Nocturnal Penile Tumescence in Healthy 20- to 59-Y ear-olds: A Revisit

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1 Sleep 12(4): , Raven Press, Ltd., New York 1989 Association of Professional Sleep Societies Nocturnal Penile Tumescence in Healthy 20- to 59-Y ear-olds: A Revisit Charles F. Reynolds III, Michael E. Thase, J. Richard Jennings, Joseph R. Howell, Ellen Frank, Susan R. Berman, Patricia R. Houck, and David J. Kupfer Sleep Evaluation Center, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania Summary: This report presents data on normative nocturnal penile tumescence (NPT), based on a study of 48 healthy men aged years, without complaints of erectile dysfunction. In general, the current measures show good concordance with those reported by Karacan and colleagues in The effect of "pathology-free" aging (from age 20 to 59) on electrographic measures of NPT is relatively modest, accounting for % of the variance. Furthermore, no age effect on visual estimates of erectile fullness or on buckling force estimates of penile rigidity were present. Maximum buckling force and maximum erectile fullness showed stability across the four decades of the Pittsburgh sample. Key Words: Nocturnal penile tumescence-aging. With the increasing use of all-night nocturnal penile tumescence (NPT) studies as a diagnostic test to assess erectile dysfunction, the availability of data from age-equated healthy men not complaining of erectile dysfunction has become essential for the appropriate interpretation of laboratory data in patients. The ontogeny of NPT was studied systematically by Karacan and colleagues (1), who published data from NPT recordings in 125 healthy boys and men between the ages of 3 and 79. These data demonstrated that NPT occurs in virtually all healthy males and is significantly affected by the age of the individual. Similarly, in 1969, Edwin Kahn, working in Fisher's laboratory, reported NPT data from a sample of 21 men between the ages of 71 and 96, showing that these older healthy men had significantly less NPT than young adults (2). Jovanovic (3), in studies of boys as young as 6 months up to men in their 70s, showed age-dependent decreases in NPT parameters similar to those noted by Kahn and Fisher and confirmed by Karacan et al. (1,2). To our knowledge, no other normative NPT data have been published, thus limiting the normative database in the world literature to under 200 subjects. Accepted for publication October Address correspondence and reprint requests to Dr. C. F. Reynolds III at Sleep Evaluation Center, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, 3811 O'Hara Street, Pittsburgh, PA 15213, U.S.A. 368

2 NOCTURNAL PENILE TUMESCENCE 369 An important limitation of the available data is that all measures reported have been electrographic. Despite the increasing recognition of the importance and utility of visual inspection data and the measurement of penile rigidity, virtually no normative data on visual inspection or buckling force determination have been published. Yet, visual inspection procedures and buckling force determinations are routinely included in clinical NPT protocols, since it is now widely recognized that NPT episodes can be characterized by full tumescence despite an absence of penile rigidity (4). In 1985, Karacan and colleagues published their preliminary observation that a buckling force of >500 g corresponds to the minimum penile rigidity necessary for vaginal penetration (5). To our knowledge, no other published data bearing on this issue have appeared. In this article, we report a replication, updating, and extension of the normative NPT data published 12 years ago by the Houston group, in their pioneering ontogenetic study of sleep-tumescence characteristics in healthy individuals. Similar to Karacan's investigations (1), our study of the ontogenetic changes in NPT has focused on the effects of pathology-free aging on this important biological parameter. Not only are electrographic measures reported in the current study, but visual estimation data and buckling force determinations are reported as well. Since both of the latter are now considered to be a necessary part of the standard NPT evaluation, the availability of ageappropriate norms is important. SUBJECTS AND METHODS Our methods for screening and evaluating healthy control subjects have been