Clinical Endocrinology (1979) 11,549-552.
TESTICULAR ENDOCRINE FUNCTION IN PARAPLEGIC MEN P. J . HAYES, K. R . K R I S H N A N , M . J . D I V E R , L. J . H I P K I N A N D J . C . DAVIS Royal Liverpool Hospital, Liverpool Regional Spinal Injuries Centre and University Sub- Department of Endocrine Pathology, Alder Hey Hospital, Liverpool (Received 2 April 1979; reLlised 21 May 1979,-accepred 26 M a y 1979)
SUMMARY
The responses of FSH and LH to the injection of LHRH were studied in fifteen paraplegic men and ten normal controls. The basal FSH levels in the paraplegic men were elevated in eight cases, basal LH being raised in nine cases. The responses of FSH were exaggerated in fourteen patients, and LH responses were exaggerated in nine patients. Only one patient was normal in respect of both hormones. Subnormal plasma testosterone was found in three patients. This depressed testicular function could not be explained as being due to spread of urinary tract infection and a direct neurological effect is the probable explanation. It has been known since 1837 that atrophy of the testes, sometimes associated with ‘preternatural enlargement of the breasts’ can occur in men with paraplegia (Thomson, 1837-8). The mechanism and frequency of this complication remain obscure, and this paper reports the findings of a sensitive test of gonadal function in such patients.
PATIENTS A N D METHODS Fifteen men with paraplegia were studied. Their ages ranged from 18 to 66 years (mean 40.5 years), and the durations of the spinal cord lesions were from 13 months to 30 years (mean 8.1 years). In two cases the causative lesion was a tumour; the paraplegia in the remaining cases was due to trauma. The level of the cord lesion was L 1-2 in three cases, thoracic in six cases and C 5-8 in six cases. Informed consent was obtained from all the patients studied. The normal controls for the LHRH test were ten healthy male volunteers aged 2 1 to 60 years. Basal levels of FSH, LH, prolactin and testosterone were available from a further group ofcontrol men. In the LHRH test 100 pg of the releasing-hormone were injected i.v. and blood was withdrawn before the injection and at intervals for 3 h afterwards. Correspondence: Dr J . C. Davis. Endocrine Unit, Alder Hey Hospital, Eaton Road, West Derby, Liverpool L12 ZAP.
0300-0664/79/1100-0549$02.00
0 1979 Blackwell Scientific Publications 549
P . J . Hayes el al.
5 50
Prolactin, FSH and LH were estimated by radioimmunoassay, using an lzSI labelled tracer and a double antibody separation technique (Institut National des Radioelements, Belgium). One mg of LH standard is equivalent to 4200 IU of M R C 68/40; 1 mg of FSH to 3 150 IU of M R C 68/39; the prolactin standard was M R C 7 1 /772. Testosterone was estimated by radioimmunoassay using antisera raised in rabbits and a dextran-charcoal separation method. RESULTS The responses to LHRH are summarized in Figs 1 and 2. The basal levels in the forty-one controls were 1.70+ 0.77 (SD) for FSH and 1.94kO.58 ng/ml for LH; the upper limits of normal were therefore taken as 3.2 ng/ml and 3.1 ng/ml respectively. Of the fifteen paraplegic patients, basal levels were above normal in eight cases (FSH) and nine cases (LH). Basal levels of both hormones were normal in only five of the fifteen cases. The responses of FSH to LHRH were exaggerated in fourteen of the patients, and LH responses were exaggerated in nine. In fact only one of the fifteen patients was normal in respect of both hormones. Serum prolactin levels in fifty normal men were 275 ( f99) mU/l. All the paraplegic patients were within the normal range (mean 243, range 106 to 386 mU/I). Mean serum testosterone levels in the paraplegic men were 13.0 nmol/l, range 6.0 to 22.7 nmol/l; the levels in all but three patients (6.0, 8. I and 6.0 nmol/l) fell within the normal range (8.2 to 27.8 nmol/l).
