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Prolactin and TSH responses to TRH and to ECT in pre- and postmenopausal women with major depression
Prolactin and TSH Responses to TRH and to ECT in Pre- and Postmenopausal Women with Major Depression Manolis Markianos, Lefteris Lykouras, and Costas Stefanis
The patterns of prolactin and thyrotropin (TSH) release after thyrotropin-releasing hormone (TRH) (0.4 mg i.v.) and during the first session of a course of electroconvulsive treatment (ECT) were studied in women with major depression, 16 in pre- and 29 in postmenopausal status. The prolactin responses to both stimuli were lower in postmenopausal women, whereas the TSH responses were not different. The known correlation between the maximal prolactin response to ECT and the maximal response to TRH was significantly stronger in the group of premenopausal women (r = .8648, versus .4249 in the postmenopausal group, p < .02). A common underlying mechanism promoting prolactin release for both stimuli can be suggested, which diminishes after menopause, probably an influence of estradiol on the affini O, of dopaminergic and serotonergic receptors. That mechanism does not interfere with the TSH release either by ECT or by TRH.
Key Words: Prolactin, depression
thyrotropin,
electroconvulsive
treatment,
TRH,
menopause,
BIoL PSYCHIATRY 1996;40:403--406
Introduction Although the positive effect of estrogens on the release of prolactin (PRL) and thyrotropin (TSH) is rather well documented (Jaffe et al 1973; Ramey et al 1975; Raymond et al 1976; De Lean et al 1977), the influence of circulating estradiol levels on the thyrotropin-releasing hormone (TRH)-induced PRL and TSH responses remains controversial (Jacobs et al 1973; Wenzel et al 1974; Erfurth et al 1984, 1992). Pharmacologic doses of estrogens promote From Athens University Medical School. Psychiatric Clinic, Eginition Hospital, Athens. Greece. Address reprint requests to Dr. Manolis Markianos. Athens University Medical School, Psychiatric Clinic, Eginition Hospital, Vas. Sophias 74. Athens 11528, Greece. Received February 13, 1995; revised July 14, 1995.
. © 1996 Society of Biological Ps2cchiatry
the synthesis and release of PRL by the pituitary (Yen et al 1978), probably by stimulating the regulation of PRL gene transcription (Maurer 1982). In menopause, a decrease in PRL plasma levels is observed that parallels the decline in plasma estradiol, so that postmenopausal women have lower basal PRL plasma levels than premenopausal women (Djursing et al 1981). It has been reported that in postmenopausal women, treatment with estradiol benzoate increases basal PRL levels and enhances the TRH-stimulated PRL release (Joseph et al 1986; Couzinet et al 1989), which has been found to be blunted (Linkowski et al 1980), or unaltered (Erfurth et al 1992) compared to the responses of premenopausal women. Regarding the TSH response to TRH, significant (Maes ") 0006-3.23/96/$15.00 SSD1 0006-3223(95)00396-X
404
BIOL PSYCHIATRY 1996;40:403-406
et al 1989) and nonsignificant (Erfurth et al 1992) reductions have been reported in postmenopausal women. Rutlin et al (1977) had reported no differences between menstruating and postmenopausal women, and no effect of estradiol treatment. This issue is of specific interest for biological psychiatry, since it has to be considered in evaluating the possibly blunted TSH-response to TRH in depressive patients compared to normal women (Maes et al 1989). Electroconvulsive treatment (ECT) causes substantial PRL release (Ohman et al 1976), and small but consistent release of TSH (Aperia et al 1985; Papakostas et al 1990). The elucidation of the underlying mechanisms is important for the understanding of the therapeutic mode of ECT action, and several reports have been published on this subject in recent years. The participation of TRH in the PRL response to ECT has been hypothesized, since a significant correlation has been found between the magnitudes of PRL responses to ECT and to TRH (Papakostas et al 1986; Devanand et al 1989). In the two lastmentioned studies the menopausal status was not taken into consideration. In this study, we performed the TRH test in 45 women with major depression who were assigned to ECT, and assessed also the PRL and TSH responses during the first ECT session, 2 - 4 days later. Sixteen of the patients were normally menstruating, and 29 were postmenopausal. We compared the patterns of PRL and TSH release during TRH and during ECT between the two groups, and examined the strength of the correlations between the PRL responses to TRH and to ECT for the whole group, and the pre- and postmenopausal subgroups separately.
