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Can Steroid Treatment Cause A Decrease Of Endogonous Hormones In Pre Pubertal Boys?

Posted on Fri, 29 Nov 2013

Question: Hi. I read a study online that 3 month steroid treatment (oxandrolone) caused a decrease of endogonous hormones in pre pubertal boys. Does this suggest negative feedback mechanism is present, even at this age? Best Regards

Answered by Dr. Lohit K (1 hour later)

Brief Answer: yes there will be negative feedback at every age Detailed Answer: Hi XXXXXX, thanks for using XXXXXXX yes at every age there will be feedback mechanism wih the steroid / hormone supplements. That is the basic reason behind gradual withdrawal of steroids on chronic therapy. Steroids should not be taken without doctor's advice and without any indication. Hope this answered your query. Feel free to ask if any related query and I will be glad to answer them. Wish you good health. Regards

Above answer was peer-reviewed by : Dr. Chakravarthy Mazumdar

Follow up: Dr. Lohit K (3 hours later)

Thanks for reply. Does it exist after birth....or even feotal stage? Or does it only come into effect in later life ie teenage years? Any studies links would be great Beat regards

Answered by Dr. Lohit K (18 hours later)

Brief Answer: Yes, even from foetal age group. Detailed Answer: Hi XXXXX, thanks for the reply. Yes the negative feedback mechanism present even in feotal age. I am giving you the direct sentence from the text book Katzung Basic and clinical pharmacology for your reference. Cortisol (also called hydrocortisone) exerts a wide range of physiologic effects, including regulation of intermediary metabolism, cardiovascular function, growth, and immunity. Its synthesis and secretion are tightly regulated by the central nervous system, which is very sensitive to negative feedback by the circulating cortisol and exogenous (synthetic) glucocorticoids. Hope this will help you to clarify the doubt.. Regards

Above answer was peer-reviewed by : Dr. Chakravarthy Mazumdar

Follow up: Dr. Lohit K (2 hours later)

Dear Dr Lohit K. Thank you for that. But I'm referring to sex steroids presence during foetal age and 0-6 month age (the baby boy testosterone surge) Or does above apply to sex steroids also? Kind Regards

Answered by Dr. Lohit K (2 hours later)

Brief Answer: yes sex steroids have negative feedback mechanism Detailed Answer: Hi XXXXX, Yes there will be feedback mechanism for sex steroids also. The genetic makeup, race, ethnicity and other properties of an individual has influence on the level of sex steroids secretion. The use of anabolic steroids (manufactured androgenic hormones) can lead to a perceived high level of testosterone by the hypothalamus, resulting in reduced luteinising hormone secretion from the pituitary gland and, in turn, a decrease in the amount of testosterone produced within the testes, while artificial testosterone levels remain high. I think there is slight confusion about the steroidal hormones secreted by human beings, I like to give the explanation to clarify the confusion. The testes and ovaries, generate the sex steroids that are required for gametogenesis, secondary sexual characteristics and reproduction. However, the adrenal glands of adult human beings secrete generous quantities of the C19 steroids dehydroepiandrosterone (DHEA) and DHEA-sulphate (DHEA-S). Neither DHEA nor DHEA-S activate the androgen receptor, but in peripheral tissues they act as precursors for the potent androgens testosterone and dihydrotestosterone. The onset of DHEA-S production from the adrenal zona reticularis leads to the phenomenon of adrenarche. In order for adrenarche to occur, a specific cell type with the capacity to synthesize DHEA-S must arise within the adrenal glands. Cell biology experiments have shown that these cells are the zona reticularis cells of the adrenal cortex, and biochemical studies of the steroidogenic enzymes expressed in these cells explain why steroidogenesis proceeds readily to DHEA-S and no further. Hope this explanation is both informative and helpful to you. Regards

Above answer was peer-reviewed by : Dr. Chakravarthy Mazumdar

Follow up: Dr. Lohit K (13 minutes later)

Thanks. I want to know if testosterone negative feedback mechanism exists in foetal stage of a male? And does it exist after he is born, as there are high circulating levels of testosterone up to 6 months?? Best Regards

Answered by Dr. Lohit K (35 minutes later)

Brief Answer: Yes, negative feedback mechanism exists Detailed Answer: Hi, Yes, In all age there will be negative feedback (decreases the GnRH pulse frequency and decrease pituitary release of LH hormone) for the high circulating testosterone levels. Ref: XXXXXXX Principles of Pharmacology, 2nd edition. Hope this helps you. Regards

Above answer was peer-reviewed by : Dr. Chakravarthy Mazumdar

Follow up: Dr. Lohit K (14 hours later)

Thanks Dr Lohit K Is there evidence to support this or is XXXXXXX reference based on theory? Im very grateful for your advice. Best Regards XXXXX

Answered by Dr. Lohit K (3 hours later)

Brief Answer: Yes, there is negative feedback Detailed Answer: Hi, XXXXX I appreciate your interest to know the mechanism behind hormonal secretion in detail. Even I searched in many articles and text books for the same. I like to give some direct sentences from the well know textbook Goodman and Gillman's Pharmacological basis of therapeutics which is universally accepted and is based on evidence. Testosterone in 1st trimester: Principal factor in male sex differentiation. 2nd trimester: Level similar to mid puberty, then falls by the end of 2nd trimester but by birth again raises due to stimulation of fetal Leydig cells by LH hormone, then again the levels falls in first few days of birth and peaks by 2-3 months and falls by 6 months and remains same till puberty. The pulsatile secretion of LH is positively regulated by GnRH and testosterone directly inhibits its secretion by negative feedback. (Crowley et al. Recent Prog Horm Res, 1985, 41:473-571). I hope this will help you in clarifying your doubt. Feel free to ask if any query or clarifications. If satisfied you can close the query and write a review as well. Wish you happy life. Regards

