Estrogen therapy for depression in postmenopausal women

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Estrogen therapy for depression in postmenopausal women
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  Ž . International Journal of Gynecology & Obstetrics 65 1999 35  38  Article Estrogen therapy for depression in postmenopausal women S. Carranza-Lira  , M.L. Valentino-Figueroa Gynecologic Endocrinology Ser    ice, Hospital de Gineco-Obstetricia‘Luis Castelazo Ayala’, Instituto Mexicano del SeguroSocial, Mexico City, Mexico Received 30 September 1998; received in revised form 6 January 1999; accepted 7 January 1999  Abstract Objecti    e : To look at the modification in depressive mood in postmenopausal depressed women after estrogen Ž . replacement therapy ERT .  Method : Twelve depressed patients divided into two groups of six women each were Ž . studied. One group received conjugated equine estrogens CEE 0.625 mg  day; the other did not receive any Ž . treatment control group . Mood was assessed in all the subjects at baseline and at 6 months with Hamilton RatingScale score and considered as depression when it was   15. Differences between groups were determined byMann  Whitney  U  -test, and in each group between baseline and 6-month values with Wilcoxon test.  Results : The Ž . ERT group had a statistically significant decrease in depressive mood 21 vs. 13 points,  P   0.03 , while in the control Ž . group no significant change was found. Final Hamilton scale scores were significantly lower  P   0.05 in those underERT, when compared with those in the control group.  Conclusion : Depressive mood decreased after 6 months withCEE, so the prescription of ERT can be useful in postmenopausal women with depressive mood.    1999International Federation of Gynecology and Obstetrics.  Keywords:  Depressive mood; Postmenopause; Climactery; Estrogen replacement therapy; Conjugated equine estrogens  Corresponding author. Puente de piedra, Col. Toriello Guerra C.P., Mexico City, Mexico. Tel.:   52 5 5284657; fax:   52 5 ´ 5284657; e-mail: scarranzal@mexis.com0020-7292  99  $20.00   1999 International Federation of Gynecology and Obstetrics. Ž . PII: S 0 0 2 0 - 7 2 9 2 9 9 0 0 0 1 7 - X  ( )S. Carranza-Lira,M.L. Valentino-Figueroa   International Journal of Gynecology & Obstetrics 65 1999 35   38 36 1. Introduction During climactery, physical and psychologicalchanges occur, the latter includes anxiety, irri-   tability and depression 1 . It is difficult to evalu-ate which symptoms depend on hormonal distur-bances, and which are due to the aging process   2 . Psychological re-adjustments occur in most of    the women after the fourth decade of life 2  4 .Depression in women during perimenopause has   been described to be as high as 35% 5 . An epidemiological study has shown that theincidence of depression in postmenopause wasnot higher due to hormonal causes, but it can bedue to other stimuli, such as family problems, that   may trigger the problem 6 . Women with previ-ous affective disorders related to reproductive   events, are at increased risk at menopause 7 .However, other authors have suggested an in-crease in psychological symptoms during the peri-   menopause 5,8 , particularly in those at risk for   depressive recurrences 9 . Affective disturbances have been related withchanges in amine production, principally nora-   drenaline in the limbic system 10 . Biochemicaland pharmacological studies have shown that es-trogen levels modify the synthesis and metabolism   of cerebral catecholamines 2,3 . Hypothalamicnoradrenaline metabolism is diminished by estro-   gen 10 , and a similar situation occurs with do-   pamine 11 . Serotonin level increases after estro-   gen administration 12 , and monoamine-oxidase Ž . MAO seems to be modified by gonadal hor-mones, as suggested by the inhibitory action of    estrogens over the MAO 13 .Estrogen use for postmenopausal depressivesymptoms has had variable results, some studiesconclude that estrogen has a beneficial effect   14  16 , others indicated that this effect is only   seen after a long-term treatment 17 , and an-other has found that it seems to be dose-related   18 .So the objective of the present work was tolook how depressive mood is modified after estro- Ž . gen replacement therapy ERT with conjugated Ž . equine estrogens CEE in postmenopausal women. 