Aromasin, Arimidex, Letrozole, Oh My!

[Sassy69]

So FOR WOMEN, most will be pointed to nolvadex for estrogen manipulation before a show. If you are using an aromatizing testosterone, you might be lookign to use an AI. But would you look to any of the others for estrogen blocking for competition?

Aromasin or Letro seems to be the less harsh for men. What about for women?

Any thoughts? I've seen adex recommended for women, but not aromasin.

[Mike Arnold]

There is no doubt that either Aromasin or Letro, especially Letro, is able to dry one out much more effectively than Nolva, but it is also much harder on a woman's entire system, as it eliminates all systematic estrogen completely if the dose is high enough.

As you know, E causes whole body water retention and fat gain. Eliminating whole body E will cause a woman to drop all the water she holds from her natural E, as well as reverse the trend of E induced fat gain.

A-dex is just as potent as Aromasin for estrogen reduction. The primary difference is that Aromasin is a suicide inhibitor, which meas it completely deactrivates the estrogen molecule; there is no estrogen rebound like what can occur with A-dex or letro.

However, Letro is the most potent of them all for reducing estrogen, despite it not being a suicide inhibitor.

At least with Nolva, there is systematic E floating around for physiological functioning, although it will be impaired to a degree. With AI's, it is possible to take away nearly all systematic estrogen, leaving the female in a totally estrogen deprived state. This will result in what could be considered severe side effects...especially if estrogen is kept low for some time.

[Kaladryn]

There is no doubt that either Aromasin or Letro, especially Letro, is able to dry one out much more effectively than Nolva, but it is also much harder on a woman's entire system, as it eliminates all systematic estrogen completely if the dose is high enough.

Isn't this only true in post menopasual women? My understanding is that most aromatase in pre menopasual women is placental aromatase. This aromatase is protected from many things, much like the blood brain barrier keeps many things out of the brain. My understanding is that current AIs don't pass into the placenta and therefore cannot affect placental aromatase, which is the majority of female aromatase.

[Mike Arnold]

Isn't this only true in post menopasual women? My understanding is that most aromatase in pre menopasual women is placental aromatase. This aromatase is protected from many things, much like the blood brain barrier keeps many things out of the brain. My understanding is that current AIs don't pass into the placenta and therefore cannot affect placental aromatase, which is the majority of female aromatase.

You got me and that doesn't happen very often....LOL. Something for me to research now. Thank you. One thing I do know for certain is that AI's will dry women out considerably, as I have seen it witnessed many times. ...sides are more extreme compared to Nolva, though (dependong on dose). However, you raise a great question pertaining to possible differences regarding an AI's effects on women when compared to men.

I will look into this and get back with you.

[SisterSteel]

Isn't this only true in post menopasual women? My understanding is that most aromatase in pre menopasual women is placental aromatase. This aromatase is protected from many things, much like the blood brain barrier keeps many things out of the brain. My understanding is that current AIs don't pass into the placenta and therefore cannot affect placental aromatase, which is the majority of female aromatase.

Your stating that postmenopausal women get most of their estrogen from the conversion of androgens into estrogen by the aromatase enzyme, while premenopausal women get most of their estrogen directly from their ovaries, is a fairly accurate observation. However, we are talking about supplementing with a synthetic aromatisable androgen. The aromatase inhibitor will serve its purpose of reducing estrogen by blocking the aromatase enzyme and keeping it from converting androgens into estrogen. Let me add that AIs can be effective in some premenopausal women after the application of a gonadotropin releasing hormone agonist which itself results in postmenopausal plasma oestrogen concentrations. In layman, a premanopausal female can benefit from an AI if menopause is induced with medication by suppressing ovarian functions and decreasing estrogen levels.

[Mike Arnold]

Your stating that postmenopausal women get most of their estrogen from the conversion of androgens into estrogen by the aromatase enzyme, while premenopausal women get most of their estrogen directly from their ovaries, is a fairly accurate observation. However, we are talking about supplementing with a synthetic aromatisable androgen. The aromatase inhibitor will serve its purpose of reducing estrogen by blocking the aromatase enzyme and keeping it from converting androgens into estrogen. Let me add that AIs can be effective in some premenopausal women after the application of a gonadotropin releasing hormone agonist which itself results in postmenopausal plasma oestrogen concentrations. In layman, a premanopausal female can benefit from an AI if menopause is induced with medication by suppressing ovarian functions and decreasing estrogen levels.

