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Estrogen therapy for depression in postmenopausal women
International Journal of Gynecology & Obstetrics 65 Ž1999. 35]38
Article
Estrogen therapy for depression in postmenopausal women S. Carranza-LiraU , M.L. Valentino-Figueroa Gynecologic Endocrinology Ser¨ ice, Hospital de Gineco-Obstetricia ‘Luis Castelazo Ayala’, Instituto Mexicano del Seguro Social, 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 replacement therapy ŽERT.. Method: Twelve depressed patients divided into two groups of six women each were studied. One group received conjugated equine estrogens ŽCEE. 0.625 mgrday; the other did not receive any treatment Žcontrol group.. Mood was assessed in all the subjects at baseline and at 6 months with Hamilton Rating Scale score and considered as depression when it was ) 15. Differences between groups were determined by Mann]Whitney U-test, and in each group between baseline and 6-month values with Wilcoxon test. Results: The ERT group had a statistically significant decrease in depressive mood Ž21 vs. 13 points, P- 0.03., while in the control group no significant change was found. Final Hamilton scale scores were significantly lower Ž P- 0.05. in those under ERT, when compared with those in the control group. Conclusion: Depressive mood decreased after 6 months with CEE, so the prescription of ERT can be useful in postmenopausal women with depressive mood. Q 1999 International Federation of Gynecology and Obstetrics. Keywords: Depressive mood; Postmenopause; Climactery; Estrogen replacement therapy; Conjugated equine estrogens
U
Corresponding author. Puente de piedra, Col. Toriello Guerra C.P., Mexico City, Mexico. Tel.: q52 5 5284657; fax: q52 5 ´ 5284657; e-mail: [email protected] 0020-7292r99r$20.00 Q 1999 International Federation of Gynecology and Obstetrics. PII: S 0 0 2 0 - 7 2 9 2 Ž 9 9 . 0 0 0 1 7 - X
36
S. Carranza-Lira, M.L. Valentino-Figueroa r International Journal of Gynecology & Obstetrics 65 (1999) 35]38
1. Introduction During climactery, physical and psychological changes occur, the latter includes anxiety, irritability and depression w1x. It is difficult to evaluate which symptoms depend on hormonal disturbances, and which are due to the aging process w2x. Psychological re-adjustments occur in most of the women after the fourth decade of life w2]4x. Depression in women during perimenopause has been described to be as high as 35% w5x. An epidemiological study has shown that the incidence of depression in postmenopause was not higher due to hormonal causes, but it can be due to other stimuli, such as family problems, that may trigger the problem w6x. Women with previous affective disorders related to reproductive events, are at increased risk at menopause w7x. However, other authors have suggested an increase in psychological symptoms during the perimenopause w5,8x, particularly in those at risk for depressive recurrences w9x. Affective disturbances have been related with changes in amine production, principally noradrenaline in the limbic system w10x. Biochemical and pharmacological studies have shown that estrogen levels modify the synthesis and metabolism of cerebral catecholamines w2,3x. Hypothalamic noradrenaline metabolism is diminished by estrogen w10x, and a similar situation occurs with dopamine w11x. Serotonin level increases after estrogen administration w12x, and monoamine-oxidase ŽMAO. seems to be modified by gonadal hormones, as suggested by the inhibitory action of estrogens over the MAO w13x. Estrogen use for postmenopausal depressive symptoms has had variable results, some studies conclude that estrogen has a beneficial effect w14]16x, others indicated that this effect is only seen after a long-term treatment w17x, and another has found that it seems to be dose-related w18x. So the objective of the present work was to look how depressive mood is modified after estrogen replacement therapy ŽERT. with conjugated equine estrogens ŽCEE. in postmenopausal women.
