Library of Excerpts

Testosterone, Estrogen, Related Hormones and Heterochronic Patterns: Part 1

"The structures most immediately involved in regulating hormone levels in both sexes are the hypothalamus, the pituitary gland, and the gonads (ovaries and testes). The hypothalamus is believed to act as a "relay station," integrating hormonal stimuli which travel through the bloodstream, and neural stimuli from many other parts of the brain. The hypothalamus is also involved in the production of "neurohormones," or releasing factors, which pass through the pituitary portal vessels into the anterior pituitary, stimulating the snythesis and release of pituitary gonadotrophic hormones, including luteinizing hormone (LH), and follicle stimulating hormone (FSH). These pituitary hormones are carried in the blood to the gonads, where they regulate the production and secretion of gonadal or steriod hormones; primarily testosterone in males, primarily estrogen and progesterone in females. In turn, these steroid hormones are released into the blood and registered in the hypothalamus as part of the complex feedback mechanism contributing to hormonal regulation." (Dan AJ (1979) The menstrual cycle and sex-related differences in cognitive variability in Sex-Related Differences in Cognitive Functioning: Developmental Issues. Wittig MA, Petersen AC (eds.) Academic Press, New York p. 241-260)

"No one, least of all WIlliams and Kafatos, expect the eventual story to be so simple. But it does seem likely that normal development is controlled by gradually decreasing concentration of a hormone acting primarily at high levels of the regulatory system. This is also an ideal mechansim for the simple and rapid production of heterochronic effects. Any acceleration of adult characters by reduction in the titer of juvenile hormone, or extension of juvenile traits by maintenance of a high titer, represents heterochrony. Since minor alterations in the concentration of a hormone can lead to substantial changes in morphology, heterochrony may play an important role in geographic variation (secretion of juvenile hormone is influened by temperature and photoperiod, for example), polymorphism (including sex, caste, and phase) and speciation itself." (Gould, S.J. (1977) Ontegeny and Phylogeny. Cambridge: Belknap Press. p. 295-6)

"The relationships of cigarette smoking, age, relative weight, and dietary intake to serum dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), androstenedione, cortisol, 3-alpha-androstanediol, 3-alpha-androstanediol-glucuronide, testosterone, albumin-bound testosterone, free testosterone, dihydrotestosterone (DHT), and sex hormone-binding globulin (SHBG) were examined cross-sectionally in 1241 randomly sampled middle-aged U.S. men. Compared with nonsmokers and independent of relative weight (body mass index) and age, cigarette smokers had increased serum levels of DHEA (18% higher, P = 0.0002), DHEAS (13% higher, P = 0.0007), cortisol (5% higher, P = 0.01), androstenedione (33% higher, P = 0.0001), testosterone (9% higher, P = 0.009), DHT (14% higher, P = 0.004), and SHBG (8% higher, P = 0.004). Androstenedione, total plasma testosterone, albumin-bound testosterone, DHT, and SHBG decreased with increasing relative weight. Age was positively associated with serum SHBG and negatively associated with albumin-bound testosterone, DHEA, and DHEAS. An association was found between alcohol intake and DHEA (r = 0.15; P = 0.0001), cortisol (r = 0.10; P = 0.0007), and 3-alpha-androstanediol-glucuronide (r = 0.08; P = 0.0004). Cortisol was the only hormone that was associated with carbohydrate intake (r = -0.09; P = 0.002). The only hormones associated with dietary lipids were DHT (for vegetable fat, r = 0.07; P = 0.02), cortisol (for total fat, r = 0.08; P = 0.007), and SHBG (for animal fat, r = -0.06; P = 0.05). In addition, SHBG was positively associated with dietary (r = 0.07; P = 0.008) and crude (r = 0.08; P = 0.007) fiber. These data suggest that serum adrenal steroid and sex hormone concentrations in middle-aged men are more influenced by cigarette smoking, age, and obesity than by dietary intake; however, serum adrenal steroids were influenced by alcohol intake." (Field AE, Colditz GA, Willett WC, Longcope C, McKinlay JB (1994) 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 Clinical Endocrinological Metabolism 79: 1310)

"Geschwind and Galaburda (1987) cite several studies that document the finding that testosterone and progesterone diminish the size of the thymus gland during development (e.g., Dougherty, 1952; Frey-Wettstein & Craddock, 1970). In terms of the theoretical position that we have adopted, there is an important consequence of the aforementioned processes. The simultaneous effect of testosterone on the development of the left hemisphere and the thymus and other organs results in the prediction that there would be a greater incidence of immune disorders among left-handed individuals. The first evidence for this relationship came from Geschwind and Behan (1982, 1984). They showed that autoimmune diseases (especially those involving the intestinal tract an the thyroid gland) and atopic diseases (allergies, asthma, eczema, and hay fever) are 2.5 times as frequent in strong left-handers. These results have been essentially confirmed in several subsequent studies (e.g.. Penninton, Smith, Kimberling, Green, & Haith, 1987; Smith, 1987)." (Coren, S. & Halpern, D.F. (1991) Left-handedness: A marker for decreased survival fitness. Psychological Bulletin 109: 100)

“Several diseases, e.g., coronary heart disease, cancer, etc., have been related to sex hormones. Thus, research on the epidemiology of sex hormones may be productive. The epidemiologic study of testosterone has been limited due to the circadian and circannual variations and the wide interindividual variability. The authors evaluated the reliability and repeatability of a single blood draw to measure individual plasma testosterone levels in three pilot studies. The results indicated that the measurements of the hormone level are highly repeatable and a single morning specimen appeared to be sufficient for characterization of individual testosterone levels. Research then focussed on 243 men in the Multiple Risk Factor Intervention Trial to investigate the determinants of plasma testosterone level. The results indicated that age and obesity were significantly correlated with plasma testosterone level. (The multiple R of these two variables in the multiple regression analysis for plasma total testosterone was 0.32.) Smoking was positively related to testosterone through a relationship with age. Daily physical activity, history of alcohol intake, and behavior factors of A and B behavior types were not found to be related to testosterone concentrations.” (Dai WS, Kuller LH, LaPorte RE, Gutai JP, Falvo-Gerard L, Caggiula A (1981) The epidemiology of plasma testosterone levels in middle-aged men. Am J Epidemiol 114 (6): 804)

"Bakan (1987) further supports it with the observation that offspring from mothers who smoke are more apt to be left-handed." (Coren, S. & Halpern, D.F. (1991) Left-handedness: A marker for decreased survival fitness. Psychological Bulletin 109: 98)

“Nonright-handedness (NRH) has been attributed to hypoxia-induced brain changes in the fetus and associated pregnancy and birth complications (PBCs). Maternal smoking during pregnancy is known to produce prenatal hypoxia for the fetus, which may result in low birth weight and other PBCs. It was hypothesized that maternal smoking during pregnancy results in a leftward shift of handedness in the offspring. This study compared the distribution of handedness in the offspring of mothers who did and did not smoke cigarettes during pregnancy. Information on maternal smoking, handedness, and PBCs was analyzed for 803 university students. There was a significant shift to the left in the distribution of handedness scores for the offspring of smoking mothers (N = 216), as compared to those of nonsmoking mothers (N = 587). Offspring of smoking mothers also reported significantly more PBCs. Results are consistent with the hypothesis that NRH is associated with pathological neurodevelopment.” (Bakan P (1991) Handedness and maternal smoking during pregnancy. Int J Neurosci 56 (1-4): 161)

“We traced spatial, verbal and musical abilities through a seven-year period of adolescence. When we started our study, 60 boys had reached a mean age of 11.72, 60 girls were 11.52 on average. Menarche and mutation served as markers for maturation. We found that early, mid, and late maturers differed on spatial orientation and on tactile-visual discrimination as measured with the Witelson task. No differences between the maturational groups emerged on verbal fluency and on Wing's Standardized Tests of Musical Intelligence. At some stages, sex differences on spatial, verbal, and musical tests emerged, and disappeared at others. The sex differences in performance levels were not associated with a sex-specific relationship between maturation rate and performance levels. We found indications of the usefulness of sex hormone measurement in relation to cognitive and musical development in adolescence.” (Hassler M (1991) Maturation rate and spatial, verbal, and musical abilities: a seven-year-longitudinal study. Int J Neurosci 58 (3-4): 183)

“Musical composers, instrumentalists, and painters were compared with nonmusicians from a student and from an nonstudent population on testosterone levels in saliva. This steroid served as a marker for physiological androgyny. The ANOVA showed a significant group by sex interaction. Male composers attained significantly lower mean testosterone values than male instrumentalists and male nonmusicians; female composers had significantly higher mean testosterone values than female instrumentalists and female nonmusicians. Painters of both sexes did not differ significantly from controls. Spatial ability was assessed in the five groups. Significant differences on spatial test performance were not reflected in differences on salivary testosterone. Our results showed that musical composers of both sexes were physiologically highly androgynous. Creative musical behavior was associated with testosterone levels that minimized sex differences.” (Hassler M (1991)Testosterone and artistic talents. Int J Neurosci 56 (1-4): 25)

