Mr. H:
I respect your education and level of knowledge, but not your arrogance, so pull the ivory tower out of your ass and save your insults (
"Sigh, this is tedious, where the hell did you come up with this, etc...") and I will save mine.
NPP is a 19-nor. As a result it cannot be converted by aromatase into an estrogen. Androgen to estrogen ratio related gyno is related to AAS. The concern with 19-nors is prolactin related progesterone gynecomastia.
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Acta Endocrinol (Copenh). 1982 Sep;101(1):108-12.
Influence of nandrolondecanoate on the pituitary-gonadal axis in males.
Bijlsma JW, Duursma SA, Thijssen JH, Huber O.
Abstract
Different anabolic steroids can exercise different effects on the pituitary-gonadal axis in males. During a pilot study regarding the possible beneficial effect of the anabolic steroid nandrolondecanoate (ND) on bone metabolism in patients with rheumatoid arthritis additional endocrinological parameters were studies. A significant decrease was found in the serum levels of testosterone, androstenedione and FSH and the ratio of testosterone/oestradiol. There was a significant increase in the serum levels of oestrone. The levels of oestradiol, SHBG, LH and cortisol remained unchanged. An inhibitory effect of ND on testicular testosterone secretion is assumed. The decrease in androstenedione levels is explained by the diminished testosterone secretion. The rise in oestrone levels is explained by peripheral aromatizing of ND to oestrogens. The presented findings are in accordance with the hypothesis that sex steroids can act directly on the pituitary resulting in selective FSH and LH secretion. The possible role of the ratio testosterone/oestradiol in controlling gonadotrophin output is discussed.
PMID: 6812344
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Nippon Naibunpi Gakkai Zasshi. 1986 Jan 20;62(1):18-25.
[Aromatization of androstenedione and 19-nortestosterone in human placenta, liver and adipose tissues]
[Article in Japanese]
Yoshiji S, Yamamoto T, Okada H.
Abstract
Aromatization of C-19-steroid (androstenedione; delta 4 A) and C-19 norsteroid (19-nortestosterone; NT) was measured in human placenta, liver and adipose tissues. The tissue homogenates (0.5 approximately 1.0 g w.w.) were incubated with [6, 7-3H]-delta 4 A or [6, 7-3H]-NT (10 microCi) and NADPH (1 mg/ml of 0.1M-bisodium phosphate buffer) at 37 degrees C for 2 hr in air. The enzyme reaction was terminated with 3 volumes of ethyl acetate, and [4-14C]-estrone (E1) and [4-14C]-estradiol-17 beta (E2) (10,000 dpm, 250 micrograms) were added in the incubated sample. The extract with ethyl acetate was subjected to Bio-Rad AG1-X2 column chromatography. The phenol fraction thus obtained was subjected to thin layer chromatography (TLC) (cyclohexane-ethyl acetate = 2:1, V/V and chloroform-ethyl ether = 4:1, V/V). The resulting E1 and E2 were finally isolated by co-crystallization to constant specific activity and 3H/14C ratio of crystal crops. In human placental microsomes, estrogen formation from delta 4 A and NT was 8.10 and 1.84 pmol E1 + E2/hr/mg protein, respectively. In adult liver homogenates, only E1 (35-76 fmol/hr/g) was formed from delta 4 A, but E1 and E2 were formed (70 and 31-61 fmol/hr/g, respectively) from NT. On the other hand, adipose tissue had the ability to aromatize delta 4 A to E1 (38-69 fmol/hr/g), but its ability to aromatize NT was significantly lower than that for delta 4 A. These results show that NT is readily aromatized to estrogens in the liver.
PMID: 3699194
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Climacteric. 2007 Aug;10(4):344-53.
Can 19-nortestosterone derivatives be aromatized in the liver of adult humans? Are there clinical implications?
Kuhl H, Wiegratz I.
Department of Obstetrics & Gynecology, J.W. Goethe University Frankfurt, Frankfurt am Main, Germany.
Comment in:
Climacteric. 2008 Apr;11(2):175; author reply 175-6.