2. Materials and methods Twelve hysterectomized postmenopausal women, 40 years of age and older, who were not receiving nor had received HRT were studied. All had serum levels of follicle stimulating hormone ŽFSH. and estradiol ŽE 2 . measured. Mood was assessed with the Hamilton Rating Scale at baseline and after a 6-month follow-up period w19,20x, ‘depressed mood’ was defined as a score higher than 15 points. Both a FSH level ) 30 mIUrml and Hamilton rating scale score ) 15 were required to be included in the study. They were divided in a non-blind manner into two groups of six women each; one received CEE in a continuous daily dose of 0.625 mg p.o. for 6 months. The control group did not receive any ERT due to medical contraindication or patient personal decision. No cross-over was done during the study. Before the study began, age Žyears., body mass index ŽBMI, weight in kgrheight in m2 . and the waist]hip ratio ŽWHR, waist perimeter in cmrhip perimeter in cm. were analyzed. The number of pregnancies, deliveries, abortions and cesarean sections were also investigated. Differences between both groups were assessed with the Mann]Whitney U-test, and those in each group between baseline and after treatment scores with Wilcoxon test. The study was approved by the Ethics Committee of the ‘Luis Castelazo Ayala’ Gynecology and Obstetrics Hospital, from the Instituto Mexicano del Seguro Social in Mexico City, and the patients gave their informed consent to participate. 3. Results Clinical characteristics of both groups are shown in Table 1. There were no statistical differences between them in age, BMI, WHR, pregnancies, deliveries, abortions, cesarean sections, FSH and E 2 levels. Baseline Hamilton scores did not show any difference between the groups. Comparison in each group between baseline and 6-month posttreatment Hamilton scores, showed a statistically significant decrease in those of ERT group Ž21 vs. 13, P- 0.03., while in the control group, there
S. Carranza-Lira, M.L. Valentino-Figueroa r International Journal of Gynecology & Obstetrics 65 (1999) 35]38 Table 1 Clinical and laboratory characteristics in two groups of postmenopausal patients
Age Žyears. BMI WHR Pregnancies Deliveries Abortions Cesareans FSH ŽmIUrml. E2 Žpgrml.
Control group
ERT group
Median
Range
Median
Range
50 28.3 0.72 5 4 1.3 0 77.4 19
45]56 23.3]31.2 0.79]0.9 1]6 1]4 0]3 0 36.6]100 8.1]41
48 27.7 0.86 3 1.5 0.5 0.5 56.4 19
41]53 24.1]44 0.79]0.91 2]8 0]7 0]2 0]2 30.4]125.4 7.9]40.2
Abbre¨ iations: ERT, estrogen replacement therapy; BMI, body mass index; WHR, waist]hip ratio; FSH, follicle stimulating hormone; E 2 , estradiol.
were no changes Ž22 vs. 22.. Comparison between groups at 6 months showed significantly lower Hamilton scale scores in the group with ERT Ž22 vs. 13, P- 0.05. ŽTable 2.. 4. Discussion In this study, the effect of ERT on menopause-associated depressive mood, was evaluated with an objective instrument, the Hamilton Rating Scale w19,20x. Depressive mood significantly decreased in women treated with CEE, as has been reported w14x. Also, there was a significant difference between treated and untreated groups in final Hamilton scores. The beneficial effect of ERT was evident at 6 months after the beginning of treatment, which disagrees with a previous report that indicates Table 2 Hamilton scores in two groups of postmenopausal women
Initial score Final score P
Control group
ERT group
Median
Median
Range
21 13 - 0.03
20]45 12]22
22 22 NS
Range 15]34 12]30
P
NS - 0.05
Abbre¨ iations: ERT, estrogen replacement therapy; NS, nonsignificant.