Methods All patients were women hospitalized in the Psychiatric Clinic of the Athens University Medical School, Eginition Hospital. They suffered from major depression (DSMIII-R criteria), with a mean score on the 17-item Hamilton Depression Rating Scale of 27.4 (SD = 3.9, range 18-35). Electroconvulsive treatment was considered to be the appropriate therapeutic approach. They were drug-free for 1 week, with the exception of low doses of lorazepam (usually 2 rag) given at bedtime. Forty-five patients were included in the study. Their ages ranged from 24 to 73 years (mean 51.6, SD = 12.8). Sixteen of them were premenopausal (mean age 37.9, SD = 9.1), and 29 postmenopausal (mean age 59.2, SD = 6.6). The menopausal status was confirmed by estimations of plasma levels of estradiol, luteinizing hormone, and folliclestimulating hormone. Regarding diagnostic features, 14 of the 45 patients suffered from psychotic (delusional) depression, and 4 were bipolar. The number of psychotic vs.
M. M a r k i a n o s et al
nonpsychotic patients in the subgroups were 4 vs. 12 in the premenopausal group, and 10 vs. 19 in the postmenopausal group, i.e., they were similarly distributed (chisquare = 0.43, p = .51). From the 4 bipolar patients, 1 was pre- and 3 were postmenopausal (chi-square = 0.21, p = .64). The TRH test was performed by injection of 0.4 mg i.v., and blood sampling at times 0, 20, 40, and 60 rain. Two to four days later, during the first ECT session, blood samples were withdrawn at times 0, 15, 30, and 60 min. The ECT procedure included administration of sodium thiopental, succinylcholine, and oxygenation. ECT was given with the electrodes placed in the bitemporal position, using a pulse current device (Thymatron) at dial settings appropriate for the patient's age as recommended by the manual. The seizure was monitored by the cuff method, and the seizure duration had values between 18 and 45 sec (mean = 29.6 sec, SD = 6.7). In all patients included in the study the seizure was elicited with the first electrical stimulation. The first blood sample (time zero) was taken after succinylcholine administration. Plasma was separated by centrifugation, and stored at - 3 0 ° C until estimations. Prolactin and TSH were estimated using commercial radioimmunoassay kits. The coefficients of variation were around 5% for prolactin (Serono Diagnostics, Switzerland), and less than 5% for TSH (Medgenix, Belgium). For the statistical evaluation of the response patterns of PRL and of TSH to the two stimuli, we used analysis of variance with repeated measures (ANOVAR). When comparing the responses to ECT, the seizure duration was used as covariate, to compensate for possible influence of this variable on the magnitude of hormone secretion. Linear correlation coefficients between the maximal PRL and TSH responses to the two stimuli were also calculated for the whole group of 45 patients, and separately for the preand postmenopausal groups.
