Subnormal serum testosterone levels in male internal medicine residents Frank
Singer* and Barnett Zumoff
Division o f Endocrinology, D e p a r t m e n t o f Medicine, Beth Israel Medical Center and The M o u n t Sinai School o f Medicine ( C U N Y ) , N e w York, N e w York, U S A
The consequences of sleep deprivation and stress in residency training have not been quantified. In the course of assembling a control group for other studies, we unexpectedly observed a significant (P < 0.005) and marked depression of serum testosterone levels in healthy male internal medicine residents (~ = 11.8 4- 1.1 nmollL, n = 7) compared with other hospital personnel (£ = 20.6 +- 5.3 nmol/L, n = 18). Testosterone concentrations in the two groups were entirely nonoverlapping, while luteinizing hormone levels were not significantly different. We conclude that the stress of residency training leads to a quantifiable depression of gonadal function, and that gonadal steroid concentrations may be useful in evaluating measures intended to reduce that stress. (Steroids 57: 86-89, 1992)
Keywords:testosterone in male residents; steroids; hypogonadotropic hypogonadism; stress; residency, effects on testosterone
Introduction
Experimental
It is generally believed that the stress and sleep deprivation o f r e s i d e n c y training h a v e negative effects on the well-being o f residents, I-6 but there is little concrete e v i d e n c e to s u p p o r t this belief. 6 T h e r e are data indicating that a significant p r o p o r t i o n o f residents exp e r i e n c e d e p r e s s i v e s y m p t o m s . 7-9 M a n y residents also r e p o r t m a j o r p r o b l e m s in their relationships with s p o u s e s o r lovers, w h i c h t h e y attribute to their resid e n c y training.l° It has b e e n suggested that the e m o tional p r o b l e m s e x p e r i e n c e d b y residents are as m u c h a f u n c t i o n o f certain individuals' p r e m o r b i d personalities a n d genetic predisposition to d e p r e s s i o n as t h e y are due to stress. 7 In the c o u r s e o f assembling a control g r o u p for o t h e r studies, w e u n e x p e c t e d l y o b s e r v e d s u b n o r m a l s e r u m t e s t o s t e r o n e levels in a g r o u p o f healthy internal medicine male residents. O u r finding in these subjects is, to o u r k n o w l e d g e , the first d e m o n s t r a t i o n o f a quantifiable stress-related b i o c h e m i c a l a b n o r m a l i t y in physicians during r e s i d e n c y training.
Normal healthy male subjects were solicited from among hospital personnel and housestaffat Beth Israel Medical Center (New York, New York, USA) to serve as controls in a study of male hypogonadism. Venous blood was withdrawn from an antecubital vein between the hours of 9:00 AM and 12:00 noon, and serum was separated for radioimmunoassay of testosterone and luteinizing hormone. The subjects included seven members of the medicine residency program, including four at the PGY-I level and three at the PGY-II level. All residents were working "on the floors" and were on call once every fourth night. During on-call nights, it is estimated that these residents were averaging between 2 and 4 hours of sleep. The subjects also included 18 male hospital employees who were not members of the medicine residency program; one was a pathology resident and the remainder were not physicians. These subjects were all working during regular daytime hours and were .sleeping at night. They were selected to exclude subjects with known causes for hypogonadism; specifically, none were marathon runners, H marijuana smokers, ~2obese) 3 or on a severely calorie-restricted diet. J4 Radioimmunoassays of testosterone were done using tritiated testosterone, obtained from Amersham Corp. (Arlington Heights, IL, USA), purified monthly on 50-ml columns of Sephadex LH-20 (Pharmacia Fine Chemicals, Piscataway, NJ, USA) equilibrated with toluene-methanol (85 : 15 v/v). ~5Nonradioactive testosterone obtained from Steraioids, Inc. (Wilton, NH, USA) was used. Testosterone concentration was determined by the method of Boyar et al.,~6 with the following modifications. Ether extracts of the serum were evaporated to dryness under nitrogen, redissolved in small volumes (0.2 ml) of isooctane-
*Present address: Harlem Hospital Center, Department of Medicine (12th floor), 135th Street and Lenox Avenue, New York, NY 10037, USA. Address reprint requests to Dr. Frank Singer, at the Department of Medicine (12th floor), Harlem Hospital Center, 135th Street and Lenox Avenue, New York, NY 10037, USA. ReceivedApril 15, 1991; accepted AUgust 7, 1991.
