HORMONES
AND
BEHAVIOR
24,
435-441 (1990)
BRIEF REPORT The Effects of Testosterone Administration and Visual Erotic Stimuli on Nocturnal Penile Tumescence in Normal Men C. CARANI,* *Departments Italy,
A. SCIJWXRI,* P. MARRAMA,*
AND J. BANcRoFrt
of Endocrinology and Physiology, Zstituto de Patologia Medica, and TMRC Reproductive Biology Unit, Edinburgh, Scotland, United Kingdom
Modena,
Nocturnal penile tumescence (NPT), as circumference change and rigidity, and REM sleep were measured in eight normal eugonadal men in two controlled experiments. In the first, exposure to erotic film prior to sleep had no effect on frequency of REM or on NPT. In the second placebo controlled experiment 150 mg im testosterone enanthate administration was associated with enhanced rigidity of NPT but with no effect on frequency or circumference change of NPT and no effect on frequency of REM. o 1990 Academic PXSS. IW.
The role of androgens in the sexuality of men is becoming increasingly clear. Controlled studies of hypogonadal men have shown consistently that androgens are necessary (though not sufficient) for the maintenance of normal sexual desire (e.g., Davidson, Camargo, and Smith, 1979; Skaakebaek, Bancroft, Davidson, and Warner, 1981) and that these effects are dose related (Salmimies, Kockott, Pirke, Vogt, and Schill, 1982; O’Carroll, Shapiro, and Bancroft, 1985). The role of androgens in erectile function is more complex. Erections in response to visual erotic stimuli appear to be androgen independent (Bancroft and Wu 1983; Kwan, Greenleaf, Mann, Crapo, and Davidson, 1983). Spontaneous erections during sleep (nocturnal penile tumescence or NPT) are, however, androgen dependent. NPT is impaired in hypogonadal men (Cunningham, Karacan, Ware, Lautz, and Thornby, 1982) and is improved by androgen replacement (Kwan el al., 1983; O’Carroll et al., 1985). NPT is also often impaired in men with loss of sexual desire (Schiavi, 1988). This has led to the suggestion that sexual desire and NPT are in some way linked, being cognitive and physiological manifestations of the same androgen-dependent central system. Erectile responses to visual erotic stimuli, apparently independent of androgens, are mediated by other central mechanisms (Bancroft, 1988). 435 0018-506X190 $1.50 Copyright 0 1990 by Academic Press. Inc. All rights of reproduction in any form reserved.
436
CARANI
ET AL.
While this picture is beginning to take shape, a number of issues remain unclear. First, is there a threshold level of circulating testosterone (T) above which additional testosterone has no effect on sexuality-a point of considerable clinical relevance? Up till now most of the evidence comes from studies of men with hypogonadism or with androgen levels altered by drugs. In eugonadal men, correlational studies have been inconsistent in their results. Correlations between T and sexual interest or activity have been generally lacking (Raboch and Starka 1973; Brown, Monti, and Corriveau, 1978), with orgasmic frequency they have been inconsistent (Kraemer, Becker, Brodie, Doering, Moos, and Hamburg, 1976; Knussman, Christiansen, and Couwenbergs, 1986), and with erectile response to erotic stimuli they have been inconclusive, showing a relationship with the latency but not the degree of erection (Lange, Brown, Wincze, and Zwick, 1980; Rubin, Henson, Falvo, and High, 1979). Given the considerable inter- and intrasubject variability in circulating T levels, such inconsistent evidence is perhaps not surprising. Studies in which T levels have been manipulated provide a more direct method of investigating the question. So far there is very little evidence of this kind. The use of antiandrogens produced effects very similar to those of hypogonadal states (Bancroft et al., 1974). A placebo controlled evaluation of intramuscular testosterone in eugonadal men complaining of loss of sexual desire showed a modest but significant positive effect of exogenous T on sexual desire (O’Carroll & Bancroft 1984). There have been no controlled studies of the effects of exogenous T on erectile function in normal eugonadal men. A further issue, in studies of erectile responsiveness, concerns the method of assessing erection. All the studies cited have used simple measurement of penile circumference change. Measurement of rigidity, technically difficult, is increasingly recognized as important in the diagnostic assessment of erectile dysfunction. Such measurement has not been reported in studies of hormone behavior relationships. In this study we report a placebo controlled evaluation of the effects of exogenous T on NPT in sexually normal, eugonadal young men. An additional question, of methodological importance, is whether exposure to visual erotic stimuli before going to sleep influences the pattern of NPT. Measures of both penile circumference and rigidity are reported. METHODS Subject
Eight male medical students, ages 20-28 years, volunteered for this study. They reported no sexual dysfunction and were drug free and in good health.
