Vaginal embryogenesis, estrogens, and adenosis

The recent outbreak of vaginal adenocarcinoma and the associated genital tract anomalies in women with histories of prenatal exposure to diethylstilbestrol (DES) has generated interest in vaginal embryogenesis and the influence of hormones on the developing genital tract. In this report the embryology of the vagina and the role of sex hormones in normal and abnormal sex duct development are presented and discussed in relation to the DES-induced anomalies. Although the teratogenic activity of DES in humans has been confirmed, the available evidence suggests that the clear cell carcinomas are initiated by endogenous estrogens and not the prenatally administered DES.     

Environmental endocrine modulators and human health: an assessment of the biological evidence

Recently, a great deal of attention and interest has been directed toward the hypothesis that exposure, particularly in utero exposure, to certain environmental chemicals might be capable of causing a spectrum of adverse effects as a result of endocrine modulation. In particular, the hypothesis has focused on the idea that certain organochlorine and other compounds acting as weak estrogens have the capability, either alone or in combination, to produce a variety of adverse effects, including breast, testicular and prostate cancer, adverse effects on male reproductive tract, endometriosis, fertility problems, alterations of sexual behavior, learning disability or delay, and adverse effects on immune and thyroid function. While hormones are potent modulators of biochemical and physiological function, the implication that exposure to environmental hormones (e.g., xenoestrogens) has this capability is uncertain. While it is reasonable to hypothesize that exposure to estrogen-like compounds, whatever their source, could adversely affect human health, biological plausibility alone is an insufficient basis for concluding that environmental endocrine modulators have adversely affected humans. Diethylstilbestrol (DES) is a potent, synthetic estrogen administered under a variety of dosing protocols to millions of women in the belief (now known to be mistaken) that it would prevent miscarriage. As a result of this use, substantial in utero exposure to large numbers of male and female offspring occurred. Numerous studies have been conducted on the health consequences of in utero DES exposure among the adult offspring of these women. There are also extensive animal data on the effects of DES and there is a high degree of concordance between effects observed in animals and humans. The extensive human data in DES-exposed cohorts provide a useful basis for assessing the biological plausibility that potential adverse effects might occur following in utero exposure to compounds identified as environmental estrogens. The effects observed in both animals and humans following in utero exposure to sufficient doses of DES are consistent with basic principles of dose response as well as the possibility of maternal dose levels below which potential non-cancer effects may not occur. Significant differences in estrogenic potency between DES and chemicals identified to date as environmental estrogens, as well as an even larger number of naturally occurring dietary phytoestrogens, must be taken into account when inferring potential effects from in utero exposure to any of these substances. The antiestrogenic properties of many of these same exogenous compounds might also diminish net estrogenic effects. Based on the extensive data on DES-exposed cohorts, it appears unlikely that in utero exposure to usual levels of environmental estrogenic substances, from whatever source, would be sufficient to produce many of the effects (i.e., endometriosis, adverse effects on the male reproductive tract, male and female fertility problems, alterations of sexual behavior, learning problems, immune system effects or thyroid effects) hypothesized as potentially resulting from exposure to chemicals identified to date as environmental estrogens.     

Sister chromatid exchanges and cell division delays induced by diethylstilbestrol, estradiol, and estriol in human lymphocytes

It had been found previously that exposure of human lymphocytes in vitro to diethylstilbestrol (DES), a synthetic estrogen and known human carcinogen, led to the induction of sister chromatid exchanges. More sister chromatid exchanges were induced in cells from pregnant women than from men. To see if the effects of DES could be induced by other estrogens, lymphocytes from a man and a pregnant woman were treated in vitro with the natural estrogens estradiol and estriol. These did not induce sister chromatid exchanges. To see if the presence of exogenous female hormones might be responsible for the increase in DES-induced sister chromatid exchanges seen in cells from pregnant women, lymphocytes from a man and a pregnant woman were also treated in vitro simultaneously with DES, estradiol, estriol, and progesterone. Treatments with these exogenous hormones did not alter the number of DES-induced sister chromatid exchanges. Our previous studies showed that DES also inhibits in vitro proliferation of lymphocytes. The results reported here show that estradiol also strongly inhibits this proliferation but that estriol is only a weak inhibitor. The cause of delayed cell proliferation induced by DES and estradiol was 2-fold: some of the cells were delayed in phytohemagglutinin-mediated blast cell transformation but, additionally, most cells had a prolonged cell cycle because of an extended G2 phase. These studies also showed that DES, but not estradiol or estriol, induced a low level of polyploidy in human lymphocytes.     

