Please Scroll Down to See Forums Below 
Lift Chief
New member
1)Femara
2)Aromasin
3)Arimidex. l-dex
Not including nolva, proviron, etc... would you agree with this?
2)Aromasin
3)Arimidex. l-dex
Not including nolva, proviron, etc... would you agree with this?
Ranking anti-es based on strength???
- Thread starter Lift Chief
- Start date
DeepZenPill
New member
I think that's what the general consensus is.
Some people like aromasin better than femara, but technically femara is supposed to be the strongest.
Some people like aromasin better than femara, but technically femara is supposed to be the strongest.
Seth Roberts
New member
aromatase inhibitors
These are all very strong inhibitors of the aromatase enzyme. Percent inhibition of aromatisation in clinical trials for given doses:
Letrozole (Femara): 0.5 mg/day 98.4%
2.5 mg/day 98.9%
Anastrazole (Arimidex): 1.0 mg/day 96.7%
10.0 mg/day 98.0%
Exemestane (Aromasin): 25.0 mg/day 97.9%
So, at the above doses, they all give greater than 90% inhibition.
Anastrazole and exemestane take 7 days to reach steady state plasms levels while letrozole takes 60 days. This is due to the half lives of the drugs which are 41 hours for anastrazole, 27 hours for exemestane and 2-4 days for letrozole. It takes anastrazole 3-4 days to reach maximal suppression of estradiol levels, letrozole 2-3 days and exemestane 7 days.
Anastrazole and letrozole are reversible inhibitors of aromatase while exemestane is irreversible.
Exemestane has androgenic properties.
Anastrazole and letrozole serum concentrations are reduced when taken in combination with tamoxifen -- no evidence with exemestane.
Anastrazole has no effect on lipid levels or cortisol levels, letrozole increases total cholesterol and LDL and effects cortisol and aldosterone levels (may lead to increased levels through biofeedback over time), Exemestane decreases total cholesterol, HDL and triglycerides and has no effect on cortisol or aldosterone levels.
Exemestane has been shown to decrease SHBG levels (whereas tamoxifen increases SHBG levels) and to a lesser extent, so has anastrazole but letrozole increases SHBG.
Given these facts, I would choose exemestane first, anastrazole second and letrozole last.
Seth
These are all very strong inhibitors of the aromatase enzyme. Percent inhibition of aromatisation in clinical trials for given doses:
Letrozole (Femara): 0.5 mg/day 98.4%
2.5 mg/day 98.9%
Anastrazole (Arimidex): 1.0 mg/day 96.7%
10.0 mg/day 98.0%
Exemestane (Aromasin): 25.0 mg/day 97.9%
So, at the above doses, they all give greater than 90% inhibition.
Anastrazole and exemestane take 7 days to reach steady state plasms levels while letrozole takes 60 days. This is due to the half lives of the drugs which are 41 hours for anastrazole, 27 hours for exemestane and 2-4 days for letrozole. It takes anastrazole 3-4 days to reach maximal suppression of estradiol levels, letrozole 2-3 days and exemestane 7 days.
Anastrazole and letrozole are reversible inhibitors of aromatase while exemestane is irreversible.
Exemestane has androgenic properties.
Anastrazole and letrozole serum concentrations are reduced when taken in combination with tamoxifen -- no evidence with exemestane.
Anastrazole has no effect on lipid levels or cortisol levels, letrozole increases total cholesterol and LDL and effects cortisol and aldosterone levels (may lead to increased levels through biofeedback over time), Exemestane decreases total cholesterol, HDL and triglycerides and has no effect on cortisol or aldosterone levels.
Exemestane has been shown to decrease SHBG levels (whereas tamoxifen increases SHBG levels) and to a lesser extent, so has anastrazole but letrozole increases SHBG.
Given these facts, I would choose exemestane first, anastrazole second and letrozole last.
Seth
DeepZenPill
New member
Great post Seth.
And regards to serge's comment that aromasin is stronger than femara, people thought this at first because of how aromasin works. It greatly reduces the amount of available aromatase enzyme, but femara still seems to edge it out.
