Arimidex~Anastrozole

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TweetArimidex

(Anastrozole)



Arimidex is an aromatase inhibitor used to lower circulating estrogen. It was developed to help fight breast cancer as estrogen plays a role in the growth of cancer cells. 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 than 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 h) with a slow apparent clearance of 1.54 liters/h and a terminal half-life of 46.8 h. Because Arimidex reversibly binds to the aromatase enzyme, once you stop taking it the aromatase enzyme is free to convert androgens such as testosterone into estrogen again. This is sometimes referred to as estrogen rebound. Other aromatase inhibitors like Aromasin are irreversible and therefore are less likely to cause estrogen rebound.


Figure 1. Changes in testosterone and E2 concentrations in normal young men (15–22 yr old) before () and after 10 days of oral anastrozole at 0.5 and 1 mg.

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, inflammatory markers of cardiovascular risk or insulin resistance.

Arimidex 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 on steroids. This is excessive and can potentially cause water retention, gynecomastia (the formation of female breast tissue) 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 preexisting 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.

Arimidex 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. However because Arimidex is a reversible aromatase inhibitor it may not be the best AI for PCT. From the data I have read and my years of experience with this medication, 0.5mg of Arimidex every other day is a good starting point on moderate doses of testosterone. If testosterone doses are raised then 0.5mg to 1mg 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 dose of Arimidex.

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

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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.

OBJECTIVE: 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.

DESIGN: 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 (n = 12), anastrozole 1 mg twice weekly (n = 11), or daily placebo (n = 14) for 12 weeks in a double-blind fashion.

PATIENTS: Men aged 62-74 years with mild hypogonadism defined by testosterone levels less than 350 ng/dl.

MEASUREMENTS: Serum levels of fasting lipids, C-reactive protein (CRP), interleukin-6 (IL-6), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and homeostatic model assessment (HOMA) scores were measured at 4-week intervals.

RESULTS: Treatment with anastrozole did not significantly affect fasting lipids, inflammatory markers (IL-6, CRP), adhesion molecules (ICAM-1, VCAM-1) or insulin sensitivity (HOMA). There was, however, a positive correlation between changes in serum triglycerides and changes in serum oestradiol levels (P = 0.04).

CONCLUSIONS: While short-term administration of anastrozole 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.

PMID: 15670201 [PubMed - indexed for MEDLINE]

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These two studies were summarized and showed Arimidex decreased Estradiol by about 50% while raising Testosterone by about 58% in males.


Estrogen suppression in males: metabolic effects.

Mauras N, O'Brien KO, Klein KO, Hayes V.
Nemours Research Programs at the Nemours Children's Clinic, Jacksonville, Florida 32207, USA. nmauras@nemours.org


Comment in:
J Clin Endocrinol Metab. 2001 Apr;86(4):1836-8.
We have shown that testosterone (T) deficiency per se is associated with marked catabolic effects on protein, calcium metabolism, and body composition in men independent of changes in GH or insulin-like growth factor I production. It is not clear,,however, whether estrogens have a major role in whole body anabolism in males. We investigated the metabolic effects of selective estrogen suppression in the male using a potent aromatase inhibitor, Arimidex (Anastrozole). First, a dose-response study of 12 males (mean age, 16.1 +/- 0.3 yr) was conducted, and blood withdrawn at baseline and after 10 days of oral Arimidex given as two different doses (either 0.5 or 1 mg) in random order with a 14-day washout in between. A sensitive estradiol (E2) assay showed an approximately 50% decrease in E2 concentrations with either of the two doses; hence, a 1-mg dose was selected for other studies. Subsequently, eight males (aged 15-22 yr; four adults and four late pubertal) had isotopic infusions of [(13)C]leucine and (42)Ca/(44)Ca, indirect calorimetry, dual energy x-ray absorptiometry, isokinetic dynamometry, and growth factors measurements performed before and after 10 weeks of daily doses of Arimidex. Contrary to the effects of T withdrawal, there were no significant changes in body composition (body mass index, fat mass, and fat-free mass) after estrogen suppression or in rates of protein synthesis or degradation; carbohydrate, lipid, or protein oxidation; muscle strength; calcium kinetics; or bone growth factors concentrations. However, E2 concentrations decreased 48% (P = 0.006), with no significant change in mean and peak GH concentrations, but with an 18% decrease in plasma insulin-like growth factor I concentrations. There was a 58% increase in serum T (P = 0.0001), sex hormone-binding globulin did not change, whereas LH and FSH concentrations increased (P < 0.02, both). Serum bone markers, osteocalcin and bone alkaline phosphatase concentrations, and rates of bone calcium deposition and resorption did not change. In conclusion, these data suggest that in the male 1) estrogens do not contribute significantly to the changes in body composition and protein synthesis observed with changing androgen levels; 2) estrogen is a main regulator of the gonadal-pituitary feedback for the gonadotropin axis; and 3) this level of aromatase inhibition does not negatively impact either kinetically measured rates of bone calcium turnover or indirect markers of bone calcium turnover, at least in the short term. Further studies will provide valuable information on whether timed aromatase inhibition can be useful in increasing the height potential of pubertal boys with profound growth retardation without the confounding negative effects of gonadal androgen suppression.

PMID: 10902781 [PubMed - indexed for MEDLINE]

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J Clin Endocrinol Metab. 2009 Aug;94(8):2975-8. Epub 2009 May 26.

Pharmacokinetics and pharmacodynamics of anastrozole in pubertal boys with recent-onset gynecomastia.

Mauras N, Bishop K, Merinbaum D, Emeribe U, Agbo F, Lowe E.

Source

Nemours Children's Clinic, 807 Children's Way, Jacksonville, FL 32207, USA. nmauras@nemours.org

Abstract

CONTEXT:
Use of aromatase inhibitors to suppress estrogen production is being actively investigated in a variety of experimental conditions in both females and males. Anastrozole (Arimidex) is a potent and selective reversible inhibitor of the aromatase enzyme in females.
OBJECTIVE:
Our objective was to characterize the pharmacokinetics (PK) and pharmacodynamics (PD) of anastrozole in adolescent males with gynecomastia of less than 1 yr duration. The effect of anastrozole on breast size was also assessed as an exploratory aim.
DESIGN:
We conducted a PK/PD open-label study.
SETTING:
This clinical research center study was undertaken at pediatric academic centers.
PATIENTS:
Forty-two boys with gynecomastia (mean age 13 +/- 1.8 yr; duration of gynecomastia 7.0 +/- 2.5 months; body mass index 28.3 +/- 5.9 kg/m(2)) were recruited. Interventions: Anastrozole, 1 mg, was given daily for 6 months.
MAIN OUTCOMES:
We assessed PK/PD of anastrozole after 14 d daily dosing and changes in breast size (exploratory aim) by manual tape measurements (area) and ultrasound (volume) after 6 months.
RESULTS:
Anastrozole was rapidly absorbed orally (time to reach maximum concentration, 1 h) with a slow apparent clearance of 1.54 liters/h and a terminal half-life of 46.8 h. Testosterone/estradiol ratios increased significantly with concomitant increase in LH/FSH concentrations indicating aromatase blockade. There was a reduction in breast area (approximately 63%) and breast volume (approximately 57%) in the study group as compared with baseline (P = 0.004). The drug was well tolerated.
CONCLUSIONS:
Anastrozole is a potent aromatase inhibitor in adolescent males, with rapid absorption and slow elimination kinetics after oral dosing. Exploratory analysis of changes in breast size showed breast reduction in the cohort; this deserves further study.

PMID:19470631 [PubMed - indexed for MEDLINE]

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