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Transdermal oestrogen replacement therapy in a Finnish population
Mururitas. 13 (WI)
275-181
275
Elsevier Scientific Publishers Mand Ltd. MAT 00629
Transdemal oestrogen replacement therapy in a IFinnish population R. Erkkolaa, P. Holmab, T. J&vi’, S. Nunmid, R. Pumonene, T. Raudaskoski’; K. Rehng, M. Ryyn5nenh, P. Sip%‘, E. Tunkeloj, A. Virkkunen’, T. Virtavuo’ and 0. Ylikorkala” aDepurmwnt of Obstetrics und Gynaecology. University Central Hospitul. Tub: “C’ntral Hospital of Cimra! lGnhm4 +&sky&: ‘Titra L.fhri; &mkunta Central Hospital, Pori: eUniversity Central Hospital, T-e; fGjweko, Ouiu; EKotka Cmtral HospitaI. Kotka: hUniversity Central Hospital. Kuopio; i Universiiy Cemrul Iiaspimi. O&t; &ou~h Ostrobothnia Central Hospital, Seimijoki; ‘Kahuu Central Hospital @bani: ‘Twun Gywkok@hkus. Turku, mUniversity Central Hosgital, Helsinki ( Finkmd)
(Received 8 October 1990, revision received II January 1991; accepted 12 January 1991)
In an open, multicentre study, transdermal administration of oestradiol ( E2) by means of skin patches was investigated in a Finnish patient population suffering from typical post-menopausal symptoms. A total of 249 women applied a patch twice weekly for 6 months. Whereas 85% of the subjects were experiencing hot flushes and %3.5%sweating before therapy, only 5.7% and I 1.8%. respectively, reported LW symptoms at the end of the trial. Furthermore. 97.6%. 95.7% and 94.8% of the subjects reported that depression, headache and sleep disturbances, respectively, had disappeared during therapy. Skin irritation occurred in 18.2% of these predominantly fair-skinned women. Frequent sauna bathing did not interfere with the patch therapy. General acceptance of the treatment was excellent, 84.8% of the patien*s completing the treatment, of whom 78% were willing to continue the treatment after the trial. These rest&s show that transdd administration of Ez is effective in relieving post-menopausal symptoms. Local tolerability was good and the majority of the patients considered the transdermai treatment to be superior to their previous oral replacement therapy. [Key wordsz Oestrogen replacement therapy. Post-menopause. Transdertnal administration )
As in other countries, the use of oestrogen replacement therapy (ERT) in Finland has increased tremendously over the past two decades. The reasons for this are obvious - its success in alleviating subjectively unpleas;int post-menopausal symptoms and an enhanced awarenessof its general health advantages. Formerly,ERT was ad-
ministeredvia the oral route. One of the first reports on transdermalERT using a Coyeqnut&n#
IO: Dr Risto Erkkola. Department of Obstetrics and Gynaecoiogy. University Cenrral
Hospital. SF 20!!20 Turku, Finland. 037&5122#1/503.50 0 1931 Elsevier !ScientifE Publishers Ireland Ltd. Printed and Publishul in imhtnd
276
17&oestradiol (E2) releasing patch was published in 1983 [ 1J. Since the oestrogen patch became available in Finland at the end of 1988, this means of administration has rapidIy gained popularity, although some concerns regarding its acceptability have been expressed. The Finnish population has two peculiar features as regards transdermal treatment, first, the fair, sensitive quality of the skin and, second, the traditional habit of sauna bathing at ambient temperatures of between 78°C and fOO*C.The latter practice was thought to interfere with the use of patches or even render them ineffective. This open, multicentre study was accordingly designed to investigate the efficacy and tolerability of transdermal oestrogen replacement therapy (TERT) in a Finnish population. Subjects and methods
Thirteen gynaecologists working in private clinics all over Finland participated in the study. The study population consisted of 249 women, whose physical characteristics are shown in Table I. All volunteered to participate in the trial, which was approved by the local ethical committees. None of the subjects had any known contraindications to the use of oestrogen or progestogen. The average duration of their post-menopausal symptoms was 4.0 f 4.4 years (mean f S.D., range O-34 years). Within the sample, 120 women (48.2%) had undergone hysterectomy and 186 (74.7%) had used oral ERT previously. In two subjects, oral ERT had previously been discontinued because of elevated liver transaminase levels. The post-menopausal women included in the study had either been treated previously (but had received no treatment for at least one month), or were new patients in whom the progestogen challenge test was negative. Normal contraindications for oestrogen substitution therapy were taken into consideration. Patients rec&ing other concomitant hormone treatment, or who had had a history of active skin disease, heart failure, severe hypertension or previous unopposed oestrogen treatment, were excluded. TERT was administered in the form of E2-releasing patches (Estraderm, CibaGeigy, Basle, Switzerland). The patches were applied twice week!y on the buttocks or hips. Patients having one fixed day for sauna bathing each week were advised to change their patch on that day, removing the old one before the sauna and applying
TABLE I CHARAaERISTICS
Age (van) Weight (kg) Height (cm)
OF THE STUDY POPULATION
(n = 249)
Mean
SD.
