COPY AND PASTE FROM ANOTHER FORUM. PLEASE GIVE YOUR OPINIONS, I ONLY WANT TO REDUCE ESTRO BETWEEN 50%-75%:
Aromasin - Exemestane
Chemical Name: Exemestane
Drug Class: Type-I Aromatase Inhibitor
The below article about Aromasin-Exemestane discusses how it works and gives a history of the drug.
Aromasin (Exemestane) is a Type-I aromatase inhibitor, or suicidal aromatase inhibitor. It’s called this because it lowers estrogen production in the body by attaching to the aromatase enzyme, and permanently deactivating it. (1)
Personally, I find this to be a very interesting mechanism of action when compared to type-II aromatase inhibitors, which bind competitively to the aromatase enzyme, and eventually unbind, rendering it active again. In the case of Aromasin, this doesn’t happen, and once it does its job on the enzyme, those particular enzymes will no longer function. Your body will eventually create more of the aromatase enzyme, so this isn’t dangerous, despite the really odd “suicide” thing in the first paragraph. As with all aromatase inhibitors, Aromasin was developed to fight breast cancer primarily in post-menopausal women, but we in the athletic community use it to combat estrogenic side effects from aromatizable steroids, or for post cycle therapy.
Estrogen is responsible for many of the effects we’re trying to avoid when we’re on a cycle, including excess water retention and development of gynocomastia (breast tissue development in males. Thus, limiting the conversion of testosterone into estrogen is of use for steroid using athletes, when they’re trying to avoid side effects. In this case, the advantage of using a suicidal aromatase inhibitor is that it really won’t cause much, if any, noticeable “rebound” in estrogen when you cease using it.
The hard numbers on Aromasin are reasonably impressive, as it averages an 85% rate of estrogen suppression (2), and this translates to an overall reduction in estradiol levels of about 50%, as well as raising testosterone to a significant degree.(3).
It is also known as a “steroidal” aromatase inhibitor. This is really interesting, because it has been known to actually cause side effects (androgenic sides) that include increased aggressiveness and a pretty decent hardening effect. (4) I wouldn’t usually suggest that women should use Aromasin in large doses for any extended period of time, for this reason (possible virilization, or development of male sexual characteristics could occur with its use). It should, therefore, be reserved for use by women to brief periods of time in a possible pre-contest phase or for a form of post cycle therapy after a cycle.
Interestingly (and almost paradoxically) exemestane not only increases testosterone and lowers estrogen, but it also increases levels of insulin-like growth Factor (IGF). (5) I find this to be interesting, because although the rise in testosterone is most likely responsible for the increase in IGF levels, IGF is known to be an aggravating factor in the growth of breast tumors, like the kind found in breast cancer. However, since estrogen is the primary culprit in breast cancer, the large reduction in estrogen levels, even when combined with a rise in IGF, is enough to make Aromasin a very effective breast cancer medication. /div> Aromasin isn’t too harsh on blood lipids (6) (cholesterol), unlike some of the other AIs’ like Letrozole.
Exemestane reaches steady blood plasma levels of after a week of administration and this is also when we see it begin its maximal effect on reducing circulating estrogen levels. It’s also has a ½ life of 27 hours (4), so taking it once per day is going to build up blood plasma levels to a very effective level.
References:
1. A predictive model for exemestane pharmacokinetics/pharmacodynamics incorporating the effect of food and formulation.Br J Clin Pharmacol. 2005 Mar;59(3):355-64.
2. Eur. J. Cancer. 2000, May;36(8):976-82
3. The Journal of Clinical Endocrinology & Metabolism Vol. 88, No. 12 5951-5956Copyright © 2003 by The Endocrine Society
4. Clin Cancer Res. 2003 Jan;9(1 Pt 2):468S-72S
5. Anticancer Res. 2003 Jul-Aug;23(4):3485
6. J Clin Endocrinol Metab. 2003 Dec;88(12):5951-6.
Aromasin
(exemestane)
Aromasin (Exemestane) is a steroidal suicide aromatase inhibitor, which means that it lowers estrogen production in the body by blocking the aromatase enzyme, the enzyme responsible for estrogen synthesization. (1)(2)(3)
This stuff was developed to fight breast cancer in post-menopausal women, who need a particularly aggressive therapy, and for whom first line defenses such as SERMS (Tamoxifen) have not worked. This should be our first clue in inferring that this stuff is pretty strong, or at least stronger than some of the other compounds which are used to fight breast cancer.