TESTOSTERONE
AND
NPT
IN EUGONADAL
MEN
437
Design Each subject was tested on four occasions, two pairs of tests, each pair representing a separate balanced experiment. Experiment 1. After a first adaptation night of sleep and NPT recording, half the subjects viewed an explicit erotic film; the other half viewed a sexually neutral documentary film at 10 PM before retiring to bed. After 7 days the groups were reversed and the procedure was repeated. This allowed a comparison of the effects of erotic and neutral stimuli in the waking state on subsequent NPT. Experiment 2. All subjects received an intramuscular injection at 8 PM. In half the subjects this contained 150 mg of testosterone enanthate (Testoviron Depot); the other half received placebo. Two days later NPT and sleep pattern were recorded. Thirty days later the two groups were reversed and the procedure was repeated. This permitted a comparison of the effects of testosterone and placebo on NPT and sleep pattern. Measures During each of the four sessions of the two experiments, subjects were monitored from 10 PM until the following morning. Nocturnal penile tumescence. Circumference change and rigidity of spontaneous erections during sleep were measured using a commercially available system (Rigiscan; Dacomed Co., Minneapolis, MN). This device incorporates a penile strain gauge consisting of two recording loops applied to the base and the tip of the penis, a data recording unit, and a microcomputer system. The loops allow continuous measurement of penile circumference and intermittent measurement of rigidity. For the latter, tension is applied repeatedly to the loops and the degree of displacement (i.e., the compressability of the penile shaft) is recorded. Rigidity is expressed as percentage of full rigidity, which would occur with a solid, noncompressable rod (Bradley, Timm, Gallagher, and Johnson, 1985; Kaneko and Bradley, 1986). Penile circumference is measured in millimeters. The following parameters have been analyzed for each night: (1) Number of erectile “events” during sleep per night. An event is an increase in penile circumference at the base of the penis of 30 mm or more for a minimum of 10 min. (2) Duration of events in min. (3) The maximum circumference increase for any event. (4) Mean maximum circumference increase for all events. (5) The maximum rigidity for any event. (6) The mean maximum rigidity for all events. (7) The duration of rigidity exceeding 60%. Sleep. Standard EEG, EOG, and EMG leads were fitted to assess REM sleep and total sleep time (Rechtschaffen and Kales, 1968). They
438
CARANI
ET AL.
were recorded on a Grass Model 7D polygraph situated in the adjoining room. The number of episodes of REM per night have been analyzed. Hormones. Three venous blood samples were taken at 15min intervals between 8 and 9 AM after each night’s monitoring. Serum was separated and frozen at - 20” until assayed. Serum testosterone concentration was assayed by RIA after ether extraction (Baraghini et al., 1984). The sensitivity of the assay and intra- and interassay coefficients of variation were 0.9 pg and 5.9 and 12.4%, respectively. Results are expressed as means of the three serial samples. Analysis Statistics. Paired t tests were carried out for each experiment
for each
variable. RESULTS
The number of events (i.e., erections) and of REM episodes are shown in Table 1. There were no significant differences between conditions in either experiment 1 or 2. The remaining variables are shown in Table 2. Experiment I. Exposure to an erotic film prior to sleep did not modify the NPT response. There was no difference in the testosterone levels in these two conditions. Experiment 2. Serum testosterone levels were, as to be expected, substantially higher following the testosterone injections than following placebo. There was no significant difference between the testosterone and placebo conditions in any of the three variables measuring circumference change. With rigidity, however, testosterone administration was associated with significantly greater mean maximum rigidity and a significantly longer period of rigidity in excess of 60%.
