Tren/Deca induced progestin/prolactin induced gyno and it's relationship to thyroid hormone levels....

[MisterX]

This is a thread at Eleete, worth checking out...I'll post the highlights and you can discern for yourself wether or not it has merit. Thoughts on PR gyno??


http://boards.elitefitness.com/forum...0&pagenumber=1

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The potential relationship between trenbolone, thyrotropin-releasing hormone (TRH) and prolactin. TRH stimulates the synthesis and release of thyrotropin (thyroid stimulating hormone) from the pituitary. Thyrotropin in turn stimulates the release of the thyroid hormones. A negative feedback loop exists whereby low levels of T4 stimulate the release of TRH (1).

It has been established that in humans TRH is also capable of stimulating the release of prolactin (2). In hypothyroid patients there is often an elevation of TRH and prolactin due to diminished levels of T4. (3) Galactorrhea often presents as a symptom of hypothyroidism.

In sheep, administration of trenbolone acetate results in 45% decrease in thyroxine levels (4). This should exert a stimulatory effect on TRH. ( Interestingly, the same study shows that unlike in humans prolactin levels in the sheep remained unchanged. This is due to the fact that in sheep, unlike in humans, TRH and prolactin are secreted independently of each other (5).)

If it assumed that trenbolone acetate also lowers thyroxine levels in humans, the resulting rise in TRH would stimulate prolactin release, leading to galactorrhea and gynecomastia.

Due to the lack of human studies involving tren, we are all forced to speculate, and try to extrapolate from animal studies.

(1)Endocrinology 1999 Jan;140(1):43-9

Feedback regulation of thyrotropin-releasing hormone gene expression by thyroid hormone in the caudal raphe nuclei in rats.

Yang H, Yuan P, Wu V, Tache Y.
Digestive Diseases Research Center, West Los Angeles VA Medical Center, Department of Medicine and Brain Research Institute, UCLA, California 90073, USA. hoyang@ucla.edu

(2)Goodman and Gilman's The Pharmacological Basis of Therapeutics 8th ed. pp.1345-1346

(3) : Endocr J 1997 Feb;44(1):89-94

Incidence of hyperprolactinemia in patients with Hashimoto's thyroiditis.
Notsu K, Ito Y, Furuya H, Ohguni S, Kato Y.
Department of Medicine, Shimane Prefectural Central Hospital, Izumo, Japan.

(4)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.

(5) Endocrinol 1988 Apr;117(1):115-22

Release of prolactin is independent of the secretion of thyrotrophin-releasing hormone into hypophysial portal blood of sheep.

Thomas GB, Cummins JT, Yao B, Gordon K, Clarke IJ.
Medical Research Centre, Prince Henry's Hospital, Melbourne, Australia.

It is my understanding that the reason tren and estradiol are so potent when used in cattle is that the estrogen elevates IGF-1 and the tren somehow sensitizes muscle satellite cells to the effects of the IGF. There is no evidence that tren itself raises IGF levels.

Trenbolone alters the responsiveness of skeletal muscle satellite cells to fibroblast growth factor and insulin-like growth factor I.

Thompson SH, Boxhorn LK, Kong WY, Allen RE.

Department of Animal Sciences, University of Arizona, Tucson 85721.

The potential role of satellite cells in mediating the effect of trenbolone [17 beta-hydroxyestra-4,9-11-trien-3-one (TBOH)] on skeletal muscle hypertrophy was examined. Young female Sprague-Dawley rats received TBOH injections daily for 2 weeks; growth, body composition, and the composition of selected muscles were assessed. Treated rats grew more rapidly and deposited less body lipid and more protein. The semimembranosus muscle from treated rats was larger and had approximately 60% more DNA per muscle than muscles from control rats. The addition of trenbolone directly to the medium of cultured satellite cells did not stimulate cell proliferation,
nor did it augment the stimulatory response of these cells to fibroblast growth factor (FGF) or insulin-like growth factor I (IGF-I). In contrast, satellite cells cultured from TBOH-treated rats exhibited greater proliferative responses to FGF and IGF-I than satellite cells from control rats. In addition, serum from TBOH-treated rats stimulated greater cell proliferation in satellite cell cultures than serum from control rats. These experiments suggest that one possible mechanism responsible for the ability of TBOH to stimulate skeletal muscle hypertrophy may be through enhanced proliferation and differentiation of satellite cells as a result of the increased sensitivity of these cells to IGF-I and FGF.


