Feminization in males exposed prenatally to DES

What Do Animal Research Findings Reveal About Future DES Health Effects?

This excerpt is from a teleconference with Dr. John McLachlan, a long time researcher on the effects of DES exposure, and Scott P. Kerlin, Ph.D., DES Sons International Network,


Abstract (pages 17 to 20)

Dr. McLachlan, it’s Scott Kerlin from the DES Sons Network. Good to make a connection with you here. I appreciate your presentation on many different levels, but I’ll try to be fairly specific on my own topic question. Our network in the past year did a poll to try to find out what were the leading concerns of DES sons and, as you’ve pointed out and other’s have, there’s a lot less research that has documented the effects on DES sons than on daughters.

We learned quite a bit though from network members that: endocrine system problems, gender identity problems, and mental health problems seem to be among the top three areas, closely followed by cancer. I wonder if you could just briefly comment from your own long-term research about two somewhat questionable or controversial topics; one being feminization in males, and the other being various endocrine disorders in males, particularly hypogonadism, and whether you’ve seen linkages in your research over the years in animal research that might point to a significant predominance of hypogonadatropic hypogonadism, I guess is what it would be called.

Dr. McLachlan : Right. Hypogonadatropic hypogonadism, is a low level of pituitary hormone telling the testicle, the gonad, to make testosterone and sperm. It is something that has been seen occupationally in men who have acute exposure to DES. So if an adult male takes estrogen or is exposed to estrogen, the obvious results will be gynecomastia (enlarged breasts),, and hypogonadotropic hypogonadism, (small testicles, low libido).

I haven’t seen the same kind of thing reported from prenatal exposure to DES. Mice that get treated with DES prenatally have a smaller than normal testicular size and a lower than normal sperm count that’s dose related. Testosterone levels in these mice are pretty much normal, although estrogen levels are higher than normal. I don’t know of any comparable studies that have been done in humans, but you might know.

Scott Kerlin : I’ve been looking hard.

Dr. McLachlan : The other issue you mentioned was feminization. All mammals – mice, rats, and humans – as fetuses start out as bisexed beings. We have a gonad that’s going to be either a testis or an ovary, depending on the genetics. Once that happens that little organ secretes some things that do one of two things.

In the case of a genetic male, the testis will start making testosterone, which keeps the male reproductive system intact during fetal life. They also make another protein called Mullerian inhibiting substance, which is specifically set to wipe out the female reproductive system that the fetus has at this time.

If there is no genetically determined male gonad that makes androgen to keep the male tract alive, and then makes this other inhibitor to kill the female tract, invariably you end up with a female. There are genetic disorders or genetic syndromes where those things can change resulting in a genetic male that may have a complete functioning cervix or uterus. This could happen, it seems in mice or humans exposed to DES, though it hasn’t been shown clearly in many human cases. In a mouse whose mother is given DES, you feminize the reproductive system such that a genetically born male, has testis, is usually not making as many sperm as normal, has slightly lower androgen levels, and has higher estrogen levels. That male mouse will have a prostate seminal vesicle, all the other plumbing to get the sperm from the gonad out, but it will also literally have a functioning set of fallopian tubes, uterus, cervix, and an upper portion of the vagina.

The penis of this mouse is also feminized to the extent that there is a higher prevalence of a condition called hypospadias, which is a congenital defect wherein the penis doesn’t totally close in the right way. There is an opening that might be along the shaft of the penis or is often at the end of the penis where there’s almost another kind of — I hate to use the term because it’s not scientific — quasi-vaginal like orifice. It means that estrogen has prevented the total masculinization of what could just as easily end up being the clitoral structure and vaginal structure.

Scott Kerlin : Right.

Dr. McLachlan : We also know that femininization can even happen inside a cell, and from a molecular level there’s a kind of feminization that we and others have shown in mice.

Coming back to one of the earlier questions about hormonal changes in the brain and how this might relate to gender identity. That’s been a really tough one for a lot of people. In the mouse and rat you can certainly do prenatal or neonatal treatment with estrogens or androgens to feminize or masculinize behavior. But in humans it’s very controversial and unknown as to whether this can happen at all. It seems as if the network is hardwired in a different way. Having said that, I’m not sure if anybody is really dealing directly with this.

Scott Kerlin : I will let go at this point so everyone else can ask their questions, but one of the documents that we have actually posted to our Sons Network home page is from the National Toxicology Program fact sheet on DES. I was intrigued when I read the list of symptoms from physical exposure taken by adults. It says right in the text, not only can it cause male impotence, but it can cause transsexual changes, and it indicates it can cause gynecomastia.

Dr. McLachlan : This is in adults though, right?

Scott Kerlin : I think so as best as I can tell. My understanding was that if one time DES was used for male to female transsexuals who were transitioning.

Dr. McLachlan : It is actually

Scott Kerlin : Is it? Okay.

Dr. McLachlan : Yes.

Scott Kerlin : But the prenatal exposure and transsexual effects, that has never been clear to me exactly how that works.

Dr. McLachlan : Yes. We are talking about, in both humans and mice, a feminization of structures. An example in terms of the genital tract is that with undescended testicles the male gonads stay right where they were when they were both male and female. But again, even though animal studies suggest that you can feminize male rats or mice with developmental exposure to estrogens or androgens, this is not clearly the same case, and I think is pretty much considered impossible, with humans. I don’t think that has really been tested in all of the kinds of subtlety that would be required when one considers the complexity of an issue like gender identity.

Scott Kerlin : Yes, that would concur. Thank you so much. “


2 Replies to “Feminization in males exposed prenatally to DES”

  1. The way that doctor replied in that excerpt is a good example of how medicine is an art, not a science, and that doctors and lawyers are often two very closely related species! It reinforces my view that the medical industry will never voluntarily admit that, by administering synthetic hormones with gender bending properties (DES and progestins), they’ve inadvertently created millions of gender blended people, who had parts of their prenatal development occur as male and parts as female.

    One thing that doctor has admitted though, is that they exposed millions of unborn babies to high doses of a drug that was, at one time, the mainstay of transgender hormone treatment. The typical dose of DES used in transgender HRT was apparently 5mg per day. The doses being used for miscarriage prevention were considerably larger than that (under the standard treatment regimen, more than 20x greater during the later stages of the pregnancy).

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