Hello all,

My daughter was diagnosed with CAIS when she was 1 month old. She had a double hernia and needed surgery. Low and behold they found testicles instead of ovaries and her uterus is missing. Well, we tried to find out all the information we could, and proceeded to deal with the situation as best we knew how. We figured she would have the surgery to remove the gonads next year at age 2, and then start on the HRT when the time came. She is very tall for her age, very intelligent and very active. An all around healthy little girl.

Well, we just received letter from her endocrinologist stating that they found no genetic defect in the Androgen Receptor. Which means that they do not know at this moment what or where (genetically) her exact defect is. The letter states that perhaps it is possibe that the defect is in another Gene.

WHAT? I don't understand this. If the damage is somewhere else, will she still grow up in the same manner as CAIS? Or should we hold off on this surgery, as maybe she would need to make up her own mind as to whether she is a girl or boy? I told her endo that there is a very good possibility that my mother took DES while pregnant with me and my older brother. Should I have him investigate this more? We live in Switzerland, and it is very difficult for me with the language. He didn't even recognize the term "DES" when I said it and that kind of scared me as my Swiss Gyno knew what it meant, so shouldn't my very important and well respected Professor of Endo recognize this also? He works at a very good uni clinic in Zurich.

I would love to hear your reactions to my ramblings. And any suggestions as to where we could perhaps get some better info would be greatly appreciated.

Thanks in advance, and thank you for letting me vent a little!

Butkus

Dear Butkus,

I have AIS but that doesn’t mean I can answer all you questions. But I’ll do my best…



Quite often (C)AIS is used as a kind of “pre-diagnosis” for a girl with an XY,46 karyotype. It can take months and a lot of tests before you get a “final diagnosis”. And sometimes it is just impossible to find the reason of AIS. Actually it is even impossible to give a diagnosis of CAIS before the child reaches puberty. The difference between CAIS (or AIS grade 7) and PAIS grade 6 is not visible in newborns.

In about 5 percent of CAIS and about 20 percent of PAIS it is not possible to find a genetic defect. That doesn’t mean that your child doesn’t have AIS. But… it is possible that your child has one of the other conditions like 5ARD, 17BHSD, Sweyer’s or Leydig cell hypoplasia.

Only with high grade AIS your child is insensitive for androgens. With the other conditions your child is unable to make androgens or to convert them to more potent androgens.



If your daughter is diagnosed with CAIS she probably doesn’t show any signs of virilization. In that case you can safely expect that she never wants to be a boy. But if she had an enlarged clitoris and/or fused labia it is more difficult to predict her future. If she has PAIS, she most likely will have a completly female gender. With conditions like 5ARD and 17BHSD a change of genderrole is a bit more common.

Unfortunately, even if you know for certain that she has 5ARD or 17BHSD it is impossible to predict her gender. But especially with those conditions not removing the gonads will have a terrible effect on people who identify female. During puberty the amount of androgens will rise to a level that partly compensates for the lack of enzymes that are the cause of 5ARD and 17BHSD. Because of that, male secondary sex characteristics will start to develop: deepening of the voice, facial hair, etc.

And then there is the possibility of malignant tumors. In CAIS that chances is really small, but with ambiguous genitals and the chance is significant higher.

I’m not a medical professional, but even if I would be qualified to answer your question I really don’t know what to advise. There are also other - not very well documented - arguments against gonadectomy. Many adults complain about feeling very tired after their gonads were removed. And it seems that people who had their gonads removed later in life have not as many problems with osteoporosis as people who had their gonads (almost) immediately after birth.

All I can advise is to talk to a doctor who has seen many people with an intersex condition. I know that several people in Switzerland go to Germany for a diagnosis.



Officially there is no relation between XY intersex conditions and DES. But that doesn’t explain why in the Dutch AIS support group more women than average told me that their mother took DES…



You’re welcome! If you have AIS related questions that you don’t want to ask here in the public forum, you can always send me a PM.

Met vriendelijke groet,

Miriam

__________________
The Truth, The Whole Truth, and Nothing But The Truth.

Most of all current knowledge about DES centers on carcinogenic effects, although some sourecs admit to "relatively" minor reproductive tract effects compared to significantly presented congenital conditions (ambiguous genitalia etc). However research done by the National Institute of Health (NIH) some time ago using mouse/rat models in their research (along with human observations)came up with this excerpt (taken from their website with link below). It must be noted that anatomic/physiologic variations occur with each individual which can be accounted for, perhaps, by when, how long, dosage amount and concentration of DES was ingested during pregnancy:

"Other effects observed in mice that parallel those in humans include infertility and subfertility; oviductal, cervical, and uterine malformations; paraovarian cysts of mesonephric origin; salpingitis isthnica nodosa of the oviduct (an epithelial change in the oviduct); immune dysfunction; and vaginal adenosis. Observations in DES-exposed male offspring (both humans and mice) include subfertility and infertility, decreased sperm counts, hypoplastic cryptorchid testes, epididymal cysts, testicular tumors, anatomical feminization, microphallus, hypospadias, retained Müllerian remnants, and prostatic inflammation. Thus, the prenatally DES-exposed mouse model appears to be valid and to parallel the human condition. To that end, the model has been used to replicate and predict many of the lesions observed in similarly exposed humans. Exposure to DES early in gestation results in structural, functional, and long-term changes, including neoplasia, in both humans and mice".

