# Letrozole



## johnjuanb1 (Apr 19, 2014)

* Letrozole* is currently the most powerful aromatase inhibitor available. It has been shown to reduce estrogen levels by 98% or more. Intravenous administration of Letrozole lowered Estrogen by 46% in the young men tested, and 62% in the elderly subjects. Because estrogen is part of the negative feedback loop of the HPTA, Letrozole (and other anti-estrogens) are able to raise testosterone in male subjects. Letrozole was studied in men, and found to significantly increase LH levels to a 339 and 323% in the young and the elderly, respectively and Testosterone by 146 and 99%, respectively. 

Letrozole was also able to produce a peak LH response to Gonadatropin Releasing Hormone equal to a 152 and 52% increase from baseline in either young or older men, respectively. In a similar study 0.02 mg of Letrozole increased testosterone by 45% after 2 days. That same twenty micrograms of Letrozole was also enough, in one study done on men, to reduce estrogen levels by roughly a third. Letrozole has a 2-4 day half-life, and it needs to be taken for up to 60 days to get a steady blood plasma level. Letro is best dosed from 0.125-2.5 mgs depending on the desired effect.


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## Elvia1023 (Apr 19, 2014)

I think letro is an amazing AI for competitors or guys who want to get ripped/dry. I notice after 1 week on it I am so dry (lowered water retention)and look like I have lost a few bf%. Obviously not saying it lowers bf that fast it just gives you that look as we carry a lot of water. I think it is the most effective AI for these purposes.


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## johnjuanb1 (May 2, 2014)

*Letrozole once a week normalizes serum testosterone in obesity-related male hypogonadism.*

AuthorsLoves S, et al. Show all Journal
Eur J Endocrinol. 2008 May;158(5):741-7. doi: 10.1530/EJE-07-0663.

Affiliation
*Abstract*
OBJECTIVE: Isolated hypogonadotropic hypogonadism (IHH) is frequently observed in severely obese men, probably as a result of increased estradiol (E(2)) production and E(2)-mediated negative feedback on pituitary LH secretion. Aromatase inhibitors can reverse this process. This study evaluates whether letrozole once a week can normalize serum testosterone in severely obese men and maintain its long term effect.

DESIGN: Open, uncontrolled 6-month pilot study in 12 severely obese men (body mass index>35.0 kg/m(2)) with obesity-related IHH and free testosterone levels <225 pmol/l, treated with 2.5 mg letrozole once a week for 6 months.

RESULTS: Six weeks of treatment reduced total E(2) from 123+/-11 to 58+/-7 pmol/l (P<0.001, mean+/-s.e.m.), and increased serum LH from 4.4+/-0.6 to 11.1+/-1.5 U/l (P<0.001). Total testosterone rose from 5.9+/-0.5 to 19.6+/-1.4 nmol/l (P<0.001), and free testosterone from 163+/-13 to 604+/-50 pmol/l (P<0.001). Total testosterone rose to within the normal range in all subjects, whereas free testosterone rose to supraphysiological levels in 7 out of 12 men. The testosterone and E(2) levels were stable throughout the week and during the 6-month treatment period.

*CONCLUSION: Letrozole 2.5 mg once a week produced a sustained normalization of serum total testosterone in obese men with IHH. However, free testosterone frequently rose to supraphysiological levels. Therefore, a starting dose <2.5 mg once a week is recommended.*


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## MattG (May 2, 2014)

Good studies. Also has gotten me out of many nerve racking nip situations.lol. Letro= gyno b gone


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## johnjuanb1 (May 10, 2014)

*Letrozole attaches to the aromatase enzyme and prevents it from converting androgens to estrogen.*


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## Elvia1023 (May 10, 2014)

I am getting ripped so I decided I am gonna introduce Letro in about 4 weeks to get me dry etc.


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## johnjuanb1 (May 13, 2014)

*Letrozole is known to be very potent at lowering LDL, and it can also raise HCL, and has been known to increase HGH levels.*


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## johnjuanb1 (May 13, 2014)

*Letrozole is currently the most powerful aromatase inhibitor available. *


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## johnjuanb1 (May 14, 2014)

*Use of the aromatase inhibitor letrozole to treat male infertility.*

AuthorsPatry G, et al. Show all Journal
Fertil Steril. 2009 Aug;92(2):829.e1-2. doi: 10.1016/j.fertnstert.2009.05.014. Epub 2009 Jun 12.

