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Psychosomatic Medicine 63:822-829 (2001)
© 2001 American Psychosomatic Society

ORIGINAL ARTICLES

Changes in Premenstrual Symptoms in Women With Schizophrenia: A Prospective Study

So-Hyun Choi, MD, PhD, Sang-Bum Kang, MD and Sook-Haeng Joe, MD, PhD

Yong-In Mental Hospital (S.-H.C., S.-B.K.), Yongin City, Kyunggi Province, South Korea; and Department of Psychiatry, College of Medicine, Korea University, Seoul, Korea.

Address reprint requests to: So-Hyun Choi, MD, PhD, Yong-In Mental Hospital, 4 Sangha-Ri, Kusung-Myun, Yongin City, Kyunggi Province, South Korea 449-910. Email: cshi{at}unitel.co.kr


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
OBJECTIVE: We investigated whether the psychiatric symptoms and clinical features of schizophrenia change during the premenstrual phase in female patients.

METHODS: We observed 30 female schizophrenic inpatients over one menstrual cycle. All subjects met DSM-IV criteria for schizophrenia, and all had a regular menstrual cycle. All subjects completed the Daily Rating Form (DRF) every evening, and one psychiatrist rated the subjects (using the Brief Psychiatric Rating Scale [BPRS]) once during each of the three menstrual phases (premenstrual, menstrual, and postmenstrual). Serum levels of estradiol (E2) and progesterone were measured on the fifth to seventh day of both the premenstrual and postmenstrual phases. Data from the 24 subjects who completed the DRF correctly and completely were used for statistical analysis.

RESULTS: The mean total BPRS score for the 24 subjects was highest in the premenstrual phase and lowest in the postmenstrual phase, and a statistically significant difference was found among the three menstrual phases. Mean subtotal BPRS scores showed statistically significant differences among the three menstrual phases in anxiety/depression and withdrawal/retardation, but not in the psychotic symptom subscales. Mean serum E2 level showed a trend of increasing from the premenstrual phase to the postmenstrual phase. However, there was no significant correlation between {Delta}BPRS and {Delta}E2. When the criterion of 30% change was applied, the DRF items of depressed mood, anxious/nervous/restless, hostile/aggressive, and less/impaired work showed high frequencies of change in the premenstrual phase. Somatic items of abdominal pain, breast pain, and headache showed significant change with the 30% change rule on the DRF. On both the BPRS and DRF scores, premenstrual change of affective and behavioral symptoms was prominent, whereas the change of psychotic symptoms was minimal on the BPRS. In addition, in the premenstrual phase, there was a statistically significant correlation between the total BPRS score and the mean total DRF score. There was no correlation between premenstrual change in symptoms and hormonal levels of E2, progesterone, and the estradiol/progesterone (E/P) ratio.

CONCLUSIONS: The findings of this study suggest that premenstrual exacerbation of schizophrenic symptoms in female patients may not be a worsening of the schizophrenic symptoms but a concurrence of affective, behavioral, and somatic symptoms.

Key Words: premenstrual symptom change • schizophrenia • premenstrual syndrome • estrogen • Daily Rating Form • Brief Psychiatric Rating Scale

Abbreviations: BPRS = Brief Psychiatric Rating Scale; DRF = Daily Rating Form; DSM-IV = Diagnostic and Statistical Manual of Mental Disorders, fourth edition; E2 = estradiol; E/P ratio = estradiol/progesterone ratio; MDS = menstrual distress syndrome; PG = progesterone; PMDD = premenstrual dysphoric disorder; PMS = premenstrual syndrome


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Several studies have demonstrated that symptoms of psychotic disorders such as schizophrenia or affective disorders are aggravated before or during menstruation (1, 2) and that psychiatric admissions increase during these times (3, 4). Several reports (5–8) have noted that psychotic symptoms appear suddenly before or during menstruation and then resolve after cessation of menstruation even in normal women. Because of this, much attention has been paid to the relationship between psychiatric illnesses and the menstrual cycle. Although many studies (9–12) have been conducted to demonstrate the relationship between PMS and other psychiatric disorders, especially affective disorders, there remains some debate because of the difficulties of diagnosing and assessing PMS. Dennerstein et al. (13) categorized the premenstrual changes in symptoms into PMS and MDS and described a diagnosable psychiatric disorder and symptoms of at least moderate intensity throughout the menstrual cycle with exacerbation during the premenstrual period for MDS. Contrary to the concept of MDS that the underlying depressive symptoms are exacerbated premenstrually, DSM-IV implies the possibility of coexistence of PMDD and affective disorder, using the term PMDD instead of PMS with more descriptive and strict diagnostic criteria.

