Archives of
Gynecology
Arch. Gynecol. 227, 341-347 (1979)
© J. F. Bergmann Verlag 1979
Studies with Clonldlne (Dlxarlt) in Menopausal Women A. E. Schindler 1, D. Miiller 1, E. Keller 1, R. G6ser ~, and F. Runkel 2 1Universitiits-Frauenklinik(Geseh~iftsffihrenderDirektor: Prof. Dr. H. A. Hirsch), SchleichstraBe 4, D-7400 Tiibingen,Federal Republic of Germany 2Dieckmann Arzneimittel,Klasingstrat3e 1-11, D-4800 Bielefeld,Federal Republic of Germany
Untersuehungen mlt Clonidln bel menopausalen Frauen Zusammenfassung. Bei 11 Frauen mit menopausaler Symptomatik wurde eine Behandlung mit 150 ~g Clonidin (Dixarit) tiiglich durchgef/ihrt. Die Beschwerden wurden mittels des Kupperman-Index erfal3t. Die Probandinnen ffihrten augerdem tiigliche Aufzeichnungen fiber die Zahl und das zeitliche Auftreten von Hitzewallungen. Vor und wiihrend der Therapie wurde Ostradiol- 17/3, LH, FSH und Prl im Plasma radioimmunologisch gemessen. Hitzewallungen nahmen w~ihrend der Therapie unabh/ingig vonder Tageszeit hochsignifikant ab (p < 0,001). Ebenso verbesserte sich der Kupperman-Index. Signifikante Puls- und Blutdruckver/inderungen wurden nicht beobachtet. Die Plasmahormone zeigten keine Ver~inderungen w~ihrend des Beobachtungszeitraums. Die Vertr/iglichkeit des Medikaments war gut. Bei Kontraindikationen ffir eine Ostrogenbehandlung stellt die Therapie der menopausalen Beschwerden mit Clonidin eine gute Alternative dar. Sehliisselwiirter: Menopause - Clonidin - Kupperman-Index - Plasmahormone Summary. Eleven women with menopausal symptoms were treated with 150 ~g Clonidine (Dixari0 daily. Before and during therapy, plasma estradiol-17/3, LH, FSH and prolactin levels were measured by specific radio-immunoassays. In addition, each patient recorded the number of hot flushes a day and symptoms were monitored by the Kupperman-index. A highly significant fall in the number of hot flushes by day and night occurred during therapy (t7 < 0.001) and the Kupperman-index similarly improved. Significant pulse and blood pressure changes were not noted and plasma hormone concentrations remained unaltered. Medication was well tolerated. Clonidine therapy would appear to be the treatment of choice for menopausal symptoms if estrogens are contraindicated. Key words: Menopause - Clonidine - Kupperman-index -- Plasma hormones Offprint requests to: Prof. Dr. A. E. Schindler (address see above)
0170-9925/79/0227/0341/$ 01.40
342
A.E. Schindler et al.
There is still controversy about the use of estrogens for treatment of menopausal symptoms because of a possible connection between estrogen therapy and cancer of the endometrium or breast (Schindler, 1977). Thus, several nonhormonal preparations have been evaluated (Lebherz, 1969; Erkkolla et al., 1973; Hauser and Wenner, 1974; Barr, 1975; Coope et al., 1978). One of these, clonidine [2-(2,6-dichlorophenylamino)2-imidazoline hydrochloride; Dixarit] was first used by Clayden (1972) for treatment of postmenopausal symptoms, having been found to be effective in low doses for migraine (Wilkinson, 1969; Zaimis and Harnington, 1969; Heathfield and Raiman, 1972; Shafar et al., 1972) and in high doses as an antihypertensive agent (MacDougall et al., 1970; Hoobler and Sagastome, 1971). There are only few (and conflicting) reports about the value of clonidine in the treatment of menopausal symptoms (Clayden, 1972; Williams, 1973; Clayden et al. 1974; Barr, 1975; Bolli and Simpson, 1975; Ylikorkola, 1975, Lindsay and Hart, 1978). The aim of this study was to obtain further information on the effectiveness ofclonidine treatment and to examine the effect of the drug on plasma hormone concentrations.
