Comments Influence of Surgical Stress Under General Anesthesia on Serum Gonadotropin Levels in Male and Female Patients T. AONO, 1 K. KURACHI, 1 M. MIYATA, 2 A. NAKASIMA, 3 K. KOSHIYAMA, 3 T. UOZUMI, 4 AND K. MATSUMOTO 5 Departments of Obstetrics and Gynecology,1 Surgery,2 and Pathology,5 Osaka University Medical School, Osaka, Department of Neuro surgery,4 Hiroshima University Medical School, Hiroshima and National Sanatorium Toneyama Hospital,3 Toyonaka, Osaka, Japan ABSTRACT. Effects of surgical stress under the same general anesthesia (nitrous oxide, oxygen and halothane following induction with thiopental and succinylcholine chloride) on serum LH levels were studied in 18 postmenopausal females, 15 menstruating females and 17 males. In addition, serum FSH levels in female patients and
increase in LH levels was found in female patients. In male and female patients, the LH levels decreased slightly 5-6 h and 2 days after onset of anesthesia, though the decreases were not statistically significant except in postmenopausal females. On the 7th post-operative day, the LH levels returned toward the baseline. In female patients, no significant intra-operative changes in FSH levels were found. In male patients, there were significant intra- and post-operative decreases in testosterone levels. In control subjects, no significant changes in serum levels of LH, FSH and testosterone were demonstrated. These observations suggest that significant intraoperative increases in serum LH levels occur in males but not in females. (J Clin Endocrinol Metab 42: 144, 1976)
testosterone
levels in male patients were estimated. As controls without surgery and anesthesia, serum levels of LH, FSH and testosterone were estimated at identical time intervals to the experimental group in 15 normal postmenopausal females, 15 normal menstruating females and 10 normal males. In male patients, serum LH levels at 30 min and 1 h after onset of anesthesia increased significantly over those of pre-anesthesia, while no significant intra-operative
I
N previous papers (1,2), we reported in male patients that serum LH levels increased significantly from pre-anesthesia levels during operation under general anesthesia. At the end of operation, the LH levels returned to their pre-anesthesia levels. However, Charters et al. (3) found no significant intra-operative increase in the concentration of LH in 13 patients comprising 10 females and only 3 males. With regard to serum gonadotropins after operation under general anesthesia, we (1,2) and Charters et al. (3) found a decrease in serum LH and FSH levels on the first 2 post-operative days in both male and female patients. These results seem to suggest that the intra-operative response of serum LH in males might be different from that in postmenopausal females with very high basal LH level and in menstruating females. In the present study, estimations of serum LH, FSH and testosterone were made in 17 males, Received January 22, 1975. Reprints: Dr. T. Aono, Dept. of Obstetrics and Gynecology, Osaka University Medical School, Fukushima-ku, Osaka, Japan.
18 postmenopausal females and 15 menstruating females before, during and following operations under the same general anesthesia. Materials and Methods Blood samples were taken from 17 males, aged 24-58 years who underwent pulmonary lobectomy (12 patients), gastrectomy (4 patients) or cholecystectomy (1 patient), 18 postmenopausal females, aged 48-71 years who underwent pulmonary lobectomy (11 patients), gastrectomy (4 patients) or cholecystectomy (3 patients) and 15 menstruating females, aged 19-43 years who underwent pulmonary lobectomy (12 patients), gastrectomy (1 patient) or cholecystectomy (2 patients). None of these patients had any disorders of the endocrine system, liver or kidney functions as judged by routine tests. None of them had received ACTH, gonadotropins, corticosteroids or sex steroids. The patients had not been exposed to any particular kind of stress before operation. One hour before operations, all the patients were injected with 50 mg of hydroxyzinepamoate and 0.5 mg of atropine sulphate. Our previous investigation (2) revealed that these pre-anesthetic medications were not responsible for the intra- and post-operative changes in serum levels of LH and testosterone. The levels of LH and testosterone exhibited no significant changes
144
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145
COMMENTS during and following fiberoptic bronchoscopy under local anesthesia in males pre-treated with hydroxyzinepamoate and atropine sulfate (2). All the operations, which began at 9 AM, were carried out at room temperature and the duration of surgery from incision to closure ranged 2-4 h. Anesthesia was maintained with nitrous oxide, oxygen and halothane following induction with thiopental and succinylcholine chloride in all the patients. The interval between the induction of anesthesia and the beginning of incision was about 30 min. About 500 ml of plasma substitutes and 1000 ml of electrolyte solution were infused into each of the patients during and shortly following operation. None of the patients showed any complications following their operations. Control serum samples were taken immediately before anesthesia. Subsequent samples were obtained from the patients 30 min, 1 and 5-6 h after onset of anesthesia and at 9 AM on the 2nd and 7th post-operative days. As controls without surgery and anesthesia, serum samples were obtained at identical time intervals to the experimental group from 10 normal males aged 30-55 years, 15 normal postmenopausal females aged 50-70 years and 15 normal menstruating females aged 22-40 years. The serum was separated soon by centrifugation, stored at -20 C until required and used within 4 weeks. Concentrations of serum testosterone were measured by the competitive protein binding method of Mayes and Nugent (4). Serum levels of LH and FSH were measured by the radioimmunoassay method (5,6) with slight modifications as previously described (1). All samples from a given patient were run in the same assay. The evaluation of the LH, FSH and testosterone assays including specificity studies was satisfactory as previously reported (1,7). For LH and
FSH assays, the Second International Reference Preparation of Human Menopausal Gonadotropin was employed as the standard material and the value was expressed in fig of LER 907 per 100 ml of serum. The conversion factors, 219 mIU//x.g for LH and 38 mlU/fig for FSH, were applied according to the report of Albert, et al. (8). The intra- and inter-assay coefficient of variation in a normal male range obtained from 10 assays were 8.8 and 13.6%, respectively in the LH assay and 10.1 and 15.4%, respectively in the FSH assay and 8.9 and 9.7%, respectively in the testosterone assay. Evidences for the follicular and luteal phases in menstruating females were obtained by urinary 5/8-pregnane-3a,20a-diol excretions, serum progesterone levels and basal temperature curves.