Abstract
CONTEXT: Previous studies in postmenopausal women have demonstrated that, after oral administration of norethisterone, a small proportion of the compound is rapidly converted into ethinylestradiol. The shape of the concentration - time curve suggested that this occurred in the liver. The results were confirmed by in vitro investigations with adult human liver tissue. In 2002, it was shown that, after oral treatment of women with tibolone, aromatization of the compound occurred, resulting in the formation of a potent estrogen, 7 alpha-methyl-ethinylestradiol. The result has been called into question, because the adult human liver does not express cytochrome P450 aromatase, which is encoded by the CYP 19 gene. Moreover, it has been claimed that the serum level of 7 alpha-methyl-ethinylestradiol measured by gas chromatography/mass spectrometry was an artifact. REPLY: Aromatization of steroids is a complex process of consecutive oxidation reactions which are catalyzed by cytochrome P450 enzymes. The conversion of the natural C19 steroids, testosterone and androstenedione, into estradiol-17beta and estrone is dependent on the oxidative elimination of the angular C19-methyl group. This complex key reaction is catalyzed by the cytochrome P450 aromatase, which is expressed in many tissues of the adult human (e.g. ovary, fat tissue), but not in the liver. However, 19-nortestosterone derivatives are characterized by the lack of the C19-methyl group. Therefore, for the aromatization of these synthetic steroids, the action of the cytochrome P450 aromatase is not necessary and the oxidative introduction of double bonds into the A-ring can be catalyzed by other hepatic cytochrome P450 enzymes. The final key process in the formation of a phenolic A-ring, both in natural androgens and 19-nortestosterone derivatives, is the enolization of a 3-keto group to the C2-C3-enol or the C3-C4-enol moiety, which occurs without the action of enzymes. CONCLUSION: 19-nortestosterone derivatives (norethisterone, norethynodrel, tibolone) can readily be aromatized in the adult human liver. This leads to the formation of the potent estrogens ethinylestradiol from norethisterone or norethynodrel and 7 alpha-methyl-ethinylestradiol from tibolone. This may have clinical consequences, e.g. the elevated risk of venous thromboembolic disease in premenopausal women treated with high doses of norethisterone for bleeding disorders, or the elevated risk of stroke or endometrial disease in postmenopausal women treated with tibolone.
PMID: 17653961
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You're right-Nandrolone cannot possibly be aromatized. Where did I get that idea...
Sigh this is getting tedious going to list format.
1.) He is not talking about tren.
I know that. I did make it far enough through 3rd grade to learn how to read.
I was talking about tren. Sorry for the apparent confusion it seems to have caused you.
2.) Gynecomastia is not the only symptom related to increased estrogen.
Really? Thank you for that; very edifying. Did I say it was the only symptom?
3.) As a first cycle are you really suggesting he stack test and NPP?
Without looking back at my post b/c I don't really care, IIRC, I said something like, if the OP is hellbent on running NPP for his first cycle, then it would make sense to combine it with something a bit more androgenic such as testosterone. But if solo nandrolone cycles float your boat, have at it.
1.) Finasteride has no effect on HPTA shutdown. It is not an exogenous source of testosterone.
Yes, finasteride isn't laced with testosterone, I will admit that much. However, if one were to run a test-only stack for example, then the inclusion of finasteride alongside the test would reduce the amount of androgenic negative feedback to the HPTA since DHT conversion would be diminished. Hence, HPTA shutdown would be reduced to some degree-it might be negligible depending on how much estrogenic negative feedback is being produced given that estrogen is much more suppresive to the HPTA in males, but the point remains. If coupled with a SERM instead of an Aromatase inhibitor (AI) to keep estrogen levels reasonable but also avoiding estro-related sides such as mammary ER stimulation (the worrisome one for most people), the finasteride/test/SERM combo would greatly reduce HPTA shutdown versus a typical test only cycle. This isn't a cycle I would run personally, but I would never run finasteride either, so I thought hypothetical discussion would be permissible instead.
2.) 19-Nor's work through increased nitrogen retention. Why are you talking about cortisol?
My memory sucks, but ALL AAS promote increased nitrogen retention in the presence of sufficient calories and protein. The 19-nors aren't special in this regard. However, and again I guess I confused the matter by even mentioning tren, tren has signficant GR affinity and anti-glucocorticoid effects not unlike anavar. Strong suppression of cortisol on cycle due to tren, tren + var, etc can produce a significant cortisol rebound effect when the cycle ends. Consequently, it makes some degree of sense to stop the tren (for example) a few weeks before stopping testosterone (if running alongside) or else ending the tren cycle with a few weeks of replacement dosing of test before ending the cycle completely.
3.) Cortisol levels are directly associated with estrogen blood values. We have not even broached the subject of AI's but unless he was using 2.5mg of letro a day for over a month there would be no estrogen rebound thus no cortisol increase. Where the hell did you come up with cortisol rebound. Rebound signifies a suppression of cortisol which would signify that there would be no break down and rebuilding of tissues on cycle thus no growth.
Cortisol rebound-where the hell did I come up with it? I read it in a book
.
