The aim of this section of the support group is to provide help, information and support to men with Partial Androgen Sensitivity Syndrome (PAIS).

We believe that there are many individuals with PAIS who were raised as males, but due to the stigma and secrecy associated with the condition, there are very few who have actually sought help and support.

This group hopes to put us together.

Our condition has in the past been cloaked in secrecy and shame, forcing the individual into a world of isolation, unable to speak openly about our true feelings of shame and inadequacy, being in constant fear of your secret being revealed and being made to feel as if you have no right to live as a man.

There are those with PAIS who were raised (and surgically & hormonally assigned) as female, but have never felt comfortable with the gender that was forced upon them. In fact, some have indeed sought correction to be assigned as male with Testosterone treatment, etc. This group is for you too.

If you need any kind of help with your condition, please contact us for completely confidential advice and support. Our one and only aim is to allow you to enjoy your life without the secrecy and shame associated with PAIS.

Contact other Men with AIS

To get in touch with the official AIS Support Group Australia representative for Men with AIS, contact us.

Biographies

Graham's Story

Tony's Story

Story of a man with PAIS on the UK Intersex Association website

DHT treatment for Men with AIS

By Andie from dAISy, March 2002.

Most people with AIS understand that cellular response to androgens is affected by the condition. Many with AIS will also understand to a greater or lesser degree, the feedback loops within the human body that control production of testosterone and why it is regulated this way. There has been some discussion amongst support group members both male and female, and by some parents of affected children about the possible benefits of dihydrotestosterone (DHT) treatment for males with AIS. I hope this article will explain sufficiently some of the basic concepts of the way hormones work in the human body and why it is that DHT may be of benefit. I say may be of benefit for two reasons, firstly because limited trials on some individuals have shown promising results, and secondly because most endocrinologists that the support group President and I have spoken with about DHT agree that in theory, DHT is likely to have the best chance of working on someone with androgen receptor variations.

I apologise in advance to those people who already understand the principles outlined in the biology lesson below, but I wanted to ensure everyone had a good understanding of some basic principles before discussing the possible benefits of DHT treatment.

The human body is made up of millions of cells. Each of these cells has an outer membrane through which some substances may pass to eventually access the nucleus (centre) of the cell. The outer membrane is partly made up of lipids (a group of fats) so hormones that are lipid soluble are able to pass through the outer membrane and gain direct access to the nucleus. Hormones need to bind to a receptor to work. Some receptors are located on the cell membrane (and bind with water soluble hormones that send what are called second messengers to get inside the cell), but the one we are most concerned with here is the androgen receptor, which is located in the nucleus of the cell. Most of you will understand that it is the androgen receptor that is either missing or has some variation in those with AIS and is the receptor that allows a cell to respond to testosterone.

Testosterone is synthesised (converted) from cholesterol by the testes. As testosterone is lipid based it is able to pass through the cell membrane because, as was explained earlier, the cell membrane is also partly made up of lipids. Once the testosterone gets through the membrane it is able to bind with the androgen receptor in the nucleus (what is called an intracellular receptor for those remotely interested), where it then turns on or off particular genes (this is called altering gene expression). Once this takes place, a type of chemical messenger (called RNA - ribonucleic acid) leaves the nucleus of the cell and enters the cell 'tissue' (called the cytosol), and causes physical changes to the cell (usually because enzymes direct production of new proteins - 'building material'). Response by the cell to certain hormones is controlled by the concentration of the hormone and the number of receptors in the cell (called down-regulation and up-regulation, again for those even remotely interested).

Testosterone produced by the testes can be used by some cells as is, but other cells need testosterone in a further converted form, dihydrotestosterone (DHT). Some testosterone is also converted into oestrogen and this is especially important in the case of AIS. Pre-natally, testosterone stimulates development of the male reproductive system and descent of testes and DHT stimulates development of external male genitalia. Oestrogen has an important part in development of certain brain structures and development of bone mineral density. Oestrogen is also the principle hormone for female pre-natal development including development of female external genitalia. For males at puberty, testosterone and DHT play an important role in the development of secondary male sexual characteristics, and for women oestrogen again plays the most important role.

Production of testosterone by the testes is regulated by the pituitary gland and the hypothalamus as part of a system that detects the level of testosterone in the body and regulates production accordingly. This testosterone regulatory system is called the brain-testicular axis, and without getting into too much detail suffice to say that a part of the pituitary gland releases a hormone called luteinising hormone that acts on cells in the testes (called endocrinocytes, or interstitial Leydig cells!) that secrete testosterone. In the case of AIS, cells in the body that have a missing or varied androgen receptor include those in the brain-testicular axis so they are unable to accurately detect the amount of testosterone in the body. As a result, testosterone production in people with AIS is generally much higher than is usual.

The level of response to the testosterone produced is what determines development as male or female in those with AIS. As mentioned earlier, some of the testosterone produced is converted to oestrogen. Because production levels of testosterone in people with AIS is usually very high, the amount of testosterone converted to oestrogen is also very high and in the case of very limited response or no response to testosterone (such as CAIS) means the body naturally develops as female because there is still full response to oestrogen whilst response to testosterone is minimal or zero.