Results The baseline PRL plasma levels (samples taken at zero time during the TRH test) were lower in the postmenopausal women (mean = 7.2 ng/mL, SD = 3.3) compared to those of premenopausal (mean = 13.6, SD = 7.3, F = 16.55, p = .001), as has been reported previously by several authors (i.e., Djursing et al 1981). As expected, both ECT and TRH administration caused significant increases in both TSH and PRL. The patterns of these responses for the two groups are shown in Figure 1. Statistical evaluation, shown in Table I, revealed that the TSH responses to both stimuli were similar in the groups of pre- and postmenopausal women (group-time interactions not significant), but the PRL responses were differ-
Prolactin and TSH Responses to TRH and ECT
BIOLPSYCHIATRY
405
1996;40:403-406
100
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Figure 1. Patterns of prolactin (ng/mL) and TSH (mlU/mL) responses to ECT and TRH in 16 pre- (open circles) and 29 post- (filled circles) menopausal depressive patients. Mean values and SEM. X axis: time in minutes. ent, with the postmenopausal women having attenuated PRL responses both to ECT and to TRH compared to the premenopausal women. The significant positive correlation between the PRL responses to ECT and to TRH that has been reported by our group and by others (see Introduction), was present in the whole population of 45 subjects in this study (r =
.6817, p < .001). We calculated the correlation coefficients separately for the groups of pre- and of postmenopausal patients, and found that the correlation was significantly stronger in the group of premenopausal (r = .8716, n = 16) than in the group of postmenopausal (r = .4815, n = 25) women (difference between correlations, twosided test, p = .017).
Table 1. Statistical Evaluation (Repeated Measures ANOVA) of the Differences in the PRL and TSH Release Patterns a after TRH and after ECT, in Groups of Pre- (16 Patients) and Post(29 Patients) Menopausal Women with Major Depression, and for TRH in a Group of Male Depressive Patients, 21 in the Age Range 2 5 - 4 5 Years and 16 in the Range 5 0 - 6 6 Years
Discussion
PRL
TSH
ECT Effect
F
TRH p
F
Group (G) 4.06 .05 11.92 Time (T) 93.64 .000 153.65 G×T 3.28 .023 6.97 Male patients Group 0.54 Time 127.56 G×T 0.68 ~Shown in Figure 1.
ECT p
F
TRH p
F
p
.001 0.05 .83 0.01 .92 .000 15.08 .000 122.40 .000 .000 1 . 2 5 .29 0.21 .89 .47 .000 .56
0.20 .65 68.07 .000 0.30 .82
A blunted PRL response to TRH in depressive postmenopausal women, compared to premenopausal, has been previously reported (Linkowski et al 1980). Here we additionally report a similar finding for the PRL responses to ECT. This indicates that the factor affecting these responses is common in the mechanisms of PRL release by TRH and by ECT, and the most probable candidate is estradiol. Estrogen exerts a direct facilitating effect on PRL release, possibly by influencing the affinity status of dopaminergic and serotonergic receptors. The stronger correlation between the PRL responses to ECT and to TRH in the premenopausal women fits well to this assumption. An influence of endogenous TRH is not expected, since it has been found that the hypothalamic content of TRH in postmenopausal women is similar to
406
BIOL PSYCHIATRY
M. Markianos et al
1996;40:403-406
that of young women (Parker and Porter 1984). The exclusion of a TRH action is further supported by our finding that the TSH responses to both TRH and ECT were not related to menopause. The possibility that the effects we describe are not due to the menopausal status but are simply age effects cannot be ruled out. Data from a male population could be of help in elucidating this question. In our laboratory, we have data from male patients, adequate for analysis, only for the TRH test, and from 37 male depressive patients in the age range 2 5 - 6 6 years. We looked at these data, building two groups, one in the age range 2 5 - 4 5 years (mean = 33.9, SD = 5.4, 21 patients), and the other in the age range 5 0 - 6 6 years (mean = 58.6, SD = 4.7, 16 patients), and compared the patterns of PRL and TSH responses to TRH.
No indication of differences for either PRL or TSH responses was found (see Table 1). In addition, the correlations of age to PRL (r = .0503) and to TSH (r = .1512) responses to TRH for the whole group of male patients were not significant, and the same was true for the correlations between age and PRL responses to TRH or to ECT in the female pre- or postmenopausal subgroups. In conclusion, in depressive women, the PRL responses to TRH but also to ECT diminish after menopause, and this effect seems to be not an ageing effect but to be related to the circulating estrogens. Estradiol may facilitate directly the release of PRL by these stimuli, possibly by altering the affinity status of dopaminergic and serotonergic receptors.
