Wednesday, 6 July 2011

Hormonal contributions to sexually dimorphic behavioral development in humans

From Science Direct, a paper about the organisational effects of hormones on the pre-natal brain, and what it means to be male or female : Hormonal contributions to sexually dimorphic behavioral development in humans Reinich et al, Psychoneuroendocrinology Volume 16, Issues 1-3, 1991, Pages 213-278
Nineteen studies on the behavioral effects of prenatal exposure to hormones administered for the treatment of at-risk human pregnancy are reviewed. Because the role of prenatal exposure to hormones in the development of human behavioral sex differences is potentially confounded by society's differential treatment of the sexes, comparisons between exposed and unexposed subjects were evaluated and summarized separately for male and female subjects. Therefore, this review focuses on data for individuals whose prenatal hormone environments were atypical relative to what is normal for their own sex.

Overall, it appears that prenatal exposure to androgen-based synthetic progestin exerted a masculinizing and/or defeminizing influence on human behavioral development, whereas prenatal exposure to natural progesterone and progesterone-based synthetic progestin had a feminizing and/or demasculinizing influence, particularly among female subjects. The data on prenatal exposure to synthetic estrogen derive primarily from subjects exposed to diethylstilbestrol (DES). DES-exposed male subjects appeared to be feminized and/or demasculinized, and there is some evidence that exposed female subjects were masculinized.

These findings are discussed in the context of prenatal hormonal contributions to sexually dimorphic behavioral development both within and between the sexes. Recommendations for the conduct of future research in developmental behavioral endocrinology are presented.
...
Three issues that qualify research in the area of human behavioral endocrinology must be considered in order to appropriately interpret the findings (see Reinisch & Gandelman, 1978, for a more detailed discussion).

The first qualifier relates to the inability to implement true experimental design (i.e., random assignment to treatment conditions) in research on human behavioral endocrinology. Because this area of human research is subject to strict ethical, moral, and legal constraints, true experimental design is precluded when studying potentially harmful interventions in humans.

Consequently, interpretation of the relationship between prenatal hormones and human behavioral development is limited to correlative rather than causal explanation. It is only through thoughtful comparison of conclusions derived from human "experiments of nature" or of medical treatmems with those derived from carefully controlled experimems with laboratory animals that confidence in the former can be attained. The role of hormones in organizing the neural substrate for behavior in nonhuman animals has been clearly established with two basic
experimental paradigms: perinatal androgen administration to genetic females, resulting in defeminization and/or masculinization, and perinatal androgen deprivation of genetic males, resulting in demasculinization and/or feminization, of sexually dimorphic behaviors and gonadotropin secretion in adolescence and adulthood. Extensive reviews of the nonhuman animal literature are provided by Ellis (1982), Hines (1982), and Reinisch (1974; 1983).

The second qualifier relates to the fact that the behavioral repertoires of males and females are not mutually exclusive, but rather, are overlapping. It is rare for one sex to display a behavior that is never exhibited by the other sex (menstruation, gestation, lactation, and impregnation being the notable exceptions). Typically, differences between males and females occur in the average frequency with which particular behaviors are exhibited by each sex. Thus, behavioral sex differences reflect quantitative, not qualitative, differences (Goy, 1970).

The third qualifier relates to the fact that masculinity and femininity are multidimensional. Masculinity and femininity are no longer conceptualized as opposite ends of a single, unidimensional, bipolar continuum (Fig. 2a), but are now understood to be a multidimensional matrix of independent or semi-independent factors.

The orthogonal or independent model (Fig. 2b: Constantinople, 1973; Bem, 1974; Whalen, 1974; Spence & Helmreich, 1978; Heilbrun, 1976; Berzins et al., 1978) and the oblique or correlated model (Fig. 2c: Reinisch, 1976; Reinisch & Sanders, 1987) suggest that masculinity and femininity are, with regard to many behavioral dimensions, relatively independent.


These models imply that an increase in the frequency or strength of masculine behavior (masculinization) is not necessarily associated with a decrease in feminine behavior (defeminization). Conversely, feminization is not necessarily concomitant with demasculinization. Thus, an individual may 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).

The difference between the orthogonal and oblique models resides in the extent to which masculinity and femininity are considered to be independent. Whereas the orthogonal model proposes total independence, the oblique model suggests that there is some degree of correlation between masculinization and defeminization and between feminization and demasculinization.
OK, so what were the conclusions?
Our review suggests that endogenous hormones present prenatally influence at least some aspects of sexually dimorphic behavioral development in normal male and female subjects, perhaps by establishing particular behavioral predispositions. In general, play-related activities and interests, aggression/assertion, and gender identity/role emerged as the behavioral categories most often affected by prenatal exposure to exogenous hormones. These effects are not simple, however. For example, although prenatally DES-exposed male subjects appear to have been demasculinized in terms of interest in active participation in sports, they were masculinized with regard to interest in passive viewing of sports. Prenatal exposure to some of these hormonal treatments was associated with delayed or diminished sexual maturation and behavior, while in other instances these dimensions were enhanced.
Unfortunately, it's behind a paysite firewall, but if your library has access, you should be able to view it. I'm accessing it at home using my ANU library privileges, as both PhD candidate and lecturer.