Range
51.9 65.9 162.8
5.2 9.9 5.4
3% 70 47- 95 150-176
a new one afterwards on dry skin. Women taking saunas more often were then advised to remove the patch temporarily and to apply it again afterwards on dry skin. Patches were not taken off during normal baths, showers or swimming. TERT was initiated with patches releasing 50 &24 h. The dose was then either decreased to 25 &24 h or increased to 100 pgI24 h if needed. The main reason for decreasing the dose was breast tenderness. while hot flushes and sweating were the reasons for increasing it. In addition, all the participants received 10 mg of medroxyprogesterone acetate (MPA, Provera. Upjohn) for the first 12 days of each calendar month to induce withdrawal bleeding. The MPA dose was aiso individually adjusted between 5 mg and 20 mg. The main reasons for dose reduction were nausez, breast tenderness and headache, while it was increased where withdrawal bleeding was absent. In hysterectomized subjects, the ‘highest dose of MPA was 10 mg for 12 days. All the participants were interviewed and underwent physical examination, including breast palpation, before the trial and after the first, third and sixth months of TERT. Weight and blood pressure were also monitored at each visit. The data were statistically evaluated using the analysis of variance (ANOVA) supplied in the BMDP (Biomedical Computer Programs) Statistical Software Package [2]. The effect of treatment on the number of hot flushes was analyzed by ANOVA and the baseline values were compared with the values at each visit using the f-test for paired data. Non-parametric data, such as those on treatment effect, were analyzed by Friedman’s ANOVA and the differences between baseline values and those at each visit by means of the Wilcoxon test. The trial was conducted in accordance with the Helsinki Declaration and approved by the local ethical committees. The informed verbal consent of all the participants was obtained.
The results relate to all subjects remaining in the study at the time of each interview. of the initial 249 participants, 236 continued until the end of the first month, 217 until the end of the third month and 211 subjects completed the full 6-month study period. Efficacy Prior to receiving TERT, the subjects had experienced an average of 5.2 f 0.3 (SE-M., range O-25) hot flushes per day. Subjective assessments of hot flushes and of sweating before and during TERT are shown in Figs. 1 and 2, respectively. Both decreased highly significantly (P < 0.001) during treatment. The average number of (lushes per day decreased to 0.62 f 0.10 by the first visit, to 0.19 * 0.05 by the second visit and, finally, to 0.13 f 0.04 by the third visit (P < 0.001 in relation to the baseline level). After 6 months of treatment the maximum number of flushes per day experienced by any of the subjects was five. Furthermore, the number of subjective reports of depression, headache and sleep disturbances decreased significantly. as can be seen from Table II. At the end of the study 85.4% of the subjects were using the 50-&24 h patch. while 8% had changed to the 25-pg patch and 6.6% to the lOO-pg patch. The MPA
278
Fig. I. &cumncc of hot iIusks Wore and during tramdenml acstrop
rqhemnt
therapy.
