The studies seem to go back and forth on this .. but I think that Nolva does increase PgR in breast tissue .. Which in turn can give more of the nasty deca / tren metabolites to bind too .. and could possibly increase the chance of getting gyno( but it is not a problem for all people )..
If you do a search you will see that there are peeps that report that they have problems when using 19 nor and nolva ( so we are sorta left with a shortage of info in the medical studies because they tend to go back and forth on this topic . But we do have an accumulation of independent anecdotal observations that can at least provide some idea how much of an issue it really is.
That said I will post some studies that show that nolva does increase PgR..
Here is one study showing nolva increases PgR . Like I said it gives more for the 19 nors metabolites to bind to and because of this it could possibly increase your chances of getting gyno..
Estrogen receptor (ER) and progesterone receptor (PgR), by ligand-binding assay compared with ER, PgR and pS2, by immuno-histochemistry in predicting response to tamoxifen in metastatic breast cancer: a Southwest Oncology Group Study.
Elledge RM, Green S, Pugh R, Allred DC, Clark GM, Hill J, Ravdin P, Martino S, Osborne CK.
Baylor College of Medicine, Houston, TX, USA.
[email protected]
Results of estrogen receptor (ER) and progesterone receptor (PgR) ligand-binding assays (LBAs) are strongly correlated with ER and PgR by immuno-histochemistry (IHC). To investigate whether ER and PgR by IHC are also strongly correlated with tamoxifen response, time to treatment failure (TTF) and overall survival (OS), the results of the 2 methods were directly compared in 205 patients with ER(+) metastatic breast cancer treated with daily tamoxifen (Southwest Oncology Group protocol 8228) with 9 years median follow-up. pS2, another estrogen-regulated molecule, was also analyzed. Tumors were scored for IHC from 0 to 5, according to the proportion of positively stained cells. These IHC scores for both ER and PgR were significantly associated with LBA levels (p < 0.001).
There was a significant direct relationship between higher IHC ER, PgR and pS2 and increasing response to tamoxifen. TTF and OS were also significantly longer for patients with higher ER or PgR, but not pS2, IHC scores. Low, intermediate and high ER or PgR categories showed similar differences in response rates whether defined by LBA or IHC. In logistic regression models which included ER, PgR and pS2 by IHC; ER and PgR by LBA; and menopausal status, only ER (IHC) and pS2 (IHC) retained significance for predicting tamoxifen response (p = 0. 02 and p = 0.005, respectively), along with menopausal status (for PgR by IHC, p = 0.09). Increasing ER and PgR by IHC, as by LBA, are thus significantly associated with a progressively better response and longer survival in ER(+) metastatic breast cancer. pS2 is also predictive in this setting. Copyright 2000 Wiley-Liss, Inc.
PMID: 10754487 [PubMed - indexed for MEDLINE]
You're misreading the abstract. The study did not find that nolva increases PgR. It found that PgR levels (along with ER levels, etc) were predictive of how well the tissue would respond to hormonal therapy (tamoxifen). Basically, if there are more steroid receptors in the tissue (e.g. ER+/PgR+), the tissue is going to be more responsive to hormonal therapy. They did not examine the effect of tamoxifen on PgR expression.
And this one
The PgR gene is an estrogen-regulated gene (34) , so drugs with estrogenic activity will increase its expression. Accordingly, tamoxifen has been shown to increase PgR levels (35) , whereas initial work on primary breast tumors found that a short-acting formulation of ICI 182,*** reduced PgR levels (30) , suggesting that it is devoid of estrogen-agonist activity and may have a different mechanism of action to that of tamoxifen. Additional evidence that ICI 182,*** and tamoxifen have different underlying modes of action comes from studies showing that tamoxifen-resistant tumors remain sensitive to ICI 182,*** treatment in vitro (18 , 19) , in vivo (36 , 37) , and in the clinic (38, 39, 40) .
http://cancerres.aacrjournals.org/cg...ull/61/18/6739
If you look at what reference 35 says, you'll see that when they administered tamoxifen, 40% (21/52) had an increase in PgR, 37%(19/52) has a decrease in PgR, and the remaining (12/52) were negative for the receptor. The overall increase in PgR was statistically significant, but as you can see, the results were far from uniform.
Also
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.
[email protected]
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.
PMID: 16002280 [PubMed - indexed for MEDLINE]
The full text of this paper explains, "In a small series of PgR-positive cancers treated with tamoxifen, a different pattern of change was seen. Thus, only 17% of cases showed a decrease and the most common change was a paradoxical increase in staining." In table 2, we see that 24% the tamoxifen group had down-regulation of the PgR, 26% had no change, and 50% showed up-reguation.
And this one is good also
Estrogen Receptor Downregulators
Dr. Tony Howell,[10] of the University of Manchester and the Christie Hospital, Manchester, UK, spoke concerning work with ER downregulators (formerly called "pure" antiestrogens). The prototype of these drugs is the steroidal compound fulvestrant, which induces ER downregulation[11] in animal and cell models.
Dr. Robertson's group has shown that tamoxifen induces mild downregulation of ER but upregulation of PgR, whereas fulvestrant downregulates both ER and PgR. Aromatase inhibitors may produce similar effects to those produced by fulvestrant, but they do so by completely removing all estrogen.
http://www.medscape.com/viewarticle/440361
It looks like this wasn't a peer-reviewed paper, but an article from medscape that's no longer there. If anyone can find it or find the references for it, I'd be interested in looking at them.
Merc.
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Originally Posted by CHUCKYthentic
