Psychoneuroendocrinology, 1975, Vol. I, pp. 165-178. Pergamon Press. Printed in Great Britain

47,XYY AND 46,XY MALES WITH ANTISOCIAL AND/OR SEX-OFFENDING BEHAVIOR: ANTIANDROGEN THERAPY PLUS COUNSELING J. MONEY, C. WIEDEKING, P. WALKER, C. MIGEON, W. MEYER and D. BORGAONKAR Department of Psychiatry and Behavioral Sciences, Department of Pediatrics, and Division of Medical Genetics, The Johns Hopkins University and Hospital, Baltimore, MD 21205, U.S.A. SUMMARY (1) Thirteen males with the 47,XYY genotype and ten with 46,XY were given the androgendepleting (antiandrogenic) steroid, medroxyprogesterone acetate, in combination with a counseling program. (2) Those with the XY genotype were all sex offenders and those with the XYY genotype were antisocial offenders (primarily robbery and destructiveness), with or without sexual offences. (3) The combined treatment program was beneficial in helping sex offenders to regulate their behavior and, in five instances (three XY and two XYY), there was a remission of paraphiliac symptoms. (4) The effect of treatment on aggressive-destructive antisocial behavior was less clear, and was probably due to a placebo-like response.

INTRODUCTION MEDROXYPROGESTERONE acetate was first used as an androgen-depleting agent for a sex offender in 1966 (Money, 1968, 1970). A t that time it was not, and still is not, permissible to use c y p r o t e r o n e acetate in the U.S.A.; this is the anti-androgen o f choice in E u r o p e (West G e r m a n y , Great Britain and Switzerland). Over the last 8 yr we have continued to use medroxyprogesterone acetate (Depo-Provera, Upjohn) as an androgen-depleting steroid in c o m b i n a t i o n with counseling therapy in a small investigative and treatment p r o g r a m to facilitate the self-regulation o f behavior in 4 7 , X Y Y men, with a history o f antisocial behavior, and in 46,XY men, with a history o f imprisonable sex offences. The purpose o f this paper is to report the findings o f this preliminary investigation. This study adhered to the code o f ethics o f the world medical association and there was no infringement o f h u m a n rights. METHODS

Subjects 47,XYY males, impulsiveant/soc/al. In the cytogenetic laboratory of the Johns Hopkins medical genetics clinic, there are on record 28 cases of the XYY karyotype. In 20 cases, patients were seen in person, and 18 of those were available for behavioral evaluation and follow-up. Two were too young (aged 10) for inclusion in the present report, and in three others there was no current, antisocial, impulsive behavior to warrant treatment with Depo-Provera. The remaining sample of 13 is known to be skewed in favour of antisocial, impulsive behavior, because cytogenetic screening was done specifically on individuals, many of them institutionalized with known histories of antisocial behavior, with or without sexual offences. Three of the XYY cases were ascertained in cytogenetic screening of local penal and detention centers, and two in a private reform school for adolescent boys. The remaining eight cases were referred because of impulsive and 165

19

18

20 25

16

22

22 16 28

15

25 35 29 29 42 23 36 24

22 29

4

5

6 7

8

9

10 11 12

13

14 15 16 17 18 19 20 21

22 23

46,XY 46,XY

46,XY 46,XY 46,X'Y 46,XY 46,XY 46,XY 46,XY 46,XY

47,XYY

47,XYY 47,XYY 47,XYY

46,XY/ 47,XYY* 47,XYY

47,XYY 47,XYY

47,XYY

47,XYY

47,XYY 47,XYY 47,XYY

185 180

178 179 180 185 160 169 178 173

188

183 196 193

198

186

207 202

185

176

181 188 205

100 125

108 112 124 117 111 114 110 79

116

82 97 120

111

110

121 114

92

95

92 103 125

Referral

DESCRIPTIVE DATA OF SAMPLE

Local Commuting distance Local Local

Physician (psychiatrist) Physician (psychiatrist)

Minister Psychologist (court appointed)

Minister

Local Geneticist, screening Local Mother Commuting Physician (psychiatrist) distance Commuting Geneticist, screening distance Commuting Physician (neurologist) distance Local Psychologist Commuting Attorney distance Commuting Physician (pediatrician) distance Commuting Physician (dermatologist) distance Local Geneticist, screening Local Physician (endocrinologist) Commuting Geneticist, screening distance Long Physician (pediatrician) distance Local Psychologist (court appointed) Local Physician (psychiatris0 Local Other patient (room-mate), self Local Self Local Minister

* Chromosomal mosaic with karyotype 46,XY/47,XYY.

