Reproduced for educational purposes only, here is the most recent journal publication of Melissa Hines' research with DES daughters that I've been able to track down using Highwire and Elsevier (Science Direct).
Note how this study (from 1999) was funded by a NIH grant--undoubtedly because the focus of the study is largely non-controversial and not related to anything sexual.
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Language lateralization and handedness in women prenatally exposed to diethylstilbestrol (DES)
Laurel L. Smith and Melissa Hines
Abstract link:
http://highwire.stanford.edu/cgi/medline/pmid;10818283
Full text (minus tables, which cannot be reproduced here)
Psychoneuroendocrinology
Volume 25, Issue 5 , July 2000, Pages 497-512
Copyright © 2000 Elsevier Science Ltd. All rights reserved.
Language lateralization and handedness in women prenatally exposed to diethylstilbestrol (DES)
Laurel L. Smith (a) and Melissa Hines (a, b)
(a) Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, CA, USA
(b) Department of Psychology, City University, London EC1V 0HB, UK
Received 27 July 1999; accepted 6 December 1999. Available online 15 May 2000.
Abstract
Hand preferences and language lateralization were assessed in women exposed prenatally to the synthetic estrogen, diethylstilbestrol (DES), and in their unexposed sisters. The DES-exposed women showed an increased degree of hand preference (regardless of direction) and were more likely to be left handed for writing. However, the groups did not differ ignificantly on a dichotic listening measure of language lateralization. Perhaps as a result of the alterations in hand preferences, the typical relationship between hand preferences and language lateralization was disrupted in the DES-exposed group. Also, within the DES-exposed group, exposure early in gestation correlated with left handedness whereas exposure late in gestation correlated with reduced left ear (right hemisphere) scores on the verbal dichotic task. Results are discussed in terms of theoretical perspectives predicting hormonal influences on sexual differentiation of hemispheric asymmetry and in terms of separate critical periods for hormonal effects on individual sexually differentiated characteristics.
Author Keywords: Handedness; Language lateralization; Diethylstilbestrol; Sex differences; Estrogen; Prenatal
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Article Outline
1. Introduction
1.1. Sex differences in language lateralization
1.2. Sex differences in handedness
2. Method
2.1. Subjects.
2.2. Materials and procedure
2.2.1. Dichotic listening
2.2.2. Handedness
3. Results
3.1. Hand preferences
3.2. Language lateralization
3.3. Language lateralization related to hand preferences
3.4. Timing and duration of exposure
4. Discussion
Acknowledgements
References
1. Introduction
Gonadal steroids have been hypothesized as one potential source of individual differences in human behaviors that show sex differences. In a wide range of non-human species, hormones exert powerful influences on behavior during early critical periods when testosterone levels are elevated in males. During these periods, administration of testosterone or its metabolites (including estrogen) to females increases male-typical behavior and decreases female-typical behavior (Goy; Phoenix; Beach; Beatty and Goy). There is some evidence of similar hormonal influences on development of human behaviors that show sex differences ( Collaer and Hines, 1995). However, the range of behaviors influenced is not well understood. There is substantial evidence of hormonal influences on childhood play behavior, some evidence of influences on sexual orientation and aggression, and weaker evidence of influences on language lateralization and hand preferences. The purpose of the present study was to provide additional evidence regarding these last two characteristics.
1.1. Sex differences in language lateralization
Kimura and Kimura found that adults are more accurate in reporting verbal information presented to the right than the left ear. This has been replicated repeatedly and is accepted as evidence for a left hemispheric dominance for language in adults. However, not all individuals demonstrate the same degree of left hemispheric advantage. For instance, left handers are less reliant on the left hemisphere for language processing. Sex also is associated with differences in lateralization, such that on average men are somewhat more lateralized to the left hemisphere for verbal materials than are women ( Bryden; Bryden and Voyer).
