Mental Health and Quality of Life in Patients with Premenstrual Exacerbation: A Cross- Sectional Study in Japan

doi:10.21203/rs.3.rs-3319591/v1

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Mental Health and Quality of Life in Patients with Premenstrual Exacerbation: A Cross- Sectional Study in Japan

https://doi.org/10.21203/rs.3.rs-3319591/v1

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Background: Premenstrual symptoms in women affect their social life and require treatment based on an appropriate diagnosis. In the classification of premenstrual disorders (PMDs), premenstrual exacerbations of the underlying medical conditions are listed as premenstrual exacerbation (PME) as one of the variants of PMDs along with core premenstrual disorder (PMD). However, the incidence of PME and its impact on mental health and quality of life have not been studied. Therefore, we examined the prevalence of PME among women seeking treatment for premenstrual symptoms in Japan and compared the degree of anxiety, depression, and quality of life between women with PME and premenstrual syndrome (PMS).

Methods: Women who presented to the obstetrics and gynecology department of our hospital for the treatment of premenstrual symptoms and were diagnosed with PMDs using forward-pointing records were included in the study. Based on the diagnosis, patients were divided into three groups (PMS, PMDD, and PME), and their responses to a mental health and quality of life questionnaire during the initial visit were analyzed.

Results: Overall, 32 women were diagnosed with PMDs (53.1% with PMS, 15.6% with PMDD, and 31.3% with PME). All underlying medical conditions in women with PME were psychiatric disorders. Except for parity, there were no significant differences in various factors among the PMS, PMDD, and PME groups. Regarding mental health, the PME group had higher anxiety and depression scores than the PMS group. In terms of quality of life, the PME group had lower scores in all domains, except physical functioning, compared to the PMS group, while the PMDD group had lower scores in social functioning.

Conclusions: Approximately 30% of women with PMD had PME. Women with PME were more anxious and depressed than those with PMS, and their quality of life was extremely low in both physical and psychological domains. Patients with premenstrual symptoms should be managed with the consideration of the possibility of PME.

premenstrual disorders

premenstrual exacerbation

premenstrual syndrome

premenstrual dysphoric disorder

mood disorder

anxiety

depression

Premenstrual syndrome (PMS) is the cyclic recurrence of symptoms during the luteal phase of the menstrual cycle (1). Meanwhile, premenstrual dysphoric disorder (PMDD) is defined by the American Psychiatric Association as the cyclical recurrence of severe emotional symptoms that occur during the luteal phase of the menstrual cycle that subside shortly after the onset of menstruation (2). Many women experience some symptoms before menstruation. Up to 95% of Japanese women of reproductive age experience premenstrual symptoms, while the prevalence rates of moderate to severe PMS and PMDD are 5.3% and 1.2%, respectively (3). Premenstrual symptoms are associated with impaired interpersonal or workplace functioning. However, more than half of women with PMS are undiagnosed and poorly treated (4).

In 2011, the International Society for Premenstrual Disorders defined precise criteria for core premenstrual disorder (core PMD), which includes PMS and PMDD. Simultaneously, they differentiated between core PMD and its variants, which include premenstrual exacerbation (PME), PMD due to nonovulatory activity, progestogen-induced PMDD, and PMDD with absent menstruation (5). PME is defined as the cyclical recurrence of symptoms that are relieved by menstruation; however, there are no symptom-free periods, and symptoms are present even outside of the menstrual cycle. Among women, several conditions are aggravated by the menstrual cycle before menstruation, including acne, asthma, diabetes, epilepsy, erythema multiforme, and irritable bowel syndrome (6). Additionally, several mental health disorders are exacerbated by the menstrual cycle, including anxiety, bipolar disorder, and eating disorders (6). The Royal College of Obstetricians and Gynaecologists (RCOG) recommends that treatment of PME should be aimed at the underlying medical, physical, or psychiatric condition and/or to suppress ovulation (4). Therefore, core PMD and PME should be distinguished.

PMS is one of the most common gynecological disorders. Obstetrician–gynecologists have several opportunities to serve as primary care providers for women with premenstrual symptoms. Therefore, they are in a position to recognize the presence of disorders that are exacerbated during the premenstrual period (6). There is consensus that most women seeking initial treatment for PMS or PMDD actually have PME, which is mainly caused by premenstrual exacerbation of psychiatric disorders (7, 8). Therefore, it is assumed that these women will first seek care from a gynecologist. However, actual data are lacking (9). Additionally, the prevalence of PME in Japan has not been studied. Furthermore, there have been no reports on the effects of PME on anxiety, depression, and quality of life.