The link: http://planning.cancer.gov/whealth/DES/index.html

And here is another link:

http://www.cdc.gov/DES/

One interesting, but very disturbing and sad fact, is that some women were not aware of taking DES. That is because they were given as prenatal vitamins not indicatoing that DES was an "ingredient" :


In the years between 1938 and 1971, the advice of a medical professional was rarely questioned. Patients believed that the physician knew best, and the concept of informed consent was unknown at the time. It was widely believed that DES would make a pregnancy healthier. Many women were unaware they were taking DES because the drug was marketed in combination with vitamins. In fact, DES and similar DES-type drugs were marketed under dozens of brand names (see Table: “Names of DES and DES-Type Drugs ”), and manufactured by over 200 U.S. drug companies at different times. 2

Look under Background and Epidemiology in this additional link:

http://www.nursingcenter.com/prodev...p?tid=417395#15

As a final note: I am providing these Internet links to better familiarize yourselves with DES and related resources...... not as any medical advice or diagnosis. It's always good to know about such matters when they pertain to us directly.

I'm sorry that I haven't anything from your area of Europe.

Dana

__________________
Andy Dufresne (from the movie Shawshank Redemption): "It's my life. Don't you understand? IT'S MY LIFE!'

I would let this individual grow up , but tell her about her life , do not hide the abnormal gene.
I am ther and I was not of or knew I was Intersexed. That is a tradegy in its own right.
I did not have a choice about anything.
I wish I had the decision about my surgerical endeovours when I was at a young age , I do not think I would have had all the problems in life that I had when I was growing up.
I wanted to hide , I did not have many friends and I just wanted to die.
I still do not have friends because they do not comprehend I was born with XXy.
I request on to you be truthful and repspect this individuals right to be Az1.

Thank you, everyone, for the information and advice.

Miriam and Dana, I appreciate the info. You know, we are starting from scratch here. My husband and I were totally unprepared for the diagnosis, we had no idea how special our little girl was/is. We are of the opinion that the more information we have, the better equipped we are to help her find her way in the world. Of course, her doctor is just a little bit against that. He is of the mind that we should just do what he says, and not try to find anything out, as we would probably find only bad information. I tried to explain that we are halfway intelligent adults, and can distinguish the good from the bad, but he still worries that I will come to him with something off the wall (and what's wrong with "off the wall"?).

We discuss our situation quite frequently, and have decided to go forth with the gonadectomy early next year, as it has only been one year since the hernia operation (thank goodness hernia's run in my husband's family, or we wouldn't have found this so early).

Az1, I am sorry that you had such a confusing childhood. And I am proud that you are hear, giving advice and helping out someone else to ensure that they do not have such a time. Thank you for that. As far as raising our daughter, we will definitely tell her what is going on. Genitalia-wise, she is a normal little girl. No fused labia, no oversized clitoris. We will continue to raise her as a girl, and hopefully figure out the best way and time to tell her of her circumstances. We haven't told anyone in our families, except our parents, as we wanted to make sure that she wasn't told by a cousin or friend before we had a chance to discuss it with her. After that, it is her body, she will then make the decision who to tell. I don't advocate secrecy in these things, only the chance to present the correct facts, and not some ignorant family member's version of "her little problem" (can't find a "tongue in cheek" icon!).

We love our little munchkin, more than life itself. She is definitely our little ray of sunshine. I hope you all don't mind if I bug you from time to time with questions. You are definitely better informed, and can give us a different perspective, to make sure that we aren't just looking at this thing one-sided. I hope and pray that one day DD will be able to offer assistance to someone else in this situation. To me it is just so frustrating to not be able to get more up-to-date information. And we keep running into the "no funds available for research" wall. What's that all about? The DES link, to me, is just too coincidental. I am sure that my mother was prescribed DES with me and my older brother after a total of 7 miscarriages during her childbearing years. I am the youngest of 8 children (5 girls, 3 boys), and the only case of AIS out of 20 grandchildren and great-grandchildren (half girls) is my daughter. Go figure. I am eager to learn more about this. Not just to lay blame, but for the fact that how many other drugs are they prescribing out there with side effects that last into another whole generation? Amazing. And sad.

I have probably rambled enough. Be warned, you haven't heard the last of us! Thank you all again for your replies....and for being here! Looking forward to the future!

All the best,

Butkus

Good luck. From your description of the situation of your daughter, it seems that you are doing many things right. In the past, doctors often recommended that parents not tell their children about their situation. Denial is often very psychologically damaging to children. It is good that you are seeking out information and have posted your concerns on this forum. I agree with you that your daughter should be fully informed. In my childhood, I was routinely beaten by other children at school because they had found out about my situation from my brother. As my parents were ashamed of my situation, I was not able to go to them for support when being abused by other children.
While DES may be a factor in some intersex cases, I doubt that it would do the type of genetic damage that would pass from your mother to your daughter. I suspect that DES acts more at the hormonal and bio-chemical level. If you took DES, a possible link would be much stronger.