Aromasin can be considered better because of its effects on cholesterol and SHBG levels. On the other hand Aromasin decreases IGF-1 while Femara increases it. Each drug has its pro's and con's.
Here's a good post with some more details:
http://boards.elitefitness.com/forum/showthread.php?s=&threadid=168886
And regards to serge's comment that aromasin is stronger than femara, people thought this at first because of how aromasin works. It greatly reduces the amount of available aromatase enzyme, but femara still seems to edge it out.
Aromasin can be considered better because of its effects on cholesterol and SHBG levels. On the other hand Aromasin decreases IGF-1 while Femara increases it. Each drug has its pro's and con's.
Here's a good post with some more details:
http://boards.elitefitness.com/forum/showthread.php?s=&threadid=168886
Seth,
Why are you quoting statistics on women? None of that applies to men on a cycle. Anti Aromatese are nowhere near as effective in men as they are in women. And men on cycle is an even greater disparity.
I agree with the order of effectiveness lift cheif posted.
Why are you quoting statistics on women? None of that applies to men on a cycle. Anti Aromatese are nowhere near as effective in men as they are in women. And men on cycle is an even greater disparity.
I agree with the order of effectiveness lift cheif posted.
Seth Roberts
New member
Studies
Quoting studies done in women because not too many clinical trials done in men. The aromatase enzyme is the same in men and women. The quantities of aromates are probably higher in women. Therefore, these drugs should be more effective in men. There are very few studies out there that will tell you exactly what you want to know -- you have to use your knowledge and experience to interpret them and apply the information as best as possible to the specific question you are asking -- then test your new hypothesis. I don't know how you can say hat none of that applies to men on a cycle. Men have aromatase, these drugs bind and inhibit aromatase. That's like saying that a specific study wasn't done in me so, therefore, it can't apply to me -- that is not how it works.
Seth
Quoting studies done in women because not too many clinical trials done in men. The aromatase enzyme is the same in men and women. The quantities of aromates are probably higher in women. Therefore, these drugs should be more effective in men. There are very few studies out there that will tell you exactly what you want to know -- you have to use your knowledge and experience to interpret them and apply the information as best as possible to the specific question you are asking -- then test your new hypothesis. I don't know how you can say hat none of that applies to men on a cycle. Men have aromatase, these drugs bind and inhibit aromatase. That's like saying that a specific study wasn't done in me so, therefore, it can't apply to me -- that is not how it works.
Seth
Last edited:
Seth Roberts
New member
side effects etc...
The side effects of long term use are not really kown. Of more importance are the EFFECTS of these drugs -- namely HDL lowering, cholesterol elevations and bone resorption where apllicable. These effects can have long term detrimental effects on one's health.
For Ulter
Here are some studies done with aromatase inhibitors in males:
1. J Clin Endocrinol Metab. 2001 Oct;86(10):4887-94. Related Articles, Links
Inhibition of P450 aromatase enhances gonadotropin secretion in early and midpubertal boys: evidence for a pituitary site of action of endogenous E.
Wickman S, Dunkel L.
