligo/anovulation, omega-3 supplements were beneficial for fertility; for overweight/obese women with PCOS, significantly higher odds of becoming pregnant were associated with omega-3 supplementation compared to placebo, along with lower BMI and higher values of endometrial thickness [71]. Compared with placebo, coenzyme Q10 supplementation for 12-weeks resulted in significant decreases in depression and anxiety scores, high-sensitivity C-reactive protein, total testosterone, dehydroepiandrosterone sulfate, hirsutism, and a significant rise in sex hormone-binding globulin (SHBG) [72]. Vitamin D treatment ranging from 12 to 24 weeks demonstrated a significant effect on FSH and LH/FSH ratio and improved androgen levels, hirsutism score, menstrual regularity, ovarian volume, and follicle numbers and size [73, 74]. Magnesium was observed to reduce inflammatory biomarkers and oxidative stress when combined with melatonin [75] and improved lipid profile and insulin resistance [76]. Berberine phospholipid supplementation was also shown to improve PCOS metabolic and hormonal [77], and use of curcumin was considered a safe and useful supplement for managing insulin resistance, blood glucose, and androgen levels [78]. Although these studies provide preliminary evidence of nutritional supplements compared with placebo on PCOS-related symptoms that could also improve mood symptoms, future research should evaluate the unique or additive effect of non-pharmacological treatments in the context of with typical pharmacotherapy for PCOS.

Dietary Patterns

While there is limited evidence to support one specific diet type for PCOS [2], recent studies suggest that behavioral dietary patterns may impact QoL by improving physical and emotional symptoms. While 130 participants with PCOS experienced emotional distress regardless of dietary patterns, those with healthier eating patterns determined by the Food Frequency Questionnaire [79] experienced fewer mood swings, were less distressed in social situations, and had reduced urge for binge eating [80]. Additionally, 29 overweight/obese women with PCOS followed a very-low-carbohydrate diet and utilized skills to improve mindfulness and positive affect for 16-weeks, which yielded significant decreases in percent weight and glycated hemoglobin level and increases in SHBG levels, menstrual predictability, and QoL which in a single-arm prospective pilot study [81].

Alternative Medicine

Although preliminary in nature, an herbal treatment formulation focused on herbs with phytoestrogenic and antioxidant qualities was effective in improving menstrual regularity in 150 PCOS patients in Pakistan with notable changes in ovarian size and free testosterone levels [82]. Additionally, 4-months of acupuncture treatment, compared to sham, appeared to improve emotional well-being, QoL, and lipid profiles in Chinese women with PCOS [83]. In a separate study, acupuncture was also more effective in improving glucose metabolism compared with metformin and with fewer reported side effects after 4-months of treatment, although acupuncture did not yield improvements in insulin sensitivity [84].

Conclusion

Psychiatric symptoms of PCOS are significant and impactful. Despite the high prevalence of psychiatric disorders in PCOS, considerable research is needed to understand the pathophysiology and contributors of psychiatric symptoms in PCOS, particularly across the menstrual cycle. In this review, we focused on emerging biological mechanisms and psychosocial influences in need of further investigation. While studies on PCOS-related mood symptoms across the menstrual cycle are limited, studies summarized in this review support the potential for premenstrual exacerbations of psychiatric symptoms. PCOS has been proposed as a state of chronic inflammation, characterized by increased circulation of stress hormones and inflammatory markers. Coupled with neuroendocrine dysregulation and sensitivity to ovarian hormone fluctuations, this likely establishes a predisposition towards the development of PCOS-related psychiatric disorders. The experiences of ACEs and certain demographic and related factors further contribute to an increase in mood symptoms. It is clear that the experience of anovulation and irregular menses negatively affect QoL scores, one’s identity and self-worth, and sexual functioning. Elucidating these biopsychosocial mechanisms will be critical for determining targeted and timely treatment approaches, given the limited evidence on the optimal treatment approach for PCOS-related mood symptoms.

Studies summarized in this review represent a wide body of research understanding PCOS-related psychiatric symptoms. However, the overall available evidence is limited and vary in methodological quality. To date, prior research has been cross sectional with small sample sizes and limited attention to the effects of PCOS-specific neuroendocrine functioning and psychosocial contributors across the menstrual cycle. Considering that ovulatory functioning and menstrual bleeding can vary across PCOS phenotypes, population-based cohort studies are needed to determine whether specific subtypes of ovulatory functioning increase risk for psychiatric symptoms. Future research can build upon this review by utilizing high-quality, sufficiently powered, longitudinal methods, consistent use of the preferred Rotterdam diagnostic criteria for PCOS, and appropriate inclusion of covariates and matched comparison samples. Significant advances in research are needed to fully appreciate and understand the unique psychiatric needs of people with PCOS as well as identify subpopulations who may be at highest risk for psychiatric disorders within PCOS and its phenotypes.

Data Availability

No datasets were generated or analysed during the current study.