Pergaswn Pros

Life Sciences vol . 17, PP " 661-668 Printed in the O.S .A .

MINII~VIEiP DHDGS AIm S~CÜAL BSHIIVIOS IN MAN Leo S . Hollister, M.D . Veterans Administration Hospital, Palo Alto, CA .

Drugs for trutiag diminished sexual function in man remain largely unsatisfactory, but new basic kaooalsdge about the roles of the naurotranamitters, dopamine sad serotonin, may silos the forsulatian of more effective caspounds. Drugs for decreasing sexual activity are more mm+arow and more affective although far lass desired . The tatiandrogan, cyproterone, is being studied as a trutsent for sexual offenders. Drugs wad for treatment of non-sexual disorders say have saocual effects and iafosaation should be collected about concurrent drug-taking is as3yone with a caasplaint about sazual function . Syspatholytics, ganglionie blocking drugs, antipaychotics and lithius may all impair saswl functions. Of the social drugs, alcohol is most clurly deleterious is its effacte . 1Such mystique has grayn about the use of illicit social drugs as saxwl stimulants . Szcapt for their affects as disinhibiting agents, little rationale ezists for most of the clams made . Like alcohol, heroin and other opiates decrease sexual activity . lsphatamiaas era bast documented as sexual stimulants, although such affects usually require anbstantial doses . Saxwl behavior, ordinarily thought of simply "doing what casts naturally," turns out to be much more canplex . It is dapendaat upon the interplay of bioganic :mines and hozmonas within the body, as wll as such extraneous influences as psychological conditioning, physical health and prevailing mood and circumstances . Although few persons are so unlucky as to be completely lacking in sexual drive, the variations in intensity of sexual drive are enormous between different individuals . Variations in the ezprassion of sazual drive are becoming incrusingly recognized, and quite possibly promoted by extensive publicity. To sat drugs within such a camplicatad framework of behavior is not an usy task . With so many variables operating simultaaeoualy, most of which can not be controlled, assessing is toy scientific fashion the influence of drugs on "normal" sexual behavior is not usily done . Aphrodisiac drugs have been alleged to have three major baaeficial effacte on saxwl behavior . First, to promote increased libido . Second, to increase sexual performance . Third, to increase sexwl pleasure . Sach of these manifestations ie somewhat interdnpandent, so that the specific mechanisms bq which these various claims are realized may overlap . Co~ersely, adverse effects of drugs on sexwl behavior decrease these throe areas of function . Changes of the latter type are much more easily measured . Therapeutic Drone Sex hormones am the coat popular prescribed treatments for enhancing 661

662

Drugs and Sexual Behavior in Man

Vol . 17, No . 5

sexual vigor . Eatrogens are given to women and androgens to men with the hope that declining sexual activity in the middle and latter yearn of life can be prevented or remedied . Except is clear cases of deficiency of either type of hormone, evidence for the desired effect is scanty . A popular remedy for impotence consists of a combination of two old drugs reputed to be sexual stimulants, strychnine and yohimbine . The former is thought to act as an excitant of the whole neuraxis, especially the spinal cord . Yohimbine acts by producing a state of parasympathetic predominance and vasodilatation . geceat reports of the use of pituitria for impotence are difficult to evaluate and the rationale is unclear . Of all drugs used therapeutically other than as sexual treatments, levodopa hoe been beat documented ae increasing sexual function . The stimulating effects on sexual behavior from increasing brain concentrations of dopamine or decreasing concentration of aerotonin in rats have been recently reviewed in this journal (1) . Ten of 41 patients treated for Parkinson's disease in one clinic sheared signs of increased sexual activity (2) . In another clinic, 7 of 19 patients showed increased sexual behavior at acme point is treatment, both news being affected . In 3 cases, increased sexual activity was secondary to improvement is the neurological disability, is 3 others due to direct stimulation, and is one patient secondary to disinhibition associated with a mild drug-induced organic brain syndrome (3) . Difficulty in separating a primary from a secondary action ie also encountered is reports of aaxual stimulation following corticoateroid treatment for severe rheumatoid arthritis or other collagen diseases . Decreasing aerotonin concentrations in brain would be expected to stimulate sexual function by enhancing the effects of endogenous testosterone . Parachlorphenylalaniae, which blocks aerotonin synthesis, was not more effec tive than placebo or testosterone when each was given alone . The addition of testosterone to treatment with the aerotonin-depleting agent caused s marked degree of sexual stimulation is men (4) . Impairment of sexual functions is men ie fairlq common with drugs with aaticholinargic or alpha-adrenergic receptor blocking actions . Difficulty in maintaining erection and delayed or absent ejaculation are the moat fre quent camplainta . Loss of libido in men has bean frequently reported from chronic treatment with aatipaychotice . Thioridazine, the moat potent anticholinergic and alpha-adrenergic receptor blocking drug in this aeries, has caused the greatest difficulty . Serum testosterone levels may decrease during chronic treatment with antipaychotica, but whether such minor decreases are important in determining the level of sexual function is questionable (5) . ßeserpiae also impairs sexual function, not only by means of the mechanisms mentioned above, but quite probably because of the attendant mental depression it often evokes . Baeerpine, as well ae the antipaychotics, decreases dopaminergic transmission in the central nervous system, which may directly decrease sex drive . These attributes of antipaychotic drugs have been employed therapeutically to treat premature ejaculation or the aberrant behavior of sexual deviants . Ia the latter case, to assure compliance with a coatinuad treatment program, depot preparations of fluphenaziae enanthate have been used (6) . Disturbed sexual function was found in 5 of 33 patients treated with lithium carbonate for mania . That erective potency wan related to lithium was clearly demonstrated in 2 patients treated under double-blind condi tions with lithium or placebo . Substitution of placebo relieved the symptom but impairment returned with resumption of lithium treatment (7) . Lithium also would be expected to decrease dopaminergic activity, s number of

