Ž .International Journal of Gynecology & Obstetrics 73 2001 169�171

Brief communication

Modification of vasomotor symptoms after varioustreatment modalities in the postmenopause

S. Carranza-Lira�, E. Cortes-Fuentes´Gynecologic Endocrinology Ser�ice, Hospital de Gineco-Obstetricia ‘Luis Castelazo Ayala’, Instituto Mexicano del Seguro

Social, Mexico D.F., Mexico

Received 11 May 2000; received in revised form 29 June 2000; accepted 27 July 2000

Keywords: Conjugated equine estrogens; Clonidine; Veralipride; Propranolol; Placebo; Vasomotor symptoms

Ž .Vasomotor symptoms VS are a common cli-� �macteric complaint 1 . Several mechanisms seem

� �to be responsible for this disorder 2,3 . Manydrugs have been used with variable efficiency in

� �its control 4 .The objective of this study was to evaluate the

efficiency of various treatments in postmeno-pausal patients with VS.

Seventy-five healthy postmenopausal womenŽ .�1�5 years were studied. None of them hadreceived hormones nor any other treatment for

Ž .hot-flushes HF . FSH and estradiol levels were in

� Corresponding author. Puente de piedra 150-422 Torre I,Col. Toriello Guerra, C.P. 14050, Mexico D.F. Tel.: �525-´5284657; fax: �525-5284657.

Ž .E-mail address: scarranzal@mexis.com S. Carranza-Lira .

Žthe postmenopausal range. All had VS HF,.sweating , and insomnia. The following variables

were considered: frequency of presentation of HFŽ . Žnumber of HF per day ; intensity of HF with ananalogous visual scale, considering zero as

.absence and 10 as the maximum intensity ; dura-Ž .tion time in minutes that the HF last ; insomnia

Žand the sweating that accompanies the HF pre-.sent or absent . All these were investigated by a

physician blinded to the type of treatment theywere receiving.

Ž .Five groups 15 patient each , received orallyŽ .one of the following treatments: i conjugated

Ž . Žequine estrogens CEE , 0.625 mg a day hyster-.ectomized patients . Those with contraindication

for CEE, were randomly distributed in the otherŽ . Ž .four groups: ii clonidine, 0.10 mg every 12 h; iii

Ž .propranolol, 20 mg every 12 h; iv veralipride 100

0020-7292�01�$20.00 � 2001 International Federation of Gynecology and Obstetrics. All rights reserved.Ž .PII: S 0 0 2 0 - 7 2 9 2 0 0 0 0 3 3 2 - 5

( )S. Carranza-Lira, E. Cortes-Fuentes � International Journal of Gynecology & Obstetrics 73 2001 169�171´170

Table 1Differences in symptoms between several goups of patients according to the type of treatment

Estrogens Clonidine Propranolol Veralipride PlacebobMedian Range Median Range Median Range Median Range Median Range

aHot-flushes frequency 0 7� 3�20 6� 3�20 8 4�15 10�� 5�30 10 5�20Hot-flushes intensity 0 9�†† 5�10 7.6� 3.4�10 6.5†� 4.8�9.7 8.7� 2.8�9.8 7.4† 4.2�9.4Hot-flushes duration 0 4 1�30 2 0.7�20 3� 2�10 5�† 2�11 3† 1�10Insomnia presence 0 80% yes 87% yes 74% yes 93.3% yes 73.3% yes

20% no 13% no 26% no 6.7% no 26.7% noInsomnia frequency 0 4� 0�7 5�� 0�7 3� 0�7 4 0�7 3�� 0�7Sweating presence 0 100% yes 94% yes 100% yes 100% yes 93.3% yes

6% no 6.7% nobHot-flushes frequency 3 0�‡†‡ 0�3 1�‡�� 0�8 4‡‡ 1�10 2†� 0�10 5‡† 2�15

Hot-flushes intensity 3 0�††‡ 0�5.7 1.3�‡‡� 0�5 4.5†‡ 1�8.7 2.5†� 0�7.8 6.4‡‡ 1�8.4Hot-flushes duration3 0†‡†‡ 0�2 0.9†† 0�3 2‡†� 0.9�15 0.9†� 0�3 1‡ 0.9�8Insomnia presence 3 8% yes† 22% yes� 70% yes †�� 13.3% yes � 46.7% yes

92% no 78% no 30% no 86.6% no 53.3% noInsomnia frequency 3 0† 0�1 0† 0�2 2†† 0�7 0 0�1 0 0�6Sweating presence 3 100% no †† 8% yes †† 70% yes †† 33.3% yes 73.3% yes ††

92% no 30% no 66.6% no 26.7% no

a 0�baseline, 3� third month.bP values ��0.05, �0.06, †�0.01, ‡0.001. The data and the significances must be analyzed in each row separately. Hot flushes

frequency per day, Hot flushes duration in minutes, Insomnia freqencies in days per week. Of the 75 patients, 4 abandoned theŽtreatment, 1 in the group of CEE due to drug intolerance, 2 in the group of propranolol 1 because the patient did not wish to

.continue the treatment, and other due to lack of response , and one in the group of veralipride because of drug intolerance. In thegroups with clonidine and placebo there were no abandons.

mg daily, from Monday to Friday resting SaturdayŽ .and Sunday; and v placebo, a capsule each 12 h.