20 21 37

1 2 3

Patient Age Chromosomal Height I.Q. OVALS) Domicile status (cm) (WISC)

TABLEI.

2 1"5

17

8

12 6 17 20 10

8

5

5 2 4"5

34

25

12 35

15

20

12 25 13

Duration of treatment (months)

102 95

65 142 78 64 74 58 89 76

100

79 92 79

112

78

82 91

74

69

81 85 111

102 97

69 142 78 " 85 68 58 95 78

O

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100

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95 103

167

88

100 105

90

77

86 110 135

Weight (kg) before during therapy

ANTIAI'qDROGEN THERAPY AND SEX OffENDERS

167

antisocial behavior problems in association with tallness by: a pediatrician (2); a neurologist (1); an endocrinologist (1); a psychiatrist (1); a psychologist (1); an attorney (1);and a parent (1). Four XYY patients did not complete the treatment. Six others completed an adequate term of treatment; two of them are now deceased. The remaining three are still r~civing treatment. 46,XY males, sex offenders. This sample was composed of 10 men all referred because of severe paraphiliac problems that threatened eventually to get them in jail. T h r ~ were re£err~ by psychiatrists, two by court appointed psychologists, three by clergymen, and two were self-ref(m~:l. One of the latter learned of the program through his room-mate, who was a participant. Both were homosexual pedophiliacs, as was one other case. The other seven diagnoses comprisezt: bisexual pedophiliac (1); heterosexual pedophiliac and voyeur (1); homosexual masochist (1); homosexual incestuous pedophiliac and transvestite (1); and heterosexual exhibitionists (3). In this group, eight men stayed on hormonal treatment for what was considered a therapeutically sufficient period of time, whereas two others dropped out prematurely. Data for all these patients are given in Table I. Note that patient 8 is a 46,XY]47,XYY chromosomal mosaic.

Behavioral data The patients' behavioral records included data from psychologic tests and transcribed taped interviews. Interviews were conducted according to a standard schedule of inquiry (Money & Primrose, 1969). The records also included data from social agencies and other institutions, and from interviews with those family members who made themselves available. From each behavioral record, data wore abstracted on large charts under the headings utilized in the figures and results in this report. Four people did the abstracting so that at least two people worked on each record, cross-checking with one another. From the abstracts, frequency counts and ratings w e ~ tabulated, with a consensus achieved by all four investigators. The ¢xiterion of whether to count a type of behavior present or absent was strict rather than lenient. That is to say, the evidence had to he unequivocal. Frequency counts and ratings were made separately for three periods: (1) the 2 yr before the start of treatment (except for animal assault which had o c e u r r ~ only in childhood); (2) the period of treatment which ranged from 6 months to 2 yr 11 months (Table I) with a median of 11 months, except for the six cases of dropout prior to the completion of 6 months of treatment; (3) the period of post-trcattmmt follow-up, taken as starting 6 weeks after the last injection, and applicable to the six dropouts as well as to the nine who satisfactorily completed more than 6 months of treatment, but not to the eight still continuing treatnmat. The duration of post-treatment follow-up was from 3 months to 4 yr 9 months, with a median of 21 months. Two patients had a history of treatment, relapse, and m e w e d treatment. In one instance the interval betw~n treatments was 8.5 months, and in the other, 3.75 yr, with the relapse into sex offending behavior occurring 5"5 yr after the patient first began treatment. Untreated for an additional year, this patient tben re-entered the program. Two years later, he is still on maintenance therapy. In the present calculations, only the duration of the second treatment period and subsequent follow-up was used.

Follow.up Information for this report was abstracted from the patients' psychohormonal research records, and then tabulated. The r~ords contained data pertaining to chromosomal status, and to initial and follow-up physical examinations, plasma hormone determinations, and behavioral histories. The duration of follow-up varied. The longest follow-up was from 1966, when Depo-Provera was first used in a sex-offender case. The shortest follow-up was for 6 months, since September 1974, when the final patient was enrolled in the study. No patients have been lost to follow-up. Those no longer under active treatment were re~ntly recalled for behavioral follow-up, or else interviewed by telephone.

