Impact of premenstrual syndrome and premenstrual

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Introduction

Antenatal depression is a risk factor for preterm delivery, low birth weight, impaired growth among infants, decreased appetite, insomnia, and easy fatigability in mothers [1, 2]. It is also associated with a high risk of postpartum depression [3, 4]. A structured interview study by Kitamura et al. [5] reported a 5.6% prevalence of antenatal depression in Japan, making it the most prevalent mental disorder during pregnancy. A meta-analysis of perinatal depression in Japanese women by Tokumitsu et al. [6] showed a prevalence of 14.0% in the first 3–6 months of pregnancy, 16.3% from 6 months to delivery, 15.1% from 0–1 month postpartum, 11.6% from 1–2 months postpartum, 11.5% from 3–6 months postpartum, and 11.5% from 6 months to 1 year postpartum. This suggests a relatively high risk of antenatal depression postpartum. Therefore, identifying risk factors and taking preventive measures is crucial to prevent antenatal depression.

Risk factors for antenatal depression include various psychosocial factors; however, an association with changes in sex hormone levels has been reported [7]. Sex hormone changes can impact various physical disorders associated with menstruation, with premenstrual syndrome (PMS) and premenstrual dysphoric mood disorder (PMDD) being the most represented [8]. The International Classification of Diseases [9] defines PMS as "characterized by specific environmental, metabolic, or behavioral factors that occur during the luteal phase of the menstrual cycle, which leads to cyclic emotional, physical, or behavioral symptoms that interfere with an individual’s lifestyle." The American Psychiatric Association’s diagnostic criteria (DSM-5) [10] defines PMDD as “mood instability, irritability, discomfort, or anxiety that recurs during the premenstrual phase of the menstrual cycle and resolves before or immediately after the start of menstruation, occurring during most menstrual cycles in the past year.”

Estrogen and progesterone are involved in the regulation of mood-related biological systems, neural networks, and behavior; therefore, changes in their levels are thought to induce depressive symptoms [11]. A decreased level of allopregnanolone, a metabolite of progesterone, has been associated with depressive symptoms during pregnancy and the postpartum period [12, 13]. Previous studies show that allopregnanolone levels do not differ between patients with PMS and healthy individuals in the follicular phase; however, they are significantly lower in the PMS group during the luteal phase [14]. Similarly, allopregnanolone levels are reportedly lower in the PMDD group compared with healthy individuals during the luteal phase [14, 15]. These findings suggest a potential common mechanism underlying the onset of PMS, PMDD, and perinatal depression.

A systematic review of risk factors for postpartum depression by Gastaldon et al. [16] showed that the risk of developing postpartum depression was approximately double in women with a history of PMS. Sylvén et al. [17] also found a significant association between a history of PMS or PMDD and postpartum depression.

Antenatal depression may be associated with a history of PMS or PMDD; however, only a few studies have reported this. Pataky et al. [18] reported an approximately three-fold increased risk of depression at 32–42 weeks of pregnancy among individuals with a history of PMS or PMDD. Tokumitsu et al. [6] also reported a high prevalence of antenatal depression from the sixth month of pregnancy. Evidence suggests that interventions for women at risk of antenatal depression effectively prevent postnatal depression and improve pregnancy outcomes [19]. Therefore, we believe that early evaluation of at-risk individuals is necessary.

Thus, in this study, we aimed to determine the relationship between a history of PMS or PMDD and depression during the second trimester of pregnancy.

Material and methods

Study population

A survey recruitment page was posted on an information website for pregnant women between May 2022 and June 2022 (Milcare, Tokyo) [20]. The women surveyed from across Japan participated in the study after seeing this survey recruitment page on an information site for pregnant women. The survey participants were pregnant women aged ≥20 years with singleton pregnancies of 24–28 weeks of gestation at the time of consent. Participants were informed in advance that it would take 20 min to complete the questionnaire. The exclusion criteria were 1) psychiatric disorders, such as major depressive disorder or bipolar disorder; 2) difficulty completing the questionnaire; and 3) multiple pregnancies.

Notably, 238 respondents answered the web-based questionnaire. We excluded 26 respondents with irrelevant information. These included 13 who gave incorrect answers, as an error was observed between the expected delivery date and the current gestational weeks, and 13 who did not provide valid answers regarding their delivery history. Finally, 212 respondents were included in the analysis.

Data collection procedures

The questionnaire included basic demographics (age, pre-pregnancy body mass index, marital status, age of partner, employment status, financial status, education history, smoking, and drinking history) and clinical information (history of childbirth, gestational age, and history of gynecological and psychiatric disorders). Factors reportedly associated with antenatal depression (desire to become pregnant, feelings at the time of pregnancy discovery, whether or not the patient lived with someone, returning to the patient’s parent’s house to give birth, whether or not someone was willing to help during pregnancy and postpartum, and sleep quality) were also assessed [21, 22].