described in recent articles reporting differences in NPT parameters between depressed men and control subjects (e.g., ref. 6). We made a special effort to select only those control subjects in good physical and mental health. Based on Schedule for Affective Disorders and Schizophrenia-Lifetime Version evaluation, control subjects were found to have no history of psychiatric illness (7). None of the control subjects had a history of erectile dysfunction. All controls completed a minimum 14-day drug- and alcoholfree interval before NPT studies, with drug-free status verified by urine screen for drugs. All were judged to be in good physical health after a history was taken, and physical and laboratory studies were done, including a complete blood count, chemistry screen of renal, hepatic, and electrolyte indices, thyroid function tests, serologic test for syphilis, and electrocardiogram. Most controls also completed the Derogatis Sexual Function Inventory (8). Finally, during the 2 weeks before laboratory studies, controls completed the Brief Sexual Function Questionnaire (9). This questionnaire provides data on factors of sexual interest, activity, and physiological functioning. It is accompanied by a daily log that provides concurrent information about daily fluctuations in libido and in sexual activity leading to orgasm. NPT recordings were conducted using methods described by Karacan and colleagues in ,11), where mercury-ftlled strain gauges were placed at the base and tip of the penis. We used NPT calibration parameters similar to those of Karacan, with a I5-mm pen deflection corresponding to a 15-mm change in penile circumference. Consistent with our prior studies, an episode of NPT was defined as a gradual increase in base circumference corresponding to a change in pen deflection of ~3 mm over a 60-s period and persisting for at least 5 min. The end of an episode of tumescence was defined by a I-min return of the polygraph pens to baseline. The reliability of our scoring procedures has been established and is reported by Campbell et al. (2). In a further effort to ensure comparability of NPT recording and visual estimation

3 370 C. F. REYNOLDS III ET AL. procedures, the senior author (C.P.R.) and his colleague (J.R.J.) visited Di. Karacan's laboratory in Houston on two separate occasions, with a I-year interval between visits. In addition, Dr. Karacan has visited our laboratory and has inspected representative recordings. Our NPT protocol consisted of three consecutive nights of NPT recording during all-night polygraphic assessment of sleep. Visual estimation procedures and buckling force determinations were completed on night 3. The electrographic data reported in this article are from night 2. Our visual inspection procedures involved waking the subject at the point of maximal tumescence during each NPT episode (three to four times per nights) and obtaining independent visual estimates of erectile fullness from both the technologist and the subject using a 0-100% scale, with 100% representing a maximum, rigid erection. Immediately after making the visual estimates, erectile rigidity was determined using a buckling force technique. Buckling force was measured in our laboratory using a device consisting of a large syringe with a rubber cap on one end and a sphygmomanometer on the other. The buckling force represents the pressure applied to the tip of the penis by the capped syringe at the time the subject's penis first bends. The device was calibrated before each buckling force determination, using a 500-g weight to produce a pressure of 60 mm Hg. Dependent variables used in statistical analyses were minutes of tumescence time (total tumescence time), tumescence time divided by time spent asleep (TT/TSA), tumescence time divided by rapid eye movement sleep time (TT/RT), total number of NPT episodes, maximum technologist and maximum subject visual inspection ratings, and maximum penile buckling force. Significance of differences among age groups was determined using a series of one-way analyses of variance. To estimate further the actual magnitude of age-related variance in these dependent measures, a Pearson product moment correlation was calculated, regressing each measure on subject age. The following is a summary of the similarities and differences of methods in the 1976 Houston (1) and our 1988 