86
Steroids, 1992, vol. 57, February
© 1992 Butterworth-Heinemann
Serum T in male internal medicine residents: Singer and Zumoff toluene-methanol (90:5:5 v/v/v), and chromatographed on columns containing 1,000 rag Sephadex LH-20 (QS columns; Isolab, Inc., Akron, OH, USA) equilibrated with the same solvent system. The fractions of column eluate containing testosterone (but not dihydrotestosterone) were evaporated to dryness under nitrogen and redissolved in 0.01 M phosphatebuffered saline, pH 7.4, containing 0.1% gelatin and 0.02% NAN3. Aliquots were counted to determine recovery, and other aliquots were assayed from Radioassay Systems Laboratories, Inc. (Carson, CA, USA). The sensitivity of this assay has previously been shown to be 1.3 pg/tube. Iv Serum luteinizing hormone concentration was determined by a double-antibody procedure, using radioimmunoassay reagents from the National Hormone and Pituitary Program, NIDDK, a n d goat anti-rabbit gamma globulin obtained from Pantex (Santa Monica, CA, USA). The antiserum to human luteinizing hormone has a relative potency in terms of the second IRPHMG of 0.277 mIU/ng LET-907. The sensitivity of the assay for luteinizing hormone is 0.6 mIU/tube.~7 The radioimmunoassay data were analyzed as described by Davis et al.18 The intraassay and interassay coefficients of variation were less than 10%, using charcoal-treated plasma 19supplemented with known amounts of steroid or control serum samples (RIATRAC Plus) purchased from Becton-Dickinson Immunodiagnostics (Orangeburg, NY, USA).
20 m
18
m
1
1
A J
Z 0
16
m
14
m
m
m
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O0
= 0
12
m
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i
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I
MALE MEDICAL RESIDENTS
Figure 2 Serum luteinizing hormone in male hospital employees and medical residents. The mean concentration for male residents (x -- 9.7 -+ 2.2 IU/L) is not significantly different from that for other hospital employees (~ = 10.3 -+ 3.6 IU/L).
O0 O0
20
MALE HOSPITAL EMPLOYEES
m
W O0
o
16
Significance of differences between the two groups studied was evaluated by Student's t test, two-tailed.
$ W 2~ ','
Results
& 8
m
I
4 0
MALE HOSPITAL EMPLOYEES
MALE MEDICAL RESI DENTS
Rgure 1 Serum testosterone in male hospital employees and medical residents. The mean concentration for male residents (~ = 11.8 - 1.06 nmol/L) is significantly (P < 0.0005) lower than that for other male hospital employees (~ = 20.6 + 5.28 nmol/L).
The mean serum testosterone concentration for the seven medicine residents was 11.8 -+ 1.06 nmol/L, with a range from 10.6 to 13.0 nmol/L. This was 43% lower than the mean serum testosterone for the 18 male hospital employees, which was 20.6 - 5.28 nmol/ L, with a range from 13.1 to 30.8 nmol/L (Figure 1). The testosterone levels in the two groups were entirely nonoverlapping, and the difference between the two mean values was highly significant ( P < .0.0005). The serum testosterone levels in the male hospital employees were similar to previous results in normal controls in our laboratory and in the published literature. 2° The coefficient of variation of the values in the male hospital employees was 0.26, similar to that of other hormone determinations in normal subjects, 21,22 while the coefficient of variation of the values in the medi-
Steroids, 1992, vol. 57, February
87
Papers cine residents was much lower at 0.09, with all the values tightly bunched in the lower end of the normal range. The mean serum luteinizing hormone concentration for the seven medicine residents was 9.7 -+ 2.2 IU/L compared with a mean of 10.3 -+ 3.6 IU/L for the 18 male hospital employees (Figure 2); this difference was not significant.