Methods Elevenwomenwereincludedin this study.The mean age was 50.9 years (range 34 to 68 years); the average weight was 71 kg (range 53 to 93 kg); and the averageheight was 163 cm (range 151 to 172 cm). In fiveof these women hysterectomy with bilateral salpingo-ophorectomyhad been done.
Fig. 1. Number ofhot flushesa weekobservedby patients during clonidinetherapy (n = 10).The unbroken line showsthe mean, the hatching 1 SD above and belowthe mean. Thep valuesreferto comparisonswith the results during the first week of clonidine therapy
Studies with Clonidine (Dixarit) in Menopausal Women
343
Treatment consisted of a total of 150 ~g of clonidine daily given in three divided doses. Plasma estradiol-17/3, LH, FSH and prolactin (Prl) were measured by specific radioimmunoassays (Friedrich et al., 1974; Joel et al., 1974) before and at 5, 9, and 12 weeks of clonidine therapy. Menopausal symptoms were evaluated before and at 5, 9, and 12 weeks of elonidine therapy by the Kupperman-index (Kupperman et al., 1953) and the patient was making a continuous record of the number of hot flushes herself by day and by night, One patient stopped therapy after four weeks. The data were examined statistically by the Student's t-test.
Results
As shown in Fig. 1 treatment produced a significant decrease in the number of hot flushes. Significant changes were also observed in the Kupperman-index as shown in Fig. 2. Pulse and blood pressure did not change significantly throughout the observation period (Table 1). The plasma estradiol- 17/3, LH, FSH and Prl levels also remained unchanged (Table 2). Two patients had high plasma estradiol values and normal LH and FSH concentrations. The numer of hot flushes diminished and the Kupperman-index fell with treatment regardless of differences in plasma hormone values. Neither hormone levels nor response to treatment appeared to have any relation to previous oophorectomy. Menopausal Index
50
40
~
20
+SD
10 -SD
0
I
I
I
5 ~
9
12 ,
Weeks of treatment
_ p
Gynecology
Arch. Gynecol. 227, 341-347 (1979)
© J. F. Bergmann Verlag 1979
Studies with Clonldlne (Dlxarlt) in Menopausal Women A. E. Schindler 1, D. Miiller 1, E. Keller 1, R. G6ser ~, and F. Runkel 2 1Universitiits-Frauenklinik(Geseh~iftsffihrenderDirektor: Prof. Dr. H. A. Hirsch), SchleichstraBe 4, D-7400 Tiibingen,Federal Republic of Germany 2Dieckmann Arzneimittel,Klasingstrat3e 1-11, D-4800 Bielefeld,Federal Republic of Germany
Untersuehungen mlt Clonidln bel menopausalen Frauen Zusammenfassung. Bei 11 Frauen mit menopausaler Symptomatik wurde eine Behandlung mit 150 ~g Clonidin (Dixarit) tiiglich durchgef/ihrt. Die Beschwerden wurden mittels des Kupperman-Index erfal3t. Die Probandinnen ffihrten augerdem tiigliche Aufzeichnungen fiber die Zahl und das zeitliche Auftreten von Hitzewallungen. Vor und wiihrend der Therapie wurde Ostradiol- 17/3, LH, FSH und Prl im Plasma radioimmunologisch gemessen. Hitzewallungen nahmen w~ihrend der Therapie unabh/ingig vonder Tageszeit hochsignifikant ab (p < 0,001). Ebenso verbesserte sich der Kupperman-Index. Signifikante Puls- und Blutdruckver/inderungen wurden nicht beobachtet. Die Plasmahormone zeigten keine Ver~inderungen w~ihrend des Beobachtungszeitraums. Die Vertr/iglichkeit des Medikaments war gut. Bei Kontraindikationen ffir eine Ostrogenbehandlung stellt die Therapie der menopausalen Beschwerden mit Clonidin eine gute Alternative dar. Sehliisselwiirter: Menopause - Clonidin - Kupperman-Index - Plasmahormone Summary. Eleven women with menopausal symptoms were treated with 150 ~g Clonidine (Dixari0 daily. Before and during therapy, plasma estradiol-17/3, LH, FSH and prolactin levels were measured by specific radio-immunoassays. In addition, each patient recorded the number of hot flushes a day and symptoms were monitored by the Kupperman-index. A highly significant fall in the number of hot flushes by day and night occurred during therapy (t7 < 0.001) and the Kupperman-index similarly improved. Significant pulse and blood pressure changes were not noted and plasma hormone concentrations remained unaltered. Medication was well tolerated. Clonidine therapy would appear to be the treatment of choice for menopausal symptoms if estrogens are contraindicated. Key words: Menopause - Clonidine - Kupperman-index -- Plasma hormones Offprint requests to: Prof. Dr. A. E. Schindler (address see above)
0170-9925/79/0227/0341/$ 01.40
342
A.E. Schindler et al.