Sexual orientation and the second to fourth finger length ratio: A meta-analysis in men and women.

The ratio of the lengths of the second and fourth fingers (2D:4D) may serve as a marker for prenatal androgen signaling. Because people are typically unaware of their 2D:4D, its use allows possible effects of early sex hormone regimes and socialization to be disentangled. We conducted a meta-analysis on relationships between 2D:4D and sexual orientation in men and women in 18 independent samples of men and 16 independent samples of women. Collectively, these samples comprised 1,618 heterosexual men, 1,693 heterosexual women, 1,503 gay men, and 1,014 lesbians. In addition to identifying the normative heterosexual sex difference in 2D:4D for both hands, we found that heterosexual women had higher (more feminine) left- and right-hand 2D:4D than did lesbians, but we found no difference between heterosexual and gay men. Moderator analyses suggested that ethnicity explained some between-studies variation in men. These results add to a literature suggesting that early sex hormone signaling affects sexual orientation in women, and highlight the need for further research exploring the relationships among 2D:4D, sexual orientation, and ethnicity in men. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Sexual orientation and handedness in men and women: A meta-analysis.

Recent findings suggest that sexual orientation has an early neurodevelopmental basis. Handedness, a behavioral marker of early neurodevelopment, has been associated with sexual orientation in some studies but not in others. The authors conducted a meta-analysis of 20 studies that compared the rates of non-right-handedness in 6,987 homosexual (6,182 men and 805 women) and 16,423 heterosexual (14,808 men and 1,615 women) participants. Homosexual participants had 39% greater odds of being non-right-handed. The corresponding values for homosexual men (20 contrasts) and women (9 contrasts) were 34% and 91%, respectively. The results support the notion that sexual orientation in some men and women has an early neurodevelopmental basis, but the factors responsible for the handedness-sexual orientation association require elucidation. The authors discuss 3 possibilities: cerebral laterality and prenatal exposure to sex hormones, maternal immunological reactions to the fetus, and developmental instability. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Sexual orientation and human development: An overview.

What part does sexual orientation play in human development? Despite the apparent significance of sexual identities in shaping lives, developmental research and theory on sexual orientation have, until recently, been relatively limited. Today, as lesbian women, gay men, and bisexual people become more open about sexual identities, psychological knowledge about the ways in which developmental processes affect and in turn are affected by sexual orientation is growing rapidly. Groundbreaking research is being conducted, from a variety of perspectives, by investigators from many different traditions. Research on sexual orientation and human development has the potential to make important contributions both to the theory and to the practice of developmental psychology. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Psychosexual development of women with congenital adrenal hyperplasia

Women with congenital adrenal hyperplasia (CAH) (N = 31) and their unaffected sisters or female cousins (N = 15) participated in a study of psychosexual development. All participants were > or = 18 years of age (mean age, 25 years; range, 18-40). Comparisons were also made between the CAH women with the salt-wasting (SW) form of the disorder and those with simple virilization (SV). A psychosexual assessment protocol examined six variables: (1) sex assignment at birth (probands only); (2) recalled sex-typed behavior during childhood; (3) gender identity and gender role identification in adulthood; (4) relationship status; (5) sexual orientation in fantasy; and (6) sexual orientation in behavior. Salt-wasting status and sex assignment at birth were also ascertained for the CAH women who either refused to participate in the study (N = 10) or could not be traced (N = 13). Compared to the controls, the women with CAH recalled more cross-gender role behavior and less comfort with their sense of "femininity" during childhood. The two groups did not differ in degree of gender dysphoria in adulthood, although the probands showed more cross-gender role identification. Three of the nonparticipant probands were living, as adults, in the male social role (2 reared from birth as boys and 1 who changed from the female to the male social role during adolescence). The CAH women and the controls did not differ in relationship status (married/cohabiting vs. single). The CAH women had lower rates of exclusive heterosexual fantasy and fewer sexual experiences with men than the controls; however, the CAH women did not have more sexual experiences with women than the controls. Comparisons between the SW and SV revealed several differences: the SW were less likely to be assigned to the female sex at birth, recalled more cross-gender role behavior during childhood, were less likely to be married or cohabiting, and had lower rates of sexual experiences with men. The results were discussed in relation to the effects of prenatal androgens on psychosexual differentiation.     