Treatment regime The dosage of Depo-Provera administered in the early years of the study was 100 mg (1 crn s) a week, or 200 mg every 10 days. Subsequently, it was found that the initial dosage, for optimal lowering of plasma testosterone, needed to be changed to 2 ~ - 4 0 0 m g a week, the exact dosage being dependent on body mass. On the higher dosage, behavioral changes were optimized. Dependent on individual circumstances, the dosage could subsequently be lowered in progressive increments, and the frequency of injections could be changed to once every 10 days until a threshold was reached at which testosterone levels remained lowered. At this threshold level, erection with erotic expression was sometimes possible, though in reduced frequency. Sexual potency was in general more important to XYY men than to sex offenders. ~E¢

!/2--e

168

J. MONEY, C. WIEDEKING, P. WALK~g, C. M~OeO~, W. M~Y~R a n d D. BOaOAO~gAR

Karyotyping and plasma hormone determinations Karyotyping was done in the Division of Medical Genetics. In all cases, chromosome analysis was performed from blood cultures and also in some cases was confirmed from studies of skin fibroblast culturm. Identification of the two Y chromosomes was confirmed by quinacrine mustard fluortsc~c¢ analysis. Plasma testosterone determinations were done in the laboratories of pediatric endocrinology. Determinations wexc made by the three stage process of extraction, paper chromatography, and radioimmunoassay.

RESULTS The results are summarized in Figs. I-3. The numerical data of the figures are self-evident.

Changes in plasma testosterone For the normal adult male, the mean value for plasma testosterone in this laboratory is 575 -4- 150 ng/100 ml. For the normal adult female, the mean value is 49 :[: 13 ng/100 ml. In the present study, pretreatment plasma testosterone levels of the XYY men ranged from 384 to 995 (median, 568) ng/100 ml. Among the XY men, the range was from 212 to 1170 (median, 607) ng/100 ml. During treatment, plasma testosterone was lowered in XYY men so that the lowest levels ranged from 23 to 236 (median, 140) ng/100 ml. In the XY men, the corresponding levels were 31-196 (median, 70) ng/100 ml. These ranges include patients who were sometimes irregular in returning for their injections, but even they, like the others, showed a dramatic fall in the level of plasma testosterone in response to DepoProvera. Changes in behavior (I) Assaultive behavior against persons. The types of assault for which a positive rating was given included beating, hurling, cutting, shooting or otherwise attacking with intent to No. d

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A N T I A N D R O G E N T H E R A P Y A N D SEX O F F E N D E R S

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injure or kill. In some instances assault led to arrest. For each period of assessment, before, during and after treatment, one act of assault was sufficient to warrant a positive rating. 47,XYY males, impulsive antisocial. Eleven of the 13 X Y Y patients had a history of pretreatment assault of persons. The two exceptions were among those who stayed on treatment and were not dropouts; one has now terminated treatment and still has no history of assault. Among the remaining 11, six changed sufficiently during the treatment period so as to warrant a negative assault rating. One of these six is still on treatment. Of the remaining five, one discontinued treatment prematurely and reverted to assaultive behavior as did two others who completed a term of treatment. The remaining two of the six also completed their term of treatment and have no further history of assaults.

170

J. MONEY,C. WIEDEKING,P. WALKER,C. MZO~ON,W, MEYERand D. BOROAONKAR

There were five patients whose assault ratings remained positive during treatment and, so far as is known, have not improved since. Three of the five dropped out of treatment prematurely. The foregoing statistics indicate that assault of persons constituted a widespread problem for the group of XYY men investigated in this study. The improvement rate while on treatment was approx 50 %. Recidivism was 100 % among the treatment dropouts. It was less (60 %) among those who were not dropouts from treatment. These findings suggest that a program of androgen-depleting steroid treatments followed by prolonged periods of counseling, augmented with additional treatment periods as needed, might prove to be the ideal way of helping XYY men avoid the problem of assaulting other people. 46,XY males, sex offending. Two of the I0 men in this category had assaulted a person during the period prior to treatment. Both their assaults were sex related. In one case, the patient, a transvestite with homosexual incest-pedophilia, in an act of jealousy concerning his wife, assaulted another man. In the other case, a sickly youth of 16 had a history of threatening boys aged I0 or 11 with a knife unless they permitted him to engage in interfemoral intercourse with them. In both cases, there were no further assaults during the treatment period, nor afterwards. (2) Assaultive behavior against animals. A positive rating for this type of behavior was made if there was a history of violence against animals on at least one occasion, and if the animals died as a consequence. There were only two instances of such a history, both in XYY patients, and both we.re reported retrospectively ag having'occurred in childhood. Violence against animals was, thus, significant by reason of its absence in adulthood in both groups of men, before, during, or after treatment. (3) Destructive behavior against things. Positive ratings for this behavioral category were made for the before, during and after treatment periods, respectively, when valuable property, or objects of high personal and sentimental value were impulsively or methodically destroyed or severely damaged on at least one occasion. Fortuitous or accidental destructive behavior was not included. 47,X Y Y males, impulsive antisocial. Ten of the 13 XYY men were destructive of property. Three of the ten were rated as showing improvement under treatment. One of these three is still on treatment and remains undestructive; one other completed treatment and later relapsed into stealing but not destructiveness; the third dropped out of treatment and reverted to both stealing and destructiveness. From these statistics, it is obvious that outbursts of destructiveness do not yield readily to control in 47,XYY men. Said another way, they have a quick temper, and flare up easily. Impressionistically, there is some possibility of a lessened severity and frequency of outbursts as a function of treatment, but not a complete remission of impulsive outbursts of temper, defiance and vandalism, which may result in arrest. It is typical that XYY men are quite articulate concerning this trait in themselves, and their inability to regulate it (see also stealing). 46,XY males, sex offending. Destructiveness and vandalism were not characteristic of this group of 46,XY men either before, during or after treatment. (4) Stealing. A positive rating in this category was made for each of the three periods,

