Letrozole (Femara, LiquiLetro) Profile

[The Anonymizer]

profile coming soon...

[glock40_1979]

Abstract

Two third-generation aromatase inhibitors, letrozole and anastrozole, and the antiestrogen tamoxifen, were compared for growth-inhibiting activity in two estrogen receptor (ER)-positive aromatase-overexpressing human breast cancer cell lines, MCF-7aro and T-47Daro. Inhibition of hormone (1 nM testosterone)-stimulated proliferation was evaluated in both monolayer cultures and in three-dimensional spheroid cultures. Letrozole and anastrozole were also compared for effectiveness of aromatase inhibition, and relative affinity for aromatase, under both monolayer and spheroid growth conditions.

Letrozole was an effective inhibitor of MCF-7aro monolayer cell proliferation, with an estimated 50% inhibitory concentration (IC50) of 50–100 nM, whereas an IC50 was not reached with anastrozole at any concentration tested (100–500 nM). An IC50 of tamoxifen was 1000 nM. Proliferation of T-47Daro monolayer cells was more sensitive to inhibition by all three agents; as with MCF-7aro cells, letrozole was the most effective inhibitor.

MCF-7aro spheroids were slightly less sensitive than monolayer cells proliferation-inhibiting effects of letrozole (IC50 about 200 nM), and there was no significant inhibition with 100–200 nM anastrozole or 200–1000 nM tamoxifen. Letrozole and anastrozole significantly inhibited T-47Daro spheroid cell proliferation, at 15–25 and 50 nM, respectively, consistent with the greater sensitivity of T-47Daro monolayer cells to inhibition of proliferation by these agents. Tamoxifen failed to significantly inhibit T-47Daro spheroid cell proliferation over a 100–500 nM concentration range.

Determination of aromatase inhibition in monolayers of both cell lines by a direct-access microsomal assay and an intact-cell assay revealed that letrozole was more active than anastrozole in monolayers of both cell lines and in both assays. In MCF-7aro spheroids following cell lysis, only letrozole significantly inhibited aromatase activity, supporting the conclusion that letrozole binds stronger to aromatase than anastrozole does. Our results demonstrate that MCF-7aro and T-47Daro spheroids could be a suitable model for evaluation of growth-inhibitory effects of agents used in hormonal therapy of breast cancer.

[glock40_1979]

Abstract

Recent clinical trials indicate that the third-generation aromatase inhibitors may be more effective than tamoxifen as first line endocrine therapy in ER+ metastatic breast cancer in postmenopausal women. This review will focus exclusively on the pharmacology of the non-steroidal inhibitor letrozole. Aromatase derived from a variety of sources is inhibited at low nM concentrations of the drug. In non-cellular systems, letrozole is 2–5 times more potent than anastrozole and exemestane in its inhibition of aromatase, whilst in cellular systems it is 10–20 times more potent. Anti-tumour effects of letrozole have been demonstrated in several animal models. In postmenopausal women, letrozole commonly suppresses circulating concentrations of estrone and estradiol to below the sensitivity limit of the assays used to measure them. In a recent randomized cross-over study, letrozole (2.5 mg daily) achieved a significantly greater suppression of the plasma concentrations of both estrone and estrone sulphate than anastrozole (1 mg daily) and a greater inhibition of in vivo aromatization.Letrozole appears to have a small effect on adrenal steroidogenesis such that a small number of patients exhibit an abnormal response to synthetic ACTH during letrozole therapy. This is unlikely to have any clinical significance. In short-term studies letrozole has been shown to increase markers of bone resorption indicating the need to monitor bone integrity when the drug is used for extended periods of time. A consistent effect of letrozole on serum lipids has not been demonstrated.

[2thepain]

Letro is by far the most effective AI however it may be too effective. I personally know of several individuals who have used Letro to lesson already occuring gyno and had good success in doing so. I once tried to use letro as a sole AI in a cycle and found that by the end of the cycle I had extreme joint pain and a horrible lipid profile. Both are signs of having too low of estrogen. For this reason I would not suggest someone use letro for the duration of a long cycle. Just my .02.

[Lucca Brassi]

Originally Posted by 2thepain

Letro is by far the most effective AI however it may be too effective. I personally know of several individuals who have used Letro to lesson already occuring gyno and had good success in doing so. I once tried to use letro as a sole AI in a cycle and found that by the end of the cycle I had extreme joint pain and a horrible lipid profile. Both are signs of having too low of estrogen. For this reason I would not suggest someone use letro for the duration of a long cycle. Just my .02.

Dear Members:

I took a blood test and my TT=367 (220-1000) and my FT=42 (40-240). I had horrible symptoms of low testosterone. I started Testim, 2 tubes per day, as 1 tube was not doing it for me.