Aromasin and Side Effects
Aromasin averages an 85% rate of estrogen suppression (4), so it´s clearly a very effective agent for bodybuilders and other athletes wanting to avoid estrogen related side effects such as gyno, acne, or water-retention brought on by aromatizing steroids. Specifically, Exemestane dose this by selectively inhibiting aromatase activity in a time-dependent and irreversible manner (hence the "suicidal" portion of it´s name, I guess).(7)
As with most of the compounds in this class, it also causes a reasonable rise in testosterone levels (6), and as you may have guessed, this rise in testosterone means that Exemestane can also cause androgenic sides(8)(9)(10). As you can see from the chart below, exemestane is very effective at both lowering estrogen (estradiol) and raising testosterone:
FIG. 1. Estrogen and androgen plasma levels after 10 d of daily exemestane (25 or 50 mg) in healthy young males (mean ± SD; n = 9-11). To convert to Systeme International units: estradiol, picomoles per liter (x3.671); estrone, picomoles per liter (x3.699); androstenedione, nanomoles per liter (*0.003492); and testosterone, nanomoles per liter (x0.03467). (13)
So we can see that 25mgs is a very effective dose from that chart, right? As an added benefit, exemestane not only increases testosterone and lowers estrogen, but it also increases IGF levels (11).Additionally Worth noting is that Aromasin may possibly be less harsh on blood lipids (14)than some of the other (similar) compounds we use in the world of bodybuilding or athletics (other AI´s). It also has, at best no effect on IGF, and at worst could lower (13) it. AI´s are very tricky with regards to inconsistencies in IGF levels.
Unfortunately, you need to take Exemestane for a week to reach steady blood plasma levels of it, and exemestane has a ½ life of 27 hours (12.).
The ability of exemestane to lower estrogen levels by the aforementioned 85% makes it a very nice choice for use in any cycle where aromatizing steroids are used. In addition, since it´s not too harsh at all on blood lipid profiles, it´s a very good choice for longer cycles. It´s ability to raise both testosterone levels also seem to suggest that it would be a very nice addition to a Post-Cycle-Therapy (PCT).
References:
A predictive model for exemestane pharmacokinetics/pharmacodynamics incorporating the effect of food and formulation.Br J Clin Pharmacol. 2005 Mar;59(3):355-64.
Exemestane for breast cancer prevention: a feasible strategy?Clin Cancer Res. 2005 Jan 15;11(2 Pt 2):918s-24s.
Endocrinology and hormone therapy in breast cancer: Aromatase inhibitors versus antioestrogens, Anthony Howell1 and Mitch Dowsett2. 1CRUK Department of Medical Oncology, University of Manchester, Christie Hospital, Manchester, UK. 2Academic Department of Biochemistry, Royal Marsden Hospital, London, UK. Breast Cancer Res 2004, 6:269-274 doi:10.1186/bcr945. Published 6 October 2004
Eur. J. Cancer. 2000, May;36(8):976-82
Breast Cancer Res Treat. 1995;36(3):287-97.
J Clin Endocrinol Metab. 2003 Dec;88(12):5951-6.
Nippon Yakurigaku Zasshi. 2003 Oct;122(4):345-54.
Clin Cancer Res. 2003 Jan;9(1 Pt 2):468S-72S.
J Clin Endocrinol Metab 2000 Jul;85(7):2370-7
J Steroid Biochem Mol Biol 1997 Nov-Dec;63(4-6):261-7
Anticancer Res. 2003 Jul-Aug;23(4):3485-91
Clin Cancer Res. 2003 Jan;9(1 Pt 2):468S-72S
The Journal of Clinical Endocrinology & Metabolism Vol. 88, No. 12 5951-5956Copyright © 2003 by The Endocrine Society
J Clin Endocrinol Metab. 2003 Dec;88(12):5951-6.
Pharmacokinetics and Dose Finding of a Potent Aromatase Inhibitor, Aromasin (Exemestane), in Young Males
Suppression of estrogen, via estrogen receptor or aromatase blockade, is being investigated in the treatment of different conditions. Exemestane (Aromasin) is a potent and selective irreversible aromatase inhibitor. To characterize its suppression of estrogen and its pharmacokinetic (PK) properties in males, healthy eugonadal subjects (14–26 yr of age) were recruited. In a cross-over study, 12 were randomly assigned to 25 and 50 mg exemestane daily, orally, for 10 d with a 14-d washout period. Blood was withdrawn before and 24 h after the last dose of each treatment period. A PK study was performed (n = 10) using a 25-mg dose. Exemestane suppressed plasma estradiol comparably with either dose [25 mg, 38% (P 0.002); 50 mg, 32% (P 0.008)], with a reciprocal increase in testosterone concentrations (60% and 56%; P 0.003 for both). Plasma lipids and IGF-I concentrations were unaffected by treatment. The PK properties of the 25-mg dose showed the highest exemestane concentrations 1 h after administration, indicating rapid absorption. The terminal half-life was 8.9 h. Maximal estradiol suppression of 62 ± 14% was observed at 12 h. The drug was well tolerated. In conclusion, exemestane is a potent aromatase inhibitor in men and an alternative to the choice of available inhibitors. Long-term efficacy and safety will need further study.
full study;
http://jcem.endojournals.org/cgi/con...ll/88/12/5951/