ANTIANDROGEN THERAPY AND SEX OFFENDEKS

171

separately, when acts of stealing were reported by self or others as having occurred at least twice in a given period. In younger patients stealing consisted typically of pilfering. With increased age, it increased in seriousness to include car theft, arson and, in one instance, armed robbery. 4 7 , X Y Y males, impulsive antisocial. Ten of the 13 men in this group had a history of stealing prior to treatment. Three of the 10 were known to steal again during the treatment period. Treatment was brief, for only one of the three, and he dropped out of the program prematurely, and continued to steal. Three other XYY men were premature dropouts; one has continued not to steal, for one the presumed positive evidence of continued chronic stealing is inconclusive, and the third has only recently become a dropout. Among the nine nondropouts, the five who completed their term of Depo-Provera treatment include two who have repeated their former stealing habit. The foregoing statistics indicate approx a 75% reduction, during treatment, in the number of patients who reported stealing. This improvement was counterbalanced by approx a 50 % relapse into stealing after the termination of treatment. XYY men who stole usually reported their stealing in a quite matter-of-fact way. It seemed as if it was understood that they were expected to steal when in need, and had a moral dispensation to do so. They were neither covert nor sneaky in this regard. 46, X Y males, sex offending. Among the 10 paraphiliacs, only one had a history of stealing, namely shoplifting, in association with acts of exhibitionism in a department store. There was a remission of both types of behavior during the course of therapy, punctuated by a relapse when the patient once dropped out of treatment for a temporary period of 3 weeks. He is still on the active treatment list. (5) Threatening behavior. A positive rating for threatening behavior was made when by means of either body movement, body language, or vocal language, a patient intimidated people to an extent that they were seriously concerned for the safety of themselves, other persons, or property. 4 7 , X Y Y males, impulsive antisocial. Ten of the 13 XYY men had a history of violent threatening behavior before treatment. One of the three former nonthreateners had, while on treatment, a blow-up in which he threatened to hit his father, and on another occasion, while reputedly on an LSD trip, he threatened his father with a knife. The other two nonthreateners remained pacific. While the 10 former threateners were on treatment, seven continued their threats. The remaining three discontinued threats while on treatment and maintained the change after completion of treatment. The threat as well as the actuality of destruction or assault is obviously a form of impulsive behavior that XYY men have great difficulty in restraining. In the three patients who gained a new degree of self-regulation, the change appeared unmistakable, and was personally approved. In the others, treatment may have ameliorated impulsive threats in ome patients, but not to the optimally desired degree. 46,XY males, sex offending. Only one of the ten men in this group had a history of threatening behavior. He was an exhibitionist who on one lone occasion, prior to treatment,

