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From the * Division of Endocrinology, Department
of Medicine, Harbor-UCLA Medical Center and Research and Education Institute,
Torrance, California; University Department of
Medicine, Queen Mary Hospital, Hong Kong, China;
Department of Pediatrics, Harbor-UCLA Medical
Center and Research and Education Institute, Torrance, California; and
Department of Psychology, Texas A & M
University, College Station, Texas.
| Correspondence to: Christina Wang, General Clinical Research Center, Harbor-UCLA Medical Center and Research and Education Institute, 1000 W Carson St, Torrance, CA 90509 (e-mail: wang{at}gcrc.rei.edu). |
| Received for publication January 21, 2003; accepted for publication March 21, 2003. |
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Abstract |
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Key words: Sexual function, mood, testosterone
During the assessment of sexual function and mood in hypogonadal men, different self-reporting questionnaires have been developed for each individual study by different investigators. These questionnaires usually do not include all aspects of sexual desire and sexual performance as well as positive and negative mood changes. We have developed and utilized a simple, daily self-report psychosexual diary at the Harbor-UCLA Medical Center and Research and Education Institute. Over the past several years, we have used this questionnaire for testosterone replacement therapy studies in hypogonadal men and male contraceptive trials in eugonadal men. We describe the validation and field performance of this questionnaire for the assessment of the psychosexual state of hypogonadal and eugonadal research subjects and its use in detecting change after testosterone therapy.
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Subjects and Methods |
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Study Groups
Comparison Data Set 1, Hypogonadal Group—
Sixty-seven hypogonadal men, aged 19-62 (28% and 7% were over the age of 50
years and 60 years, respectively), were recruited from four centers for the
study of the effects of sublingual testosterone replacement (Biotechnology
General Corporation, Iselin, NJ), 5 mg, three times a day
(Wang et al, 1996a). All
subjects had baseline serum testosterone cyclodextrin concentration less than
the lower limit of the normal adult male range, (10.4 nmol/L or 300 ng/dL) and
were all in good health except for hypogonadism. If the subjects had
hypopituitarism, they were on adequate replacement of other hormones. The
hypogonadal subjects had never received testosterone treatment or had been
withdrawn from their testosterone replacement treatment for 4-6 weeks. They
were studied before treatment and monthly for 6 months after they began
therapy.
Eugonadal Group—
Forty-two healthy male volunteers (between 19 and 50 years) were recruited
for participation in longitudinal studies of agents that may suppress
spermatogenesis. The data from these eugonadal men were obtained at
pretreatment (baseline) before any therapeutic intervention. They had no
significant medical history, normal physical examination, normal serum
testosterone (
10.4 nmol/L, 300 ng/dL) and normal semen analyses (sperm
concentration >20 million/mL, sperm motility >50%, and sperm morphology
>10% normal by strict criteria). Comparison Data Set 2, Hypogonadal
Group—Two hundred twenty-seven subjects from 15 centers were
enrolled in a study that compared transdermal applications of a testosterone
gel given at 2 different doses to an androgen patch
(Swerdloff et al, 2000 for
details). Testosterone gel (AndrogelTM), either 5 g/d (5 g of gel
containing 50 mg testosterone) or 10 g/d (10 g of gel containing 100 mg
testosterone) was applied to 4 sites over the body (over both shoulders and
arms and the abdomen) daily. Subjects assigned to the patch applied 2
testosterone patches (AndrodermTM) daily, each delivering 2.5 mg/d
of testosterone. The subjects completed the questionnaire daily for 7 days
before clinic visits at baseline and monthly after that for 3 months and again
after 6 months. Aside from the hypogonadism, the subjects were in good health
with no history of chronic medical illnesses or alcohol or drug abuse.
Subjects were either naïve to testosterone treatment or were withdrawn
from testosterone ester injection for at least 6 weeks and oral or transdermal
androgens for 4 weeks before the screening visit. The age range of the
subjects was between 19 and 68 years (57% and 29% of the hypogonadal men were
over the age of 50 and 60 years, respectively). In this report, only the
hypogonadal men with a basal serum testosterone (before start of testosterone
replacement) equal to or less than 10.8 nmol/L (300 ng/dL) were included for
the data analyses (153 men).
Eugonadal Group— Forty healthy male volunteers aged between 19 and 50 years were recruited for clinical trials of potential male contraceptive studies. They had no significant medical illness, normal physical examinations, normal serum testosterone levels, and normal semen analyses. Only pretreatment data are reported for these subjects.
Stability Test Group— Six healthy eugonadal men were treated with placebo in a 3-month, double-blind study to investigate spermatogenic suppressive effect of an oral agent. These 6 subjects completed the daily questionnaire for the week preceding each of 5 clinic visits over the period of 84 days.