vol. 17, No .

5

66 3

Drugs and Sexual Behavior in Man

diffeenat mechanisms having been postulated, such as decreasiag receptor sensitivity, increasing iatraaeuramal turnover or impairing transmitter release. Any class of drugs so widely used as the gestagen-estrogen oral contraceptives is likely to have same reported effects on sexual behavior . As compared with a group of vamen using iatrauteriae devices for coatracaptioa, women on oral contraceptives had a higher prevalanae of headaches, depression and loss of libido (8) . Hwever, a controlled trial found no difference in aexwl drive in women on active agents or placebo. ühan sexual interest vas lwernd, it was always secondary to depressive or dysphoric mood changes (9) . Although it is far osier to find drugs which twin saxwl drive off, there is less demand for such agents . Such drugs have been wad mainly in the treatment of sexual offenders, either child molesters or exhibitionists . Results of treatment have been reported to be good, but lack sufficient controls . A controlled comparison of ethiayl estradiol (0 .02 mg daily) and cyproterone, an antiandrogen (100 mg daily) shoved that both substances were equivalent in reducing the frequency of sexual thoughts and activity in men. Cyprotsrone, is these doses, had a weak effect is reducing arectile ruponsas to erotic stimuli (10) . The use of anti-androgens for sazwl offenders is far preferable to castration, although the efficacy of such treatment seeds further proof . Licit Social Droite Alcohol has long been recognised as a disinhibiting agent which might "provoke lechery" but detract from its parformaace. The Ogdan Nosh couplet about seduction put it more briefly : "Candy is dandy, but liquor is quicker ." Loagtezm use of alcohol may lead to premature loss of virility . One such alcoholic was quoted : "I started out ßarly Times, but quickly wooed up as Old Graadad." It has beam speculated that these changes are due to sacral plexus aeuropathy, the sme type of change which has been described in patients with long-standing diabetes mellites (11) . Loss of saxwl desire and frigidity may also occur in vomaa who era chronic alcoholics, but to a lesser extent than the analogous changes in men. Caffeine has bees condemned as leading to immorality, when the word almost ezclusively deaotad sexual immorality, while oa the other hand, it has been described as hot, black eater whose property is "to sterilise nature sad extinguish carnal desires" (12) . Probably both assessments are inaccurate . One can imagine that the stimulant effect of caffeine may be beneficial for enhancing sexwl perfonuace is someone who may otherwise be disinterested because of physical or mental fatigue . No specific effect of caffeine on sexual L~mction has been demonstrated at doses customarily taken. Higher doses might mimic to same extent the effect of amphetamines (see below) . Moat of the affects of tobacco use may be psychological rather than The advertising slogan for a pharmacological conaequeaces of nicotine . cigarette directed at the market for women, "You've came a long way, baby," contrasts the attitudes toward vaman smoking today with those which prevailed 60 years ago. The original liberation of women which oacurrad in the 1920e vas characterised by the flapper with a cigarette holder is hand . More than we appreciate, smoking by vamen has been symbolically linked with increasing sexwl freedom and civil rights . Illicit Social Drugs The gcneral impression, based on almost all possible evidence, 16 that