University of Helsinki, Hospital for Children and Adolescents, FIN-00029 Helsinki, Finland. [email protected]
In early pubertal boys, E concentrations are very low. We studied the role and site of action of endogenous E in the regulation of gonadotropin secretion in early and midpubertal boys by inhibiting the action of E with a potent and specific P450 aromatase inhibitor, letrozole. A total of 35 boys who were referred to us because of suspicion of delayed puberty were included in the study. The boys were in either early or midpuberty, and they composed 3 groups: 10 boys did not receive any treatment, 12 boys received T alone, and 13 boys received T and letrozole. In the untreated group during the 5-month follow-up, no changes were observed in 17beta-E2, T, basal gonadotropin, or inhibin B concentrations or in the GnRH-induced gonadotropin responses. In the T-treated group during the 5-month treatment, the T concentration increased by 55% (P < 0.05), and the 17beta-E2 concentration increased by 130% (P < 0.02). Concurrently, basal gonadotropin concentrations were suppressed, but the GnRH-induced gonadotropin responses and the inhibin B concentration remained unchanged. In the T- plus letrozole-treated group during the 5-month treatment, an increase in T concentration of 606% was observed (P < 0.001), but the 17beta-E2 concentration remained unchanged. The changes in the 17beta-E2 concentration within 5 months in the untreated and the T- plus letrozole-treated groups were different (P < 0.02), indicating significant inhibition of endogenous E synthesis during letrozole treatment. During the T plus letrozole treatment, basal gonadotropin concentration, the GnRH-induced LH response, and inhibin B concentration increased, and the GnRH-induced FSH response did not change significantly. Serum nocturnal gonadotropin pulses were determined in 5 boys treated with T and in 5 boys treated with T plus letrozole. In the T- plus letrozole-treated group, the nocturnal LH pulse amplitude increased, and the LH pulse frequency and interpulse interval remained unchanged. In conclusion, in early and midpubertal boys, suppression of the action of E by the P450 aromatase inhibitor increased LH concentration, LH pulse amplitude, and the GnRH-induced LH response, which indicates that in boys during early and midpuberty, endogenous E regulates LH secretion at the site of the pituitary.
PMID: 11600558 [PubMed - indexed for MEDLINE]
--------------------------------------------------------------------------------
2: J Clin Endocrinol Metab. 2001 Jun;86(6):2869-74. Related Articles, Links
The effect of aromatase inhibition on sex steroids, gonadotropins, and markers of bone turnover in older men.
Taxel P, Kennedy DG, Fall PM, Willard AK, Clive JM, Raisz LG.
Division of Endocrinology and Metabolism, Center on Aging, University of Connecticut Health Center, Farmington, Connecticut 06030-1317, USA. [email protected]
There is evidence that estrogen decreases bone turnover in men as well as women. We therefore hypothesized that older men would show increased bone resorption in response to inhibition of the aromatase enzyme, which converts androgens to estrogen. Fifteen eugonadal men over 65 yr were treated for 9 weeks with 2.0 mg/day of anastrozole, an aromatase inhibitor. After 9 weeks of treatment, there were significant decreases in estradiol, estrone, and sex hormone-binding globulin levels by 29%, 73%, and 16%, respectively, and total testosterone increased significantly by 56%. Despite the limited decrease of estrogen and the increase in testosterone, C-telopeptide of type 1 collagen showed a progressive significant increase of 11%, 24%, and 33% (P for trend = 0.033) above baseline at 3, 6, and 9 weeks, respectively. N-telopeptide of type 1 collagen values were highly correlated with C-telopeptide of type 1 collagen, but the change in N-telopeptide of type 1 collagen was not statistically significant. Bone-specific alkaline phosphatase and N-terminal type I procollagen peptides showed significant decreases of 8% and 11% of baseline at 9 weeks. Osteocalcin decreased significantly by 30% at 18 weeks. We conclude that aromatase inhibition can reduce estrogen levels in older men, but this effect is limited, perhaps because of feedback stimulation of testosterone production, and that endogenous estrogen derived from aromatization of testosterone plays a role in bone metabolism of older men by limiting the rate of bone resorption.
PMID: 11397902 [PubMed - indexed for MEDLINE]
--------------------------------------------------------------------------------
3: J Clin Endocrinol Metab. 2000 Sep;85(9):3027-35. Related Articles, Links
Comment in:
J Clin Endocrinol Metab. 2000 Sep;85(9):3024-6.
Aromatase inhibition in the human male reveals a hypothalamic site of estrogen feedback.
Hayes FJ, Seminara SB, Decruz S, Boepple PA, Crowley WF Jr.