37
that a longer time is needed to observe a beneficial effect w17x. With the daily 0.625-mg CEE dose, changes were observed, in disagreement with other study in which a daily dose of 1.25 mg of CEE was needed to correct the depressive mood w18x. One study has attributed the changes in depressive mood after ERT to the decrease in other climacteric symptoms w16x. Another study reported a greater frequency of depression in those under HRT, but as they explain, it could have been due to a selection bias, so a greater number of depressed women look for help w17x. If depressive symptoms are detected in the absence of other climacteric complaints, other specific anti-depressive therapy must be considered as the first treatment choice w7x. Long-term studies are needed to verify if this response is maintained, and also to look for other possible related factors, that are independent of hormonal status. The effect of progestin addition must also be investigated. In postmenopausal women with depressive mood and climacteric symptoms, ERT with CEE can be helpful, and it might be tried before any other anti-depressive drug is used. Acknowledgments To Martha E. Corral M.D., for her advice in the Hamilton Rating Scale. References w1x Carranza LS. Cuadro clınico ŽClinical data y diagnostico ´ ´ and diagnosis.. In: Carranza LS, editor. Atencion ´ integral del climaterio ŽIntegral attention of the climactery.. Mexico: McGraw-Hill Interamericana, 1998:19]28. ´ w2x Coulam C. Edad, estrogenos y psique ŽAge, estrogens ´ and psyche.. Clin Obstet Ginecol 1981;1:225]233. w3x Sherwin B. The effect of sex steroids on brain mechanisms relating to mood and sexuality. In: Lorrain J, editor. Comprehensive management of menopause. New York: Springer-Verlag, 1993:327]333. w4x Depression in women. ACOG Technical Bulletin No. 182, July 1993. Int J Gynecol Obstet 1993;43:203]211. w5x Hay A, Bancroft J, Johnstone EC. Affective symptoms in women attending a menopause clinic. Br J Psychiatry 1994;164:513]516. w6x Kaufert PA, Gilbert P, Tate R. The Manitoba project, a re-examination of the link between menopause and depression. Maturitas 1992;14:143]155.
38
S. Carranza-Lira, M.L. Valentino-Figueroa r International Journal of Gynecology & Obstetrics 65 (1999) 35]38
w7x Pearlstein T, Rosen K, Stone AB. Mood disorders and menopause. Endocrinol Metab Clin North Am 1997; 26:279]294. w8x Coleman P. Depression during the female climacteric period. J Adv Nurs 1993;18:1540]1546. w9x Pearlstein TB. Hormones and depression: what are facts about premenstrual syndrome, menopause, and hormone replacement therapy? Am J Obstet Gynecol 1995;173:646]653. w10x Munaro NI. The effect of ovarian steroids on hypothalamic norepinephrine neuronal activity. Acta Endocrinol ŽCopenhagen. 1977;86:235]242. w11x Cotzias GC, Miller ST, Nicholson AR, Jr, Maston WH, Tang LC. Prolongation of the life-span in mice adapted to large amounts of L-dopa. Proc Natl Acad Sci USA 1974;71:2466]2469. w12x Lippert TH, Filshie M, Muck AO, Seeger H, Zwirner M. Serotonin metabolite excretion after postmenopausal estradiol therapy. Maturitas 1996;24:37]41. w13x Klaiber EL, Broverman DM, Vogel W, Kobayashi Y, Moriarty D. Effects of estrogen therapy on plasma MAO activity and EEG driving responses in depressed women. Am J Psychiatry 1972;128:1492]1498. w14x Zweifel JE, O’Brien WH. A meta analysis of the effect
w15x
w16x
w17x w18x
w19x w20x
of hormone replacement therapy upon depressed mood. Psychoneuroendocrinology 1997;22:189]212. Korhonen S, Saarijarvi S. Oestradiol treatment helped a depressed postmenopausal woman to stop her psychotropic medication: a case report. Acta Psychiatr Scand 1996;94:480]481. Pansini F, Albertazzi P, Banaccorsi G, Calisesi M, Campobasso C, Zanotti ? et al. The menopausal transition: a dynamic approach to the pathogenesis of neurovegetative complaints. Eur J Obstet Gynecol Reprod Biol 1994;57:103]109. Palinkas L, Barret-Connor E. Estrogen use and depressive symptom in postmenopausal women. Obstet Gynecol 1992;80:30]36. Sherwin B. The impact of different doses of estrogen and progestin on mood and sexual behavior in postmenopausal women. J Clin Endocrinol Metab 1991;72:336]343. Bailey J, Coppen A. A comparison between the Hamilton rating scale and the Beck inventory in the measurement of depression. Br J Psychiatry 1976;128:486]489. Ramos-Brieva JA, Cordero-Villafafila A. A new validation of the Hamilton rating scale for depression. J Psychiatr Res 1988;22:21]28.