172

J. MONEY, C. WIEDEKING,P. WALKEa,C. MIGEON,W. MEYERand D. BORGAONKAR

g a b b e d and squeezed a girlfriend around the throat in a fit of rage when she alternately solicited and rejected him. (6) Self-harming behavior. A positive rating for this behavior category was made for each of the three study periods if the patient had at least once seriously hurt or injured himself, or threatened to do so, either to induce pain, or injury, or to attempt suicide. 4 7 , X Y Y males, impulsive antisocial. Six of the 13 men in this group had a pretreatment history of self-harming behavior. One, in adolescence, several times lay in the path of an oncoming train, escaping only at the last moment. Three cut themselves, two by smashing a window or wall with a bare fist, and one, in jail, by repeated mutiple incisions to both arms. These same three threatened suicide and two of them, plus one other, attempted suicide by taking pills. One of the three did eventually kill himself by jumping off a bridge, following an insult and rejection by a male lover at a cocktail party. The man who cut his own arms, as well as threatening suicide, contributed to his own death by engaging in a shootout with police from a house which he probably intended to rob. He then walked out, unarmed, into a barrage of police bullets. His death terminated a month's relapse which began when his wife capriciously and abruptly left him while he was hospitalized postsurgically. This was 9 months after the conclusion of a 3-yr course of treatment with Depo-Provera. Two of the six self-harming people manifested an improvement while on treatment. Only one of these two, the one who 8 yr ago courted death on the railroad tracks, has completed his course of treatment and has had no recurrence of self-harming. The follow-up for all patients off treatment includes two deaths and no known remissions of self-harming moods or episodes. The foregoing statistics indicate that XYY men are at risk for self-harming behavior and death to approximately the same degree as they are for threatening or harming others. According to their subjective report, it is not uncommon for them to feel despaired and depressed, as well as angry and enraged, at not being able to live at ease and not frustrated by their fellow men and women. They are as impulsive about harming themselves as in threatening or harming others or indestroying things. 46,XY males, sex offending. Nine of the 10 men in this group reported no self-harming practices or tendencies. The exception was, one young man, a homosexual masochist. He regularly enacted a masochistic fantasy in which a sexual partner, or partners, were stagemanaged to insult and threaten him with violence. There was always a risk that someone would overstep the mark from fantasy into reality, and there had, in fact, been some occasions of serious, near-fatal injuries. Four years after the premature termination of a brief trial on treatment, he made a suicide attempt by ingesting a sublethal dose of Sominex. (7) Imagistic eroticism. For each of the three periods, that is, before, during and after treatment, a positive rating was made in this category when, regardless of the content or theme of the imagery, a person reported having sexual or erotic sleeping dreams, daydreams, masturbation fantasies or copulation fantasies. In the pretreatment period, the presence of such fantasies earned a positive rating, irrespective of individual differences in absolute frequencies. During the course of treatment the rating was changed to negative if the patient reported a self-recognized substantial reduction in the frequency of erotic

ANTIANDROGEN THERAPY AND SEX OFFENDERS

173

imagery. Typically this decrease was paralleled by an increase in erotic inertia and a reduction in frequency of erection and orgasm--in two extreme cases to zero. Total disappearance of imagery, erection and orgasm was not set as a criterion of effective treatment, since erotic imagery and erection occur in the prepubertal years when plasma androgen levels are low. 47,XYY males, impulsive antisocial. Among the 13 patients in this group, one adolescent of 17 was electively mute on all matters pertaining to sex and eroticism. Another youth was sexually and erotically inert and indifferent, before, on and off treatment, and has remained so until the present. Among the remaining 11, four were assessed as having only the imagery of ordinary heterosexual gender identity, though three youths among them were extremely reticent in dating and romance. The remaining seven were varied in their imagery and gender identity. One, while having an isolation psychosis in jail, reported not only ordinary heterosexual imagery but also vengeful heterosexual incest imagery: in jail he also serviced homosexual fellators. Another youth claiming to be heterosexual only, was known from a parent's report to have engaged in several episodes of fetishistic transvestism, masturbating and ejaculating over his mother's apparel. One man was an exhibitionist, several times arrested, whose imagery and practice was also heterosexual and multiple partnered. Four others were bisexual: two predominantly heterosexual with casual homosexual encounters; one with a long-standing history, including arrests, of encounters with young adolescent males until, at the time of treatment, he underwent a religious conversion and settled down in a heterosexual marriage; and one predominantly homosexual (the patient who committed suicide), with a few trial episodes of being a masochistic 'slave'. There were only two patients who, despite the antiandrogenic effect of treatment, made claims that erotic imagery and masturbation were not substantially reduced. These two shy youths probably were euphemizing. The electively mute youth continued to be uncommunicative, and the sexually inert youth remained indifferent. The reports about the remainingnine patients all indicated a definite antiandrogenic reduction of erotic imagery, and in the case of the eight older adolescent and adult men, reduction of penile erotic function also (see section 8). This dual reduction proved reversible upon withdrawal of treatment, though two patients dubiously claimed to be sexually more quiescent. These 13 patients showed an extraordinary pretreatment range in distribution of eroticism from inertia to vigorously active, so that one suspects there may be as great a variability in erotic threshold in XYY men as there is in plasma testosterone level (Baghdassarian, Bayard, Borgaonkar, Arnold, Solez & Migeon, 1975). The preliminary evidence from the present sample shows, however, no correlation between testosterone level and either erotic threshold or the varied thematic and paraphiliac content of erotic imagery and practice. Regardless of erotic type, the eroticism of XYY men was reduced by treatment with Depo-Provera, the effect being reversible upon cessation of treatment. The reduction of eroticism had beneficial long-term side-effects. In one case it helped a man quit a long history of homosexuality with adolescents, in favor of a reorganized religious and married heterosexual life now of 3 yr duration. A second beneficial effect was that observed in helping the psychotic man in jail (later killed in the police shoot-out) as he recovered to revert to ordinary heterosexual imagery exclusively. In the case of the other paraphilias in