“The relationship between serum testosterone level and Hoffmann (H) reflex from right to left thumb flexors was studied in right-handed young men and women. The subjects were divided into two subgroups: fast and slow in right-hand skill, but no difference in left-hand skill (peg moving). The mean serum testosterone level was found to be significantly lower in subjects with fast right hand than those with slow right hand. The mean H reflex from right was significantly smaller in subjects with fast right hand than those with slow right hand. There was a negative, linear relationship between serum testosterone level and amplitude of H-reflex from right thumb. This was more pronounced in females than males. The H reflex from left was not significantly associated with serum testosterone levels. It was concluded that testosterone may affect the somatomotor system ofthe left brain during adolescence impairing the right-hand skill especially in females. These results also appear to be in accord with the testosterone theory of cerebral lateralization.” (Tan U (1991) The relationship between serum testosterone level and Hoffmann reflex from the long flexor thumb muscle in right-handed young adults. Int J Neurosci 56 (1-4): 1)

“The serum levels of estradiol (E2) and testosterone (T), the metabolic clearance rates of estradiol (MCRE2) and testosterone (MCRT), and the production rates of estradiol and testosterone (PRE2) and (PRT) were examined in 22 male smokers and 21 male nonsmokers. Seminal fluid indexes (sperm count, % motility, grade of motility, and % of sperm with abnormal morphology) were also assessed. The mean E2 level and the mean PRE2 were significantly greater in smokers than in nonsmokers (P less than 0.001 and P less than 0.01, respectively); however, the means of MCRE2, MCRT, PRT, and T did not differ significantly in smokers compared to nonsmokers. No significant product-moment correlations were found between the various hormonal measures and the seminal fluid indexes in the overall sample. However, the smokers with sperm counts below the median sperm count of the sample had significantly higher mean levels of E2 and PRE2 than did the smokers with sperm counts above that median. Mechanisms that might mediate the greater PRE2 of smokers and a negative relationship between estradiol and sperm count are discussed.” (Klaiber EL, Broverman DM (1988) Dynamics of estradiol and testosterone and seminal fluid indexes in smokers and nonsmokers. Fertil Steril 50 (4): 630)

“Using a new sample of 16 human brains (F = 8, M = 8), it was found that the splenial portion of the corpus callosum was larger and more bulbous in females than in males. In addition, the total area of the corpus callosum was both absolutely and relatively larger in females than in males, with the relative measurements (i.e., to brain weight) differing significantly. This was also true when using exponential values of brain weight commensurate with the areas and linear distances of the corpus callosum. These results, which replicate the findings of earlier work, were found by the two authors using different methods, and working independently of each other. We believe these findings provide a partial anatomical basis for purported gender differences in cognitive task behaviour, and are related to early gonadal steroidal influences during prenatal development.” (Holloway RL, de Lacoste MC (1986) Sexual dimorphism in the human corpus callosum: an extension and replication study. Hum Neurobiol 5 (2):87)

“Salivary testosterone levels are reported for 65 Nepalese males between the ages of 15 and 48 years who were drawn from 2 different ethnic populations (Tamang [Tibetans] and Kami [Hindu Aryans]) from the central highlands of Nepal. Subjects collected morning and evening saliva samples on five consecutive days in two contrasting seasons, the winter dry season and the summer monsoon season. Anthropometric indexes of acute and chronic nutritional status were also measured. Morning and evening salivary testosterone levels in the winter averaged 233 +/- 14 (SE) pmol/L and 166 +/- 8 pmol/L, respectively, for the Tamang and 249 +/- 14 pmol/L and 163 +/- 13 pmol/L, respectively, for the Kami. In the summer the corresponding values were 219 +/- 12 pmol/L and 156 +/- 8 pmol/L for the Tamang and 249 +/- 19 pmol/L and 147 +/- 12 pmol/L for the Kami. These levels are significantly lower than those reported for Western populations and close to those reported for other non-Western populations. The magnitude of diurnal variation in salivary testosterone levels and the absence of significant age variation are also comparable with observations made on other populations. Weak relationships were observed between testosterone levels and indexes of acute and chronic nutritional status in the winter only. The absence of pronounced variation in salivary testosterone levels between populations and the absence of strong associations between salivary testosterone levels and indexes of acute and chronic nutritional status contrast with the prominent ecological and interpopulation variation reported for salivary progesterone levels in women. Male gonadal function seems less sensitive to moderate energetic stress than female gonadal function, probably reflecting the fact that energy availability is less crucial to male reproductive success than to female reproductive success. Variation in testosterone level associated with chronic energetic stress may be an adaptive somatic response to avoid the maintenance costs of a large active metabolic mass with little direct impact on male fecundity.” (Ellison PT, Panter-Brick C (1996) Salivary testosterone levels among Tamang and Kami males of central Nepal. Hum Biol 68 (6): 955)

“OBJECTIVE: To test predictions that basal salivary testosterone and cortisol are related to antisocial and internalizing behaviors, respectively, and that cortisol moderates the testosterone-aggression relationship. METHOD: Saliva samples were assayed to determine testosterone and cortisol levels in 40 clinic-referred disruptive children (aged 7 through 14 years) who were rated on aggression, inattention/overactivity, and internalizing behavior by parents, teachers, and clinic staff members. RESULTS: Results indicated significant positive relationships between testosterone and staff-rated aggression and between cortisol and parent-rated internalizing behavior. A significant negative relationship was found between cortisol and staff-rated inattention/overactivity. No interactions between testosterone and cortisol were found. These results were maintained regardless of age, racial background, height, weight, diagnosis, or medication status. CONCLUSIONS: Results suggest moderate relationships between testosterone and observed aggression, and between cortisol and emotional behaviors, in a group of disruptive children. Cortisol did not moderate the testosterone-aggression relationship in this population.” (Scerbo AS, Kolko DJ (1994) Salivary testosterone and cortisol in disruptive children: relationship to aggressive, hyperactive, and internalizing behaviors. J Am Acad Child Adolesc Psychiatry 33 (8): 1174)

“To determine whether ethanol per se affects testosterone metabolism, alcohol was administered to normal male volunteers for periods up to four weeks, resulting in an initial dampening of the episodic bursts of testosterone secretion followed by decreases in both the mean plasma concentration and the production rate of testosterone. The volunteers received adequate nutrition and none lost weight during the study, which tended to exclude a nutritional disturbance as the cause of the decreased testosterone levels. The changes in plasma luteinizing hormone suggested both a central (hypothalamus-pituitary) and gonadal effect of alcohol. In addition, alcohol consumption increased the metabolic clearance rate of testosterone in most subjects studied, probably owing to the combined effects of a decreased plasma binding capacity for the androgen and increased hepatic testosterone A-ring reductase activity. These results indicate that alcohol markedly affects testosterone metabolism independently of cirrhosis or nutritional factors.” (Gordon GG, Altman K, Southren AL, Rubin E, Lieber CS (1976) Effect of alcohol (ethanol) administration on sex-hormone metabolism in normal men. N Engl J Med 295 (15): 793)

“Plasma gonadotropin levels throughout the regular menstrual cycle in 10 Japanese women were measured daily using radioimmunoassay. At the peak of ovulation, mean FSH levels were 17.6 +/- 7.9 mlU/ml and mean LH levels were 75.2 +/- 26.0 mlU/ml. At midcycle, the mean gonadotropin levels were significantly lower in Japanese women than in Nigerian womenwho, as reported by Nylander (1973), had a high frequency of twinning. It is, therefore, suggested that the low frequency of dizygotic twinning in Japanese women might be related to their low output of gonadotropin. “ (Soma H, Takayama M, Kiyokawa T, Akaeda T, Tokoro K (1975) Serum gonadotropin levels in Japanese women. Obstet Gynecol 46 (3): 311)

“Theoretical speculation in humans (S.F. Witelson, Psychoneuroendocrinology 16 (1991) 131-153) and empirical findings in animals (R.H. Fitch, P.E. Cowell, L.M. Schrott, V.H. Denenberg, Int. J. Dev. Neurosci. 9 (1991) 35-38) suggest that testosterone (T) may play a significant role in the development of the corpus callosum (CC). However, there are currently no empirical studies directly relating T concentrations to callosal morphology in humans. The purpose of the present study was to investigate the relationship between free T concentrations as determined by radioimmunoassay, and the mid-sagittal area of the corpus callosum, as determined by magnetic resonance imaging (MRI). Subjects were 68 young adult (20-35 years), neurologically normal, right-handed males. All subjects underwent MRI and provided two samples of saliva for radioimmunoassay of T and cortisol. Anatomical regions of interest included total brain volume, left and right hemisphere volume and regional areas of the CC. CC regions were defined using two different measurement techniques, each dividing the CC into six sub-sections. Anatomical measurements were performed blind with respect to the hormone levels of subjects. A significant positive correlation between T concentration and cross-sectional area of the posterior body of the CC was found. This finding was consistent across the two measurement techniques and was not attributable to individual differences in total brain volume. All correlations between cortisol and CC sub-regions were non-significant. The results of this study are consistent with the notion that T, at an earlier stage in development, may play a significant role in modulating cortical/callosal architecture in humans.” (Moffat SD, Hampson E, Wickett JC, Vernon PA, Lee DH (1997) Testosterone is correlated with regional morphology of the human corpus callosum. Brain Res 767 (2):297)