Several studies and case reports on the premenstrual changes in symptoms in women with schizophrenia have also been published. Supporting the concept of MDS are reports (14–16) that schizophrenic symptoms are exacerbated during the premenstrual phase, when the blood estrogen level is low. Recently there have been several reports of a close relationship between estrogen level and severity of psychotic symptoms in schizophrenia. In studies of schizophrenic patients, Reicher-Rossler et al. (17, 18) found a close relationship between the exacerbation of psychotic symptoms and low estrogen level. Some animal studies have shown that estrogen increases the density of dopamine D2 receptors (19) and attenuates the development of dopamine receptor supersensitivity (20).

There remains a question of whether the premenstrual exacerbation of the symptoms of schizophrenia is a worsening of the schizophrenic symptoms related to the low estrogen level or a concurrence of a specific syndrome characterized by a cluster of affective, behavioral, and somatic symptoms. Of the studies that have assessed symptoms related to the menstrual cycle, however, few prospective studies have assessed affective, somatic, and behavioral symptoms in addition to schizophrenic symptoms. Hurt et al. (21) reported that the prevalence of premenstrual depression in female schizophrenics was approximately 65%. In a study of the changes in symptoms related to the menstrual cycle in schizophrenic women, Harris (22) found that the most exacerbated symptoms were affective and somatic symptoms rather than psychotic symptoms specific to schizophrenia. The author suggested that change in menstrual cycle-related symptoms may be a discrete phenomenon with its own symptom profile that is superimposed on schizophrenia.

This study had three objectives: 1) to observe how psychotic symptoms change throughout the menstrual cycle and to examine whether psychotic symptoms are exacerbated by the lowering of the estrogen level during the premenstrual phase, 2) to assess how female schizophrenics experience symptoms related to the menstrual cycle, and 3) to determine whether premenstrual exacerbation of schizophrenic symptoms in women is one aspect of the exacerbation of psychotic symptoms or the result of a concurrence of a cluster of affective, behavioral, and somatic symptoms.


   METHODS
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
Subjects
Subjects for this study were 30 female schizophrenic inpatients aged 20 to 45 years. All subjects met DSM-IV criteria for schizophrenia.

At the first stage of subject selection, we administered a questionnaire concerning menstrual regularity and the duration of menstrual flow (days). We then selected 49 patients who reported a regular menstrual cycle for at least 3 months and a menstruation period of 4 to 7 days. Patients with a history of schizoaffective or other affective disorder were excluded from the study, as were those being treated with mood stabilizers or antidepressants.

At the second stage of subject selection, we observed the 49 patients over one complete menstrual cycle. Finally, 30 patients who had a regular menstrual cycle length from 25 to 35 days and a menstruation period lasting 4 to 7 days were selected as the subjects for this study. Data for 24 of these 30 subjects were used for data analysis. The data of six patients were excluded because the patients did not fill out the DRF correctly or completely. All 24 subjects were premenopausal and aged 20 to 45 years (mean age, 36 ± 6.4 years). Mean menstrual cycle length was 29.8 ± 2.5 days, and mean number of menstrual flow days was 5.3 ± 1.5 (Table 1). All 24 subjects were inpatients and had taken antipsychotic medication for at least six consecutive months. No evidence of medical illness, particularly endocrinological or gynecological illness, was found on medical history, physical examination, or hematological and biochemical laboratory tests.


