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    Super Moderator heavyiron's Avatar
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    Default Exemestane

    Exemestane

    Aromasin, the brand name for exemestane is a steroidal aromatase inactivator used to lower circulating estrogen. It was developed to help fight breast cancer as estrogen plays a role in the growth of cancer cells. Exemestane binds irreversibly to the aromatase enzyme. This suppresses the conversion of androgens into estrogen. Circulating estrogen can be reduced by nearly 85% in women using exemestane. A common misconception is that aromatase inhibition is similar in men than women. However in trials when males were administered 25mg of exemestane daily, maximal estradiol suppression of 62% +/- 14% was observed at 12 hours. The reason for the difference may be related to the much higher testosterone concentrations in young males than in postmenopausal women and the shorter half-life of exemestane in males. The terminal half-life in males (8.9 h) was considerably shorter than the published value of 27 h in females. This may be a basis for more frequent administration in men (or women administering testosterone) that want maximal E2 supression.

    Exemestane acts as a false substrate for the aromatase enzyme, and is processed to an intermediate that binds irreversibly to the active site of the enzyme causing its inactivation, an effect also known as "suicide inhibition." In other words, Exemestane, by being structurally similar to the target of the enzymes, permanently binds to those enzymes, thereby preventing them from ever completing their task of converting androgens into estrogens. When we compare this mode of action against other AI's the benefit becomes clear. Arimidex can unbind from the aromatase enzyme when you stop taking it but exemestane will not. Therefore, there may be less chance of estrogen rebound with exemestane.

    Exemestane can be employed during a steroid cycle when aromatizing compounds such as testosterone are administered in order to control estrogen from getting out of control. During the course of a typical steroid cycle estrogen can rise quite high. Estrogen has been measured as much as 7 times higher than normal in men using steroids. This is excessive and can potentially cause water retention, gynecomastia (the formation of female breast tissue), negatively effect libido or cause benign prostatic hyperplasia. Therefore in order to avoid these side effects estrogen must be controlled.

    Exemestane not only lowers circulating estrogen and sex hormone binding globulin but it also increases free testosterone by a whopping 117%! Total testosterone increases about 60%. Check out the performance of exemestane after just 10 days of treatment in males.


    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).

    Exemestane may be used during a steroid cycle with aromatizing compounds and during PCT to help keep the estrogen to testosterone balance in favor of testosterone. Out of all the compounds to control estrogen, exemestane seems to be the most well balanced. It raises testosterone similar to Arimidex and lowers estradiol about 10% better than arimidex in males and is likely to cause less estrogen rebound than Arimidex. Keep in mind that 50mg of exemestane daily kept estradiol in the normal range for men so if you think using an aromatase inhibitor will crush estrogen too much this science supports the opposite. Additionally, plasma lipids and IGF-I concentrations in men were unaffected by exemestane treatment. From the data I have read and my years of experience with this compound, 25mg of exemestane every other day is a good starting point on moderate doses of testosterone. If testosterone doses are raised then 25mg daily may be needed to control estrogen. Since either high and low estrogen can cause side effects such as low libido only labs can determine the appropriate amount of exemestane.

    References

    Pharmacokinetics and Dose Finding of a Potent Aromatase Inhibitor, Aromasin (Exemestane), in Young Males

    Pharmacology and pharmacokinetics of the newer generation aromatase inhibitors

    ~John Connor

    Information is for educational purposes ONLY. Consult a medical doctor before using any medication. heavyiron does not advocate readers engage in any illegal activity. Research chemicals are not meant for human consumption.
    Last edited by heavyiron; August 6th, 2014 at 12:52 PM.
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    Pharmacokinetics and Dose Finding of a Potent Aromatase Inhibitor, Aromasin (Exemestane), in Young Males

    Nelly Mauras, John Lima, Deval Patel, Annie Rini, Enrico di Salle, Ambrose Kwok and Barbara Lippe
    Nemours Children’s Clinic and Research Programs (N.M., J.L., A.R.), Jacksonville, Florida 32207; and University of Florida Health Sciences Center (D.P.) and Amersham Pharmacia Biotech (E.d.S., A.K., B.L.), Peapack, New Jersey 07977

    Address all correspondence and requests for reprints to: Nelly Mauras, M.D., Nemours Children’s Clinic, 807 Children’s Way, Jacksonville, Florida 32207. E-mail: nmauras@nemours.org.

    Abstract

    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.
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    Super Moderator heavyiron's Avatar
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    Pharmacology and pharmacokinetics of the newer generation aromatase inhibitors.

    Buzdar AU.
    Department of Breast Medical Oncology, The University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA. abuzdar@mdanderson.org

    The newer generation aromatase inhibitors (AIs) as a class show efficacy and tolerability benefits over previously established treatments in postmenopausal women with advanced breast cancer. At clinically administered doses, the plasma half-lives of anastrozole (1 mg once daily), letrozole (2.5 mg once daily), and exemestane (25 mg once daily) are 41-48 h, 2-4 days, and 27 h, respectively. Time to steady-state plasma levels is 7 days for both anastrozole and exemestane and 60 days for letrozole. Androgenic side effects have only been reported with exemestane. Anastrozole treatment has no impact on plasma lipid levels, whereas both letrozole and exemestane have an unfavorable effect. From indirect comparisons, anastrozole shows the highest degree of selectivity compared with letrozole and exemestane, in terms of a lack of effect on adrenosteroidogenesis. To date, there are no data suggesting any major differences in clinical efficacy between the newer generation AIs anastrozole and letrozole. Based on the observed pharmacological profiles, however, it cannot be assumed that the AIs will display the same tolerability and safety profiles when given for extended periods of time in the adjuvant setting. The effects of anastrozole, letrozole, and exemestane are being investigated in the adjuvant setting, and these data will elucidate the possible long-term consequences of the pharmacological effects reported after short-term exposure.

    PMID: 12538502 [PubMed - indexed for MEDLINE]
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