1.2. Sex differences in handedness
Most people use their right hands for writing and other skilled manual tasks. However, this right hand preference is more marked in women than in men. Women are more likely to show a right hand preference across a range of tasks and are less likely than men to use their left hand for writing (Oldfield; Calnan; Schachter and Lansky). Thus, although language lateralization is more marked in men than in women, motoric lateralization, as reflected in right hand preferences, shows a sex difference in the opposite direction, being more marked in women than in men.
For both language lateralization and hand preferences it is not known whether the sex difference is in the degree of asymmetry or its direction (see, e.g. McManus, 1983, for a discussion of this issue). A mean handedness or lateralization score does not distinguish degree from direction. A neutral score, for instance, could indicate that all activities are performed by the two hands without a preference, or that some activities are performed exclusively by the right hand and others by the left hand. Because this issue has not been studied systematically, it has not been determined whether sex differences in asymmetry are differences in degree (i.e. less dramatic hemispheric dominance for language in women and less dramatic handedness in men) or kind (i.e. more right hemispheric dominance for language in women and more left handedness in men).
The underlying mechanisms responsible for sex differences in language lateralization and handedness are not clear. Because these characteristics show sex differences, one hypothesis is that they are influenced by testosterone, or estrogen derived from it, during prenatal or neonatal development. The human testes secrete testosterone prenatally, beginning at about gestational weeks 8 to 10 and peaking at around 13 to 15 weeks (Smail et al., 1981). Testosterone in male fetuses then declines by week 24 to levels comparable to those of female fetuses. There is a second testosterone surge postnatally causing elevated levels in males during approximately the first 6 months of life ( Smail et al., 1981). These two periods could represent times when hormone exposure influences human development.
Because it is unethical to administer hormones to developing humans to study behavioral outcomes, information must be obtained from individuals exposed for other reasons to unusual hormonal environments. Some support for the predicted influence of hormones on language lateralization has come from a study of women whose mothers were prescribed the synthetic estrogen, diethylstilbestrol (DES), during pregnancy and from a study relating testosterone levels in second trimester amniotic fluid to language lateralization at age 10. The prenatally DES-exposed women resembled men in showing increased right ear left hemisphere) dominance for language when compared to their unexposed sisters (Hines and Shipley, 1984). Similarly, girls with higher prenatal testosterone levels in amniotic fluid had stronger left hemisphere lateralization for language than girls with lower levels ( Grimshaw et al., 1995).
Support for the predicted influence of hormones on handedness has been found in increased left-handedness or a shift from strong right-handedness in females exposed to excess androgen prenatally because they have the genetic disorder, congenital adrenal hyperplasia (CAH) (Nass et al., 1987), or to excess estrogen prenatally because their mothers were prescribed DES ( Schachter and Scheirs). However, the study of testosterone levels obtained from second trimester amniotic fluid suggested an effect in the
opposite direction; girls with higher prenatal testosterone levels were more strongly right-handed (Grimshaw et al., 1995).
In other species, and perhaps in humans, testosterone from the testes is normally converted to estradiol within the brain and then acts through neural estrogen receptors to masculinize and defeminize some aspects of neurobehavioral development (Goy and MacLusky). The synthetic estrogen, DES, was formerly prescribed during pregnancy because it was mistakenly thought to prevent miscarriage ( Heinonen and Noller). Due to its nonsteroidal structure, DES reaches the fetal brain in a biologically active form where it can stimulate neural estrogen receptors ( McEwen, 1980). As a consequence, DES masculinizes and defeminizes many aspects of brain structure and behavior when administered to genetic female animals during early critical periods. Female rodents exposed to DES prenatally or neonatally display masculine-typical behavior ( Goy and Hines), and brain structure (Dohler et al., 1982) similar to that of normal males. Although most of the evidence for these masculinizing effects of DES has come from studies of rodents, one report suggests similar influences in rhesus macaques ( Goy and Deputte, 1996).
