Relation between metabolic syndrome and psychiatric symptoms severity in women with premenstrual syndrome

Background Premenstrual syndrome (PMS) is a clinical condition characterized by recurrent moderate‑to‑severe affective, physical, and behavioral symptoms during the menstrual cycle. The present study aimed to assess the rela‑ tion between metabolic syndrome (MetS) and symptoms severity in patients with premenstrual syndrome (PMS). This multicentric propensity score matched analysis included 300 women with PMS. They comprised 150 women with MetS and 150 women without MetS. Diagnosis of PMS was based on the validated Arabic version of Premen‑ strual Symptoms Screening Tool (PSST). For the diagnosis of MetS, we adopted the Harmonized Joint Scientific State‑ ment (HJSS) on metabolic syndrome recommendations. Results The present study included 300 patients with PMS. They comprised 150 patients with MetS and 150 patients without MetS. Comparison between the studied groups regarding the demographic and clinical data showed that patients with MetS had significantly higher BMI (30.5 ± 3.0 versus 25.2 ± 3.5 kg/m 2 , p < 0.001) and longer symp‑ toms duration (4.4 ± 0.9 versus 3.3 ± 1.1 days, p < 0.001). Patients with MetS included higher frequency of moderate‑to‑ severe PMS (35.3% versus 20.7%, p = 0.005). In patients with MetS, it was found that patients with moderate‑to‑severe PMS have significantly higher BMI, younger age at menarche and longer symptoms duration. Multivariate logistic regression analysis identified age at menarche [OR (95% CI): 0.7 (0.55–0.9), p = 0.005], PMS symptoms duration [OR (95% CI): 4.45 (3.0–6.6), p < 0.001] and MetS [OR (95% CI): 1.67 (1.34–2.53), p = 0.017] as significant predictors of moder‑ ate‑to‑severe PMS. Conclusions MetS is related to symptoms severity in PMS patients.


Introduction
Premenstrual syndrome (PMS) is a clinical condition characterized by a cluster of recurrent affective, physical, and behavioral symptoms of variable severity occurring during the luteal phase of menstrual cycle and usually fading within few days of menstruation [1,2].While most women experience premenstrual symptoms in the reproductive age, the condition presents with severe and debilitating symptoms in only 5.0% of women [3].The premenstrual dysphoric disorder (PMDD) constitutes the most severe form of psychiatric premenstrual symptoms [4].Interestingly, PMS was linked to postpartum depression (PPD) in affected women [5].One third of women were found to have PPD as shown by one study [6] with endocrinal imbalance reported as a contributing factor [7].
Severe somatic forms of PMS may respond to nutritional supplements, herbal remedies, lifestyle modifications, exercise or hormonal treatment.However, efficacy of these interventions remains debatable.So, identification of factors related to severe forms of PMS may be crucial for appropriate management of the condition [16,17].
Metabolic syndrome (MetS) is a cluster of clinical and biochemical risk factors including obesity, elevated blood pressure, hyperglycemia and dyslipidemia.The estimated prevalence of MetS among premenopausal women ranges from 5.4% and 55.5% [18].The condition is related to a wide range of morbidities affecting almost all body systems [19].
While the medial literature is replete with studies discussing the relation between MetS and many clinical conditions, no study assessed the clinical significance of MetS in PMS patients.So, the present study sought to assess the prevalence of MetS in a group of Egyptian women with PMS and to discover the relation between various parameters of MetS and clinical severity of PMS.

Methods
This cross-sectional study was conducted at outpatient clinics of gynecology and obstetrics departments.The study protocol was approved by the Institutional Review Board, and all patients gave informed consent before enrollment.The study findings were reported according to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) initiative recommendations [20].
The study included 300 women with PMS.All patients were submitted to thorough clinical and gynecological examination.Diagnosis of PMS was based on the validated Arabic version of Premenstrual Symptoms Screening Tool (PSST).PSST includes 19 items assessing patients' psychiatric symptoms including anger, anxiety, depression and others in line with DSM-IV.The tool showed high internal consistency (Cronbach's α = 0.92) and good construct validity [21].Every item is rated as "not at all, " "mild, " "moderate, " or "severe." Patients were classified to have moderate-to-severe PMS if at least one of the first 4 items was severe AND at least 4 of the first 14 items were moderate to severe AND at least one of the last five items was severe according to the instructions of Steiner and colleagues [22].
Exclusion criteria were receiving treatment for PMS or PMDD, associated psychosomatic disorders, associated gynecological conditions or other psychiatric conditions.
Patients included 150 patients with MetS and 150 patients without MetS.The studied groups were matched using a propensity score matching analysis calculated by logistic regression.Factors included in the score were age, age at menarche and cycle duration.
For the diagnosis of MetS, we adopted the Harmonized Joint Scientific Statement (HJSS) on metabolic syndrome recommendations.MetS criteria included elevated waist circumference (≥ 80 cm), elevated triglycerides levels (≥ 150 mg/dL), reduced high-density lipoprotein cholesterol (HDL-C) (< 50 mg/dL), elevated blood pressure (systolic ≥ 130 and/or diastolic ≥ 85 mm Hg) and elevated fasting glucose (≥ 100 mg/dL).MetS was diagnosed in the presence of any three criteria [23].Data obtained from the present study was statistically analyzed using statistical package of social sciences (SPSS) 20 (IBM, USA).Numerical data were expressed as mean ± SD while categorical data were presented as number and percent.Numerical data were compared using t test and categorical data were compared using Chi-square test.Logistic regression analysis was used to identify predictors of PMS severity.p value less than 0.05 was considered statistically significant.

