Testosterone and Depression in Aging Men
1999; Elsevier BV; Volume: 7; Issue: 1 Linguagem: Inglês
10.1097/00019442-199924710-00004
ISSN1545-7214
AutoresStuart N. Seidman, B. Timothy Walsh,
Tópico(s)Hormonal and reproductive studies
ResumoIn men, testosterone secretion affects neurobehavioral functions such as sexual arousal, aggression, emotional tone, and cognition. Beginning at approximately age 50, men secrete progressively lower amounts of testosterone; about 20% of men over age 60 have lower-than-normal levels. The psychiatric sequelae are poorly understood, yet there is evidence of an association with depressive symptoms. The authors reviewed 1) the physiology of the hypothalamic-pituitary-gonadal axis and its changes with age in men; and 2) the evidence linking testosterone level and major depression in men. Data on this relationship are derived from two types of studies: observational studies comparing testosterone levels and secretory patterns in depressed and nondepressed men, and treatment studies using exogenous androgens for male depression. The data suggest that some depressed older men may have state-dependent low testosterone levels and that some depressed men may improve with androgen treatment. In men, testosterone secretion affects neurobehavioral functions such as sexual arousal, aggression, emotional tone, and cognition. Beginning at approximately age 50, men secrete progressively lower amounts of testosterone; about 20% of men over age 60 have lower-than-normal levels. The psychiatric sequelae are poorly understood, yet there is evidence of an association with depressive symptoms. The authors reviewed 1) the physiology of the hypothalamic-pituitary-gonadal axis and its changes with age in men; and 2) the evidence linking testosterone level and major depression in men. Data on this relationship are derived from two types of studies: observational studies comparing testosterone levels and secretory patterns in depressed and nondepressed men, and treatment studies using exogenous androgens for male depression. The data suggest that some depressed older men may have state-dependent low testosterone levels and that some depressed men may improve with androgen treatment. Testosterone secretion in adult men has multiple determinants, and this androgen has actions that are neurobehavioral, somatic, and metabolic.1Bagatell CJ Bremner WJ Androgens in men—uses and abuses.New Engl J Med. 1996; 334: 707-714Google Scholar Central nervous system (CNS) effects include organizing and activating actions on male sexual arousal and behavior and some influence on energy and mood.2Rubinow DR Schmidt PJ Androgens, brain, and behavior.Am J Psychiatry. 1996; 153: 974-984Google Scholar Moreover, in animal models, testosterone plays a role in regulating some male social behaviors, particularly those related to male–male competition, dominance, and submission. Because of such effects, the relationship between testosterone secretion and major depression and the use of androgens to treat male depression or male "climacteric," have long been issues of speculation and anecdotal reports. Yet very few studies have systematically addressed these issues, and those doing so have produced inconsistent results. Furthermore, in aging men, specifically, among whom the prevalence of clinically significant hypogonadism may be 20%,3Field AE Colditz GA Willett WC et al.The relation of smoking, age, relative weight, and dietary intake to serum adrenal steroids, sex hormones, and sex hormone-binding globulin in middle-aged men.J Clin Endocrinol Metab. 1994; 79: 1310-1316Google Scholar there have been no published studies addressing the psychiatric implications of this endocrinologic hypofunction. In this article, we will first describe the physiology of testosterone secretion in men, with a focus on the changes that occur with aging, and the complicated interaction between testosterone and behavior. Then we will explore the following clinically relevant questions regarding the relationship between testosterone and depressive illness in men: 1.What is the relationship between testosterone level and male depressive illness? Specifically, do men who have a low testosterone level have an increased risk of developing major