“The relationship between serum testosterone level and visuomotor of learning of hand skill was studied in right-handed young men. Hand skill was assessed by a peg moving task. Peg moving times for the right and left hands linearly decreased at each successive trial (visuomotor learning). The peg moving times for the right and left hands were found to be negatively linearly related to serum testosterone levels: there was a direct relationship between hand skill and testosterone, which was more prominent for the right than the left hand. The slopes of the learning curves for the right hand were found to be equal in subjects with low, normal, and high testosterone. The intercepts of these curves exhibited a shift toward a better hand skill from low- to high-testosterone subjects. The visuomotor learning for the left hand was found to be better in subjects with normal and high testosterone than those with low testosterone. It was concluded that testosterone would favor the visuomotor development especially of the left cerebral hemisphere, probably at puberty; the motor learning of this hemisphere does not seem to be associated with testosterone. Testosterone seems to be advantageous for the visuomotor performance as well as for the motor learning of the right cerebral hemisphere. “ (Tan U(1991) The relationship between serum testosterone level and visuomotor learning in right-handed young men. Int J Neurosci 56(1-4):19)

“In a case-control study of testis cancer 259 cases with testicular cancer, 238 controls treated at radiotherapy centres and 251 non-radiotherapy hospital in-patient controls were interviewed about some possible prenatal and familial risk factors for the tumour. For firstborn men, the risk of testis cancer increased significantly according to maternal age at the subject's birth, and this effect was most marked for seminoma. The association with maternal age was not apparent for cases other than firstborn. The risk of testis cancer was also significantly raised for men from small sibships and of early birth order. These results accord with the theory that raised maternal levels of available oestrogen during the early part of pregnancy are aetiological for testicular cancer in the son, although other explanations are possible; there is evidence that seminoma risk may particularly be affected.” (Swerdlow AJ, Huttly SR, Smith P G(1987) Prenatal and familial associations of testicular cancer. Br J Cancer 55 (5):571)


“To determine the effect of androgen insensitivity on cognitive abilities, subjects with the syndrome of complete androgen insensitivity (AI) were compared to control males and females from the same kindred on the Spanish version of the Wechsler Adult Intelligence Scale (WAIS). All subjects had similar sociocultural backgrounds and only right-handed subjects were used in the primary analysis. This design was chosen to diminish the effect of critical variables on test performance, thereby highlighting the effect of androgen unresponsiveness on cognition. The results indicated that control males and females were superior to androgen insensitive subjects on the Perceptual Organization factor, which included five visuospatial subtests. Separate analysis of these subtests revealed that males performed significantly better than females on Block Design, Picture Completion, and Object Assembly, and better than androgen insensitive subjects on all five subtests. Females were superior to androgen insensitive subjects on four subtests (Block Design, Picture Completion, Digit Symbol, and Picture Arrangement). Despite the small sample size, when female siblings were compared to their AI sisters, they were also superior on these four visuospatial subtests. The difference between the Verbal Comprehension and Perceptual Organization factors was greatest in androgen-insensitive subjects, while control males demonstrated the least difference. Females and AI subjects did not differ from one another on the Freedom from Distractibility factor nor on the subtests comprising it, but their performances were poorer than control males. None of the groups differed significantly on Full Scale IQ, Verbal IQ, the Verbal Comprehension factor, or any subtests included in this category.” (Imperato-McGinley J, Pichardo M, Gautier T, Voyer D, Bryden MP(1991) Cognitive abilities in androgen-insensitive subjects: comparison with control males and females from the same kindred. Clin Endocrinol (Oxf) 34(5): 341)

“Serum testosterone levels were determined in female and male subjects. Hand preference was assessed by the Edinburgh Handedness Inventory. Subjects with anomalous dominance (left-handers, mixed-handers, and right-handers with familial sinistrality) were compared to subjects with standard dominance (right-handers without familial sinistrality). The mean serum testosterone levels were found to be significantly higher in subjects with anomalous dominance than those with standard dominance. It was concluded that the results are in accord with the testosterone hypothesis of cer bral lateralization.” (Tan U(1991) Serum testosterone levels in male and female subjects with standard and anomalous dominance.Int J Neurosci 58(3-4):211)

“The relationship between serum testosterone level and motor learning in hand skill was studied in right-handed young women. Hand skill was assessed by a peg moving task. Subjects were required to shift 25 pegs from one of two parallel rows to the corresponding holes as fast as possible, first with right and then with left hand. One trial consisted of the time elapsed to move 25 pegs with one hand. Ten trials were performed by each hand. Peg moving times for the right and left hands linearly decreased at each successive trial (visuomotor learning). Subjects were divided into two subgroups as those having serum testosterone concentrations below and above the mean. The right hand skill and its motor learning was found to be better in subjects with low testosterone than those with high testosterone. The left hand skill was better in subjects with low testosterone than those with high testosterone; there was no significant difference in the left-hand learning in subjects with low and high testosterone (parallel regression lines). Motor learning linearly decreased with testosterone for the right hand, not for the left hand. These results seem to be in accord with the testosterone theory of cerebral lateralization (Geschwind & Behan, 1982).” (Tan U (1991) The relationship between serum testosterone and visuomotor learning in hand skill in right-handed young women.Int J Neurosci 56(1-4):13-8)

“The relationship between serum testosterone level and nonverbal intelligence was studied in right-handed young adults with regard to handedness. Hand preference was assessed by the Edinburgh Handedness Inventory. Hand skill was measured by a peg moving task. Serum testosterone level was determined using tritium-marked-radioimmunoassay. Visual-spatial performance (nonverbal intelligence) was measured by Cattell's Culture Fair Intelligence Test. In men with consistent right-hand preference (GSs: 80 to 100), IQ was found to be positively linearly related to serum testosterone, which exhibited two regression lines belonging to low and high difference in skill between hands. In females with consistent right-handedness, there was a negative linear correlation between IQ and serum testosterone, which also exhibited two different regression lines according to difference in skill between hands. In males with moderate right-hand preference (GSs 50 to 75), IQ was found to be positively linearly related to serum testosterone, exhibiting two different (same slopes) regression lines according to difference in skill between hands. In females with moderate right-hand preference, IQ first increased and then decreased with serum testosterone, exhibiting a quadratic relationship. These results suggested that serum testosterone in young adults may be associated with visual-spatial performance depending upon sex, hand preference, and hand skill.” (Tan U (1990) Relationship of testosterone and nonverbal intelligence to hand preference and hand skill in right-handed young adults. Int J Neurosci 54(3-4): 283)

“The relationship between serum testosterone level and hand performance was studied in right-handed young adults without familial sinistrality. Hand performance was measured by a dot-filling task, which was found to be associated with serum testosterone depending upon sex. In women, the right- and left-hand performance was found to be negatively linearly related to testosterone; there was no significant correlation between the right- minus left-hand performance and testosterone. In men, right- and left-hand performance were found to be directly and inversely related to testosterone, respectively. This pattern exhibited some variations depending on eye and foot preferences. The difference in performance between hands was found to be positively linearly related to serum testosterone levels in men.” (Tan U(1990) Testosterone and hand performance in right-handed young adults. Int J Neurosci 54 (3-4): 267)

“The relationship between serum testosterone level and the degree of hand preference was studied in right-handed young adults. Hand preference was assessed by the Edinburgh Handedness Inventory. Serum testosterone level was determined using tritium-marked-radioimmunoassay. There was no significant correlation between these variables in males without FS. In males with FS and in females with and without FS, the serum testosterone levels were found to be negatively linearly correlated with the degree of the right-hand preference. Similar results were obtained with respect to foot and eye preferences. It was concluded that not only prenatal testosterone but adult testosterone also may exert a life long influence on cerebral lateralization; this effect seems to be much more pronounced in the female than male brain, which may exert a female-like pattern under genetic control.” (Tan U(1990) Relation of testosterone and hand preference in right-handed young adults to sex and familial sinistrality. Int J Neurosci 53(2-4): 157)

“In Malaya, mean testicular weights of T. glis and T. minor were highest in spring and early summer; 60g and 0.54g fro April-June compared with 0.81g and 0.20g for October-December in these two species (Harrison, 1955).” (Michael, R.P., Wilson, M., & Plant, T.M. (1973) Sexual Behavior of Male Primates and the Role of Testosterone in Comparative Ecology and Behavior of Primates. R.P. Michael and J.H. Crook, eds. New York: Academic Press Pp. 239) (rhesus monkeys?]

