Tuesday, April 12, 2011

Increasing height with Letrozole?

Estrogen is a needed compound that needs to be at an equilibrium point to maximize height.  Estrogen has positive effects on cellular proliferation however ER-alpha and ER-Beta receptors in the growth plate may reduce height.  However, some of the positive benefits of can be replicated by compounds like Alfalfa without the negative effects on the ER-alpha and ER-Beta receptors in the growth plate.  Tamoxifen is an aromatase inhibitor that has benefits independent of it's Estrogen inhibition.  However, sustained usage of Tamoxifen has negative consequences thus a proper cycling regime of Tamoxifen has to be in place before starting to take Tamoxifen to get only the good benefits of Tamoxifen.  Tamoxifen is unique as it targets directly the estrogen receptor that reduces height.

Can you use Letrozole and Alfalfa plus other estrogenic compounds to get the benefits of estrogen without the ER-Alpha and ER-Beta mediated side effects?

However, it may be that ER-Alpha can be activated even during Aromatase inhibition.

An “Omics” Approach to Determine the Mechanisms of Acquired Aromatase Inhibitor Resistance

"Although these drugs work effectively,  [individuals acquire] resistance to the AIs. To characterize the resistant mechanisms, a set of MCF-7aro cell lines that acquired resistance to the AIs was generated. Through an “Omics” approach, we found that the resistance mechanisms of the three AIs (anastrozole, letrozole, and exemestane) differ and activation of estrogen receptor alpha (ERα) is critical for acquired AI resistance. Our results reveal that growth factor/signal transduction pathways are upregulated after ERα-dependent pathways are suppressed by AIs, and ERα can then be activated through different crosstalk mechanisms[ER-alpha can still be activated after aromatase has been inhibited]."

"One clinical feature associated with AI treatment is the lack of crossresistance among the three AIs, suggesting that the different AIs use different resistance mechanisms or that AI-resistant cells developed supersensitive responses to ER"<-So you may want to cycle between three aromatase inhibitors

"We found that T or E2 induced proliferation of MCF-7aro cells at a rate six times faster than the untreated cells. In addition, the T-induced proliferation of MCF-7aro cells was effectively suppressed by LET, ANA, or TAM."<-this is the problem with aromatase inhibitors it decreases cellular proliferation by a factor of 1/6.  Although this can be mediated somewhat with Ipriflavone(Alfalfa).

If Letrozole can be effective without other compounds replicating the good effects of estrogen, imagine if letrozole was used with estrogen-like compounds that stimulated cellular proliferation.

A double-blind, placebo-controlled comparison of letrozole to oxandrolone effects upon growth and puberty of children with constitutional delay of puberty and idiopathic short stature.

"We compared the effects of letrozole with that of oxandrolone on predicted adult height (PAH), puberty, bone mineral density, serum insulin-like growth factor 1 (IGF-1) and blood lipoproteins.
 In a prospective, double-blind, randomized, placebo-controlled clinical trial, 91 CDGP boys (12.6-14.6 years old) with predicted short stature were treated with letrozole (2.5 mg/day), oxandrolone (2.5 mg/day), or placebo, at the outpatient pediatric endocrine clinic of Mofid Children's Hospital in Tehran for 2 years.[this is a pretty long time]
Letrozole differed from oxandrolone and placebo in significantly increasing PAH (p < 0.05), and slightly but significantly decreasing HDL-cholesterol. Oxandrolone, and to a lesser degree letrozole, significantly increased the height standard deviation score and bone age compared to placebo[interesting that both increased cellular proliferation rate which is not what you would expect with estrogen inhibition, maybe the boys had too high estrogen and the aromatase inhibitors knocked them down to the optimal range].
This first randomized controlled clinical trial in CDGD teenage boys with predicted short stature shows that letrozole increases PAH more than oxandrolone and advances pubertal stage and bone mineralization less."

"There was no significant difference [in BMD] between the letrozole and the placebo group during treatment[this is not what you'd expect as you'd think that with estrogen levels decreasing BMD would go down, this again makes it seem like the boys had above equilibrium levels of estrogen and these aromatase inhibitors knocked them down to equilibrium]. BMD in the oxandrolone group progressively increased over the 2-year period to 1.2 ± 0.8 in the lumbar spine and 1.1 ± 0.7 in the femoral neck. These both became significantly higher than on (p < 0.001) letrozole (–1.5 ± 0.9 and –1.2 ± 0.7, respectively) or placebo (–1.5 ± 1.1 and –1.2 ± 0.6, respectively), which did not differ significantly"

Aromatase inhibitors in pediatrics.

"Aromatase, an enzyme located in the endoplasmic reticulum of estrogen-producing cells, catalyzes the rate-limiting step in the conversion of androgens to estrogens in many tissues. The clinical features of patients with defects in CYP19A1, the gene encoding aromatase, have revealed a major role for this enzyme in epiphyseal plate closure, which has promoted interest in the use of inhibitors of aromatase to improve adult height. The availability of the selective aromatase inhibitors letrozole and anastrozole--currently approved as adjuvant therapy for breast cancer--have stimulated off-label use of aromatase inhibitors in pediatrics for short stature in boys.  Although aromatase inhibitors appear effective in increasing adult height of boys with short stature and/or pubertal delay, safety concerns, including vertebral deformities, a decrease in serum HDL cholesterol levels and increase of erythrocytosis, are reasons for caution."

Normal individuals would have to be treated with letrozole to see if the benefits of letrozole are due to high estrogen individuals knocked down to the equilibrium way as only people with short stature were used which are expected to have some differentiation from mean.  Alternatively, higher doses of letrozole could be used to see how much the benefits are dose dependent.  Given that letrozole was shown to decrease height in prepubertal rats and prepuberty it's expected that estrogen levels are below equilibrium, it is likely that the benefits of letrozole are based on your deviation from equilbrium in addition to acquired estrogen receptor alpha resistance.


  1. so apparently alkoclar said that estrogen is needed to increase levels of fgf for final growth..

    so estrogen is neccesary ,but its also bad.
    so would weaker estrogens be better using DIM estrogen metabolizers or
    the ipriflavone and a.i?

    or both or what?..

  2. can you find any supplements or extracts that can increase fgf? thats what alklar said needs to be increased, but inhibiting estrogen will decrease it.

  3. does this have any relation to height growth>http://www.ncbi.nlm.nih.gov/pubmed/9632141

  4. just in case you didn't dl the paper here it is
    im interested in hearing your thoughts on the fgfs and bmps

  5. you may have seen this but just in case you haven't or anyone else

    1. Unfortunately, I do not have access to the full article. One of the things I found interesting is that chondrocytes exit the cell cycle to form the zones of the growth plate.

  6. ya i cant find a free article either
    i will share if i do

    tyler can you do a post on growth plate vascularization?
    fgfs increase vascularization so im a bit worried