depression? Do men who are depressed develop a state-dependent impairment in testosterone secretion?2.What is the relationship between testosterone administration and male depressive illness? a) Does testosterone replacement (i.e., for men with below-normal levels) lead to improvement in depressive symptoms or to remission of major depressive disorder? b) Does administration of testosterone to depressed men who have normal testosterone levels lead to remission of the depressive illness? The testes and adrenals secrete several male sex hormones, called androgens. All are steroid hormones—that is, derived from cholesterol and containing a basic skeleton of four fused carbon rings (Figure 1). Testosterone is the primary androgen—by far the most abundant and most potent. It binds to the intranuclear androgen receptor, which is distributed widely throughout the body and the central nervous system (CNS), including limbic and cortical tissue.4Laycock JF Wise PH Male reproductive endocrinology.Essential Endocrinology. 3rd Edition. Oxford University Press, New York1996Google Scholar, 5Weinbauer GF Gromoll J Simoni M et al.Physiology of testicular function.in: Nieschlag E Behre H Andrology: Male Reproductive Health and Dysfunction. Springer-Verlag, Berlin, Germany1997: 25-60Google Scholar Dehydroepiandrosterone (DHEA) is an adrenal androgen that may play a protective role in many aspects of cellular functioning (particularly age-related deficits),6Morales AJ Nolan JJ Nelson JC et al.Effects of replacement dose of dehydroepiandrosterone in men and women of advancing age.J Clin Endocrinol Metab. 1994; 78: 1360-1367Google Scholar although it has a relatively minute amount of male androgenic activity. Neural activity in the medial basal hypothalamus controlled by adrenergic, dopaminergic, serotonergic, and endorphinergic inputs—and the surrounding hormonal milieu—stimulates the pulsatile release of gonadotropin-releasing hormone (GnRH), a decapeptide, into the hypothalamic-hypophysial portal system. GnRH promotes anterior-pituitary release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). LH stimulates the interstitial cells of Leydig in the testes to synthesize and secrete testosterone. Secretion occurs in pulsatile bursts, about six per day, with a morning peak and an early-evening trough; in total, approximately 7 mg of testosterone is secreted daily. Secretion is regulated through a negative feedback on the hypothalamus and pituitary.1Bagatell CJ Bremner WJ Androgens in men—uses and abuses.New Engl J Med. 1996; 334: 707-714Google Scholar, 4Laycock JF Wise PH Male reproductive endocrinology.Essential Endocrinology. 3rd Edition. Oxford University Press, New York1996Google Scholar, 5Weinbauer GF Gromoll J Simoni M et al.Physiology of testicular function.in: Nieschlag E Behre H Andrology: Male Reproductive Health and Dysfunction. Springer-Verlag, Berlin, Germany1997: 25-60Google Scholar In the bloodstream, testosterone is about 98% protein-bound: of this, just over half is weakly bound to albumin, and the remainder is tightly bound to sex-hormone–binding globulin (SHBG).1Bagatell CJ Bremner WJ Androgens in men—uses and abuses.New Engl J Med. 1996; 334: 707-714Google Scholar, 4Laycock JF Wise PH Male reproductive endocrinology.Essential Endocrinology. 3rd Edition. Oxford University Press, New York1996Google Scholar, 5Weinbauer GF Gromoll J Simoni M et al.Physiology of testicular function.in: Nieschlag E Behre H Andrology: Male Reproductive Health and Dysfunction. Springer-Verlag, Berlin, Germany1997: 25-60Google Scholar SHBG, a β-globulin produced in the testes and the liver, consists of different protein subunits, and one androgen binding site. Circulating free testosterone, the fraction that dissociates readily from albumin, and the fraction that dissociates less readily from SHBG (i.e., through molecular configuration changes in the capillaries), all diffuse into the target cell and bind to the androgen receptor.4Laycock JF Wise PH Male reproductive endocrinology.Essential Endocrinology. 