Results The pre-, during- and post-anesthesia levels of serum LH, FSH and testosterone are shown in Table 1. Figure 1 shows the average percentage changes of serum LH levels from the pre-anesthesia levels in the same patients. In male patients, the levels of serum LH increased significantly from those of the control (preanesthesia) 30 min and 1 h after the beginning of general anesthesia, while no significant intraoperative increase in LH levels was found in female patients. In male and female patients, the LH levels decreased slightly 5-6 h and 2 days after onset of anesthesia, though the decreases were not statistically significant except in postmenopausal females. The LH levels returned toward the baseline on the 7th postoperative day.
TABLE 1. Effects of surgery under general anesthesia on serum LH, FSH and testosterone levels in males and females After onset of anesthesia No. of patients
Preanesthesia
30 min
Post-anesthesia 2nd day
5-6 h
lh
7th day
LH (Mean ± SE fig/WO ml) Postmenopausal females Femnles with menses Follicular phase Luteal phase Males
18 15 11 4 17
33.0 :t 6.4 it 6.0 Ht 7.6 :t 6.2 :b
3.3 1.5 1.5 4.3 0.7
33.7 4.8 4.5 5.5 9.1
st it i: :t :i
3.0 0.7 0.7 2.1 1.2*
38.6 ± 7.4 ± 5.7 ± 11.8 ± 11.5 ±
4.4 2.0 1.4 5.6 1.3t
26.1 4.9 4.8 5.1 4.7
it it i: it it
3.8* 1.2 1.2 2.8 0.7
26.9 6.3 6.7 5.3 5.4
± ± ± ± ±
168 20.7 21.7 18.4
± ± ± ±
3.2* 1.1 1.1 3.1 0.6
29.9 7.2 9.0 2.8 6.6
± ± ± ± ±
3.8
176 22.2 25.8 13.2
± ± ± ±
15* 3.0 3.6 2.3
1.2
1.2 1.3 0.5
FSH (Mean ± s : ugllO -)ml) Postmenopausal females Females with menses Follicular phase Luteal phase
18 15 11 4
219 22.7 24.0 18.9
± :t :t .t
17 1.9 2.4 2.6
232 23.1 24.0 20.0
± :t :t :t
18 2.1 2.7 3.6
276 21.5 23.4 16.6
±32
± 2.6 ± 2.9 ± 4.7
183 20.0 23.5 17.9
± 15 :b 2.9 ± 2.9 :t 6.2
16t 2.3 3.1 2.0
Testosterone (Mean ± SE fig/100 ml) Males
17
0.58 t 0.03
0.51 t 0.03*
0.53 ± 0.03
0.47 t 0.03t
0.35 ± 0.04 f
0.51 ± 0.04
Differences from "Pre-anesthesia" P: * < 0.05, j < 0.01 (A t test for paired observations was used).
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146
JCE & M • 1976 Vol 42 • No 1
COMMENTS
SERUM LH
**
+80
period, those of postmenopausal females showed a significant decrease in the same period. In male patients, significantly decreased levels of serum testosterone from pre-anesthesia levels were found during and up to 2 days following surgery. In each group, patients who had undergone pulmonary lobectomy, gastrectomy or cholecystectomy, showed similar intra- and post-operative response of serum gonadotropin and testosterone levels. In menstruating females, there were no significant differences in the intraand post-operative change of serum gonadotropin levels between the patients in follicular and luteal phases. Concentrations of LH, FSH and testosterone in serum collected from normal males and females at identical time intervals to the experimental group are shown in Table 2. In control subjects, no significant changes in serum levels of LH, FSH and testosterone were demonstrated.