Hence, this study aimed to investigate the prevalence of PMS/PMDD/PME in women seeking care from obstetrician–gynecologists for premenstrual symptoms and to examine the severity of anxiety, depression, and quality of life in each of these conditions.

Participants

This study included women who visited the Department of Obstetrics and Gynecology at Tokyo Dental College Ichikawa General Hospital, Chiba, Japan, for the treatment of PMS between September 2014 and January 2021. As part of the diagnostic process for PMDs, patients were asked to keep a daily record of their symptoms starting from their first day of visit. The method of recording premenstrual symptoms was optional. Based on the records, the patients were diagnosed with PMS, PMDD, or PME.

The diagnosis of PMS was based on the American College of Obstetricians and Gynecologists guidelines (1), which require that the patient report at least one of the affective and somatic symptoms in the 5 days prior to menstruation. The diagnosis of PMDD was based on the Diagnostic and Statistical Manual of Mental Disorders (2). Additionally, based on the Green Top Guidelines (4), PME was diagnosed in patients in whom premenstrual symptoms were confirmed to be PME of any disease. The diagnosis of underlying medical conditions in women with PME was made by psychiatrists.

Questionnaire

The Hospital Anxiety and Depression Scale (HADS) was used to assess mental health, while the Short Form (36) Health Survey (SF-36) was used to assess quality of life.

The HADS is a widely used measure of anxiety and depression. Comprised of 14 items on a 4-point verbal rating scale, the HADS can be used to measure anxiety (7 items), depression (7 items), and general emotional distress (all 14 items). Total scores range from 0 (low level) to 42 (high levels of anxiety and depression) (10). The validity of the Japanese version of the HADS has been confirmed (11).

To assess the participants’ quality of life, the SF-36 was used. The SF-36 consists of 36 questions that evaluate eight health concept subscales: physical functioning, physical role, bodily pain, general health, vitality, social functioning, emotional role, and mental health (12). The SF-36 has been validated (13) and widely used in Japan.

Statistical analysis

The chi-square and Fisher’s exact tests were used for normally distributed variables. For numerical variables with normal distribution, the Kruskal–Wallis test and the Mann–Whitney U test were used. A p value of < 0.05 was considered significant. Statistical analysis was carried out using SPSS Statistics version 26.0 (IBM Corp., Armonk, NY, USA).

Ethics

This study was conducted in accordance with the principles outlined in the Declaration of Helsinki. The ethics committee of Tokyo Dental College Ichikawa General Hospital approved this study (approved No. I 21–65, 2022). Patient informed consent was obtained in the form of opt-out on the website; those who rejected were excluded.

Overall, 55 patients who sought treatment for premenstrual symptoms in our hospital were included in this study. Of these, 22 were excluded because of the following: did not record symptoms daily (n = 6), did not answer the questionnaire correctly (n = 1), and nondiagnosis of PMD due to the absence of fluctuation of symptoms during the menstrual cycle (n = 16). Based on their daily records, 32 were diagnosed with PMD, 17 (53.1%) with PMS, 5 (15.6%) with PMDD, and 10 (31.3%) with PME. The flow diagram is shown in Fig. 1.

The distribution of the underlying medical conditions of all women with PME was psychiatric disorders, including three patients with adjustment disorder, three with depressive disorder, two with bipolar disorder, one with anxiety disorder, and one with neurodevelopmental disorder.

No significant differences were found in age, body mass index, age of menarche, menstrual cycles, marital status, or employment status between the PMS, PMDD, and PME groups. The number of women with a history of delivery was significantly higher in the PMS group than in the PME group (Table 1).

Table 1

Characteristics of study participants
	PMS (n = 17)	PMDD (n = 5)	PME (n = 10)	P value*
Age (year), median (IQR)	39 (33–43)	41 (28–43)	32 (30.25–40.5)	0.551
BMI (kg/m²) median (IQR)	21.2 (19.6–22.9)	19.6 (19.1–20.4)	21.1 (19.5–22.7)	0.401
Age of menarche (year), median (IQR)	12 (12–12)	13 (13–15)	13.5 (11–25)	0.202
Menstrual cycles				0.971
Regular	13	4	8
Irregular	4	1	2
Marital status				0.140
Married	5	4	5
Never married	12	1	4
Divorced	0	0	1
Parity	12	1	2†	0.044
Employment status				0.367
Student	1	1	0
Employed	7	2	5
Part time	4	0	0
Unemployed	5	2	5

* Any difference among PMS, PMDD, PME groups.

