AROMASIN – Exemestane
Type-I Aromatase Inhibitor
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.
Aromasin averages 90% rate of estrogen suppression, which equals a reduction in estradiol levels of about 50%, as well as significantly raising testosterone .(up to 60%)
Aromasin not only increases testosterone and lowers estrogen, but it also increases levels of insulin -like growth Factor (IGF). And Aromasin is not too harsh on lipid panel (cholesterol), unlike some of the other AIs’ like Letrozole (Femara)
Aromasin 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 has a terminal half life of 9 hours in MEN, so taking it once per day will build up blood plasma levels to a very effective level.
Also, there have been some additional researches related to Aromasin in men in pharmacokinetics. The results of the research are the following:
24 hours after one 25mg dose, estrogen levels are reduced by 70-80%;
72 hours later estrogen levels are still 40% below the baseline;
120 hours after initial dose, estrogen levels return to baseline.
Additionally, the University of Florida conducted a study in healthy young men:
Pharmacokinetics and Dose Finding of a Potent Aromatase Inhibitor, Aromasin (Exemestane), in Young Males.
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
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 Aromasin 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 Blood was withdrawn before and 24 h after the last dose of each treatment period.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 using a 25-mg dose. Aromasin suppressed plasma estradiol comparably with either dose [25 mg, 38%; 50 mg, 32%], with a reciprocal increase in testosterone concentrations (60% and 56%; for both).
The following observations were made:
1. Plasma lipids and IGF-I concentrations were unaffected by treatment.
2. The PK properties of the 25-mg dose showed the highest concentrations 1 h after administration, indicating rapid absorption.
3. Maximal estradiol suppression of 62 ± 14% was observed at 12 h.
4. The drug was well tolerated.
5. The terminal half-life was 8.9 hours in the male subjects.
In conclusion, Aromasin (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.
References and Supporting Data:
1. A predictive model for exemestane pharmacokinetics/pharmacodynamics incorporating the effect of food and formulation.Br J Clinical Pharmacology. 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.
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ARIMIDEX - Anastrozole
Type-II Aromatase Inhibitor
Arimidex binds reversibly to the aromatase enzyme through competitive inhibition. This suppresses the conversion of androgens into estrogen. Circulating plasma estrogen can be reduced by nearly 85% in women using Arimidex. A common misconception is that aromatase inhibition is similar in men and women.
However in trials when males were administered 1mg of Arimidex daily, circulating estrogen was only reduced by about 50%. Anastrozole is rapidly absorbed orally (time to reach maximum concentration, 1 hour) with a slow apparent clearance of 1.54 liters/h and a terminal half-life of 46.8 h.
But unlike Aromasin, once you stop taking Arimidex, the aromatase enzyme is free to convert androgens (testosterone) into estrogen again. This is referred to as estrogen rebound.
Estrogen has been measured as much as 7 times higher than normal in men on steroids . This is excessive and can potentially cause water retention, gynecomastia or benign prostatic hyperplasia. Therefore, in order to avoid these side effects, estrogen must be controlled.
Reduction in breast area and breast volume have been observed in young men treated for 6 months with Arimidex (1 mg daily). These subjects had recent pre-existing gynecomastia (less than one year). However boys with longstanding gynecomastia (more than one year) were unresponsive to 6 months of Arimidex treatment, possibly due to development of dense breast fibrosis. Therefore using Arimidex to treat recent gynecomastia is supported by the data.
From all the data available, 0.25-.50mg of Arimidex every other day is a good starting point on moderate doses of testosterone. If testosterone doses are raised, then an increase 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 dose of Arimidex.
Arimidex not only lowers circulating estrogen but it also increases LH and FSH concentrations in addition to increasing testosterone by about 58% in men. In one study elderly men with mild hypogonadism were administered 1mg daily of Arimidex for 12 weeks. This treatment normalized serum testosterone levels in those men without adversely affecting lipids, precursors of cardiovascular risk or insulin resistance. Please see excerpt from ATAC study below.
“Clinical Study - Cholesterol
During the ATAC 5 year trial (Arimidex, Tamoxifen , Alone, or in Combination) more patients receiving ARIMIDEX were reported to have an elevated serum cholesterol compared to patients receiving tamoxifen (9% versus 3.5%, respectively). A post-marketing trial also evaluated any potential effects of ARIMIDEX on lipid profile. In the primary analysis population for lipids (ARIMIDEX alone), there was no clinically significant change in LDL-C from baseline to 12 months and HDL-C from baseline to 12 months.
In secondary population for lipids (ARIMIDEX+risedronate), there also was no clinically significant change in LDL-C and HDL-C from baseline to 12 months. In both populations for lipids, there was no clinical significant difference in total cholesterol (TC) or serum triglycerides (TG) at 12 months compared with baseline.“
The difference in the elevated serums levels during the ATAC trial between patients receiving Arimidex and those receiving Tamoxifen were, (9% versus 3.5%, respectively) Only a 5.5% difference. Again, in this trial, treatment for 12 months with ARIMIDEX alone had a neutral effect on lipid profile. Combination treatment with ARIMIDEX and risedronate also had a neutral effect on lipid profile. Please see link for complete study:
http://dailymed.nlm.nih.gov/dailymed...l1231180697883
*So for average users of AAS who chooses to include Arimidex as their primary aromatase inhibitor, there is no cause for concern. However, monitoring your Cholesterol levels while using AAS, is recommended.
Other Clinical Studies
Effect of aromatase inhibition on lipids and inflammatory markers of cardiovascular disease in elderly men with low testosterone levels.
Dougherty RH, Rohrer JL, Hayden D, Rubin SD, Leder BZ.
Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA.
Although androgen replacement has been shown to have beneficial effects in hypogonadal men, there is concern that androgens may deleteriously affect cardiovascular risk in elderly men.
Anastrozole is an oral aromatase inhibitor that normalizes serum testosterone levels and decreases oestradiol levels modestly in elderly men with mild hypogonadism. Thirty-seven elderly hypogonadal men were randomized to receive either anastrozole 1 mg daily, anastrozole 1 mg twice weekly, or daily placebo for 12 weeks in a double-blind fashion. Men aged 62-74 years with mild hypogonadism defined by testosterone levels less than 350 ng/dl.
Treatment with Arimidex did not significantly affect fasting lipids, inflammatory markers adhesion molecules or insulin sensitivity. There was, however, a positive correlation between changes in serum triglycerides and changes in serum oestradiol levels. And while short-term administration of Arimidex is an effective method of normalizing serum testosterone levels in elderly men with mild hypogonadism, it does not appear to adversely affect lipid profiles, inflammatory markers of cardiovascular risk or insulin resistance.
Note: These studies were summarized and showed Arimidex decreased Estradiol by about 50% while raising Testosterone by about 58% in males.
References
1. Effect of aromatase inhibition on lipids and inflammatory markers of cardiovascular disease in elderly men with low testosterone levels.
2. Estrogen suppression in males: metabolic effects.
3. Pharmacokinetics and pharmacodynamics of anastrozole in pubertal boys with recent-onset gynecomastia.
4. Influence of Neoadjuvant Anastrozole (Arimidex) on Intratumoral Estrogen Levels and Proliferation Markers in Patients with Locally Advanced Breast Cancer.