3rd Edition. Oxford University Press, New York1996Google Scholar, 5Weinbauer GF Gromoll J Simoni M et al.Physiology of testicular function.in: Nieschlag E Behre H Andrology: Male Reproductive Health and Dysfunction. Springer-Verlag, Berlin, Germany1997: 25-60Google Scholar This receptor is a typical steroid receptor: it contains an N-terminal domain, a DNA-binding domain, and a hormone-binding domain.1Bagatell CJ Bremner WJ Androgens in men—uses and abuses.New Engl J Med. 1996; 334: 707-714Google Scholar, 4Laycock JF Wise PH Male reproductive endocrinology.Essential Endocrinology. 3rd Edition. Oxford University Press, New York1996Google Scholar, 5Weinbauer GF Gromoll J Simoni M et al.Physiology of testicular function.in: Nieschlag E Behre H Andrology: Male Reproductive Health and Dysfunction. Springer-Verlag, Berlin, Germany1997: 25-60Google Scholar The steroid-receptor complex binds to specific sequences of genomic DNA, and thereby influences the production of messenger RNA, which modulates protein synthesis in the cell.4Laycock JF Wise PH Male reproductive endocrinology.Essential Endocrinology. 3rd Edition. Oxford University Press, New York1996Google Scholar, 5Weinbauer GF Gromoll J Simoni M et al.Physiology of testicular function.in: Nieschlag E Behre H Andrology: Male Reproductive Health and Dysfunction. Springer-Verlag, Berlin, Germany1997: 25-60Google Scholar In target cells, testosterone is converted to two active metabolites: dihydrotestosterone (DHT) and estradiol (E2). There is tissue variability in the concentration of the cytoplasmic enzymes required for this conversion (5α-reductase and aromatase, respectively) and differential tissue sensitivity to each of these metabolites. Both testosterone and DHT bind to the androgen receptor; some androgen-responsive genes respond preferentially to intracellular DHT, making it the more potent androgen. For example, DHT is required for testosterone's effects on external genitalia and accessory sex glands; 5α-reductase enzymes are, therefore, abundant in reproductive tissues and skin. Estradiol binds to the estrogen receptor, and is required for some of testosterone's CNS and metabolic effects. Aromatase is most abundant in CNS, liver, and adipose tissue.1Bagatell CJ Bremner WJ Androgens in men—uses and abuses.New Engl J Med. 1996; 334: 707-714Google Scholar, 4Laycock JF Wise PH Male reproductive endocrinology.Essential Endocrinology. 3rd Edition. Oxford University Press, New York1996Google Scholar, 5Weinbauer GF Gromoll J Simoni M et al.Physiology of testicular function.in: Nieschlag E Behre H Andrology: Male Reproductive Health and Dysfunction. Springer-Verlag, Berlin, Germany1997: 25-60Google Scholar Psychological, social, seasonal, and biological factors affect testosterone secretion transiently: levels are elevated at times of decisive victory in competition, when social status is enhanced, during REM sleep, during cigarette smoking, after sexual activity, after exercise, and during the autumn. They are decreased at times of defeat or submission, during physical or emotional stress, during heavy alcohol use, and in the spring.7Kemper TD Social Structure and Testosterone. Rutgers University Press, New Brunswick, NJ1990Google Scholar, 8Dai WS Kuller LH LaPorte RE et al.The epidemiology of plasma testosterone levels in middle-aged men.Am J Epidemiol. 1981; 114: 804-816Google Scholar, 9Kreuz LE Rose RM Jennings JR Suppression of plasma testosterone levels and psychological stress.Arch Gen Psychiatry. 1972; 26: 479-482Google Scholar Testosterone level typically reverts to baseline soon after such stimuli, although there is some evidence from nonhuman primates that an aggression-induced low testosterone level can persist for weeks.10Rose RM Bernstein IS Gordon TP Consequences of social conflict on plasma testosterone levels in rhesus monkeys.Psychosom Med. 1975; 37: 50-61Google Scholar It is unknown whether a chronic or prolonged stimulus (such as the stress occurring during a major depressive episode) can lead to a new testosterone setpoint. Testosterone secretion varies through life. Prenatally, the genital ridge, and then testes, are stimulated by chorionic gonadotropin from the placenta to produce testosterone. Such secretion begins about the seventh week of embryonic life, peaks from Weeks 9–14, and continues until the first few weeks after birth.4Laycock JF Wise PH Male reproductive endocrinology.Essential Endocrinology. 