Article
Estrogen therapy for depression in postmenopausal women S. Carranza-LiraU , M.L. Valentino-Figueroa Gynecologic Endocrinology Ser¨ ice, Hospital de Gineco-Obstetricia ‘Luis Castelazo Ayala’, Instituto Mexicano del Seguro Social, 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 replacement therapy ŽERT.. Method: Twelve depressed patients divided into two groups of six women each were studied. One group received conjugated equine estrogens ŽCEE. 0.625 mgrday; the other did not receive any treatment Žcontrol group.. Mood was assessed in all the subjects at baseline and at 6 months with Hamilton Rating Scale score and considered as depression when it was ) 15. Differences between groups were determined by Mann]Whitney U-test, and in each group between baseline and 6-month values with Wilcoxon test. Results: The ERT group had a statistically significant decrease in depressive mood Ž21 vs. 13 points, P- 0.03., while in the control group no significant change was found. Final Hamilton scale scores were significantly lower Ž P- 0.05. in those under ERT, when compared with those in the control group. Conclusion: Depressive mood decreased after 6 months with CEE, so the prescription of ERT can be useful in postmenopausal women with depressive mood. Q 1999 International Federation of Gynecology and Obstetrics. Keywords: Depressive mood; Postmenopause; Climactery; Estrogen replacement therapy; Conjugated equine estrogens
U
Corresponding author. Puente de piedra, Col. Toriello Guerra C.P., Mexico City, Mexico. Tel.: q52 5 5284657; fax: q52 5 ´ 5284657; e-mail: [email protected] 0020-7292r99r$20.00 Q 1999 International Federation of Gynecology and Obstetrics. PII: S 0 0 2 0 - 7 2 9 2 Ž 9 9 . 0 0 0 1 7 - X
36
S. Carranza-Lira, M.L. Valentino-Figueroa r International Journal of Gynecology & Obstetrics 65 (1999) 35]38
1. Introduction During climactery, physical and psychological changes occur, the latter includes anxiety, irritability and depression w1x. It is difficult to evaluate which symptoms depend on hormonal disturbances, and which are due to the aging process w2x. Psychological re-adjustments occur in most of the women after the fourth decade of life w2]4x. Depression in women during perimenopause has been described to be as high as 35% w5x. An epidemiological study has shown that the incidence of depression in postmenopause was not higher due to hormonal causes, but it can be due to other stimuli, such as family problems, that may trigger the problem w6x. Women with previous affective disorders related to reproductive events, are at increased risk at menopause w7x. However, other authors have suggested an increase in psychological symptoms during the perimenopause w5,8x, particularly in those at risk for depressive recurrences w9x. Affective disturbances have been related with changes in amine production, principally noradrenaline in the limbic system w10x. Biochemical and pharmacological studies have shown that estrogen levels modify the synthesis and metabolism of cerebral catecholamines w2,3x. Hypothalamic noradrenaline metabolism is diminished by estrogen w10x, and a similar situation occurs with dopamine w11x. Serotonin level increases after estrogen administration w12x, and monoamine-oxidase ŽMAO. seems to be modified by gonadal hormones, as suggested by the inhibitory action of estrogens over the MAO w13x. Estrogen use for postmenopausal depressive symptoms has had variable results, some studies conclude that estrogen has a beneficial effect w14]16x, others indicated that this effect is only seen after a long-term treatment w17x, and another has found that it seems to be dose-related w18x. So the objective of the present work was to look how depressive mood is modified after estrogen replacement therapy ŽERT. with conjugated equine estrogens ŽCEE. in postmenopausal women.