“Following castration, there was a marked decline in the number of ejaculations and intromissions per test for both groups: this was more conspicuous for adults which had a higher level of performance when intact (Fig 5.) Whereas ejaculations ceased entirely in the sub-adult group about 12 weeks after castration, they persisted in some adult males, as did intromissions, throughout the 32 week period in which these observations refer. In contrast, a marked decline in mounting activity was observed during this time in sub-adults, and mounting continued more or less unchanged in the adult group. There was no explanation for the transient increase in mounting by some sub-adults 18 weeks after castration. (Fig.5). These data refer to the initial 32 weeks after castration, but the behavior of the castrated adults was followed for an additional 6-90 weeks. During this extended period of observation, sexual activity declined further, and all four males ceased ejaculating by 109 weeks. Mounting also declined to very low levels (Fig. 8) but, unlike ejaculation and intromission, mounting continued to occur in occasional tests throughout the entire period of study.” (Michael, R.P., Wilson, M., & Plant, T.M. (1973) Sexual Behavior of Male Primates and the Role of Testosterone in Comparative Ecology and Behavior of Primates. R.P. Michael and J.H. Crook, eds. New York: Academic Press Pp. 281-4) (rhesus monkeys]

“The changes in plasma testosterone after castration were extremely rapid, and Fig. 7 shows the levels had fallen by 50% within 30 min of gonadectomy. This was also the case when LH treatment (HCG) prior to castration produced exceptionally high intact plasma levels, and within 24 hr plasma testosterone values were in the range of those of long-term castrates.” (Michael, R.P., Wilson, M., & Plant, T.M. (1973) Sexual Behavior of Male Primates and the Role of Testosterone in Comparative Ecology and Behavior of Primates. R.P. Michael and J.H. Crook, eds. New York: Academic Press Pp. 285) (rhesus monkeys]

“Thus, some 22 weeks of daily treatment with testosterone, although producing a marked improvement, did not fully restore the behavioral patterns to those observed before castration in either group. This is perhaps more clearly shown in the group data (Fig 9) where for both the sub-adults and adults, ejaculatory performance during testosterone replacement treatment reached only some 50% that of intact levels. However, individual differences in the effects of replacement treatment on behavior were as marked as were the effects of castration. In on male, ejaculation was fully restored in about 16 weeks of treatment whereas, in another male paired with the same females, although ejaculation reappeared earlier, it failed to reach pre-castration levels during the following 6 months of treatment (Fig. 10).” (rhesus monkeys] (Michael, R.P., Wilson, M., & Plant, T.M. (1973) Sexual Behavior of Male Primates and the Role of Testosterone in Comparative Ecology and Behavior of Primates. R.P. Michael and J.H. Crook, eds. New York: Academic Press Pp. 288)

“Masturbation seems a bizarre, maladaptive behavior because it wastes sperm, but the practice is almost universal among U.S. males and is particularly common in adolescents (Kinsey et al. 1948, Sorensen 1973). Masturbation is also commonly observed in some captive primates. It has been said that “primates masturbate, because they can,” but if autoeroticism were maladaptive, the tendency should have been repressed by natural selection. A clue to a possible function is found in the fact that males who do not ejaculate byu coitus or masturbation for some period of time experience nocturnal emissions, i.e. spontaneous seminal discharge chring sleep. This suggests that stored sperm and/or accessory gland products may have definite “shelf life” after which they are best discarded and replaced with new in order to stay competitive. Another possibility that has not been properly investigated is that frequent ejaculation may activate some feedback machansim (e.g. testosterone/inhibin) to stimulate higher levels of spermatogenesis and accessory gland secretion.” (Robert L. Smith (1984) Human Sperm Competition. in Sperm Competition and the Evolution of Animal Mating Systems pp. 633)

“One could argue, by extension, that children exposed to higher levels of testosterone in utero and during early childhood might have greater right-hemisphere capabilities, thereby earning scores within the high performance - low verbal classification of scores on the Wechsler Intelligence Scale for Children. However, it is probably not reasonable to assume a simplistic model in which testosterone secretion alone is responsible for differential hemispheric and cognitive development. A more plausible explanation lies in the influence of both androgen and estrogen upon the central nervous system (Benbow & Benbow, 1984; Christiansen, 1993; Kirkpatrick, et al., 1993)” (Kirkpatrick SW, Campbell PS, Wharry RE, MacDonald PM (1994) Performance on the Wechsler Intelligence Scale for Children as related to salivary testosterone in children with learning disabilities: a poststudy analysis. Percept Mot Skills 79(1 Pt 2):578)

"Although our findings are consistent with the few studies of adults that found testosterone levels to be higher among smokers than among nonsmokers, our interpretation of the findings differ from those studies. Most other studies considered smoking the cause and testosterone the effect. We have reasoned that testosterone might be a cause of adolescent smoking. Because both smoking onset and testosterone levels increase so markedly during adolescence and because testosterone and smoking were positively associated in our study, the possible causal impact of testosterone on smoking should not be readily dismissed." (Bauman KE, Foshee VA, Koch GG, Haley NJ, Downton MI (1989) Testosterone and cigarette smoking in early adolescence. J Behav Med 12 (5): pp. 430-31)

citations removed) "In some studies no associations between smoking and serum levels of testosterone and SHBG have been seen, whereas other have found either that smokers have lower or higher testosterone concentratons. Both female and male smokers had elevated levels of adrenal androgens. Yeh and Barbieri have proposed that smoking directly influences steroid production and metabolism." (Field AE, Colditz GA, Willett WC, Longcope C, McKinlay JB (1994) 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 Clinical Endocrinological Metabolism 79: 1310)

"A recent meta-analysis of 88 studies of the age-testosterone relationship found that the discrepant results in the literature were due to the fact that studies which included only healthy men found a decrease in testosterone levels with age, whereas studies which included ill men did not find such a decrease. In comparison, after controlling for illness, we found a decrease with age in all of the androgen levels." (Field AE, Colditz GA, Willett WC, Longcope C, McKinlay JB (1994) 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 Clinical Endocrinological Metabolism 79: 1314)

"...Hill et al. found a decline in testosterone concentration among men who were briefly switched from a western higher fat diets to vegetarian diets." (Field AE, Colditz GA, Willett WC, Longcope C, McKinlay JB (1994) 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 Clinical Endocrinological Metabolism 79: 1314)

"These data clearly indicate that acute increases in serum cortisol levels induce a rapid decrease in circulating T concentrations. This finding is at variance with that of Doerr and Pirke. These authors, using oral ingestion of cortisol (60-mg initial dose, followed by 30 mg at 2-h intervals), did not observe an acute suppression of plasma T during the day, but the nocturnal rise in T was suppressed. ... In men, over 95% or circulating T is derived from the Leydig cells of the testis." (Cumming DC, Quigley ME, Yen SSC (1983) Acute suppression of circulating testosterone levels of cortisol in men. J Clinical Endocrinological Metabolism 57: 672)

"Male offspring of rats subjected to stress from days 14 to 21 of pregnancy show a persistence of female behavioral potentials and an inability to exhibit normal male copulatory patterns in adulthood. Thus the processes involved in masculinization and defiminization appear to have been compromised in the male fetuses of stresses mothers. ... On the basis of the above observations, we propose that day 18 of gestation represents a distinct and critical point in the process of sexual differentiation of the fetal rat brain." (Ward IL, Weisz J (1980) Maternal stress alters plasma testosterone in fetal males. Science 207: 328-9)

"Radioimmunoassay methods have made possible the study of biorhythms which affect the levels of steroid and protein hormones in the plasma. Cyclic fluctuation over one to four weeks (1), variation with the stage of the ovarian cycle (2), circadian rhythm (3,4), and pulsatile, epicodic changes (5-10) have all been demonstrated." (Goldzieher JW, Dozier TS, Smith D, Steinberger E (1976) Improving the diagnostic reliability of rapidly fluctuating plasma hormone levels by optimized sampling techniques. J Clinical Endocrinological Metabolism 43: 824)

[citations removed] "Five dietitians supervised the subjects to follow the experimental diet. The reduction in fat was realized by replacing the regular milk, butter, fatty meat, cheese and suasages by skimmed milk, vegetable oil, margarine (high P/S-ratio) fish, vegetables and fruit as described in detail previously. ... Indeed, the diet influenced the degree of protein binding of testosterone resulting in a small but uniform rise in the percentage of free testosterone fraction as measured utilizing the precipitation method of Bergink et al. Therefore, the calculated concentrations of free (non-protein bound) testosterone decreased less than that of total unconjugated hormone (P < 0.01). ... With regard to testosterone and androstenedione, which decreased 15 and 11% respectively our results show the same tendency as those in the study of Hill el al. However, they reported a more remarkable fall in testosterone in white subjects and the change of androstenedione in black subjects, was not statistically significant. ... Interestingly, there was a negative correlation between serum prolactin and androgens during the whole study. The hypogonadic effect of hyperprolactinemia in man is well-documented. There is evidence that prolactin may interfere with the gonadal steroidogenesis in rats and man and low levels of testosterone can occur without a gonadotrophin response." (Hamalainen E, Adlercreutz H, Puska P, Pietinen P (1984) Diet and serum sex hormones in healthy men. J Steroid Biochem 20(1):459-462)

