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How Do Steroids Affect Puberty?

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Posted on Sat, 13 Sep 2014
Question: Dear Dr XXXXXXX

I still find it difficult to understand how steroids stimulate central puberty (at hypo level).

The gnrh is central nervous system controlled, so how can some mere weak steroids change this....it means our central nervous system dna and genes can be changed, along with neuronal settings, how is this possible>?

Secondly, i read some patients with congenital adrenal hyperlasia have central puberty very early on - but only in some of them. This is after prolonged exposure to high androgens....would weak steroids given at young age ie 7year old also lead to central puberty? I only ask as ive read steroids such as oxandrolone may induce puberty only in patients with testis volume of >4ml in other words speed up existing puberty.

Please could you advise on your return? Wishing you a nice vacation.

Regards,
XXXX
doctor
Answered by Dr. Binu Parameswaran Pillai (3 days later)
Brief Answer:
Hi

Detailed Answer:
Dear XXXX
Good day.
Thank you for writing back to me. Came back from vacation yesterday.
GnRH secretion is CNS regulated with so many other controlling factors involved. Oxandrolone and small dose of testosterone just prime the GnRH pulse generator and stimulate the puberty onset.

Let us compare to a car engine. There are complex computer systems controlling the car engine. Occasionally the car engine fails to start on a cold morning. It is just like giving a little push to start a lazy car engine on a cold morning. . If the engine is normal, a little pushing will start it. However, if the engine is bad, this little push will not be enough . Similarly, in constitutional delay of puberty, we presume that the GnRH pulse generator and other controlling structures are normal, but a bit lazy. In that case, a little push with oxandralone or testosterone for a short period is good enought to kick start the gnRH pulse generator firing.

in Congenital adrenal hyperplasia (CAH), there is peripheral precocious puberty first. However, in some patients, due to continues high exposure of androgens, a secondary central precocious puberty occurs. Weak steroids given in an otherwise healthy boy at 7 years will not lead to centtral puberty.

Once the testicular volume is > 4 ml, the puberty is allready started. And in that case, some pubertal process has allready been started. If there is a delay in pubertal progression at that stage, a little push wiith oxandrolone may help.
Regards
Binu
Above answer was peer-reviewed by : Dr. Chakravarthy Mazumdar
doctor
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Follow up: Dr. Binu Parameswaran Pillai (2 hours later)
Dear Dr XXXXXXX Welcome back and thanks for your valued answers.

I have one final problem regarding this past steroid treatment. As mentioned before, this treatment causes Gnrh neurons to start firing again.

This must mean a change in the neurons' morphology has taken place.

Since neurons never get replaced, does this mean the treatment has had a permanent effect? Or does the change that took place 're-change' again?


Thanks and Best Regards
XXXX
doctor
Answered by Dr. Binu Parameswaran Pillai (6 hours later)
Brief Answer:
Hi

Detailed Answer:
nope. There will not be any morphological changes inthe GNRH neurons from either Oxandrolone or Testosterone . There is only a priming or conditioning effect. Once the trigger is done, the GNRH neurons will start firing on it's own and will continue till andropause. ( andropause is the phenomenon in males equivalent to menopause in women)
Regards
Binu
Above answer was peer-reviewed by : Dr. Chakravarthy Mazumdar
doctor
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Follow up: Dr. Binu Parameswaran Pillai (3 days later)
Dear Dr XXXXXXX Sorry for late reply. I would like to ask a final followup question.

I'm uncomfortable with the the possibility that the 'first time' my gonadal testosterone interacted with my various tissues came from external stimulation (steroid stimulating increase in gonadortropins and thus gonadal steroids)

Can you advise if theres possibility gonadal steroids , in very low levels, still bind to various tissues?

Thanks and Best Regards
XXXX
doctor
Answered by Dr. Binu Parameswaran Pillai (5 hours later)
Brief Answer:
Hi

Detailed Answer:
Hi XXXX

Good day.
I had explained this some time back. Your gonadal testosterone were first produced in the intra uterine life itself before birth. This is due to increase in your pituitary LH and FSH in uterus and also due to stimulation due to hCG. That is why your testes descended from abdomen to scrotum and you had a well formed genitals at birth.
After minipuberty, gonadotropins and testosterone are very minimal until puberty. Even in low levels, testosterone binds to few tissues like bone , hair follicles etc. But low concentration may not be good enough to have a good sex life or fertility

Above answer was peer-reviewed by : Dr. Chakravarthy Mazumdar
doctor
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Follow up: Dr. Binu Parameswaran Pillai (37 hours later)
Dear Dr XXXXXXX

I know that first time gonadal testosterone binded to my genitalia is already confirmed due to normal well formed genitals.

But what about all the other tissues ie bones hair follicle skin...does the minimal testosterone in juvenile phase (before puberty) STILL bind to all the other tissues?


Secondly, in normal cases, does the activated androgen receptor also bind to sites other than AR site?
doctor
Answered by Dr. Binu Parameswaran Pillai (5 hours later)
Brief Answer:
Hi

Detailed Answer:
Yes of course. Low level androgens do attach to AR if they are on the surface of the tissue.For example, if you inject a high dose testosterone in a small boy, he will develop facial and pubic hair etc.
However these receptors are not expressed in many tissues until puberty. Hence it is thought that high circulating levels of androgens themselves will make AR to express on cell surface.

AR also bind to many other substances other than testosterone. ( these substances have structural similarity with testosterone)
Regards
Binu
Above answer was peer-reviewed by : Dr. Chakravarthy Mazumdar
doctor
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Follow up: Dr. Binu Parameswaran Pillai (40 hours later)
Thank you Dr XXXXXXX how 'high' does circulating test have to be to bring receptors to surface?