Affiliation
*Abstract*
OBJECTIVE: *Report the case of induction of spermatogenesis with the aromatase inhibitor letrozole.*

DESIGN: Case report.

SETTING: University Infertility center.

PATIENT(S):* A 31-year-old man with primary infertility, normal volume azoospermia, normal follicle stimulating hormone (FSH) levels and pattern of nonobstructive azoospermia (NOA) on a testicular biopsy.*

INTERVENTION(S): The patient was given the aromatase inhibitor letrozole for 4 months and had repeated FSH, testosterone, LH levels, semen analyses, and finally a testicular biopsy.

MAIN OUTCOME MEASURE(S): Results of a testis biopsy.

*RESULT(S): Testis biopsy showed normal spermatogenesis following 4 months of letrozole therapy.

CONCLUSION(S): This is the first case report on the use of letrozole to treat male infertility and the first case report on the induction of spermatogenesis in a man with NOA using any aromatase inhibitor.*


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## Daniel11 (May 14, 2014)

So it reduces estrogen by 46-62% in men right? Not 98% as we often hear parroted on Forums.  

I have seen that study before and it made me realize that Letro is over hyped IMO.


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## Elvia1023 (May 14, 2014)

Daniel11 said:


> So it reduces estrogen by 46-62% in men right? Not 98% as we often hear parroted on Forums.
> 
> I have seen that study before and it made me realize that Letro is over hyped IMO.



Yes. The higher percentages are for women (wipes nearly all estrogen).

Studies can be great but personal use is everything. Letro is definitely stronger than the likes of aromasin and arimidex. That can be a good or bad thing though. Have you used Letro before?


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## Daniel11 (May 14, 2014)

Yes I have.


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## Enigmatic707 (May 14, 2014)

Elvia1023 said:


> Yes. The higher percentages are for women (wipes nearly all estrogen).
> 
> 
> 
> Studies can be great but personal use is everything. Letro is definitely stronger than the likes of aromasin and arimidex. That can be a good or bad thing though. Have you used Letro before?




Letro is way over hyped, I've been saying this for years- if you look at all my cycles and info I post Letro is my AI of choice.. Also it has the most profound impact of all the serms and AI's in keeping your test levels up durring and post cycle


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## johnjuanb1 (May 14, 2014)

*Lowering estradiol levels, by administering an aromatase inhibitor, is associated with an increase in levels of LH, follicle-stimulating hormone (FSH) and testosterone *


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## Elvia1023 (May 15, 2014)

*Letrozole versus testosterone. a single-center pilot study of HIV-infected men who have sex with men on highly active anti-retroviral therapy (HAART) with hypoactive sexual desire disorder and raised estradiol levels.*

Richardson D1, Goldmeier D, Frize G, Lamba H, De Souza C, Kocsis A, Scullard G.



Author information 



Abstract

INTRODUCTION: 

Since the advent of Highly Active Anti-Retroviral Therapy (HAART), men with HIV experience good quality of life and expect to have normal sexual function. However, it appears that men infected with HIV commonly complain of sexual problems. There is evidence that men on HAART develop low sexual desire that is associated with raised estradiol levels. It has been postulated that abnormal metabolism seen in this group of men increases the aromatization of testosterone to estradiol. We hypothesized that letrozole, an aromatase inhibitor that inhibits the conversion of testosterone to estradiol, would be beneficial in these men.

AIM: 

The aim of this study was to compare the effects of testosterone vs. an aromatase inhibitor, letrazole, in HIV-infected men with raised estradiol and low sexual desire.

METHODS: 

Thirteen men who have sex with men on HAART with low sexual desire as well as raised estradiol levels (>120 pmol/L) were randomly allocated to receive either parenteral testosterone (Sustanon 250 intramuscular injection) (N = 6) or letrozole 2.5 mg orally daily (N = 7) for 6 weeks.