dose was lowered in 6 and raised in 12 subm, while 192 (91%) pdents used the initial IO mg dose throughout the trial. At these do&s bleeding among nonhystcrectomkd women was regular in 82.7%ofcases,but it was absent in lo”! of the women. In all cases where there was irreguIaror breakthrough bkcding, endcnctrial biopgicswere obtained using either a Vabra or Pistokt SuctjoIlctuette, or by means of conventional dilatation and curct?age. No cases of hrpetptasio were observed. After six months of therapy the mean duration of bkeding was 4.8 days
w --90 10 70 (0 I 40 a0 10 10
0
TABLE II PREVALdWCE OF lQST-MENOPAUSAL SYMFKMM AS PERCENTAGES OF THE STUDY lQPUIATw)IJ UEFORE AND DURING TRANSDERMAL OESTROGEN REPLACEMENT’
lP < 0.001.
(S.EM f 02), the &ensity being mild Tbemeanrlayofonsetofbkdingwasday m-tablet.
in 39.2% and moderate
in 55.7% of cases. 13.1 (S.E.M. A 0.3)afterintakeofthe
As mhmal above, 38 (15.2%) of the women discontinued the treatment. Table III shmrs the nunkrs aud their reasons. Skin irritation was the most common cause of discontinuation, there being 22 cases (8.8%). In addition, irritation which did not ~to~n~~~was~by4osubjects(16.2%)attheendofthefi~t 11188t&44 sub&c& (l&s%) at the end of the third month, and 39 subjects (18.2%)
-NS
FOR DISCOIUTINUATION OF TRANSDERMAL
OBI-ROGEN
0.4 8.8 2.8 o-4 2.a
0 12 3 0
4 TOW
13
19
REPLACEMENT
6
if3
280
Fig. 3. Occurrence and severity of skin irritation during trmsdermal oestrogen replacement therapy.
at the end of the study. Figure 3 shows the severity of such skin irritation. Adhesion of the patches was good or excellent in the majority of the patients. Side efkcts associated with the progestogen, such as headache, palpitations, oedema,weight iTncrease and breast discomfort,were the second commonest adverse reactionsand were experiencedby 7 (2.8%)of the subjects. One patient discontinued the tre”r;tment mainly because of technical difficulties encountered in using the patch. Other, varied reasons, such as amenorrhoea, irregular bleeding, poor patch adherence, weight increase, rises in blood pressure and general discomfort leading to discontinuation of the treatment were reported by 7 subjects. The two subjects who had previously had elevated transaminase levels when receiving oral oestrogen substitution therapy showed low and stable transaminase levels during TERT. Of the women who completed the study, 162 (779%) considered TERT to be superior to their previous treatment and intended to use it in the future.Thirty-three(15.9%)preferredto change back to their previous oral therapy, while 13 (6%) did not wish to receive ERT in any form. Dlloll
The delivery of oestrogen through the skin has recently been arousing growing interest as a means of administering ERT [ 1,3,4]. The main disadvantage of oral therapy is that the first-pass metabolism of oestrogen in the liver leads to unphysiological hormone concentrations in the systemic circulation and has undesirable eff’ectson hepatic functions. Among our patients, two women had in fact had elevated transaminase activity during conventional oral therapy, whem during TERT this remainedat the normal level, The treatment providedexcellent subjective relief of post-menopausal symptoms in this study. While more than 80%of our subjects had experienced hot flushes and
sweating prior to treatment, the proportion reporting these symptoms had fallen to around 20% at the end of the first month and to only about IO%at the end of 6 months of patch therapy. Similar results were observed by Padwick et al, [3] with a NJ-ergpatch. These investigators reported that lUL9O’X of flushes were suppressed by the end of the second and third treatment cycles. Steingold et al. [4] concluded that the efkct was dose-related and at the highest daily dose of 200 pg they reported a 91% reduction in the number of hot flushes. even during the first cycle. Place et al. [5], using a IO&~ patch. observed no difference in efficacy in comparison with 0.625 or I.25 mglday of conjugated oestrogens. In our study, the occurrence of headache, depression. insomnia and sleep disturbances also decreased significantly during the treatment. Our results thus confirm earlier reports 1% Discontinuation rates of 14% due to skin irritation have previously been reported [3]. In a Finnish population, given the fair, dry and rather sensitive skin quality, a substantially higher rate of irritation might be expected. In fact, skin irritation wasexperienced by less than 20% of all participants and it led to discontinuation in only 8.8% of the subjects. The irritation rate is in accordance with pooled American data, where 24% of subjects experienced skin reactions, yet only 4% discontinued the therapy (61. Interestingly, Finnish sauna habits did not have any obvious negative effect on the acceptability or efficacy of the patch therapy. The other reasons for premature discontinuation of treatment were similar to those described in other studies [S]. Side effects were generally mild and the vast majority (7ll%) considered Erpatch therapy to be superior to their previous oral treatment. This in fact exceeds the 60% preference rate reported in an earlier study (61. In conclusion, TERT, in the form of an Ez-releasing patch, proved effective in alleviating subjective post-menopausal symptoms. The therapy was well tolerated and clearly represents a new, safe treatment modality for post-menopausal symptoms.