Similar to its effects in animals, prenatal DES exposure in human females has been linked to masculinizing or defeminizing effects, including increased bisexuality (Meyer-Bahlburg et al., 1995) and, as mentioned above, enhanced language lateralization ( Hines and Shipley, 1984), and reduced right-hand preferences ( Schachter and Scheirs). The purpose of the present study was to provide further information as to whether prenatal DES exposure influences hand preferences and language lateralization. In addition, we wished to examine relationships between these two variables following DES exposure. This is because prior studies indicate that handedness and language lateralization normally covary. Although the majority of left-handers, like right-handers, have speech in the left hemisphere, right-hemisphere and bilateral speech representation is more frequent in left handers ( Milner; Rossi; Rasmussen; Segalowitz; McKeever and McCormick). Piazza (1980) also reported that left-handers demonstrated weaker language lateralization than right-handers. However, if prenatal exposure to DES increases language lateralization and decreases right hand preferences, this normal relationship could be disrupted in DES-exposed women. Finally, we investigated possible relationships between the timing and duration of DES exposure and outcomes in terms of language lateralization and hand preferences.
2. Method
2.1. Subjects.
Subjects for this study also participated in a study of cognitive development following prenatal exposure to DES (Hines and Sandberg, 1996). For both studies, DES-exposed participants were identified from two sources. The first source was files of a co-operating obstetrician/gynecologist in northern California (n=39) who had assembled files for a study of cancer risks associated with prenatal DES exposure. For that study, the timing of DES exposure had been verified from medical records. The second source was the DES-adenosis (DESAD) project (n=3), a project funded by the National Cancer Institute to identify DES-exposed women primarily by review of prenatal medical records. To recruit the first group, we sent letters describing the study to 238 women whose records indicated prenatal DES exposure and we received 102 replies. Nineteen (18%) indicated they did not wish to participate, and six of these 19 gave no reason. The other 13 indicated they lived too far away (n=6), they had no sisters (n=3), the tests were too long (n=2), they were too busy (n=1), or they were having a baby (n=1). Letters were returned as undeliverable in 76 cases and in 60 cases there was no response. Of the 83 positive replies we were able to test 39 women. Others were not tested because they lived too far away or because it was difficult to schedule a time for the test procedures. The DESAD participants were recruited with the aid of the DESAD project physicians. They sent letters to DESAD sister pairs (in which one sister had been exposed to DES and one had not) who were residing in southern California. Interested women then contacted us to participate in the study. The 39 DES-exposed women recruited through physician files from northern California had 24 unexposed sisters who also participated in the study. The three women recruited through the DESAD project had two unexposed sisters who participated. Unexposed sisters were used as the control group because they provide a partial control for genetic constitution and socioeconomic status. Two of the DES-exposed women and one of the unexposed women who were initially recruited for the study of cognitive development did not complete the measures of hand preferences, leaving a sample of 40 DES-exposed women and 25 sisters. Six women, four DES-exposed and two unexposed, did not complete the dichotic listening measure, leaving a sample of 38 DES-exposed women and 24 unexposed women for that portion of the study. Within the 23 family groups in the study, 11 of the DES-exposed women were younger than the unexposed sisters and 12 were older. Thus, DES had not been prescribed systematically for earlier (or later) pregnancies.
The subjects ranged in age from 18 to 43 years (M=30.2, SD=5.41). DES-exposed women (M=30.8, SD=4.8) did not differ in age from unexposed women (M=29.3, SD=6.3). Onset of DES exposure ranged from week 4 to week 17 of gestation (M=9.4, SD=3.5) and the end of exposure ranged from week 14 to week 42 of gestation (M=32.6, SD=6.5). Exposure duration ranged from 4 to 35 weeks (M=23.3, SD=6.2). Dosage information was not available consistently and so was not analyzed. One of the DES-exposed participants had been part of a double-blind, placebo-controlled study of the efficacy of DES for pregnancy maintenance. The remaining women were exposed to DES non-experimentally, typically as a treatment for existing or anticipated threats to the pregnancy (e.g. a history of miscarriage, or bleeding during the pregnancy), or as a prophylactic measure during a normal pregnancy.