I 0
1
I
I
30
60
90
I I20
I
180
Time (min)
Fig. 1. Responses of FSH to LHRH. The normal levels (mean 2 SD) are shown by the stippled areas; the individual results in the paraplegic men are shown by the continuous lines.
Testes in paraplegia
55 1
30 28 26 24
A
I
\
22
20 18
-
E 16
\ 0 C
I
5
14 12
10 8 6
0
30
60
90
I20
I80
Time (min)
Fig. 2. Response of LH to LHRH. The normal levels (mean & 2 SD) are shown by the stippled areas; the individual results in the paraplegic men are shown by the continuous lines.
No correlation was observed between the duration or level of the cord lesion and the hormone findings. DISCUSSION The LHRH test is a sensitive test for the endocrine function of the testis and by this criterion fourteen out of the fifteen cases were abnormal. The testosterone levels were normal or only slightly depressed; these results are in accord with histological studies of the testes in men with cord lesions, which show atrophy of germ cells but normal or sometimes hyperplastic Leydig cells (Cooper & Hoen, 1949; Stemmerman et af., 1950; Bors et af.,1950; Planansky et al., 1956; Leriche et al., 1977). The mechanism by which paraplegia causes depression of testicular function remains obscure. It has been suggested that bladder sepsis is responsible, either by direct spread or by causing repeated febrile episodes. The occurrence of urinary tract infection was common to all these patients. However, in no case was there any clinical evidence of
552
P . J . Hayes et al.
spread to the scrotum and this factor was probably not significant; the importance of this mechanism has previously been discounted (Bors ef af.,1950). Other causes suggested are abnormal vasomotor control of the testicular blood vessels and contraction of the creniaster causing a rise in the mean intrascrotal temperature; however. no significant rise in temperature in the scrotum has been found in paraplegic patients (Morales & Hardin. 1958). Interference with nerve supply to the epithelial elements of the testis remains ;i possibility. Interest has recently been aroused by the possible use of artificial insemination o f tile wives by semen from the paraplegic husband. The present hormone findings, however, show impaired testicular endocrine function which is in keeping with the clinical experience that most paraplegics show oligospermia. ACKNOWLEDGEMENTS
Our thanks are due to Messrs. Hoechst Pharmaceuticals and Ayerst Laboratories Limited for their generous support of the project.
REFERENCES ROKS, E., ENGLE, E.T., ROSENQUIST, R.C. & HOLBIGER, V . H . (1950) Fertility in paraplegic II1;iIes. Journal I,/ Clinical Endocrinology and Meiabolism. 10, 39 1-398 COOPER. I.S. & HOEN, T.I. (1949) Gynecomasiia in paraplegic males: report of seven cases JOUJ-IIOI( I # Clinical Endocrinolo~ymid M~iabolisni,9, 4 5 7 4 6 1 . LEKICHE, A., BERAND. E., VAUZELLE. J.L., MINAISE, P.. GIKAKD, R . . ORCHIMBAUD. J P & BOURNET, J . ( I 977) Histological and hormonal testicular changes in spinal cord patients. Pnru/drgw. 15, 274-279 MORALES, P.A. & HARDIN, J . (1958) Scrota1 and testicular studies in paraplegics. Journcrl o/~Llro/o,qi,,79, 972 975 I'LANANSKY, K . , PILLAR, S. & SELBAK, G . (1956) Spinal cord lesion wilh hypogonadism and gynecomnstia. chromosomal sex. Jolrrnal of Clinical Endocrinology arid Melaholr.oii. 16, 1607 1613 SfiAHWAN, M . M . , SPATHIS. G.S., FRY, D . E . , WOOD, P . J .& MARKS, V. (1978) Differences In p~tuit;rry and testicular function between diabetic patients on insulin and oral antidiabetic agents. Dioheiologlu. 15, 13 17. STEMMEKMAN, G . N . , WEISS, L., ANSBACH, 0. & FRIEDMAN, M. (1950) A study of the germinal epithelium in male paraplegics. American Journal oJClinical Parhology, 20, 24-34. I'HOMSON. H . (1837-38) Preternatural enlargement of the breasts in a man. h n c e r . i, 356 357.