Peter

I think it is extremely irresponsible for your doctor to reccommend gonadectomy without a proper diagnosis. In some cases, such as Swyer syndrome, there is no potential for fertility and an increased risk of cancer. In such a case, gonadectomy may be justified. However, in other cases, such as 5aRD, the child is fertile and it would be cruel to remove the testes until she was certain that she never wanted to be a man and never wanted to have children. In cases of true CAIS there is no clear benefit to removing the gonads, as the risk of cancer is small. Why are you considering gonadectomy at such a young age and without a proper diagnosis?

(Or, to put it more pointedly, suppose your child starts showing male behavioral characteristics. How are you going to explain to him that you cut off his balls? This is a serious question.)

The other thing I feel needs to be pointed out is that your daughter will need an endocrine evaluation before puberty. If sufficient estrogen is not produced, or the gonads have been removed, there can be serious problems with bone growth. Also, lack of proper hormone production can cause many psycological problems, sleep disturbance, etc. This is all too often overlooked. (It was in my case, although that was a very different situation as I don't have AIS.)

About disclosure, well, since your daughter will never get her period, obviously you are going to have to explain this. And of course you will need to explain the doctor visits. Being evasive is not helpful, as kids are pretty good at figuring out when you're lying to them.

Finally, as others have said, DES does not cause AIS. If there is any connection, it might be that whatever caused your mother's miscarraiges could be genetically related to your daughter's condition. But that is purely speculative.

Lots of doctor visits and examinations can be rather traumatic for such a young child. Unless there is a serious medical problem, maybe you should just worry about raising a happy little girl.

Dear neko,

Who said there was no proper diagnosis? Butkus said that with genetic testing no defect in the Androgen Receptor was found. If such a defect would was found it would have been the ultimate proof that the diagnosis is correct. But not finding a defect on the AR gene doesn’t mean the diagnosis was incorrect.



Recent research, some of it not published yet, shows that all children born with a high grade AIS (unambiguous female genitalia) will develop a female genderidentity. So the risk of an incorrect sex-assignment doesn’t play a role in the case of Butkis’ daughter. Although we are women with balls, even after the gonadectomy ;) our gonads are not of much use to us. We don’t produce sperm cells, so we can’t “father” a child. (yikes, just the thought of it makes my stomach turn: ‘hi dear daughter, I’m your mother, I look like a woman, I identify female, yet I’m your biological father. Oh, btw, half of your x-chromosomes contain an AR-gene defect, so you can pass this wonderfull genetic condition to your children’ – NO WAY!.) But it also is not absolutely clear that the estrogens converted from testosterone (by aromatase) are better than those from a pill; some people think that with aromatase not enough estrogens are produced to prevent the bones from osteoporosis. Yeah I know, we need more research….

But there is one very good reason to remove the gonads. The hernia isn’t a real hernia. Actually it are the testes that want to descend and when nobody is expecting testes, it looks like the girl has a hernia. Those descending testis sometimes make it difficult to pee in a downward stream, especially if they reach the labia. And since even little girls don’t like to pee over their legs, descending testes are a good reason for a gonadectomy in childhood.

What is better? I don’t know. Most women of who the gonads where removed in childhood say that they are happy with it. And most women who have their gonads removed later on in life say that they are happy that it wasn’t done in childhood.



Do you really have to be rude? A bit more respect for the difficult decisions parents have to face would help if you want to convince them of your point of view.


DES does not cause AIS, but many women with AIS say that their mother has used DES. A possible explanation of that would be that with AIS there often is a history of miscarriages and DES was meant to prevent miscarriages. My sister is 11 years older and if my mother would not have had so many miscarriages, my sister and I would have had at least zeven siblings.


After the diagnosis, with can require several visits to a hospital, most doctors in the Netherlands, Germany and (as far as I know) also in Switzerland want to see a girl with AIS only once per year. On a personal not I can add that it is not the number of doctor visits that are traumatic. It is the way the doctor sees you, as a interesting genetic condition or as a human being.


And that is valid for all children, not only for girls with AIS ;)

Groeten, Miriam.

__________________
The Truth, The Whole Truth, and Nothing But The Truth.

Sorry, I didn't mean to be rude. If it is truly CAIS then there is no potential for fertility, so that is not an issue. There seemed to be some concern that this might not be CAIS though.

And I agree if the decending testes are causing problems, then surgery is warranted. But surgery of any kind is traumatic for a child. I was subjected to some childhood surgeries (not IS-related) and I was damn furious about it at the time.

The issue with HRT is more complicated. There IS a difference between the estrogens which are produced by aromatization of testosterone and estrogen from a pill. Injested estradiol is primarilly converted to estrone. Also some doctors like to use ethinylestradiol - I've tried this drug and it certainly does not feel the same as natural estradiol.