Unfortunately, the authors of the paper described below do not state which anabolic steroids were used, but did note a significant drop in serum thyroid hormone levels.

Am J Sports Med 1987 Jul-Aug;15(4):357-61

Androgenic-anabolic steroid effects on serum thyroid, pituitary and steroid hormones in athletes.

Alen M, Rahkila P, Reinila M, Vihko R.

Department of Health Sciences, University of Jyvaskyla, Finland.

Endocrine responses in seven power athletes were investigated during a 12 week strength training period, when the athletes were taking high doses of androgenic-anabolic steroids, and during the 13 weeks following drug withdrawal. During the use of steroids significant decreases (P less than 0.05 to 0.001) in the serum concentrations of thyroid stimulating hormone, thyroxine, triidothyronine, free thyroxine, and thyroid hormone-binding globulin (TBG) were found, whereas the value of triidothyronine uptake increased (P less than 0.001). In relation to the changes in the thyroid function parameters measured, we suggest that the primary target of androgen action was TBG biosynthesis. In five of the seven subjects, serum concentrations of growth hormone increased at some point of the study 5 to 60-fold. Because of the use of exogenous testosterone, serum testosterone concentration tended to increase. This increase was associated with a corresponding increase (P less than 0.001) in serum estradiol. Furthermore, there were major decreases in
serum LH (P less than 0.01) and FSH (P less than 0.01) concentrations, and testicular testosterone production was therefore decreased. This was characterized by a very low serum testosterone concentration (5.1 +/- 1.8 nmol/l) 4 weeks following drug withdrawal. Cessation of drug use resulted in return of all the variables measured to the initial values, except for serum testosterone, which was at a low level (14.6 +/- 8.8 nmol/l) 9 weeks after drug withdrawal, indicating prolonged impairment of function. No consistent changes were found in the eight control athletes.


[Plasma prolactin levels and pubertal gynecomastia]

[Article in German]

Butenandt O.

Twenty-three boys with pubertal gynecomastia had higher mean levels of prolactin than boys of similar development but without gynecomastia (10.1 vs. 6.2 ng/ml). In girls of comparable pubertal staging prolactin level was 12.3 ng/ml. In boys no hyperprolactinemia was found, not even after stimulation with TRH, prolactin levels were not elevated in two boys with secreting mammary glands. Therapy with bromocriptine stopped the secretion. During therapy, prolactin levels could not be raised by stimulation. The results contradict the hypothesis that prolactin is involved in the development of gynecomastia.

PMID: 6413841 [PubMed - indexed for MEDLINE]
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[Prolactin secretion and gynecomastia]

[Article in Bulgarian]

Kumanov F.

Nine males with gynecomastia were examined. The serum levels of LH, FSH, prolactin, testosteron, estradiol were determined, in some of the patients--progesteron. A stimulation with thyreoliberin was carried out to follow up prolactin reaction. The same examinations were performed with a control group of healthy males. Contrary to the healthy subjects, the patients with gynecomastia had a significantly higher levels of FSH and progesteron and testosteron was reduced with statistical significance. The basal level of prolactin in the patients with gynecomastia was not significantly increased and no deviations in the parameters of prolactin reaction was observed after the stimulation by thyreoliberin. On the base of those results progesteron in the males with gynecomastia is admitted to be able to support the mammo--tropic effect of estrogens, together with the reduced androgens and the altered receptivity of the mammary glands. Prolactin is of no great importance for gynecomastia.