References Aperia B, Thoren M, Wetterberg L (1985): Prolactin and thyrotropin in serum during electroconvulsive therapy in patients with major depressive illness. Acta Psychiatr Scand 72:302-308. Couzinet B, Dorey F, Schaison G (1989): Effects of vasoactive intestinal polypeptide, TRH, and dopamine on prolactin secretion in estrogen-primed postmenopausa! women. Acta Endocrinol (Copenh) 121:235-240. De Lean A, Garon M, Kelly PA, Labile F (1977): Changes in pituitary thyrotropin-releasing hormone receptor levels and prolactin responses to TRH during the rat estrous cycle. Endocrinology 100:1505-1510. Devanand DP, Sacheim HA, Pierson D, Novacenko H, Prudic J, Ross F (1989): Prolactin response to TRH and to ECT: A common mechanism? Biol Psychiatry 205:106A. Djursing H, Hagen C, Moeller J, Christianses C (1981): Short and long-term fluctuations in plasma prolactin concentration in normal subjects. Acta Endocrinol 97:1-6. Erfurth EM, Norden NE, Hedner P, Nilsson A, Ek A (1984): Normal reference interval for thyrotropin response to thyroliberin: Dependence on age, sex, free thyroxine index, and basal concentrations of thyrotropin. Clin Chem 30:196-199. Erfurth EM, Erfurth E, Ericsson UB (1992): The role of estrogen in the TSH and prolactin responses to thyrotropin-releasing hormone in postmenopausal as compared to premenopausal women. Horm Metab Res 24:528-531. Jacobs LS, Snyder PJ, Utiger RD, Daughaday WH (1973): Prolactin response to thyrotropin-releasing hormone in normal subjects. J Clin Endocrinol Metab 36:3845-3850. Jaffe RB, Yuen WR, Keye JR, Midgley AR (1973): Physiological and pathological profiles of circulating human prolactin. Am J Obstet Gynecol 117:757-773. Joseph PJ, Couzinet B, Brallly S, Rigaud C, Raynaud JP, Schaison G (1986): Interactions of oestradiol benzoate and promegestone upon basal and TRH-induced prolactin secretion in postmenopausal women. Clin Endocrinol 24:497-503. Linkowski P, Brauman H, Mendlewicz J (1980): Prolactin
secretion in women with unipolar and bipolar depression. Psychiat Res 3:265-271.
Maes M, Vandewoude M, Maes L, Schotte C, Cosyns P (1989): A revised interpretation of the TRH test results in female depressed patients. J Affective Disord 16:203-213. Maurer RA (1982): Estradiol regulates the transcription of the prolactin gene. J Biol Chem 257:2133-2136. Ohman R, Balldin J, Walinder J, Wallin L (1976): Prolactin response to electconvulsive therapy. Lancet i:936-938. Papakostas Y, Markianos M, Papadimitriou G, Stefanis C (1986): Prolactin response induced by ECT and TRH. Br J Psychiatry 148:721-723. Papakostas Y, Markianos M, Papdimitriou G, Stefanis C (1990): Thyrotropin and prolactin secretion during ECT: Implications for the mechanism of ECT action. Convuls Ther 6:214-220. Parker CR, Porter JC (1984): Luteinizing hormone-releasing hormone and thyrotropin-releasing hormone in the hypothalamus of women: Effects of age and reproductive status. J Clin Endocrinol Metab 58:488-491. Ramey JN, Burrow GN, Polackwich RJ, Donabedian RK (1975): The effect of oral contraceptive steroids on the response to thyroid-stimulating hormone. J Clin Endocrinol Metab 40: 712-714. Raymond M, Lemarchund-Beraud T (1976): Effects of estrogens on prolactin and thyrotropin response to TRH in women during the menstrual cycle and under oral contraceptive treatment. Clin Endocrinol Metab 5:429-437. Rutlin E, Hang E, Torjesen PA (1977): Serum thyrotropin, prolactin and growth hormone response to TRH during oestrogen treatment. Acta Endocrinol 84:23-35. Wenzel KW, Meinhold H, Herplich M, Adlkofer F, Schleusener H (1974): TRH-Stimulationstest mit alters- und gescblechtsabhaengigem TSH--Anstieg bei Normalpersonen. Klin Wochenschr 52:722-727. Yen SSC (1978): Physiology of human prolactin. In Yen SSC, Jaffe RB (eds), Reproductive Endocrinology, Philadelphia: W.B. Saunders Co, pp 152-170.