The Edinburgh Postnatal Depression Scale (EPDS) was used to evaluate association; Cox et al. [23] developed the EPDS to quantitatively assess postpartum depression. However, a Japanese version was developed by Okano et al. [24]; it includes 10 items associated with mood depression and is scored on a four-point scale from 0 to 3. The total score ranges from 0 to 30 points, with a cut-off of 9 points. The scale was developed to screen for postpartum depression and is mainly used during the postnatal period; however, it is also currently being used to screen for antenatal depression. Usuda et al. [25] identified a cut-off score of 9 among Japanese women, validating its use from pregnancy onwards. With a cut-off score set at 13 points, the area under the curve was 0.956, sensitivity and specificity were 90.0% and 92.1%, respectively, and positive and negative predictive values were 54.5% and 98.9%, respectively. Therefore, women with an EPDS score ≥9 were considered a positive group for suspected gestational depression, and those with an EPDS score <9 were considered a negative group.

PMS and PMDD were assessed using the PMDD Rating Scale, a Japanese version of the scale developed by Miyaoka et al. [26] based on the premenstrual symptoms screening tool developed by Steiner et al. [27] using the DSM-5 PMDD diagnostic criteria. The Japanese version has a Cronbach’s alpha of 0.91, and its reliability and validity have been verified. We have also obtained permission to use the scale. The scale consists of a four-point scale (not at all: 1 point, mild: 2 points, moderate: 3 points, and severe: 4 points) that indicates whether each questionnaire item applies to PMDD, beginning 1–2 weeks before the start of menstruation and ending within a few days after the start of menstruation, during most menstrual cycles in the past year. The questionnaire consists of Item I (12 items relating to symptoms) and Item II (five items relating to difficulties at work, home, and school). The PMDD and PMS assessments were based on the premenstrual symptoms screening tool criteria developed by Steiner et al. [27], which were categorized into three groups: 1) PMDD (PMDD group), 2) moderate to severe PMS (PMS group), and 3) no or mild PMS (Non-interference group).

Statistical analyses

χ^² tests were performed to assess the associations between antenatal depression and baseline characteristics, clinical information, factors reported to be associated with antenatal depression [21, 22], and the PMDD rating scale (PMDD group, PMS group, and non-interference group). Forced entry binomial logistic regression analysis was then performed using the results of the χ^² tests, with significance levels < 25%, as covariates to exclude variables that were evidently not significant. The IBM SPSS Statistics ver. 29 was used to perform this analysis at a 5% significance level. In addition, post hoc power analysis with alpha = 0.05 representing the statistical power was conducted using the G-power software (G-power v3.1.9.2, Universitat Kiel, Kiel, Germany).

Ethics statement

This study was approved by the Ethics Review Committee for Clinical Research, Department of Medical Sciences, Kyushu University (approval number 22010 00).

This study was designed according to the ethical principles of the Declaration of Helsinki and followed the Ethical Guidelines for Medical and Health Research Involving Human Subjects. Written informed consent was obtained from all the participants before answering the questionnaire.

Results

Study population characteristics

Table 1 presents the basic characteristics of the participants analyzed. The mean age of the participants was 31.9 (standard deviation: 4.0) years. Thirty-five (16.5%) participants were underweight, 150 (70.8%) had normal weight, and 27 (12.7%) had obesity based on the non-pregnancy body mass index. Regarding employment status, 158 (74.5%) were currently employed, 23 (10.9%) left employment after the current pregnancy, and 31 (14.6%) have not been employed since before this pregnancy.

[Figure omitted. See PDF.]

Descriptive statistics for each scale

Table 1 presents the descriptive statistics for each scale. The EPDS had a mean score of 7.0 (standard deviation 5.1) and a median score of 6 (range 0–23), with 65 (30.7%) and 147 (69.3%) in the positive (≥ 9 points) and negative (< 9 points) groups, respectively (Table 1). Consequently, the proportion of positives suspected of pregnancy-related depression was 30.7%.

For the PMDD rating scale, 24 (11.3%), 66 (31.1%), and 122 (57.6%) were in the PMDD, PMS, and non-interference groups, respectively (Table 1).

EPDS scores based on participants’ attributes

EPDS scores and EPDS (positive and negative groups) based on attributes are listed in Table 1. Significant differences between the positive and negative EPDS groups were observed for the following: “presence of a history of psychiatric disorders,” “sleep quality (good, bad),” and “PMDD scale” (p < 0.05) (Table 1).

Association of a history of PMS or PMDD on the EPDS.