Pittsburgh studies: Both investigations made a special effort to select only subjects in good physical and mental health. Both studies involved three consecutive nights in the laboratory. However, while the Houston study used averaged data from nights 2 and 3, our study reported electrographic data only from night 2 because sleep was interrupted on night 3 to obtain visual inspection and buckling force measurements. Neither study used data from night 1 in determining its norms to allow for possible first-night effects. Both studies used similar NPT recording and calibration procedures at the start and finish of the night. Both studies used minute-by-minute scoring. Similar criteria were also used to determine the presence of NPT episodes. Both studies used ratio data to assess changes in NPT parameters across age, independent of age-related changes in sleep-period time and in REM time. Both studies used analysis of variance and regression (correlation) statistical approaches to evaluate the magnitude of age-dependent changes. It is not clear if the Houston study used the same 14-day drug-free interval before laboratory evaluation that was used in the Pittsburgh study. Karacan and colleagues do report that subjects were drug free (and nap free) during the laboratory procedure itself, however (1). We used a narrower age range (20-59 years) than was used in the Houston study (3-79 years). The age range reported here is, nonetheless, pertinent to the majority of men seen in clinical practice. We also used two strain gauges, one at the base and one at the tip of the penis; apparently, only one strain gauge was used in the Houston work. Although we chose to report fewer electrographic-dependent measures than in the original Houston work, which described

4 NOCTURNAL PENILE TUMESCENCE , we focused on those variables most widely used in clinical practice (including visual and buckling force estimates of penile rigidity). RESULTS Age-group comparisons of electrographic, visual, and rigidity measures in healthy subjects are presented in Table 1. Where possible, comparable data from the 1976 Karacan study (1) are presented: number of NPT episodes, total tumescence time, TT/TSA, and TTIRT. Comparing the Pittsburgh and Houston data, there appears to be excellent concordance in three of the four decades and in three of the four electrographic parameters. It appears that the 20-year-olds studied in Pittsburgh had more episodes of NPT and more NPT time than 20-year-olds studied in Houston. It also appears that the TTIRT values were generally greater in the Pittsburgh data than in the Houston data, except for men in the year-old groups. Our data set showed a significant age-related decline in the number of NPT episodes from age 20 to 59 (F = 2.91, P < 0.05). This was a modest effect, however, as evidenced by a Pearson correlation coefficient of (p < 0.05). Karacan reported an F value of for the age-dependent decrease in the number of REM-related tumescence episodes in subjects aged 3-79, reflecting the broader age range in the Houston data (1). One other electrographic measure in our data set also showed significant age effects (by analysis of variance): TT/RT (F = 2.84, p < 0.05). However, variance explained by age was modest, as evidenced by a Pearson r value of (p < 0.02). Karacan reported an F ratio of 2.04 for TTlRT, again measured across a much larger age span. In our data set, total tumescence time per se did not show a significant F ratio for comparison across age groups (F = 2.47, p < 0.07). However, using the Pearson correlation coefficient, which confers the additional statistical power resulting from using variables TABLE 1. NPT measures by decade in healthy subjects Pittsburgh (1988) Age group (n) Karacan et al. (I) SO-S SO-S9 (16) (14) (9) (9) (17) (8) (10) (15) Number of episodes (1.6) (1.3) (1.1) (1.0) (0.8) (1.3) (0.8) (1.2) Total tumescence los time (min) (4S.7) (SS.4) (61.0) (32.5) (35) (43) (5 I) (34) TTTfTSA S (0.13) (0.15) (0.18) (0.07) (0.08) (0.10) (0.13) (0.09) TITIRT (1.04) (0.68) (0.82) (0.52) (0.3S) (0.64) (0.61) (0.40) Maximum buckling force (g) (232.0) (439.7) (438.2) (563.6) Maximum visual inspection Technician (%) S (20.0) (17.1) (21.8) (27.3) Patient (%) (2S.0) (24.8) (22.0) (20.8) TTTfTSA, total tumescence time/time spent asleep; TTTIRT, total tumescence timelrem time. Values are mean (SD).