It's common sense that AI's would still prevent the conversion of exogenous AAS to estrogens in pre-menopausal women, as an AI's effect on aromitase inhibition is unifrom across the board when it comes to exogenous AAS. Therefore, an AI would be beneficial for drying an AAS using women out, but only in part, as you state that ovarian estrogen will remain.

Therefore, in the end, what I hear you saying is that the only way to thoroughly dry out an AAS using woman is to block the conversion of estrogen from exogenous AAS with an AI, while also blocking ovarian aromatase with a GRH agonist.

Am I on track? Like everything with you women...nothing is ever simple.

[Sassy69]

It's common sense that AI's would still prevent the conversion of exogenous AAS to estrogens in pre-menopausal women, as an AI's effect on aromitase inhibition is unifrom across the board when it comes to exogenous AAS. Therefore, an AI would be beneficial for drying an AAS using women out, but only in part, as you state that ovarian estrogen will remain.

Therefore, in the end, what I hear you saying is that the only way to thoroughly dry out an AAS using woman is to block the conversion of estrogen from exogenous AAS with an AI, while also blocking ovarian aromatase with a GRH agonist.

Am I on track? Like everything with you women...nothing is ever simple.

Practically speaking, I doubt any women would be using a long-acting AAS that converts anywhere near show time, so it begs the question what would be the purpose of using any of the AIs available? If we're speaking specifically pre-menopausal women who have not been using anything long enough to induce early menopause, then nolva is really the only thing that applies?

[Mike Arnold]

Practically speaking, I doubt any women would be using a long-acting AAS that converts anywhere near show time, so it begs the question what would be the purpose of using any of the AIs available? If we're speaking specifically pre-menopausal women who have not been using anything long enough to induce early menopause, then nolva is really the only thing that applies?

There are plenty of women using aromatizable AAS close to show time, primarily the "heavier" users, just as there are men. I do not think this is the best way to go about it, but many do.

Even if test prop is dropped 3 weeks before the show, the remaining test will still be interacting with aromatase for 7-10 days afterward, with the converted estrogen sticking around longer than that....which will result in additional water retention.

Anyone doing the smart thing and who has dropped the test prop 2-3 weeks pout, shoud still be running an AI right up until the show. A woman already has to worry about her ovarian estrogen, so any additional estrogen resulting from exogenous aromatizable AAS should be dealt with.

Ideally, whether a man or a woman (if side effects are not considered), maximum condition should be a priority when competing. After dealing dealing with the estrogen from exogenous aromatizable AAS, then ovarian aromatase should definitely be dealth with, as this is a large contributer in regards to the softness and watery look that most women carry, in comparison to a man.

As SS stated above (which is new to me), the only way to bloack ovarian aromatase is through the use of a GRH agonist. Being that estrogen is our #1 enemy come contest day, it makes sense to eliminate as much of it as possible in an attempt to come in at 100%. Doing anything less gives up ground to a harder and dryer woman.

For women not using any aromatizable AAS, then an AI would not be needed, but for all those that do, it is without a doubt a good idea....in additon to the implementation of a GRH agonist.

Therefore, in the cases where a woman does use an AI and a GRH agonsit, I ee no advantage to using Nolva along witn it. For those not using a GRH agonsit, Nolva would be mandatory. Women's "trouble" spots are no longer an issue once estrogen is eliminated, as estrogen itself was/is the cause of this issue.

For a woman using aromatizable AAS, using Nolva alone would still allow systematic estrogen to impair fat loss and cause whole body water retention, as Nolva is not very effective at drying one out, especially in comparison to completely eliminating all circulating estrogen through the use of AI/GRH agonsists.

However, I do have a question. The above response assumes a GRH agonist is able to basically eliminate ovarian aromatase, but how much ovarian aromatase can a GRH agonist deactivate?

The answer to this question is vital because the degree of deactivation tells us whether or not Nolva would be a necessity in women who are using an AI and GRH agonist. If a GRH agonsit can only partially deactivate ovarian aromatase, then this changes the whole picture and Nolva would still be mandatory, but if not, then Nolva would have no place in a woman's protocol under these circumstances...which is a woman using aromatizable AAS, along with an AI and GRH agonist.

[heavyiron]

There is no doubt that either Aromasin or Letro, especially Letro, is able to dry one out much more effectively than Nolva, but it is also much harder on a woman's entire system, as it eliminates all systematic estrogen completely if the dose is high enough.

As you know, E causes whole body water retention and fat gain. Eliminating whole body E will cause a woman to drop all the water she holds from her natural E, as well as reverse the trend of E induced fat gain.