"The MCR [metabolic clearance rate] of testosterone is mainly influenced by environmental factors rather than genetic whereas the PR [production rate] of testosterone is affected by genetic factors. Those findings and the results of this study suggest that environmental factors may account for the elevated MCR of testosterone observed in men with protatic cancer rather than a gentic factor. The patients and controls undoubtedly have a familial contribution to the plasma antrogen levels, and their PR of DHT and testosterone. It therefore appears that hereditary factors could regulate the PR of testosterone in men who develop prostatic cancer. .. Men with apparent stress and evidence of dissemination of the cancer were excluded as were those who had received endocrine therapy." (Meikle AW, Smith JA, Stringham JD(1989) Estradiol and testosterone metabolism and production in men with prostatic cancer. J Steroid Biochem 33(1):21)

"The testosterone level for nearly 85% of children in the learning-disabled group ranked above the median testosterone value of nonlearning-disabled children (see Fig 1). Mean testosterone level for children with learning disabilities was 17.1 pg/ml, although the mean value for children without learning disability was 10.8 pg/ml for the large control sample. ... Of the children 9 years or younger, 71% of the learning disabled had above median testosterone secretion while only 45% of the nonlearning-disabled sample exceeded this level. ... At an optimal androgen/estrogen ratio, spatial abilities, for example, may be highest among males low in androgen and among females high in androgen." (Kirkpatrick SW, Campbell PS, Wharry RE, Robinson SL (1993) Salivary testosterone in children with and without learning disabilities. Physiol Behav 53(3): 583-585)

"Women exposed prenatally via their pregnant mothers to diethylstilbestrol (DES, a synthetic nonsteroidal estrogen with masculinizing effects in female mammals) received higher ratings of homosexual behavior (Ehrhardt et al., 1985) and showed an increased incidence of left-hand preference (Geschwind & Galaburda, 1985b) compared to female controls. Similarly, women with congenital adrenal hyperplasmia (CAH, an inherited condition which involves an excessive secretion of andrenal androgens) received higher ratings of homosexual behavior (Money et al., 1984; Money, 1987) and showed an increased incidence of left-hand preference (Nass et al., 1987) compared to female controls. In summary, there appears to be an association, at least in women, among excessive prenatal exposure to masculinizing hormones, homosexual behavior, and increased left-hand preference. The associations appear different for men. Among CAH men, who may have higher prenatal androgens, homosexual behavior was extremely rare (Money & Lewis, 1982, 1987; Money, 1987). Also, CAH men did not show increased left-hand preference compared to male siblings (Nass et al., 1987). Similarly, DES-exposed men showed no increase in homosexual behavior (Kester et al., 1980). In contrast, men with Klinefelter's syndrome (KS, 47XXY karyotype, a syndrome associated with reduced development of male secondary sex characteristics and possibly lower levels of prenatal androgens (Ratcliffe, 1976; Sorenson et al., 1981; Nielson et al., 1982)) showed a greater prevelance of left-hand preference than control males (Netley & Rovet, 1982; Braun, 1988). There does not appear to be a higher prevalence of homosexuality in KS men (Nielsen, 1969). However, given the lower libido of KS men (Nielsen, 1969; Raboch et al., 1979), comparisons of prevalence of atypical sexual behavior between KS men and normal men might not be appropriate. In sum, the available evidence suggests that, in contrast to women, higher exposure to masculinizing sex hormones in men is not associated with homosexual behavior and increased left-hand preference. It is open to question whether the latter two behavioral manifestations are associated with lower exposure to masculinizing hormones." (McCormick CM, Witelson SF, Kingstone E (1990) Left-handedness in homosexual men and women. Neuroendocrine implications. Psychoneuroendocrinology 15: 70-71)

"The proportion of homosexual women who showed non-CRH (22/32, 69%) was significantly greater than that of the general population (35%) (z=3.55, p=0.0005, two-tailed). If the most common definition of hand preference was considered -- hand used for writing -- the female homosexuals showed only a trend toward greater left-hand preference (6/32, 19%) than in the general population (10%) (z=1.71, p=0,09, two-tailed). The proportion of homosexual men who showed non-CRH (17/38, 45%) was not statistically different from that of the general population (35%) (z=1.20, p=0.23, two-tailed). The male homosexuals showed a similar proportion of left-hand preference based on writing hand (4/38, 11%) as in the general population (10%)." (McCormick CM, Witelson SF, Kingstone E (1990) Left-handedness in homosexual men and women. Neuroendocrine implications. Psychoneuroendocrinology 15: 72)

"It seems possible that an optimal testosterone range exists for the expression of creative musical behavior and that exceeding this optimal range in the course of puberty may contribute to a stop of musical production in boys. Such optimal testosterone levels may be lower than male average in adult men and higher than female average in adult women (Hassler, 1991; Hassler & Nieschlag, 1989). ... Handedness proved to be an important variable with respect to musical talent in boys. Male left-handers attained significantly higher mean test scores than male right-handers on Wing's Standardized Tests of Musical Intelligence (Hassler & Birbaumer, 1988) at each stage of the study." (Hassler, M & Nieschlag, E. (1991) Salivary testosterone and creative musical behavior in adolescent males and females. Developmental Neuropsychology 7: 504)

"By comparing adolescent girls' testosterone results derived from saliva sampled during the follicular phase (Day 1 to 15) with testosterone results obtained from saliva sampled during the luteal phase (from Day 16 to the onset on menstuation) of the menstrual cycle, we found no significant differences between the phases at Stage 4 when girls' mean age was 14.43. At Stage 5, when girls were 15.40 years old on average, significant differences emerged in testosterone means of the day.... Testosterone means were higher in the luteal than in the follicular phase of the menstrual cycle." (Hassler & Birbaumer, 1988) at each stage of the study." (Hassler, M & Nieschlag, E. (1991) Salivary testosterone and creative musical behavior in adolescent males and females. Developmental Neuropsychology 7: 516)

"Most of those boys and girls who demonstrated creative musical behavior at the beginning of our study lost the ability to compose and improvise in the course of adolescence." (Hassler & Birbaumer, 1988) at each stage of the study." (Hassler, M & Nieschlag, E. (1991) Salivary testosterone and creative musical behavior in adolescent males and females. Developmental Neuropsychology 7: 518)

“The relationship between serum testosterone level and hand skill was studied in right-handed young adults. Hand preference was assessed by the Edinburgh Handedness Inventory. Hand skill was assessed by the peg moving task. Serum testosterone level was determined using tritium-marked-radioimmunoassay. In the total sample, only the right-hand skill showed a direct correlation and an inverse correlation with serum testosterone for men and women, respectively. In male subjects with right-eye preference, both hand skills exhibited a direct relation to serum testosterone. In the total sample, there was a direct and and inverse relationship between the difference in skill between hands and serum testosterone in men and women, respectively. This was, however, affected by right-eye and right-foot preference. It was concluded between men and women; the left cerebral hemisphere seems to be the main target of testosterone.” (Tan, U. (1990) Testosterone and hand skill in right-handed men and women. International Journal of Neuroscience 53: 179) [subjects were 42 male and 17 female right-handed students]

“The results of the present work indicated a different organization within the human brain with respect to relation of testosterone to skilled movement compared to hand preference. Namely, the serum testosterone was found to be associated mainly with right-hand skill in men and women. However, there were fundamental differences in the male and female patterns. Except for male right-handers with right-eye preference, the right hand skill was found to be directly related to serum testosterone in men, and inversely related to serum testosterone in women. In other words, the right-hand skill increased with serum testosterone in men, which contrasts with the Geschwind-Behan hypothesis. In women, the right-hand skill decreased with serum testosterone in accord with the Geschwind-Behan hypothesis. It is, however, interesting that mainly the left-cerebral hemisphere is involved in testosterone actions, except for men with right-hand and right-eye preference exhibiting involvement of both cerebral hemispheres. As expected form the above presented results, there was a direct relationship between the difference in skill between hands and serum testosterone in men. That is, as testosterone increased, the right-hand skill with testosterone causes an increase in L-R hand skill depending upon improvement in the left hemisphere functions for skilled movments with testosterone. In contrast, as testosterone increased, the difference in skill between hands decreased in women. This result was also expected, since right-hand skill deceased with testosterone in these subjects. Thus, testosterone seems to exert a negative effect on the left cerebral hemisphere for skilled movements. However, these effects were found to be also dependent on eye and foot preferences. Here again, men and women showed different patterns. In right-handed men with right-eye preference, the difference in skill between hands was found to be directly related to serum testosterone, but there was not a significant relationship between these parameters in women with right-eye preference. On the contrary, there was not a significant correlation between serum testosterone and L-R hand skill in men with right-foot preference, but there was a marginally significant inverse correlation between these two parameters in women with right-foot preference. In summary, the results of the present work showed that serum testosterone levels are associated with hand skill in right-handed yound adults without FS. There were, however, fundamental sex-related differences in this organization, which were also associated with eye and foot preferences. Testosterone seems to be advantageous for the male brain, but detrimental for the female brain with regard to skilled movements. Moreover, testosterone seems to create a more asymmetrical brain in men, and a more symmetrical brain in women.” (Tan, U. (1990) Testosterone and hand skill in right-handed men and women. International Journal of Neuroscience 53: 188-9)