That's funny; I get a pretty noticeable estro rebound after just a few weeks of .625mg/day of letrozole. Very pronounced at 2.5mg a day for a few short weeks.
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Eur J Cancer. 1999 Feb;35(2):208-13.
Double-blind, randomised, multicentre endocrine trial comparing two letrozole doses, in postmenopausal breast cancer patients.
Bajetta E, Zilembo N, Dowsett M, Guillevin L, Di Leo A, Celio L, Martinetti A, Marchianò A, Pozzi P, Stani S, Bichisao E.
Division of Medical Oncology B, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy.
Abstract
Letrozole is an orally competitive aromatase inhibitor. This double-blind, randomised, multicentre trial was carried out to evaluate the endocrine effects of two doses of letrozole, 0.5 mg versus 2.5 mg orally daily, in postmenopausal advanced breast cancer patients progressing after tamoxifen. The pharmacokinetics of letrozole was also assessed. 46 patients entered the trial, 22 on letrozole 0.5 mg and 24 on 2.5 mg. A significant suppression of oestrone and oestradiol levels was achieved by both letrozole doses. Neither letrozole dose induced any changes in cortisol and aldosterone production at rest or after Synacthen stimulation. Androstenedione, testosterone, 17 alpha-OH progesterone, triiodothyronine (T3) thyroxine, (T4) and thyroid-stimulating hormone (TSH) plasma levels did not show any significant changes. Sex hormone binding globulin (SHBG), follicle-stimulating hormone (FSH) and luteinising hormone (LH) levels increased significantly over time. Plasma letrozole concentrations increased until reaching steady-state values after 1 month at the dose of 0.5 mg and after 2 months at 2.5 mg. In conclusion, both letrozole doses suppressed oestrogen levels without affecting adrenal activity.
PMID: 10448261
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J Clin Oncol. 2009 Jul 1;27(19):3192-7. Epub 2009 Apr 20.
Endocrine effects of adjuvant letrozole compared with tamoxifen in hormone-responsive postmenopausal patients with early breast cancer: the HOBOE trial.
Rossi E, Morabito A, Di Rella F, Esposito G, Gravina A, Labonia V, Landi G, Nuzzo F, Pacilio C, De Maio E, Di Maio M, Piccirillo MC, De Feo G, D'Aiuto G, Botti G, Chiodini P, Gallo C, Perrone F, de Matteis A.
Clinical Trials Unit, National Cancer Institute of Naples, Via Mariano Semmola, 80131, Napoli, Italy.
Comment in:
J Clin Oncol. 2010 Feb 20;28(6):e101-2; author reply e103-4.
Abstract
PURPOSE We compared the endocrine effects of 6 and 12 months of adjuvant letrozole versus tamoxifen in postmenopausal patients with hormone-responsive early breast cancer within an ongoing phase III trial. PATIENTS AND METHODS Patients were randomly assigned to receive tamoxifen, letrozole, or letrozole plus zoledronic acid. Serum values of estradiol, follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, dehydroepiandrosterone-sulphate (DHEA-S), progesterone, and cortisol were measured at baseline and after 6 and 12 months of treatment. For each hormone, changes from baseline at 6 and 12 months were compared between treatment groups, and differences over time for each group were analyzed. Results Hormonal data were available for 139 postmenopausal patients with a median age of 62 years, with 43 patients assigned to tamoxifen and 96 patients assigned to letrozole alone or combined with zoledronic acid. Baseline values were similar between the two groups for all hormones. Many significant changes were observed between drugs and for each drug over time. Namely, three hormones seemed significantly affected by one drug only: estradiol that decreased and progesterone that increased with letrozole and cortisol that increased with tamoxifen. Both drugs affected FSH (decreasing with tamoxifen and slightly increasing with letrozole), LH (decreasing more with tamoxifen than with letrozole), testosterone (slightly increasing with letrozole but not enough to differ from tamoxifen), and DHEA-S (increasing with both drugs but not differently between them). Zoledronic acid did not have significant impact on hormonal levels. CONCLUSION Adjuvant letrozole and tamoxifen result in significantly distinct endocrine effects. Such differences can explain the higher efficacy of letrozole as compared with tamoxifen.
