Nandrolone & HPTA suppression  

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Black Baccara
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13/10/2018 7:26 am  

In the bodybuilding world, nandrolone has the reputation to strongly suppress the HPTA. Some of us even think that it could be more suppressive than Testosterone itself. In regard to this study it does not seem to be the case.

Suppression of spermatogenesis to azoospermia by combined administration of GnRH antagonist and 19-nortestosterone cannot be maintained by this non-aromatizable androgen alone.
Behre HM, Kliesch S, Lemcke B, von Eckardstein S, Nieschlag E.
Institute of Reproductive Medicine of the University (WHO Collaborating Centre for Research in Human Reproduction), D-48129 Munster, Germany.

BACKGROUND: For male hormonal contraception, combined administration of gonadotrophin-releasing hormone (GnRH) antagonists and androgens effectively suppresses spermatogenesis to azoospermia. In non-human primates this suppression can be maintained more easily by androgens alone. METHODS: A clinical trial with six healthy volunteers was performed to test this approach in man. Loading doses of 10 mg/day of the GnRH antagonist cetrorelix were given subcutaneously for 5 days, followed by maintenance doses of 2 mg/day up to week 12. At 2 weeks after the first GnRH antagonist injection, androgen substitution was initiated with a loading dose of 400 mg 19-nortestosterone hexyloxyphenylpropionate (19NT-HPP) intramuscularly, followed by injections of 200 mg 19NT-HPP every 3 weeks up to week 26. RESULTS: Serum concentrations of LH, FSH and testosterone were effectively suppressed by cetrorelix administration. Within 12 weeks, azoospermia was achieved in all six volunteers. After cessation of cetrorelix injections in week 12, gonadotrophins and testosterone increased significantly despite continued 19NT-HPP injections. In parallel, spermatogenesis was restimulated in five of six volunteers. CONCLUSIONS: Combined administration of cetrorelix and 19NT-HPP leads to azoospermia within 3 months. However, complete azoospermia cannot be maintained by continued injections of the non-aromatizable 19NT-HPP alone.

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ARTICHOKE
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13/10/2018 8:09 am  

Instersting, but i think that to keep a man in state of azoospermia is necessary a great inhibition! Look that according to the author, even with testosterone injections alone [200 mg Testosterone Enanthate (TE) per week], spermatogenesis was suppressed to azoospermia only in two-thirds of Caucasian men within 6 months .

In a addition, the dosage was not so high...they received 400 mg as loading, and maintenance dose injections of 200 mg were given every 3 weeks.


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Nandi
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13/10/2018 9:04 am  

I think if you compare the testosterone versus nandrolone levels in this often cited paper by Minto et al you will see that indeed nandrolone is suppressive

 

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Black Baccara
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13/10/2018 9:52 am  
Posted by: ARTICHOKE
Instersting, but i think that to keep a man in state of azoospermia is necessary a great inhibition! Look that according to the author, even with testosterone injections alone [200 mg testosterone enanthate (TE) per week], spermatogenesis was suppressed to azoospermia only in two-thirds of Caucasian men within 6 months .

Yes, I have read some papers where TE are not always able to inhibit totally endogenous T production and spermatogenesis.

@Nandi
I agree, of course nandrolone is suppressive, but because estrogens are an important key to HPTA inhibition, nandrolone is maybe not more suppressive than T ... do you think that at the same plasmatic concentration, nandrolone will achieve a more stronger inhibition that T ?


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Nandi
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13/10/2018 10:52 am  

Nandrolone binds with 20% of progesterone's affinity to the progesterone receptor (1), so this likely has a lot to do with nandrolones ability to suppress the HPTA. (Trenbolones RBA for the progesterone receptor is 60.)

(1) Cancer Res 1978 Nov;38(11 Pt 2):4186-98
Unique steroid congeners for receptor studies.
Ojasoo T, Raynaud JP.


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Black Baccara
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13/10/2018 11:51 am  

Yes I know but in some papers, 19-Nor forms and especially trien structures are said to be antagonist of the PR.
Maybe nandrolone is as suppressive as T (and maybe even a little more) but I just want to say that its inhibition power could be sometimes a little exagerated. And the same thing with some steroids that have been claimed to do not suppress hpta, in fact all steroids can suppress your endogenous T production, the 3 keys could be : aromatisation, androgenic power and progestational activity.


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Andy13
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13/10/2018 12:24 pm  

J Clin Endocrinol Metab. 1992 Jan;74(1):84-90.

