Tamoxifen citrate increases expression of progesterone receptor.

[Vegas]

J Steroid Biochem Mol Biol. 2005 May;95(1-5):83-9.

Aromatase inhibitors: cellular and molecular effects.

Miller WR, Anderson TJ, White S, Larionov A, Murray J, Evans D, Krause A, Dixon JM.

Breast Unit, Western General Hospital, Edinburgh, Scotland, UK. w.r.miller@ed.ac.uk

Marked cellular and molecular changes may occur in breast cancers following treatment of postmenopausal breast cancer patients with aromatase inhibitors. Neoadjuvant protocols, in which treatment is given with the primary tumour still within the breast, are particularly illuminating. In Edinburgh, we have shown that 3 months treatment with either anastrozole, exemestane or letrozole produces pathological responses in the majority of oestrogen receptor (ER)-rich tumours (39/59) as manifested by reduced cellularity/increased fibrosis. Changes in histological grading may also take place, most notably a reduction in mitotic figures. This probably reflects an influence on proliferation as most tumours (82%) show a marked decrease in the proliferation marker, Ki67. These effects are generally more dramatic than seen with tamoxifen given in the same setting. Differences between aromatase inhibitors and tamoxifen are also apparent in changes in steroid hormone expression. Thus, immuno-staining for progesterone receptor (PgR) is reduced in almost all cases by aromatase inhibitors, becoming undetectable in many. This contrasts with effects of tamoxifen in which the most common change on PgR is to increase expression. Changes in proliferation occur rapidly following the onset of exposure to aromatase inhibitors. Thus, neoadjuvant studies with letrozole in which tumour was sampled before and after 14 days and 3 months treatment show that decreased expression of Ki67 occur at 14 days and, in many cases, the effect is greater at 14 days than 3 months. These early changes precede evidence of clinical response but do not predict for it. However, this study design has allowed RNA analysis of sequential biopsies taken during the neoadjuvant therapy. Based on clustering techniques, it has been possible to subdivide tumours into groups showing distinct patterns of molecular changes. These changes in tumour gene expression may allow definition of tumour cohorts with differing sensitivity to aromatase inhibitors and permit early recognition of response and resistance.

[crushershockey]

k i'm a kinda stupid and odn't understand some of that medical shit... can u explain what exactly that article is saying for me pls...

[RRAdam]

This was done in post menopausal women?

The reaction can be quite different in men.

[Vegas]

Originally Posted by crushershockey

can u explain what exactly that article is saying for me pls...

If you use nolva while running tren, nandrolone, etc. you are more likely to experience prolactin-related gyno. And if you treat prolactin-related gyno with nolva, as I know some do, you may be asking for a whole heap of trouble.

Originally Posted by RRAdam

This was done in post menopausal women?

The reaction can be quite different in men.

Yes, but if we relied on only the studies that were conducted using physically fit, recreational anabolic steroid users we'd be having very short conversations.

[GymLift]

Originally Posted by *****

If you use nolva while running tren, nandrolone, etc. you are more likely to experience prolactin-related gyno. And if you treat prolactin-related gyno with nolva, as I know some do, you may be asking for a whole heap of trouble.

Finally a study to back up practical experience. Hello vit B6.

[Insane_Man]

Originally Posted by *****

If you use nolva while running tren, nandrolone, etc. you are more likely to experience prolactin-related gyno. And if you treat prolactin-related gyno with nolva, as I know some do, you may be asking for a whole heap of trouble.

fuck, i wish i knew this about this time last year


I ran a fairly high dose of nolva all the way through bc I seem to be gyno prone. I was on a low dose of tren 50mg eod and developed leaky nips.

[GymLift]

Maybe I should go back and bump the threads where I argued with the 'study guys' about this topic.

[Insane_Man]

Oh and I ran lots of b6, didnt do shit.

I'm talkign 600-800mg a day

[GymLift]

Originally Posted by Insane_Man

Oh and I ran lots of b6, didnt do shit.

I'm talkign 600-800mg a day

Yeah, B6 doesn't work for everyone. But who knows, maybe it would have been good enough if you hadn't used the nolvadex.

[Insane_Man]

That's true.

To this day I can squeeze small amts out every now and then.

[ManOfMuscle]

Originally Posted by Insane_Man

That's true.

To this day I can squeeze small amts out every now and then.

Do you develop lumps with this or just the liquid?

[Insane_Man]

Originally Posted by LiftTillIDie

Do you develop lumps with this or just the liquid?

I had pre existing gyno which may or may not have gotten worse, can't really tell to be honest.

[Ponderosa]

great info. thanx.

