Tohoku J. exp. Med., 1975, 116, 81-86 A New Method for the Screening of Unidentified Complaints Syndrome in Pre-, Mid- and Post menopausal Women TETSURO ABE, NOBUAKI FURUHASHI, ICHIO OHASHI, MASAKUNI SUZUKI and TAKEJIRO MORITSUKA* Department of Obstetrics and Gynecology, Tohoku University School of Medicine, Sendai and Department of Obstetrics and Gynecology,* National Sendai Hospital, Sendai ABE, T., FURUHASHI, N., OHASHI, I., SUZUKI, M. and MORITSUKA, T. A New Method for the Screening of Unidentified Complaints Syndrome in Pre-, Midand Postmenopausal Women. Tohoku J. exp. Med., 1975, 116 (1), 81-86 - A new simple test for the screening of pre-, mid- and post-menopausal women with unidentified complaints overlaid by psychiatric disorders has been devised. This test is performed by intravenous injection of conjugated estrogen and by comparing Kupperman's menopausal indices before and after the injection. That is, the discriminant function between groups with and without psychiatric abnormalities was obtained from Kupperman's menopausal indices before and after intravenous injection of conjugated estrogen, and from this function was made a calculative differential diagnosis between the two groups. The calculative diagnosis agreed fairly well with the clinical diagnosis by the psychiatrist. climacteric symptoms; menopausal symptoms; discriminant function; conjugated estrogen; Kupperman's menopausal index It has been generally accepted that the basic treatment for the menopausal symptoms should include hormonal therapy designed to correct estrogen insuffi ciency and psychotherapy (Dilts et al. 1971; Kistner 1972). However, symptom atological and therapeutical analyses of the menopausal symptoms are not yet complete and need more precise and objective studies. Unidentified complaints syndrome has been defined as a group of symptoms composed of vague somatic complaints, such as hot flushes, sweats, chilly sensation, numbness, general malaise, dull headache, etc., without any identifiable objective signs accountable for the complaints. The authors administered conjugated estrogen to pre-, mid- and post-meno pausal women with the unidentified complaints syndrome in an attempts to differentiate the psychiatrically disordered cases among them according to the effect of conjugated estrogen on their symptoms. Receivad for publication. February 3, 1975. Reprint requests: Dr. Tetsuro Abe, Dept. of Ob/Gyn., Tohoku University School of Medicine, 1-1 Seiryo-machi, Sendai 980, Japan. 81
82 T. Abe et al. SUBJECTS AND METHODS Eighty six women with the unidentified complaints who showed no sign of either gynecological or any other somatic diseases were subjected to this study. First, they were requested to fill a questionnaire (Table 1) containing 11 items concern ing various kinds of symptoms, and on the basis of which Kupperman's menopausal index (Kupperman et al. 1959) was calculated. Then, the patients were given an intravenous injection of 20 mg of conjugated estrogen (Premarin) and the menopausal index was calculated again at 3 or 4 days after injection. Subsequently, they were entrusted to psychiatrists to determine the presence or absence of psychiatric abnormalities. They were divided into two groups, one with and the other without psychiatric abnormalities, accord ing to the diagnosis by the psychiatrists. A comparison was made between the two groups with respect to the effect of conjugated estrogen on the menopausal index. Secondly, the conjugated estrogen or placebo was injected intravenously into the women without psychiatric abnormalities in order to evaluate the effect of conjugated estrogen on the unidentified complaints by the double blind test, comparing menopausal indices before and after injection. TABLE 1. Questionnaire for the calculation of Kupperman's menopausal index Items representing symptoms are the same as in Kupperman's method (Kupperman 1959). EXPERIMENTAL RESULTS Of 86 women 17 were with psychiatric abnormalities and 69 without them. There was no significant difference in age between the two groups of the patients, as shown in Table 2. Psychiatric abnormalities included neurosis in 16 cases (94 %) and schizophrenia in 1 case (6%). Fig. 1 shows the menopausal indices calculated before and after administration of conjugated estrogen. The indices before administration are represented on the abscissa and those after administration on the ordinate. The psychiatrically abnormal group is indicated by the closed circles and the psychiatrically normal group by the open circles. The majority of the patients in the normal group
Screening of Unidentified Complaints in Menopausal Women 83 TABLE 2. Composition of the groups with and without psychiatric abnormalities of women complaining of the unidentified complaints as for the age Fig. 1. Effect of intravenous injection of conjugated estrogen on Kupperman's menopausal indices of women with the unidentified complaints. œ, psychiatrically abnormal group; ü, psychiatrically normal group. showed a decrease of the menopausal index after intravenous injection of conjugat ed estrogen, while most of the abnormal group showed little change. This difference in the reaction to the conjugated estrogen between the two groups was proved to be significant by the t-test (p<0.01) (Table 3). With Kupperman's menopausal indices determined before and after admin istration of conjugated estrogen, expressed as variables X0 and X1, respectively, a discriminant function between the two groups was calculated by the following formula: The values of X0 and Xl of each woman were applied to this formula. When Y was positive, she was classified into the normal group ; when negative, she was classified into the abnormal group. This calculative diagnosis was consistent with the clinical one in about 88.2% of the cases of the abnormal group and about 75.4% of the cases of the normal group.