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  		Table 1. Subject Characteristicsa
 

Procedure
All subjects signed informed consent statements. Dosages of antipsychotic drugs were fixed throughout this study. All subjects were assessed over one complete menstrual cycle, from the first day of menstrual flow to the onset of the next menstrual flow period. A psychiatrist, who was blind to the subjects’ menstrual cycle phase, used the BPRS to rate patients. The psychiatrist rated each patient once during each of three menstrual phases: 1) at the fifth to seventh day of the premenstrual phase (the week before menstruation), 2) at the third to fourth day of the menstrual phase, and 3) at the sixth to seventh day of the postmenstrual phase (the week after cessation of menstruation). Subjects completed the DRF every evening during one complete menstrual cycle with the assistance of psychiatric nurses fully trained to administer the DRF. Serum levels of E2 and PG were measured on the fifth to seventh day of both the premenstrual and postmenstrual phases. Blood sampling was done in the morning before medication was dispensed (around 7 AM), and serum was kept frozen at -70°C. All laboratory analyses were performed in a single batch after all blood samples were collected to avoid methodological variation. Serum levels of E2 and PG were measured by radioimmunoassay.

Instruments and Outcome Measures
Menstrual cycle-related affective, somatic, and behavioral symptoms were measured with a prospective questionnaire (DRF) developed by Endicott and Halbreich (23). The DRF consists of 21 items (Table 2); each item is rated on a six-point scale ranging from 1 (no symptom) to 6 (extremely severe symptom). Schizophrenic symptoms were evaluated with the BPRS of Overall and Gorham (24); each item is rated on a seven-point scale ranging from 0 (no symptom) to 6 (extremely severe symptom).


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  		Table 2. Number of Subjects With Significant Premenstrual Symptom Change for the 21 DRF Items
 

For each of the 21 DRF items, we compared the mean symptom score of the premenstrual phase with that of the postmenstrual phase for each subject. The 30% change rule, as suggested by the National Institute of Mental Health (25), Rubinow et al. (26, 27), and DeJong et al. (28), was applied to determine the degree of symptom change during the premenstrual phase. A significant premenstrual change was defined as an increase in symptom severity of at least 30% during the premenstrual phase as compared with the postmenstrual phase. In addition to the 30% change rule, we also applied the 50% change rule suggested by Steiner et al. (29). We considered the premenstrual symptom change as nonsignificant when the mean score for each DRF item during the premenstrual phase was less than three points (mild) even if the change satisfied the 30% or 50% change rule. Using these criteria, we determined the frequency of significant premenstrual symptom change for each of the 21 items (Table 2).

Mean total BPRS scores of the 24 subjects were compared among the premenstrual, menstrual, and postmenstrual phases. The items of the BPRS were classified into four symptom subgroups (thought, paranoid, withdrawal/retardation, anxiety/depression), and the mean subtotal BPRS scores of each symptom subgroup were compared among the premenstrual, menstrual, and postmenstrual phases (Table 3).


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  		Table 3. Change of Mean Total and Mean Subtotal BPRS Scores Over the Menstrual Cycle of All 24 Subjectsa
 
We examined the relationship between total BPRS score and mean total DRF score during the premenstrual phase. We then classified the DRF items into somatic and psychological/behavioral clusters and examined the relationship between total BPRS score and mean subtotal DRF score of each symptom cluster during the premenstrual phase.

We also examined the relationship between the change in BPRS score and the change in serum E2 level over the menstrual cycle. We defined change in BPRS score ({Delta}BPRS) as the difference between the premenstrual and postmenstrual total BPRS scores. Change in serum E2 level ({Delta}E2) was defined as the difference between the premenstrual and postmenstrual serum levels of E2.

In addition, we examined the relationship between hormone levels and each of the two DRF symptom clusters mentioned above during the premenstrual phase. Within each symptom cluster, subjects were classified into low and high symptom groups on the basis of their mean DRF score during the premenstrual phase. The low symptom group included subjects whose premenstrual mean DRF scores were below the mean DRF score of all 24 subjects. The high symptom group included subjects whose premenstrual mean DRF scores were above the mean DRF score of all 24 subjects. The low and high symptom groups were compared with respect to premenstrual mean serum levels of E2, PG, and E/P ratio (Table 4).


