DavidZ said:
coz, I usually wait at least 2 weeks before getting blood tests for any change in protocol. I can't say whether or not one week is enough time to get a good reading.
I apply it once a day in the morning after my shower. Don't know what the half life is, but that dosing schedule works fine for me.
What's the rest of your protocol? What are you looking to achieve by adding DHT?
I did some research on DHT. Here's an interesting link:
http://home.vicnet.net.au/~aissg/testosterone.htm
And here's the full text. It is written for people with AIS, but nevertheless it is a really good read with lots of new information on DHT....For the ones that don't want to read the full text: just read the things I have marked in bold...it summarizes the text more or less.... (At your service!)
FULL TEXT:
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.