There is still controversy about the use of estrogens for treatment of menopausal symptoms because of a possible connection between estrogen therapy and cancer of the endometrium or breast (Schindler, 1977). Thus, several nonhormonal preparations have been evaluated (Lebherz, 1969; Erkkolla et al., 1973; Hauser and Wenner, 1974; Barr, 1975; Coope et al., 1978). One of these, clonidine [2-(2,6-dichlorophenylamino)2-imidazoline hydrochloride; Dixarit] was first used by Clayden (1972) for treatment of postmenopausal symptoms, having been found to be effective in low doses for migraine (Wilkinson, 1969; Zaimis and Harnington, 1969; Heathfield and Raiman, 1972; Shafar et al., 1972) and in high doses as an antihypertensive agent (MacDougall et al., 1970; Hoobler and Sagastome, 1971). There are only few (and conflicting) reports about the value of clonidine in the treatment of menopausal symptoms (Clayden, 1972; Williams, 1973; Clayden et al. 1974; Barr, 1975; Bolli and Simpson, 1975; Ylikorkola, 1975, Lindsay and Hart, 1978). The aim of this study was to obtain further information on the effectiveness ofclonidine treatment and to examine the effect of the drug on plasma hormone concentrations.
Methods Elevenwomenwereincludedin this study.The mean age was 50.9 years (range 34 to 68 years); the average weight was 71 kg (range 53 to 93 kg); and the averageheight was 163 cm (range 151 to 172 cm). In fiveof these women hysterectomy with bilateral salpingo-ophorectomyhad been done.
Fig. 1. Number ofhot flushesa weekobservedby patients during clonidinetherapy (n = 10).The unbroken line showsthe mean, the hatching 1 SD above and belowthe mean. Thep valuesreferto comparisonswith the results during the first week of clonidine therapy
Studies with Clonidine (Dixarit) in Menopausal Women
343
Treatment consisted of a total of 150 ~g of clonidine daily given in three divided doses. Plasma estradiol-17/3, LH, FSH and prolactin (Prl) were measured by specific radioimmunoassays (Friedrich et al., 1974; Joel et al., 1974) before and at 5, 9, and 12 weeks of clonidine therapy. Menopausal symptoms were evaluated before and at 5, 9, and 12 weeks of elonidine therapy by the Kupperman-index (Kupperman et al., 1953) and the patient was making a continuous record of the number of hot flushes herself by day and by night, One patient stopped therapy after four weeks. The data were examined statistically by the Student's t-test.
Results
As shown in Fig. 1 treatment produced a significant decrease in the number of hot flushes. Significant changes were also observed in the Kupperman-index as shown in Fig. 2. Pulse and blood pressure did not change significantly throughout the observation period (Table 1). The plasma estradiol- 17/3, LH, FSH and Prl levels also remained unchanged (Table 2). Two patients had high plasma estradiol values and normal LH and FSH concentrations. The numer of hot flushes diminished and the Kupperman-index fell with treatment regardless of differences in plasma hormone values. Neither hormone levels nor response to treatment appeared to have any relation to previous oophorectomy. Menopausal Index
50
40
~
20
+SD
10 -SD
0
I
I
I
5 ~
9
12 ,
Weeks of treatment
_ p