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  		Table 4. Comparison of Premenstrual Mean Serum Levels of E2 and PG and E/P Ratio Between Group 1 and Group 2 Within Each Somatic Cluster and Psychological/Behavioral Cluster on the DRFa
 

Statistical Analysis
Data were analyzed using SPSS/PC software. Mean total BPRS scores and mean subtotal BPRS scores for each of the four symptom subgroups of the 24 subjects were compared among the premenstrual, menstrual, and postmenstrual phases with repeated-measures analysis of variance. When the analysis indicated significant differences, the differences were analyzed with post hoc Bonferroni tests. The relationship between {Delta}BPRS and {Delta}E2 was analyzed with Pearson’s correlation coefficient. We analyzed the relationships among total BPRS score, mean total DRF score, and mean subtotal DRF score for each of the two symptom clusters during the premenstrual phase with Pearson’s correlation coefficient. Within each of the two symptom clusters, we analyzed the difference between the high and the low symptom groups with respect to premenstrual mean serum levels of E2, PG, and E/P ratio using the t test. A p value <.05 was considered significant for all tests.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
DRF Findings
The frequencies of significant premenstrual symptom change for each of the 21 items are shown in Table 2. We considered premenstrual symptom change as significant when the mean score during the premenstrual phase was >=3 points (mild) and the premenstrual symptom change satisfied the 30% or 50% change rule. The items of depressed mood, anxiety/nervousness/restlessness, irritability/anger/impatience, and more sexuality showed higher frequencies than the other items when both the 30% and 50% change criteria were applied (Table 2).

When the criterion of 30% change was applied, 37% of the subjects (9 of 24) did not show a significant change in symptoms for any of the items, whereas 63% of the subjects (15 of 24) showed a significant symptom change for at least one item. Among the 24 subjects, 21% (5 of 24), 21% (5 of 24), 13% (3 of 24), and 8% (2 of 24) showed a significant change in symptoms for one, two, four, and five items, respectively. When the criterion of 50% change was applied, 58% of the subjects (14 of 24) did not show a significant symptom change for any of the items, whereas 42% of the subjects (10 of 24) showed significant change in symptoms for at least one item.

BPRS Findings
Mean total BPRS scores and mean subtotal BPRS scores for the three menstrual cycle phases are shown in Table 3. The mean total BPRS score was 33.4 ± 8.5 for the premenstrual phase, 32.2 ± 9. 2 for the menstrual phase, and 30.1 ± 8.9 for the postmenstrual phase. There was a statistically significant difference among the three menstrual phases (df = 2, F = 4.2, p < .05). Post hoc analysis revealed a significant difference between the premenstrual and postmenstrual phases (p < .01). The mean subtotal BPRS score for the withdrawal/retardation group was 5.7 ± 2.2 for the premenstrual phase, 4.6 ± 1.4 for the menstrual phase, and 5.0 ± 1.8 for the postmenstrual phase. There was a statistically significant difference among the three menstrual phases (df = 2, F = 3.7, p < .05). Post hoc analysis revealed a significant difference between the premenstrual and menstrual phases (p < .05). The mean subtotal BPRS score for the anxiety/depression group was 6.8 ± 1.8 for the premenstrual phase, 5.9 ± 2.0 for the menstrual phase, and 5.2 ± 2.1 for the postmenstrual phase. There was a statistically significant difference among the three menstrual phases (df = 2, F = 10.1, p < .0001). Post hoc analysis revealed a significant difference between the premenstrual phase and both the postmenstrual phase (p < .0001) and menstrual phase (p < .05). However, the mean subtotal BPRS scores for both the thought and paranoid symptom groups did not show statistically significant differences among the three menstrual phases.

Relationships Among BPRS Score, DRF Score, and Serum E2 Level
Relationship between BPRS and DRF scores.
In the premenstrual phase, there were statistically significant correlations between total BPRS score and both mean total DRF score (r = 0.44, p < .05) and mean subtotal DRF score for the psychological/behavioral symptom cluster (r = 0.47, p < .05). However, there was no statistically significant correlation between total BPRS score and mean subtotal DRF score for the somatic symptom cluster. In the postmenstrual phase, there was no statistically significant correlation between total BPRS score and both mean total DRF score and mean subtotal DRF scores of both symptom clusters.

