Environmental endocrine modulators and human health: an assessment of the biological evidence, 1998
Several studies have addressed the potential effects of prenatal DES exposure on sexual behavior in adult human males and females. Due to the inherent complexity of human sexuality, the results of these studies are difficult to interpret; however, they do not appear to corroborate the findings observed in rats following in utero exposure to TCDD. Unfortunately, many of the studies investigating potential DES effects on human sexual behavior do not describe maternal DES dosages. While some subtle effects on sexual behavior of male and female offspring exposed to DES in utero have been observed, limited dose-response data suggest that these are likely associated with high total maternal DES doses and durations of exposure.
Psychosexual behavior was investigated in 62 adult males following in utero exposure to DES (n = 17), DES + natural progesterone (n = 22), natural progesterone only (n = 10), or synthetic progesterone (n = 13). DES dosages ranged from 50 to 14,000 mg with a mean of 3979 mg; duration of administration was from 0.5 to 29 weeks with a mean of 13.5 weeks. A large number of psychological tests were administered to subjects exposed and unexposed; sexual fantasies and behavior were also assessed. Comparison with matched unexposed men revealed a few subtle differences of unknown importance. Relative to the unexposed men, the DES-exposed group showed higher scores on the feminine scale of a sex role inventory, but also showed a greater interest in sports. With respect to adult sexual orientation, there were no differences between DES-exposed men and unexposed in either homosexual fantasies or behavior.
The relation between prenatal hormone exposure and sexual behavior in both men and women was evaluated in an extensive review of 19 relevant studies. Total mean DES doses in the few studies that reported such data averaged approximately 2500 mg administered for an average (mean) of 14 weeks during pregnancy. Findings from the 19 studies reviewed were classified into eight behavioral categories: play and recreation interests, peer relations, aggression/assertion, interest in marriage and maternalism, gender identity/role and personality, sexual maturation and behavior, cognitive abilities and academic achievement, and athletic ability/physical coordination. Compared with unexposed males, DES-exposed males were significantly less likely to categorize themselves as “likes to fight” (aggression/assertion) and somewhat less likely to report “usually wins fights”, responses that were considered “feminized”. Overall, there was a non significant tendency toward feminization on the aggregate aggression score. In another study of males exposed in utero to DES, in the category of vocational interest, DES-exposed males, relative to unexposed males, reported an increased interest in social services and in writing (although the latter was non significant). Although these traits were characterized as “feminized”, DES-exposed males were (non significantly) more likely relative to unexposed males, to have an increased number of male friends and elevated interest in sports and in TV shows with aggressive themes (“masculinized” characteristics). With respect to sexual orientation there were no differences between DES exposed and unexposed men. For women exposed in utero to DES, one initial study suggested a tendency toward bisexual or homosexual ratings on a number of measurement scales. However, in a larger follow-up study, DES-exposed women were not different from unexposed women on the same measurement tests employed in the initial study. In their discussion of the potential effects of prenatal hormone exposure on sexual behavior, Reinisch et al. noted that the behavioral repertoires of males and females overlap to a large extent; thus, no particular behavior is exclusively male or female. In addition, individuals can exhibit high frequencies of both masculine and feminine behavior (androgynous), low levels of both kinds of behavior (undifferentiated), or high levels of one type of behavior and low levels of the other (masculine or feminine).
Another extensive review of studies addressing gender-related behavior in women exposed in utero to DES concluded that there was no clear-cut difference between unexposed and DES-exposed women. In all seven studies reviewed there were more behavior trait similarities between DES-exposed and unexposed women than differences. This finding was considered striking by the investigators considering that the bias of their studies was that there would be differences between groups because the experimental protocols employed were specifically designed to detect differences and not similarities. Consideration of pre- and postnatal influences, including social, economic, and environmental factors suggests that unexplained individual variation appears more important than in utero exposure to DES.
A recent, extensive study investigated the effects of prenatal exposure to DES and sexual orientation in three groups of DES-exposed women (DES1, DES2, and DES3).The DES1 and DES2 groups had a high prevalence of DES-related vaginal or cervical abnormalities (90% and 97%, respectively).
In 13 of the 30 DES1 women with sufficient exposure information, total maternal DES dosage ranged from 210 to 10,475 mg with a median of 1800 mg. In 5 of 30 DES2 women with sufficient data, total maternal DES dosage ranged from 252 to 19,800 with a median of 3600 mg. While the precise maternal dosages in the DES3 group were unknown, vaginal epithelial changes associated with DES were present in 50% of the woman, and the available records suggested that total maternal DES dosages were lower than the recommended regimens of the time.
This study demonstrated that more DES-exposed than unexposed women were rated as bisexual or homosexual. Although the DES-exposed women were significantly more likely than the unexposed women to report bisexuality and homosexuality, the actual differences between the two groups were modest; a predominantly homosexual orientation was reported as lifelong by only 4 of 96 DES-exposed women, while only six women reported current homosexual orientation. Most of the differences between DES-exposed and unexposed women were limited to degrees of bisexuality, and for many, bisexuality was confined to imagery and not behaviorally expressed. Of interest is the fact that most of the differences were observed when the DES1 and DES2 groups were compared with unexposed women; only one difference was noted when the DES3 group was compared with unexposed women. While there were significant overall differences between DES-exposed and unexposed women, the relative absence of effects for the DES3 group suggests a dose-related effect on sexual orientation. It is also worth noting that, even though this was a study that focused predominantly on women, potential effects in men in the same cohort were also evaluated with the same set of questions. In men, there was no apparent relation between in utero DES exposure and alterations in sexual behavior.
- Environmental endocrine modulators and human health: an assessment of the biological evidence, Critical reviews in toxicology, NCBI PubMed, PMID: 9557209, 1998.