Subjects were screened for self-reported hearing problems. The adequacy and comparability of hearing in both ears also was verified by determining ascending and descending thresholds at 250, 500, 1000, 2000, 4000, and 8000 Hz. All subjects had hearing thresholds within the normal range in both ears. In those cases for which right- and left-ear thresholds were not identical, they were within 15 dB for each of the six frequencies.
2.2. Materials and procedure
2.2.1. Dichotic listening
The measure of language lateralization was composed of 120 presentations of pairs of consonant–vowel, nonsense syllables (Berlin et al., 1973). The stimuli were the voiced stop consonants b, d, and g and the unvoiced stop consonants p, t, and k, each followed by the vowel A. Each presentation included two of six possible syllables (ba, da, ga, pa, ta, ka); in each presentation, the two syllables were presented simultaneously, one to each ear. Each syllable was presented to each ear an equal number of times and was paired with each other syllable an equal number of times. Initial headphone position was assigned randomly and subjects reversed their headphones after the first 60 presentations.
Subjects were instructed to attend to both ears and to record both sounds heard. To compute an index of ear advantage, a count was made of the number of times that the subject correctly identified the stimulus presented to each ear. Both responses were considered.
Because information from the right ear has preferential access to the left hemisphere and information from the left ear has preferential access to the right hemisphere, language lateralization is reflected in the difference between scores on items presented to the right and left ears. Traditionally, the raw difference score has been adjusted in various ways to compensate for overall performance. There is no general consensus that one measure is preferred over others (Kuhn; Birkett; Zaidel; Hellige and Springer), and so we calculated three indices:
1. percent right correct−percent left correct (PRC−PLC);
2. an index of ear advantage computed according to the formula (R−L)/(R+L)×100 (Studdert-Kennedy and Shankweiler, 1970);
3. the ‘phi’ coefficient (R−L)/((R+L)(2T−(R+L))1/2) (Kuhn, 1973).
For all three indices, positive scores reflected a right ear (left hemisphere) advantage whereas negative scores reflected a left ear (right hemisphere) advantage.
2.2.2. Handedness
The Edinburg–Crovitz Handedness Inventory (Crovitz and Oldfield) included 18 items that could be performed with the left or right hand. Subjects responded for each activity on a nine-point scale that ranged from left always to right always, with additional anchor points at left mostly, and right mostly. The possible range of scores was 18 (all activities always done with the left hand) to 162 (all activities always done with the right hand). Subjects also completed a brief questionnaire that included information on being forced to change hands.
3. Results
The hypothesis that DES exposure was related to a more masculine pattern of handedness and cerebral lateralization was tested using several different statistical procedures, including Chi-square, Fisher's Exact test, t-tests and correlation coefficients. All statistical tests, including background analyses, were two-tailed except where specifically noted. For t-tests, we report effect size indices along with other statistics when group differences are not statistically significant. The effect size index (d) is the difference in means for the two groups divided by the standard deviation. It provides a standardized measure of the magnitude of group differences that can be compared across samples of different size (Cohen, 1988).
3.1. Hand preferences
Eight women (seven DES-exposed (17.5%), one unexposed (4%)) reported they were left-handed when writing, whereas 57 women (33 DES-exposed (82.5%), 24 unexposed (96%)) reported they were right-handed when writing. Two DES-exposed women (5%) reported they were forced to change from writing left-handed to right-handed when they were children; none of the unexposed women (0%) reported being forced to change. Handedness for writing differed significantly for the DES-exposed versus unexposed women (p=0.015) using Fisher's exact test. Scores on the hand preference inventory ranged from 34 to 162 (M=130.70±40.27 SD) for the DES-exposed women and from 54 to 162 (M=141.40±20.99 SD) for the unexposed women (see Fig. 1). An independent-samples t-test indicated that the handedness scores for the two groups did not differ significantly, t(61)=−1.40, p=0.17, d=0.33, using separate variance estimates. A separate set of analyses was conducted of only the DES-exposed women whose unexposed sisters participated. Scores on the hand preference inventory for this subsample of DES-exposed women ranged from 35 to 159 (M=128.91±39.12 SD) and from 54 to 162 (M=141.40±20.99 SD) for their matched unexposed sisters. The results of a dependent-samples t-test resembled those for the independent samples test. There was only a small correlation between handedness scores for sisters (r=0.11, ns) and the two groups did not differ significantly in the paired analysis, t(21)=−1.33, p=0.20, d=0.42.