Relationship between BPRS score and serum E2 level.
The mean total BPRS score for all subjects showed a trend of decreasing from 33.4 ± 8.5 for the premenstrual phase to 30.1 ± 8.9 for the postmenstrual phase, and mean serum E2 level showed a trend of increasing from 13.2 ± 9.5 pg/ml for the premenstrual phase to 38.8 ± 43.8 pg/ml for the postmenstrual phase. However, there was no significant correlation between {Delta}BPRS and {Delta}E2 (r = -0.21, p = .30).

Relationships Between DRF Score and Serum E2 Level, Serum PG Level, and E/P Ratio
Mean serum levels of E2 and PG and mean E/P ratios for the premenstrual and postmenstrual phase are shown in Table 5.


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  		Table 5. Mean Serum Levels of E2 and PG and E/P Ratio for the Premenstrual and Postmenstrual Phasesa
 

Applying the criterion of 30% change, we classified the subjects into two groups: one group (N = 9) with no items of significant premenstrual change and the other group (N = 15) with at least one item of significant premenstrual change. No statistically significant difference was found between the two groups for premenstrual mean serum levels of E2 and PG or E/P ratio. E/P ratio showed no significant difference between the premenstrual and postmenstrual phases within the group with at least one item of significant premenstrual change.

The premenstrual mean subtotal score for the somatic cluster of the DRF was 8.3; the scores of 10 subjects were above the mean, and the scores of 14 subjects were below the mean. Within the somatic cluster, no statistically significant difference was found between the two symptom groups for premenstrual mean serum levels of E2 and PG or E/P ratio. The premenstrual mean subtotal score for the psychological/behavioral cluster of the DRF was 38.9; the scores of 11 subjects were above the mean, and the scores of 13 subjects were below the mean. Within the psychological/behavioral cluster, no statistically significant difference was found between the two symptom groups for premenstrual mean serum levels of E2 and PG or E/P ratio (Table 4).


   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
In this study the mean total BPRS score for all subjects was significantly different among the three menstrual phases, being highest in the premenstrual phase and lowest in the postmenstrual phase. The mean subtotal BPRS scores for the anxiety/depression group and withdrawal/retardation group was significantly different among the three menstrual phases, being highest in the premenstrual phase and lowest in the postmenstrual phase. However, the mean subtotal BPRS scores for both the thought and paranoid symptom groups was not significantly different among the three menstrual phases. There was no statistically significant correlation between {Delta}E2 and {Delta}BPRS. These findings suggest that the premenstrual increase in BPRS score is caused by factors other than the exacerbation of psychotic symptoms related to the premenstrual decrease of serum E2.

We suggest two possibilities to explain why the premenstrual increase in total BPRS score was not accompanied by exacerbation of psychotic symptoms. First, all subjects in this study had been taking antipsychotic medication for at least 6 months, and their dosages were fixed at an average of 573.4 ± 456. 3 mg of chlorpromazine equivalent throughout the study. Because their psychotic symptoms were already greatly alleviated when the study was started (Table 3), exacerbation of psychotic symptoms may have been prevented by antipsychotic medications. Second, there is the possibility of concurrence of a specific syndrome characterized by a cluster of affective, behavioral, and somatic symptoms. As mentioned before, the symptom groups that showed significantly high BPRS scores in the premenstrual phase were the anxiety/depression and withdrawal/retardation groups, not the psychotic group. When the criterion of 30% change was applied, 15 subjects showed significant symptom change for at least one item of the DRF, and the items of depressed mood, anxious/nervous/restless, hostile/aggressive, and less/impaired work showed higher frequencies than the other items. On both the BPRS and DRF scores, change of affective and behavioral symptoms was prominent, whereas the change of psychotic symptoms was minimal on the BPRS in the premenstrual phase. In addition, in the premenstrual phase, there was a statistically significant correlation between total BPRS score and both mean total DRF score and mean subtotal DRF score for the psychological/behavioral symptom cluster. However, in the postmenstrual phase, there was no statistically significant correlation between total BPRS score and both mean total DRF score and mean subtotal DRF score for the psychological/behavioral symptom cluster. These findings support the idea that premenstrual exacerbation of symptoms in schizophrenia that is not predominantly affective in nature may result from a concurrence of a specific syndrome characterized by a cluster of affective and behavioral symptoms. The findings of this study are inconsistent with the concept of MDS and the findings (14–16) that psychotic symptoms are exacerbated premenstrually in schizophrenic women. Harris (22) studied 39 schizophrenic women and reported that the most exacerbated symptoms were affective and somatic symptoms rather than psychotic symptoms more specific to schizophrenia. His suggestion that menstruation-related symptom changes may be superimposed on schizophrenia is consistent with the second of our two explanations.