Results
The present study included 300 patients with PMS.They comprised 150 patients with MetS and 150 patients without MetS.Comparison between the studied groups regarding the demographic and clinical data showed that patients with MetS had significantly higher BMI (30.5 ± 3.0 versus 25.2 ± 3.5 kg/m 2 , p < 0.001) and longer symptoms duration (4.4 ± 0.9 versus 3.3 ± 1.1 days, p < 0.001).Patients with MetS included higher frequency of moderate-to-severe PMS (35.3% versus 20.7%, p = 0.005) (Table 1, Fig. 1).
In patients with MetS, it was found that patients with moderate-to-severe PMS have significantly higher BMI, younger age at menarche and longer symptoms duration.In patients without MetS, it was found that patients with moderate-to-severe PMS have significantly younger age at menarche and longer symptoms duration (Table 2).
In patients with MetS, it was found that patients with moderate-to-severe PMS have longer waist circumference, higher triglycerides levels, higher diastolic blood pressure and higher number of MetS criteria (Table 3).

Discussion
PMS particularly its severe form is a challenging clinical condition.Available treatment options frequently fail to achieve satisfactory clinical response.Integrated approach for management of the condition requires identification of possible risk factors.Considering the high prevalence of MetS and its relation to many morbidities, the present study aimed to assess the clinical significance of MetS in PMS patients and its relation to its severity.
Many previous studies identified some MetS components as risk factors for PMS.In the study of Masho and colleagues [24], the authors concluded that obesity is Fig. 1 PMS severity in women with MetS and women without strongly associated with PMS.Likewise, the study of Bertone-Johnson and colleagues [25] noted a significant linear relation between increased BMI and incident PMS.In contrast, the study of Sharifan and colleagues [26] found no relation between BMI and severity of PMS.In another study, increased cholesterol level was reported as a risk factor for PMS [27].
Interestingly, the current study noted patients with MetS experienced significantly severe form of PMS.Previous studies identified as association between MetS and some elements of severe PMS.For example, the association between MetS and sleep troubles was reported in younger [28] and older [29] women and in the general population [30].Moreover, it was found that MetS patients significantly higher frequency of severe joint aches.While none of the studied patients   had clinical diagnosis of joint pathologies, the association between MetS and inflammatory joint diseases is well-documented [31].
Our study recognized patients age at menarche, symptoms duration and MetS as significant independent predictors of PMS severity.The relation between older age and severity of PMS was previously reported [32].The association between MetS and severity of PMS may be explained by the inflammatory background of both conditions.PMS is characterized by elevated levels of proinflammatory cytokines [33].The low-grade inflammation in MetS can produce augmented release of many proinflammatory cytokines like tumor necrosis factor α and interleukin 6 [34].Of note, the recent study of Ter Horst and colleagues [35] suggested that women with MetS may also have lower expression of the anti-inflammatory adipokine adiponectin.

Conclusions
MetS is associated more severe form of PMS.It's recommended to conduct interventional study to assess if control of MetS components can affect PMS symptoms.Conclusions of the present study may be limited by its cross-sectional design.Probably, longitudinal studies assessing the relation between changes in MetS components and PMS symptoms may provide better approach to judge the relation between MetS and severity of PMS symptoms.

Table 1
The reported demographic and clinical data in the studied patients (n = 300) BMI body mass index, MetS metabolic syndrome, PMS premenstrual syndrome

Table 2
Relation between PMS severity and clinical data in the studied groups (n = 300) BMI body mass index, MetS metabolic syndrome, PMS premenstrual syndrome

Table 3
Relation between PMS severity and MetS components in MetS patientsBMI body mass index, DBP diastolic blood pressure, FBG fasting blood glucose, HDL high-density lipoprotein, MetS metabolic syndrome, PMS premenstrual syndrome, SBP systolic blood pressure

Table 4
Predictors of moderate-to-severe PMS in the studied patients BMI body mass index, MetS metabolic syndrome, PMS premenstrual syndrome, SBP systolic blood pressure