1
hufer LR. De Ftio LJ. Lu JKH. Me!drum DR. Eggena P. Sambhi MP. Hershman MJ. Judd HL. m @acement therapy by transdermal estradiol administration. Am J Obstet Gynecol 1983; 146: 53’538. 2 Dixon WJ, Brown MB. Engehnan L. Franc JW. Hill MA. Jennrich RI. Toporek JD. BMDP !Stati&al S&ware. Berkeleyz University of California Press. 1985. 3 Padwick ML, Endacott J. Whitehead MI. Efficy. acceptability. and metabolic elkcts of transdermal estmdbl in the management of postmenopausal women. Am J Obstet Gynecol 1985; 152: 1085-l 106. 4 -gold KA. La&r L. Chetkowski RJ, Ds Fazio JD. Matt DW. Meldrum DR. Judd HJ. TreatI estradiol administration. J Clin Endocrinol Metab 1985: 61: mentofhotflashcswithtran&rma 627--632. 5 Piace VA. Powers M. Da&y PE. ym.: A double blind comparative study of estraderm and premarin postmenopausal symptoms. Am J Obstet Gynecol 198% 152: 1092--1099. inam&olationof estradiol overall saCety profile. Am J Ohstet Gynecol 1987: 156: 6 Utian WH: -l-m 1335-1338.
275-181
275
Elsevier Scientific Publishers Mand Ltd. MAT 00629
Transdemal oestrogen replacement therapy in a IFinnish population R. Erkkolaa, P. Holmab, T. J&vi’, S. Nunmid, R. Pumonene, T. Raudaskoski’; K. Rehng, M. Ryyn5nenh, P. Sip%‘, E. Tunkeloj, A. Virkkunen’, T. Virtavuo’ and 0. Ylikorkala” aDepurmwnt of Obstetrics und Gynaecology. University Central Hospitul. Tub: “C’ntral Hospital of Cimra! lGnhm4 +&sky&: ‘Titra L.fhri; &mkunta Central Hospital, Pori: eUniversity Central Hospital, T-e; fGjweko, Ouiu; EKotka Cmtral HospitaI. Kotka: hUniversity Central Hospital. Kuopio; i Universiiy Cemrul Iiaspimi. O&t; &ou~h Ostrobothnia Central Hospital, Seimijoki; ‘Kahuu Central Hospital @bani: ‘Twun Gywkok@hkus. Turku, mUniversity Central Hosgital, Helsinki ( Finkmd)
(Received 8 October 1990, revision received II January 1991; accepted 12 January 1991)
In an open, multicentre study, transdermal administration of oestradiol ( E2) by means of skin patches was investigated in a Finnish patient population suffering from typical post-menopausal symptoms. A total of 249 women applied a patch twice weekly for 6 months. Whereas 85% of the subjects were experiencing hot flushes and %3.5%sweating before therapy, only 5.7% and I 1.8%. respectively, reported LW symptoms at the end of the trial. Furthermore. 97.6%. 95.7% and 94.8% of the subjects reported that depression, headache and sleep disturbances, respectively, had disappeared during therapy. Skin irritation occurred in 18.2% of these predominantly fair-skinned women. Frequent sauna bathing did not interfere with the patch therapy. General acceptance of the treatment was excellent, 84.8% of the patien*s completing the treatment, of whom 78% were willing to continue the treatment after the trial. These rest&s show that transdd administration of Ez is effective in relieving post-menopausal symptoms. Local tolerability was good and the majority of the patients considered the transdermai treatment to be superior to their previous oral replacement therapy. [Key wordsz Oestrogen replacement therapy. Post-menopause. Transdertnal administration )
As in other countries, the use of oestrogen replacement therapy (ERT) in Finland has increased tremendously over the past two decades. The reasons for this are obvious - its success in alleviating subjectively unpleas;int post-menopausal symptoms and an enhanced awarenessof its general health advantages. Formerly,ERT was ad-
ministeredvia the oral route. One of the first reports on transdermalERT using a Coyeqnut&n#
IO: Dr Risto Erkkola. Department of Obstetrics and Gynaecoiogy. University Cenrral
Hospital. SF 20!!20 Turku, Finland. 037&5122#1/503.50 0 1931 Elsevier !ScientifE Publishers Ireland Ltd. Printed and Publishul in imhtnd
276