The serum E2 level was extremely low in both the premenstrual and postmenstrual phases in this study. In the premenstrual phase, the mean serum E2 level for all subjects was as low as 13.2 ± 9.5 pg/ml (range, 5.0–49.5 pg/ml), and it did not reach the lower limit of normal for this phase. In the postmenstrual phase, mean serum E2 level for all subjects was also as low as 38.8 ± 43.8 pg/ml (range, 5.6–2 16.8 pg/ml); it also did not reach the lower limit of normal for this phase. There are conflicting reports about serum E2 levels in schizophrenic women. Prentice and Deakin (30) reported that serum the E2 level is within the normal range for all menstrual cycle phases in schizophrenic women. However, consistent with this study, Riecher-Rossler et al. (17) and Carter et al. (31) reported that the serum E2 level was extremely low in schizophrenic women. One possible explanation for the low serum E2 level in schizophrenic women is suppression of ovarian estradiol production due to neuroleptics-induced hyperprolactinemia. However, it is also possible that a low serum E2 level is one aspect of the schizophrenic process. Riecher-Rossler et al. (17) and Carter et al. (31) reported that there was no significant relationship between antipsychotic medication and serum E2 level. Furthermore, there are reports supporting this possibility. Brambilla et al. (32) reported that the serum luteinizing hormone level was abnormally low in women with chronic schizophrenia before antipsychotic medication. In addition, Ripley and Papanicolaou (33) reported that a high percentage of female schizophrenics show menstrual disturbances before antipsychotic medication. There is no consensus on the influence of antipsychotic medication on serum E2 level, and this issue requires further study to elucidate the relationship between antipsychotic medications and serum E2 level.

In this study we used the DRF for prospective assessment of menstruation-related symptom changes. In several studies (23, 26, 28), 40% to 60% of the subjects who were diagnosed with PMS on retrospective rating did not meet the criteria of PMS on prospective rating. These findings suggest that prospective rating is essential in evaluating menstruation-related affective, somatic, and behavioral symptom changes. Halbreich et al. (34) pointed out that clinical features and the severity of the premenstrual symptom change are highly variable and that some of these changes are not detrimental to the subjects; those authors suggested the term "premenstrual changes (PMC)" to emphasize the affective and behavioral changes that occur during the premenstrual phase. In this context, it is necessary to compare the premenstrual phase with other menstrual phases to determine the presence of premenstrual changes in symptoms. In this study we compared the premenstrual DRF score to the postmenstrual score, as done in the study of Endicott et al. (35), and we defined the premenstrual phase as the week before menstruation and the postmenstrual phase as the week after the cessation of menstruation, as did Rubinow et al. (26, 27) and DeJong et al. (28). Although there are various methods for evaluating premenstrual changes in symptoms, we applied the 30% change rule (25–28) and the 50% change rule as suggested by Steiner et al. (29). However, the 30% and 50% change rules do not take into account inter-individual variability, so a statistically significant but clinically insubstantial symptom change (from nonexistence to very mild) may be considered a significant change. To avoid this problem, we considered a premenstrual symptom change as nonsignificant when the mean score for each DRF item during the premenstrual phase was less than three points (mild) even if the premenstrual symptom change satisfied the 30% or 50% rule. In this study, with the 30% change rule, two subjects showed significant symptom change for five items, and these subjects had three items (anxious/nervous/restless, irritable/angry/impatient, and hostile/aggressive) in common. These two subjects might satisfy the DSM-IV diagnostic criteria for PMDD if they were observed for several menstrual cycles. The items of depressed mood, anxious/nervous/restless, irritable/angry/impatient, and more sexuality showed higher frequencies of change than the other items when both the 30% and 50% change criteria were applied, so these symptoms can be considered characteristic findings of premenstrual symptom change in this study. It is noteworthy that there were items of favorable change, such as increased enjoyment, increased well-being, more sexuality, and passionate.