The patterns of prolactin and thyrotropin (TSH) release after thyrotropin-releasing hormone (TRH) (0.4 mg i.v.) and during the first session of a course of electroconvulsive treatment (ECT) were studied in women with major depression, 16 in pre- and 29 in postmenopausal status. The prolactin responses to both stimuli were lower in postmenopausal women, whereas the TSH responses were not different. The known correlation between the maximal prolactin response to ECT and the maximal response to TRH was significantly stronger in the group of premenopausal women (r = .8648, versus .4249 in the postmenopausal group, p < .02). A common underlying mechanism promoting prolactin release for both stimuli can be suggested, which diminishes after menopause, probably an influence of estradiol on the affini O, of dopaminergic and serotonergic receptors. That mechanism does not interfere with the TSH release either by ECT or by TRH.
Key Words: Prolactin, depression
thyrotropin,
electroconvulsive
treatment,
TRH,
menopause,
BIoL PSYCHIATRY 1996;40:403--406
Introduction Although the positive effect of estrogens on the release of prolactin (PRL) and thyrotropin (TSH) is rather well documented (Jaffe et al 1973; Ramey et al 1975; Raymond et al 1976; De Lean et al 1977), the influence of circulating estradiol levels on the thyrotropin-releasing hormone (TRH)-induced PRL and TSH responses remains controversial (Jacobs et al 1973; Wenzel et al 1974; Erfurth et al 1984, 1992). Pharmacologic doses of estrogens promote From Athens University Medical School. Psychiatric Clinic, Eginition Hospital, Athens. Greece. Address reprint requests to Dr. Manolis Markianos. Athens University Medical School, Psychiatric Clinic, Eginition Hospital, Vas. Sophias 74. Athens 11528, Greece. Received February 13, 1995; revised July 14, 1995.
. © 1996 Society of Biological Ps2cchiatry
the synthesis and release of PRL by the pituitary (Yen et al 1978), probably by stimulating the regulation of PRL gene transcription (Maurer 1982). In menopause, a decrease in PRL plasma levels is observed that parallels the decline in plasma estradiol, so that postmenopausal women have lower basal PRL plasma levels than premenopausal women (Djursing et al 1981). It has been reported that in postmenopausal women, treatment with estradiol benzoate increases basal PRL levels and enhances the TRH-stimulated PRL release (Joseph et al 1986; Couzinet et al 1989), which has been found to be blunted (Linkowski et al 1980), or unaltered (Erfurth et al 1992) compared to the responses of premenopausal women. Regarding the TSH response to TRH, significant (Maes ") 0006-3.23/96/$15.00 SSD1 0006-3223(95)00396-X
404
BIOL PSYCHIATRY 1996;40:403-406
et al 1989) and nonsignificant (Erfurth et al 1992) reductions have been reported in postmenopausal women. Rutlin et al (1977) had reported no differences between menstruating and postmenopausal women, and no effect of estradiol treatment. This issue is of specific interest for biological psychiatry, since it has to be considered in evaluating the possibly blunted TSH-response to TRH in depressive patients compared to normal women (Maes et al 1989). Electroconvulsive treatment (ECT) causes substantial PRL release (Ohman et al 1976), and small but consistent release of TSH (Aperia et al 1985; Papakostas et al 1990). The elucidation of the underlying mechanisms is important for the understanding of the therapeutic mode of ECT action, and several reports have been published on this subject in recent years. The participation of TRH in the PRL response to ECT has been hypothesized, since a significant correlation has been found between the magnitudes of PRL responses to ECT and to TRH (Papakostas et al 1986; Devanand et al 1989). In the two lastmentioned studies the menopausal status was not taken into consideration. In this study, we performed the TRH test in 45 women with major depression who were assigned to ECT, and assessed also the PRL and TSH responses during the first ECT session, 2 - 4 days later. Sixteen of the patients were normally menstruating, and 29 were postmenopausal. We compared the patterns of PRL and TSH release during TRH and during ECT between the two groups, and examined the strength of the correlations between the PRL responses to TRH and to ECT for the whole group, and the pre- and postmenopausal subgroups separately.