TABLE 1 Comparison of Erotic and Neutral Films (Experiment 1) and 150 mg of im Testosterone Enanthate and Placebo (Experiment 2) on Number of Sleep Erections and Episodes of REM (Means and (SD) Experiment
Number of total events Number of REM sleep
Experiment
1
2
Erotic film
Neutral film
Paired t test
Testosterone im
Placebo im
Paired t test
4.62 (0.74) 4.12 (0.81)
4.12 (0.99) 3.95 (0.85)
n.s.
4.25 (1.28) 4.05 (1.05)
3.87 (0.83)
n.s.
3.15 (0.78)
n.s
n.s.
in min
Mean maximum rigidity for all events (%) Serum testosterone (ng/lOO ml)
Maximum circumference increase (mm) Mean maximum circumference increase for all events (mm) Duration of rigidity greater than 60% (mitt) Maximum rigidity (%)
Duration of “events”
57.5 (8.9) 510.4 (86.0)
(6.0)
WI 59.8 (10.5) 516.6 (62.1)
(1.6) 37.8 (4.3) 42.5 (25.2) 73.3
72.8 (25.3) 40.9
Neutral film
Experiment N=8
1
n.s.
n.s.
n.s.
n.s.
n.s.
n.s.
n.s.
Paired t test
61.6 (33.9) 75.4 (6.5) 66.6 (9.5) 1035.0 (154.0)
(4.6)
79.8 (37.2) 37.1 (4.5) 35.8
Testosterone
TABLE 2 1) and 150 mg im Testosterone and Placebo (Experiment NPT (Means + SD)
12.4 (18.2) 39.6 (1.5) 37.4 (1.4) 47.5 (17.8) 71.5
Erotic film
Comparison of Erotic and Neutral Films (Experiment
58.1 (10.3) 517.1 (54.0)
(6.0)
(5.9) 49.1 (33.7) 71.6
74.1 (38.0) 38.5 (5.0) 35.1
Placebo
Experiment N=8
2
P
AND
BEHAVIOR
24,
435-441 (1990)
BRIEF REPORT The Effects of Testosterone Administration and Visual Erotic Stimuli on Nocturnal Penile Tumescence in Normal Men C. CARANI,* *Departments Italy,
A. SCIJWXRI,* P. MARRAMA,*
AND J. BANcRoFrt
of Endocrinology and Physiology, Zstituto de Patologia Medica, and TMRC Reproductive Biology Unit, Edinburgh, Scotland, United Kingdom
Modena,
Nocturnal penile tumescence (NPT), as circumference change and rigidity, and REM sleep were measured in eight normal eugonadal men in two controlled experiments. In the first, exposure to erotic film prior to sleep had no effect on frequency of REM or on NPT. In the second placebo controlled experiment 150 mg im testosterone enanthate administration was associated with enhanced rigidity of NPT but with no effect on frequency or circumference change of NPT and no effect on frequency of REM. o 1990 Academic PXSS. IW.
The role of androgens in the sexuality of men is becoming increasingly clear. Controlled studies of hypogonadal men have shown consistently that androgens are necessary (though not sufficient) for the maintenance of normal sexual desire (e.g., Davidson, Camargo, and Smith, 1979; Skaakebaek, Bancroft, Davidson, and Warner, 1981) and that these effects are dose related (Salmimies, Kockott, Pirke, Vogt, and Schill, 1982; O’Carroll, Shapiro, and Bancroft, 1985). The role of androgens in erectile function is more complex. Erections in response to visual erotic stimuli appear to be androgen independent (Bancroft and Wu 1983; Kwan, Greenleaf, Mann, Crapo, and Davidson, 1983). Spontaneous erections during sleep (nocturnal penile tumescence or NPT) are, however, androgen dependent. NPT is impaired in hypogonadal men (Cunningham, Karacan, Ware, Lautz, and Thornby, 1982) and is improved by androgen replacement (Kwan el al., 1983; O’Carroll et al., 1985). NPT is also often impaired in men with loss of sexual desire (Schiavi, 1988). This has led to the suggestion that sexual desire and NPT are in some way linked, being cognitive and physiological manifestations of the same androgen-dependent central system. Erectile responses to visual erotic stimuli, apparently independent of androgens, are mediated by other central mechanisms (Bancroft, 1988). 435 0018-506X190 $1.50 Copyright 0 1990 by Academic Press. Inc. All rights of reproduction in any form reserved.