Depot gonadotropin-releasing hormone agonist blunts the androgen-induced suppression of spermatogenesis in a clinical trial of male contraception.

Behre HM, Nashan D, Hubert W, Nieschlag E.

Thus far, when tested as male contraceptives, GnRH agonists in combination with androgens were not very effective in producing azoospermia. Since in previous studies androgens were always given simultaneously with the GnRH agonist or later, we tested whether GnRH agonist administration after an initial androgen suppression phase might yield better results. After a control period, 3 groups of young healthy men (n = 8/group) received an initial loading dose of 400 mg 19-nortestosterone hexyloxyphenylpropionate (19NT-HPP), followed by 200 mg of the ester every 3 weeks for 24 weeks. One week after the first 19NT-HPP injection, 2 groups were given a single sc implant injection of 3.3 or 6.6 mg of the GnRH agonist buserelin, respectively, whereas a placebo implant was given to the third group. In the group receiving only 19NT-HPP, serum LH and FSH were markedly suppressed and remained low during the treatment phase. In the 16 volunteers receiving the buserelin implant LH and FSH were also suppressed on day 7, followed by a marked increase in the gonadotropins up to 2 weeks after buserelin implant injection. While LH was consistently suppressed for the remaining treatment phase, FSH returned to almost normal values in weeks 9-15. In contrast to the group treated with 19NT-HPP alone, in which sperm concentrations were reduced to oligozoospermia after only 3 weeks of treatment, the first suppressive effect in the 19NT-HPP/buserelin-treated groups was not seen before week 9. After 30 weeks, when the maximal suppression of spermatogenesis was seen, 4 of 8 volunteers in the group treated with 19NT-HPP alone were azoospermic, and the remaining 4 volunteers were oligozoospermic. In the groups treated with 19NT-HPP/buserelin, no more than 4 of 16 volunteers were azoospermic, and no more than 8 of 16 volunteers were oligozoospermic at any time point. It is concluded that GnRH agonist depot preparations have a blunting effect on the suppression of pituitary and testicular function caused by androgens in men participating in contraceptive trials.

PIP: Administration of a depot gonadotropin-releasing hormone agonist (buserelin, Hoechst, Frankfurt am Main, Germany, GnRH) 7 days after full suppression of spermatogenesis with depot androgen, nortestosterone enanthate, reduced the degree of azoospermia compared to treatment with androgen alone. 3 groups of 8 men were given 400 mg 19-nortestosterone hexyloxyphenylpropionate (Anadur, Pharmacia Arzneimittel, Ratigen, Germany, 19NT-HPP) then 200 mg every 3 weeks for 24 weeks. The 3 groups then received a single sc implant of 3.3 or 6.6 mg GnRH or a placebo. In the 19NT-HPP-placebo group, LH and FSH both were fully suppressed throughout treatment, and 1 to 4 men were azoospermic from weeks 6-30. In contrast, in the men given GnRH agonist, LH and FSH were suppressed at first, spiked initially, then FSH rose to a maximum at 12 weeks, declined, and again rose to normal levels after week 27. Testosterone mirrored LH in remaining suppressed throughout. The appearance of azoospermia was noted in 6 weeks in Group 1, in 12 weeks in Group 2, and in 24 weeks in Group 3. Azoospermia lasted longest in Group 1 (median length 21 weeks), shortest in Group 3 (median 6 weeks). Testicular volume, sperm concentration and motility followed similar trends. The only change in clinical findings was increased hemoglobin and hematocrit in all groups. These results corroborate previous studies which showed less inhibition of spermatogenesis in men given GnRH in addition to androgens. Apparently androgens with GnRH antagonists are more effective in male effective in male contraception than GnRH agonists.


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Andy13
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13/10/2018 1:06 pm  

The authors of this article report azoospermia and reduction of testosterone from just 200mg/week 19-nortestosterone. ( The ester was not specified in the abstract but it was probably deconate. )

While 200mg/week is a low dose for a BBer, it seems rather high for fertility control. More recent publications indicate that doses much less than 200mg/week are effective for azoospermia.

Today, the practice of 'bridging' between cycles with a low dose ester is considered to be outdated, and so I think most of us already realize that as little as 100mg/week of an ester is can be quite inhibitory. The part of the abstract I found most striking is the duration of supression following the last 200mg injection-- Incredibly, 4-14 weeks!!

Lancet. 1984 Feb 25;1(8374):417-20.

