Menstrual Disorders Are Associated With Depressive Symptoms Among Women of Reproductive Age: Findings From the Korean Women's Health Survey for Sexual and Reproductive Health.

Depressive disorders are common mental disorders, with a global prevalence of 3.8% in 2019. 1 The exact cause of depression remains unknown; however, the burden of depressive disorders is higher in women than in men. 2 According to the 2022 nationwide survey in Korea, the prevalence of depressive disorders was estimated at 3.9% among men and 6.1% among women. 3 Several biological processes may be involved in the development of depression in women, including genetic determinants and hormonal fluctuations related to reproductive function. 4 Additionally, some mental health components such as depression, anxiety, and stress have been associated with menstrual disorders. 5 6 Menstrual disorders are common gynecological problems in women of reproductive age. 7 Dysmenorrhea refers to the difficulty or pain associated with menstruation. 8 A meta-analysis of 37 studies found that more than two-thirds of young women experience dysmenorrhea. 9 Premenstrual syndrome is a cyclical recurrence of distressing physical or mood changes in the days before menstruation. 10 In a large international study, most women reported premenstrual symptoms, including premenstrual food cravings, mood changes, and fatigue, during each cycle. 11 Abnormal uterine bleeding, i.e., menorrhagia, refers to abnormal uterine bleeding in regularity, volume, frequency, or duration, 12 13 affecting approximately 10–30% of reproductive-age women. 6 14 Menstrual disorders impair overall health, 8 academic and occupational functioning, 6 9 daily activities, 15 and quality of life. 6 16 According to a report from the National Health Insurance Service-National Sample Cohort, the prevalence of menstrual disorders in Korean women aged 15–49 years increased from 8.6% in 2009 to 11.6% in 2016. 17 However, there is a lack of national-level data on the types and severity of menstrual disorders and their relationship with mental health. Therefore, despite the limitations inherent in observational study designs, exploring the association between menstrual disorders and depressive symptoms could provide valuable insights for improving women's health. In this cross-sectional study, we investigated the association between menstrual disorders and depressive symptoms among reproductive-age women in Korea using national-level data. We hypothesized that greater severity and abundance of menstrual disorders would be associated with more severe depressive symptoms.

The 2022 Korean Women’s Health Survey for Sexual and Reproductive Health is a nationwide, cross-sectional study conducted between July and September 2022, 18 and funded by the National Institute of Health at the Korea Disease Control and Prevention Agency. The sample was stratified into three age groups: adolescents (13–18 years), adults (19–64 years), and older adults (≥ 65 years). Considering the need for stable estimation of key indicators and the distribution of primary variables, the target sample size was 5,500 participants: 1,000 adolescents, 3,500 adults, and 1,000 older adults. Stratified random sampling was conducted based on region, age, and educational level. To ensure population representation, the regional and age distribution was derived from national resident registration statistics as of May 2022, while the distribution of educational level for adults was based on the 2020 Population and Housing Census data. Adolescents and adults were recruited through an online survey. Adolescents and adults (n = 37,896) were selected from a sampling frame of 231,246 women in a nationwide survey panel comprising 787,759 members recruited by Hankook Research—a leading research firm in Korea. A link to the online questionnaires was sent by email to the selected women. Meanwhile, due to limited access to online platforms, older adults were recruited through household visits by trained surveyors in 175 enumeration districts, selected from an initial sample of 224 districts. The online survey was conducted from August to September, while household face-to-face interviews took place from July to September. Ultimately, the total number of participants recruited was 1,019 adolescents, 3,533 adults, and 1,015 older adults. The questionnaires comprised of six to nine sections according to age group, including menstruation, pregnancy and childbirth, sex and contraception, and sexual health services. Menstrual cycle data were collected for adolescents and adults. Among the 4,552 women aged 13–64 years, those who had not yet achieved menarche (n = 54), were not menstruating (n = 103), were in menopausal transition (n = 206), or were postmenopausal (n = 1,101) were excluded. Finally, 3,088 women aged 13–55 years (960 adolescents and 2,128 adults) were included in this study. A detailed flow diagram is