The Mann�Whitney U-test and Wilcoxon testwere used for statistic analysis. The HospitalEthics Committee approved the protocol and thepatients gave their consent to participate.

Ž .At the third month Table 1 , the frequency ofpresentation of HF was lower in CEE and cloni-dine groups when compared with propranolol,veralipride and placebo groups. The intensity ofHF was lower in CEE users, in comparison withthe other four groups, also when clonidine wascompared with the propranolol and placebo users.

The duration of HF was lower in CEE users,when compared with the other four groups. Inclonidine and veralipride groups it was lower whencompared with the propranolol group. The insom-nia presence was greater in the propranolol groupwhen compared with CEE, clonidine and ver-alipride groups. The frequency of presentation ofthe insomnia was greater in the propranolol group,when compared with CEE and clonidine groups.The presence of sweating was lower in CEE and

clonidine groups, when compared with propra-nolol and placebo groups. At the first and secondmonth, the CEE group had the greater decreasein analyzed parameters, except that clonidine hadthe greater decrease in sweating at the first month.

Ž .At the third month Table 2 , the frequency ofpresentation of HF was reduced in all the groups.Intensity of the HF decreased in all of themexcept in the placebo group. Duration of the HFwas reduced in all groups except in the propra-nolol group. Insomnia presence, frequency of pre-sentation of the insomnia and presence of sweat-ing decreased in the groups with CEE, clonidineand veralipride.

It can be concluded that when it is possible,estrogen must be administered for the managingof VS, but other alternatives such as clonidineand veralipride can be useful.

Acknowledgments

To Dr Rafael Dominguez Henkel, Medical Di-

( )S. Carranza-Lira, E. Cortes-Fuentes � International Journal of Gynecology & Obstetrics 73 2001 169�171´ 171

Table 2Changes in symptoms in each treatment group

Estrogens Clonidine Propranolol Veralipride PlacebobMedian Range Median Range Median Range Median Range Median Range

aHot-flushes frequency 0 7� 3�20 6† 3�20 8� 4�15 10� 5�30 10� 5�20Hot-flushes intensity 0 9� 5�10 7.6† 3.4�10 6.5‡ 4.8�9.7 8.7† 2.8�9.8 7.4 4.2�9.4Hot-flushes duration 0 4� 1�30 2† 0.7�20 3 2�10 5� 2�11 3� 1�10Insomnia presence 0 80% yes� 87% yes� 74% yes 93.3% yes‡ 73.3% yes

20% no 13% no 26% no 6.7% no 26.7% noInsomnia frequency 0 4� 0�7 5� 0�7 3 0�7 4� 0�7 3 0�7Sweating presence 0 100% yes† 94% yes� 100% yes 100% ‡ 93.3% yes

6% no 6.7% nobHot-flushes frequency 3 0� 0�3 1† 0�8 4‡ 1�10 2� 0�10 5� 2�15

Hot-flushes intensity 3 0� 0�5.7 1.3† 0�5 4.5� 1�8.7 2.5† 0�7.8 6.4 1�8.4Hot-flushes duration3 0� 0�2 0.9† 0�3 2 0.9�15 0.9� 0�3 1� 0.9�8Insomnia presence 3 8% yes� 22% yes� 70% yes 13.3% yes ‡ 46.7% yes

92% no 78% no 30% no 86.6% no 53.3% noInsomnia frequency 3 0� 0�1 0� 0�2 2 0�7 0� 0�1 0 0�6Sweating presence 3 100% no † 8% yes � 70% yes 33.3% yes‡ 73.3% yes

92% no 30% no 66.6% no 26.7% no

a 0�baseline, 3� third month.bP values �0.06, �‡�0.05, �†�0.01, †�0.001. The data and the significances must be analyzed in each row separately. Hot

flushes frequency per day, Hot flushes duration in minutes, Insomnia freqencies in day per week.

rector of Schering Plough, for the donation of theclonidine; to the Centro AF de EstudiosTecnologicos for the donation of the placebo and´to Dr Alfonso Alarcon, Medical Director of Searle´de Mexico S.A. de C.V. for the donation of ver-´alipride.

References

� �1 Lobo R.A., editor. Treatment of the postmenopausal

woman: basic and clinical aspects . New York: RavenPress, 1994.

� �2 Rebar RW, Spizer IB. The physiology and measurementof hot flushes. Am J Obstet Gynecol 1987;156:1284�1288.

� �3 Ginsburg J, Hardinam P. What do we know about thepathogenesis of the menopausal hot flush? The meno-pause: a hormonal replacement therapy. New York: Mar-cel Dekker, 1991:15�46.

� �4 Carranza LS. Integral attention of the climactery.� �Atencion integral del climaterio . Mexico: McGraw-Hill´ ´Interamericana, 1998.