436
CARANI
ET AL.
While this picture is beginning to take shape, a number of issues remain unclear. First, is there a threshold level of circulating testosterone (T) above which additional testosterone has no effect on sexuality-a point of considerable clinical relevance? Up till now most of the evidence comes from studies of men with hypogonadism or with androgen levels altered by drugs. In eugonadal men, correlational studies have been inconsistent in their results. Correlations between T and sexual interest or activity have been generally lacking (Raboch and Starka 1973; Brown, Monti, and Corriveau, 1978), with orgasmic frequency they have been inconsistent (Kraemer, Becker, Brodie, Doering, Moos, and Hamburg, 1976; Knussman, Christiansen, and Couwenbergs, 1986), and with erectile response to erotic stimuli they have been inconclusive, showing a relationship with the latency but not the degree of erection (Lange, Brown, Wincze, and Zwick, 1980; Rubin, Henson, Falvo, and High, 1979). Given the considerable inter- and intrasubject variability in circulating T levels, such inconsistent evidence is perhaps not surprising. Studies in which T levels have been manipulated provide a more direct method of investigating the question. So far there is very little evidence of this kind. The use of antiandrogens produced effects very similar to those of hypogonadal states (Bancroft et al., 1974). A placebo controlled evaluation of intramuscular testosterone in eugonadal men complaining of loss of sexual desire showed a modest but significant positive effect of exogenous T on sexual desire (O’Carroll & Bancroft 1984). There have been no controlled studies of the effects of exogenous T on erectile function in normal eugonadal men. A further issue, in studies of erectile responsiveness, concerns the method of assessing erection. All the studies cited have used simple measurement of penile circumference change. Measurement of rigidity, technically difficult, is increasingly recognized as important in the diagnostic assessment of erectile dysfunction. Such measurement has not been reported in studies of hormone behavior relationships. In this study we report a placebo controlled evaluation of the effects of exogenous T on NPT in sexually normal, eugonadal young men. An additional question, of methodological importance, is whether exposure to visual erotic stimuli before going to sleep influences the pattern of NPT. Measures of both penile circumference and rigidity are reported. METHODS Subject
Eight male medical students, ages 20-28 years, volunteered for this study. They reported no sexual dysfunction and were drug free and in good health.
TESTOSTERONE
AND
NPT
IN EUGONADAL
MEN
437
Design Each subject was tested on four occasions, two pairs of tests, each pair representing a separate balanced experiment. Experiment 1. After a first adaptation night of sleep and NPT recording, half the subjects viewed an explicit erotic film; the other half viewed a sexually neutral documentary film at 10 PM before retiring to bed. After 7 days the groups were reversed and the procedure was repeated. This allowed a comparison of the effects of erotic and neutral stimuli in the waking state on subsequent NPT. Experiment 2. All subjects received an intramuscular injection at 8 PM. In half the subjects this contained 150 mg of testosterone enanthate (Testoviron Depot); the other half received placebo. Two days later NPT and sleep pattern were recorded. Thirty days later the two groups were reversed and the procedure was repeated. This permitted a comparison of the effects of testosterone and placebo on NPT and sleep pattern. Measures During each of the four sessions of the two experiments, subjects were monitored from 10 PM until the following morning. Nocturnal penile tumescence. Circumference change and rigidity of spontaneous erections during sleep were measured using a commercially available system (Rigiscan; Dacomed Co., Minneapolis, MN). This device incorporates a penile strain gauge consisting of two recording loops applied to the base and the tip of the penis, a data recording unit, and a microcomputer system. The loops allow continuous measurement of penile circumference and intermittent measurement of rigidity. For the latter, tension is applied repeatedly to the loops and the degree of displacement (i.e., the compressability of the penile shaft) is recorded. Rigidity is expressed as percentage of full rigidity, which would occur with a solid, noncompressable rod (Bradley, Timm, Gallagher, and Johnson, 1985; Kaneko and Bradley, 1986). Penile circumference is measured in millimeters. The following parameters have been analyzed for each night: (1) Number of erectile “events” during sleep per night. An event is an increase in penile circumference at the base of the penis of 30 mm or more for a minimum of 10 min. (2) Duration of events in min. (3) The maximum circumference increase for any event. (4) Mean maximum circumference increase for all events. (5) The maximum rigidity for any event. (6) The mean maximum rigidity for all events. (7) The duration of rigidity exceeding 60%. Sleep. Standard EEG, EOG, and EMG leads were fitted to assess REM sleep and total sleep time (Rechtschaffen and Kales, 1968). They
438
CARANI
ET AL.