"Musical talent is related to above-average spatial ability in children before and during puberty..." (Hassler, M. (1992) Creative musical behavior and sex hormones: musical talent and spatial ability in
the two sexes. Psychoneuroendocrinology 17 (1): pp. 55)

"Women with congenital adrenal hyperplasmia (CAH) have been exposed to above average androgen levels in utero. These women have been reported to display higher spatial ability than matched controls as adults (Resnick et al., 1986; but see also Ehrhardt & Meyer-Bahlburg, 1981; Reinisch, 1983). They ordinarily do not have elevated T levels as adults, but T levels of CAH women were not presented in the above-cited studies. Women with Turner's syndrome, whose gonads develop improperly and produce only minute amounts of sex homones (Nyborg, 1984), are hypoandrogenized both prenatally and in adulthood. They were found to perform poorly on spatial taks in adulthood (Nyborg & Nielson, 1981; Nyborg, 1984). Fetally nonandrogenized genetic males with androgen insensitivity syndrome (AIS) produce a normal amount of T, but their tissue is insensitive to the steroid, both pre- and post-natally. AIS patients also were found to perform poorly on spatial tasks (Nyborg, 1984). From their study with androgen-deficient men, Hier and Crowley (1982) concluded that androgens exert a permanent organizing influence on the brain before puberty or at puberty in boys. Those with hypoandrogenization in their early development did not improve on spatial tasks when treated with T as adults. Nyborg (1984) has suggested that, in addition to prenatal organizing T effects, current levels of estradiol (E2), or aromatized T, or the possibility of T antagonizing estradiol at the plasma level, influence spatial faculties. According to his General Trait Covariance Model, there is a curvilinear relationship between circulating E2 and spatial performance. This model predicts that spatial performance is highest when E2 levels are in an optimum range, below and above which spatial performance decreases. This model is in line with experimental (Broverman et al., 1968) and descriptive (Petersen, 1976) studies showing that physically androgynous persons in both sexes tend to attain higher test scores on spatial measures than do either masculine men or feminine women." (Hassler, M. (1992) Creative musical behavior and sex hormones: musical talent and spatial ability in
the two sexes. Psychoneuroendocrinology 17 (1): pp. 56)

"There is evidence that musicians are androgynous persons (Kemp, 1982; 1985; Hassler et al., 1985; Hassler & Nieschlag, 1989). Due to the relationship between spatial and musical capacities, sex hormones, particularly T as the pre-hormone for its biologically active metabolites, may contribute to the development of both musical talent and spacial ability." (Hassler, M. (1992) Creative musical behavior and sex hormones: musical talent and spatial ability in the two sexes. Psychoneuroendocrinology 17 (1): pp. 56)

"Sex differences in T levels were minimal among musical composers. T levels that differ from average values were not found in instrumentalists or in painters (Hassler, 1991a), though painters' T levels were between those of composers on the one hand and those of instrumentalists and nonmusicians on the other (Hassler, 1991a). Nonmusicians in that study had significantly higher T levels than composers." (Hassler, M. (1992) Creative musical behavior and sex hormones: musical talent and spatial ability in the two sexes. Psychoneuroendocrinology 17 (1): pp. 64)

"Our data obtained from adults allow for the hypothesis that an optimal T range may exist for the expression of creative musical behavior. This range may be at the bottom of the normal male T range and at the top of the normal female T range. T may be one component of a complex biological system contributing to musical creativity. ... The limitation given by the measurement of only one hormone must be overcome in future research in order to get more information about the hormone/behavior relationship in adolescence. For instance, E2 surges in girls occurring at age 13 should be taken into account. In women, creative musical capacities may emerge, or emerge again, in adulthood, when female hormone levels have reached the adult state. Though we have no indication of a reemergence of musical creativity in our adolescent girls, who have not yet reached the adulthood, there are clues from our study with adults (Hassler et al., 1990). Half our adult female composers began composing after puberty. General musical ability as measured with the Wing test showed some fluctuation during the course of adolescence. In 1987, when children had reached a mean age of 15.5 yr, the only significant correlation between T and Wing test scores was in girls and was positive. No other clue was found to indicate that general musical ability was related to T levels." (Hassler, M. (1992) Creative musical behavior and sex hormones: musical talent and spatial ability in the two sexes. Psychoneuroendocrinology 17 (1): pp. 66)

"T exerts its influence together with other hormones and with neurotransmitters (Hutchinson & Steimer, 1984; Whalen, 1984), and it may act on the brain as T, or by its metabolites estradiol and dihydrotestosterone." (Hassler, M. (1992) Creative musical behavior and sex hormones: musical talent and spatial ability in the two sexes. Psychoneuroendocrinology 17 (1): pp. 66)

"The critical periods, as Dorner (1988) has argued, are not completely identical but are overlapping. The assumption that androgens influence brain differentiation during the midtrimester of gestation (Dorner, 1985; 1988) has been questioned by Money (1988, p. 23), who cited the findings of Abramovich et al. (1987) who undertook an extensive neurochemical search of tissues from fetal brains, age 14-20 wk of gestation, for evidence of receptors that would take up estrogenic, androgenic, or progentinic sex hormones. The evidence was nil. Money (1988, p. 23) concluded that the stage in development what hormones influence the differentiation of the human brain as dimorphically male or female remains to be discoverd. It may be in the third trimester of pregnancy, or it may extend through the first 3 postnatal months of age. (Hassler, M. (1992) Creative musical behavior and sex hormones: musical talent and spatial ability in the two sexes. Psychoneuroendocrinology 17 (1): pp. 66-67)

(summary] 'Recent studies hinting that estrogen replacement therapy may help prevent Alzheimer's disease fosters new appreciation of importance of the hormone to health of brain, where it assures production of critical enzymes and maintains densest possible mesh of fibers connecting one nerve cell to the next; men's supply of testosterone could account for fact that they get Alzheimer's less frequently than women, since much of a man's circulating testosterone is converted to estrogen in the brain and since m en's testosterone levels do not decline with age like women's natural estrogen levels.' (New York Times Article March 8, 1994? How Estrogen May Protect Against Alzheimer's by Natalie Angier SEC, PG:COL: C, 3:1)

"Right-handers (RH) had higher T concentrations than left-handers (LH). This was also true within each sex independently (see Fig. 1). Although males overall had much higher T concentrations than females, as expected (F(1,76)=366.56, P<0.001), male RH had higher T concentrations than male LH (t (38)=2.15, P=0.038) and female RH had higher T concentrations than female LH(t (38)= 1.99, P=0.054). The magnitude of the left handedness effect approaches 3/4 of a standard deviation in both males and female." (Moffat, S.D. & Hampson, E. (1996) Salivary testosterone levels in left- and right-handed adults. Neuropsychologia 34 (3): pp. 227)

"To summarize, results indicated that LH of both sexes had significantly lower salivary T concentrations than RH. All means were nevertheless within the normal physiological range. A possible further association between T and language lateralization was suggested by the tendency, among males, for LH who showed a REA on the Fused Dichotic Words Test to have lower salivary T concentrations than LH who showed a LEA." (Moffat, S.D. & Hampson, E. (1996) Salivary testosterone levels in left- and right-handed adults. Neuropsychologia 34 (3): pp. 229)

"instead, we found a trend for LH males with a REA [right ear advantage] to have lower T concentrations than LH males with a LEA." (Moffat, S.D. & Hampson, E. (1996) Salivary testosterone levels in left- and right-handed adults. Neuropsychologia 34 (3): pp. 231)

[citations removed] "Schacter reported that women exposed in utero to the synthetic estrogen diethylstilbestrol had a handedness distribution on the Edinburgh Handedness Inventory (EHI) that was shifted away from strong right-handedness. Nass et al found that females with congenital adrenal hyperplasia (CAH), a disorder that results in increased androgen production during gestation, displayed a lesser degree of right-hand preference than unaffected sibling controls on the EHI. However, males with CAH displayed a trend in the opposite direction. More recently, Helleday et al. reported that females with CAH did not differ from controls in either degree of right-hand preference or in dichotic listening asymmetry." (Moffat, S.D. & Hampson, E. (1996) Salivary testosterone levels in left- and right-handed adults. Neuropsychologia 34 (3): pp. 225)

