Br. J. clin. Pharmac. (1976), Supplement, 83-90
EVALUATION OF THE EFFECTS OF DRUGS ON SEXUAL BEHAVIOUR J.H.J. BANCROFT Department of Psychiatry, University of Oxford
Three main types of drug effect on sexual behaviour need to be considered: 1. Sexual side-effects of drugs 2. The therapeutic effects of drugs on sexual dysfunction 3. The use of drugs to control deviant or antisocial sexual behaviour.
Side-effects Of the drugs causing sexual side-effects, probably the most important are the adrenergic blocking hypotensive drugs, especially bethanidine and guanethidine (Prichard et al., 1968). Several studies have reported ejaculatory failure and to a lesser extent erectile impotence as common effects but these reports do not tell us whether this dysfunction is accompanied by loss of sexual interest and arousabiity or, if it is, whether this precedes or follows the peripheral dysfunction-both questions of theoretical and clinical importance. Oral contraceptives are also important in this respect. Again a number of studies have reported effects on sexual behaviour, although the evidence is often conflicting. One of the most recent and better controlled studies is that of Cullberg (1972) who concluded that the effects of oral contraceptives on sexual drive, if they occur, are probably secondary to mood changes. In this and most other studies, the measures of sexual effects have been extremely crude, and this fact alone could account for some of the conflicting evidence, considering the care that is required to get good information about sexual behaviour. There are of course particular problems in studying side-effects-clinicians are often reluctant to ask about side-effects for fear of suggesting them to the patient. This is particularly relevant in the case of sexual dysfunction, when concern about sexual performance can be sufficient in the vulnerable individual to precipitate failure. When one adds to this the frequent reluctance of patients to volunteer information about sexual dysfunction it is not surprising that our information is incomplete. Nevertheless, these are extremely important and possibly avoidable side-effects. 6*
Treatment of sexual dysfunction When considering the therapeutic use of drugs for sexual dysfunction we are concerned mainly with the use of androgens to increase sexual responsiveness and anxiolytics to reduce sexual anxiety. Only with androgens have we any controlled or systematic data (Bruhl & Leslie, 1963; Jakobovitz, 1970). Not only is this limited but once again it lacks any adequately comprehensive measure of change. In some respects assessment is easier in such studies than in many others because usually there is a partner who can corroborate the patient's report. For the same reason, however, assessment is also more complex as one needs to consider the effects of treatment not only on the patient receiving the drug but also on the partner.
Control ofantisocial sexual behaviour When control of antisocial sexual behaviour is the issue we have other methodological problems to consider. Here the motivation of the patient or recipient is not straightforward and we cannot necessarily rely on self-reports. Only two controlled studies of the sexually suppressive effects of drugs have been reported. In the first, benperidol, chlorpromazine and placebo were compared (Tennent et al., 1974), and in the second, cyproterone acetate and ethinyl oestradiol were compared (Bancroft et al., 1974). For these purposes there is a lack of measures which are both sufficiently comprehensive and adequately validated, which is greater when studying women who have the added complication of the menstrual cycle. Before discussing the measures currently in use let us first consider the various aspects of human sexuality which may be affected by drug action, and which therefore require to be measured. The following components should be considered: (a) Gender identity That aspect of identity which involves our sense of masculinity or femininity. (b) Sexual preferences and other sexual attitudes Whom we prefer as sexual partners and how we prefer to relate to them, together with other beliefs and expectations about sex. (c) Sexual arousability The facility with which we
84
J.H.J. BANCROFT
Sexual intercourse with an attractive girl E. S. A. E. S. A. S. E. A. S.
unpleasant
pleasant seductive __placid bad sexless ._ _ anxious == exciting kind * tense l l __0 frigid (Da) >
- - repulsive - - jittery * = good sexy calm dull -- _ cruel _ relaxed erotic __
-
a
4-
a 0CU $ -~ o0 o
o
E
0
a,) c-
.
CM a
Score 2 3 4 2 2 3 2 3 3 3
, > >
0) -o 0
E
E. General evaluation (3-21) S. Sexual evaluation (4-28) A. Anxiety (3-21)
Score 7 10 10
Figure 1 A semantic differential form for the concept 'sexual intercourse with an attractive girl'. The subject's scoring is indicated with a 0 in each line and the score for each scale is given in the column on the right. A score of 1 is most positive, 7 most negative and 4 neutral. The total scores for the three factors E, S, and A, given below the form, are obtained by summing the individual scales for each factor.
respond to erotic stimuli with an increase in sexual arousal. (d) Sexual behaviour Both fantasized and overt. (e) Sexual function The efficiency of key physiological responses, such as erection or orgasm, during overt sexual acts. (f) Sexual gratification The quality of the sexual experience. These components are not independent of one another but the relationship between them varies considerably from individual to individual; for example the extent to which gender identity is affected by sexual behaviour will vary and may be in part dependent on the level of sexual arousability (further discussion see Bancroft, 1972). Let us consider how each component may be appropriately measured.