2. Materials and methods Twelve hysterectomized postmenopausal women, 40 years of age and older, who were not receiving nor had received HRT were studied. All had serum levels of follicle stimulating hormone ŽFSH. and estradiol ŽE 2 . measured. Mood was assessed with the Hamilton Rating Scale at baseline and after a 6-month follow-up period w19,20x, ‘depressed mood’ was defined as a score higher than 15 points. Both a FSH level ) 30 mIUrml and Hamilton rating scale score ) 15 were required to be included in the study. They were divided in a non-blind manner into two groups of six women each; one received CEE in a continuous daily dose of 0.625 mg p.o. for 6 months. The control group did not receive any ERT due to medical contraindication or patient personal decision. No cross-over was done during the study. Before the study began, age Žyears., body mass index ŽBMI, weight in kgrheight in m2 . and the waist]hip ratio ŽWHR, waist perimeter in cmrhip perimeter in cm. were analyzed. The number of pregnancies, deliveries, abortions and cesarean sections were also investigated. Differences between both groups were assessed with the Mann]Whitney U-test, and those in each group between baseline and after treatment scores with Wilcoxon test. The study was approved by the Ethics Committee of the ‘Luis Castelazo Ayala’ Gynecology and Obstetrics Hospital, from the Instituto Mexicano del Seguro Social in Mexico City, and the patients gave their informed consent to participate. 3. Results Clinical characteristics of both groups are shown in Table 1. There were no statistical differences between them in age, BMI, WHR, pregnancies, deliveries, abortions, cesarean sections, FSH and E 2 levels. Baseline Hamilton scores did not show any difference between the groups. Comparison in each group between baseline and 6-month posttreatment Hamilton scores, showed a statistically significant decrease in those of ERT group Ž21 vs. 13, P- 0.03., while in the control group, there
S. Carranza-Lira, M.L. Valentino-Figueroa r International Journal of Gynecology & Obstetrics 65 (1999) 35]38 Table 1 Clinical and laboratory characteristics in two groups of postmenopausal patients
Age Žyears. BMI WHR Pregnancies Deliveries Abortions Cesareans FSH ŽmIUrml. E2 Žpgrml.
Control group
ERT group
Median
Range
Median
Range
50 28.3 0.72 5 4 1.3 0 77.4 19
45]56 23.3]31.2 0.79]0.9 1]6 1]4 0]3 0 36.6]100 8.1]41
48 27.7 0.86 3 1.5 0.5 0.5 56.4 19
41]53 24.1]44 0.79]0.91 2]8 0]7 0]2 0]2 30.4]125.4 7.9]40.2
Abbre¨ iations: ERT, estrogen replacement therapy; BMI, body mass index; WHR, waist]hip ratio; FSH, follicle stimulating hormone; E 2 , estradiol.
were no changes Ž22 vs. 22.. Comparison between groups at 6 months showed significantly lower Hamilton scale scores in the group with ERT Ž22 vs. 13, P- 0.05. ŽTable 2.. 4. Discussion In this study, the effect of ERT on menopause-associated depressive mood, was evaluated with an objective instrument, the Hamilton Rating Scale w19,20x. Depressive mood significantly decreased in women treated with CEE, as has been reported w14x. Also, there was a significant difference between treated and untreated groups in final Hamilton scores. The beneficial effect of ERT was evident at 6 months after the beginning of treatment, which disagrees with a previous report that indicates Table 2 Hamilton scores in two groups of postmenopausal women
Initial score Final score P
Control group
ERT group
Median
Median
Range
21 13 - 0.03
20]45 12]22
22 22 NS
Range 15]34 12]30
P
NS - 0.05
Abbre¨ iations: ERT, estrogen replacement therapy; NS, nonsignificant.