"We therefore assessed handedness in patients with classic congenital adrenal hyperplasia (CAH), in which lack of adrenal 21-hydroxylase results in depressed glucocorticoid production (simple virilizer (SV)) and in some cases depressed mineralocortocoid (salt wasters (SW)) production. Low glucocorticoid levels result in failure of feedback inhibition of hypothalamic-pituitary-adrenal axis and therefore is excess testerosterone production." (Nass R, Baker S, Speiser P, Virdis R, Balsamo A, Cacciari E, Loche A, Dumic M, New M. (1987) Hormones and handedness: Left-hand bias in female congenital adrenal hyperplasia patients. Neurology 37: 711)

"An excess of left-handers among males has been attributed to early androgen exposure. This theory was supported by our observation that girls with congenital adrenal hyperplasmia (CAH) are more left-biased than their normal sisters. Male CAH patients, with prenatal andogen exposure similar to that of unaffected brothers, had typical male-handedness patterns." (Nass R, Baker S, Speiser P, Virdis R, Balsamo A, Cacciari E, Loche A, Dumic M, New M. (1987) Hormones and handedness: Left-hand bias in female congenital adrenal hyperplasia patients. Neurology 37: 711) [note: high T uterus for females makes a lefty female. Are they strong lefties or mild ambi lefties?]

"The differences in dizygotic twin frequency, and presumably ovulaton rate, are in the same direction as the differences in testis size. The frequencies of dizygotic twins are even higher (up to 49 per 1,000 births) among African blacks. ... Yoruba women, with the world's highest frequency of dizygotic twins, have higher FSH and LH levels at the time of ovulation than do Japanese women, who have the lowest frequency of dizygotic twins. This variation in female hormone levels may contribute to the distribution of the incidence of breast cancer, which is known to be related to oestrogen levels. Even after all other risk factors for breast cancer have been taken into account, the incidence among Japanese women remains inexplicably low. Perhaps this puzzel, the so-called 'Japanese factor' of (breast cancer, is related to the low double-ovulation frequencies and low hormone levels." Diamond, JM (1986) Variation in human testis size. Nature (London) 320: 488-489)

"Perhaps the facial proportions that Jones interprets in terms of age cues also indexed some other aspect(s) of female mate value. One possibility is hormonal status, which Jones considers unlikely. Yet high androgen levels in women are positively correlated with reproductive system dysfunctions, and observable indices of high androgen levels, such as acne, hirsutism, and a high waist-to-hip ratio--seem to be systematically percieved as unattractive. To my eye, the faces in Jone's figure I apear to differ more in "masculinity" than in age." (Symons, D (1995) response to...Sexual selection, physical attractiveness, and facial neoteny: cross-cultural evidence and implications. Current Anthropology 36 (5): pp. 741-43)

Females actually play differently than males do (Walters 1987). In species that live in highly complex social groups, males play more frequently and engage in rough-and-tumble play more often than females do (Caine and Mitchell 1979). ... The difference is apparently hormonally based. When female rhesus monkey fetuses given male androgen hormones become juveniles they played more like males than females juveniles (Goy and Resko 1972). (Small, Meredith F. (1993) Female choices: Sexual behavior of female primates. Cornell Univ. Press, Ithaca, 1993 pp. 63)

"Sex hormone levels were found to be normal in the majority of homosexual women, but prenatal androgen excess, heterosexuality appears to be more frequent than bisexuality, an exclusive homosexuality is rare. ... Conversely, the removal of the adrenal, which is the major androgen-producing organ in the female, decreases labido (Waxenburg et al., 1959). These findings have led to the hypothesis that androgens are the libido hormone in women as well as in men (Money, 1961). ... We can conclude that the majority of female homosexuals appear to have testosterone and estogen levels within normal female range, whereas there seems to be a significant subgroup of about one-third of all subjects screened with an elevation of male sex hormone levels." (Meyer-Bahlburg, H. (1979) Sex hormones and female homosexuality: A critical examination. Archives of Sexual Behavior 8: 101-108)

"It has been proposed that prenatal testosterone (T) may contribute to the development of hand preference and cerebral functional asymmetry in humans. To investigate any persisting association between T and asymmetry in adulthood, left-handed (LH) and right-handed (RH) men and women were administered a hand preference questionnaire and the Fused Dichotic Words Test. Testosterone was measured in samples of saliva. Results showed that LH subjects of both sexes had lower salivary T concentrations than their RH counterparts. Among LH males, subjects with a right-ear advantage in dichotic listening tended to have lower T concentrations than subjects with a left-ear advantage. These results are consistent with the notion that T may be involved in the development of hand preference and cerebral functional asymmetry." (Moffat SD, Hampson E (1996) Salivary testosterone levels in left- and right-handed adults. Neuropsychologia 34(3):225)

[abstract] "The nature of the relationship, if any, between performance on visuo-spatial tests in humans and circulating testosterone (T) concentrations remains controversial. We investigated possible relationships between salivary T and cortisol (C) concentrations and performance on visuo-spatial and verbal cognitive tests in a sample of healthy young adults. Among right-handers, salivary T was found to be negatively correlated with spatial performance in males, but was positively correlated with a measure of spatial visualization in females. This pattern was not evident in left-handers. Across the entire observed range of T, the relationship between spatial cognition and T was best described by an inverted quadratic function in right-handers, but not in left-handers. A significant difference in spatial accuracy was seen among right-handers tested in early vs. late morning testing sessions, in accordance with the expected diurnal change in circulating T. No significant relationships between salivary C and visuo-spatial performance were found. These results are consistent with prior literature suggesting a curvilinear relationship between spatial performance and circulating T concentrations, with intermediate levels of T being associated with better spatial functioning, but raise the possibility that hand preference may be one factor that moderates the observed relationship." (Moffat SD, Hampson E (1996) A curvilinear relationship between testosterone and spatial cognition in humans: possible influence of hand preference. Psychoneuroendocrinology 21(3):323-37)


[abstract] "Sex-related differences have been reported for some brain neuroanatomical structures and several measures of brain function. We studied the cerebral glucose metabolic rates of normal men (n = 7) and women (n = 7) with positron emission tomography and the fluorodeoxyglucose method. Women were studied between days 5 and 15 of the menstrual cycle. Women had whole brain glucose metabolic rates that were 19% higher than those of men. All neuroanatomical structures surveyed showed significant female greater than male rates, with no particular regions being outstanding. The higher cerebral glucose metabolic rates we observed in women may have been related to the effects of the high estrogen levels that can obtain in the phase of the menstrual cycle during which we tested our female subjects." (Baxter LR Jr, Mazziotta JC, Phelps ME, Selin CE, Guze BH, Fairbanks L (1987) Cerebral glucose metabolic rates in normal human females versus normal males. Psychiatry Res 21(3):237-45)

"20 children with idiopathic precocious puberty, 27 adolescents with clinically delayed puberty, and an equivalent number of controls matched for age, sex, and IQ were given a battery of tests. These included measures of verbal and spatial abilities and a task assessing hemispheric lateralization using a dichotic listening procedure. Comparisons with matched controls revealed poorer verbal and spatial abilities for precocious males and poorer verbal, but better spatial, abilities for precocious females. Delayed developing males demonstrated superior verbal skills compared with controls, whereas delayed developing females did more poorly than controls in both verbal and spatial areas. On the dichotic task, the only group differing from controls was the delayed developing males, who demonstrated stronger lateral asymmetries. It was suggested that the present findings, which are not consistent with those of former investigations, may reflect methodological differences between studies and the disruptive influence of atypical pubertal onset on normal patterns of sex difference in cognitive functioning." (Rovet, J. (1983) Cognitive and neuropsychological test performance of persons with abnormalities of adolescent development: A test of Waber’s hypothesis. Child Development 54: pp. 941)

"Titers of testosterone in plasma were determined by radioimmunoassay in male rat fetuses of stressed and control mothers on days 17, 18, 19, 21, and 23 (the day of birth) after conception. In fetuses of stressed mothers, testosterone concentrations were highest on day 17, declined on days 18 and 19, and then remained unchanged. In the control fetuses, testosterone increased from relatively low concentrations on day 17 to the highest amounts on days 18 and 19, and then declined. Thus, the persistence of feminine and impaired masculine sexual behavior in male offspring of stressed mothers could be due to the absence of a surge of circulating testosterone during days 18 and 19 after conception, a period postulated to be critical in the development of the central nervous sy tem in the rat." (Ward IL, Weisz J (1980) Maternal stress alters plasma testosterone in fetal males. Science 207: 328)