Table 2 shows the effect of a history of PMS or PMDD on the EPDS (positive and negative groups). Therefore, to identify factors significantly associated with antenatal depression, a forced entry binomial logistic regression analysis was performed with EPDS (positive and negative groups) as the dependent variable and each factor below the 25% significance level in the above χ² test as the independent variable. The results showed that the following factors were significantly associated with positive EPDS: “having” a history of mental illness (odds ratio [OR]: 5.05, 95% confidence interval [CI]: 1.35–18.88), “poor” sleep quality (OR: 3.39, 95% CI: 1.63–7.07), “PMDD” on the PMDD scale (OR: 3.54, 95% CI: 1.26–9.93), and “PMS” on the PMDD scale (OR: 2.31, 95% CI: 1.10–4.87). Post hoc power calculations indicated that the study sample size yielded > 80% power for the primary outcomes.

[Figure omitted. See PDF.]

Discussion

The results of this study indicate a significant association between PMS and PMDD and antenatal depression.

Pataky et al. [18] reported that a history of PMS or PMDD approximately triples the risk of depression during late pregnancy (32–42 weeks), and the present study showed a similar OR of 2.31 for PMS and 3.54 for PMDD, with a different association from that in early pregnancy. This suggests a need for earlier intervention. Regarding postpartum depression, Cao et al. [11] found that changes in estrogen and progesterone can cause depressive symptoms, and women sensitive to hormonal fluctuations may develop both PMS or PMDD and postpartum depression, as the sudden drop in hormone levels occurs during the luteal phase and after birth. Yang et al. reported that using the Swedish nationwide registers, a bidirectional association was observed between premenstrual disorders and pre- and postpartum depression. These findings suggest that a history of premenstrual disorders influences susceptibility to postpartum depression and vice versa, supporting a common etiology for both disorders [28]. The decline during pregnancy is less rapid than in the postpartum period; however, a study by Fan et al. [7] investigating the association between sex hormones and psychological distress during pregnancy reported that estrogen and progesterone blood levels were negatively correlated with the development of depression.

Furthermore, lower serum allopregnanolone levels were associated with the development of depressive symptoms during late pregnancy (37–40 weeks age of gestation) [29]. Allopregnanolone has sedative and anxiolytic effects and has also been negatively associated with the development of PMS or PMDD and postpartum depression [12, 13]. A history of PMS or PMDD may affect sex hormone levels during pregnancy, resulting in depressive symptoms; however, these levels were not measured in the present study. Thus, the association between sex hormone levels in patients with PMS or PMDD during pregnancy and depression should be investigated in the future.

Evidence suggests that interventions targeting antenatal depression risk can prevent postnatal depression and improve pregnancy outcomes [19]. This observation is supported by a systematic review and meta-analysis [30]. Therefore, the early identification of prenatal depression can mitigate its incidence and associated pregnancy outcomes, underscoring the importance of routine screening, diagnosis, and timely treatment during pregnancy [31]. However, failure to address antenatal depression promptly may escalate into postpartum depression [32]. Therefore, early identification of at-risk cases during pregnancy is crucial for safeguarding mothers from postpartum depression. Furthermore, it has been reported that PMS history also affects mother-infant bonding [33]. Thus, the results of this study may help identify at-risk cases.

This study has some limitations. First, this study used the results of the EPDS to assess risk factors for antenatal depression; however, the EPDS is a screening test for perinatal depression and is not used for the final diagnosis of perinatal depression. Second, there may have been a selection bias and issues with data reliability due to the web-based nature of the survey. For example, there may have been an information bias, such as recall bias, because the survey was self-administered and included questions about past information. Third, PMDD and PMS were assessed using questionnaires rather than being diagnosed through interviews. Finally, this was a cross-sectional study, and future longitudinal studies are necessary.

In conclusion, we found that having PMDD or PMS was significantly associated with maternal antenatal depression. Our findings suggest that screening for a history of PMS or PMDD during early antenatal interviews by healthcare providers, including sexual and reproductive health practitioners, may be useful in identifying patients for mental health care services to prevent perinatal depression during early pregnancy.

Supporting information

S1 File.

https://doi.org/10.1371/journal.pone.0315628.s001

Acknowledgments

We would like to express our gratitude to all the participants of this study and all individuals involved in the data collection.

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Citation: Ihara N, Sato Y, Ikeda S, Matsufuji H, Kikuchi K, Suetsugu Y, et al. (2024) Impact of premenstrual syndrome and premenstrual dysphoric disorder on maternal antenatal depression. PLoS ONE 19(12): e0315628. https://doi.org/10.1371/journal.pone.0315628

About the Authors:

Nozomi Ihara

Roles: Conceptualization, Data curation, Formal analysis, Writing – original draft