The effect of an original analog of the C-terminal fragment of vasopressin on the behavior of white rats

Ethinylestradiol (EE) has evident paradoxical effects on cancer risk for human breast and hepatic cancer which parallel in some respects its effects on estrogen-induced neoplasms in the hamster kidney and liver. EE has been shown to be only weakly carcinogenic in the hamster kidney, but the most potent carcinogenic estrogen in the hamster liver following prolonged treatment. Unexpectedly, when EE and potent carcinogenic estrogens, such as diethylstilbestrol (DES), 17beta-estradiol (E2) and Moxestrol (MOX), are administered concomitantly, estrogen-induced carcinogenesis in the kidney is completely prevented. In studying this novel finding, we found that, compared with E2 exposure alone, EE at 0.05 and 1.0 nM significantly (P < 0.001) inhibited the rise in proliferation of cultured primary hamster proximal renal tubular (PRT) cells in the presence of E2 (1.0 nM). Consistent with these findings, combined EE + DES treatment for 5.0 months reduced hamster kidney c-myc, c-fos and c-jun RNA expression to 43, 37 and 52%, respectively, compared with levels observed after DES treatment alone. Interestingly, TAM + DES treatment for the same period also resulted in the same low level of RNA expression of these proto-oncogenes. c-MYC, c-FOS and c-JUN protein products were comparably reduced after either EE + DES or TAM + DES treatment. It appears that c-fos expression and c-FOS protein levels in the hamster kidney were more responsive to TAM inhibition. These data demonstrate that EE possesses unique anti-tumorigenic properties in vivo in the hamster kidney. Additionally, the observed anti-estrogen-like effect of EE on cell proliferation of cultured PRT cells suggests that EE may interfere critically with estrogen receptor (ER)-mediated mitogenic pathway(s) affected by potent carcinogenic estrogens, thus preventing subsequent gene dysregulation and, hence, tumor development. Based on competition studies, the differential binding of EE to hamster kidney ER relative to that of the other estrogens (E2, DES, MOX) appears not to contribute to the prevention of estrogen carcinogenesis at this organ site by EE.     

Gender and sexual orientation differences in sexual response to sexual activities versus gender of actors in sexual films.

In this study, the authors investigated the hypothesis that women's sexual orientation and sexual responses in the laboratory correlate less highly than do men's because women respond primarily to the sexual activities performed by actors, whereas men respond primarily to the gender of the actors. The participants were 20 homosexual women, 27 heterosexual women, 17 homosexual men, and 27 heterosexual men. The videotaped stimuli included men and women engaging in same-sex intercourse, solitary masturbation, or nude exercise (no sexual activity); human male-female copulation; and animal (bonobo chimpanzee or Pan paniscus) copulation. Genital and subjective sexual arousal were continuously recorded. The genital responses of both sexes were weakest to nude exercise and strongest to intercourse. As predicted, however, actor gender was more important for men than for women, and the level of sexual activity was more important for women than for men. Consistent with this result, women responded genitally to bonobo copulation, whereas men did not. An unexpected result was that homosexual women responded more to nude female targets exercising and masturbating than to nude male targets, whereas heterosexual women responded about the same to both sexes at each activity level. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Measuring attitudes regarding bisexuality in lesbian, gay male, and heterosexual populations.