The Sexual Function and Mood Questionnaire
The questionnaire is shown in Appendix
1. It is a self-reporting instrument designed for the assessment
of sexual function and mood on a daily basis (Wang et al,
1996a,b;
Alexander et al, 1997; Wang et al, 2000). The sexual
function parameters utilized in the diary were similar to those reported by
O'Carroll and Bancroft (1984)
and Davidson et al (1983). The
subjects were asked to complete the questionnaire daily for 7 consecutive days
before each clinic visit. At each clinic visit when the diaries were
collected, the study coordinator reviewed the questionnaires for completeness
and clarified all missing data. The questionnaire covered 3 different domains:
1) sexual desire, enjoyment, and performance; 2) sexual activity score; and 3)
mood. Sexual desire and sexual enjoyment with and without partners were rated
on a 7-point Likert-type scale from 0 to 7, with 0 indicating none and 7
indicating very high. Sexual performance included self assessment of
satisfaction of erection that was rated using the 7-point Likert-type scale
described above, and percent full erection, which varied from 10% to 100%. The
latter two items were left blank if the subject did not have an erection. The
weekly value for these items were the simple average of the score for the 7
days. Sexual activity was assessed using a checklist format. The subjects
recorded whether they had sexual daydreams; anticipation of sex; flirting (by
themselves or others); sexual interactions with partner; and erection,
masturbation, intercourse, orgasm, and ejaculation on each of the 7 days. The
value was recorded as 0 (none) or 1 (any) for analysis. The weekly value for
the sexual activity items was the sum of the number of "any"
responses for the week. The sexual activity score was then calculated as the
average of the weekly values for all of the items.
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The mood parameters were assessed on the 7-point Likert scale. These included alert; full of pep/energy; friendly; well/good (positive mood parameters); and angry, irritable, sad or blue, tired, and nervous (negative mood parameters). The weekly value of each of these items was the average of the 7 days. Positive mood was the average of the 4 positive mood parameters (alert, full of pep, friendly, well). Negative mood was the average of the 5 negative mood parameters (angry, irritable, sad or blue, tired, and nervous).
Thirty-one hypogonadal subjects and 18 normal subjects from the first comparison data set completed the Profile of Mood States (POMS) at the same time as they completed their baseline questionnaires. The POMS is a well-known and thoroughly validated instrument. It consists of 65 items and provides 6 subscales (tension/anxiety, depression/dejection, fatigue/inertia, anger/hostility, confusion/bewilderment, vigor/activity) and a total mental distress (which equals to tension + depression + fatigue + anger + confusion - vigor subscales) (McNair et al, 1971).
Statistical Analyses
Repeated-measures analysis of variance was used to show the longitudinal
consistency of the sexual function and mood measures over time in the 6
placebo-treated eugonadal men. Concurrent validity for the mood scales was
assessed by computing correlations between the mood items and scales and the
well-validated POMS subscales. The correlations were run separately in the
hypogonadal and normal groups. To show the discriminant validity of the
questionnaire, comparisons between eugonadal and hypogonadal men on the mood
scales, sexual desire, performance and enjoyment, and sexual activity scores
were done using Student's t tests or, for the activity score,
Wilcoxon's test for independent groups. To indicate the ability to detect
change with testosterone treatment in the hypogonadal men, paired Student's
t tests or Wilcoxon's rank tests were used to test for change after
30 days of treatment.
For brevity, only results from the summary scores for sexual activity, positive and negative mood parameters, or stand-alone items (sexual desire, sexual enjoyment, satisfaction with erection, and percent full erection) are shown except for the concurrent validation of mood parameters using the POMS scales and test-retest reliability in the 6 eugonadal men studied over time. If one of the diaries was missing, the mean scores used the mean of the available data. If all the data were missing, then the subject was excluded from the analysis of that time period.
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Results |
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Concurrent Validity of the Mood Scales
The concurrent validity of the mood parameters was studied by comparison
with POMS scales. Table 1 shows
that the correlations of the parameters assessed by the sexual diary with
those assessed by POMS in 31 hypogonadal men and 18 normal subjects. On the
POMS questionnaire, vigor is the only positive mood item; all other parameters
were considered negative. In the group of 31 hypogonadal men, almost all the
diary items correlated significantly with the items in the POMS and in the
direction expected. The positive mood scale and positive mood items assessed
by the diary correlated positively with vigor on the POMS and negatively with
the negative parameters of POMS in the hypogonadal men. Conversely, the
negative mood scale and items of the diary correlated positively with the
negative parameters of the POMS and correlated negatively with vigor on the
POMS in the group of hypogonadal men. In the smaller group of 18 eugonadal
subjects, the positive mood score showed significant correlation with vigor on
the POMS and negative correlation with tension and depression. The negative
score was not significantly correlated with any POMS items, but the negative
item "tired" was highly correlated with tension, depression, and
confusion and negatively (but not statistically) correlated with vigor. These
results demonstrated that the mood items in the diary showed consistent
relationships with a well-validated mood question (POMS).