Discussion The results of this study clearly indicate that the male medicine residents had much lower serum testosterone levels than the other nonphysician male hospital employees or than is reported in normal controls) ° If these low values were due to primary testicular hypofunction, luteinizing hormone values would be expected to be elevated by approximately 70%23; since the luteinizing hormone values were not elevated, but normal, the low testosterone values represent hypogonadotropic hypogonadism. Interviews were held with the residents in an attempt to discover possible causes of their hypogonadal status. No subjects were obese, on a severely calorierestricted diet, or marathon runners. The mean age of the residents was slightly, though significantly, younger than the male hospital employees: 27 -+ 1.3 versus 32 -+ 7.1 years (P < 0.05). One resident was a jogger, a second did heavy exercise, and a third smoked marijuana, but the testosterone levels in these three were in the same narrow range as the values in the other four residents: the coefficient of variation for testosterone levels within the residents' group was very low (0.09), unlike the normal hospital employees (0.26). Thus, it is unlikely that these potential factors were contributing significantly to the low testosterone levels in the residents' group. It has been suggested that serum levels of gonadotropins and sex steroids be assayed from two or three pooled samples to avoid measuring peaks and troughs of episodic secretion, which could increase the sample variation and lead to excessive deviation of the sample mean from the true mean. The single serum sample testosterone concentrations from our male hospital employees showed no greater coefficient of variation (0.26) than found in normal mean 24-hour testosterone levels (0.25) from samples drawn at 20-minute intervals. 22 Thus, our use of single serum sample testosterone measurements did not lead to this potential artifact. The coefficient of variation for the residents' testosterone levels was even lower; it is highly improbable that their decreased serum testosterone levels were caused by a coincidence of secretory troughs. Severe stress, such as from s u r g e r y 24 o r myocardial infarction, 25 is known to cause suppression of gonadal steroids. Sleep deprivation has also been reported to cause hypogonadotropic hypogonadism. 26,27 Plasma testosterone levels decreased an average of 32% during a period of severe psychological stress in a group of men enrolled in officer candidate school, while fac-
88
Steroids, 1992, vol. 57, February
tors such as exercise, diet, and sleep schedules remained constant. 28 The degree of decrease in serum testosterone levels in this group of medicine residents was striking and unexpected. Since most of the residents studied had no other known cause for their hypogonadism, it is quite probable that both psychological stress and sleep deprivation, which are prominent features of this type of training, contribute to the significantly subnormal testosterone levels. The uniformity and severity of the hypogonadism reflect the magnitude of the stresses involved and provide a potential tool both to quantify the stress and to evaluate whether corrective measures, such as the limitation of a resident's duty hours to 80 per week, 29 have any real stress-reducing effect. Male hypogonadism can have important consequences for the resident, as it does for other people. Testosterone levels in the 10 to 13 nmol/L range may contribute to relative sexual inadequacy. In turn, this can interfere with both established and desired sexual relationships with spouses and lovers. Since a young male's ego is at least partly sexual in identity, this can further lead to loss of self-esteem. Depressive symptoms under these circumstances would not be surprising. We did not do psychological testing of the residents in our study. A future study to correlate residents' depressive and sexual symptomatology with gonadal steroid levels would be of interest.
References I. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14.
McCue JD (1985). The distress of internship: causes and prevention. N Engl J Med 312:449-452. Hardison JE (1986). The house officer's changing world. N Engl J Med 314:1713-1715. Blackwell B (1986). Prevention of impairment among residents in training. ,lAMA 225:1177-1178. Weinstein HM (1983). A committee on well-being of medical students and house staff. J Med Educ 58:373-381. McCall TB (1988). The impact of long working hours on resident physicians. N Engl J Med 318:775-778. Asken MJ, Raham DC (1983). Resident performance and sleep deprivation: a review. J Med Edac 58:382-388. Valko RJ, Clayton PJ (1975). Depression in the internship. Dis Nerv Syst 36:26-29. Reuben DB (1985). Depressive symptoms in medical house officers: effects of level of training and work rotation. Arch Intern Med 145:286-288. Clark DC, Salazar-Greso E, Grabler P, Fawcett J (1984). Predictors of depression during the first 6 months of internship. Am J Psychiatry 141:1095-1098. Landau C, Hall S, Wartman SA, Macko MB (1986). Stress in social and family relationships during the medical residency. J Med Edac 61:654-660. Reichlin S (1985). Neuroendocrinology. In: Wilson JD, Foster DW (eds), Williams Textbook of Endocrinology, 7th ed. Saunders, Philadelphia, pp. 492-567. Kolodny RC, Masters WH, Kolodner RM, Tom G (1974). Depression of plasma testosterone levels after chronic intensive marihuana use. N Engl'J Med ~10:872-874. Strain GW, Zumoff B, Kream J, et a~ (1982). Mild hypogonadotropic hypogonadism in obese men. Metabolism 31:871875. HotTer LI, Beitins IZ, Kyung N-H, B/st/an BR (1986). Effects of severe dietary restriction on male reproductive hormones. `l Clin Endocrinol Metab 62:288-292.