66 4

Druga and Sexual Behavior in Man

Vol . 17, rlo . 5

opiates seriously impair sexual fvactions . Although it has aaaetimea been said that initially opiates may enhance sexual enjoyment, such a process holds only with small doses which act as disinhibiting agents . As tolerance or physical depeadeace develops, sexual life suffers (13) . Chronic opiate use was associated vith lov serum testosterone levels . A similar decrease was found in patients on high-dose (80 to 150 mg/day) methadone maintenance, but those on low-dose (10 to 60 mg/day) maintenance had essentially normal levels (14) . Both methadone and, to a lesser extent, heroin diminished the function of secondary male sex organs, reducing ejaculate volume sad sperm motility (15) . Methadone, like heroin, may also impair sexual performance (16) . As one can never be sure of the doses of heroin that addicts take, a heavily addicted individual may ahoy a great improvement in sexual function if placed on small doaea of methadone following detoxification, while a mildly addicted person may notice no change . Complete cessation o£ opiates generally improves function to a normal level . Clinical reports of endocrinological or metabolic complications of opiate abuse have been exceedingly rare . Addicts show a partial decrease in gonadotropia raleaae manifested by decreased urinary excretion of 17-keto ateroids ; response to exogenous chorionic gonadotropiaa ie increased (17) . It is tempting to relate diminished gonadal activity to the lose of sexual desire universally experienced by addicts, but part may be due to the orgastic sensation evoked by each successive intravenous bolus of heroin and its subsequaat sedation . Diminished or absent menstrual periods, infertility and spontaneous abortion are frequent in addicted women and may be regarded as evidence of diminished release of pituitary gonadotzopias (18) . Neither methadone-maintained or heroin-dependent patients shoved any marked deviation from normal hypothalamo-pituitary-adrenal function other than a disturbed diurnal cortisol tide (19) . Scarcely say contentions were made that sedatives provided sexual benefits until the recent npiaoda of abuse of methaquslone in the United States (20) . Although this sedative drug had bean widely abused on two contiannta before making its way to the U .S ., it took the ingenuity of our drug-using culture to spread the word that this dnig had mystical sexual properties . At present, use of the drug aeeats to be decreasing sad claims for its special sazual properties am seldom heard . No one who took the drug as a prescription sedative-hypnotic ever noticed such effects . Methaqualone resao,bles mary prior drugs of this clans, being a totally unneeded addition to a plethora of such agents . Barbiturates are said to decrease release of pituitary gonadotropina, similar to that produced bq morphine . One is forced to conclude that for moat people, except those who require lose of inhibition, sexual performance under the influsace of sedative drugs is more likely to be diminished rather than enhanced . During the 1940a and 1950a, when abuse of amphetamines as exclusively by the oral route and doses were measured in tens of milligrams, they were alleged to incite young people to sexual orgies . In the 1960s and 1970s, use of stimulants has changed . Taking drugs is episodic, the route of admiaiatratioa is intravenous and repetitive, and doses are measured in 100a or 1000a of milligrams per day . Many other drugs may also be tried, including heroin . The effects obtained from intravenous injection of massive doses of amphetamines are qualitatively different from those obtained from smaller oral doaea (21) . Just as with heroin, an initial "rush," described as a visceral numbneae and tingling akin to a diffuse orgasm, is experienced followed by the customary signs of excessive stimulation, sympathetic nervous system ovar-