17&oestradiol (E2) releasing patch was published in 1983 [ 1J. Since the oestrogen patch became available in Finland at the end of 1988, this means of administration has rapidIy gained popularity, although some concerns regarding its acceptability have been expressed. The Finnish population has two peculiar features as regards transdermal treatment, first, the fair, sensitive quality of the skin and, second, the traditional habit of sauna bathing at ambient temperatures of between 78°C and fOO*C.The latter practice was thought to interfere with the use of patches or even render them ineffective. This open, multicentre study was accordingly designed to investigate the efficacy and tolerability of transdermal oestrogen replacement therapy (TERT) in a Finnish population. Subjects and methods
Thirteen gynaecologists working in private clinics all over Finland participated in the study. The study population consisted of 249 women, whose physical characteristics are shown in Table I. All volunteered to participate in the trial, which was approved by the local ethical committees. None of the subjects had any known contraindications to the use of oestrogen or progestogen. The average duration of their post-menopausal symptoms was 4.0 f 4.4 years (mean f S.D., range O-34 years). Within the sample, 120 women (48.2%) had undergone hysterectomy and 186 (74.7%) had used oral ERT previously. In two subjects, oral ERT had previously been discontinued because of elevated liver transaminase levels. The post-menopausal women included in the study had either been treated previously (but had received no treatment for at least one month), or were new patients in whom the progestogen challenge test was negative. Normal contraindications for oestrogen substitution therapy were taken into consideration. Patients rec&ing other concomitant hormone treatment, or who had had a history of active skin disease, heart failure, severe hypertension or previous unopposed oestrogen treatment, were excluded. TERT was administered in the form of E2-releasing patches (Estraderm, CibaGeigy, Basle, Switzerland). The patches were applied twice week!y on the buttocks or hips. Patients having one fixed day for sauna bathing each week were advised to change their patch on that day, removing the old one before the sauna and applying
TABLE I CHARAaERISTICS
Age (van) Weight (kg) Height (cm)
OF THE STUDY POPULATION
(n = 249)
Mean
SD.
Range
51.9 65.9 162.8
5.2 9.9 5.4
3% 70 47- 95 150-176
a new one afterwards on dry skin. Women taking saunas more often were then advised to remove the patch temporarily and to apply it again afterwards on dry skin. Patches were not taken off during normal baths, showers or swimming. TERT was initiated with patches releasing 50 &24 h. The dose was then either decreased to 25 &24 h or increased to 100 pgI24 h if needed. The main reason for decreasing the dose was breast tenderness. while hot flushes and sweating were the reasons for increasing it. In addition, all the participants received 10 mg of medroxyprogesterone acetate (MPA, Provera. Upjohn) for the first 12 days of each calendar month to induce withdrawal bleeding. The MPA dose was aiso individually adjusted between 5 mg and 20 mg. The main reasons for dose reduction were nausez, breast tenderness and headache, while it was increased where withdrawal bleeding was absent. In hysterectomized subjects, the ‘highest dose of MPA was 10 mg for 12 days. All the participants were interviewed and underwent physical examination, including breast palpation, before the trial and after the first, third and sixth months of TERT. Weight and blood pressure were also monitored at each visit. The data were statistically evaluated using the analysis of variance (ANOVA) supplied in the BMDP (Biomedical Computer Programs) Statistical Software Package [2]. The effect of treatment on the number of hot flushes was analyzed by ANOVA and the baseline values were compared with the values at each visit using the f-test for paired data. Non-parametric data, such as those on treatment effect, were analyzed by Friedman’s ANOVA and the differences between baseline values and those at each visit by means of the Wilcoxon test. The trial was conducted in accordance with the Helsinki Declaration and approved by the local ethical committees. The informed verbal consent of all the participants was obtained.