Methods All patients were women hospitalized in the Psychiatric Clinic of the Athens University Medical School, Eginition Hospital. They suffered from major depression (DSMIII-R criteria), with a mean score on the 17-item Hamilton Depression Rating Scale of 27.4 (SD = 3.9, range 18-35). Electroconvulsive treatment was considered to be the appropriate therapeutic approach. They were drug-free for 1 week, with the exception of low doses of lorazepam (usually 2 rag) given at bedtime. Forty-five patients were included in the study. Their ages ranged from 24 to 73 years (mean 51.6, SD = 12.8). Sixteen of them were premenopausal (mean age 37.9, SD = 9.1), and 29 postmenopausal (mean age 59.2, SD = 6.6). The menopausal status was confirmed by estimations of plasma levels of estradiol, luteinizing hormone, and folliclestimulating hormone. Regarding diagnostic features, 14 of the 45 patients suffered from psychotic (delusional) depression, and 4 were bipolar. The number of psychotic vs.
M. M a r k i a n o s et al
nonpsychotic patients in the subgroups were 4 vs. 12 in the premenopausal group, and 10 vs. 19 in the postmenopausal group, i.e., they were similarly distributed (chisquare = 0.43, p = .51). From the 4 bipolar patients, 1 was pre- and 3 were postmenopausal (chi-square = 0.21, p = .64). The TRH test was performed by injection of 0.4 mg i.v., and blood sampling at times 0, 20, 40, and 60 rain. Two to four days later, during the first ECT session, blood samples were withdrawn at times 0, 15, 30, and 60 min. The ECT procedure included administration of sodium thiopental, succinylcholine, and oxygenation. ECT was given with the electrodes placed in the bitemporal position, using a pulse current device (Thymatron) at dial settings appropriate for the patient's age as recommended by the manual. The seizure was monitored by the cuff method, and the seizure duration had values between 18 and 45 sec (mean = 29.6 sec, SD = 6.7). In all patients included in the study the seizure was elicited with the first electrical stimulation. The first blood sample (time zero) was taken after succinylcholine administration. Plasma was separated by centrifugation, and stored at - 3 0 ° C until estimations. Prolactin and TSH were estimated using commercial radioimmunoassay kits. The coefficients of variation were around 5% for prolactin (Serono Diagnostics, Switzerland), and less than 5% for TSH (Medgenix, Belgium). For the statistical evaluation of the response patterns of PRL and of TSH to the two stimuli, we used analysis of variance with repeated measures (ANOVAR). When comparing the responses to ECT, the seizure duration was used as covariate, to compensate for possible influence of this variable on the magnitude of hormone secretion. Linear correlation coefficients between the maximal PRL and TSH responses to the two stimuli were also calculated for the whole group of 45 patients, and separately for the preand postmenopausal groups.