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Demonstration of Discrimination Between Normal and Hypogonadal
Men
To test whether the responses to the various parameters in the diary are
different among clinically distinct groups of men, we compared sexual and mood
parameters between normal (before any intervention) and hypogonadal men (after
treatment withdrawal and before testosterone replacement in the hypogonadal
men) at baseline. The comparison data between eugonadal and hypogonadal men
are given in Table 2. Serum
testosterone levels were not different between the two hypogonadal groups
(mean ± SD, 119 ± 95 ng/dL and 187 ± 115 ng/dL in data
set 1 and 2, respectively) or between the two eugonadal groups (546 ±
192 ng/dL and 495 ± 139 ng/dL in data set 1 and 2, respectively). Serum
testosterone levels were significantly different between the hypogonadal and
eugonadal men (P < .0001)
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Sexual Desire and Performance
In both comparison data sets, hypogonadal men had significantly reduced
scores, compared with normal men on sexual desire (P < .0001),
sexual enjoyment without a partner (P < .0001), satisfaction with
erection (P < .0001), and percent full erection (P <
.0001). The hypogonadal men in comparison data set 2 had significantly lower
scores in sexual enjoyment with a partner (P < .0001). Scores of
sexual enjoyment with a partner were not different between eugonadal and
hypogonadal men in comparison data set 1 (P = 0.68).
Sexual Activity
Figure 2 shows the
distribution of the activity scale in eugonadal (right panels) and hypogonadal
(left panels) subjects in comparison group 1 (upper panel) and comparison
group 2 (lower panel). Hypogonadal men had significantly fewer sexual
activity-related events than eugonadal men in both comparison groups.
Eugonadal men, with the exception of one subject in comparison group 1, all
had some sexual activity, and only 12% and 2.5% had a weekly average of fewer
than 2 events in comparison groups 1 and 2, respectively. In contrast, 26 and
31% of the hypogonadal men in comparison group 1 and 2 reported no sexual
activity; 34% and 37% reported a weekly average or less than one event; and
50% and 64% reported a weekly average of less than 2 events in comparison
groups 1 and 2, respectively.
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Mood Scores
In comparison data set 1, the hypogonadal subjects demonstrated
significantly higher negative mood scores than the normal subjects (P
< .0001). These negative mood scores were not different between eugonadal
and hypogonadal men in comparison data set 2. The baseline positive mood
scores were not different between eugonadal and hypogonadal men in either data
sets (Table 2).
Responsiveness of the Parameters to Testosterone Replacement in
Hypogonadal Men
Average serum testosterone concentrations in the hypogonadal subjects over
a 24-hour period increased into the normal range after testosterone
replacement (from 119 ± ng/dL to ± ng/dL and from 187 ±
ng/dL to ± ng/dL in data set 1 and 2, respectively). To assess whether
the diary can detect meaningful changes over time with testosterone treatment,
we assessed the values of sexual and mood parameters in response to
testosterone treatment in hypogonadal men, compared with their baseline scores
and also to values of normal men at baseline
(Figure 3). Sexual desire,
enjoyment without partner, and performance improved significantly after 30
days of treatment in both comparison groups (P < .001 for all).
Sexual activity increased in both groups (P < .0001). After 30
days of treatment, only 6.6% of subjects in group 1 and 3% of subjects in
comparison group 2 had no sexual activity. The numbers reporting less than 1
event and less than 2 events decreased to 13% and 26% in comparison group 1
and 12% and 29% in comparison group 2. Most of the parameters the hypogonadal
men improved to values similar to eugonadal men, but the sexual activity
scores remained lower than those in the eugonadal men in both data sets
(P < .001 in both groups).
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Hypogonadal men in comparison group 1 improved significantly on positive mood (P = .0028) but did not change significantly on negative mood (P = .2674). Hypogonadal men in comparison group 2 showed significant improvement in both positive and negative mood (P = .0001 and .0003, respectively).