84 T. Abe et al. TABLE 3. Factor analysis, with F-ratio, of the difference in Kupperman's menopausal indices between before and after administration of the psychiatrically abnormal and normal groups P, factor of group difference between the psychiatrically abnormal (Pl) and normal (P2) group; B (P), individual difference in Pl and P2; W, factor of time difference between before (W1) and after (W2) admin istration of conjugated estrogen; E, residue. * Significant difference at 1% level. In the next experiment, the patients without psychiatric abnormalities were given an intravenous injection of conjugated estrogen or placebo by the double blind method, in order to confirm the effect on the menopausal index. Fig. 2 shows the menopausal indices before and after intravenous injection: those before injection on the abscissa and those after injection on the ordinate. The closed circles indicate the conjugated estrogen group, and the open circles the placebo group. The results were analyzed by dividing the cases into two groups; one showed Fig. 2. Effect of intravenous injection of conjugated estrogen on Kupperman's menopausal indices of the psychiatrically normal group of women with the unidentified complaints. œ, conjugated estrogen-administered group; ü, placebo-administered group.
Screening of Unidentified Complaints in Menopausal Women 85 the menopausal index before intravenous injection less than 20, and the other showed the index of 20 or more. In the latter group, significant decreases of the index were observed after administration of conjugated estrogen (p<0.05 by t-test); while, in the former group, the conjugated estrogen did not exert any significant effect. DISCUSSION Although the basic treatment for the pre-, mid- and post-menopausal unidentified complaints has been thought to include hormonal therapy and psychotherapy (Dilts et al. 1971; Kistner 1972), indication of these therapies is not always clear at the moment. Only some, not all, of women complaining of the unidentified complaints seem to need psychotherapy. The presence or absence of psychiatric disorders is important for the choice of treatments because psychiatric treatments such as psychotherapy, rather than hormonal therapy, have to be primarily applied to the cases of women with psychiatric disorders. However, it is not easy for many busy physicians in gynecology to perform psychiatric examinations such as psychoanalysis, and a simple screening test for detection of psychiatric disorders is obviously useful for them. This is a reason why the author tried to devise a new method for screening psychiatrically disordered cases among women with unidentified complaints. On etiology of the menopausal symptoms, it has been said (titian 1972; Aitken et al. 1974) that the only symptom directly associated with the menopause is hot flushes and that other symptoms, such as depression, irritability, angina pectoris, insomnia and palpitation, are most likely of psychological origin. In the present study, the conjugated estrogen was proved, by the double blind test, to be strongly suggestive of exerting some specific effect for relief of the unidentified complaints of the pre-, mid- and post-menopausal women. However, since the physiological mechanism of the onset of menopausal symptom in relation to estrogen secretion has not yet been established at the moment, the significance of the decrease of Kupperman's menopausal index after intravenous injection of conjugated estrogen found in the cases of psychiatrically normal group should be studied in more detail in future. From the results of clinical evaluation of the author's new method for the screening of psychiatrically abnormal women (tentatively designated as 'Premarin test'), it was found that women diagnosed as having psychiatric disorders by the psychiatrist were screened by this method with about 88.2% accuracy. This suggests that the test is useful in actual clinical practice as a method for the screening of psychiatrically disordered cases among pre-, mid- and post menopausal women with unidentified complaints syndrome. References 1) Aitken, J.M., Davidson, A., England, P., Govan, A.D.T., Hart, D.M., Kelly, A., Rindsay, R. & Moffat, A. (1974) The relationship between menopausal vasomotor
86 T. Abe et al. symptoms and gonadotrophin excretion in urine after oophorectomy. J. Obstet. Gynec. Brit. Comm., 81, 150-154. 2) Dilts, P.V., Jr., Greene, J.W., Jr. & Roddick, J.W., Jr. (1971) Climacteric and menopause. In: Core Studies in Obstetrics and Gynecology, The Williams & Wilkins Co., Baltimore, p. 46. 3) Kistner, R.W. (1972) The menopause. In: Gynecology, Principles and Practice. 2nd ed., edited by R.W. Kistner, Year Book Medical Publishers, Inc., Chicago, p. 662. 4) Kupperman, H.S., Wetchler, B.B. & Blatt, M.H.G. (1959) Contemporary therapy of the menopausal syndrome. J. Amer. med. Ass., 171, 1627-1637. 5) Utian, W.H. (1972) The true clinical features of postmenopause and oophorectomy and their response to oestrogen therapy. S. Afr. med. J., 46, 732-737.