Department of Medicine and National Center for Infertility Research, Massachusetts General Hospital, Boston 02114, USA. [email protected]
The preponderance of evidence states that, in adult men, estradiol (E2) inhibits LH secretion by decreasing pulse amplitude and responsiveness to GnRH consistent with a pituitary site of action. However, this conclusion is based on studies that employed pharmacologic doses of sex steroids, used nonselective aromatase inhibitors, and/or were performed in normal (NL) men, a model in which endogenous counterregulatory adaptations to physiologic perturbations confound interpretation of the results. In addition, studies in which estrogen antagonists were administered to NL men demonstrated an increase in LH pulse frequency, suggesting a potential additional hypothalamic site of E2 feedback. To reconcile these conflicting data, we used a selective aromatase inhibitor, anastrozole, to examine the impact of E2 suppression on the hypothalamic-pituitary axis in the male. Parallel studies of NL men and men with idiopathic hypogonadotropic hypogonadism (IHH), whose pituitary-gonadal axis had been normalized with long-term GnRH therapy, were performed to permit precise localization of the site of E2 feedback. In this so-called tandem model, a hypothalamic site of action of sex steroids can thus be inferred whenever there is a difference in the gonadotropin responses of NL and IHH men to alterations in their sex steroid milieu. A selective GnRH antagonist was also used to provide a semiquantitative estimate of endogenous GnRH secretion before and after E2 suppression. Fourteen NL men and seven IHH men were studied. In Exp 1, nine NL and seven IHH men received anastrozole (10 mg/day po x 7 days). Blood samples were drawn daily between 0800 and 1000 h in the NL men and immediately before a GnRH bolus dose in the IHH men. In Exp 2, blood was drawn (every 10 min x 12 h) from nine NL men at baseline and on day 7 of anastrozole. In a subset of five NL men, 5 microg/kg of the Nal-Glu GnRH antagonist was administered on completion of frequent blood sampling, then sampling continued every 20 min for a further 8 h. Anastrozole suppressed E2 equivalently in the NL (136 +/- 10 to 52 +/-2 pmol/L, P < 0.005) and IHH men (118 +/- 23 to 60 +/- 5 pmol/L, P < 0.005). Testosterone levels rose significantly (P < 0.005), with a mean increase of 53 +/- 6% in NL vs. 56 +/- 7% in IHH men. Despite these similar changes in sex steroids, the increase in gonadotropins was greater in NL than in IHH men (100 +/- 9 vs. 58 +/- 6% for LH, P = 0.07; and 85 +/- 6 vs. 41 +/- 4% for FSH, P < 0.002). Frequent sampling studies in the NL men demonstrated that this rise in mean LH levels, after aromatase blockade, reflected an increase in both LH pulse frequency (10.2 +/- 0.9 to 14.0 +/- 1.0 pulses/24 h, P < 0.05) and pulse amplitude (5.7 +/- 0.7 to 8.4 +/- 0.7 IU/L, P < 0.001). Percent LH inhibition after acute GnRH receptor blockade was similar at baseline and after E2 suppression (69.2 +/- 2.4 vs. 70 +/- 1.9%), suggesting that there was no change in the quantity of endogenous GnRH secreted. From these data, we conclude that in the human male, estrogen has dual sites of negative feedback, acting at the hypothalamus to decrease GnRH pulse frequency and at the pituitary to decrease responsiveness to GnRH.
Publication Types:
Clinical Trial
PMID: 10999781 [PubMed - indexed for MEDLINE]
--------------------------------------------------------------------------------
4: J Clin Endocrinol Metab. 2000 Jul;85(7):2370-7. Related Articles, Links
Comment in:
J Clin Endocrinol Metab. 2001 Apr;86(4):1836-8.
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. [email protected]
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.
Publication Types:
Clinical Trial
PMID: 10902781 [PubMed - indexed for MEDLINE]
--------------------------------------------------------------------------------
5: Endocr Relat Cancer. 1999 Jun;6(2):181-5. Related Articles, Links
Drug and hormone interactions of aromatase inhibitors.
Dowsett M.
Academic Department of Biochemistry, The Royal Marsden NHS Trust, London, UK.