(8K)
Fig. 1. Scattergrams indicating scores on the handedness inventory for DES-exposed women for whom data on the timing of DES exposure were available (left) and unexposed women (right). The left hand panel also indicates the gestational week when DES treatment began. Earlier onset of treatment is related to left hand preferences and, within the DES-exposed group, only those women exposed to DES before week 9 show strong left hand preferences.
This standard method of analyzing data from hand preference questionnaires can confound direction and degree of preference. Therefore, we conducted two additional analyses. To study degree of handedness alone, we compared the absolute value of normalized scores on the inventory for the two groups of women. To evaluate direction alone, we conducted a non-parametric analysis of the direction of the standardized scores. The first test indicated a greater degree of lateralization in DES-exposed women compared to unexposed controls (t(61)=2.01, p<0.05, using separate variance estimates). The second suggested no difference in the direction of lateralization (2=0.59, df(1), p=0.44).
3.2. Language lateralization
Means and standard deviations for variables derived from the dichotic listening task are presented in Table 1. Independent-samples t-tests indicated that DES-exposed women and unexposed women did not differ on either the ear scores or asymmetry indices. Both groups of women, however, did display the expected right-ear (left hemisphere) advantage: for the DES-exposed women, t(37)=4.27, p=0.000, and for the unexposed women, t(23)=3.11, p=0.005, for right-ear versus left-ear scores. Analyses were also conducted on the subsample of DES-exposed women and their matched unexposed sisters. As can be seen in Table 2, these two groups did not differ from each other on the ear scores or asymmetry indices, although there were moderate correlations between sisters on all variables (r=0.35 to 0.43. All ns, except r=0.43, p=0.05).
Table 1. Right- and left-ear scores, asymmetry indices, and effect sizes in DES-exposed and unexposed women
Table 2. Right- and left-ear scores, asymmetry indices, and effect sizes in DES-exposed and their matched unexposed sisters
As was the case for handedness data, the standard methods for analyzing dichotic listening data confound degree and direction of asymmetry. We therefore analyzed for differences in degree of asymmetry by comparing the absolute value of normalized lateralization indices, and for differences in direction by conducting a non-parametric analysis of the direction of the standardized asymmetry indices. Neither test revealed significant differences between DES-exposed women and unexposed controls. For degree of asymmetry (t(60)=0.58 for (R−L)/(R+L)×100 and t(60)=0.52 for phi, both ns) and for differences in direction (2=0.18, df(1), ns).
Correlations among the lateralization indices and between these indices and scores on the handedness inventory are presented in Table 3. As expected, the lateralization indices correlated highly with one another for both the DES-exposed and unexposed women. The correlations among different lateralization indices are similar in magnitude and direction to those reported in previous studies of normals (Hellige
and Hines).
Table 3. Correlations among lateralization indices and scores on the handedness inventory in DES-exposed and unexposed women
3.3. Language lateralization related to hand preferences
Based on prior research on normals, a positive correlation between right-handedness and language lateralization would be expected (Bryden, 1988). This expected relationship was seen for unexposed women; those who were more right-handed displayed stronger right-ear (left hemisphere) advantages (r(24)=0.43, p<0.05). Contrary to this usual situation, however, a positive relationship between right-hand preference and language lateralization was not seen in the DES-exposed group (r(38)=0.04, ns) (see Table 3).