Gender identity Although most drugs are unlikely to have a direct effect on gender identity, important changes could occur indirectly particularly when hormones are involved. Unfortunately there are no satisfactory
measures for this purpose. Early tests such as the Terman and Miles MF test are of very little value in this respect. The repertory grid technique offers the most interesting approach but is generally too cumbersome for use in drug studies. Some simpler method such as the semantic differential technique is probably the most applicable at the present time (Osgood et al., 1957) but as yet there have been very few reports of satisfactorily measured change in gender identity as a result of drugs or any other treatment (Bancroft, 1974).
Sexual preferences and other attitudes Sexual preferences are also unlikely to be directly affected by drugs although there may be an indirect effect on the partner. Androgens given to the female, for example, might render her less attractive to her male partner possibly because of interference with erotic cues such as pheromones or by inducing behaviour which is unattractive. Measures of sexual preferences have been either psycho-physiological (for example, measuring erection in response to different types of erotic stimuli) or
EVALUATION OF THE EFFECTS OF DRUGS ON SEXUAL BEHAVIOUR
85
al., 1971). This type of test has not so far been used in drug studies. There is currently a lack of any well validated measure of sexual anxiety, except for further modification of the SOM (Harbison et al., 1973).
Positive 1 Neutral 4 5
Negative 7-
Sexual arousability
t
After After 6 weeks Initially After 1 week 1 week Testosterone Placebo Testosterone Semantic differential scores (mean for 3 sexual concepts)
Figure 2 Changes in the semantic differential in a man with hypogonadism. His sexual attitudes were measured before treatment, after 1 week on placebo, and after 1 and 6 weeks on sublingual methyltestosterone (25 mg daily). The changes on the drug were significant. Scores represent the means for three sexual concepts (from Beaumont et al., 1972).
'pencil and paper' attitude measures. Of the latter the two most commonly used are the semantic differential, as modified by Marks & Sartorius (1968) and the sexual orientation method (SOM) of Feldman et al. (1966) (Figures 1, 2 and 3). The SOM is a very much more time-consuming and cumbersome measure than the semantic differential though it has the possible advantage of being less easily dissimulated. As originally devised it was simply a measure of homosexual and heterosexual preferences. It has been modified by the Belfast group to measure other types of sexual attitude (Graham et
t
.>
Pre-treatment 4
This is probably one of the components of sexuality most relevant to drug effects. Sexual arousal has a variety of physiological manifestations, though most of these are relatively non-specific, each being insufficient alone to distinguish between sexual and non-sexual arousal. In the male, penile erection is a relatively specific and easily measured response (Bancroft, 1971, 1974). In the female, intra-vaginal temperature change and clitoral enlargement have both been measured recently and appear to be good indicators of sexual response (Jovanovic, 1971). However, more work will need to be done before they can be reliably used as measures of change in the female. In the male, however, we are in a position to measure penile responses to specific erotic stimuli in controlled laboratory conditions (Figures 4 and 5). There are a number of methodological problems to consider. Repeated measurement of erectile response may have contrary effects-it may lead either to adjustment to the testing situation, reduction in inhibition and hence increasing responsiveness, or alternatively to habituation and reduction of response to the erotic stimuli. Which effect predominates may depend on the time interval between testing as well as the nature of the stimulus. Reifler et al. (1971)
No treatment Ethinyl
loestradiol
Cyproterone acetate
a)(n
Th
0
0
a)
CO
8
D
>
20
F2 -=1.91
N.S.
n= 12
oI)
z +
28
Figure 3 In this study (Bancroft et al., 1974) 12 sexual offenders each received three 'treatments', cyproterone acetate, ethinyl oestradiol and 'no treatment', each for 6 weeks. The order of treatments was balanced. Measurement of sexual attitudes using the semantic differential was carried out at the end of each 6week period. Neither in this study nor in the other study comparing benperidol, chlorpromazine and placebo (Tennent et al., 1974) was there any significant drug effect on attitudes.
86
J.H.J. BANCROFT
We found the response was significantly greater to film than to either slide or fantasy. In order to observe the maximum response to such stimuli it is probably advisable to expose them for no less than 2 minutes (Bancroft, 1974). Subjective ratings of sexual arousal can also be made during such testing though the correlation between such ratings and erectile response varies considerably from subject to subject (Bancroft, 1971).