Reversible azoospermia induced by the anabolic steroid 19-nortestosterone.

Schurmeyer T, Knuth UA, Belkien L, Nieschlag E.

Esterified 19-nortestosterone, an anabolic steroid which has been in clinical use for over 20 years, was administered intramuscularly to five healthy volunteers in doses of 100 mg/week for 3 weeks followed by 200 mg/week for a further 10 weeks. Azoospermia occurred 7 to 13 weeks after initiation of treatment and persisted for 4-14 weeks after the last injection. Serum gonadotropin and testosterone levels were reduced, but androgenic effects were maintained as indicated by unchanged libido and potency. No serious side-effects were noted. 19-nortestosterone appears to be a potential agent for male fertility control.


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Black Baccara
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13/10/2018 1:46 pm  

Thanks Andy ! my idea was to show that nandrolone 'suppressive effect has sometimes been exagerated, and in the other hand some other products has been claimed to don't suppress the hpta despite some evidences that they do.
But of course nandrolone is a potent androgen and it is able to shut down your hpta, but maybe not more (or just slighty) T.


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Andy13
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13/10/2018 2:41 pm  

Consider the following statement from the abstract:

Azoospermia occurred 7 to 13 weeks after initiation of treatment and persisted for 4-14 weeks after the last injection.

Many will misinterpret this and assume that 4-14 weeks is how long the ester stays in the body, period, without consideration for the accumulated dose. Azoospermia persisted for 4-14 weeks following 200mg/week dosing. This duration of time absolutely depends on the amount of drug administered.

Following a cycle of 400mg/week for 6-10 week, the recovery time will be considerably longer than the 4-14 weeks reported for 200mg/week dosing.


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Black Baccara
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13/10/2018 3:24 pm  

Yes, I agree but you will be "under the juice" for a longer period after your last injection too. Your recovery time start when your nandrolone blood levels have dropped.
Another point, I agree that pharmacokinetic depends from the ester you have choice AND the dose you have used. But with low amounts the plasmatic concentration is proportionnal to the amount you have injected with little to no change in the drug's half-life. With big amounts, like 3 to 4 times the normal dose, your plasmatic concentration will not rise in the same manner (i mean the answer will not be proportionnal) and the drug's half life will be lenghtened.


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Andy13
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13/10/2018 3:55 pm  
Posted by: Black Baccara
Yes, I have read some papers where TE are not always able to inhibit totally endogenous T production and spermatogenesis.

I've believe seeing a case where TE fails to inhibit spermatogenesis. Are you sure about endogenous T not being inhibited by TE? This I have not read in a publication.

quote:


I agree, of course nandrolone is suppressive, but because estrogens are an important key to HPTA inhibition, nandrolone is maybe not more suppressive than T ...?

To clarify- Are you saying that nandrolone may be less inhibitory because nandrolone treatment (alone) would decrease estrogen (below normal levels) (?)

quote:


do you think that at the same plasmatic concentration, nandrolone will achieve a more stronger inhibition that T ?

You could probably find a paper where this was looked at. I think anecdotal reports seem to suggest that nandrolone, mole per mole, is more inhibitory than testosterone. On the other hand, deca has a considerably longer halflife compared to the usual T esters (prop, cyp). This translates into considerably longer length of time after a cycle before exogenous nandrolone levels become low enough to permit natural T production (compared to a similar cycle with T esters).


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Black Baccara
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13/10/2018 4:48 pm  

1) Yes I have read some papers where TE was not a perfect contraception method for male. In some case it did not achieve totally the goal, and some men have kept intratesticular testosterone. So they suggest new way of researchs like MENT (19-Nor derivative).

2) I cannot say if nandrolone is less or more inhibitory than T. But I assume that Nandrolone's inhibitory effects have sometimes been exagerated.
About estrogen I mean : if I use T with an AI, I will need a higher plasmatic concentration to suppress my HPTA. That's how AI and SERM work to increase T levels.

3) Yes maybe you are true, maybe mole per mole, nandrolone is more inhibitoy than T, maybe ... but nandrolone is also more potent mole per mole, that's mean that you will need a less higher plasmatic concentration to achieve the same goals. We can compare them mole per mole, I agree, but we can also compare HPTA suppression for the same anabolic effect because muscles hypertrophy is our goal.

The choice of the ester is another problem but like I have said before, your recovery time does not start after your last injection ! It starts when your AAS plasmatic concentration has dropped under the normal range.