TESTICULAR ENDOCRINE FUNCTION IN PARAPLEGIC MEN P. J . HAYES, K. R . K R I S H N A N , M . J . D I V E R , L. J . H I P K I N A N D J . C . DAVIS Royal Liverpool Hospital, Liverpool Regional Spinal Injuries Centre and University Sub- Department of Endocrine Pathology, Alder Hey Hospital, Liverpool (Received 2 April 1979; reLlised 21 May 1979,-accepred 26 M a y 1979)
SUMMARY
The responses of FSH and LH to the injection of LHRH were studied in fifteen paraplegic men and ten normal controls. The basal FSH levels in the paraplegic men were elevated in eight cases, basal LH being raised in nine cases. The responses of FSH were exaggerated in fourteen patients, and LH responses were exaggerated in nine patients. Only one patient was normal in respect of both hormones. Subnormal plasma testosterone was found in three patients. This depressed testicular function could not be explained as being due to spread of urinary tract infection and a direct neurological effect is the probable explanation. It has been known since 1837 that atrophy of the testes, sometimes associated with ‘preternatural enlargement of the breasts’ can occur in men with paraplegia (Thomson, 1837-8). The mechanism and frequency of this complication remain obscure, and this paper reports the findings of a sensitive test of gonadal function in such patients.
PATIENTS A N D METHODS Fifteen men with paraplegia were studied. Their ages ranged from 18 to 66 years (mean 40.5 years), and the durations of the spinal cord lesions were from 13 months to 30 years (mean 8.1 years). In two cases the causative lesion was a tumour; the paraplegia in the remaining cases was due to trauma. The level of the cord lesion was L 1-2 in three cases, thoracic in six cases and C 5-8 in six cases. Informed consent was obtained from all the patients studied. The normal controls for the LHRH test were ten healthy male volunteers aged 2 1 to 60 years. Basal levels of FSH, LH, prolactin and testosterone were available from a further group ofcontrol men. In the LHRH test 100 pg of the releasing-hormone were injected i.v. and blood was withdrawn before the injection and at intervals for 3 h afterwards. Correspondence: Dr J . C. Davis. Endocrine Unit, Alder Hey Hospital, Eaton Road, West Derby, Liverpool L12 ZAP.
0300-0664/79/1100-0549$02.00
0 1979 Blackwell Scientific Publications 549
P . J . Hayes el al.
5 50
Prolactin, FSH and LH were estimated by radioimmunoassay, using an lzSI labelled tracer and a double antibody separation technique (Institut National des Radioelements, Belgium). One mg of LH standard is equivalent to 4200 IU of M R C 68/40; 1 mg of FSH to 3 150 IU of M R C 68/39; the prolactin standard was M R C 7 1 /772. Testosterone was estimated by radioimmunoassay using antisera raised in rabbits and a dextran-charcoal separation method. RESULTS The responses to LHRH are summarized in Figs 1 and 2. The basal levels in the forty-one controls were 1.70+ 0.77 (SD) for FSH and 1.94kO.58 ng/ml for LH; the upper limits of normal were therefore taken as 3.2 ng/ml and 3.1 ng/ml respectively. Of the fifteen paraplegic patients, basal levels were above normal in eight cases (FSH) and nine cases (LH). Basal levels of both hormones were normal in only five of the fifteen cases. The responses of FSH to LHRH were exaggerated in fourteen of the patients, and LH responses were exaggerated in nine. In fact only one of the fifteen patients was normal in respect of both hormones. Serum prolactin levels in fifty normal men were 275 ( f99) mU/l. All the paraplegic patients were within the normal range (mean 243, range 106 to 386 mU/I). Mean serum testosterone levels in the paraplegic men were 13.0 nmol/l, range 6.0 to 22.7 nmol/l; the levels in all but three patients (6.0, 8. I and 6.0 nmol/l) fell within the normal range (8.2 to 27.8 nmol/l).