† Significant differences from the PMS group.

Abbreviations: BMI, body mass index; PMS, premenstrual syndrome; PMDD, premenstrual dysphoric disorder; PME, premenstrual exacerbation, IQR, interquartile range

Regarding the HADS total, anxiety, and depression scores, the PME group had significantly higher HADS total, anxiety, and depression scores than the PMS group (Table 2).

Table 2

Median scores of the HADS
	PMS (n = 17)	PMDD (n = 5)	PME (n = 10)	P value*
	Median (IQR)	Median (IQR)	Median (IQR)
HADS total	13 (11–17)	21 (11–23)	20† (18.25–22.75)	0.017
HADS Anxiety	8.0 (5–10)	7.0 (6–11)	11.5† (9.25–13)	0.022
HADS Depression	6.0 (4–8)	9.0 (4–12)	9.0† (9–10.75)	0.052
* Any difference among PMS, PMDD, PME groups.
†Significant differences from the PMS group.
Abbreviations: HADS; the Hospital Anxiety and Depression Scale, BMI, body mass index; PMS, premenstrual syndrome; PMDD, premenstrual dysphoric disorder; PME, premenstrual exacerbation, IQR, interquartile range

For the eight domains of the SF-36, social functioning was significantly lower in the PMDD group than in the PMS group. Meanwhile, in the PME group, all domains, except physical functioning, were significantly lower than those in the PMS group (Table 3).

Table 3

Median scores of SF-36 components
	PMS (n = 17)	PMDD (n = 5)	PME (n = 10)	P value*
	Median (IQR)	Median (IQR)	Median (IQR)
Physical functioning	85 (80–95)	95 (90–100)	87.5 (80–95)	0.545
Role physical	68.7 (56.2–67.5)	75 (50–81.25)	46.8† (34.3–54.6)	0.046
Bodily pain	52 (41–62)	41 (32–52)	31† (22–32)	0.001
General health	52 (45–62)	50 (40–57)	42.5† (40–45)	0.109
Vitality	50 (37.5–56.2)	37.5 (18.75–37.5)	12.5† (7.8–31.2)	0.003
Social functioning	75 (62.5–67.5)	25† (12.5–50)	50† (25–62.5)	0.001
Role emotional	75 (50–91.6)	66.6 (50–75)	45.8† (25–50)	0.021
Mental health	55 (55–70)	45 (40–60)	40† (27.5–48.7)	0.026
* Any difference among PMS, PMDD, PME groups.
† Significant differences from the PMS group.
Abbreviations: BMI, body mass index; PMS, premenstrual syndrome; PMDD, premenstrual dysphoric disorder; PME, premenstrual exacerbation, IQR, interquartile range

We examined the prevalence of PMS/PMDD/PME in women seeking care for premenstrual symptoms from an obstetrician–gynecologist and examined the anxiety, depression, and quality of life of women with each of these conditions. In this study, we found that patients seeking gynecological care for premenstrual symptoms included several women with PME. Additionally, women with PME had more severe depression and anxiety than those with PMS. Moreover, both the mental and physical components of quality of life in women with PME were poor.

In this study, 31.3% of women with PMD were diagnosed with PME. Furthermore, all underlying disorders of women with PMS were psychiatric. Reports on the prevalence of PME are limited. A Taiwanese PMS clinic showed that 37% of patients who sought treatment for PMS had PME caused by a previously diagnosed psychiatric condition (14). Another study that evaluated the distribution of patients attending a PMS clinic found that 24% had premenstrual magnification syndrome (15). Our findings support the results of previous studies, although there are differences in whether the clinic specializes in PMS or general gynecology, country, and culture. Meanwhile, there are several reports of psychiatric disorders worsening during the luteal phase. One study found that 58% of women with a current depressive disorder experienced worsening of one or more depressive symptoms during the premenstrual period (16). A recent review showed that there is clear evidence of symptom exacerbation during the perimenstrual phase for psychotic disorders, panic disorder, eating disorders, depression, and borderline personality disorder but less consistent evidence for anxiety, and there was a different pattern of symptom exacerbation for bipolar disorder (17). Moreover, women with depression who experience premenstrual symptoms have a higher lifetime risk of suicide attempts than women who do not experience premenstrual symptoms (18). This suggests that it is important to be aware of the presence of psychiatric disorders in the management of patients with premenstrual symptoms.