08 a~~~~~~~~~~Ja CDCl a8 -C) ~ 0 ~ a 6
(DB(DC
0
0
-oz
0~~~~~ 4-
G)
D
EVALUATION OF THE EFFECTS OF DRUGS ON SEXUAL BEHAVIOUR J.H.J. BANCROFT Department of Psychiatry, University of Oxford
Three main types of drug effect on sexual behaviour need to be considered: 1. Sexual side-effects of drugs 2. The therapeutic effects of drugs on sexual dysfunction 3. The use of drugs to control deviant or antisocial sexual behaviour.
Side-effects Of the drugs causing sexual side-effects, probably the most important are the adrenergic blocking hypotensive drugs, especially bethanidine and guanethidine (Prichard et al., 1968). Several studies have reported ejaculatory failure and to a lesser extent erectile impotence as common effects but these reports do not tell us whether this dysfunction is accompanied by loss of sexual interest and arousabiity or, if it is, whether this precedes or follows the peripheral dysfunction-both questions of theoretical and clinical importance. Oral contraceptives are also important in this respect. Again a number of studies have reported effects on sexual behaviour, although the evidence is often conflicting. One of the most recent and better controlled studies is that of Cullberg (1972) who concluded that the effects of oral contraceptives on sexual drive, if they occur, are probably secondary to mood changes. In this and most other studies, the measures of sexual effects have been extremely crude, and this fact alone could account for some of the conflicting evidence, considering the care that is required to get good information about sexual behaviour. There are of course particular problems in studying side-effects-clinicians are often reluctant to ask about side-effects for fear of suggesting them to the patient. This is particularly relevant in the case of sexual dysfunction, when concern about sexual performance can be sufficient in the vulnerable individual to precipitate failure. When one adds to this the frequent reluctance of patients to volunteer information about sexual dysfunction it is not surprising that our information is incomplete. Nevertheless, these are extremely important and possibly avoidable side-effects. 6*
Treatment of sexual dysfunction When considering the therapeutic use of drugs for sexual dysfunction we are concerned mainly with the use of androgens to increase sexual responsiveness and anxiolytics to reduce sexual anxiety. Only with androgens have we any controlled or systematic data (Bruhl & Leslie, 1963; Jakobovitz, 1970). Not only is this limited but once again it lacks any adequately comprehensive measure of change. In some respects assessment is easier in such studies than in many others because usually there is a partner who can corroborate the patient's report. For the same reason, however, assessment is also more complex as one needs to consider the effects of treatment not only on the patient receiving the drug but also on the partner.
Control ofantisocial sexual behaviour When control of antisocial sexual behaviour is the issue we have other methodological problems to consider. Here the motivation of the patient or recipient is not straightforward and we cannot necessarily rely on self-reports. Only two controlled studies of the sexually suppressive effects of drugs have been reported. In the first, benperidol, chlorpromazine and placebo were compared (Tennent et al., 1974), and in the second, cyproterone acetate and ethinyl oestradiol were compared (Bancroft et al., 1974). For these purposes there is a lack of measures which are both sufficiently comprehensive and adequately validated, which is greater when studying women who have the added complication of the menstrual cycle. Before discussing the measures currently in use let us first consider the various aspects of human sexuality which may be affected by drug action, and which therefore require to be measured. The following components should be considered: (a) Gender identity That aspect of identity which involves our sense of masculinity or femininity. (b) Sexual preferences and other sexual attitudes Whom we prefer as sexual partners and how we prefer to relate to them, together with other beliefs and expectations about sex. (c) Sexual arousability The facility with which we
84
J.H.J. BANCROFT
Sexual intercourse with an attractive girl E. S. A. E. S. A. S. E. A. S.
unpleasant
pleasant seductive __placid bad sexless ._ _ anxious == exciting kind * tense l l __0 frigid (Da) >
- - repulsive - - jittery * = good sexy calm dull -- _ cruel _ relaxed erotic __
-
a
4-
a 0CU $ -~ o0 o
o
E
0
a,) c-
.
CM a
Score 2 3 4 2 2 3 2 3 3 3
, > >
0) -o 0
E
E. General evaluation (3-21) S. Sexual evaluation (4-28) A. Anxiety (3-21)
Score 7 10 10
Figure 1 A semantic differential form for the concept 'sexual intercourse with an attractive girl'. The subject's scoring is indicated with a 0 in each line and the score for each scale is given in the column on the right. A score of 1 is most positive, 7 most negative and 4 neutral. The total scores for the three factors E, S, and A, given below the form, are obtained by summing the individual scales for each factor.
respond to erotic stimuli with an increase in sexual arousal. (d) Sexual behaviour Both fantasized and overt. (e) Sexual function The efficiency of key physiological responses, such as erection or orgasm, during overt sexual acts. (f) Sexual gratification The quality of the sexual experience. These components are not independent of one another but the relationship between them varies considerably from individual to individual; for example the extent to which gender identity is affected by sexual behaviour will vary and may be in part dependent on the level of sexual arousability (further discussion see Bancroft, 1972). Let us consider how each component may be appropriately measured.