A-dex is just as potent as Aromasin for estrogen reduction. The primary difference is that Aromasin is a suicide inhibitor, which meas it completely deactrivates the estrogen molecule; there is no estrogen rebound like what can occur with A-dex or letro.

However, Letro is the most potent of them all for reducing estrogen, despite it not being a suicide inhibitor.

At least with Nolva, there is systematic E floating around for physiological functioning, although it will be impaired to a degree. With AI's, it is possible to take away nearly all systematic estrogen, leaving the female in a totally estrogen deprived state. This will result in what could be considered severe side effects...especially if estrogen is kept low for some time.

Keep in mind that if a woman administers an aromatizing compound like testosterone then it is unlikely there will be complete inhibition of aromatase activity with an AI. One of the reasons AI's are less effective at reducing E2 in men is because we produce more T than woman so if a woman administers T the reduction in E2 from an AI will likely be similar to men. The following excerpt from a human trial in men comments on this;

The maximal suppression evoked by exemestane at the single dose of 25 mg in the present study was similar to published results in postmenopausal women, but the time course differed (24). Evans et al. (24) reported that a single 25-mg oral dose of exemestane maximally suppressed estradiol concentrations by 72% 3 d after administration, and estradiol levels returned to baseline only 8–11 d after drug administration. In the present study maximal suppression of estradiol of 62% was observed 12 h after exemestane administration and returned to baseline 3–6 d after administration. The reason for this difference is not clear, but may be related to the shorter half-life of exemestane in males, the lower exposure to exemestane, and the higher levels of the aromatase substrates androstenedione (1 ng/ml in young males vs. 0.5 ng/ml in postmenopausal women), particularly the much higher testosterone concentrations in young males than in postmenopausal women (700 ng/dl vs. 20 ng/dl, respectively) (25). This is supported by the observation that in the 10-d study in young males reported here, the suppression of estradiol is weaker (due to the very high levels of the precursor testosterone) than that of estrone (due to androstenedione levels not very different from those in postmenopausal women). A limited suppression of circulating estradiol (50%) has been reported in a similar study in young males treated with 1 mg daily anastrozole (7), a dose that reduces estradiol by 85% in postmenopausal women (23).

Therefore if a female administers Testosterone complete inhibition is unlikely.

[Mike Arnold]

^^^^^^^^

Great link. Thanks.

The good news is, it will still result in significant inhibition, just not total. None of us ever get total inhibition anyway. Well, it gets as close as it will get with Letro.

[heavyiron]

^^^^^^^^

Great link. Thanks.

The good news is, it will still result in significant inhibition, just not total. None of us ever get total inhibition anyway. Well, it gets as close as it will get with Letro.

I have never seen data to confirm this. In fact Letro is not as strong in men as some think. Again the circulating T in men makes AI's less effective so relying on a female trial does not have application to us.

Comparative Assessment in Young and Elderly Men of the Gonadotropin Response to Aromatase Inhibition

Guy G. T’Sjoen, Vito A. Giagulli, Hans Delva, Patricia Crabbe, Dirk De Bacquer and Jean-Marc Kaufman

Department of Endocrinology (G.G.T., H.D., P.C., J.-M.K.), Ghent University Hospital, 9000 Ghent, Belgium; Department of Public Health (D.D.B.), Ghent University, 9000 Ghent, Belgium; and Department of Internal Medicine Subdivision Endocrinology (V.A.G.), Ospedale Putignano-Noci, 70017 Bari, Italy
Address all correspondence and requests for reprints to: G. T’Sjoen, M.D., Department of Endocrinology, Ghent University Hospital, De Pintelaan 185, 9000 Ghent, Belgium. E-mail: guy.tsjoen@ugent.be .

Context: Aging in men is associated with a decline in serum testosterone (T) levels.
Objective: Our objective was to assess whether decreased T in aging might result from increased estradiol (E2) negative feedback on gonadotropin secretion.
Design and Setting: We conducted a comparative intervention study (2004) in the Outpatient Endocrinology Clinic, Ghent University Hospital.
Participants: Participants included healthy young and elderly men (n = 10 vs. 10).
Interventions: We used placebo and letrozole (2.5 mg/d) for 28 d, separated by 2 wk washout.
Main Outcome Measures: We assessed changes in serum levels of free E2, LH, and FSH, free T, SHBG, and gonadotropins response to an iv 2.5-µg GnRH bolus.
Results: As assessed after 28 d of treatment, letrozole lowered E2 by 46% in the young men (P = 0.002) and 62% in the elderly men (P < 0.001). In both age groups, letrozole, but not placebo, significantly increased LH levels (339 and 323% in the young and the elderly, respectively) and T (146 and 99%, respectively) (P value of young vs. elderly was not significant). Under letrozole, peak LH response to GnRH was 152 and 52% increase from baseline in young and older men, respectively (P = 0.01). Conclusions: Aromatase inhibition markedly increased basal LH and T levels and the LH response to GnRH in both young and elderly men. The observation of similar to greater LH responses in the young compared with the elderly does not support the hypothesis that increased restraining of LH secretion by endogenous estrogens is instrumental in age-related decline of Leydig cell function.