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jboldman
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13/10/2018 5:43 pm  

This might shed some light.

jb

======================================

J Clin Endocrinol Metab. 2005 Feb 15; [Epub ahead of print] Related Articles, Links

Pharmacokinetic Evaluation of Three Different Intramuscular Doses of Nandrolone Decanoate: Analysis of Serum and Urine Samples in Healthy Men.

Bagchus WM, Smeets JM, Verheul HA, DE Jager-VAN DER Veen SM, Port A, Geurts TB.

Department of Clinical Pharmacology and Kinetics, Organon, Oss, the Netherlands; International Regulatory Affairs, Organon, Oss, the Netherlands; Xendo Laboratories, Groningen, the Netherlands;Focus Clinical Drug Development, Neuss, Germany; International Medical Services, Organon, Oss, the Netherlands.

Pharmacokinetics of nandrolone in serum and urine was investigated in healthy young men after a single intramuscular injection of 50 mg (n = 20), 100 mg (n = 17) or 150 mg (n = 17) nandrolone decanoate. Blood samples were collected pre-dose and for up to 32 days after dosing. In addition, in the 50 and 150 mg groups 24-hours urine samples were collected at pre-dose and during days 1, 7 and 33, and in the 150 mg group additional samples were collected after 3 and 6 months. Serum concentrations and area-under-curve of nandrolone increased proportionally with the dose administered. Peak serum concentration (Cmax) ranged from 2.14 ng/mL in the 50 mg group to 4.26 ng/mL in the 100 mg group and to 5.16 ng/mL in the 150 mg group. Cmax was reached after 30 (50 and 100 mg) and 72 h (150 mg), whereas the terminal half-life was 7-12 days. In urine, pre-dose concentrations of 19-NA and/or 19-NE were detected in 5/37 subjects (14%). In the 50 mg group, 19-NA and/or 19-NE could be detected at least until 33 days after injection in 16/17 subjects (94%). In the 150 mg group of subjects presumed to have not previously used nandrolone, nandrolone metabolites could be detected up to 6 months in 8/12 subjects (67%) for 19-NE to 10/12 subjects (83%) for 19-NA.


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Black Baccara
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13/10/2018 6:39 pm  

Comparison between testosterone enanthate-induced azoospermia and oligozoospermia in a male contraceptive study. I: Plasma luteinizing hormone, follicle stimulating hormone, testosterone, estradiol, and inhibin concentrations

EM Wallace, SM Gow and FC Wu
Department of Clinical Biochemistry, Royal Infirmary Edinburgh, Scotland.

Sex-steroid based male contraceptive regimes induce azoospermia in only 40-70% of Caucasian men. The reason(s) why the remainder maintains a low level of spermatogenesis (oligozoospermia) despite gonadotrophin suppression is unclear. In order to improve our understanding of this phenomenon, we examined the changes in sperm density and plasma LH, FSH, testosterone (T), oestradiol (E2), and inhibin (IN) in 28 normal men who received 200 mg testosterone enanthate (TE) im weekly during a male contraceptive efficacy trial. Gonadotrophins were measured by an ultrasensitive time-resolved immunofluorometric assay (DELFIA) with a sensitivity of 0.04 U/L, to determine the adequacy of suppression. Seventeen of the 28 men achieved azoospermia; the other 11 remained oligozoospermic (sperm density 3.3-4.7 x 10(6)/mL) after 6 months of TE exposure. Azoospermic subjects displayed a more rapid decline in sperm density, a significant difference being apparent by 5 weeks after starting TE. During TE treatment, both LH and FSH were consistently suppressed to below the limits of detection, whereas there was a 2.5- fold rise in T and E2 with a similar decrease in IN. There were no consistent differences in any of these hormone concentrations between the azoospermic and oligozoospermic groups. Recovery of sperm density to baseline levels or above 20 x 10(6)/mL was significantly slower in the azoospermic group. During the recovery phase, the azoospermic men exhibited significantly higher LH and FSH levels compared to baseline and to the oligozoospermic subjects even though no differences in circulating T, E2, or IN were observed. We conclude that incomplete gonadotrophin suppression or differences in sex steroid or inhibin levels are unlikely to be responsible for the maintenance of minor degrees of spermatogenesis in some men during TE administration. The rebound rise in gonadotrophins in azoospermic but not oligozoospermic responders during recovery may reflect a more profound degree of spermatogenic suppression in the former group.


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