Gender identity Although most drugs are unlikely to have a direct effect on gender identity, important changes could occur indirectly particularly when hormones are involved. Unfortunately there are no satisfactory
measures for this purpose. Early tests such as the Terman and Miles MF test are of very little value in this respect. The repertory grid technique offers the most interesting approach but is generally too cumbersome for use in drug studies. Some simpler method such as the semantic differential technique is probably the most applicable at the present time (Osgood et al., 1957) but as yet there have been very few reports of satisfactorily measured change in gender identity as a result of drugs or any other treatment (Bancroft, 1974).
Sexual preferences and other attitudes Sexual preferences are also unlikely to be directly affected by drugs although there may be an indirect effect on the partner. Androgens given to the female, for example, might render her less attractive to her male partner possibly because of interference with erotic cues such as pheromones or by inducing behaviour which is unattractive. Measures of sexual preferences have been either psycho-physiological (for example, measuring erection in response to different types of erotic stimuli) or
EVALUATION OF THE EFFECTS OF DRUGS ON SEXUAL BEHAVIOUR
85
al., 1971). This type of test has not so far been used in drug studies. There is currently a lack of any well validated measure of sexual anxiety, except for further modification of the SOM (Harbison et al., 1973).
Positive 1 Neutral 4 5
Negative 7-
Sexual arousability
t
After After 6 weeks Initially After 1 week 1 week Testosterone Placebo Testosterone Semantic differential scores (mean for 3 sexual concepts)
Figure 2 Changes in the semantic differential in a man with hypogonadism. His sexual attitudes were measured before treatment, after 1 week on placebo, and after 1 and 6 weeks on sublingual methyltestosterone (25 mg daily). The changes on the drug were significant. Scores represent the means for three sexual concepts (from Beaumont et al., 1972).
'pencil and paper' attitude measures. Of the latter the two most commonly used are the semantic differential, as modified by Marks & Sartorius (1968) and the sexual orientation method (SOM) of Feldman et al. (1966) (Figures 1, 2 and 3). The SOM is a very much more time-consuming and cumbersome measure than the semantic differential though it has the possible advantage of being less easily dissimulated. As originally devised it was simply a measure of homosexual and heterosexual preferences. It has been modified by the Belfast group to measure other types of sexual attitude (Graham et
t
.>
Pre-treatment 4
This is probably one of the components of sexuality most relevant to drug effects. Sexual arousal has a variety of physiological manifestations, though most of these are relatively non-specific, each being insufficient alone to distinguish between sexual and non-sexual arousal. In the male, penile erection is a relatively specific and easily measured response (Bancroft, 1971, 1974). In the female, intra-vaginal temperature change and clitoral enlargement have both been measured recently and appear to be good indicators of sexual response (Jovanovic, 1971). However, more work will need to be done before they can be reliably used as measures of change in the female. In the male, however, we are in a position to measure penile responses to specific erotic stimuli in controlled laboratory conditions (Figures 4 and 5). There are a number of methodological problems to consider. Repeated measurement of erectile response may have contrary effects-it may lead either to adjustment to the testing situation, reduction in inhibition and hence increasing responsiveness, or alternatively to habituation and reduction of response to the erotic stimuli. Which effect predominates may depend on the time interval between testing as well as the nature of the stimulus. Reifler et al. (1971)
No treatment Ethinyl
loestradiol
Cyproterone acetate
a)(n
Th
0
0
a)
CO
8
D
>
20
F2 -=1.91
N.S.
n= 12
oI)
z +
28
Figure 3 In this study (Bancroft et al., 1974) 12 sexual offenders each received three 'treatments', cyproterone acetate, ethinyl oestradiol and 'no treatment', each for 6 weeks. The order of treatments was balanced. Measurement of sexual attitudes using the semantic differential was carried out at the end of each 6week period. Neither in this study nor in the other study comparing benperidol, chlorpromazine and placebo (Tennent et al., 1974) was there any significant drug effect on attitudes.
86
J.H.J. BANCROFT
We found the response was significantly greater to film than to either slide or fantasy. In order to observe the maximum response to such stimuli it is probably advisable to expose them for no less than 2 minutes (Bancroft, 1974). Subjective ratings of sexual arousal can also be made during such testing though the correlation between such ratings and erectile response varies considerably from subject to subject (Bancroft, 1971).
08 a~~~~~~~~~~Ja CDCl a8 -C) ~ 0 ~ a 6
(DB(DC
0
0
-oz
0~~~~~ 4-
G)
D