2. Materials and methods Twelve hysterectomized postmenopausal women, 40 years of age and older, who were notreceiving nor had received HRT were studied. Allhad serum levels of follicle stimulating hormone Ž . Ž . FSH and estradiol E measured. Mood was 2 assessed with the Hamilton Rating Scale at base-   line and after a 6-month follow-up period 19,20 ,‘depressed mood’ was defined as a score higherthan 15 points. Both a FSH level   30 mIU  mland Hamilton rating scale score   15 were re-quired to be included in the study. They weredivided in a non-blind manner into two groups of six women each; one received CEE in a continu-ous daily dose of 0.625 mg p.o. for 6 months. Thecontrol group did not receive any ERT due tomedical contraindication or patient personal deci-sion. No cross-over was done during the study. Ž . Before the study began, age years , body mass Ž  2 . index BMI, weight in kg  height in m and the Ž  waist  hip ratio WHR, waist perimeter in cm  hip . perimeter in cm were analyzed. The number of pregnancies, deliveries, abortions and cesareansections were also investigated.Differences between both groups were assessed with the Mann  Whitney  U  -test, and those ineach group between baseline and after treatmentscores with Wilcoxon test.The study was approved by the Ethics Commit-tee of the ‘Luis Castelazo Ayala’ Gynecology andObstetrics Hospital, from the Instituto Mexicanodel Seguro Social in Mexico City, and the patientsgave their informed consent to participate. 3. Results Clinical characteristics of both groups areshown in Table 1. There were no statistical dif-ferences between them in age, BMI, WHR, preg-nancies, deliveries, abortions, cesarean sections,FSH and E levels. 2 Baseline Hamilton scores did not show anydifference between the groups. Comparison ineach group between baseline and 6-month post-treatment Hamilton scores, showed a statistically Ž significant decrease in those of ERT group 21 vs. . 13,  P   0.03 , while in the control group, there  ( )S. Carranza-Lira,M.L. Valentino-Figueroa   International Journal of Gynecology & Obstetrics 65 1999 35   38  37Table 1Clinical and laboratory characteristics in two groups of postmenopausal patientsControl group ERT groupMedian Range Median Range Ž .  Age years 50 45  56 48 41  53BMI 28.3 23.3  31.2 27.7 24.1  44WHR 0.72 0.79  0.9 0.86 0.79  0.91Pregnancies 5 1  6 3 2  8Deliveries 4 1  4 1.5 0  7 Abortions 1.3 0  3 0.5 0  2Cesareans 0 0 0.5 0  2 Ž . FSH mIU  ml 77.4 36.6  100 56.4 30.4  125.4 Ž . E pg  ml 19 8.1  41 19 7.9  40.2 2  Abbre   iations:  ERT, estrogen replacement therapy; BMI, bodymass index; WHR, waist  hip ratio; FSH, follicle stimulatinghormone; E , estradiol. 2 Ž .  were no changes 22 vs. 22 . Comparison betweengroups at 6 months showed significantly lower Ž Hamilton scale scores in the group with ERT 22 . Ž .  vs. 13,  P   0.05 Table 2 . 4. Discussion In this study, the effect of ERT onmenopause-associated depressive mood, was eval-uated with an objective instrument, the Hamilton   Rating Scale 19,20 . Depressive mood signifi-cantly decreased in women treated with CEE, as   has been reported 14 . Also, there was a signifi-cant difference between treated and untreatedgroups in final Hamilton scores.The beneficial effect of ERT was evident at 6months after the beginning of treatment, whichdisagrees with a previous report that indicates Table 2Hamilton scores in two groups of postmenopausal womenControl group ERT group  P  Median Range Median RangeInitial score 22 15  34 21 20  45 NSFinal score 22 12  30 13 12  22   0.05  P   NS   0.03  Abbre   iations:  ERT, estrogen replacement therapy; NS, non-significant. that a longer time is needed to observe a benefi-   cial effect 17 .With the daily 0.625-mg CEE dose, changes were observed, in disagreement with other studyin which a daily dose of 1.25 mg of CEE was   needed to correct the depressive mood 18 .One study has attributed the changes in de-pressive mood after ERT to the decrease in other   climacteric