Males
Postmenopausal females
+60 +40 +20
o-o
/* \ /
Females with menses
\
1
/ /
v
•
••.
\
0 in
-20
t
--'>
i
JC
in 0)
-40 L
c
increase in LH levels was found in female patients. In male and female patients, the LH levels decreased slightly 5-6 h and 2 days after onset of anesthesia, though the decreases were not statistically significant except in postmenopausal females. On the 7th post-operative day, the LH levels returned toward the baseline. In female patients, no significant intra-operative changes in FSH levels were found. In male patients, there were significant intra- and post-operative decreases in testosterone levels. In control subjects, no significant changes in serum levels of LH, FSH and testosterone were demonstrated. These observations suggest that significant intraoperative increases in serum LH levels occur in males but not in females. (J Clin Endocrinol Metab 42: 144, 1976)
testosterone
levels in male patients were estimated. As controls without surgery and anesthesia, serum levels of LH, FSH and testosterone were estimated at identical time intervals to the experimental group in 15 normal postmenopausal females, 15 normal menstruating females and 10 normal males. In male patients, serum LH levels at 30 min and 1 h after onset of anesthesia increased significantly over those of pre-anesthesia, while no significant intra-operative
I
N previous papers (1,2), we reported in male patients that serum LH levels increased significantly from pre-anesthesia levels during operation under general anesthesia. At the end of operation, the LH levels returned to their pre-anesthesia levels. However, Charters et al. (3) found no significant intra-operative increase in the concentration of LH in 13 patients comprising 10 females and only 3 males. With regard to serum gonadotropins after operation under general anesthesia, we (1,2) and Charters et al. (3) found a decrease in serum LH and FSH levels on the first 2 post-operative days in both male and female patients. These results seem to suggest that the intra-operative response of serum LH in males might be different from that in postmenopausal females with very high basal LH level and in menstruating females. In the present study, estimations of serum LH, FSH and testosterone were made in 17 males, Received January 22, 1975. Reprints: Dr. T. Aono, Dept. of Obstetrics and Gynecology, Osaka University Medical School, Fukushima-ku, Osaka, Japan.
18 postmenopausal females and 15 menstruating females before, during and following operations under the same general anesthesia. Materials and Methods Blood samples were taken from 17 males, aged 24-58 years who underwent pulmonary lobectomy (12 patients), gastrectomy (4 patients) or cholecystectomy (1 patient), 18 postmenopausal females, aged 48-71 years who underwent pulmonary lobectomy (11 patients), gastrectomy (4 patients) or cholecystectomy (3 patients) and 15 menstruating females, aged 19-43 years who underwent pulmonary lobectomy (12 patients), gastrectomy (1 patient) or cholecystectomy (2 patients). None of these patients had any disorders of the endocrine system, liver or kidney functions as judged by routine tests. None of them had received ACTH, gonadotropins, corticosteroids or sex steroids. The patients had not been exposed to any particular kind of stress before operation. One hour before operations, all the patients were injected with 50 mg of hydroxyzinepamoate and 0.5 mg of atropine sulphate. Our previous investigation (2) revealed that these pre-anesthetic medications were not responsible for the intra- and post-operative changes in serum levels of LH and testosterone. The levels of LH and testosterone exhibited no significant changes
144
The Endocrine Society. Downloaded from press.endocrine.org by [${individualUser.displayName}] on 05 November 2015. at 12:49 For personal use only. No other uses without permission. . All rights reserved.
145
COMMENTS during and following fiberoptic bronchoscopy under local anesthesia in males pre-treated with hydroxyzinepamoate and atropine sulfate (2). All the operations, which began at 9 AM, were carried out at room temperature and the duration of surgery from incision to closure ranged 2-4 h. Anesthesia was maintained with nitrous oxide, oxygen and halothane following induction with thiopental and succinylcholine chloride in all the patients. The interval between the induction of anesthesia and the beginning of incision was about 30 min. About 500 ml of plasma substitutes and 1000 ml of electrolyte solution were infused into each of the patients during and shortly following operation. None of the patients showed any complications following their operations. Control serum samples were taken immediately before anesthesia. Subsequent samples were obtained from the patients 30 min, 1 and 5-6 h after onset of anesthesia and at 9 AM on the 2nd and 7th post-operative days. As controls without surgery and anesthesia, serum samples were obtained at identical time intervals to the experimental group from 10 normal males aged 30-55 years, 15 normal postmenopausal females aged 50-70 years and 15 normal menstruating females aged 22-40 years. The serum was separated soon by centrifugation, stored at -20 C until required and used within 4 weeks. Concentrations of serum testosterone were measured by the competitive protein binding method of Mayes and Nugent (4). Serum levels of LH and FSH were measured by the radioimmunoassay method (5,6) with slight modifications as previously described (1). All samples from a given patient were run in the same assay. The evaluation of the LH, FSH and testosterone assays including specificity studies was satisfactory as previously reported (1,7). For LH and
FSH assays, the Second International Reference Preparation of Human Menopausal Gonadotropin was employed as the standard material and the value was expressed in fig of LER 907 per 100 ml of serum. The conversion factors, 219 mIU//x.g for LH and 38 mlU/fig for FSH, were applied according to the report of Albert, et al. (8). The intra- and inter-assay coefficient of variation in a normal male range obtained from 10 assays were 8.8 and 13.6%, respectively in the LH assay and 10.1 and 15.4%, respectively in the FSH assay and 8.9 and 9.7%, respectively in the testosterone assay. Evidences for the follicular and luteal phases in menstruating females were obtained by urinary 5/8-pregnane-3a,20a-diol excretions, serum progesterone levels and basal temperature curves.