Five studies on the development and validation of the Attitudes Regarding Bisexuality Scale (ARBS) were conducted. Factor analysis of an initial pool of 80 items yielded 2 factors assessing the degree to which bisexuality is viewed as a tolerable, moral sexual orientation (Tolerance) and a legitimate, stable sexual orientation (Stability). Three forms of the ARBS were created: a form to assess attitudes about female and male bisexuality (i.e., ARBS-FM) and forms to assess attitudes about female bisexuality (i.e, ARBS-F) and male bisexuality (ARBS-M). These forms evidenced moderate-to-high internal consistency reliability in both lesbian and gay samples and heterosexual samples. In heterosexual women and men, subscale were most strongly related to attitudes toward lesbians and gay men; frequency of religious attendance; political ideology; and prior contact with lesbian, gay, and bisexual people. In lesbians and gay men, subscales correlated with prior experiences with bisexual people, desired contact with bisexual people, contact with homosexual people, and sexual orientation identity. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Phytoestrogens: potential endocrine disruptors in males

Exposure to diethylstilbestrol (DES) induces persistent structural and functional alterations in the developing reproductive tract of males. It is possible that xenoestrogens other than DES alter sexual differentiation in males and account for the increasing incidence of developmental disorders of the reproductive tract in men and wild animals. Phytoestrogens (coumestans, isoflavonoids, flavonoids, and lignans) present in numerous edible plants are quantitatively the most important environmental estrogens when their hormonal potency is assessed in vitro. They exert their estrogenic activity by interacting with estrogen receptors (ERs) in vitro. They may also act as antiestrogens by competing for the binding sites of estrogen receptors or the active site of the estrogen biosynthesizing and metabolizing enzymes, such as aromatase and estrogen-specific 17 beta-hydroxysteroid oxidoreductase (type 1). In theory, phytoestrogens and structurally related compounds could harm the reproductive health of males also by acting as antiestrogens. There are very little data on effects of phytoestrogens in males. Estrogenic effects in wildlife have been described but the evidence for the role of phytoestrogens is indirect and seen under conditions of excessive exposure. In doses comparable to the daily intake from soybased feed, isoflavonoids such as genistein were estrogen agonists in the prostate of adult laboratory rodents. When given neonatally, no persistent effects were observed. In contrast, the central nervous system (CNS)-gonadal axis and the male sexual behavior of the rat appear to be sensitive to phytoestrogens during development. The changes were similar but not identical to those seen after neonatal treatment with DES, but higher doses of phytoestrogens were needed.     

Present versus future time perspective and HIV risk among heterosexual college students.

Because safer sex behaviors require planning and forethought and their primary motivations lie in the future, the hypothesis that behaviors that might reduce exposure to HIV would positively correlate with future time orientation, whereas risky behaviors would correlate with present time orientation, was tested in a survey of 188 heterosexual college students. As expected, those high in future time orientation were less likely to be sexually experienced and had fewer sexual partners. In contrast, present time orientation positively related to those measures. Those high in future orientation were more likely to use alternate methods of reducing exposure to HIV (e.g., inquiring about partner's sexual history, delaying or abstaining from sex). Time perspective also interacted with both gender and fear of AIDS. The responses of women and individuals low in fear were more related to time orientation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

"Mostly straight" young women: Variations in sexual behavior and identity development.

Researchers have begun to explore and identify various gradations in sexual orientation identity, paying attention to alternative sexual identity categories and attempting to clarify potential subtypes of same-sex sexuality, particularly among women. This study utilizes both quantitative and qualitative data to explore the behavioral experiences and identity development processes among women of a particular sexual identity subtype, "mostly straight." Participants were 349 female college students whose primary sexual identities included exclusively straight, mostly straight, bisexual, and lesbian. Results indicated that, on most behavioral variables, mostly straight women fell directly between and were significantly different from exclusively straight and bisexual/lesbian women. Mostly straight women were also distinct from exclusively straight women but were similar to bisexual women and lesbians on several quantitative measures of identity. Narratives about sexual identity development for mostly straight women revealed the complexities of sexual identity exploration, uncertainty, and commitment within this population. As a whole, this study encourages researchers to begin to recognize and examine mostly straight as a distinct sexual identity subtype in young women. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Human sexual orientation has a heritable component

We present an overview of behavioral genetics research on homosexual and heterosexual orientation. Family, twin, and adoptee studies indicate that homosexuality and thus heterosexuality run in families. Sibling, twin, and adoptee concordance rates are compatible with the hypothesis that genes account for at least half of the variance in sexual orientation. We note observations of homosexual behavior in animal species, but the analogy to human sexual orientation is unclear. We discuss the reproductive disadvantage of a homosexual orientation and present possible mechanisms that could maintain a balanced polymorphism in human populations.     