I 0
1
I
I
30
60
90
I I20
I
180
Time (min)
Fig. 1. Responses of FSH to LHRH. The normal levels (mean 2 SD) are shown by the stippled areas; the individual results in the paraplegic men are shown by the continuous lines.
Testes in paraplegia
55 1
30 28 26 24
A
I
\
22
20 18
-
E 16
\ 0 C
I
5
14 12
10 8 6
0
30
60
90
I20
I80
Time (min)
Fig. 2. Response of LH to LHRH. The normal levels (mean & 2 SD) are shown by the stippled areas; the individual results in the paraplegic men are shown by the continuous lines.
No correlation was observed between the duration or level of the cord lesion and the hormone findings. DISCUSSION The LHRH test is a sensitive test for the endocrine function of the testis and by this criterion fourteen out of the fifteen cases were abnormal. The testosterone levels were normal or only slightly depressed; these results are in accord with histological studies of the testes in men with cord lesions, which show atrophy of germ cells but normal or sometimes hyperplastic Leydig cells (Cooper & Hoen, 1949; Stemmerman et af., 1950; Bors et af.,1950; Planansky et al., 1956; Leriche et al., 1977). The mechanism by which paraplegia causes depression of testicular function remains obscure. It has been suggested that bladder sepsis is responsible, either by direct spread or by causing repeated febrile episodes. The occurrence of urinary tract infection was common to all these patients. However, in no case was there any clinical evidence of
552
P . J . Hayes et al.
spread to the scrotum and this factor was probably not significant; the importance of this mechanism has previously been discounted (Bors ef af.,1950). Other causes suggested are abnormal vasomotor control of the testicular blood vessels and contraction of the creniaster causing a rise in the mean intrascrotal temperature; however. no significant rise in temperature in the scrotum has been found in paraplegic patients (Morales & Hardin. 1958). Interference with nerve supply to the epithelial elements of the testis remains ;i possibility. Interest has recently been aroused by the possible use of artificial insemination o f tile wives by semen from the paraplegic husband. The present hormone findings, however, show impaired testicular endocrine function which is in keeping with the clinical experience that most paraplegics show oligospermia. ACKNOWLEDGEMENTS
Our thanks are due to Messrs. Hoechst Pharmaceuticals and Ayerst Laboratories Limited for their generous support of the project.
REFERENCES ROKS, E., ENGLE, E.T., ROSENQUIST, R.C. & HOLBIGER, V . H . (1950) Fertility in paraplegic II1;iIes. Journal I,/ Clinical Endocrinology and Meiabolism. 10, 39 1-398 COOPER. I.S. & HOEN, T.I. (1949) Gynecomasiia in paraplegic males: report of seven cases JOUJ-IIOI( I # Clinical Endocrinolo~ymid M~iabolisni,9, 4 5 7 4 6 1 . LEKICHE, A., BERAND. E., VAUZELLE. J.L., MINAISE, P.. GIKAKD, R . . ORCHIMBAUD. J P & BOURNET, J . ( I 977) Histological and hormonal testicular changes in spinal cord patients. Pnru/drgw. 15, 274-279 MORALES, P.A. & HARDIN, J . (1958) Scrota1 and testicular studies in paraplegics. Journcrl o/~Llro/o,qi,,79, 972 975 I'LANANSKY, K . , PILLAR, S. & SELBAK, G . (1956) Spinal cord lesion wilh hypogonadism and gynecomnstia. chromosomal sex. Jolrrnal of Clinical Endocrinology arid Melaholr.oii. 16, 1607 1613 SfiAHWAN, M . M . , SPATHIS. G.S., FRY, D . E . , WOOD, P . J .& MARKS, V. (1978) Differences In p~tuit;rry and testicular function between diabetic patients on insulin and oral antidiabetic agents. Dioheiologlu. 15, 13 17. STEMMEKMAN, G . N . , WEISS, L., ANSBACH, 0. & FRIEDMAN, M. (1950) A study of the germinal epithelium in male paraplegics. American Journal oJClinical Parhology, 20, 24-34. I'HOMSON. H . (1837-38) Preternatural enlargement of the breasts in a man. h n c e r . i, 356 357.