MAIN OUTCOME MEASURES: 

Sex steroid hormone assays, sex hormone-binding globulin, virological, hematological, and biochemical parameters were measured before and after treatment. Each subject was given the Spector Sexual Desire Inventory and the Depression/Anxiety Stress Scale before and immediately after treatment. Subjects were also asked to estimate the number of actual sexual acts before and after treatment. *Results. Inventory data showed a rise in dyadic desire in both treatment arms. Mean actual sexual acts rose from 0.33 to 1.5 in the testosterone group and from 0.43 to 1.29 for the letrozole group. Luteinizing hormone increased in seven of seven men on letrozole. Serum testosterone increased in seven of seven men on letrozole. There were no adverse events from either medication.*
CONCLUSION: 

*Letrozole may be useful in the management of men on HAART who have low sexual desire. *


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## johnjuanb1 (May 16, 2014)

*Short-term aromatase inhibition: effects on glucose metabolism and serum leptin levels in young and elderly men*

*Abstract*

*Objective *To assess and compare the effects of short-term aromatase inhibition on glucose metabolism, lipid profile, and adipocytokine levels in young and elderly men.
Design and methods Ten elderly and nine young healthy men were randomized to receive letrozole 2.5 mg daily or placebo for 28 days in a crossover design.
*Results    Both in young and elderly men, active treatment significantly increased serum testosterone (+128 and +99%, respectively) and decreased estradiol levels (−41 and −62%, respectively). *Fasting glucose and insulin levels decreased in young men after active intervention (−7 and −37%, respectively) compared with placebo. Leptin levels fell markedly in both age groups (−24 and −25%, respectively), while adiponectin levels were not affected by the intervention. Lipid profile was slightly impaired in both groups, with increasing low density lipoprotein-cholesterol levels (+14%) in the younger age group and 10% lower levels of APOA1 in the elderly. A decline in IGF1 levels (−15%) was observed in the younger age group. No changes in weight or body mass index were observed in either young or old men.
*Conclusions * Short-term aromatase inhibition appears to affect glucose metabolism in young men, and lipid metabolism, including leptin secretion, in young and elderly men. Furthermore, the short period of exposure suggests that these changes might be mediated by direct effects of sex steroids rather than by changes in body composition.


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## Elvia1023 (May 16, 2014)

I plan to order some of our letrozole on the w/e 



johnjuanb1 said:


> *Short-term aromatase inhibition: effects on glucose metabolism and serum leptin levels in young and elderly men*
> 
> *Abstract*
> 
> ...


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## johnjuanb1 (May 16, 2014)

Limits Advanced Journal list Help
Journal ListIndian J Endocrinol Metabv.17(Suppl1); Oct 2013PMC3830326

Indian J Endocrinol Metab. Oct 2013; 17(Suppl1): S259–S261.
doi:  10.4103/2230-8210.119594
PMCID: PMC3830326
*Aromatase inhibitors in male sex*

Santosh Kumar Singh
Author information ► Copyright and License information ►
Go to:

*ABSTRACT


Aromatase inhibitors (AI) have been used in males in idiopathic short stature, constitutional delay of puberty, precocious puberty, gynecomastia, oligospermia, hypogonadism related to obesity and ageing. *This retrospective study echoed the benefit of AI in Indian males in varied conditions.
Keywords: Aromatase inhibitors, constitutional delay of puberty, hypogonadism
Go to:
Introduction
Aromatase inhibitors (AI) have been used in the treatment of idiopathic short stature (ISS), constitutional delay of puberty (CDP) and precocious puberty in boys to increase adult height. Moreover, it has been used in the management of gynecomastia, oligospermia and male hypogonadism related to obesity and ageing.[1,2,3] *This retrospective study was carried out to assess the efficacy of letrozole, *an AI, in varied conditions in Indian males.
Go to:
Case Reports
Case A
A 15-year-old male presented with macromastia. He had delayed puberty.
Wt - 62.7 kg; Ht - 155 cm; Sexual Maturation Rate (SMR) - G1P1, testes - 3 ml, stretched penile length (SPL) - 5 cm.
LH - 6.3 IU/L, follicle-stimulating hormone (FSH) - 2.9 IU/L, prolactin (PRL) - 5.1 ng/ml, normal thyroid-stimulating hormone (TSH) and T4.
Testosterone (T) - 43.8 ng/dl and estradiol (E2) - 9.79 pg/ml. T/E2 = 4.4:1. He was prescribed letrozole 2.5 mg - 3 times/week.
After 6 months of AI therapy:
Wt - 68.8 kg; Ht - 158.5 cm; SMR - G3P3, testes 10 ml, SPL - 6 cm. There was insignificant change in breast enlargement.
T - 331.62 ng/dl; E2-8.05 pg/ml. T/E2 = 41.2.
There was 650% increase in T and 17.9% decrease in E2.
Case B
A 14-year-old male was referred for obesity. He had delayed puberty.
Wt - 66.6 kg; Ht - 158 cm; SMR - G1P1, SPL - 4 cm.
LH - 3.59 IU/L; FSH - 2.48 IU/L; PRL - 13.8 ng/ml, normal TSH and T4.
T - 25.81 ng/dl; E2 - 141.3 pg/ml; T/E2 = 0.18:1.
He was prescribed injection T - 100 mg monthly and letrozole 2.5 mg - 3 times/week for 4 months. After 3 weeks of last dose of injection T and 3 days of last dose of letrozlole: Wt - 68.9 kg; Ht - 159.5 cm; SMR-G2P2, SPL ~5 cm.
T - 310.6 ng/dl; E2 - 13.15 pg/ml; T/E2 = 23.6:1.
There was ~1100% increase in T and 90% decrease in E2.
Case C
A 23-year-old male was referred for management of hypogonadism.
Wt - 55.9 kg; Ht - 161 cm; body mass index - 21.6; no anosmia; SMR - G1P1, SPL - 4 cm. LH <0.07 IU/L, FSH - 0.032 IU/L, PRL - 4.93 ng/ml, T - 13 ng/dl.
He was prescribed injection T - 100 mg every 3 weeks along with letrozole 2.5 mg - 2 times/week. After 3 weeks of last (4th) injection T and 3 days of last letrozole dose: T - 74 ng/dl.
There was 469% increase in T.
Case D
A 27-year-old male was referred for poor semen quality. His total functional sperm fraction (TFSF), denoted by sperm count (×106) by normal morphology (%) by normal motility (%), was 70 × 106/ml × 30% × 30% =6.3.
T - 257.9 ng/dl; E2 - 35.8 pg/ml; T/E2 = 7.2:1.
He was prescribed letrozole - 2.5 mg - 2 times/week.
After 1 month of therapy: T - 754.9 ng/dl; E2 - 28.5 pg/ml; T/E2 = 26.5:1.
There was 200% increase in T and 20% decrease in E2.
TFSF - 80 × 106 × 70% × 30% =16.8.
Go to:
Discussion
AI have been used in boys with ISS and CDP to increase adult height.[1,4,5] Boys with ISS with a mean age of 11 years were treated with letrozole 2.5 mg once daily or placebo for 2 years. There was a gain of 5.9 cm in predicted adult height in the letrozole treated group.[4] A significant increase in predicted adult height has also been observed in boys with CDP who were treated with a combination of T and letrozole.[5] AI slow down epiphyseal maturation by lowering E2 levels. This approach proved successful in other conditions, too, viz. aromatase excess syndrome, sertoli cell tumors and testotoxicosis (along with antiandrogen).[1] AI have limited efficacy in the treatment of gynecomastia; hence, they are not recommended as a first line treatment for gynecomastia.[1] Significant improvement in SMR was observed in CDP cases (Case A and B). There was marked improvement in SMR in case A with “sole” therapy with letrozole, but insignificant response in gynecomastia. Case B was treated with a “combination” of T and letrozole.
AI therapy is associated with a sustained increase in FSH and a positive effect on sperm concentration and motility.[1] Case D (T <300 ng/dl; T/E <10:1) showed improvement in semen quantity and quality with letrozole even though sperm count was normal. Some men with severe oligospermia (<5 × 106/ml), low T levels (<300 ng/dl), T (ng/dl) to E2 (pg/ml) ratio <10 and normal gonadotropins concentration may have a treatable endocrinopathy. AI have been successfully used in this subset of patients.[1,3,6] 2.5 mg/d letrozole for 6 months has been shown to improve seminal parameters (denoted by TFSF).[3]
AI have been used in the treatment of hypogonadism related with obesity and ageing. Letrozole 2.5 mg once a week produced sustained normalization of serum total T in males with obesity related hypogonadism; however, free T rose to supraphysiological levels emphasizing the need for estimation of free T during AI treatment.[2]
It has been suggested that aromatase is less suppressed in the testis compared with adipocytes and muscle tissue. It is questionable whether AI are able to stimulate T production sufficiently in men with truly low T levels.[1] There was a marked increase in T with combination treatment with T and letrozole in CDP (Case B) as compared with Idiopathic Hypogonadotropic Hypogonadism (IHH) (Case C) where there was lesser response with the same combination therapy. The marked increased in T with letrozole in CDP as compared to lesser response in IHH can aid in distinguishing the two conditions with the use of AI.
Most of the recent studies with AI in boys and adult men do not show a major detrimental effects (including bone).[1] The harmful effects are unlikely if the dose is carefully adjusted (even weekly) based on T and E2 levels.[3]
This retrospective study in Indian males showed insignificant effect of AI in gynecomastia and IHH, significant effect in CDP and some benefit in improving seminal parameters. Moreover, this study highlights the importance of estimating E2 (along with T and gonadotropins) in various endocrinopathies, which can be benefitted by reducing E2 by AI.
Further prospective, randomized, blinded, placebo-controlled, long-term studies are needed to clarify the role of AI in the management of growth impairment, male infertility and hypogonadism.