Sin, sickness, or status? Homosexual gender identity and psychoneuroendocrinology.

Contends that animal experiments show conclusively that sex hormones influence the male/female dimorphism of the brain, prenatally, in 4 possible ways (i.e., masculinizing, demasculinizing, feminizing, defeminizing). The human counterparts of devised animal experiments are clinical intersexual (hermaphroditic) syndromes that occur spontaneously as experiments of nature. The 2 sources of data supplement one another. Both lead to the conclusion that prenatal hormonalization of the brain influences the subsequent sexual status or orientation as bisexual, heterosexual, or homosexual. This effect is more robot-like in subprimate than in primate species. As in subhuman primates, in the human species sexuoertic status is dependent not only on prenatal hormonalization, but also on postnatal socialization effects. There are several different human hermaphroditic syndromes each of which makes its own specific contribution to the science of homosexology and to the understanding of genetic, prenatal-hormonal, pubertal-hormonal, and socialization determinants of being gay, straight, or bisexual. In combination, they indicate that sexual orientation is not under the direct governance of chromosomes and genes, and that, whereas it is not foreordained by prenatal brain hormonalization, it is influenced thereby, and is also strongly dependent on postnatal socialization. The latter is, like native language, programmed into the brain through the senses. Postnatal programming may become incorporated into the brain's immutable biology. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Are 2D:4D finger-length ratios related to sexual orientation? Yes for men, no for women.

The ratio of index and ring finger lengths (2D:4D) is thought to be a marker of prenatal androgen exposure. In a sample of over 2,000 participants, men had significantly lower 2D:4D ratios than women (d = .36 and .23 for right and left hands, respectively), and these results were consistent across ethnic groups. Heterosexual men had significantly lower (more male typical) 2D:4D ratios than gay men (d = .32 and .31 for right and left hands, respectively), and these results tended to be consistent across ethnic groups. Heterosexual and lesbian women showed no significant differences in 2D:4D ratios, after ethnicity was taken into account. The current findings add to evidence that prenatal hormonal factors may be linked to men's sexual orientation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Selective sexual orientation-related differences in object location memory.

The present study examined sexual orientation-related differences in object location memory by using 3 object arrays (testing object exchange, object shift, and novel objects conditions) and 1 metric positional memory array. Heterosexual women and homosexual men significantly outperformed heterosexual men in all 3 object arrays. However, there were no group differences in metric positional memory. Heterosexual males expectedly outperformed the other groups in spatial perception (Judgment of Line Orientation; A. L. Benton, K. D. Hamsher, N. R. Varney, & O. Spreen, 1983). Regression modeling revealed that sexual orientation and spatial perception predicted object exchange performance, whereas recalled childhood gender nonconformity, a robust developmental marker of adult sexual orientation, predicted object shift and novel object performance alone. A measure ascribed to the actions of prenatal androgens, the 2nd to 4th finger length ratio, did not predict object location memory. These data may limit possible developmental pathways for sexual variation in selective forms of spatial memory. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Human behavioral sex differences: A role for gonadal hormones during early development?

Evidence that gonadal hormones during prenatal and neonatal development influence behavior is reviewed. Several theoretical models of hormonal influences, derived from research in other species, are described. These models are evaluated on the basis of data from humans with either normal or abnormal hormonal exposure. It is concluded that the evidence is insufficient to determine which model best explains the data. Sexual differentiation may involve several dimensions, and different models may apply to different behaviors. Gonadal hormones appear to influence development of some human behaviors that show sex differences. The evidence is strongest for childhood play behavior and is relatively strong for sexual orientation and tendencies toward aggression. Also, high levels of hormones do not enhance intelligence, although a minimum level may be needed for optimal development of some cognitive processes. Directions for future research are proposed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The role of oxytocin in relation to female sexual arousal

Oxytocin is clearly involved in human reproduction and serves an important role in sexual arousal. Oxytocin serum levels were measured before and after sexual stimulation in 12 healthy women. Values of oxytocin 1 min after orgasm were significantly higher (p < 0.05) than baseline levels. This finding supports the hypothesis that oxytocin plays a major part in human sexual response both in neuroendocrine function and postcoital behavior.