Another reason why I want a career in academe.

6 comments:

Bad hair days said...

"Masculinity and femininity are no longer conceptualized as opposite ends of a single, unidimensional, bipolar continuum (Fig. 2a), but are now understood to be a multidimensional matrix of independent or semi-independent factors."

Oh finally, someone has seen the light.

armouris said...
This comment has been removed by a blog administrator.
Sarah Murphy said...

Zoe,

I greatly appreciate your sharing the information on prenatal hormonal exposure with us and continuing to fight the good fight.

While for me this reopens fresh emotional scars that are still healing, I still need to see this, and know the science behind it. I feel privileged in that in this I have what I believe an explanation for the genesis of my GID.

I have a suspicion that at the time there was more known about DES than was being admitted to. Evidence the "news" from 1962.

http://news.google.com/newspapers?id=BmJOAAAAIBAJ&sjid=U0sDAAAAIBAJ&pg=3742%2C5111526&hl=en

Again, thank you for sharing. I can't help but wonder though. Do you suspect you may have been exposed to DES prenatally?

Zoe Brain said...

Hi Sarah.

What an interesting link...

As regards exposure to DES - I checked as far back as April 2006.

Oh yes - despite the fact that DES was commonly used in the UK in 1957 as an anti-abortifacient, and I was born in early 1958, my mother didn't take it. No, whatever caused my condition, DES is not guilty.

One of the first things I looked at, and one of the first to be eliminated.

Thanks for the kind words. I go where the evidence takes me, that's all. I'm sorry to have caused you pain - but that, I hope, will accelerate healing. You deserve as much help there as I can give. More.

Bad Hair Days - look at the date of this article. 1991. This has been known about for some time, just not as widely publicised as it should have been. A lot of the times, when I've independantly come to some conclusions based on the evidence before me, I find out that I've just re-invented the wheel.

Bad hair days said...

Omg. 20 years. If 20 years weren't enough?

Hugh said...

"Overall, it appears that prenatal exposure to androgen-based synthetic progestin exerted a masculinizing and/or defeminizing influence on human behavioral development, whereas prenatal exposure to natural progesterone and progesterone-based synthetic progestin had a feminizing and/or demasculinizing influence, particularly among female subjects. The data on prenatal exposure to synthetic estrogen derive primarily from subjects exposed to diethylstilbestrol (DES). DES-exposed male subjects appeared to be feminized and/or demasculinized, and there is some evidence that exposed female subjects were masculinized."

I'll tell you what these drugs do. Estrogens and progestins are both artificial female hormones. They have relatively modest effects in women (who naturally have high levels of female hormones). Both are completely alien to the male body though, and in quite modest doses (well below those commonly used for medical treatment in women), they completely shut down a man's testosterone production. I think exactly the same happens to a male fetus exposed to these drugs when his mother is given medical treatment with them during pregnancy.

The estrogen DES was for many years used to chemically castrate prostate cancer patients, a dose of 3mg per day being sufficient to completely shut down testosterone production. The starting dose of DES as a miscarriage treatment was 5mg per day!

Two progestins that were commonly used for miscarriage prevention during the DES era (often alongside DES) are norethisterone acetate and hydroxyprogesterone caproate. Norethisterone acetate was eventually dropped because it's actually a derivative of testosterone not progesterone, and was found to have masculinising effects on female fetuses. It was often used in conjunction with DES, and I think probably that's where the confusion about female subjects being masculinised while male subjects were feminised has come from.

Hydroxyprogesterone caproate continues to be used to this day, at doses that certainly look like they'd adversely affect male hormone production. The standard dose for miscarriage prevention is 250mg or 500mg per week. This same drug in the same form can also be used by mtf transsexuals to provide a progestin component to their HRT, only there the dosage would normally be one of the 250mg intramuscular injections every 2 weeks! (i.e. 1/2 to 1/4 the dose!).

Just to give you an idea of how high these doses are in relation to what will shut down testosterone production in adult men, the drug most commonly used to chemically castrate sex offenders is Depo Provera, an injectible form of the progestin medroxyprogesterone acetate. Apparently just one of the injections (each of which contain 150mg of MPA) every 3 months is enough to do the job, although normally they double up the dose just to make sure!

Today, hormonal treatment for prevention of miscarriage doesn't normally start until 16 weeks or more after conception, which is after development of the genitals and reproductive organs has already completed (but around the time sexually dimorphic brain development starts). The result, I think, is that you typically end up with a physically normal male baby with an incompletely masculinised brain.

DES was often started quite a bit earlier in the pregnancy, which explains why a high percentage of DES sons seem to have genital abnormalities (particularly undescended testes and a shorter than normal penis).

With all these treatments, testosterone production is suppressed during the 2nd and 3rd trimester, which is when most sexually dimorphic brain development takes place. The result is that that person may look male, but their brain has largely or completely developed as female, and they're obviously at high risk of identifying as a woman later in life! I think that if the truth were known, medical hormone use in pregnancy is likely responsible for many if not most cases of gender variance and transsexuality. What do you think?

Hugh Easton