shown in Supplementary Fig. 1 . Participants were asked to report their experiences of menstrual disorders during the past three years. Questions regarding menstrual disorders included: 1) dysmenorrhea: pain related to the menstrual cycle occurring before, during, or after menstruation; 2) premenstrual symptoms: physical or mood-related symptoms such as headaches, breast tenderness, abdominal bloating, fatigue, irritability, and mood lability, experienced approximately one week before menstruation; 3) abnormal uterine bleeding: any bleeding that differs from the normal menstrual cycle in regularity, duration, volume, or frequency; 4) amenorrhea: absence of menstruation for six months following menarche or for three consecutive months after previously regular cycles. The relationship between amenorrhea and depressive symptoms was not examined, as information on the type of amenorrhea and the symptom severity was not collected. Among the participants reporting dysmenorrhea, premenstrual symptoms, or abnormal uterine bleeding, symptom severity was rated using a visual analog scale (VAS; range: 1–10). The participants were assigned to three groups based on VAS scores for each menstrual disorder: none, mild-to-moderate (1–6), and severe (7–10). 19 The number of any menstrual disorders and severe menstrual disorders experienced by each participant were calculated, and categorized as none or 1 to 3. Participants reporting a menstrual disorder were asked about symptom management, with the following options provided (all that applied were selected): 1) no action taken; 2) visiting a medical clinic (e.g., obstetrics/gynecology or urology); 3) visiting a traditional Korean medicine clinic; 4) visiting a pharmacy (e.g., for pain relievers); 5) using health functional foods or home remedies; 6) other. Depressive symptoms were assessed using the validated Korean version 20 21 of the 11-item Center for Epidemiologic Studies Depression Scale (CES-D-11), 22 a short version of the original 20-item CES-D. 23 Participants rated how often they experienced depressive symptoms during the preceding week based on 11 items: 1) I did not feel like eating, my appetite was poor; 2) I was happy; 3) I felt depressed; 4) I felt that everything I did was an effort; 5) My sleep was restless; 6) I felt lonely; 7) I enjoyed life; 8) People were unfriendly; 9) I felt sad; 10) I felt that people dislike me; 11) I could not get “going.” Responses were scored on a four-point scale: 0 (rarely; < 1 day/week), 1 (sometimes; 1–2 days/week), 2 (often; 3–4 days/week), and 3 (mostly; ≥ 5 days/week). Positively formulated items (items 2 and 7) were scored reversely. The depressive symptom score was calculated by adding the scores for the 11 questions and multiplying by 20/11 (range: 0–60). A CES-D score ≥ 16 indicated depressive symptoms. 23 A score of 25 is suggested as the cutoff point for identifying severe depressive symptoms in Koreans. 20 Participants were categorized into normal (0–15), probable (16–24), and definite (≥ 25) depressive symptom groups. The demographic factors included age and household income. Among the adolescents, household income levels were assessed using five categories and reclassified into low, moderate, and high levels. For adults, monthly household income (million Korean-won) was divided by the number of household members and categorized into quartiles. Body mass index (BMI) was calculated as body weight divided by height squared (kg/m 2 ). Additionally, data on behavioral factors were collected, such as smoking, alcohol drinking, and physical activity. Smoking status was categorized as never smoked, former smoker, or current smoker. Data on the frequency of binge drinking (defined as ≥ 5 drinks on one occasion) were collected and categorized into less than once a week or at least once a week. Among adolescents, the frequency of moderate-to-vigorous physical activity (days/week) was calculated. Among adults, the time spent (minutes/week) on moderate and vigorous physical activities was calculated and categorized into inactive/insufficiently active or sufficiently active, according to global recommendations. 24 Reproductive factors included age at menarche (years), menstrual cycle regularity (no, yes), and pregnancy experience (no, yes). Physician-diagnosed chronic diseases (e.g., hypertension, diabetes, hyperlipidemia) and reproductive health conditions (e.g., vaginitis, uterine leiomyomata) currently experienced by participants were documented. Characteristics of participants based on depressive symptoms were compared using the Kruskal-Wallis test for continuous variables and the χ 2 test for categorical variables. The proportions of severity and number of menstrual disorders based on depressive symptoms were calculated. Modified Poisson regression with robust standard errors was used to estimate prevalence ratios (PRs) and 95% confidence intervals (CIs) of probable and definitive depressive symptoms were estimated according to the severity and number of menstrual disorders. 