We found that the HADS total, anxiety, and depression scores were significantly lower in the PME group than in the PMS group. There are several reports of patients with anxiety–depression in PMDD. One study showed that patients with PMDD had higher HADS anxiety and depression scores than patients with PMS (19). Another study showed that depression and anxiety were significantly higher in PMDD than in moderate/severe and no/mild PMS (20). Since markedly depressed mood and marked anxiety are included in the diagnostic criteria for PMDD, it is not surprising that anxiety and depression are worse in PMDD than in PMS. In this study, anxiety and depression were not significantly worse in women with PMDD; however, this may be due to the small number of cases in the PMDD group. Meanwhile, no study has reported on anxiety and depression in women with PME or compared these with women with PMS. Regardless, in this study, we found that women with PME also have severe anxiety and depression.

Based on the SF-36, women with PME had a lower quality of life in all components, except for physical functioning, compared to women with PMS. The quality of life in both women with PMS and PMDD has been reported. In a study of Turkish medical students, role-physical, general health, social functioning, and role-emotional of the SF-36 significantly decreased as PMS symptoms worsened (21). Another study from Iran showed that women who met the criteria for PMDD had low scores on all measures of the SF-36, except for physical functioning (22). Meanwhile, no study has explored the quality of life of women with PME. Notably, this study is the first to show that women with PME have a very low quality of life.

We acknowledge that there are several limitations in this study. First, the sample size was small, especially since the number of cases with PMDD was too small to compare with other groups and draw conclusions regarding anxiety, depression, and quality of life in women with PMDD. However, given the initially low prevalence of PMDD, this may reflect the current situation in Japan. Second, this study was conducted in a single center based in the obstetrics and gynecology department of a college hospital. As women seeking treatment for PMS symptoms present at gynecology clinics rather than hospitals, it is questionable whether the results of this study can be generalized; a multicenter study is needed. Third, records of symptoms that were used to diagnose PMDs are not a standardized method, such as the daily record of severity of problems (23). However, it is difficult to have patients keep a symptom diary in real-world practice; even in a study of Japanese obstetricians and gynecologists, the use of daily rating for two cycles was only 8% (24).

Despite these limitations, to the best of our knowledge, this is the first study to show the prevalence, anxiety and depression, and quality of life of women with PME and premenstrual symptoms attending a gynecological clinic. To overcome such limitations, it is necessary to increase the number of cases by conducting collaborative studies with other institutions using a unified symptom record chart.

Patients who seek treatment of premenstrual symptoms include those with PME of psychiatric disorders. Women with PME had worse anxiety, depression, and quality of life. Future research is needed to clarify how to properly diagnose and manage patients with premenstrual symptoms, including PME.

HADS

Hospital Anxiety and Depression Scale

PMD

premenstrual disorder

PMDD

premenstrual dysphoric disorder

PME

premenstrual exacerbation

SF-36

the Short Form (36) Health Survey (SF-36)

PMS

premenstrual syndrome

Ethics approval and consent to participate

This study was conducted in accordance with the principles outlined in the Declaration of Helsinki. The ethics committee of the Ichikawa General Hospital approved this study (approved No. I 21-65, 2022).

Consent for publication

Not applicable.

Availability of data and materials

The datasets generated and/or analyzed during the current study are not publicly available but are available from the corresponding author on reasonable request.

Competing interests

MO received lecture fees from Otsuka Pharmaceutical Co., Bayer Yakuhin, Ltd., and Fuji Pharma Co., Ltd. KT received lecture fees from Otsuka Pharmaceutical Co., Ltd., Bayer Yakuhin, Ltd., Tsumura & Co., Fuji Pharma Co., Ltd., and ASKA Pharmaceutical Co. Ltd.

Funding

This study was not funded by any institution.

Authors’ contributions

MO analyzed and interpreted the patient data and drafted the manuscript. KT and IY collected the data and advised on the study design. All the authors have read and approved the final version of the manuscript.

Acknowledgments

Not applicable.

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Competing interest reported. MO received lecture fees from Otsuka Pharmaceutical Co., Bayer Yakuhin, Ltd., and Fuji Pharma Co., Ltd. KT received lecture fees from Otsuka Pharmaceutical Co., Ltd., Bayer Yakuhin, Ltd., Tsumura & Co., Fuji Pharma Co., Ltd., and ASKA Pharmaceutical Co. Ltd.

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Mental Health and Quality of Life in Patients with Premenstrual Exacerbation: A Cross- Sectional Study in Japan

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Abstract

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Background

Methods

Participants

Questionnaire

Statistical analysis

Ethics

Results

Discussion

Conclusions

Abbreviations

Declarations

References

Additional Declarations

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