3rd Edition. Oxford University Press, New York1996Google Scholar Then, there is very little testosterone secretion until about age 10, when nocturnal, pulsatile LH secretion begins. Between ages 11 and 14, testosterone secretion increases until adult male levels are achieved. It peaks at age 20, and slowly declines thereafter, although not significantly until about age 50.3Field AE Colditz GA Willett WC et al.The relation of smoking, age, relative weight, and dietary intake to serum adrenal steroids, sex hormones, and sex hormone-binding globulin in middle-aged men.J Clin Endocrinol Metab. 1994; 79: 1310-1316Google Scholar, 4Laycock JF Wise PH Male reproductive endocrinology.Essential Endocrinology. 3rd Edition. Oxford University Press, New York1996Google Scholar, 5Weinbauer GF Gromoll J Simoni M et al.Physiology of testicular function.in: Nieschlag E Behre H Andrology: Male Reproductive Health and Dysfunction. Springer-Verlag, Berlin, Germany1997: 25-60Google Scholar, 8Dai WS Kuller LH LaPorte RE et al.The epidemiology of plasma testosterone levels in middle-aged men.Am J Epidemiol. 1981; 114: 804-816Google Scholar Free and total testosterone concentration are generally measured from serum or salivary samples by use of radioimmunoassay (RIA). In young-adult men, evening testosterone levels are about 25% lower than morning levels; and the reliability (r) of testosterone measurements is 0.64 from day to day, and 0.50 over 1–4 years;11Dabbs JM Salivary testosterone measurements: reliability across hours, days, and weeks.Physiol Behav. 1990; 48: 83-86Google Scholar, 12Dabbs JM Testosterone measurements in social and clinical psychology.Journal of Social and Clinical Psychology. 1992; 11: 302-321Google Scholar among middle-aged men, the reliability is greater because of decreased diurnal and seasonal variability.3Field AE Colditz GA Willett WC et al.The relation of smoking, age, relative weight, and dietary intake to serum adrenal steroids, sex hormones, and sex hormone-binding globulin in middle-aged men.J Clin Endocrinol Metab. 1994; 79: 1310-1316Google Scholar, 13Bremner WJ Vitiello MV Prinz PN Loss of circadian rhythmicity in blood testosterone levels with aging in normal men.J Clin Endocrinol Metab. 1983; 56: 1278-1281Google Scholar For example, Vermeulen and Verdonck14Vermeulen A Verdonck G Representativeness of a single-point plasma testosterone level for the long-term hormonal milieu in men.J Clin Endocrinol Metab. 1992; 74: 939-942Google Scholar measured morning plasma-testosterone level in 169 middle-aged and elderly men on eight occasions over 1 year; correlation between the first sample and the mean of the next seven samples was 0.85. The father–son heritability of total testosterone concentration in adulthood is about 30%.11Dabbs JM Salivary testosterone measurements: reliability across hours, days, and weeks.Physiol Behav. 1990; 48: 83-86Google Scholar, 12Dabbs JM Testosterone measurements in social and clinical psychology.Journal of Social and Clinical Psychology. 1992; 11: 302-321Google Scholar Large epidemiologic studies have found body mass index and smoking status to be consistent predictors of testosterone level: obese men have relatively lower levels, smokers have higher levels.3Field AE Colditz GA Willett WC et al.The relation of smoking, age, relative weight, and dietary intake to serum adrenal steroids, sex hormones, and sex hormone-binding globulin in middle-aged men.J Clin Endocrinol Metab. 1994; 79: 1310-1316Google Scholar The other known positive predictor of testosterone level is SHBG level. SHBG level increases with age and smoking, and decreases with obesity. The net age effect, as determined from large, cross-sectional studies is that 1) through adult life, free testosterone declines at a rate of 1.2% per year; and 2) total testosterone remains steady until about age 50, and then declines approximately 0.4%–0.8% per year (Figure 2).15Gray A Berlin JA McKinlay JB et al.An examination of research design effects on the association of testosterone and male aging: results of a metaanalysis.J Clin Epidemiol. 1991; 7: 671-684Google Scholar, 16Vermeulen A Kaufman JM Giagulli VA Influence of some biological indexes on sex hormone-binding globulin and androgen levels in aging or obese males.J Clin Endocrinol Metab. 