PMID: 19380451
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Two small randomized trials of 0.5 and 2.5 mg/day letrozole have been performed. The first, from Europe (15) , included 46 patients, 22 women randomized to 0.5 mg of letrozole and 24 to the higher dose. All patients had progressed on one prior antiestrogen therapy, and all had measurable or evaluable disease. After 2 weeks of letrozole treatment, serum estrogen levels were significantly reduced in both groups. By 4 weeks, 24% of women in the low-dose group and 28% of women in the higher dose group had nondetectable estrogen levels. Neither letrozole dose affected basal nor stimulated cortisol or aldosterone plasma levels. Plasma levels of triiodothyronine (T3), thyroxine (T4), and thyroid-stimulating hormone were not changed in either group. Sex hormone-binding globulin, follicle-stimulating hormone, and luteinizing hormone levels increased significantly over time. Two complete responses were noted in each treatment group, and an additional 2 women receiving 0.5 mg/day letrozole had partial responses. Median response duration was >170 days, and median TTP was ***8764;100 days.
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I don't have the level of formal education that you do, nor do I care, but am I missing something here (honest, serious, no sarcasm)? I do remember reading about a direct correlation between estrogen and cortisol, but I have read a bajillion studies on letrozole, and none of them have indicated any significant effect on adrenal steroid synthesis (in contrast to its dramatic effects on estrogen). I even had an anesthesiologist friend of mine call the manufacturer of Femara directly and they said "no effect on adrenal steroid synthesis".
1.) Are you really suggesting an oral only cycle?
No, I wasn't suggesting a cycle at all, much less an oral only cycle, just possible steroids. However, if the OP is really so concerned about his prostate, he would do best to avoid AAS altogether.
2.) All AAS are exogenous.
No, they aren't. Testosterone is an endogenously produced AAS. It can be exogenously administered, but I kind of assumed that was obvious given the audience. The only difference of importance is that for most people, typical endogenous test levels do not adversely affect HPTA function in the manner typical of say 600mg/wk of IM test cyp.
3.) Once again 19-nor gynecomastia is a result of prolacin induced progesterone gynecomastia.
That's your opinion...unless you have some clinical evidence you were planning to share with us to support this forum theory...
And granted, AAS-using BB'ers aren't castrated sheep (at least not in the literal sense), the few studies on trenbolone ace in animals are interesting nonetheless.
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Res Vet Sci. 1981 Jan;30(1):7-13.
Growth hormone, insulin, prolactin and total thyroxine in the plasma of sheep implanted with the anabolic steroid trenbolone acetate alone or with oestradiol.
Donaldson IA, Hart IC, Heitzman RJ.
Abstract
The mode of action of the anabolic steroid trenbolone acetate (19-norandrost-4,9,11-trien-3-one-17-acetate) was studied through the endogenous hormonal response of castrated male sheep to subcutaneous implantation of 140 mg of trenbolone acetate and 20 mg of oestradiol both separately and in combination. Radioimmunoassay of delta-4,9,11-trienic steroids and oestradiol-17 beta in plasma confirmed that simultaneous administration of trenbolone acetate with oestradiol led to a significantly greater persistence of oestradiol-17 beta residues in plasma (P less than 0.05) than with implantation of oestradiol alone. Oestradiol treatment increased concentrations of growth hormone and insulin (P less than 0.05; P less than 0.001 respectively) in plasma samples collected weekly. Trenbolone acetate by itself had no significant effect and the oestrogenic response was blocked on the simultaneous implantation of trenbolone acetate and oestradiol (despite higher plasma levels of oestradiol-17 beta with this treatment). Plasma total thyroxine was markedly depressed to 45 per cent of its basal level by trenbolone acetate, alone or with oestradiol (P less than 0.001) and depressed to 80 per cent of basal by oestradiol treatment alone (P less than 0.001). Plasma prolactin was unaltered by the above treatments.
PMID: 7017853
EDIT: "Backtalked to?" So it is "injudicious" to have an opinion that does not align with your own. Why is that? Because of your extensive educational credentials? Sorry (Mom), I didn't know that we weren't allowed to have our own opinions and discuss them in a semi-intelligent manner. It won't happen again, and yes, I am going to do my chores right now, before dinner, as promised. Seriously, grow up; there is no need for this high horse nonsense. Clearly I could learn a lot from you, and there are other things that you can do with your time that are more worthwhile, but it is hard to consider comments and advice when they are delivered so dogmatically, insultingly, and callously. We are all human and we are learning (well most of us are learning, I hope).
With that said, the following is not directed at Mr. H. There are definitely some people on this thread that -really- need to grow the fuck up and lose the attitude and at least give the overly helpful vets who are giving them sound advice a hearing before opening their mouths (yes, I am agreeing with Mr. H here, if I understand his above post correctly). If you can't control your poise and attitude when you are -planning- a first cycle (and a horrible one at that-NPP solo, give me a break), then what the hell do you think AAS are going to do to your negativity when you are on cycle?