were recorded on a Grass Model 7D polygraph situated in the adjoining room. The number of episodes of REM per night have been analyzed. Hormones. Three venous blood samples were taken at 15min intervals between 8 and 9 AM after each night’s monitoring. Serum was separated and frozen at - 20” until assayed. Serum testosterone concentration was assayed by RIA after ether extraction (Baraghini et al., 1984). The sensitivity of the assay and intra- and interassay coefficients of variation were 0.9 pg and 5.9 and 12.4%, respectively. Results are expressed as means of the three serial samples. Analysis Statistics. Paired t tests were carried out for each experiment
for each
variable. RESULTS
The number of events (i.e., erections) and of REM episodes are shown in Table 1. There were no significant differences between conditions in either experiment 1 or 2. The remaining variables are shown in Table 2. Experiment I. Exposure to an erotic film prior to sleep did not modify the NPT response. There was no difference in the testosterone levels in these two conditions. Experiment 2. Serum testosterone levels were, as to be expected, substantially higher following the testosterone injections than following placebo. There was no significant difference between the testosterone and placebo conditions in any of the three variables measuring circumference change. With rigidity, however, testosterone administration was associated with significantly greater mean maximum rigidity and a significantly longer period of rigidity in excess of 60%.
TABLE 1 Comparison of Erotic and Neutral Films (Experiment 1) and 150 mg of im Testosterone Enanthate and Placebo (Experiment 2) on Number of Sleep Erections and Episodes of REM (Means and (SD) Experiment
Number of total events Number of REM sleep
Experiment
1
2
Erotic film
Neutral film
Paired t test
Testosterone im
Placebo im
Paired t test
4.62 (0.74) 4.12 (0.81)
4.12 (0.99) 3.95 (0.85)
n.s.
4.25 (1.28) 4.05 (1.05)
3.87 (0.83)
n.s.
3.15 (0.78)
n.s
n.s.
in min
Mean maximum rigidity for all events (%) Serum testosterone (ng/lOO ml)
Maximum circumference increase (mm) Mean maximum circumference increase for all events (mm) Duration of rigidity greater than 60% (mitt) Maximum rigidity (%)
Duration of “events”
57.5 (8.9) 510.4 (86.0)
(6.0)
WI 59.8 (10.5) 516.6 (62.1)
(1.6) 37.8 (4.3) 42.5 (25.2) 73.3
72.8 (25.3) 40.9
Neutral film
Experiment N=8
1
n.s.
n.s.
n.s.
n.s.
n.s.
n.s.
n.s.
Paired t test
61.6 (33.9) 75.4 (6.5) 66.6 (9.5) 1035.0 (154.0)
(4.6)
79.8 (37.2) 37.1 (4.5) 35.8
Testosterone
TABLE 2 1) and 150 mg im Testosterone and Placebo (Experiment NPT (Means + SD)
12.4 (18.2) 39.6 (1.5) 37.4 (1.4) 47.5 (17.8) 71.5
Erotic film
Comparison of Erotic and Neutral Films (Experiment
58.1 (10.3) 517.1 (54.0)
(6.0)
(5.9) 49.1 (33.7) 71.6
74.1 (38.0) 38.5 (5.0) 35.1
Placebo
Experiment N=8
2
P