1996; 81: 1821-1826Google Scholar In a comprehensive meta-analysis, Gray and colleagues15Gray A Berlin JA McKinlay JB et al.An examination of research design effects on the association of testosterone and male aging: results of a metaanalysis.J Clin Epidemiol. 1991; 7: 671-684Google Scholar used 44 studies that met stringent criteria for reporting the relationship between mean testosterone level and age. Mean testosterone level for adult men was 479(±115) ng/dl. They demonstrated that the age-related decline in testosterone level is particularly pronounced among healthier men, compared with men who have any illness: healthier men's testosterone level starts higher and falls faster. In a multiple-regression model, the best predictors of both testosterone level and the slope of the age-related decline were good general health status and morning serum sampling (both of which predicted higher levels and steeper slopes).15Gray A Berlin JA McKinlay JB et al.An examination of research design effects on the association of testosterone and male aging: results of a metaanalysis.J Clin Epidemiol. 1991; 7: 671-684Google Scholar The decreasing testosterone levels in older men is due primarily to a reduction of Leydig cell functioning: testosterone synthesis is impaired, responsiveness to LH is reduced, and the circadian early-morning peak is blunted.4Laycock JF Wise PH Male reproductive endocrinology.Essential Endocrinology. 3rd Edition. Oxford University Press, New York1996Google Scholar, 5Weinbauer GF Gromoll J Simoni M et al.Physiology of testicular function.in: Nieschlag E Behre H Andrology: Male Reproductive Health and Dysfunction. Springer-Verlag, Berlin, Germany1997: 25-60Google Scholar, 13Bremner WJ Vitiello MV Prinz PN Loss of circadian rhythmicity in blood testosterone levels with aging in normal men.J Clin Endocrinol Metab. 1983; 56: 1278-1281Google Scholar Also, end-organ responsiveness may change with age. For example, the penis apparently becomes less responsive to testosterone, and the prostate becomes more responsive.4Laycock JF Wise PH Male reproductive endocrinology.Essential Endocrinology. 3rd Edition. Oxford University Press, New York1996Google Scholar, 5Weinbauer GF Gromoll J Simoni M et al.Physiology of testicular function.in: Nieschlag E Behre H Andrology: Male Reproductive Health and Dysfunction. Springer-Verlag, Berlin, Germany1997: 25-60Google Scholar With regard to clinical significance, it is not known whether the lower limit of "normal" testosterone level should be fixed, or should vary with age. Symptomatic hypogonadism apparently develops only when the total testosterone level drops below a certain threshold, typically set between 200 and 300 ng/dl. This threshold has generally been used and defined in order to assess for HPG dysfunction in relatively young men. For example, young men with testosterone levels below 250 ng/dl often have symptoms of sexual dysfunction, such as impaired nocturnal erections and low libido.17Rejeski WJ Gregg E Kaplan JR et al.Anabolic-androgenic steroids: effects on social behavior and baseline heart rate.Health Psychol. 1990; 9: 774-791Google Scholar In contrast, standards for determining the relevance of decreasing testosterone levels among healthy aging men—that is, "normative" gonadal hypofunction—may need to account for other age-related phenomena, such as changes in end-organ responsiveness and changes in HPG secretory patterns.13Bremner WJ Vitiello MV Prinz PN Loss of circadian rhythmicity in blood testosterone levels with aging in normal men.J Clin Endocrinol Metab. 1983; 56: 1278-1281Google Scholar, 18Villareal DT Morley JE Trophic factors in aging.Drugs and Aging. 1994; 4: 492-509Google Scholar Particularly regarding the psychiatric sequelae of gonadal hypofunction, it is not known where clinical significance begins. Thus, determination of an absolute lower threshold (or threshold relative to baseline) with respect to psychiatric impairment is an open question. The metabolic effects of testosterone are varied. During the embryonal stage, testosterone is responsible for the growth of the penis and scrotum, development of the prostate and seminal vesicles, descent of the testes, and suppression of the development of female genitalia.1Bagatell CJ Bremner WJ Androgens in men—uses and abuses.New Engl J Med. 1996; 334: 707-714Google Scholar, 4Laycock JF Wise PH Male reproductive endocrinology.Essential Endocrinology. 