37
that a longer time is needed to observe a beneficial effect w17x. With the daily 0.625-mg CEE dose, changes were observed, in disagreement with other study in which a daily dose of 1.25 mg of CEE was needed to correct the depressive mood w18x. One study has attributed the changes in depressive mood after ERT to the decrease in other climacteric symptoms w16x. Another study reported a greater frequency of depression in those under HRT, but as they explain, it could have been due to a selection bias, so a greater number of depressed women look for help w17x. If depressive symptoms are detected in the absence of other climacteric complaints, other specific anti-depressive therapy must be considered as the first treatment choice w7x. Long-term studies are needed to verify if this response is maintained, and also to look for other possible related factors, that are independent of hormonal status. The effect of progestin addition must also be investigated. In postmenopausal women with depressive mood and climacteric symptoms, ERT with CEE can be helpful, and it might be tried before any other anti-depressive drug is used. Acknowledgments To Martha E. Corral M.D., for her advice in the Hamilton Rating Scale. References w1x Carranza LS. Cuadro clınico ŽClinical data y diagnostico ´ ´ and diagnosis.. In: Carranza LS, editor. Atencion ´ integral del climaterio ŽIntegral attention of the climactery.. Mexico: McGraw-Hill Interamericana, 1998:19]28. ´ w2x Coulam C. Edad, estrogenos y psique ŽAge, estrogens ´ and psyche.. Clin Obstet Ginecol 1981;1:225]233. w3x Sherwin B. The effect of sex steroids on brain mechanisms relating to mood and sexuality. In: Lorrain J, editor. Comprehensive management of menopause. New York: Springer-Verlag, 1993:327]333. w4x Depression in women. ACOG Technical Bulletin No. 182, July 1993. Int J Gynecol Obstet 1993;43:203]211. w5x Hay A, Bancroft J, Johnstone EC. Affective symptoms in women attending a menopause clinic. Br J Psychiatry 1994;164:513]516. w6x Kaufert PA, Gilbert P, Tate R. The Manitoba project, a re-examination of the link between menopause and depression. Maturitas 1992;14:143]155.
38
S. Carranza-Lira, M.L. Valentino-Figueroa r International Journal of Gynecology & Obstetrics 65 (1999) 35]38
w7x Pearlstein T, Rosen K, Stone AB. Mood disorders and menopause. Endocrinol Metab Clin North Am 1997; 26:279]294. w8x Coleman P. Depression during the female climacteric period. J Adv Nurs 1993;18:1540]1546. w9x Pearlstein TB. Hormones and depression: what are facts about premenstrual syndrome, menopause, and hormone replacement therapy? Am J Obstet Gynecol 1995;173:646]653. w10x Munaro NI. The effect of ovarian steroids on hypothalamic norepinephrine neuronal activity. Acta Endocrinol ŽCopenhagen. 1977;86:235]242. w11x Cotzias GC, Miller ST, Nicholson AR, Jr, Maston WH, Tang LC. Prolongation of the life-span in mice adapted to large amounts of L-dopa. Proc Natl Acad Sci USA 1974;71:2466]2469. w12x Lippert TH, Filshie M, Muck AO, Seeger H, Zwirner M. Serotonin metabolite excretion after postmenopausal estradiol therapy. Maturitas 1996;24:37]41. w13x Klaiber EL, Broverman DM, Vogel W, Kobayashi Y, Moriarty D. Effects of estrogen therapy on plasma MAO activity and EEG driving responses in depressed women. Am J Psychiatry 1972;128:1492]1498. w14x Zweifel JE, O’Brien WH. A meta analysis of the effect
w15x
w16x
w17x w18x
w19x w20x
of hormone replacement therapy upon depressed mood. Psychoneuroendocrinology 1997;22:189]212. Korhonen S, Saarijarvi S. Oestradiol treatment helped a depressed postmenopausal woman to stop her psychotropic medication: a case report. Acta Psychiatr Scand 1996;94:480]481. Pansini F, Albertazzi P, Banaccorsi G, Calisesi M, Campobasso C, Zanotti ? et al. The menopausal transition: a dynamic approach to the pathogenesis of neurovegetative complaints. Eur J Obstet Gynecol Reprod Biol 1994;57:103]109. Palinkas L, Barret-Connor E. Estrogen use and depressive symptom in postmenopausal women. Obstet Gynecol 1992;80:30]36. Sherwin B. The impact of different doses of estrogen and progestin on mood and sexual behavior in postmenopausal women. J Clin Endocrinol Metab 1991;72:336]343. Bailey J, Coppen A. A comparison between the Hamilton rating scale and the Beck inventory in the measurement of depression. Br J Psychiatry 1976;128:486]489. Ramos-Brieva JA, Cordero-Villafafila A. A new validation of the Hamilton rating scale for depression. J Psychiatr Res 1988;22:21]28.