25 Covariates included in the final model were selected based on a literature review 26 27 28 29 30 and the change-in-estimate procedure. 31 Variables (e.g., BMI and physical activity) were included in the model as potential confounders, even if they did not show a substantial change in the estimates. The models were adjusted for age, smoking status, binge drinking, BMI, physical activity, age at menarche, menstrual cycle regularity, pregnancy experience, presence of vaginitis, other genital diseases, hypertension, diabetes, and hyperlipidemia. P values for the trend were calculated by assigning the median value of each exposure category in the model as a continuous variable. Effect modification was assessed by creating interaction terms between menstrual disorders and age groups (adolescents and adults) and calculating the likelihood ratio test statistic to compare models with and without interaction terms. After stratified analyses by age group, household income was included in the model. The PRs of depressive symptoms were estimated per score or incremental numbers of menstrual disorders. In the sensitivity analysis, the associations between menstrual disorders and depressive symptoms were examined in the following ways: 1) among adolescents at least three years post-menarche, 2) among adults aged 19–45 years, 3) by excluding participants who were visiting a medical clinic to manage their menstrual disorder symptoms, and 4) by excluding those who were currently experiencing any physician-diagnosed chronic disease or reproductive health concern. Additionally, menstrual disorders were mutually adjusted to estimate their independent associations with depressive symptoms. All statistical tests and corresponding P values were two-sided; P values < 0.05 were considered statistically significant. All analyses were conducted using the SAS statistical software package, version 9.4 (SAS Institute, Inc., Cary, NC, USA). The nationwide survey was approved by the Institutional Review Board (IRB) of the Korea Institute for Health and Social Affairs (IRB No. 2022-052). An electronic informed consent form was signed by participants or their legal guardians. This research was approved by the IRB of the Korea Disease Control and Prevention Agency (IRB No. 2021-04-02-1C-A).

The prevalence of probable and definite depressive symptoms was 19.4% and 21.2%, respectively. Characteristics of participants according to depressive symptoms are presented in Table 1 . Women with probable or definite depressive symptoms were more likely to be current smokers or binge drinkers, and have irregular menstrual cycles, vaginitis, other genital diseases, hypertension, diabetes, and low household income. Women reporting severe menstrual disorders were 41.9% for dysmenorrhea, 41.1% for premenstrual syndrome, and 7.6% for abnormal uterine bleeding ( Fig. 1 ). Most participants reported a menstrual disorder, with more than half experiencing at least one severe menstrual disorder ( Fig. 2 ). Those with more depressive symptoms were more likely to experience greater severity and more menstrual disorders. The proportions of menstrual disorders in relation to depressive symptoms for adolescents and adults are presented separately in Supplementary Table 1 . Among women reporting menstrual disorders, approximately two-thirds indicated that they engaged in symptom management ( Supplementary Table 2 ). The most common response was visiting a pharmacy for pain relief (52.0%), followed by visits to a medical clinic (19.8%). Women with multiple menstrual disorders were more likely to manage their symptoms. Additionally, those with more depressive symptoms were more likely to visit a medical clinic to manage their menstrual disorder symptoms. Data are presented as median (interquartile range) or number (%). a Sufficiently active was defined as at least ≥ 150 minutes of moderate-, ≥ 75 minutes of vigorous-, or an equivalent combination of moderate and vigorous-intensity physical activities, or if otherwise, was considered as inactive or insufficiently active. b Other genital diseases included sexually transmitted infections, ovarian cysts, endometriosis, uterine myoma, and gynecologic cancers (cervical, endometrial, or ovarian). VAS = visual analog scale. VAS = visual analog scale. The multivariate-adjusted PRs for probable and definite depressive symptoms according to menstrual disorders are presented in Table 2 . The prevalence of having probable and definite depressive symptoms increased with increasing severity or number of menstrual disorders ( P for trend < 0.001 for each), excluding the association between abnormal uterine bleeding and probable depressive symptoms. Comparing women with and without severe menstrual disorders, the PRs (95% CIs) for probable and definitive depressive symptoms were 1.43 (1.15–1.78) and 1.61 (1.38–1.88) for dysmenorrhea, 1.87 (1.48–2.37) and 2.00 (1.71–2.34) for premenstrual syndrome, and 1.23 (0.91–1.65) and 1.40 (1.17–1.67) for abnormal uterine bleeding, respectively. Comparing those reporting the three types of menstrual disorders vs. those with no menstrual disorder, the PRs (95% CIs) for probable and definitive depressive symptoms were 2.02 (1.36–3.01) and 1.91 (1.48–2.45) for mild-to-severe menstrual disorders and 1.80 (1.22–2.66) and 2.14 (1.69–2.70) for severe menstrual disorders, respectively. PRs = prevalence ratios, CIs = confidence intervals. a Adjusted for age, smoking status, binge drinking, body mass index, physical activity, age at menarche, menstrual cycle regularity, pregnancy experience, presence of vaginitis, other genital diseases, hypertension, diabetes, and hyperlipidemia. Subgroup analyses revealed that the association between dysmenorrhea and definite depressive symptoms was stronger in adults, while premenstrual syndrome was more strongly associated with definite depressive symptoms in adolescents ( Table 3 ). The association between the number of severe menstrual disorders and definite depressive symptoms was stronger in adolescents than in adults ( P for interaction = 0.009). No significant age group differences occurred in the association between menstrual disorders and probable depressive symptoms ( Supplementary Table 3 ). Consistent with the main analysis, an increase in the VAS score or number of menstrual disorders was significantly associated with increased prevalence of depressive symptoms ( Supplementary Table 4 ). The associations remained similar when the analyses were restricted to adolescents at least three years post-menarche ( Supplementary Table 5 ) or adults aged 19–45 years ( Supplementary Table 6 ). Associations remained robust after excluding participants who visited a medical clinic to manage their menstrual disorder symptoms ( Supplementary Table 7 ) and those with any chronic disease or reproductive health concern ( Supplementary Table 8 ). When menstrual disorders were mutually adjusted for, the associations were attenuated but remained significant especially for premenstrual syndrome ( Supplementary Table 9 ). PRs = prevalence ratios, CIs = confidence intervals. a Adjusted for age, smoking status, body mass index, physical activity, menstrual cycle regularity, presence of vaginitis, and household income level. b Adjusted for age, smoking status, binge drinking, body mass index, physical activity, age at menarche, menstrual cycle regularity, presence of vaginitis, other genital diseases, hypertension, diabetes, and monthly household income per capita.

This study examined the association between menstrual disorders and depressive symptoms using data from a nationwide survey of Korean women. Menstrual disorders included dysmenorrhea, premenstrual syndrome, and abnormal uterine bleeding. Women with severe or multiple menstrual disorders were more likely to have probable or definitive depressive symptoms. In our study, most participants experienced menstrual disorders, and approximately half reported severe menstrual symptoms. The proportion of menstrual disorders in the current study was comparable to that of previous reports. For instance, the pooled prevalence of dysmenorrhea was 71.1% (95% CI, 66.6–75.2) among 20,813 young women from 37 studies. 9 The pooled prevalence of premenstrual syndrome was 47.8% (95% CI, 32.6–62.9) among 18,803 women in 17 studies. 32 Additionally, the most common premenstrual symptoms experienced by 238,114 mobile application users from 140 countries every cycle were food cravings (85%), mood swings or anxiety (64%), and fatigue (57%) 11 ; 28.6% of participants reported that premenstrual symptoms interfered with their everyday life each menstrual cycle. The proportion of study participants reporting abnormal uterine bleeding was within the range of previous studies (10–30%). 6 14 Menstruation is the cyclic, orderly sloughing of the uterine lining and is regulated by hormones produced by the hypothalamus, pituitary gland, and ovaries. 33 If conception does not occur, steroid hormone levels decrease as the corpus luteum regresses and menses ensues. Progesterone withdrawal also induces the production of arachidonic acid–a precursor of prostaglandins. 8 Prostaglandins are involved in increasing uterine muscle contraction and vasoconstriction; therefore, excessive or imbalanced prostaglandins may cause dysmenorrhea associated with ovulatory bleeding. 34 35 However, the etiology of premenstrual syndrome remains unknown. Nevertheless, several biologic and neuroendocrine etiologies have been proposed. 8 36 The most common causes of abnormal uterine bleeding are described using the acronym PALM-COEIN: polyp, adenomyosis, leiomyoma, malignancy and hyperplasia, coagulopathy, ovulatory dysfunction, endometrial, iatrogenic, and not yet classified. 