174"

J. MONEY, C. WIEDEKINO, P. WAtXEn, C. MIOr.ON, W. M~YEX and D. BOROAO~ZAR

47,XYY men, change in erotic imagistic content did not occur in connection with treatment. 46,XY males, sex offending. In all 10 sex offender cases, erotic imagery was reduced during the period of treatment. In all 10 cases, it had been characteristic of the original complaint that the imagery and thoughts of the legally offensive erotic practices had been overly insistent and compulsive. The patients did not complain at the reduction of their erotic imagery, but rather experienced it as a relief. In the five cases no longer in treatment, the level of erotic imagery was restored upon cessation of Depo-Provera treatment. In three cases, among those who remained in treatment for a long enough period of time, the content of erotic imagery became reoriented and remained so. The pedophiliac homosexual youth was able to keep out of legal trouble by being responsive to imagery and actual stimuli of males of his own age. One compulsive exhibitionist was no longer bothered by imagery or implementation of his habit, but was erotically content with marriage. The transvestite, pedophiliac father was no longer bothered by imagery or enactment of either transvestism or erotic practices with his juvenile son; he experienced what he defined as a more fulfilling erotic relationship with his wife. The beneficial effect of his treatment was repeated 3-75 yr later, following a relapse which necessitated a current low-maintenance dosage of Depo-Provera. (8) Actual erotic behavior and erections. For tabulation purposes actual erotic behavior and erections were separated, since erection is not imperative to erotic behavior. They are here presented together, for the findings of the two precisely parallel one another. Ejaculation was not tabulated separately from erection, owing to possible uncertainties of ascertainment should a dry orgasm replace an actual discharge into the vagina or anus. However, such evidence as appeared reliable pointed consistently to the fact that, in sufficient amount, Depo-Provera suppressed ejaculation. It is not necessary here to report the XYY and XY findings separately. The findings are so uniform, except for the XYY boy electively mute on sexual matters, that they can be summarized as follows: Prior to treatment, all of the patients were erotically active either in masturbation or some form of heterosexual or homosexual activity. On treatment with Depo-Provera, they all experienced an unequivocal reduction in the frequency of erections and actual erotic practice by an estimated minimum rate of at least 50 ~ to a maximum of

100%. At the conclusion of treatment, return of function was clearly established in all of the XY sex offenders. Among the XYY group, the same held true, except that the two chronically hyposexual individuals and one sexually inexperienced youth gave responses of doubtful authenticity; they were, therefore, rated as reduced in actual eroticism in the posttreatment period. The electively mute youth still had nothing to say. The foregoing findings indicate that the antiandrogenic function of Depo-Provera definitely reduced genital functioning, but that the effect was reversible. Moreover, in individual cases it was possible to show that, by calibrating the dosage, the frequency of ejaculation, erection and erotic behavior could also be calibrated. In this way, it was possible for a patient to resume his sex life, though on a reduced scale, while still maintaining some of the desired suppressive effect on offending erotic imagery and arousal. None of the patients was personally concerned about a risk of infertility. Such evidence