http://jcem.endojournals.org/cgi/reprint/90/10/5717

[SisterSteel]

Random Thoughts of mine on the subject...
An agonist is a releaser basically, a substance that binds to certain receptors to induce a particular response. It’s the opposite of an antagonist which binds to receptors to block a response. Don’t confuse a gonadotropin releasing hormone agonist (GnRH) and a growth hormone receptor agonist (GHR). Now the hypothalamus secrets GnRH hormone which interacts with the GnRH receptor to induce a response which is the release of FSH and LH by the putuitary. The GnRH agonist is a peptide basically which emulates the neurohormone GnRH in mechanism. A GnRH agonist is a synthetic peptide modeled after the hypothalamic neurohormone GnRH that interacts with the gonadotropin-releasing hormone receptor to elicit a biological response, the release of the pituitary hormones FSH and LH. So initially there is an increase in the secretion of FSH and LH but this downregulation of receptors which produces a huge hypogonadal effect in a matter of days. That is ultimately our therapeutic goal. So basically GnRH agonists treat estrogen production dependent disorders in women by suppressing ovarian activity and inducing a hypoestrogenic state. The best part of all this is this process is completely reversible. Lupron is a pretty popular GnRH agonist.

Another thing about Asin. Its a suicide AI which means it binds to the aromatase enzyme and permanently deactivates it. So there is almost no estrogen rebound coming off it. So i would pick Asin overe Adex anyday. But of course with the estrogen suppression comes a whole new spectrum of issues like early onset of osteoporosis etc...but hey. You know how it goes. Nothing for free in this game.

SS

[Mike Arnold]

Random Thoughts of mine on the subject...
An agonist is a releaser basically, a substance that binds to certain receptors to induce a particular response. It’s the opposite of an antagonist which binds to receptors to block a response. Don’t confuse a gonadotropin releasing hormone agonist (GnRH) and a growth hormone receptor agonist (GHR). Thanks for pointing that out. It was actually a typo, as you can see I typed GRH at first, but later accidentally typed GHR. I know what growth hormone releasing agonist is, but I did not know what I GRH agonist was until you talked about it in this thread. It was just a typo of terms. I will go back and fix it. The hypothalamus secrets GnRH hormone which interacts with the GnRH receptor to induce a response which is the release of FSH and LH by the putuitary. The GnRH agonist is a peptide basically which emulates the neurohormone GnRH in mechanism. A GnRH agonist is a synthetic peptide modeled after the hypothalamic neurohormone GnRH that interacts with the gonadotropin-releasing hormone receptor to elicit a biological response, the release of the pituitary hormones FSH and LH. So initially there is an increase in the secretion of FSH and LH but this downregulation of receptors which produces a huge hypogonadal effect in a matter of days. That is ultimately our therapeutic goal. So basically GnRH agonists treat estrogen production dependent disorders in women by suppressing ovarian activity and inducing a hypoestrogenic state. The best part of all this is this process is completely reversible. Lupron is a pretty popular GnRH agonist.

Another thing about Asin. Its a suicide AI which means it binds to the aromatase enzyme and permanently deactivates it. So there is almost no estrogen rebound coming off it. So i would pick Asin overe Adex anyday. But of course with the estrogen suppression comes a whole new spectrum of issues like early onset of osteoporosis etc...but hey. You know how it goes. Nothing for free in this game.
You right about that.
SS

Great post. It's nice to see someone talking about something I haven't already read about. In this case, the application and differences between men and women regarding these drugs. It is quite interesting.

[Mike Arnold]

I have never seen data to confirm this. In fact Letro is not as strong in men as some think. Again the circulating T in men makes AI's less effective so relying on a female trial does not have application to us.