Serum T in male internal medicine residents: Singer and Zumoff 15. 16.
17. 18. 19. 20. 21.
Stanik S, Domfeld LP, Maxwell MH, Viosca SP, Korenman SG (1981). The effect of weight loss on reproductive hormones in obese men. J Clin Endocrinoi Metab 53:828-832. Boyar RM, Rosenfeld RS, Kapen S, Finkelstein JW, Roffwarg HP, W e i t z m ED, Hellman L (1974). Human puberty. Simultaneous augmented secretion of luteinizing hormone and testosterone during sleep. J Clin Invest ~h609-618. Rodbard D (1978). Statistical estimation of the minimal detectable concentration ("sensitivity") from radioligand assays. Anal Biochem 90:1-12. Davis SE, Munson PJ, Jaffe ML, Rodbard D (1980). RIA data processing with a small programmable calculator. J lmmunoassay 1:15-25. Lippman M, Bolan G, Huff K (1976). The effects of estrogens and anti-estrogens on hormone-responsive human breast cancer in long-term tissue culture. Cancer Res 36:4595-4601. Vermeulen A, Rubens R, Verdonck L (1972). Testosterone secretion and metabolism in male senescence. J Clin Endocrinol Metab 34:730-735. Zumoff B, Walter L, Rosenfeld RS, Strain J.l, Degen K, Strain GW, Levin J, Fukushima D (1980). Subnormal plasma adrenal androgen levels in men with uremia. J Clin Endocrinol Metab 51:801-805.
22. 23. 24.
25. 26. 27. 28. 29.
Zumoff B, Troxler RG, O'Connor J, et al (1982). Abnormal hormone levels in men with coronary artery disease. Arteriosclerosis 2:58-67. Glass AR (1986). Ketoconazole-induced simulation of gonadotropin output in men: basis for a potential test of gonadotropin reserve. J Clin Endocrinol Metab 63:1121-1125. Aono T, Kurachi K, Mizutanai S, et al (1972). Influence of major surgical stress on plasma levels of testosterone, luteinizing hormone and foUicle-stimulating hormone in male patients. J Ciin Endocrinol Metab 35-535-542. Wang C, Chan V, Tse TF, Yeung RT (1978). Effect of acute myocardial infarction on pituitary-testicular function. Clin Endocrinol (Oxf ) 9:249-253. Remes K, Kuoppasalmi K, Adlercreutz H (1985). Effect of physical exercise and sleep deprivation on plasma androgen levels: lnt J Sports Med 6:131-135. Opstad PK, Aakvaag A (1983). The effect of sleep deprivation on the plasma levels of hormones during prolonged physical strain and calorie deficiency. Eur J Appl Physio151:97-107. Kreuz LE, Rose RM, Jennings JR (1972). Suppression of plasma testosterone levels and psychological stress. Arch Gen Psychiatry 26:479--482. Glickman RM (1988). House-staff training--the need for careful reform. N Engl J Med 318:780-782.