Above answer was peer-reviewed by : Dr. Chakravarthy Mazumdar

Follow up: Dr. Lohit K (57 minutes later)

Thank you Dr Lohit. I have a theory that HPG axis, in fetal and after birth stage, is allowed to produce as much testosterone without regulation. Ie no need for feedback. Because it's only temporary activation of this axis before it goes 'to sleep' till puberty time. What would be your opinion on this?

Answered by Dr. Lohit K (28 hours later)

Brief Answer: Inactive state till the value is in normal level Detailed Answer: Hi XXXXX, There will be a rhythmic release of hormones in the body and the levels will be maintained and regulated by genetic makeup and external influence. Few example are like circadian rhythm, variation in receptor response, Blood pressure, enzymatic activity with in 24 hours, menstrual periods, attaining maturity(puberty) etc. But when there is excess amount of hormones secrete than normal level then the negative feedback will activate and get back the values to normal level. So there will be activation and inactivation of the negative feedback to maintain the levels to normal and this will be active through out the life. If defect then there will be no control of hormone levels and will lead to many problem. The feedback mechanism will be in inactive state till the value is with in normal level. Hope this helps you. Regards

Above answer was peer-reviewed by : Dr. Chakravarthy Mazumdar

Follow up: Dr. Lohit K (2 hours later)

Thank you DR LOHIT K for great advice. I have a final interesting query. You mention when hormones are high , negative feedback is activated. For testosterone, is this through aromitization to estrogen or through directly on androgen receptor? Or both? Secondly , is there evidence for this negative feedback to be activated , due to higher than normal test levels, during fetal stage, afterbirth stage? Best Regards

Answered by Dr. Lohit K (11 hours later)

Brief Answer: Both. Yes there is evedence Detailed Answer: Hi, Both will act. Testosterone is weaker than estrogen in inhibiting Gn secretion, but has effect on both FSH and LH. Evidence is there. You can refer Goodmann and Gillman textbook, XXXXXXX textbook for the same. Example in Klinefelter syndrome there will be hypogonadism with small testes but the GnRH, FSH and LH will be raised with low testosterone. The treatment is testosterone and after supplementing testosterone the FSH and LH comes to normal. If There is a problem in hypothalamus or pituitary then the patient may also suffer from hypogonadism (decreased testosterone) even with normal gonads. Hope this helps you. Regards

Above answer was peer-reviewed by : Dr. Chakravarthy Mazumdar

Follow up: Dr. Lohit K (7 hours later)

Thank you Dr Lohit K, Before I go one final query. I'd like to ask about possibilities of steroids having a stimulatory effect on gnrh pulse generator and pituitary gland. Traditionally, we understand outside sex steroids have 'negative feedback' on the endogonous levels. But suppose there is NO endogonous circulating levels to start with ie it's 0. And then sex steroids is given. In above scenario, would this 'outside sex steroid' have stimulatory effect on gnrh generator to start producing gnrh? Thank you if you can help. Wishing you all the best

Answered by Dr. Lohit K (21 hours later)

Brief Answer: Yes, there will be regulation Detailed Answer: Hi XXXXX, Yes outside (external) sex steroids have 'negative feedback' on the endogenous levels through the action on pituitary. When in 0 stage that is no endogenous hormone is secreted (intra uterine life) then also due to genetic influence there will be development of the organs and later on the regulation will start. The stimulatory or inhibitory effect depends on the level of hormone that is present and also affected by the influence of genes and external factors. But if given in 1st trimester (1st 3 months of intrauterine life) there may be teratogenic effects affecting the organs. There is not much evidence on this so I cannot comment on this. You can discuss with the endocrinologist for more clarification. Hope this helps you. Regards

Above answer was peer-reviewed by : Dr. Chakravarthy Mazumdar

Follow up: Dr. Lohit K (23 hours later)

Thank you Dr Lohit K. If i may i forgot to ask one more thing. In delayed puberty boys treated with oxandrolone, their hormones decreased during treatment but then 'rebounded higher' after the treatment. Does this mean the higher levels is now the 'new normal'? And if its sustained, does this mean oxandrolone, in a way, matured the hpg axis?? Best Regards, XXXXX

Answered by Dr. Lohit K (28 hours later)

Brief Answer: new normal can be possible Detailed Answer: Hi, Yes new normal can be possible, but this will be considered as a problem. But we cannot tell whether it is due due to oxandrolone or due to other cause. There are no studies on this. But before confirming it, the level of LH and testosterone should be measured. If testosterone is raised with low LH then the problem may be in testes (excess secretion) and if LH and testosterone both are raised then the problem may be in Pituitary. If the level of testosterone raises with the oxandralone therapy then the drug should be gradually withdrawn to get back the normal level.. Hope this answered your query. Wish you good health. Regards

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Above answer was peer-reviewed by : Dr. Chakravarthy Mazumdar