Results The pre-, during- and post-anesthesia levels of serum LH, FSH and testosterone are shown in Table 1. Figure 1 shows the average percentage changes of serum LH levels from the pre-anesthesia levels in the same patients. In male patients, the levels of serum LH increased significantly from those of the control (preanesthesia) 30 min and 1 h after the beginning of general anesthesia, while no significant intraoperative increase in LH levels was found in female patients. In male and female patients, the LH levels decreased slightly 5-6 h and 2 days after onset of anesthesia, though the decreases were not statistically significant except in postmenopausal females. The LH levels returned toward the baseline on the 7th postoperative day.
TABLE 1. Effects of surgery under general anesthesia on serum LH, FSH and testosterone levels in males and females After onset of anesthesia No. of patients
Preanesthesia
30 min
Post-anesthesia 2nd day
5-6 h
lh
7th day
LH (Mean ± SE fig/WO ml) Postmenopausal females Femnles with menses Follicular phase Luteal phase Males
18 15 11 4 17
33.0 :t 6.4 it 6.0 Ht 7.6 :t 6.2 :b
3.3 1.5 1.5 4.3 0.7
33.7 4.8 4.5 5.5 9.1
st it i: :t :i
3.0 0.7 0.7 2.1 1.2*
38.6 ± 7.4 ± 5.7 ± 11.8 ± 11.5 ±
4.4 2.0 1.4 5.6 1.3t
26.1 4.9 4.8 5.1 4.7
it it i: it it
3.8* 1.2 1.2 2.8 0.7
26.9 6.3 6.7 5.3 5.4
± ± ± ± ±
168 20.7 21.7 18.4
± ± ± ±
3.2* 1.1 1.1 3.1 0.6
29.9 7.2 9.0 2.8 6.6
± ± ± ± ±
3.8
176 22.2 25.8 13.2
± ± ± ±
15* 3.0 3.6 2.3
1.2
1.2 1.3 0.5
FSH (Mean ± s : ugllO -)ml) Postmenopausal females Females with menses Follicular phase Luteal phase
18 15 11 4
219 22.7 24.0 18.9
± :t :t .t
17 1.9 2.4 2.6
232 23.1 24.0 20.0
± :t :t :t
18 2.1 2.7 3.6
276 21.5 23.4 16.6
±32
± 2.6 ± 2.9 ± 4.7
183 20.0 23.5 17.9
± 15 :b 2.9 ± 2.9 :t 6.2
16t 2.3 3.1 2.0
Testosterone (Mean ± SE fig/100 ml) Males
17
0.58 t 0.03
0.51 t 0.03*
0.53 ± 0.03
0.47 t 0.03t
0.35 ± 0.04 f
0.51 ± 0.04
Differences from "Pre-anesthesia" P: * < 0.05, j < 0.01 (A t test for paired observations was used).
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146
JCE & M • 1976 Vol 42 • No 1
COMMENTS
SERUM LH
**
+80
period, those of postmenopausal females showed a significant decrease in the same period. In male patients, significantly decreased levels of serum testosterone from pre-anesthesia levels were found during and up to 2 days following surgery. In each group, patients who had undergone pulmonary lobectomy, gastrectomy or cholecystectomy, showed similar intra- and post-operative response of serum gonadotropin and testosterone levels. In menstruating females, there were no significant differences in the intraand post-operative change of serum gonadotropin levels between the patients in follicular and luteal phases. Concentrations of LH, FSH and testosterone in serum collected from normal males and females at identical time intervals to the experimental group are shown in Table 2. In control subjects, no significant changes in serum levels of LH, FSH and testosterone were demonstrated.
Males
Postmenopausal females
+60 +40 +20
o-o
/* \ /
Females with menses
\
1
/ /
v
•
••.
\
0 in
-20
t
--'>
i
JC
in 0)
-40 L
c