Steroids, 1992, vol. 57, February
89
Singer* and Barnett Zumoff
Division o f Endocrinology, D e p a r t m e n t o f Medicine, Beth Israel Medical Center and The M o u n t Sinai School o f Medicine ( C U N Y ) , N e w York, N e w York, U S A
The consequences of sleep deprivation and stress in residency training have not been quantified. In the course of assembling a control group for other studies, we unexpectedly observed a significant (P < 0.005) and marked depression of serum testosterone levels in healthy male internal medicine residents (~ = 11.8 4- 1.1 nmollL, n = 7) compared with other hospital personnel (£ = 20.6 +- 5.3 nmol/L, n = 18). Testosterone concentrations in the two groups were entirely nonoverlapping, while luteinizing hormone levels were not significantly different. We conclude that the stress of residency training leads to a quantifiable depression of gonadal function, and that gonadal steroid concentrations may be useful in evaluating measures intended to reduce that stress. (Steroids 57: 86-89, 1992)
Keywords:testosterone in male residents; steroids; hypogonadotropic hypogonadism; stress; residency, effects on testosterone
Introduction
Experimental
It is generally believed that the stress and sleep deprivation o f r e s i d e n c y training h a v e negative effects on the well-being o f residents, I-6 but there is little concrete e v i d e n c e to s u p p o r t this belief. 6 T h e r e are data indicating that a significant p r o p o r t i o n o f residents exp e r i e n c e d e p r e s s i v e s y m p t o m s . 7-9 M a n y residents also r e p o r t m a j o r p r o b l e m s in their relationships with s p o u s e s o r lovers, w h i c h t h e y attribute to their resid e n c y training.l° It has b e e n suggested that the e m o tional p r o b l e m s e x p e r i e n c e d b y residents are as m u c h a f u n c t i o n o f certain individuals' p r e m o r b i d personalities a n d genetic predisposition to d e p r e s s i o n as t h e y are due to stress. 7 In the c o u r s e o f assembling a control g r o u p for o t h e r studies, w e u n e x p e c t e d l y o b s e r v e d s u b n o r m a l s e r u m t e s t o s t e r o n e levels in a g r o u p o f healthy internal medicine male residents. O u r finding in these subjects is, to o u r k n o w l e d g e , the first d e m o n s t r a t i o n o f a quantifiable stress-related b i o c h e m i c a l a b n o r m a l i t y in physicians during r e s i d e n c y training.
Normal healthy male subjects were solicited from among hospital personnel and housestaffat Beth Israel Medical Center (New York, New York, USA) to serve as controls in a study of male hypogonadism. Venous blood was withdrawn from an antecubital vein between the hours of 9:00 AM and 12:00 noon, and serum was separated for radioimmunoassay of testosterone and luteinizing hormone. The subjects included seven members of the medicine residency program, including four at the PGY-I level and three at the PGY-II level. All residents were working "on the floors" and were on call once every fourth night. During on-call nights, it is estimated that these residents were averaging between 2 and 4 hours of sleep. The subjects also included 18 male hospital employees who were not members of the medicine residency program; one was a pathology resident and the remainder were not physicians. These subjects were all working during regular daytime hours and were .sleeping at night. They were selected to exclude subjects with known causes for hypogonadism; specifically, none were marathon runners, H marijuana smokers, ~2obese) 3 or on a severely calorie-restricted diet. J4 Radioimmunoassays of testosterone were done using tritiated testosterone, obtained from Amersham Corp. (Arlington Heights, IL, USA), purified monthly on 50-ml columns of Sephadex LH-20 (Pharmacia Fine Chemicals, Piscataway, NJ, USA) equilibrated with toluene-methanol (85 : 15 v/v). ~5Nonradioactive testosterone obtained from Steraioids, Inc. (Wilton, NH, USA) was used. Testosterone concentration was determined by the method of Boyar et al.,~6 with the following modifications. Ether extracts of the serum were evaporated to dryness under nitrogen, redissolved in small volumes (0.2 ml) of isooctane-
*Present address: Harlem Hospital Center, Department of Medicine (12th floor), 135th Street and Lenox Avenue, New York, NY 10037, USA. Address reprint requests to Dr. Frank Singer, at the Department of Medicine (12th floor), Harlem Hospital Center, 135th Street and Lenox Avenue, New York, NY 10037, USA. ReceivedApril 15, 1991; accepted AUgust 7, 1991.