symptoms 16 . Another study re-ported a greater frequency of depression in thoseunder HRT, but as they explain, it could havebeen due to a selection bias, so a greater number   of depressed women look for help 17 .If depressive symptoms are detected in theabsence of other climacteric complaints, otherspecific anti-depressive therapy must be con-   sidered as the first treatment choice 7 .Long-term studies are needed to verify if thisresponse is maintained, and also to look for otherpossible related factors, that are independent of hormonal status. The effect of progestin additionmust also be investigated.In postmenopausal women with depressivemood and climacteric symptoms, ERT with CEEcan be helpful, and it might be tried before anyother anti-depressive drug is used.  Acknowledgments To Martha E. Corral M.D., for her advice inthe Hamilton Rating Scale. References    Ž 1 Carranza LS. Cuadro clınico y diagnostico Clinical data ´ ´ . and diagnosis . In: Carranza LS, editor. Atencion inte- ´ Ž . gral del climaterio Integral attention of the climactery .Mexico: McGraw-Hill Interamericana, 1998:19  28. ´    Ž 2 Coulam C. Edad, estrogenos y psique Age, estrogens ´ . and psyche . Clin Obstet Ginecol 1981;1:225  233.   3 Sherwin B. The effect of sex steroids on brain mecha-nisms relating to mood and sexuality. In: Lorrain J,editor. Comprehensive management of menopause. NewYork: Springer-Verlag, 1993:327  333.   4 Depression in women. ACOG Technical Bulletin No.182, July 1993. Int J Gynecol Obstet 1993;43:203  211.   5 Hay A, Bancroft J, Johnstone EC. Affective symptomsin women attending a menopause clinic. Br J Psychiatry1994;164:513  516.   6 Kaufert PA, Gilbert P, Tate R. The Manitoba project, are-examination of the link between menopause and de-pression. Maturitas 1992;14:143  155.  ( )S. Carranza-Lira,M.L. Valentino-Figueroa   International Journal of Gynecology & Obstetrics 65 1999 35   38 38   7 Pearlstein T, Rosen K, Stone AB. Mood disorders andmenopause. Endocrinol Metab Clin North Am 1997;26:279  294.   8 Coleman P. Depression during the female climactericperiod. J Adv Nurs 1993;18:1540  1546.   9 Pearlstein TB. Hormones and depression: what are factsabout premenstrual syndrome, menopause, and hor-mone replacement therapy? Am J Obstet Gynecol1995;173:646  653.   10 Munaro NI. The effect of ovarian steroids on hypotha-lamic norepinephrine neuronal activity. Acta Endocrinol Ž . Copenhagen 1977;86:235  242.   11 Cotzias GC, Miller ST, Nicholson AR, Jr, Maston WH,Tang LC. Prolongation of the life-span in mice adaptedto large amounts of   L  -dopa. Proc Natl Acad Sci USA 1974;71:2466  2469.   12 Lippert TH, Filshie M, Muck AO, Seeger H, Zwirner M.Serotonin metabolite excretion after postmenopausalestradiol therapy. Maturitas 1996;24:37  41.   13 Klaiber EL, Broverman DM, Vogel W, Kobayashi Y,Moriarty D. Effects of estrogen therapy on plasma MAOactivity and EEG driving responses in depressed women. Am J Psychiatry 1972;128:1492  1498.   14 Zweifel JE, O’Brien WH. A meta analysis of the effectof hormone replacement therapy upon depressed mood.Psychoneuroendocrinology 1997;22:189  212.   15 Korhonen S, Saarijarvi S. Oestradiol treatment helped adepressed postmenopausal woman to stop her psy-chotropic medication: a case report. Acta PsychiatrScand 1996;94:480  481.   16 Pansini F, Albertazzi P, Banaccorsi G, Calisesi M, Cam-pobasso C, Zanotti ? et al. The menopausal transition: adynamic approach to the pathogenesis of neurovegeta-tive complaints. Eur J Obstet Gynecol Reprod Biol1994;57:103  109.   17 Palinkas L, Barret-Connor E. Estrogen use and depres-sive symptom in postmenopausal women. Obstet Gy-necol 1992;80:30  36.   18 Sherwin B. The impact of different doses of estrogenand progestin on mood and sexual behavior in post-menopausal women. J Clin Endocrinol Metab1991;72:336  343.   19 Bailey J, Coppen A. A comparison between the Hamil-ton rating scale and the Beck inventory in the measure-ment of depression. Br J Psychiatry 1976;128:486  489.   20 Ramos-Brieva JA, Cordero-Villafafila A. A new valida-tion of the Hamilton rating scale for depression. JPsychiatr Res 1988;22:21  28.
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