The results relate to all subjects remaining in the study at the time of each interview. of the initial 249 participants, 236 continued until the end of the first month, 217 until the end of the third month and 211 subjects completed the full 6-month study period. Efficacy Prior to receiving TERT, the subjects had experienced an average of 5.2 f 0.3 (SE-M., range O-25) hot flushes per day. Subjective assessments of hot flushes and of sweating before and during TERT are shown in Figs. 1 and 2, respectively. Both decreased highly significantly (P < 0.001) during treatment. The average number of (lushes per day decreased to 0.62 f 0.10 by the first visit, to 0.19 * 0.05 by the second visit and, finally, to 0.13 f 0.04 by the third visit (P < 0.001 in relation to the baseline level). After 6 months of treatment the maximum number of flushes per day experienced by any of the subjects was five. Furthermore, the number of subjective reports of depression, headache and sleep disturbances decreased significantly. as can be seen from Table II. At the end of the study 85.4% of the subjects were using the 50-&24 h patch. while 8% had changed to the 25-pg patch and 6.6% to the lOO-pg patch. The MPA
278
Fig. I. &cumncc of hot iIusks Wore and during tramdenml acstrop
rqhemnt
therapy.
dose was lowered in 6 and raised in 12 subm, while 192 (91%) pdents used the initial IO mg dose throughout the trial. At these do&s bleeding among nonhystcrectomkd women was regular in 82.7%ofcases,but it was absent in lo”! of the women. In all cases where there was irreguIaror breakthrough bkcding, endcnctrial biopgicswere obtained using either a Vabra or Pistokt SuctjoIlctuette, or by means of conventional dilatation and curct?age. No cases of hrpetptasio were observed. After six months of therapy the mean duration of bkeding was 4.8 days
w --90 10 70 (0 I 40 a0 10 10
0
TABLE II PREVALdWCE OF lQST-MENOPAUSAL SYMFKMM AS PERCENTAGES OF THE STUDY lQPUIATw)IJ UEFORE AND DURING TRANSDERMAL OESTROGEN REPLACEMENT’
lP < 0.001.
(S.EM f 02), the &ensity being mild Tbemeanrlayofonsetofbkdingwasday m-tablet.
in 39.2% and moderate
in 55.7% of cases. 13.1 (S.E.M. A 0.3)afterintakeofthe
As mhmal above, 38 (15.2%) of the women discontinued the treatment. Table III shmrs the nunkrs aud their reasons. Skin irritation was the most common cause of discontinuation, there being 22 cases (8.8%). In addition, irritation which did not ~to~n~~~was~by4osubjects(16.2%)attheendofthefi~t 11188t&44 sub&c& (l&s%) at the end of the third month, and 39 subjects (18.2%)
-NS
FOR DISCOIUTINUATION OF TRANSDERMAL
OBI-ROGEN
0.4 8.8 2.8 o-4 2.a
0 12 3 0
4 TOW
13
19
REPLACEMENT
6
if3
280
Fig. 3. Occurrence and severity of skin irritation during trmsdermal oestrogen replacement therapy.