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as is known indicates no loss of fertility from treatment with Depo-Provera. Many XYY patients are idiopathically sterile. One among the present series, no longer on treatment, claims to have produced one pregnancy. (9) Eating and sleeping. The study included information on eating and sleeping, since excesses of both were initially suspected as adverse side-effects of Depo-Provera. The findings do not confirm this suspicion. Such increases as were reported were mild and reversible. Exceptions were in three patients who were established prior to treatment as obese excessive eaters, and two (one of them an excessive eater) who had a chronic history of sleeping l0 or more hours a day. One other patient complained of feeling drowsy at work. More objective findings than the patients' own reports of eating changes were obtained by regular follow-up of their weight. Weight before treatment with Depo-Provera and maximal weight during therapy are given in Table I. The median weight increase for 17 patients who were treated for 6 months and more was 9.0 (range 55 to --6) kg. The mean was 11.9 4- 14.0 kg. Omitting the three patients with excessive eating prior to therapy, the median was 8 (range 24 to --6) kg and the mean 8.7 ± 8.5 kg. Actual timing of the number of hours spent in sleeping was not feasible. The patients' own reports were checked against those of family members, in an overall effort to confirm the effect of treatment on sleep. DISCUSSION Though the sample of XYY men is small, 13 cases constitute a sizeable number of patients karyotyped as 47,XYY at any one medical center. The 46,XY sex-offender sample is also sizeable, for it is in the nature of paraphilia that the sex offender seldom envisions himself as a candidate for medical care, for he does not feel ill. Thus, there are few who report for treatment, except under the duress of crisis, as when arrested. We were expressly forbidden to treat as patients any who were already under arrest or in jail, even if the man himself initiated a request for treatment. It is fortuitous that the sex offenders are mainly pedophiliacs and exhibitionists. Rapists would have been included had they been referred. The two genotypic groups, 47,XYY and 46,XY, constitute a pair of contrast or comparison groups. The use of placebo control groups at the present time could not be justified. In the case of 47,XYY, there were too few available patients. Moreover, the antiandrogenic effect of medroxyprogesterone acetate on sexual functioning is so pronounced that it cannot be hidden from either the patient or investigator in a double-blind study design. In the case of 46,XY sex offenders, the ethics of the situation prohibited placebo treatment of men whose sex offenses were likely to be repeated. Wehad neither the legal right to require custodial hospitalization nor the right to treat sex offenders legally held and living in jail or other custodial institutions. For prisoners, the pendulum of the ethics of medical investigation has now swung beyond the point of protecting their right of informed consent to depriving them of all rights of informed consent, regardless of circumstance. Thus, it was not possible to form either a treatment or a placebo group of volunteer prisoners. The present study does not justify the assumption of an androgen-aggression relationship in the XYY antisocial offender. By itself, aggression is too amorphous to be studied directly. Hence, in the present study it was subdivided into nonamorphous, operationally definable types of behavior, as reported under Results, above. In XYY men, the findings do not

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indicate an unequivocal change, under the influence of treatment, of the so-called aggressive types of behavior to match the definite change in sexual types of behavior. To avoid a false-positive or halo effect of treatment, the criteria for change or improvement were strict--all or none. Such strictness masked the indication of a change based on degree or frequency, with respect to a given type of behavior. There may indeed have been such partial change or improvement, which was very difficult to document. Some parents and some patients are convinced that there was. If so, then the change may not have been a direct pharmacologic effect, but a more generalized, placebo-like effect based on the total method of case management. In defense of the hypothesis of a more generalized effect, one may cite the following evidence. When a 47,XYY child, adolescent, or adult first enters our clinic with a history of antisocial behavior, he has long been the victim of a principle, both overt and covert, in the folk philosophy of our times, that if he really tried to he could control his behavior voluntarily. In like manner, the folk philosophy spelled out in some instances by professionals, victimized parents by telling them that they must have done, or must still be doing something wrong to produce their son's abnormal behavior. Implied guilt of this type has a noxious and often adverse effect on the subsequent behavior of both the patient and his family. The situation was as traumatic as if a patient with epilepsy were led to believe that he and his family were behaviorally responsible for his seizures. In the medical folk philosophy of our day, it is more honorable, real, and respectable to have a physical, organic or somatic illness than to have one that is 'all in your mind'. Thus, for an XYY male, his family, and community to learn that he has a supernumerary Y chromosome may completely change their concept of the cause of his impulsive and socially stigmatized behavior. Self-blame can be lifted. The self-righteous morality of punishment as a means of training and reform can be replaced by a new morality of incentive and reward training buttressed by medication, regardless of the latter's actual pharmacologic effect. By contrast with its indirectly possible beneficial effect on behavior in the aggressivedestructive spectrum, medroxyprogesterone acetate proved, according to the above findings, to have a very direct effect on sexual behavior in both the 47,XYY and 46,XY genotypes. This effect can be rated as beneficial when sexual behavior is of a paraphiliac type which is socially not tolerated but severely punished. The effect is manifested not only as a diminution or suppression of erection and ejaculation, along with suppression of testicular androgen, but also as a lessening of the frequency and compulsiveness of erotic imagery. All of these changes are reversible upon withdrawal of treatment. In some cases--five in the present study, two XYY and three XY--the effect was not only reversible but brought with it a change of imagery from a paraphiliac and socially stigmatized to a socially acceptable one. The change was positively endorsed by the man himself as being personally more gratifying. It permitted the establishment of an erotic involvement with a long-term partner, in place of a series of compulsive sexual enactments to produce the relief, through orgasm, of nonerotic tension. Such a degree of change represents, so to speak, a psychic realignment. Such a realignment apparently cannot take place without the temporary and reversible effect of the medication--the 'vacation from sex drive'. Probably it also cannot take place without the concurrent effect of counseling.

