This was the first study to use OS and SS twin pairs to explore the masculinizing effects of prenatal testosterone exposure on the development of DE. Overall, our data were consistent with a “free martin” effect (i.e., masculinized behavior due to in utero
exposure to testosterone41, 42
) and provide evidence that increased levels of prenatal testosterone exposure may masculinize DE. Specifically, a linear trend in mean levels of DE was observed, where SS female twins showed the least masculinized (i.e., highest) DE, followed by OS female twins, OS male twins, and SS male twins. Although several factors likely influence sex differences in eating pathology, our findings highlight that biological factors likely play a role in this process. Specifically, masculinization of the CNS by prenatal testosterone may decrease risk for DE in males versus females.
The masculinization of DE does not appear to be completely explained by levels of anxiety or by socialization effects. While anxiety partially mediated the association between prenatal testosterone exposure and disordered eating, supporting some shared transmission43
, primary conclusions remained unchanged even when controlling for levels of anxiety. Further, OS female twins had lower levels of DE than non-twin females who were raised with a brother. Admittedly, there may be something unique about having a brother the exact same age
that accounts for the significantly lower levels of DE in OS female twins compared to non-twin females. Although plausible, it is unclear how having a same-age brother (rather than a brother who is close in age, but not the same age) could fully account for the lower (i.e., masculinized) levels of DE in OS female twins compared to non-twin females. Moreover, findings remained unchanged even after controlling for age differences between non-twin females and their brothers.
The masculinized pattern of DE observed in our OS female twins parallels previous findings in animals (e.g., intrauterine position effects; see Ryan & Vandenbergh10
) and humans (e.g., girls with congenital adrenal hyperplasia44, 45
) that support the masculinization of sexually dimorphic traits by prenatal testosterone exposure. If prenatal testosterone exposure does masculinize DE, as it does with several other sexually dimorphic traits, it is important to understand the mechanisms underlying the effects.
There are at least two ways in which prenatal testosterone exposure may influence predispositions to DE: 1) testosterone may organize anatomical and functional differences between the sexes in terms of key DE characteristics (e.g., food intake, satiety) that increase risk for eating disorders, and/or 2) testosterone may have organizational effects on sensitivity to circulating ovarian hormones later in life, which then differentially activates predispositions to DE. While definitive data are not available to support either of these specific mechanisms, speculative hypotheses can be proposed on the basis of preliminary animal and human studies.
Extant animal research indicates that early testosterone exposure organizes food intake and accounts for well-documented sex differences in feeding and body weight (i.e., male rats eat and weigh more than females). These effects in animal research are isolated to feeding behaviors (i.e., increased and decreased food intake) rather than cognitive components (e.g., weight preoccupation, body dissatisfaction) of eating disorders. Nonetheless, biological mechanisms for sex differences in DE may map more directly onto these core feeding behaviors than the cognitive features of eating disorders. If so, the masculinization of DE in males and OS female twins may partially occur through the organization of brain structures or functions that influence food intake. Structural brain differences between males and females are region-specific46
, with significant sexual dimorphisms in brain areas (e.g., anterior cingulate, amygdala, orbital frontal cortex, hypothalamus, insula46
) involved in food intake and body weight (for review, see Kaye et al.47
). These areas are also marked by high levels of sex steroid receptors during critical periods of early brain development , suggesting that their structural differentiation may be influenced by prenatal and perinatal testosterone exposure46, 48, 49
Sex differences in DE may also be due to sex differences in brain function. Few studies have examined this possibility, although two studies observed sex differences in brain responses to hunger50
and satiety50, 51
in several brain regions (e.g., dorsolateral prefrontal cortex). Clearly, additional studies examining sex differences in brain function are needed, but initial results are promising in suggesting that males and females may differ in food-related brain processes that are important for eating disorders.
Prenatal testosterone exposure may also affect DE by decreasing CNS sensitivity to gonadal hormones in adulthood. Prenatal testosterone exposure in female rodents decreases their sensitivity to ovarian hormones later in life16
. These effects may be particularly important for feeding behaviors, since ovarian hormones directly influence food intake and DE in adult women. Specifically, decreased levels of estrogen, and increased levels of progesterone, are associated with increased food intake and binge eating in clinical52
samples of adult women. Indeed, changes in ovarian hormones appear to drive menstrual cycle changes in binge eating52, 53
. Therefore, lower rates of DE in adult OS female twins may be due to increased prenatal testosterone exposure which decreases sensitivity to the activating effects of ovarian hormones on DE. While all of these hypotheses are speculative, they are worthy of additional investigation as they highlight potential pathways between the masculinizing effects of testosterone and correspondingly lower levels of DE symptoms.
Despite the strengths of this study, several limitations must be noted. First, participants were not clinically diagnosed with an eating disorder. Therefore, it is unclear how well the study's findings generalize to clinical populations. Although DE symptoms lie on a continuum54-57
, show prospective associations with EDs58
, and are considered precursive58
, it will be important for future studies to replicate our results with clinical populations.
Second, the extent to which our participants are representative of the general population is somewhat unclear. Our twin samples appear to be roughly representative of the surrounding population based on racial categories. Non-twin female participants (who were college students) were comparable to OS female twins in terms of age and socioeconomic status, and roughly comparable in ethnicity. Nonetheless, future studies should use larger, population-based samples to replicate our results and ensure generalizability of the findings.
Third, we were unable to directly assess levels of prenatal testosterone exposure. The most empirically supported and accepted view (see Collaer & Hines6
) is that prenatal testosterone and its metabolites (i.e., dihydrotestoterone and 17 ß-estradiol) masculinize the brain and sexually dimorphic behavior in males and females6
; thus, prenatal testosterone exposure seems very likely to play some role in our observed effects. Evidence for the feminizing effects of prenatal estrogen in males
is conflicting, with most studies showing no significant effects6
. Nonetheless, we did not directly measure prenatal gonadal hormone exposure, and thus, cannot definitively rule-out possible feminization (or demasculinization) of DE by prenatal estrogen exposure in OS male twins. Future research therefore is needed to confirm that the masculinization effects are due to prenatal testosterone exposure.
Fourth, information on placenta type (i.e., monochorionic or dichorionic) was not available for MSUTR participants, but this information would be important to examine in future twin studies of prenatal effects. Finally, future research should also investigate differences in brain processes related to feeding (e.g., hunger, food intake, satiety) and differential sensitivity to ovarian hormones in OS versus SS twins. These investigations will likely provide new insight into how prenatal hormone exposure alters biological mechanisms, and ultimately, influences predispositions to DE in males and females.
In conclusion, findings from this study contribute to the literature on sex differences in eating disorder prevalence. Sociocultural factors (e.g., pressure for thinness in women) have typically been used to explain the sex difference in eating disorder prevalence. However, our results suggest that the masculinizing effects of prenatal testosterone, characteristic of male development, may also play a significant role.