3.4. Timing and duration of exposure
The timing and duration of DES exposure were also examined in relationship to handedness and language lateralization. As can be seen in Table 4, termination of DES exposure later in gestation or treatment for a longer period during gestation was associated with lower left ear (right hemisphere) scores on the dichotic measure. Only women exposed after week 30 of gestation showed left ear (right hemisphere) scores below 50%. On the other hand, the timing of DES exposure was not related to the right ear (left hemisphere) score. Also, none of the asymmetry indices correlated significantly with any of the three DES exposure variables (onset of exposure, termination of exposure, or duration of exposure). In regard to hand preferences, earlier onset and termination of exposure was associated with reduced right-hand preference (see Table 4). In addition, all of the women with very low scores on the handedness inventory had been exposed to DES before week 9 of gestation (see Fig. 1).
Table 4. Correlations between variables derived from the verbal dichotic listening task and the timing of DES exposure
4. Discussion
The purpose of this research was threefold: (a) to examine the effects of prenatal DES exposure on handedness and language lateralization, (b) to compare the relationship between hand preferences and language lateralization in DES-exposed and unexposed women, and (c) to examine the effects of timing and duration of DES exposure on language lateralization and handedness. Contrary to our hypotheses, DES-exposed and unexposed women did not differ significantly in regard to language lateralization. However, there was evidence that prenatal exposure to DES influenced hand preferences. It increased the degree of hand preference and produced more individuals who were left-handed for writing. In addition, DES exposure appeared to disrupt the normal relationship between hand preferences and language lateralization. Finally, the timing and duration of DES exposure related to right hemisphere scores on the dichotic listening task and the timing of exposure related to hand preferences.
The results indicating more left handedness for writing in DES-exposed women resemble results reported previously (Schachter and Scheirs). One interpretation of these findings is that DES has a masculinizing or defeminizing effect on brain development in humans similar to that seen in other species. However, DES was often prescribed because of pregnancy complications. Hence, it has been suggested that pregnancy complications could cause a shift in hand preferences ( Scheirs and Vingerhoets, 1995), a suggestion based on evidence that early injury to the left cerebral hemisphere is associated with left handedness (so-called ‘pathological’ left-handedness) ( Satz and Coren). We think hormones, rather than pregnancy complications, are the more likely explanation of the association between DES and hand preferences for several reasons. First, there is no evidence that the kind of pregnancy problems typically associated with DES exposure (e.g. bleeding during pregnancy) cause neural injury. Second, in our study, the group showing the most dramatic shift to a left hand preference began DES exposure very early in pregnancy (prior to week 9). This early treatment is more likely to have occurred because of prior miscarriages or prophylactic treatment rather than because of problems during the current pregnancy. Third, exposure to high levels of androgen during pregnancy, because of the genetic disorder, CAH has also been associated with a shift toward left-handedness ( Nass et al., 1987). Because CAH does not involve pregnancy complications, these findings suggest that hormones are more likely to be the causal factor. Fourth, a hormonal influence on hand preferences is hypothesized based on a large body of data from experimental studies of laboratory animals. There is no similar body of data from which to predict a similar outcome following pregnancy complications. Nevertheless, additional research assessing the impact of pregnancy complications on hand preferences would help resolve this issue.
Our data also may provide information regarding the critical period for hormonal influences on hand preferences. In other species, the general critical period for gonadal hormonal influences on sexual differentiation corresponds to the period when testosterone levels are higher in developing males than females. However, within this period, different characteristics are influenced at somewhat different times. In the rat, for instance, the critical period for hormonal influences on female sexual behavior occurs earlier than that for male sexual behavior (Christensen and Gorski, 1978). Similarly, in rhesus macaques, the critical period for hormonal influences on rough-and-tumble play differs from that for hormonal influences on mounting ( Goy et al., 1988). In the present study, the DES-exposed women who showed strong left hand preferences were all exposed to hormone prior to week 9 of gestation. Thus, the critical period for hormonal influences on this characteristic may occur relatively early in gestation.