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## johnjuanb1 (May 17, 2014)

*Aromatase inhibitor letrozole guards against breast cancer relapse for up to 8 years
*
Sep 25, 2011
Stockholm, Sweden: Results from the longest-running trial comparing tamoxifen with the aromatase inhibitor letrozole show unequivocally that letrozole has withstood the test of time and continues to prevent breast cancer recurrences and reduce the risk of death in post-menopausal women with hormone receptor-positive early breast cancer.

Professor Richard Gelber told delegates at the 2011 European Multidisciplinary Cancer Congress, in Stockholm today that a 12-year update of results from the Breast International Group (BIG) 1-98 trial showed that if women with early breast cancer (cancer that has not spread from the breast) were given letrozole after surgery for at least five years, they continued to do better and have fewer recurrences of the disease than those who were given tamoxifen.
"Over a median of eight years of follow-up, women who were assigned to receive five years of letrozole after surgery had an 18% reduced risk of relapse and a 21% reduced risk of death compared with those assigned to receive tamoxifen," said Prof Gelber, Director of the International Breast Cancer Study Group (IBCSG) Statistical and Data Management Center at the Dana-Farber Cancer Institute, Boston, MA, USA.

"The current 12-year update is the longest follow-up to date and includes much more information than we had after ten years. For instance, there have been 32% more relapses and 39% more deaths since the ten-year update, which increases substantially the reliability of the results and provides reassurance regarding the long-term value of letrozole. This additional follow-up and accumulation of information on relapses and deaths show that the overall survival advantage for adjuvant letrozole compared to tamoxifen continues to be statistically significant."

Adjuvant therapy (treatment that is given after surgery), using drugs that target hormones such as oestrogen, is given to patients with early breast cancer who have hormone receptor-positive tumours. These tumours occur in approximately 75% of breast cancer cases. Tamoxifen has been the "gold standard" hormone treatment for women with early, oestrogen-receptor-positive breast cancer and works by blocking the growth-promoting action of oestrogen on the cancer cells. Aromatase inhibitors, such as letrozole, are newer and alter the function of aromatase, an enzyme involved in oestrogen production. They can be used in sequence with, or as an alternative to tamoxifen for post-menopausal women.

In the BIG 1-98 trial, researchers enrolled 8,010 patients to receive letrozole and tamoxifen either alone or in sequence, with a total of 4,922 patients included in the monotherapy arms of the study.

Efficacy analyses comparing the treatment groups were conducted every two years following the initial report of results, because the patients had a long-term risk of recurrence. This 12-year update shows that, among all 8,010 patients, there were 2,074 relapses and 1,284 deaths, compared with 1,569 relapses and 923 deaths at the ten-year update.

"The data also show that the sequential use of letrozole and tamoxifen (two years of one agent followed by three years of the other) provided similar outcomes compared with five years of letrozole alone for patients who are not at high risk for recurrence," said Prof Gelber.

"The optimal regimen remains an open question in many areas of the world, and this large trial presents definitive results for the treatment of the largest group diagnosed with breast cancer: post-menopausal women with hormone-responsive early breast cancer."