at the end of the study. Figure 3 shows the severity of such skin irritation. Adhesion of the patches was good or excellent in the majority of the patients. Side efkcts associated with the progestogen, such as headache, palpitations, oedema,weight iTncrease and breast discomfort,were the second commonest adverse reactionsand were experiencedby 7 (2.8%)of the subjects. One patient discontinued the tre”r;tment mainly because of technical difficulties encountered in using the patch. Other, varied reasons, such as amenorrhoea, irregular bleeding, poor patch adherence, weight increase, rises in blood pressure and general discomfort leading to discontinuation of the treatment were reported by 7 subjects. The two subjects who had previously had elevated transaminase levels when receiving oral oestrogen substitution therapy showed low and stable transaminase levels during TERT. Of the women who completed the study, 162 (779%) considered TERT to be superior to their previous treatment and intended to use it in the future.Thirty-three(15.9%)preferredto change back to their previous oral therapy, while 13 (6%) did not wish to receive ERT in any form. Dlloll
The delivery of oestrogen through the skin has recently been arousing growing interest as a means of administering ERT [ 1,3,4]. The main disadvantage of oral therapy is that the first-pass metabolism of oestrogen in the liver leads to unphysiological hormone concentrations in the systemic circulation and has undesirable eff’ectson hepatic functions. Among our patients, two women had in fact had elevated transaminase activity during conventional oral therapy, whem during TERT this remainedat the normal level, The treatment providedexcellent subjective relief of post-menopausal symptoms in this study. While more than 80%of our subjects had experienced hot flushes and
sweating prior to treatment, the proportion reporting these symptoms had fallen to around 20% at the end of the first month and to only about IO%at the end of 6 months of patch therapy. Similar results were observed by Padwick et al, [3] with a NJ-ergpatch. These investigators reported that lUL9O’X of flushes were suppressed by the end of the second and third treatment cycles. Steingold et al. [4] concluded that the efkct was dose-related and at the highest daily dose of 200 pg they reported a 91% reduction in the number of hot flushes. even during the first cycle. Place et al. [5], using a IO&~ patch. observed no difference in efficacy in comparison with 0.625 or I.25 mglday of conjugated oestrogens. In our study, the occurrence of headache, depression. insomnia and sleep disturbances also decreased significantly during the treatment. Our results thus confirm earlier reports 1% Discontinuation rates of 14% due to skin irritation have previously been reported [3]. In a Finnish population, given the fair, dry and rather sensitive skin quality, a substantially higher rate of irritation might be expected. In fact, skin irritation wasexperienced by less than 20% of all participants and it led to discontinuation in only 8.8% of the subjects. The irritation rate is in accordance with pooled American data, where 24% of subjects experienced skin reactions, yet only 4% discontinued the therapy (61. Interestingly, Finnish sauna habits did not have any obvious negative effect on the acceptability or efficacy of the patch therapy. The other reasons for premature discontinuation of treatment were similar to those described in other studies [S]. Side effects were generally mild and the vast majority (7ll%) considered Erpatch therapy to be superior to their previous oral treatment. This in fact exceeds the 60% preference rate reported in an earlier study (61. In conclusion, TERT, in the form of an Ez-releasing patch, proved effective in alleviating subjective post-menopausal symptoms. The therapy was well tolerated and clearly represents a new, safe treatment modality for post-menopausal symptoms.
1
hufer LR. De Ftio LJ. Lu JKH. Me!drum DR. Eggena P. Sambhi MP. Hershman MJ. Judd HL. m @acement therapy by transdermal estradiol administration. Am J Obstet Gynecol 1983; 146: 53’538. 2 Dixon WJ, Brown MB. Engehnan L. Franc JW. Hill MA. Jennrich RI. Toporek JD. BMDP !Stati&al S&ware. Berkeleyz University of California Press. 1985. 3 Padwick ML, Endacott J. Whitehead MI. Efficy. acceptability. and metabolic elkcts of transdermal estmdbl in the management of postmenopausal women. Am J Obstet Gynecol 1985; 152: 1085-l 106. 4 -gold KA. La&r L. Chetkowski RJ, Ds Fazio JD. Matt DW. Meldrum DR. Judd HJ. TreatI estradiol administration. J Clin Endocrinol Metab 1985: 61: mentofhotflashcswithtran&rma 627--632. 5 Piace VA. Powers M. Da&y PE. ym.: A double blind comparative study of estraderm and premarin postmenopausal symptoms. Am J Obstet Gynecol 198% 152: 1092--1099. inam&olationof estradiol overall saCety profile. Am J Ohstet Gynecol 1987: 156: 6 Utian WH: -l-m 1335-1338.