Results The baseline PRL plasma levels (samples taken at zero time during the TRH test) were lower in the postmenopausal women (mean = 7.2 ng/mL, SD = 3.3) compared to those of premenopausal (mean = 13.6, SD = 7.3, F = 16.55, p = .001), as has been reported previously by several authors (i.e., Djursing et al 1981). As expected, both ECT and TRH administration caused significant increases in both TSH and PRL. The patterns of these responses for the two groups are shown in Figure 1. Statistical evaluation, shown in Table I, revealed that the TSH responses to both stimuli were similar in the groups of pre- and postmenopausal women (group-time interactions not significant), but the PRL responses were differ-
Prolactin and TSH Responses to TRH and ECT
BIOLPSYCHIATRY
405
1996;40:403-406
100
I
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Figure 1. Patterns of prolactin (ng/mL) and TSH (mlU/mL) responses to ECT and TRH in 16 pre- (open circles) and 29 post- (filled circles) menopausal depressive patients. Mean values and SEM. X axis: time in minutes. ent, with the postmenopausal women having attenuated PRL responses both to ECT and to TRH compared to the premenopausal women. The significant positive correlation between the PRL responses to ECT and to TRH that has been reported by our group and by others (see Introduction), was present in the whole population of 45 subjects in this study (r =
.6817, p < .001). We calculated the correlation coefficients separately for the groups of pre- and of postmenopausal patients, and found that the correlation was significantly stronger in the group of premenopausal (r = .8716, n = 16) than in the group of postmenopausal (r = .4815, n = 25) women (difference between correlations, twosided test, p = .017).
Table 1. Statistical Evaluation (Repeated Measures ANOVA) of the Differences in the PRL and TSH Release Patterns a after TRH and after ECT, in Groups of Pre- (16 Patients) and Post(29 Patients) Menopausal Women with Major Depression, and for TRH in a Group of Male Depressive Patients, 21 in the Age Range 2 5 - 4 5 Years and 16 in the Range 5 0 - 6 6 Years
Discussion
PRL
TSH
ECT Effect
F
TRH p
F
Group (G) 4.06 .05 11.92 Time (T) 93.64 .000 153.65 G×T 3.28 .023 6.97 Male patients Group 0.54 Time 127.56 G×T 0.68 ~Shown in Figure 1.
ECT p
F
TRH p
F
p
.001 0.05 .83 0.01 .92 .000 15.08 .000 122.40 .000 .000 1 . 2 5 .29 0.21 .89 .47 .000 .56
0.20 .65 68.07 .000 0.30 .82
A blunted PRL response to TRH in depressive postmenopausal women, compared to premenopausal, has been previously reported (Linkowski et al 1980). Here we additionally report a similar finding for the PRL responses to ECT. This indicates that the factor affecting these responses is common in the mechanisms of PRL release by TRH and by ECT, and the most probable candidate is estradiol. Estrogen exerts a direct facilitating effect on PRL release, possibly by influencing the affinity status of dopaminergic and serotonergic receptors. The stronger correlation between the PRL responses to ECT and to TRH in the premenopausal women fits well to this assumption. An influence of endogenous TRH is not expected, since it has been found that the hypothalamic content of TRH in postmenopausal women is similar to
406
BIOL PSYCHIATRY
M. Markianos et al
1996;40:403-406
that of young women (Parker and Porter 1984). The exclusion of a TRH action is further supported by our finding that the TSH responses to both TRH and ECT were not related to menopause. The possibility that the effects we describe are not due to the menopausal status but are simply age effects cannot be ruled out. Data from a male population could be of help in elucidating this question. In our laboratory, we have data from male patients, adequate for analysis, only for the TRH test, and from 37 male depressive patients in the age range 2 5 - 6 6 years. We looked at these data, building two groups, one in the age range 2 5 - 4 5 years (mean = 33.9, SD = 5.4, 21 patients), and the other in the age range 5 0 - 6 6 years (mean = 58.6, SD = 4.7, 16 patients), and compared the patterns of PRL and TSH responses to TRH.
No indication of differences for either PRL or TSH responses was found (see Table 1). In addition, the correlations of age to PRL (r = .0503) and to TSH (r = .1512) responses to TRH for the whole group of male patients were not significant, and the same was true for the correlations between age and PRL responses to TRH or to ECT in the female pre- or postmenopausal subgroups. In conclusion, in depressive women, the PRL responses to TRH but also to ECT diminish after menopause, and this effect seems to be not an ageing effect but to be related to the circulating estrogens. Estradiol may facilitate directly the release of PRL by these stimuli, possibly by altering the affinity status of dopaminergic and serotonergic receptors.
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