5 372 C. F. REYNOLDS III ET AL. continuously rather than grouping them, total tumescence time did show a weak but significant inverse correlation with age: (p < 0.01). Similarly, although TT/TSA did not show a significant F ratio for age effects (F = 1.62, NS), a modest age effect was demonstrated by a Pearson r value of (p < 0.05). Thus, age accounted for % of the variance in the electrographic measures of NPT. Neither the visual inspection measures nor buckling force determinations showed significant age effects, as assessed by analysis of variance or by Pearson product-moment correlation coefficients. Table 2 is a compilation of grand means and standard deviations, derived from pooling the Pittsburgh and the Houston data. DISCUSSION In our data, as in the Houston data, the effect of pathology-free aging (from age 20 to 59) on electrographic measures of NPT is modest, accounting for about % of the variance. Thus, during the mid-life decades, both electrographic and visual measures of NPT (including buckling force estimates of penile rigidity) are relatively stable and appear either to plateau or to decline slowly. Examining the Houston data, it appears that the more dramatic age-dependent changes in NPT parameters occur before the age of 20 and after the age of 60. Our electrographic findings in the 30-, 40-, and 50-year-olds appear to replicate those in the Houston study, while our findings in the 20-year-olds are somewhat higher (25-33%) on average. The 20-year-olds recorded in Pittsburgh appeared to have a greater number of NPT episodes and thus a higher ratio of NPT time to REM time; however, total tumescence time and TT/TSA were not dissimilar for 20-year-olds in the two studies. Maximum buckling force and maximum visual inspection data showed stability across the four decades of the Pittsburgh sample. Our buckling force data were also consistent with those of Karacan (5), in that most of our normal controls (75%) achieved buckling forces of ;=;500 g force (13). Given the similarity of methods and results between the 1976 Houston and our 1988 Pittsburgh studies, we believe that pooling the data to derive grand means and standard deviations is justified and that the larger sample size will afford a greater measure of confidence for use in interpreting clinical data. TABLE 2. Combined data: Pittsburgh and Houston Age (n) (33) (22) (19) (24) Number of episodes (1.3) (1.3) (1.1) (1.2) Total tumescence time (min) (41.0) (51.4) (56.2) (33.5) 1TIfTSA (0.11) (0.14) (0.16) (0.08) 1TIIRT (0.90) (0.67) (0.74) (0.45) Values are grand mean ± SD.

6 NOCTURNAL PENILE TUMESCENCE 373 Our efforts to update and extend available normative data in NPT further are now focusing on men aged and will be the subject of a subsequent report. Acknowledgment: The authors thank Ismet Karacan, M.D., and Max Hirshkowitz, Ph.D., for serving as scientific consultants. This work was supported in part by National Institute of Mental Health grants (C.F.R.), (C.F.R.), and (D.1.K.). REFERENCES 1. Karacan I, Salis PJ, Thornby JI, Williams RL. The ontogeny of nocturnal penile tumescence. Waking and Sleeping 1976;1 : Kahn E, Fisher C. REM sleep and sexuality in the aged. J Geriatr Psychiatry 1969;2: Jovanovic VJ. Sexuelle Reaktionen und Schlafperiodik bei Menschen. Eregebnisse Experimenteller Untersuchungen. Stuttgart: Ferdinand Enke Verlag, Wein AJ, Fishbein R, CarpinieUo VL, Mallou TR. Expansion without significant rigidity during penile tumescence testing: a potential source of misinterpretation. J Urol 1981 ;126: Karacan I, Moore C, Sahmay S. Measurement of pressure necessary for vaginal penetration. Sleep Res 1985;14: Thase ME, Reynolds CF, Jennings JR, et a!. Nocturnal penile tumescence is diminished in depression. Bioi Psychiatry 1988;24(1): Endicott J, Spitzer RL. A diagnostic interview: the schedule for affective disorders and schizophrenia. Arch Gen Psychiatry 1978;35: Derogatis LR, Melisanatos N. The DSFI: a multidimensional measure of sexual functioning. Journal Sex Marital Ther 1979;5: Reynolds CF, Frank E, Thase ME, et al. Comparative assessment of sexual function in depressed, impotent, and healthy men: factor analysis of a brief sexual function questionnaire. Psychiatry Res 1988;24: Karacan I, Salis PJ, Ware JC, et al. Nocturnal penile tumescence and diagnosis in diabetic impotence. Am J Psychiatry 1978a;135: Karacan I, Salis PJ, Williams RL. The role of the sleep laboratory in diagnosis and treatment of impotence. In: Williams RL, Karacan I, eds. Sleep disorders: diagnosis and treatment. New York: John Wiley and Sons, 1978b. 12. Campbell PI, Reynolds CF, Jennings JR, et al. Laboratory note: reliability of NPT scoring and visual estimates of erectile fullness. Sleep 1987;10: Thase ME, Reynolds CF, Jennings JR, et al. Diagnostic performance of nocturnal penile tumescence studies in healthy, dysfunctional, (impotent), and depressed men. Psychiatry Res 1988;26:79-87.