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Discussion |
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TopAbstractSubjects and MethodsResultsDiscussionReferences |
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We validated the measures of mood for concurrent validity by having 2 subgroups of subjects, hypogonadal men and eugonadal men prior to any treatment, complete the POMS questionnaire, a well-accepted measure of mood in different subjects, at the same time that they completed the diary and examining the correlations between the results. We demonstrated very strong agreement between the POMS and the diary in the hypogonadal group, thus giving concurrent validity to the diary. The associations were weaker in the eugonadal group, which was partially due to the smaller sample size, but there were still significant correlations of the positive mood scores with POMs items. Moreover, in both groups the significant correlations were consistently convergent toward the correct direction, ie, positive items and scales correlated positively with the positive POMs item "vigor" and negatively with all the other POMs items, which were all negative. Negative diary items correlated negatively with the POMs item "vigor" and positively with the other negative items. Hence, the mood items showed concurrent and construct validity with POMs.
To test the discriminant validity of the diary, we compared the hypogonadal men without testosterone replacement to the eugonadal men and showed that the diary distinguished the distinct clinical groups clearly in sexual desire, enjoyment, and performance as well as the scores of sexual activity. Though some of the hypogonadal men were over the age of 50 years, they all had average serum testosterone levels over the day below the lower limit normal range. The difference in their responsiveness to the questionnaire mostly likely was due to their hypogonadism rather than their age. To show that the results of these comparisons are reproducible, we ran each analysis in two different comparison data sets from different studies. In both comparison groups, the diaries detected noticeable and statistically significant differences between hypogonadal and normal subjects. The subjects were different on sexual desire, performance, and sexual activity in both comparison groups. There was a significant difference of the sexual enjoyment score (without partner) between the two groups in both studies; however, the sexual enjoyment score (with partner) was not different between the eugonadal and hypogonadal men in the first comparison group, although it was different in the second comparison group. This may be explained by the fact that many of the hypogonadal men did not have sexual partners; the subjects could have generalized the interpretation of "enjoyment," the difference in the duration of hypogonadism and the duration of treatment withdrawal. After 30 days of testosterone replacement, the diaries showed significant improvement in all the sexual function parameters assessed including sexual desire, enjoyment, performance, and sexual activity in both groups of hypogonadal men. We did not show the data after 30 days because in previous published studies, we have shown that these improvements of sexual function persist when the subjects are on replacement therapy (Wang et al, 1996a, 2000).
To assess the ability of the diary to detect change in mood scales, we compared the responsiveness to the questionnaire items from hypogonadal men after 30 days of treatment with testosterone to their values at baseline. The diaries did not show a significant difference between hypogonadal and normal men on the positive mood score at baseline. Hypogonadal men in the first comparison group had significantly lower scores than eugonadal men on the negative mood scale, but this was not significant in the second group. This may be due to the fact that the hypogonadal men had been hypogonadal for long enough to adjust to the condition. Alternatively, the period of testosterone replacement withdrawal was insufficient for the subjects to have mood deficiency. The discrepancy between the two data sets may also reflect that the self-report mood parameters may not be a useful tool to distinguish eugonadal and hypogonadal subjects after 6 weeks testosterone withdrawal. However, during testosterone replacement therapy in hypogonadal men, the positive mood scale improved significantly in both groups and the negative mood scale improved in the second comparison group. This change in mood had been previously reported by Burris et al (1992), Anderson et al (1999), O'Connor et al (2002) using other questionnaires as well as Wang et al (1996b, 2000) using this diary. We note that these changes in mood were not correlated with change in testosterone levels from baseline or value of testosterone levels after 30 days of treatment. We (Wang et al, 1996b) as well as others (O'Connor et al, 2002) observed that the improvement in mood parameter was correlated with increases in sexual desire, performance and activity. We also noted that testosterone did not have an effect of increasing negative mood items when given as replacement therapy to hypogonadal men. In prior reports when normal men were administered testosterone at supraphysiological levels, negative mood parameters such as anger, aggressive behavior, and irritability were also found not to be increased (Anderson et al, 1992; Bagatell et al, 1994; Tricker et al, 1996; O'Connor et al, 2002). There are also recent reports indicating that testosterone administration improves mood in depressed subjects (Perry et al, 2002; Pope et al, 2003).
Although this is a daily diary, it was felt that an everyday long-term assessment might be a burden to the subjects and impractical for most clinical research protocols. Therefore, the subjects were asked to fill out the diary for the consecutive 7 days before each clinic visit as a reflection of the past period. We believe that this is a reasonable compromise and we have shown that even with a 7-day period, we were able to demonstrate clear differences in sexual function between normal and hypogonadal men and in hypogonadal men before and after testosterone replacement. We conclude that this simple self-reporting questionnaire with components to assess sexual desire, enjoyment, performance, and activity as well as positive and negative mood is a useful instrument to assess psychosexual function in hypogonadal men.
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Acknowledgments |
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