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It is not yet known whether all patients on antiandrogen plus counseling treatment can expect a psychic realignment. It is known, from two cases, that a relapse may occur which requires a second course of treatment. There may be some cases in which, to prevent recidivism, the medication may need to be continued indefinitely. There is one homosexual child molester in our series who presently would elect to be on treatment throughout life, rather than to have his compulsion return. It goes without saying that there are potentially grave ethical decisions to make, and errors that could be made, in imposing antiandrogen therapy by edict on sex offenders. There is no ethically absolute criterion by which to define a sex offender. One can envisage an ethical nightmare in which antiandrogen is enforced on all prisoners--or all bisexuals, all homosexuals, all political dissidents, and so forth. The majority of paraphilias do not qualify as sex-offending, in the legal sense, no matter how bizarre they may appear to the ordinary person. They are not offenses because they involve no victim, not even an unwilling partner, and are not self-harmful. Thus, one may establish a pragmatic dividing line between offending and non-offending sexual behavior on the basis of what is imposed, especially by force, on an unwilling partner. Lust-murder, violent rape whether homosexual or heterosexual, violent child molesting, and masochistic contrivance of one's own death by sexual murder or suicide would qualify as behavior for which antiandrogen treatment should be legally enforced. Exhibitionism and voyeurism are borderline examples, for they are essentially harmless, especially to those who are sophisticated enough to know how to respond without surprise, shock, or fear. There is no reason to refuse treatment with medroxyprogesterone acetate to individuals with a socially harmless paraphilia if, for personal reasons, they might hope to change. The demasculinizing effect of the drug is looked upon favorably by male-to-female transexuals, though they prefer estrogen for its promotion of breast enlargement. The detailed mode of action of medroxyprogesterone acetate has not yet been elucidated. In biochemical structure it is an androgen. Physiologically i t can be used as a progestinic agent. Like other progestins, in a large enough dose it has an anesthetic effect. Thus, its beneficial effect in the treatment of the sex-offending paraphilias may, in part, have its site of action in sexual pathways of the brain's limbic system. If so, then this effect would be separate from the effect of lowering testicular testosterone production. All told, it seems highly likely that antiandrogen plus counseling will become accepted as the method of choice for the treatment of sex offenders. The respective merits of medroxyprogesterone acetate and cyproterone acetate remain to be evaluated. This work was supported by funds from the Grant Foundation, New York; The Upjohn Company, Kalamazoo, Mich. and Deutsche Forschungsgemeinschaft-Max Kade Foundation, New York. The authors appreciate the cooperation of the personnel of the pediatric clinical research unit and the ¢ytogeneticslaboratory, especially Ms. Sue Blair. Dean Gain, B.A. assisted in tabulating records. Ms. Mary Decker did the art work. REFERENCES BAGHDASSARIAN,A., BAYARD,F., BORGAONKAR,D. S., ARNOLD,E. A., SOLEZ,K. & MIGEON,C. J. (1975) Testicular function in XYY men. Johns Hopkins reed. J. 136, 15-24. MONEY,J. (1968) Discussion on hormonal inhibition of libido in male sex offenders. In Endocrinology and Human Behaviour, R. P. Michael (Ed.). Oxford Univ. Press, London.

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MONEY, J. (1970) Use of an androgen-depleting hormone in the treatment of male sex offenders. J. SexRes. 6, 165-172. Mo~Y, J. & ~ O S E , C. (1969) Sexual dimorphism and dissociation in the psychology of male tran. sexuals. In Transexualism and Sex Reassignment, R. Green and J. Money (Eds.). Johns Hopkins Univ. Press, Baltimore.