12 These etiologies are not mutually exclusive and can occur concurrently, potentially contributing to abnormal uterine bleeding. 12 Consistent with the current study’s findings, several observational studies have reported a significant relationship between menstrual disorders and depressive symptoms. In the US National Health Interview Survey 2002, women reporting menstrual-related problems were more likely to experience frequent depression or anxiety over the past year compared to those without such problems. 26 Two case-control studies showed that adolescents with primary dysmenorrhea had higher scores of depression than healthy individuals. 37 38 A one-year follow-up study of 1,039 Chinese adolescents found that the presence of dysmenorrhea at baseline was associated with increased rates of incident and persistent depression. 30 A US retrospective study of 1,168 adolescents found that depression diagnoses occurred more frequently among adolescents with heavy menstrual bleeding than those without. 39 A long-term cohort study of Australian women found that frequent premenstrual syndrome symptoms were associated with an increased risk of both frequent depressive symptoms and depression diagnosis in subsequent follow-up surveys. 29 Similarly, a study of 380 women recruited in Belgium and the Netherlands reported that those with severe premenstrual syndrome were more vulnerable to depression. 40 However, limited data is available regarding the association between menstrual disorders and depressive symptoms among the Korean population. A cross-sectional study observed that young Korean women with severe dysmenorrhea were more likely to have higher depressive symptom scores. 41 Another cross-sectional study of Korean nurses reported that higher levels of depressive symptoms were significantly correlated with increased menstrual distress scores during both the premenstrual and menstrual phases. 42 Although the biological mechanisms underlying the association between menstrual disorders and depressive symptoms are not fully understood, they may be partially explained by hormonal fluctuations, stress, and recurrent or chronic pain. Hormonal fluctuations induced by menstruation (e.g., estrogen, progesterone, and prostaglandins) may affect emotional regulation. Estrogen regulates the expression of genes that encode serotonin transporter, tryptophan hydroxylase, and autoreceptor (i.e., 5-TH1a), altering serotonin neurotransmission and potentially inducing mood disorders. 43 Additionally, progesterone–which regulates prostaglandin production may cause dysfunctional mood regulation by affecting neurotransmitter synthesis, release, and transport. 44 Menstrual disorders can act as stressors and exacerbate symptoms of psychological distress, such as depression and anxiety. 45 Meanwhile, psychological distress may increase sensitivity to dysmenorrheal pain and vice versa. 46 A review study suggests that the presence of pain may hinder the recognition and management of depression, while moderate to severe pain may be associated with worse depression outcomes. 47 In a 3-year longitudinal study of adolescent girls, those with more depressive symptoms consistently reported more menstrual symptoms. 28 In the current study, women affected by multiple menstrual disorders at a younger age exhibited a strong association with definite depressive symptoms. Although further research is needed due to the limited number of adolescent cases, these findings highlight the importance of early diagnosis and management of menstrual disorders. This study has several limitations. The menstrual disorders severity was self-reported using VAS, which is widely used to measure pain intensity due to its simplicity and adaptability to various populations and settings. 48 Although the prevalence of menstrual disorders was comparable to that reported previously, the validity of the measurement tools for assessing menstrual disorders requires investigation. The possibility of residual or unmeasured confounders cannot be ruled out. Detailed information regarding chronic mental health conditions and relevant medication use was not obtained. However, similar results were observed when analyses were restricted to participants reporting no chronic diseases or reproductive health concerns. Finally, owing to the observational nature of the study, causality could not be inferred. Nevertheless, this study provides national-level data on menstrual disorders and depressive symptoms among women of reproductive age. In conclusion, this study demonstrated that menstrual disorders, including dysmenorrhea, premenstrual syndrome, and abnormal uterine bleeding, are closely related to probable and definite depressive symptoms. The severity and number of menstrual disorders were positively associated with depressive symptoms. The complex and multifactorial relationships between menstrual disorders and depressive symptoms warrant further investigation.