[GymLift]

I suggest this thread me moved to The Classics forum.

[Insane_Man]

Originally Posted by mranak

I suggest this thread me moved to The Classics forum.

Agreed. Tren is a very popular drugs and I often see people recommending nolva for gyno related to it.

[SWALE]

Very interesting. I had not seen this before.

While we certainly must be mindful, as we have already been reminded, of extrapolating conclusions from studies performed on a completely different patient population, as I think back, perhaps this accounts for some of the otherwise unexplainable gyno I have seen in my practice.

[funkenstein]

This is why it's so important to run dostinex in conjunction with nolvadex for pct if deca was included in the cycle.

[FerrariF50]

Originally Posted by funkenstein

This is why it's so important to run dostinex in conjunction with nolvadex for pct if deca was included in the cycle.

what does dostinex (cabergoline), an anti-prolactin have to do with progesterone?

an anti-prolactin may be useful only if lactation is a problem.

[g1234]

yes, I would also like to know the relation between progesterone receptors activated by tren/deca and prolactin levels.

[g1234]

I found this (source: Chapter14.Gynecomastia: Etiology, Diagnosis, and Treatment)

ESTROGEN, GH AND IGF-1, PROGESTERONE, & PROLACTIN

Estrogen and progesterone act in an integrative fashion to stimulate normal adult female breast development. Estrogen, acting through its ER a receptor, promotes duct growth, while progesterone, also acting through its receptor (PR), supports alveolar development (18). This is demonstrated by experiments in ER knockout mice, which display grossly impaired ductal development, whereas PR knockout mice possess significant ductal development, but lack alveolar differentiation (31, 7).

Although estrogens and progestogens are vital to mammary growth, they are ineffective in the absence of anterior pituitary hormones (15). Thus, neither estrogen alone nor estrogen plus progesterone can sustain breast development without other mediators, such as GH and IGF-1. This was confirmed by studies involving the administration of estrogen and GH to hypophysectomized and oophorectomized female rats, which resulted in breast ductal development. The GH effects on ductal growth are mediated through stimulation of IGF-1. This is demonstrated by studies of estrogen and GH administration to IGF-1 knockout rats that showed significantly decreased mammary development when compared to age-matched IGF-1- intact controls. Combined estrogen and IGF-1 treatment in these IGF-1 knockout rats restored mammary growth (26, 45). In addition, Walden et al. demonstrated that GH-stimulated production of IGF-1 mRNA in the mammary gland itself, suggesting that IGF-1 production in the stromal compartment of the mammary gland acts locally to promote breast development (55). Furthermore, other data indicates that estrogen promotes GH secretion and increases GH levels, stimulating the production of IGF-1, which synergizes with estrogen to induce ductal development.

Like estrogen, progesterone has minimal effects in breast development without concomitant anterior pituitary hormones; again indicating that progesterone interacts closely with pituitary hormones. For example, prolonged treatment of dogs with progestogens such as depot medroxyprogesterone acetate or with proligestone caused increased GH and IGF-1 levels, suggesting that progesterone may also have an effect on GH secretion (36). In addition, clinical studies have correlated maximal cell proliferation to specific phases in the female menstrual cycle. For example, maximal proliferation occurs not during the follicular phase when estrogens reach peak levels and progesterone is low (less than 1 ng/mL [3.1nmol]), but rather, it occurs during the luteal phase when progesterone reaches levels of 10-20 ng/mL (31- 62nmol) and estrogen levels are two to three times lower than in the follicular phase (47). Furthermore, immunohistochemical studies of ER and PR showed that the highest percentage of proliferating cells, found almost exclusively in the type 1 lobules, contained the highest percentage of ER and PR positive cells (47). Similarly, there is immunocytological presence of ER, PR, and androgen receptors (AR) in gynecomastia and male breast carcinoma. ER, PR and AR expression was observed in 100% (30/30) of gynecomastia cases (48). Given these data and the fact that PR knockout mice lack alveolar development in breast tissue, it appears as if progesterone, analogous to estrogen, may increase GH secretion and act through its receptor on mammary tissue to enhance breast development, specifically alveolar differentiation (31, 21).

Prolactin is another anterior pituitary hormone integral to breast development. Prolactin is not only secreted by the pituitary gland but may be produced in normal mammary tissue epithelial cells and breast tumors. (50, 28). Prolactin stimulates epithelial cell proliferation only in the presence of estrogen and enhances lobulo-alveolar differentiation only with concomitant progesterone. Recently, receptors for luteinizing hormone/ human chorionic gonadotropin have been found in both male and female breast tissues, though its function remains to be determined (11)