86
Steroids, 1992, vol. 57, February
© 1992 Butterworth-Heinemann
Serum T in male internal medicine residents: Singer and Zumoff toluene-methanol (90:5:5 v/v/v), and chromatographed on columns containing 1,000 rag Sephadex LH-20 (QS columns; Isolab, Inc., Akron, OH, USA) equilibrated with the same solvent system. The fractions of column eluate containing testosterone (but not dihydrotestosterone) were evaporated to dryness under nitrogen and redissolved in 0.01 M phosphatebuffered saline, pH 7.4, containing 0.1% gelatin and 0.02% NAN3. Aliquots were counted to determine recovery, and other aliquots were assayed from Radioassay Systems Laboratories, Inc. (Carson, CA, USA). The sensitivity of this assay has previously been shown to be 1.3 pg/tube. Iv Serum luteinizing hormone concentration was determined by a double-antibody procedure, using radioimmunoassay reagents from the National Hormone and Pituitary Program, NIDDK, a n d goat anti-rabbit gamma globulin obtained from Pantex (Santa Monica, CA, USA). The antiserum to human luteinizing hormone has a relative potency in terms of the second IRPHMG of 0.277 mIU/ng LET-907. The sensitivity of the assay for luteinizing hormone is 0.6 mIU/tube.~7 The radioimmunoassay data were analyzed as described by Davis et al.18 The intraassay and interassay coefficients of variation were less than 10%, using charcoal-treated plasma 19supplemented with known amounts of steroid or control serum samples (RIATRAC Plus) purchased from Becton-Dickinson Immunodiagnostics (Orangeburg, NY, USA).
20 m
18
m
1
1
A J
Z 0
16
m
14
m
m
m
w
1
O0
= 0
12
m
"I"
Z N Z
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1
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m
I
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8
1
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6
1
4
m
m
32
2-
i
m
1
m
i
28 1
m
0
E 24 LU Z
o
0
I
MALE MEDICAL RESIDENTS
Figure 2 Serum luteinizing hormone in male hospital employees and medical residents. The mean concentration for male residents (x -- 9.7 -+ 2.2 IU/L) is not significantly different from that for other hospital employees (~ = 10.3 -+ 3.6 IU/L).
O0 O0
20
MALE HOSPITAL EMPLOYEES
m
W O0
o
16
Significance of differences between the two groups studied was evaluated by Student's t test, two-tailed.
$ W 2~ ','
Results
& 8
m
I
4 0
MALE HOSPITAL EMPLOYEES
MALE MEDICAL RESI DENTS
Rgure 1 Serum testosterone in male hospital employees and medical residents. The mean concentration for male residents (~ = 11.8 - 1.06 nmol/L) is significantly (P < 0.0005) lower than that for other male hospital employees (~ = 20.6 + 5.28 nmol/L).
The mean serum testosterone concentration for the seven medicine residents was 11.8 -+ 1.06 nmol/L, with a range from 10.6 to 13.0 nmol/L. This was 43% lower than the mean serum testosterone for the 18 male hospital employees, which was 20.6 - 5.28 nmol/ L, with a range from 13.1 to 30.8 nmol/L (Figure 1). The testosterone levels in the two groups were entirely nonoverlapping, and the difference between the two mean values was highly significant ( P < .0.0005). The serum testosterone levels in the male hospital employees were similar to previous results in normal controls in our laboratory and in the published literature. 2° The coefficient of variation of the values in the male hospital employees was 0.26, similar to that of other hormone determinations in normal subjects, 21,22 while the coefficient of variation of the values in the medi-
Steroids, 1992, vol. 57, February
87
Papers cine residents was much lower at 0.09, with all the values tightly bunched in the lower end of the normal range. The mean serum luteinizing hormone concentration for the seven medicine residents was 9.7 -+ 2.2 IU/L compared with a mean of 10.3 -+ 3.6 IU/L for the 18 male hospital employees (Figure 2); this difference was not significant.
