Am J Psychiatry 137:4, April 1980 LETTERS TO THE EDITOR 507 Sex Differences and Tardive Dyskinesia SIR: In ‘ ‘Sex Differences in the Prevalence of Severe Tar- dive Dyskinesia’ ‘ (August 1979 issue), James M. Smith, Ph.D., and Daniel D. Dunn compared the findings from their study of tardive dyskinesia among schizophrenic inpatients aged 20-91 years with those from our study of outpatients aged 19-67 years (I). When the authors re-analyzed their data to include only patients in the 20-67 age range, the re- sults confirmed our earlier finding of a greater prevalence of severe tardive dyskinesia among men in this age group, at- though no difference existed between the sexes in regard to the overall incidence of the disorder. However, in patients aged 67 and over the more severe forms of tardive dyskinesia were strikingly prevalent among women. Since these find- ings are derived from studies of a total of 554 patients, we propose a tentative explanation. The results of these studies suggest that the expression of severe tardive dyskinesia may be suppressed in women dur- ing middle age. This may be traced to the action of estrogens on dopaminergic activity in the brain. Raymond and associ- ates (2) have shown that estradiols have dopamine antago- fist activity. Premenopausal women treated with neurolep- tics consistently show greater elevation of prolactin plasma levels than men, which may reflect a potentiation by estro- gen of neuroleptic-induced dopaminergic antagonism at the level of the tuberoinfundibulum (3). If the same potentiation occurs in the neostriatum, prernenopausal women might cx- perience milder forms of tardive dyskinesia because of the masking effect of estrogens. Because of this potentiation of neuroleptic activity, pharmacological denervation produced by neuroleptics should be more extensive in women than men, resulting in greater dopaminergic supersensitivity. As estrogen levels decrease, tardive dyskinesia might be uncov- ered or increase in severity in postmenopausal female pa- tients. It takes some years for this to be apparent, as estro- gen secretion declines slowly after menopause. Since do- paminergic supersensitivity would be expected to be greater in women, severe forms of tardive dyskinesia should be more common in geriatric women than in geriatric men. In assessing the effect of neuroleptics on positive schizo- phrenic symptoms, we have consistently found that female patients respond to a significantly greater degree than male patients (4). This supports the above hypothesis and may re- flect the potentiation of neuroleptic-induced dopaminergic antagonism by estrogens in the doparninergic system respon- sible for schizophrenic positive symptoms. Thus a patient’s hormonal status as well as age, as Dr. Smith and Mr. Dunn have suggested, may be important factors in assessing and treating tardive dyskinesia. These same factors may also play a role in the expression of positive symptoms of schizo- phrenia. REFERENCES I . Chouinard 0, Annable L, Ross-Chouinard A, et al: Factors re- lated to tardive dyskinesia. Am J Psychiatry 136:79-83, 1979 2. Raymond V. Beaulieu M, Labrie F, et at: Potent anti- dopaminergic activity of estradiol at the pituitary level on pro- lactin release. Science 200:1173-1175, 1978 3. Jones BD, Chouinard G, Annable L, et al: Neuroleptics and p1- tuitary dopaminergic receptors. Scientific Proceedings in Sum- mary Form: 132nd Annual Meeting of the American Psychiatric Association. Washington, DC, APA, 1979 4. Chouinard G, Annable L: Pimozide in the treatment of acute schizophrenia. Scientific Proceedings in Summary Form: 132nd Annual Meeting of the American Psychiatric Association. Washington, DC, APA, 1979 Guy CHOUINARD, M.D. BARRY D. JONES, M.D. LAWRENCE ANNABLE, DIP. STAT. ANDREE Ross-CHOuINARD, M.D. Montr#{233}al, Qu#{233}. , Canada Pain Insensitivity in Psychotic Patients SIR: In “Analgesia to Painful Stimuli in Affective Illness” (September 1979 issue), Glenn C. Davis, M.D., and associ- ates found affectively ill patients more analgesic than control subjects. They questioned whether an excess of endorphins might explain this relative analgesia and the psychiatric symptoms in depressed patients. Geschwind (1) had a similar speculation with regard to pain insensitivity in psychotic pa- tients. As early as the 1930s, psychotic patients with acute surgi- cal abdominal conditions were noted to have mild or absent abdominal symptoms and signs (2). Painless myocardial in- farction in psychotic patients has also been reported (3, 4). Furthermore, Marchand and associates (5) found pain to be absent in 29 of 79 psychotic patients with the acute surgical disorders of perforated peptic ulcers, appendicitis, and frac- tured femurs. Specifically, they noted pain to be absent in 14 of 39 patients with a diagnosis of schizophrenia, 7 of 12 with alcoholic psychosis, 2 of 6 with general paresis, 2 of 6 with cerebral arteriosclerosis with psychotic reaction, I of 6 with manic-depressive psychosis, 1 of 2 with involutional melan- cholia, and 2 of 8 with miscellaneous mental disorders. Anti- psychotic medication cannot be implicated because most of these observations were made before the introduction of phenothiazines. Marchand and associates (5) felt that the meaning of pain was lost in these psychotic patients. As the endorphin story unfolds, we may learn what role endogenous opiate-like substances play in pain insensitivity and psychiatric symptoms. REFERENCES I. Geschwind N: Insensitivity to pain in psychotic patients (ltr to ed). N EngI J Med 296:1480, 1977 2. Lewis C: Diagnostic problems of acute surgical conditions of the abdomen in psychotic patients. Medical Bulletin of the Veterans Administration 13:314-320, 1937 3. Marchand WE: Occurrence of painless myocardial infarction in psychotic patients. N Engl J Med 253:51-55, 1955 4. Lieberman AL: Painless myocardial infarction in psychotic pa- tients. Geriatrics 10:579-580, 1955 5. Marchand WE, Sarota B, Marble HC, Ct al: Occurrence of pain- less acute surgical disorders in psychotic patients. N EngI J Med 260:580-585, 1959 Dr. Davis and Associates Reply DWIGHT L. EVANS, M.D. ChapeiHill, N.C. SIR: We have reported data supporting insensitivity to acute experimental pain in 17 patients with schizophrenia who were compared with age- and sex-matched controls (1).