"The effect of acute activation of the ACTH-adrenal axis on circulating testosterone (T) levels was investigated. Elevation of circulating cortisol resulting from insulin-induced hypoglycemia or the administration of hydrocortisone was followed by a rapid decrease in serum T levels, without accompanying changes in LH or PRL. These findings suggest that hypercortisolism of endogenous or exogenous sources suppresses T secretion by a direct action on the testis. This adrenal-testicular axis may have biological implications on the reproductive adaptation to stress." (Cumming DC, Quigley ME, Yen SSC (1983) Acute suppression of circulating testosterone levels of cortisol in men. J Clinical Endocrinological Metabolism 57: 671)

"When plasma hormone levels undergo rapid and large oscillations, as in the case of testosterone, FSH, and LH, a single random sample is likely to yield a result within +/-20% of the true mean value only 68%, 54%, and 30% of the time, respectively. Multiple sampling increases reliability, and computer analysis demonstrates that three equally-spaced samples taken at 6 to 18 min intervals provide the optimum schedule, given certain practical considerations. Pooling of the three plasma samples prior to radioimmunoassay avoids an increased laboratory workload." (Goldzieher JW, Dozier TS, Smith D, Steinberger E (1976) Improving the diagnostic reliability of rapidly fluctuating plasma hormone levels by optimized sampling techniques. J Clinical Endocrinological Metabolism 43: 824)

"The possible effect of dietary fat content and the ratio of polyunsaturated to saturated fatty acids (P/S-ratio) on serum sex hormones was studied in 30 healthy male volunteers. The customary diet of the subjects, which supplied 40% of energy as fat (mainly from animal sources, P/S-ratio 0.15) was replaced for a 6 weeks period by a practically isocaloric experimental diet containing significantly less fat (25% of energy) with a higher P/S-ratio (1.22) and other environmental factors were stabilized. Serum testosterone and 4-androstenedione decreased from 22.7 +/- 1.1 nmol/l to 19.3 +/- 1.2 nmol/l, (SEM, P less than 0.001) and from 4.6 +/- 0.2 nmol/l to 4.3 +/- 0.2 nmol/l (SEM, P less than 0.01), respectively. These changes were paralleled by a reduction in serum free (non-protein bound) testosterone (P less than 0.01) suggesting a possible change in biological activity. During the low fat period a significant negative correlation between serum prolactin and androgens was observed. All the changes in androgen levels were reversible. With the exception of a small but non-significant decrease in serum estradiol-17 beta, the other hormone parameters were practically unaffected by the dietary manipulation. Our results indicate that in men a decrease in dietary fat content and an increase in the degree of unsaturation of fatty acids reduces the serum concentrations of androstenedione, testosterone and free testosterone. The mechanism and importance of this phenomenon is discussed in the light of epidemiological and experimental data." (Hamalainen E, Adlercreutz H, Puska P, Pietinen P (1984) Diet and serum sex hormones in healthy men. J Steroid Biochem 20(1):459)

[abstract] "The concentrations of serum total and free testosterone were studied in 30 healthy, middle-aged men during a dietary intervention program. When men were transferred from their customary diet to an experimental diet, which contained less fat with a higher polyunsaturated/saturated ratio (P/S-ratio) and more fibre, there was a significant decrease in serum total testosterone concentrations (22.7 +/- 1.2 vs 19.3 +/- 1.1 nmol/l SEM, P less than 0.001). Furthermore, serum free, unbound testosterone fell from 0.23 +/- 0.01 to 0.20 +/- 0.01 nmol/l SEM (P less than 0.01). The hormonal changes were reversible. This observation suggests that testosterone activity in plasma can at least partly be modified by changing the composition of the diet." (Hamalainen EK, Adlercreutz H, Puska P, Pietinen P (1983) Decrease of serum total and free testosterone during a low-fat high-fibre diet. J Steroid Biochem18(3):369-70)

"Previous studies have indicated that the sex steroids have organizational effects upon neural tissue and that abnormal secretion during development may lead to functional anomalies. In this study, we explore the possibility of prepubertal steroid hormone involvement in the etiology of learning disabilities. Salivary testosterone levels in 264 children without learning disabilities (133 males, 131 females) were measured and compared to that in 32 children with learning disabilities (25 males, 7 females). The presence of learning disabilities was significantly associated with higher salivary testosterone. Data from equivalent samples of learning-disabled and control subjects also were compared separately because of disparities in sample size and variable distribution in the total group analysis. A 32-member sample of nonlearning-disabled children was created by randomly selecting individuals who exactly matched the age, race, and sex characteristics of the learning-disabled group. The matched analysis further substantiated the association between testosterone secretion and learning disabilities. Thus, it is possible that some learning disabilities may be associated in part with abnormal testosterone levels." (Kirkpatrick SW, Campbell PS, Wharry RE, Robinson SL (1993) Salivary testosterone in children with and without learning disabilities. Physiol Behav 53(3): 583)

[abstract] "In the current investigation an approach has been made to explore possible relations between musical talent, left-handedness, anomalous dominance for verbal materials, and immune vulnerability. Fifty-one young adult musicians and non-musicians were tested with Wing's Standardized Tests of Musical Intelligence, with a handedness questionnaire, a dichotic listening task, and with a questionnaire assessing asthma/allergies, migraine and myopia. In addition, IgE, Ig total, beta-endorphin, testosterone, and estradiol were measured in blood serum. Musical talent was related to left-handedness and to anomalous dominance; immune vulnerability was found in female musicians, and in subjects with reversed dominance for language functions as well as in male left-handers, independently of musical talent." (Hassler M, Gupta D (1993) Functional brain organization, handedness, and immune vulnerability in musicians and non-musicians. Neuropsychologia 31(7):655-60)

[citations removed] "In general the two experiments express the well-known left hemisphere superiority for verbal processing and right hemisphere superiority for face perception. However, while the right field advantage for lexical decisions did not change throughout the menstrual cycle, the significant left field advantage for face perception in the menstrual phase disappeared during the mentrual cycle and even shifted in the prementrual phase, suggesting that hormones may influence the balance of hemispheric activation. Such influences might at least in part be responsible for more variable results with female than with male subject groups and for contradictions between different experiment studies. ... With respect to overall speed of processing the results for face decisions indicate that during menstruation and especially during the prementrual phase, the processing of such stimuli seems to be more difficult than in the middle of the cycle, where reactions were faster and fewer errors were made (see Fig. 3). This fits rather well with reports in the literature demonstrating better performance (and lower visual thresholds in midcycle, probably due to the activating effects of oestogen. However, it is difficult to compare results because of the many different ways of defining cycle phases, and the various measures and tasks employed in the literature. Our finding of faster more correct responses in midcycle is also in certain agreement with Hampson's and Hampson and Kimura's result that speed and accuracy on nonverbal tasks were better during the luteal than during the menstrual phase. If one compares the results of Experiments I and II one realizes that during the menstrual, follicular and luteal phases face decisions tended to be faster overall than lexical decisions, while during the premenstrual phase face decisions were much slower overall than the verbal ones. The premenstrual phase showed at the same time the fastest verbal and the slowest non-verbal responses of all phases of the menstrual cycle. [study done in Germany]" (Heister, G., Landis, R., Regard, M. & Schroeder-Heister, P. (1989) Shift of functional cerebral asymmetry during the menstrual cycle. Neuropsychologia 27: 877))

"Creative musical behavior, musical intelligence, and spatial ability were investigated in relation to salivary testosterone (T). In a cross-sectional study with 117 adults and in an 8-yr longitudinal study with 120 adolescents, composers, instrumentalists, and nonmusicians of both sexes were compared by analyses of variance. Results indicate that an optimal T range may exist for the expression of creative musical behavior. This range may be at the bottom of normal male T range and at the top of normal female T range. In addition, musicians were found to attain significantly higher spatial test scores than nonmusicians, both, in an 8-yr-period of adolescent development and in adulthood." (Hassler, M. (1992) Creative musical behavior and sex hormones: musical talent and spatial ability in the two sexes. Psychoneuroendocrinology 17 (1): pp. 55)

"The main result of our study is the linear decrease of left field superiority for face decisions, as measured from menstuation (during which pituitary and gonadal hormones are low) to what we here call the premenstrual phase, where---compared with the other phases----in particular the progesterone level should be high. That is, even with respect to asymmetry, a change takes place in the premenstrual phase. Our hypothesis that the largest asymmetry, a relatively "male pattern" of lateralization, should be found during menstruation when female sex hormones are extremely low, was supported. As compared to the menstrual phase, during the premenstrual phase 10 of the 12 subjects showed a smaller or even reversed asymmetry for this task. The reliability of our findings is also supported by the analysis of errors, which yielded the same pattern of results as reaction times, that is , a shift of asymmetry in the prementrual phase. Since the main difference was obtained between the menstrual and premenstrual phases and not between the menstrual and follicular phases, one may speculate that the result is related to progesterone, since oestrogen has one peak during the follicular phase and one during the luteal phase and should be lower during the premenstrual phase." (Heister, G., Landis, R., Regard, M. & Schroeder-Heister, P. (1989) Shift of functional cerebral asymmetry during the menstrual cycle. Neuropsychologia 27: 877-8)