Comparative Assessment in Young and Elderly Men of the Gonadotropin Response to Aromatase Inhibition

Guy G. T’Sjoen, Vito A. Giagulli, Hans Delva, Patricia Crabbe, Dirk De Bacquer and Jean-Marc Kaufman

Department of Endocrinology (G.G.T., H.D., P.C., J.-M.K.), Ghent University Hospital, 9000 Ghent, Belgium; Department of Public Health (D.D.B.), Ghent University, 9000 Ghent, Belgium; and Department of Internal Medicine Subdivision Endocrinology (V.A.G.), Ospedale Putignano-Noci, 70017 Bari, Italy
Address all correspondence and requests for reprints to: G. T’Sjoen, M.D., Department of Endocrinology, Ghent University Hospital, De Pintelaan 185, 9000 Ghent, Belgium. E-mail: guy.tsjoen@ugent.be .

Context: Aging in men is associated with a decline in serum testosterone (T) levels.
Objective: Our objective was to assess whether decreased T in aging might result from increased estradiol (E2) negative feedback on gonadotropin secretion.
Design and Setting: We conducted a comparative intervention study (2004) in the Outpatient Endocrinology Clinic, Ghent University Hospital.
Participants: Participants included healthy young and elderly men (n = 10 vs. 10).
Interventions: We used placebo and letrozole (2.5 mg/d) for 28 d, separated by 2 wk washout.
Main Outcome Measures: We assessed changes in serum levels of free E2, LH, and FSH, free T, SHBG, and gonadotropins response to an iv 2.5-µg GnRH bolus.
Results: As assessed after 28 d of treatment, letrozole lowered E2 by 46% in the young men (P = 0.002) and 62% in the elderly men (P < 0.001). In both age groups, letrozole, but not placebo, significantly increased LH levels (339 and 323% in the young and the elderly, respectively) and T (146 and 99%, respectively) (P value of young vs. elderly was not significant). Under letrozole, peak LH response to GnRH was 152 and 52% increase from baseline in young and older men, respectively (P = 0.01). Conclusions: Aromatase inhibition markedly increased basal LH and T levels and the LH response to GnRH in both young and elderly men. The observation of similar to greater LH responses in the young compared with the elderly does not support the hypothesis that increased restraining of LH secretion by endogenous estrogens is instrumental in age-related decline of Leydig cell function.

http://jcem.endojournals.org/cgi/reprint/90/10/5717

Anecdotally, it would appear Letro is the most potent AI for men while in use, despite estro rebound. I have not found any studies showing another AI has been able to lower E further than Letro...have you? The low E levels after use (as shown in blood work on an individual basis, on occasion) and the reversal of gyno, may be indicative of it's potency.

The reversal of male gyno in particular, of which Letro has been shown to be the only AI capable of illiciting this response so far, would appear to go hand in hand with the belief that Letro is more potent than other AI's for lowering total E, at least in breat tissue. I don't believe this can be discounted as being possibly indicative of greater potency.

According to user reviews, Ltro appears to be garnering excellent results. It has gained a strong following for use in contest prep as being the #1 AI of choice for squashing E levels.

If you know of any literature showing that another AI is able to lower E further than Letro, I woud definitely want to know about it, as it would change my recommendation regarding Letro and contest prep. In contes prep, suicide inhibition is less of a concern, as the BB'r is more worried about E levels while on the chosen AI, not what occurs afer the contest.

[heavyiron]

Anecdotally, it would appear Letro is the most potent AI for men while in use, despite estro rebound. The super low E levels after use (as confirmed on an individual basis after blood work on occasion), the reversal of gyno, it's acknowledgement as a superior AI for women in the literature.

The reversal of male gyno in particular, of which Letro has been shown to be the only AI capable of illiciting this response so far, would appear to go hand in hand with the literature showing Letro to be supoerior in women compared to other AI's.

I don't know of any literature showing any other AI to be more potent in lowering E levels than Letro and it appears this way anecdotally as well, according to user reviews. It has gained a strong following for use in contest prep as being the #1 AI of choice for squashing E levels.

If you know of any literature showing that another AI is able to lower E further than Letro, I woud defbitely want to know about ii, as it would change my recommendation regarding Letro and contest prep.

Well, if you read the above trial you can see Letro performed about the same as Adex and Aromasin in men. Adex usually can lower E2 about 50% and Aromasin about 62% in men. The letro trial shows a range of 46-62%.

Once you factor in all the additional benefits of Aromasin it is the obvious choice for E2 supression. One thing about Letro is it seems to have a longer half life than aromasin so the differences you are seeing is likely due to half life. Dosing the Aromasin every 12 hours should address this issue.