Vol . 17, No . 5

Drugs and Sexual Behavior in Man

66 5

activity and peculiar stereotyped grimacing movements . Same users report an immediate sexual effect, with increased desire sad sometimes immediate erec tions . Women become more sexually aggressive, while men may have prolonged erections and delayed ejaculation (22) . Disinhibiting affects were prominent, with the drug provoking instances of bisexual behavior . Oral use of mmphetaminea in the more conventional doses produced essentiallq no sexual dyafuaction in men but definite impairment in women (23) . As large doses of amphataminea may have significant dopamine-mimetic activity,~it is not too surprising that sexual stimulation may occur . Chronic sustained use often tends to be associated with diminished sexual performance, the dnig bacomiag a substitute for sex . Cocaine, a powerful stimulant which resembles amphetamines pharmacologically to a caasidarable degree, may be taken in small doses intranasally to enhance sexual activity alreadq planned . The main effect of such doses ie to delay ejaculation . Larger doses taken intreveaously resemble the effects of amphetamines taken by this route . Predictably, it was not long before devotees of hallucinogenic drugs ascribed special sexual affects to them se well . Certainly, sexual congress under the influence of these drugs must have been different from usual, con eidering the vast arraq of somatic, perceptual and psychic egmptoma which relativelq modest doses produced in the majority of people (24) . Just as with ether claimed effects of these drugs, aseertioaa about their sexual effects, being entirely subjective, are impossible either to prove or to disprove . In matters such ae this, what is is the eye of the beholder, is . S®e of the amphetamine-like effects of these drugs might contribute to an increased sexual interest . Paresthesias and floating sensations might be eapectad to eahaace some of the pheacmana of orgasm . One of the major problems with hallucinogenic drugs is that the abundance of sensory inputs may diminish appreciation of any single sae, so that rather than being "turned on" sexually, it is equally possible that one might be "turned off ." Many of my experimental subjects have told me that while they had thoughts of sax while under the drug, the idea of being able to accomplish the act seemed preposterous . Long before the present resurgence in use of canaabie, much of its uen was based on the notion that it enhanced sexual behavior . The effects of the drug are complex, having same elements of etimulaats, sedatives and halluci nogens, so that all the poaaible ways that the above drugs might enhance sax might occur with marihuana . Doses of cannabis co®only used ere quite small, so that diainhibition and expectation may play the greatest role is the drug's averred sexual benefits . With larger doses, the reverse situation might occur, so that absorption with what ie happening inside oneself may lead to neglect of the iatarparaonal relationship which sexual interwureé requires . The Indian Hamp Drugs Camniasion of 1894 reported that hemp drugs have "ao aphrodisiac power whatever ; and, as a matter of fact, they are used by ascetics in this country with the ostensible object of destroying sexual appetite ." You pay your moneq and you take your choice . That one's general pattern of sexull behavior could be changed by marihuana use is entirely poaaible . The thorn question is hoe often ie the taking of the drug related to the conscious adoption of a life style in which many behaviors are altered, including that of drug takingY reports of promiscuous or polymorphous sexual behavior in chronic marihwna users are frequent, but it is difficult to separate cause from effect (25) .

666

Drugs and Sexual Behavior in Man

Vol . 17, Yo . 5

A new finding should raise a new note of caution in those who would espouse marihuana use as a way to sexual salvation . Chronic marihuana use (four days a week for a miaimtmm of six months, without the use of other drugs) was associated with decreased plasma testosterone levels in young men as compared to similar controls, a finding which was dose-related, and reversible when marihuana was discontinued . Six of the 17 men ahwed oligospermia and two were impotent (26) . Thin finding has been challenged on a number of technical grounds and has noC been confirmed by others (27) . Amyl aitrlta has became an extraordinarily popular sex drug, especially among male homosexuals . The usual pattern of use is for one or both partners to inhale the drug during sexual intercourse, often simply to release ighibi tioae (28) . The vasodilating affect may lessen the intensity of erection of the male or active partner, is which case judicious use might provide a means for delaying orgasm and ejaculation . It has also been speculated that the drug may rela4 the internal anal sphincter facilitating anal intercourse . The moat caamoa aide effect is severe headache from dilation of blood vessels in the extracraaial circulation, the typical nitrite headache . Thin discomfort ie short-lived and probably not dangerous . Hypotension, tachycardia, and diminished cardiac output may presmt daggers to persona with known or latent cardiac disease . As is thn case with many drugs alleged to enhance aeaual pleasure, the rationale is sometimes difficult to explain . The Bole pharnacologlcal action of the drug is smooth muscle relaxation, which accounts for its strong vaso dilatiag affect . Vasodilation is manifested by a drop in blood pressure with an increase in pulse raté and by cutaneoua flushing . Abruptly lowered blood pressure produces a feeling of giddiness which may actuallq proceed to syncope, should the dose be too large . Quite possibly this feeling of dizziness and faigtaeae accounts for the purported iacreasa is the intensity of orgasm . Cutmnous vasodilation may also increase aensitivity of the akin, which could play a lesser role in enhancing pleasure . References 1. 2. 3. 4. 5. 6. 7. 8. 9. 10 . 11 . 12 . 13 . 14 .