He added: "Letrozole and tamoxifen have different side effects, and clinicians should consider the individual patient's medical history when prescribing treatment. Both agents are considered to be safe, especially in view of the substantial reduction in the risk of recurrence and the improved survival provided by these two endocrine therapies. While long-term safety data are available for tamoxifen, follow-up of patients who have received letrozole or other aromatase inhibitors is still relatively short. Thus, assessment of the long-term safety of letrozole is a critical objective for the BIG 1-98 follow-up study."

The IBCSG recently launched a long-term observational study that will extend patient follow-up for an additional five years in order to provide further information on efficacy and side effects of five years of adjuvant hormone therapy. "The follow-up study includes collection of yearly updates of survival, disease status and long-term adverse events. We plan to continue to update results every two years. This study is critically important as more than 74% of the patients enrolled in BIG 1-98 were still alive without a relapse at their most recent study visit. Assessment especially of long-term side effects for these patients is critically important," he said.

"BIG 1-98 and other large randomised clinical trials have firmly established the benefits of adjuvant treatment programmes including aromatase inhibitors, such as letrozole. Improved disease control and extended survival will reduce burdens on healthcare systems by reducing the number of patients requiring treatment for metastatic breast cancer. Furthermore, the cost of aromatase inhibitor treatment will decrease in the near future as generic products become available," Prof Gelber added.

Professor Michael Baumann, president of ECCO said: "This 12-year update of the study sheds more light on the advantages of aromatase inhibitors over tamoxifen in the adjuvant treatment of early breast cancer. It also clearly demonstrates how important it is to perform long-term follow-up and analysis of clinical studies especially for breast cancer. Long-term analysis is essential for reliably ensuring the efficacy of treatments but also to detect potential long-term side-effects which may affect quality of life. Although it is very difficult and costly to perform such long-term trials, the return for optimising treatments for cancer patients cannot be overemphasised."

Commenting on the study, which he was not involved with, ESMO member Professor Christoph Zielinski from the Medical University of Vienna, Vienna, Austria, said: "The BIG 1-98 trial demonstrates the clinical benefits of the aromatase inhibitor, letrozole and also provides further insight into the biology of the disease and how to improve outcomes with the upfront use of letrozole, compared to tamoxifen. This is important for daily clinical practice."


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## johnjuanb1 (May 20, 2014)

Men who take 2.5 mg letrozole daily will notice that their testosterone levels double and the concentration of estradiol in their blood decreases by 45 percent.


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## Elvia1023 (May 21, 2014)

I should have mine 2moro   I am gonna start at 0.5mg per day but will up probably up 0.5mg every week. I want it to dry me out just another experiment of mine


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## Elvia1023 (May 23, 2014)

Fuck! That will wake you up in the mornings! That was my thoughts after trying Superiors letro for the first time last night!


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## Elvia1023 (May 27, 2014)

I have been on 50mg winny for a few weeks but in the last few days my joints have got much worst. This letro is potent and I am loving it apart from my knees starting to hurt. I am still only on 0.5mg too! Drying out like I just spent 6 hours on the beach in Turkey!


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## Elvia1023 (May 28, 2014)

This may be too much information but honestly my libido is night and day different after starting the letro. I am surprised by this. We all know what high dosed letro can do to libido. Usually my libido on tren is sky high but this time round it's been declining fast. I must have needed the letro. The size of my flaccid penis is much bigger too and I keep getting erections all the time! I am using MT2 too but have been on it for a long time so it's definitely the letro. I am sure though it will start having the opposite effect though as I bump the dose up and the longer I stay on it. I am drying out well though and have noticed lots more vascularity in my legs... even my feet are more vascular 

I still haven't added the tadalafil either  I keep forgetting but will dose it preworkout 2moro!


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## johnjuanb1 (Jun 11, 2014)

Posted in another forum....

"letro will be the most powerful AI you can use, it will inhibit 98+% of estrogen using a dose as low as .25mg and even lower. This is why I suggest you do not use a dose higher than .50mg while on cycle just trying to prevent estrogen related side effects ."


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## Elvia1023 (Jun 12, 2014)

I started 1.5mg last night... so strong... could feel the difference when I woke up.


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## Elvia1023 (Jun 26, 2014)

I have stopped my letrozole. It was a great run and helped make me look tighter but I think a break is needed. I don't want to be running high doses for long periods. Plus I don't need it for the cycle I am on as my aas doses are fairly low now. I will try and get my cholesterol etc tested to see how I am.


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