3rd Edition. Oxford University Press, New York1996Google Scholar, 5Weinbauer GF Gromoll J Simoni M et al.Physiology of testicular function.in: Nieschlag E Behre H Andrology: Male Reproductive Health and Dysfunction. Springer-Verlag, Berlin, Germany1997: 25-60Google Scholar The testosterone surge of puberty causes the genitalia to enlarge about eightfold, promotes the development and maintenance of secondary sexual characteristics, and supports anabolic activity. Testosterone affects hair distribution (including baldness); stimulates prostatic secretion and growth; masculinizes the larynx and the skin (e.g., promoting thickening, increased melanin, and increased sebaceous secretion); promotes protein anabolism, leading to muscular development, bone growth, calcium retention, and an increase in basal metabolic rate; and increases red blood cell production and hemoglobin synthesis.1Bagatell CJ Bremner WJ Androgens in men—uses and abuses.New Engl J Med. 1996; 334: 707-714Google Scholar, 4Laycock JF Wise PH Male reproductive endocrinology.Essential Endocrinology. 3rd Edition. Oxford University Press, New York1996Google Scholar, 5Weinbauer GF Gromoll J Simoni M et al.Physiology of testicular function.in: Nieschlag E Behre H Andrology: Male Reproductive Health and Dysfunction. Springer-Verlag, Berlin, Germany1997: 25-60Google Scholar Exogenous testosterone, in addition to these effects, elevates serum prostate-specific antigen (PSA) and reduces HDL cholesterol.19Tenover JS Effects of testosterone supplementation in the aging male.J Clin Endocrinol Metab. 1992; 75: 1092-1098Google Scholar It has been established in many mammalian species, that testosterone, acting during a brief developmental critical period, permanently alters brain structure and function.7Kemper TD Social Structure and Testosterone. Rutgers University Press, New Brunswick, NJ1990Google Scholar, 20McEwen BS Gonadal and adrenal steroids and the brain: implications for depression.in: Halbreich U Hormones and Depression. Raven, New York1987: 239-253Google Scholar Such "organizing" effects lead to behavioral predispositions in the setting of later reexposure to testosterone. This has been demonstrated most clearly in rodents. For example, perinatal exposure of a female rat to testosterone leads to masculinized sexual, aggressive, and exploratory behavior postpubertally (particularly when activated by testosterone), and loss of the female pattern of gonadotropin secretion.7Kemper TD Social Structure and Testosterone. Rutgers University Press, New Brunswick, NJ1990Google Scholar, 21Archer J The influence of testosterone on human aggression.Br J Psychol. 1991; 82: 1-28Google Scholar Perinatal castration of male rats leads to impaired inter-male aggression when treated postpubertally with testosterone; this impairment is prevented by perinatal testosterone replacement.7Kemper TD Social Structure and Testosterone. Rutgers University Press, New Brunswick, NJ1990Google Scholar, 20McEwen BS Gonadal and adrenal steroids and the brain: implications for depression.in: Halbreich U Hormones and Depression. Raven, New York1987: 239-253Google Scholar Some evidence suggests that perinatal testosterone organizes later serotonergic transmission in limbic and striatal areas of the brain.22Gonzalez MI Leret ML Extrahypothalamic serotonergic modification after masculinization induced by neonatal gonadal hormones.Pharmacol Biochem Behav. 1992; 41: 329-332Google Scholar The evidence for such perinatal effects among primates is less dramatic. In nonhuman primates, although male fetuses do secrete testosterone, there is only limited evidence that sex hormones organize later behavioral potential.7Kemper TD Social Structure and Testosterone. Rutgers University Press, New Brunswick, NJ1990Google Scholar In humans, prenatal exposure of female fetuses to excessive androgens (as a consequence of congenital adrenal hyperplasia) is associated with the development of male-like play behavior during childhood, male-like sexual imagery and preferences in adulthood, and more aggressive behavior compared with female relatives.23Money J Schwartz M Lewis V Adult erotosexual status and fetal hormonal masculinization and demasculinization: 46XX congenital virilizing hyperplasia and 46XY androgen-insensitivity syndrome compared.Psychoneuroendocrinology. 