PMID: 6424337 [PubMed - indexed for MEDLINE


-Nandi12

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Yes, finally!!! you hit the nail right on the head.

Fina is a VERY POWERFUL anti-glucocorticoid, so what
exactly does it do to reduce endogeneous cortisone
levels?

There is only ONE mechanism:

A reduction in the TOTAL Free T4 and T3 levels within the
body.

T3 is HIGHLY catabolic to muscle, therefore by reducing it by(
take 45% as shown by Nandi as an example), you are
exerting a ridiculously high protein-sparing effect.

YES, thats right, Fina is not THAT anabolic IN VIVO, it is
far, and I do mean FAR more of an ANTI-CATABOLIC
AAS than anything else.

Ok, now lets back-track to the problem at hand.

TSH has been reduced by the trenbolone, which in
turns signals the thyroid to reduce endogeneously
produced levels of T3 and T4.

This reduction(As Nandi mentioned) causes a VERY
sharp drop in free T3 levels because of the reduction
in both the endogeneously produced T4 and T3.
(Remember that 80% of the free T3 is produced from
the metabolically inactive T4)

These dimished levels of T3,T4 cause Thyrotropin Releasing
Hormone(TRH) to become OVER-STIMULATED.

In essence, this is your bodies feed-back loop to reduced
thyroid hormones, due to a GLUCO-CORTICOID suppresive
effect. This is however NOT like hypothyroidic patients
who have a naturally defective(or damaged) thyroid.

When TRH becomes over-stimulated the net effect is
a VERY sharp increase in prolactin levels.

Critical here.....

I.E. YOU BEGIN TO LACTATE!!!!!

Now, herein lies the problem. Everybody is bio-chemically
different, therefore the TRH increase is EXTREMELY
broad-spectrum.

While someone will stimulate TRH say X% and ultimately
cause a rise in prolactin of say Y% with a daily
dosage of 50mg ED of Fina, another person will
cause a 2X% rise in TRH and 2Y+% rise in prolactin
which will invariably lead to gyno.

This is just genetics. Nothing can be done about this.

However, there are ways to combat prolactin-elevations:

This btw, HAS TO BE EXACT. If you over-dose you cause
a progestenic shift due to severely inhibited prolactin levels,
or if you under-dose you run the risk of getting prolactin
induced gyno.

As a note: PROGESTERONE does NOT, I repeat NOT come into
play with Fina at all. It only becomes into play when you're
trying to inhibit prolactin synthetically.

The only thing that can combat Fina-induced Gyno is:

1. 2.5mgs Bromocriptine broken down to 1.25mgs 2X/day
AM and PM.

Thats it.

No Vitex/Nolva/Clomid/Arimidex or whatever. They don't
work for Fina.

-Fonz

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Fonz, you are right in pointing out the importance of proper bromocriptine dosing. Bromocriptine has been shown in numerous studies to elevate GH levels in normal humans. (Paradoxically, it reduces GH levels and is a standard treatment in patients suffering from acromegaly.)

While this may sound like a good thing, it is not if you are trying to clear up gyno. The GH receptor is structurally very similar to the prolactin receptor, and GH acts as an agonist at that receptor. Excess GH will only aggravate the gyno. (1)

(1) J Gerontol A Biol Sci Med Sci 1998 May;53(3):M183-7

Side effects resulting from the use of growth hormone and insulin-like growth factor-I as combined therapy to frail elderly patients.

Sullivan DH, Carter WJ, Warr WR, Williams LH.

Geriatric Research, Education and Clinical Center, John L. McClellan Memorial Veterans Hospital, Little Rock, Arkansas, USA.