Should I use an AI or a SERM during Testim? I would only use it if I had symptoms of Gyno. Is either OK? What should I use to get my testes and body back in working order for post Testim, if I decide to go off Testim for a while. I am hoping to use just one (SERM or AI) for both (during Testim and Post Testim). I am hoping a SERM will work for gyno, during Testim, and work for post Testim (to get my testes and body working again), that is, if I decide to give my body a break from Testim.


http://www.allthingsmale.com/publications.html:

"Once the method and dosing is set, by laboratory assay AND subjective report from the patient, then you may address any side effects due to elevated estrogen levels which have occurred. I do not use an AI initially, even when E2 is elevated, because some patients will actually see a drop in estrogen over baseline on follow-up. We would have otherwise added an unnecessary (and relatively expensive) medication. Should the patient develop any “nipple issues” secondary to accelerating serum androgen levels and/or elevated estrogen, you cannot start them on a SERM right away because doing so will invalidate your estradiol assay at follow-up. Of note, males can experience said “nipple issues” even while estrogen levels are within physiological range, due to changes in hormone levels. A drug of the class SERM is treatment of choice in this case, until symptoms subside.

If a patient has “nipple issues”, even while estrogen is within normal range, I add a SERM, emergently. I prefer Nolvadex over Clomid, and Evista is probably best of all for antagonizing estrogen (although much more expensive). Clomid often induces untoward visual effects (i.e. “tracers”), and can cause emotional lability by virtue of its estrogen agonistic effects at the more peripheral (emotion) brain sites. I do like my patients to keep some Nolvadex on hand, should they experience nipple swelling or sensitivity, so they may begin 40mg per day until the symptoms abate, and then taper to 20 mg QD for a few days, then 10mg for a few more, then finally 5mg QD to taper off."
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[Toxic Avenger]

I screwed up once and used to much test with masteron thinking that the masteron would work somewhat as an AI. In less than 2 weeks I had severe estrogenic bloat and glyno symptoms. I took Letro Mon, Wed, Fri at 0,5 mg for 2 weeks and upped the Masteron and lowered the Test and everything turned out OK. The letro stopped the bloat by the nex day and the gyno settled down over the two weeks. By that time the masteron was high enough and Test was low enough that I did not have a recurrence. One side note, the letro did give me a little more pain in the knee and hip for that 2 weeks and the gains were slowed down somewhat.

[jaws]

Originally Posted by Toxic Avenger

I screwed up once and used to much test with masteron thinking that the masteron would work somewhat as an AI. In less than 2 weeks I had severe estrogenic bloat and glyno symptoms. I took Letro Mon, Wed, Fri at 0,5 mg for 2 weeks and upped the Masteron and lowered the Test and everything turned out OK. The letro stopped the bloat by the nex day and the gyno settled down over the two weeks. By that time the masteron was high enough and Test was low enough that I did not have a recurrence. One side note, the letro did give me a little more pain in the knee and hip for that 2 weeks and the gains were slowed down somewhat.

Ahhh this is why my hips hurt when stretching, I just thought it was because of the stress on the body due to dieting and trianing pre contest.

I've have been taking Femera for almost 3 weeks now 1st week at 1.25mgs/ ED and last 2 weeks at 2.50mgs/ ED and my gyno has decreased to about 80%. The depression and low self asteam is an issue, as I am prepairing for a contest but I'm am going to lower the dose after today to 1.25mgs/ ED to hopefully get things really back on track.

How long should u run a cycle of femera for at the Max?

By the way guys great info! THANKS!

[sityslicker1]

Damn, I voted for femera by accident. I think femera would be the best AI hands down, if it wasn't for the significant estro rebound after coming off. My vote goes to Aromasin.

[Toxic Avenger]

Originally Posted by jaws

Ahhh this is why my hips hurt when stretching, I just thought it was because of the stress on the body due to dieting and trianing pre contest.

I've have been taking Femera for almost 3 weeks now 1st week at 1.25mgs/ ED and last 2 weeks at 2.50mgs/ ED and my gyno has decreased to about 80%. The depression and low self asteam is an issue, as I am prepairing for a contest but I'm am going to lower the dose after today to 1.25mgs/ ED to hopefully get things really back on track.

How long should u run a cycle of femera for at the Max?

By the way guys great info! THANKS!

I am no expert here. I have seen protocols where the letro is cycled up then down over weeks in efforts to reduce gyno and avoid rebound. Essentially over about 5 weeks or so the drug is quickly ramped up to 2.5 mg/d, maintained there for 10 days, then reduced to 2.0, 1.5, 1.0, 0.5, 0.25, 0.1 over about three weeks. that would absolutely kill my joints. The 1/2 life of this stuff is on the order of 14 days. I just don't see the point of such a long gentile tapper. The best way I have found to use it is at low dose for up to 4 weeks at o more than 0.5 mg/d then move directly into 20 mg Nolvadex for several weeks. I am prone to gyno and this seems to work well for me.. but I am not a competitive bodybuilder. I'm a former martial arts competitor and sometimes steroid user.