1984; 9: 405-414Google Scholar, 24Berenbaum SA Resnick SM Early androgen effects on aggression in children and adults with congenital adrenal hyperplasia.Psychoneuroendocrinology. 1997; 22: 505-515Google Scholar In most mammals, males are more socially aggressive than females.21Archer J The influence of testosterone on human aggression.Br J Psychol. 1991; 82: 1-28Google Scholar The ancient practice of castration as a way to control the sexual and aggressive behavior of animals (including humans) reflects the long-held recognition that there is a relationship between the male gonads and behavior. The active agent in this relationship is clearly testosterone, and a strong relationship between testosterone and behavior has been found in a wide range of vertebrate species, particularly birds and mammals.2Rubinow DR Schmidt PJ Androgens, brain, and behavior.Am J Psychiatry. 1996; 153: 974-984Google Scholar, 7Kemper TD Social Structure and Testosterone. Rutgers University Press, New Brunswick, NJ1990Google Scholar, 10Rose RM Bernstein IS Gordon TP Consequences of social conflict on plasma testosterone levels in rhesus monkeys.Psychosom Med. 1975; 37: 50-61Google Scholar, 21Archer J The influence of testosterone on human aggression.Br J Psychol. 1991; 82: 1-28Google Scholar Among mammals, there is strong evidence that testosterone regulates the sexual, aggressive, and social behaviors of rodents and ungulates (e.g., cows and goats).2Rubinow DR Schmidt PJ Androgens, brain, and behavior.Am J Psychiatry. 1996; 153: 974-984Google Scholar, 7Kemper TD Social Structure and Testosterone. Rutgers University Press, New Brunswick, NJ1990Google Scholar, 21Archer J The influence of testosterone on human aggression.Br J Psychol. 1991; 82: 1-28Google Scholar The relationship between testosterone secretion and these behaviors among primates (including humans) is less direct, and more complicated by social factors and learning.2Rubinow DR Schmidt PJ Androgens, brain, and behavior.Am J Psychiatry. 1996; 153: 974-984Google Scholar, 7Kemper TD Social Structure and Testosterone. Rutgers University Press, New Brunswick, NJ1990Google Scholar, 10Rose RM Bernstein IS Gordon TP Consequences of social conflict on plasma testosterone levels in rhesus monkeys.Psychosom Med. 1975; 37: 50-61Google Scholar, 21Archer J The influence of testosterone on human aggression.Br J Psychol. 1991; 82: 1-28Google Scholar Among primates, testosterone secretion is powerfully stimulated or suppressed in response to the social/sexual context. In isolated groups of male talapoin monkeys, testosterone levels do not discriminate male status or aggression. However, if receptive females are introduced, the dominant male increases testosterone secretion until his is the highest. Subordinate males can develop a testosterone "boost" in the presence of a receptive female only in the absence of other males.2Rubinow DR Schmidt PJ Androgens, brain, and behavior.Am J Psychiatry. 1996; 153: 974-984Google Scholar, 7Kemper TD Social Structure and Testosterone. Rutgers University Press, New Brunswick, NJ1990Google Scholar, 10Rose RM Bernstein IS Gordon TP Consequences of social conflict on plasma testosterone levels in rhesus monkeys.Psychosom Med. 1975; 37: 50-61Google Scholar, 21Archer J The influence of testosterone on human aggression.Br J Psychol. 1991; 82: 1-28Google Scholar Dominant olive baboons increase testosterone secretion when stressed, whereas submissive baboons decrease testosterone secretion.7Kemper TD Social Structure and Testosterone. Rutgers University Press, New Brunswick, NJ1990Google Scholar, 21Archer J The influence of testosterone on human aggression.Br J Psychol. 1991; 82: 1-28Google Scholar Administration of exogenous testosterone to cynomolgus monkeys leads to increased dominant behaviors and elevated heart rate among dominant males; it has the opposite effect on submissive males.17Rejeski WJ Gregg E Kaplan JR et al.A
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