Previously, DES-exposed women were found to show a more masculine pattern of performance on a dichotic listening task compared to their unexposed sisters (Hines and Shipley, 1984). Similarly, testosterone levels in second trimester amniotic fluid have been found to relate positively to stronger language lateralization (the more masculine-typical pattern) (Grimshaw et al., 1995). In the current study, DES-exposed women did not differ significantly from their unexposed sisters in dichotic listening performance. A meta-analysis of effect sizes for sex differences in language lateralization suggests that they are small ( Voyer, 1996). If effect sizes in the present study (d=0.17 to 0.19) are typical of the size of hormonal effects on language lateralization, samples of several hundreds of subjects would be needed to provide conventional power (80%) to detect group differences (Cohen, 1988).
Handedness was related to language lateralization among unexposed women but not among DES-exposed women. Thus, the normal relationship between handedness and language lateralization appears to have been disrupted by DES exposure. Although the exact timing is currently unknown, portions of the brain responsible for motor functions such as handedness appear earlier in gestation than those involved in higher cortical functions, including language (Yakovlev and Rabinowicz). Handedness also has been found to correlate with asymmetries in palm prints and fingerprints ( Cummins; Beltman; Newman; Cummins; Cromwell and Rife) which are formed by gestational week 18. McManus and Bryden (1991) point out that the precise timing of hormonal influences on human behavioral development are unknowable given the present status of embryology. Also, at present, the lineage of specific cortical neurons cannot be followed due to limitations in methodology and knowledge. But, our results suggest that DES terminated later in the pregnancy is associated with lower left ear (right hemisphere) scores whereas stronger left handedness is associated with earlier initiation of DES. These findings suggest that these different human characteristics are sensitive to hormones at different periods of gestation. The critical period for hormonal influences on neural mechanisms involved in hand preferences appears to occur earlier than that involved in hormonal influences on neural mechanisms related to language lateralization. This would be consistent with reported differences in critical periods for different traits in rats as well as in non-human primates ( Dohler; Christensen; Lieberburg; Goy; Weisz and Goy).
Finally, our results are relevant to distinguishing among theoretical perspectives that have been proposed to explain individual differences in cerebral lateralization, as manifested in hand preferences and language lateralization. As noted by Grimshaw et al. (1995) the factors that explain these individual differences remain elusive, but an association with gonadal hormones has been suggested based on three somewhat different theoretical perspectives. The first hypothesizes that prenatal exposure to high levels of hormones (androgens, or estrogens produced from androgens) promotes development of a masculine-typical pattern of lateralization (i.e. increased left handedness and increased language lateralization (Hines and Gorski, 1985). This hypothesis derives from a large body of experimental evidence indicating that administration of androgen or estrogen to developing female animals promotes masculine-typical development of brain regions and behaviors that show sex differences. A second perspective hypothesizes that high levels of these same hormones promotes increased left-handedness and decreased language lateralization by slowing the growth of the left hemisphere or enhancing the growth of the right ( Geschwind and Galaburda, 1987). The third perspective hypothesizes that high levels of hormones lead to increased right handedness and increased language lateralization by promoting pruning of axons in the corpus callosum (Witelson, 1991). The association we observed between prenatal estrogen exposure and increased left handedness, and similar associations reported previously by others ( Nass; Schachter and Scheirs) argue against the third perspective. Because we did not find any association between DES and language lateralization, it is not possible to distinguish between the first two perspectives based on our data alone. However, other studies suggest that prenatal hormone exposure (either to DES or to relatively high levels of androgen), if associated with language lateralization at all, is associated with increased asymmetry ( Hines and Grimshaw). This suggests that the first perspective may be the most consistent with all the available data.
Acknowledgements
This research was supported by National Institutes of Health Grants HD24542 and HD19644. Some of the data were collected as part of a collaborative project with Dr. Sheri Berenbaum. We thank Andre Black, Catherine Lerer, Naomi Lester, Jennifer Lawrence, Anne Maxwell and Chris Verbin for help testing subjects, Katie Johnston for help with data analyses, Drs. Eugene
Sandberg, Kenneth Noller and Leo Lagasse for help recruiting patients to the study and the research participants for their generous contributions of time
and interest.
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Corresponding author at: Department of Psychology, City University, London EC1V 0HB, UK. Tel.: +44-207-477-8351; fax: +44-207