Discussion The results of this study clearly indicate that the male medicine residents had much lower serum testosterone levels than the other nonphysician male hospital employees or than is reported in normal controls) ° If these low values were due to primary testicular hypofunction, luteinizing hormone values would be expected to be elevated by approximately 70%23; since the luteinizing hormone values were not elevated, but normal, the low testosterone values represent hypogonadotropic hypogonadism. Interviews were held with the residents in an attempt to discover possible causes of their hypogonadal status. No subjects were obese, on a severely calorierestricted diet, or marathon runners. The mean age of the residents was slightly, though significantly, younger than the male hospital employees: 27 -+ 1.3 versus 32 -+ 7.1 years (P < 0.05). One resident was a jogger, a second did heavy exercise, and a third smoked marijuana, but the testosterone levels in these three were in the same narrow range as the values in the other four residents: the coefficient of variation for testosterone levels within the residents' group was very low (0.09), unlike the normal hospital employees (0.26). Thus, it is unlikely that these potential factors were contributing significantly to the low testosterone levels in the residents' group. It has been suggested that serum levels of gonadotropins and sex steroids be assayed from two or three pooled samples to avoid measuring peaks and troughs of episodic secretion, which could increase the sample variation and lead to excessive deviation of the sample mean from the true mean. The single serum sample testosterone concentrations from our male hospital employees showed no greater coefficient of variation (0.26) than found in normal mean 24-hour testosterone levels (0.25) from samples drawn at 20-minute intervals. 22 Thus, our use of single serum sample testosterone measurements did not lead to this potential artifact. The coefficient of variation for the residents' testosterone levels was even lower; it is highly improbable that their decreased serum testosterone levels were caused by a coincidence of secretory troughs. Severe stress, such as from s u r g e r y 24 o r myocardial infarction, 25 is known to cause suppression of gonadal steroids. Sleep deprivation has also been reported to cause hypogonadotropic hypogonadism. 26,27 Plasma testosterone levels decreased an average of 32% during a period of severe psychological stress in a group of men enrolled in officer candidate school, while fac-
88
Steroids, 1992, vol. 57, February
tors such as exercise, diet, and sleep schedules remained constant. 28 The degree of decrease in serum testosterone levels in this group of medicine residents was striking and unexpected. Since most of the residents studied had no other known cause for their hypogonadism, it is quite probable that both psychological stress and sleep deprivation, which are prominent features of this type of training, contribute to the significantly subnormal testosterone levels. The uniformity and severity of the hypogonadism reflect the magnitude of the stresses involved and provide a potential tool both to quantify the stress and to evaluate whether corrective measures, such as the limitation of a resident's duty hours to 80 per week, 29 have any real stress-reducing effect. Male hypogonadism can have important consequences for the resident, as it does for other people. Testosterone levels in the 10 to 13 nmol/L range may contribute to relative sexual inadequacy. In turn, this can interfere with both established and desired sexual relationships with spouses and lovers. Since a young male's ego is at least partly sexual in identity, this can further lead to loss of self-esteem. Depressive symptoms under these circumstances would not be surprising. We did not do psychological testing of the residents in our study. A future study to correlate residents' depressive and sexual symptomatology with gonadal steroid levels would be of interest.
References I. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14.
McCue JD (1985). The distress of internship: causes and prevention. N Engl J Med 312:449-452. Hardison JE (1986). The house officer's changing world. N Engl J Med 314:1713-1715. Blackwell B (1986). Prevention of impairment among residents in training. ,lAMA 225:1177-1178. Weinstein HM (1983). A committee on well-being of medical students and house staff. J Med Educ 58:373-381. McCall TB (1988). The impact of long working hours on resident physicians. N Engl J Med 318:775-778. Asken MJ, Raham DC (1983). Resident performance and sleep deprivation: a review. J Med Edac 58:382-388. Valko RJ, Clayton PJ (1975). Depression in the internship. Dis Nerv Syst 36:26-29. Reuben DB (1985). Depressive symptoms in medical house officers: effects of level of training and work rotation. Arch Intern Med 145:286-288. Clark DC, Salazar-Greso E, Grabler P, Fawcett J (1984). Predictors of depression during the first 6 months of internship. Am J Psychiatry 141:1095-1098. Landau C, Hall S, Wartman SA, Macko MB (1986). Stress in social and family relationships during the medical residency. J Med Edac 61:654-660. Reichlin S (1985). Neuroendocrinology. In: Wilson JD, Foster DW (eds), Williams Textbook of Endocrinology, 7th ed. Saunders, Philadelphia, pp. 492-567. Kolodny RC, Masters WH, Kolodner RM, Tom G (1974). Depression of plasma testosterone levels after chronic intensive marihuana use. N Engl'J Med ~10:872-874. Strain GW, Zumoff B, Kream J, et a~ (1982). Mild hypogonadotropic hypogonadism in obese men. Metabolism 31:871875. HotTer LI, Beitins IZ, Kyung N-H, B/st/an BR (1986). Effects of severe dietary restriction on male reproductive hormones. `l Clin Endocrinol Metab 62:288-292.
Serum T in male internal medicine residents: Singer and Zumoff 15. 16.
17. 18. 19. 20. 21.
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