In the case of males with PAIS the situation is a little more difficult. Because there is some response to testosterone, some male characteristics develop, but the presence of oestrogen to which there is still full response, means unwanted characteristics such as breast development may occur at puberty.

Giving extra doses of testosterone to a boy or man with PAIS, will inevitably mean that some is converted to oestrogen causing some of the unwanted characteristics described above. This is where treatment with DHT is likely to be of benefit. The DHT has a natural advantage to start with, because it is converted from testosterone and acts on target cells without being able to be converted into oestrogen as is the case with testosterone. Elevated levels of DHT would also effect the operation of the brain-testicular axis so that testosterone produced naturally by the body is reduced, important for boys and men with AIS as it is this naturally produced testosterone that is converted to oestrogen causing negative effects like breast development, which leads to surgical correction including bilateral mastectomies and chest reconstruction.

For those with AIS who have had exposure to DHT treatment, there has not been any significant development of male secondary sexual characteristics, rather the suppression of development of female secondary sexual characteristics which of itself is important as it would mean reduced need for some surgeries. There have been some side effects noted when using DHT. Principally this seems to be nausea which one endocrinologist has attributed to effects on fluid retention by the body. There is also the possibility that use of DHT over time may limit or prevent the body from 'kick-starting' natural testosterone production again.

Given the potential theoretical advantages of DHT, resistance seems to be found mainly because of restricted access to the hormone by Government, because of fears of miss-use by some in the body building industry. Because of the very limited application in treating males with AIS, I personally cannot see why strictly controlled approval on a trial basis would not be granted should an endocrinologist consider it an issue worthy of pursuing. If DHT works in the way many believe it will, then it has to be worth trying for those males with AIS that need something to help them along the way. This is especially important for those boys with AIS just approaching puberty now or those young males still likely to get any developmental benefit from using DHT.

"Father and Son" by immagina, 2006. Creative Commons license.

Father And Son

By Cat Stevens

Father
It's not time to make a change,
Just relax, take it easy.
You're still young, that's your fault,
There's so much you have to know.
Find a girl, settle down,
If you want you can marry.
Look at me, I am old, but I'm happy.

I was once like you are now, and I know that it's not easy,
To be calm when you've found something going on.
But take your time, think a lot,
Why, think of everything you've got.
For you will still be here tomorrow, but your dreams may not.

Son
How can I try to explain, when I do he turns away again.
It's always been the same, same old story.
From the moment I could talk I was ordered to listen.
Now there's a way and I know that I have to go away.
I know I have to go.

Father
It's not time to make a change,
Just sit down, take it slowly.
You're still young, that's your fault,
There's so much you have to go through.
Find a girl, settle down,
if you want you can marry.
Look at me, I am old, but I'm happy.
(Son-- Away Away Away, I know I have to
Make this decision alone - no)

Son
All the times that I cried, keeping all the things I knew inside,
It's hard, but it's harder to ignore it.
If they were right, I'd agree, but it's them you know not me.
Now there's a way and I know that I have to go away.
I know I have to go.
(Father-- Stay Stay Stay, Why must you go and
make this decision alone?)

Research

Male Gender Identity in Complete Androgen Insensitivity Syndrome - Archives of Sexual Behaviour by Guy T'Sjoen, Griet De Cuypere, Stan Monstrey, Piet Hoebeke, F. Kenneth Freedman, Mahesh Appari, Paul-Martin Holterhus, John Van Borsel and Martine Cools on April 01, 2010. 

Abstract: Women and girls with complete androgen insensitivity syndrome (CAIS) invariably have a female typical core gender identity. In this case report, we describe the first case of male gender identity in a CAIS individual raised female leading to complete sex reassignment involving both androgen treatment and phalloplasty. CAIS was diagnosed at age 17, based on an unambiguously female phenotype, a 46,XY karyotype, and a 2660delT androgen receptor (AR) gene mutation, leading to a premature stop in codon 807. Bilateral gonadectomy was performed but a short period of estrogen treatment induced a negative emotional reaction and treatment was stopped. Since the age of 3, childhood-onset cross gender behavior had been noticed. After a period of psychotherapy, persisting male gender identity was confirmed. There was no psychiatric co-morbidity and there was an excellent real life experience. Testosterone substitution was started, however without inducing any of the desired secondary male characteristics. A subcutaneous mastectomy was performed and the patient received phalloplasty by left forearm free flap and scrotoplasty. Testosterone treatment was continued, without inducing virilization, and bone density remained normal. The patient qualifies as female-to-male transsexual and was treated according to the Standards of Care by the World Professional Association for Transgender Health with good outcome. However, we do not believe that female sex of rearing as a standard procedure should be questioned in CAIS. Our case challenges the role of a functional AR pathway in the development of male gender identity.  

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