Many studies of the possible etiologies of PMS have been conducted, and many etiological factors have been suggested. Studies concerning abnormalities of blood levels of gonadal hormones, prolactin, and aldosterone have been done steadily. However, study results have been contradictory because of variations in methodology. There have been contradictory reports about the serum E2 level and E/P ratio in the premenstrual phase of women with PMS. Some studies (36, 37) reported an elevated serum E2 level and E/P ratio, whereas others (38–40) reported no changes in the serum E2 level and E/P ratio. There have also been contradictory reports about the serum PG level in the premenstrual phase of women with PMS. Some (36, 37) reported a low serum PG level, and others reported no change in serum PG level (38, 39) or elevated serum PG level (41) in the premenstrual phase. In this study we did not find any correlation between the premenstrual symptom change and hormonal levels of E2 and PG or E/P ratio. Findings of this study are consistent with the opinion of Rubinow (42) that premenstrual syndrome defies simple explanatory models of hormonal excess or deficiency.

Limitations
In this study we compared the premenstrual phase with the postmenstrual phase to evaluate premenstrual symptom change on the DRF and the relationship between the BRPS score and serum E2 level. Because we defined the postmenstrual phase as the week after the cessation of menstruation, it is possible that the postmenstrual phase overlapped with the ovulatory period in subjects whose menstrual cycle was short and whose menstrual flow period was long, even though we selected subjects with regular menstrual cycles (25–35 days). Serum E2 level increases abruptly in the ovulatory period, and many women tend to show some change in mood and behavior around this period (34). Thus, when the postmenstrual phase overlaps with the ovulatory period, we cannot precisely evaluate premenstrual changes in symptoms. In this study only two subjects had both short cycle length (25–26 days) and long menstrual flow period (6–7 days). But it is desirable to exclude subjects whose postmenstrual phase may overlap with the ovulatory phase if possible. In this study we used the first day of menstruation as a menstrual cycle marker and estimated the ovulatory period based on cycle length. Although we selected subjects with a regular menstrual cycle length (25–35 days) to avoid the anovulatory cycle, it is desirable to confirm the ovulatory period by measuring basal body temperature or hormonal levels. To evaluate the relationship between psychopathology and the serum E2 level more precisely, it would have been better to measure the BPRS and serum E2 level more frequently. Although observation of at least two menstrual cycles is required to diagnose PMS (25–27), we observed only one menstrual cycle. In this study we used only the DRF to evaluate the change of emotional and behavioral symptoms, but the Nurses’ Observation Scale for Inpatient Evaluation (43) might have given a more comprehensive perspective to evaluate the changes in emotional and behavioral symptoms of hospital inpatients.

Despite the limitations of this study, the findings suggest that premenstrual exacerbation of symptoms in female schizophrenics may not be a worsening of schizophrenic symptoms but a concurrence of a specific syndrome characterized by a cluster of affective, behavioral, and somatic symptoms.

Therapeutic Implications
When symptoms change in female schizophrenics, close observation is required to evaluate whether the change is related to the menstrual cycle. Even after the change in symptoms is determined to be closely related to the menstrual cycle, most clinicians tend to consider the symptom change as a worsening of the schizophrenia or a treatment failure, so they tend to increase the dose of antipsychotic medication. But even when the psychotic symptoms are aggravated in the premenstrual phase, the aggravated symptoms are not alleviated by merely increasing the dose of antipsychotic medication in some patients (14, 15), so clinicians should consider various approaches before increasing the dose. Furthermore, clinicians should be aware that some female schizophrenics experience a specific syndrome characterized by affective, somatic, and behavioral symptoms in the premenstrual phase to better understand their patients and to choose more appropriate therapeutic interventions.

Received for publication March 14, 2000.

Revision received January 24, 2001.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

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