Also, i understand the sequence of puberty follows a fixed program...so would the circulating gonadal test present during time of adrenarche be enough to bind to all androgen sensitive tissues bone voice ( we know hair follicle already expressed due to appearance of hair during adrenarche)

Best Regards
XXXX
doctor
Answered by Dr. Binu Parameswaran Pillai (37 minutes later)
Brief Answer:
Hi

Detailed Answer:
Dear XXXX
A very difficult question. I am sorry to say that I do not know what is the optimum level of testosterone to induce expression of AR.

Circulating adrenal androgens during adrenarche does recruit some AR and sexual hair appears. But these adrenal androgens can not push the puberty beyond stage 3.

Almost 1 year after adrenarche, gonadarche starts and gonadal steroids are much more robust and powerful and that cause pubertal progression beyond XXXXXXX stage 3.

To answer your question, yes, adrenal steroids get converted to testosterone ( and DHT later) and bind to AR. However, it is the gonadal steroids which are the main player in puberty [rogression.

Binu
Above answer was peer-reviewed by : Dr. Chakravarthy Mazumdar
doctor
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Follow up: Dr. Binu Parameswaran Pillai (22 hours later)
Thanks again Dr XXXXXXX

just for clarification.

Does low circulating levels of androgens recruit proportionate number of AR in all the androgen sensitive tissues? Or is there a threshold that needs to be met?

My problem is whether the 'first time' gonadal androgens 'binded' with my bone voice tissues came after the steroid treatment I had?

Best Regards
XXXX
doctor
Answered by Dr. Binu Parameswaran Pillai (2 days later)
Brief Answer:
Hi

Detailed Answer:
Dear XXXX
Apologies for the delay.
In some tissues like vocal cord etc, the change happens only during puberty. so a particular concentration of androgens have to be there to recruit AR in certain tissues.

In your particular case, low levels of androgens would have bound to less number of available receptors in voice tissue prior to the treatment. However, a noticeble change would have occured only after the treatment.

But tell me XXXX why are you worried so much about it? Just curious to know

Binu
Above answer was peer-reviewed by : Dr. Chakravarthy Mazumdar
doctor
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Follow up: Dr. Binu Parameswaran Pillai (41 hours later)
Dear Dr XXXXXXX

I just want to be certain that my endogonous androgens already reacted/binded to various tissue sites like bone, voice etc to some degree BEFORE the ox treatment...when I started the treatment iwas examined and told I was in very early puberty and normal, but decided to have treatment to boost height..and after that my height would continue to grow as I was near 'a certain point' where this naturally happens.

The ox treatment can bind to sites and also increase endogonous levels by priming as previously discussed. If this subsequent increase in endogonous androgens then lead to first binding , again, I wont feel happy.
doctor
Answered by Dr. Binu Parameswaran Pillai (14 hours later)
Brief Answer:
Hi

Detailed Answer:
Hello,
I understood your concern. Please do not worry. Your own androgens have bound to the tissues. Thats why you entered in to puberty ( it could have been the adrenal androgens). Then the system was little lazy and then oxandrolone did the trick. It doesnt really affect your tetosterone system or fertility etc in any way in future.
Regards
Binu
Above answer was peer-reviewed by : Dr. Chakravarthy Mazumdar
doctor
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Follow up: Dr. Binu Parameswaran Pillai (2 days later)
Dear Dr XXXXXXX Thank you for all your valued answers .

I want to ask some brief followup on your answer' In your particular case low level of androgens would have bound to less number of receptors in voice tissue'...

In abovementioned scenario, are proteins still made?


doctor
Answered by Dr. Binu Parameswaran Pillai (4 hours later)
Brief Answer:
Hi

Detailed Answer:
Hi,
Voice change occurs in mid puberty at around stage 3-4. This may differ from person to person. If you have had breaking of voice prior to Oxandrolone, then you had voice apparatus change by androgens. But if you had voice change after the oxandrolone, probably the change happened after the treatment. I am sorry, i didnt understand the "proteins" which you mentioned

Binu
Above answer was peer-reviewed by : Dr. Chakravarthy Mazumdar
doctor
Answered by
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Dr. Binu Parameswaran Pillai

Endocrinologist

Practicing since :2003

Answered : 1439 Questions

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How Do Steroids Affect Puberty?

Brief Answer: Hi Detailed Answer: Dear XXXX Good day. Thank you for writing back to me. Came back from vacation yesterday. GnRH secretion is CNS regulated with so many other controlling factors involved. Oxandrolone and small dose of testosterone just prime the GnRH pulse generator and stimulate the puberty onset. Let us compare to a car engine. There are complex computer systems controlling the car engine. Occasionally the car engine fails to start on a cold morning. It is just like giving a little push to start a lazy car engine on a cold morning. . If the engine is normal, a little pushing will start it. However, if the engine is bad, this little push will not be enough . Similarly, in constitutional delay of puberty, we presume that the GnRH pulse generator and other controlling structures are normal, but a bit lazy. In that case, a little push with oxandralone or testosterone for a short period is good enought to kick start the gnRH pulse generator firing. in Congenital adrenal hyperplasia (CAH), there is peripheral precocious puberty first. However, in some patients, due to continues high exposure of androgens, a secondary central precocious puberty occurs. Weak steroids given in an otherwise healthy boy at 7 years will not lead to centtral puberty. Once the testicular volume is > 4 ml, the puberty is allready started. And in that case, some pubertal process has allready been started. If there is a delay in pubertal progression at that stage, a little push wiith oxandrolone may help. Regards Binu