BACKGROUND: The objective of this study was to examine the relationship between serum IGF-I concentration and the incidence
of side effects of therapy with recombinant human growth hormone (rhGH) and recombinant human insulin-like growth factor-I (rhIGF-I). METHODS: Thirteen high-risk, undernourished elderly males were started on a 15-day course of rhGH and rhIGF-I by subcutaneous injection. The dose of rhGH was held constant at .0125 mg/kg/day, whereas the dose of rhIGF-I was increased in a stepwise fashion from 10 micrograms/kg to the targeted dose of 40 micrograms/kg twice a day. RESULTS: Nine subjects completed the protocol and reached the full target dose of both hormones. .Fluid retention, gynecomastia, and orthostatic hypotension were the most common complications. The hormone injections increased the serum concentration of IGF-I (from 72.7 +/- 40.9 to 483.7 +/- 251.4 eta g/ml, p = .001) and IGFBP-3 (from 1.82 +/- 0.66 to 2.72 +/- 1.18 mg/L, p = .012), and decreased serum albumin (from 34.3 +/- 5.5 to 31.4 +/- 4.6 g/L, p = .009). The magnitude of the initial increase in the serum IGF-I concentration was a powerful risk factor for severe orthostatic hypotension, diffuse myalgias, and drug-induced hepatitis. There was no association between the serum IGF-I concentration and fluid retention or gynecomastia.CONCLUSIONS: Treatment of the undernourished frail elderly with the anabolic agents rhGH and rhIGF-I at the specified dosages may produce undesirable side effects including fluid retention, gynecomastia, and orthostatic hypotension.

While it is true that prolactin can suppress gonadotropin levels, and low levels of testosterone (T), luteinizing hormone (LH) and follicle stimulating hormone (FSH) often accompany hyperprolactemia, this is not always the case, suggesting that prolactin can lead directly to gynecomastia/galactorrhea without an effect on gonadotropin secretion. (1) (2) (3)

On the other hand there have been negative studies in which patients with elevated drug-induced prolactin but with normal gonadotropin levels did not present with gynecomastia.(4)

It would be interesting to know how many bodybuilders who take testosterone and tren, along with arimidex or nolvadex, develop gyno. If gyno occurs in these subjects it would suggest a direct action of prolactin rather than an indirect action via a depressed testosterone/estrogen ratio. Any readers out there with experience in this regard?

(1)Nephron 1986;42(1):19-22
Parlodel treatment of uremic hypogonadism in men.
Ermolenko VM, Kukhtevich AV, Dedov II, Bunatian AF, Melnichenko GA, Gitel EP.

(2)J Clin Pharm Ther 2002 Feb;27(1):75-7
Gynecomastia with sulpiride.
Kaneda Y, Fujii A.

(3) Schweiz Arch Tierheilkd 1996;138(5):241-4
[Gynecomastia in a goat buck]
Janett F, Stockli A, Thun R, Nett P.

(4) Ann Pharmacother 2001 Dec;35(12):1523-7
Effects of risperidone on gonadal axis hormones in schizophrenia.
Kaneda Y.

-Nandi12

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Very astute observation.

Fina has LOWERED T3 levels, which are INDIRECTLY
responsible for the Fina Gyno.

Now, what happens if we ADD 25mcg's of T3/day.

Hmmmm.....now things get interesting.

T3 levels go BACK TO NORMAL. TRH goes back to
normal, but TSH drops(no real problem).

Result: INCREASED Anabolism at the expense
of a portion of Fina's powerful anti-glucocorticoid
action.

BUT, you ALSO get an extra FAT-BURNING effect from the T3.

So, by adding T3 you INCREASE anabolism, fat-burning
but reduce anti-catabolism. HOWEVER, you also
reduce TRH, and therefore PROLACTIN LEVELS.

So, by adding T3 you will reduce the prolactin increase
caused by the trenbolone.

Add Bromocriptine to the mix, and your chances of getting
Fina gyno are reduced to like 0.0000001%.

-Fonz


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Credat Judaeus Apella, non ego. -

Horace's Satires, book 1, satire 5, lines 100-101

[This message was edited by MisterX on 04-14-2002 at 04:42 AM.]