G . L . GSSSA and P . TAGLIAI~DNTS, Life Sçi . 14 425-436 (1974) . M . HYYPPA, U . R . RII~, and V, SONNII~IQ, Âc a Neurol . Scand . Supvl . 43 223-224 (1970) . M . D . BOWERS, M . VAN WOSRT, and L . DAMS, Am . J . Paychiat . 127 16911693 (1971) . F . SICUTEitI, Phaxmacol . Res . Commun . 6 403-411 (1974) . P .J .V . BSIIIONT, C . S . CORER, H . G . FRIFSEN, T . KOLAROWSRA, H . M . IiANDELBROTE, J, M~AASt"T.T. ~ M,A .P . MURRAY, and D . H . WILES, Brit . J . Paychiat . 124 420-430 (1974) . A . A . BARTHOLOMEW, Am . _J . Pa cL hint . 1?4 917-923 (1968) . E . VINAROVA, 0 . UHGIF, L . STIRA, and 0 . VINAR, Activ . nerv . sug . (Praha 14 105-107 (1972) . B . N. HERZBERG, R . C . DßAPSIt, A . L . JOHNSON, and G . C . NICOL, Brit . Med . J . 3 495-500 (1971) . J . CULLBERG, i,cta Paychiat . Scaad . Suppl . 236 1-86 (1972) . J . BANCROFT, G . TE[ai~, R . LOUCAS, and J . CASS, Brit . J . Psychiat . 125 310-315 (1974) . F . LEMERE, sad J . W. SMITH, Am . J . Peychiat . 130 212-213 (1973) . L . LEitIN, Phantastica . Narcotic and Stimulating Drus . Their Uae sad Abuse , p . 257 E . P . Dutton and Campaay, New York (1964) . G . DE LEOTi, and H . R . WE]CLSit, J . Ann . Pa chol . 81 36-38 (1973) . J . H . MENDELSON, J . E . MENDSLSON, and V . D . PATCH, J . Pharmacol . Exptl . Therap . 1g 2 211-217 (1975) .

Vol. 17, No . 5

15 . 16 . 17 . 18 . 19 . 20 . 21 . 22 . 23 . 24 . 25 . 26 . 27 . 28 .

Drugs aad Sexual Behavior is Man

T . J. CICSRO, R. D. BELL, W. G. WIEST, J. H. ALLISON, K. POI~KI, aad E . ROBINS, Nev ~n~1 .J . Med . 292 882-887 (1975) . . O'HÂRE, C .P. O~EIEN, aad J. GOLDSCS3IDT, Arch . G~a. J . MIlPr2, iC Psychiat . 31 700-703 (1974) . A . J. HISEtl~lAN, H. F. FBASâR, J. SLOAN, and .H . ISBELL, J . Pharsucol. Exytl . Therav . 124 305-311 (1958) . S . S . STOFFER, Am. J . Obat . G,~n . 101 779-783 (1968) . P . CUSHßIAN, B . BORD7S8, and J . G. ßII.TON, J . Clia . Eadocrinol . !latabol . 30 24-29 (1970) . D. S . INABA, G. R. GAY, J . A . NHW!lAYSR, and C . WHITSHEAD, JAMA 224 1505-1509 (1973) . J. C . ~AT~B, V. S . FISi~tAN, and D. C . LIITLEFIELD, JAMA 201 305-309 (1967) . G. R. GAY, and C. W. 81~PPARD, Dzug Forum 2 125-140 (1973) . M. R. OOSSÛP, R. STERN, and P. H. CQ2atELL, Brit . J. Paychiat . 124 431-434 (1974) . L. E. HOLLISTER, Chamica Psychoaes . LYD and Relatnd Dru s, Clurlea C . Thamls, Springfield, Illinoia (1968) . H. KOLANSRY, and W . T. l~OOBE, J,A~lA, 216 486-492 (1971) . v ~. R. C. ROLODIiY, W. H. x~c~rvc , R . Ii . 1COLODNER, snd G. TOBO, Ne J . Med . 290 872-874 (1974) . J. H . MEl®ELSON, J . &~.E, J . SLLIIIGBOH, and T. F. BABOR, Naa Enal . J. lied . 291 1051-1055 (1974) . G. M . EVIItETP, Sexual Behavior : Pharmacology and Biochemistrs (1[ . Sandar aad G. L . Gessa, Editora), p . 98 BaveaPress, Nav York (1975) .

667

Drugs and sexual behavior in man.

Pergaswn Pros Life Sciences vol . 17, PP " 661-668 Printed in the O.S .A . MINII~VIEiP DHDGS AIm S~CÜAL BSHIIVIOS IN MAN Leo S . Hollister, M.D . Ve...
415KB Sizes 0 Downloads 0 Views