The clinical development of aromatase inhibitors has been largely confined to postmenopausal breast cancer patients and strongly guided by pharmacological data. Comparative oestrogen suppression has been helpful in circumstances in which at least one of the comparitors has caused substantially non-maximal aromatase inhibition. However, the triazole inhibitors, letrozole and anastrozole, and the steroidal inhibitor, exemestane, all cause >95% inhibition. Comparisons between these drugs therefore require more sensitive approaches such as the direct measurement of enzyme activity by isotopic means. None of these three agents has significant effects on other endocrine pathways at its clinically applied doses. Pharmacokinetic analyses of the combination of tamoxifen and letrozole have revealed that these drugs interact, resulting in letrozole concentrations approximately 35-40% lower than when letrozole is used alone.
Publication Types:
Review
Review, Tutorial
PMID: 10731107 [PubMed - indexed for MEDLINE]
--------------------------------------------------------------------------------
6: Eur J Endocrinol. 2000 Feb;142(2):164-9. Related Articles, Links
Acute inhibition of oestrogen biosynthesis does not affect serum leptin levels in young men.
Luukkaa V, Rouru J, Ahokoski O, Scheinin H, Irjala K, Huupponen R.
Department of Pharmacology, University of Turku, and Clinical Pharmacology Unit, Turku University Central Hospital, FIN-20520 Turku, Finland. [email protected]
OBJECTIVE: Leptin plays an important role in the regulation of reproduction. To explore the contribution of oestradiol to serum leptin levels in men, we measured the concentrations of serum leptin and insulin after inhibition of oestrogen biosynthesis by selective blockade of the aromatase enzyme. DESIGN: The study had a double-blind parallel group design. METHODS: The aromatase inhibitor, MPV 2213ad, was given to eight healthy male volunteers as a single dose of 100mg. Eight men received placebo. Serum leptin and insulin were determined from blood samples collected at 0800h, 1600h and 2000h both on the actual test day (day 0) and on the previous day (day -1), and from single blood samples taken in the morning of days 1, 2, 4 and 7. Changes in serum leptin were correlated with those seen in serum oestradiol, testosterone, LH, FSH, cortisol and aldosterone, which were determined earlier. RESULTS: After the aromatase inhibitor administration, mean serum oestradiol concentration was reduced by 74% from the baseline compared with a 19% reduction in the placebo group (P for difference <0.001), and returned to pre-treatment levels within four days. Despite marked changes in serum oestradiol and sustained elevations in serum testosterone, LH and FSH concentrations, serum leptin concentrations were similar in the group receiving the aromatase inhibitor and in the placebo group. We found a weak correlation between serum oestradiol and leptin, which could not be reproduced when the percentage changes in these variables were analysed. CONCLUSION: Marked short-term reduction in serum oestradiol concentration has no effect on serum leptin levels in young men.
Publication Types:
Clinical Trial
Randomized Controlled Trial
PMID: 10664525 [PubMed - indexed for MEDLINE]
--------------------------------------------------------------------------------
7: Eur J Clin Pharmacol. 1999 Mar;55(1):27-34. Related Articles, Links
A double-blind study of MPV-2213ad, a novel aromatase inhibitor, in healthy male subjects.
Ahokoski O, Irjala K, Huhtala S, Salminen E, Scheinin H, Huupponen R.
Department of Pharmacology and Clinical Pharmacology, University of Turku, Turku University Central Hospital, Finland. [email protected]
OBJECTIVE: Novel aromatase inhibitors are developed with requirements of high potency and selectivity for the aromatase enzyme. The hormonal effects of a new, non-steroidal competitive inhibitor of the aromatase enzyme, MPV-2213ad, were investigated in this study. METHODS: The study was conducted as a double-blind, placebo controlled phase I study, where 32 healthy male volunteers were randomized to receive a single oral dose of either 0.3, 3 or 100 mg of MPV-2213ad or placebo. Serum concentrations of estradiol (E2), testosterone, follicle stimulating hormone (FSH), luteinizing hormone (LH), cortisol and aldosterone were determined from samples taken 0, 4, 8 h and 12 h during the day of drug administration and 1, 2, 4 and 7 days after drug intake. The individual diurnal variation of circulating hormone concentrations was determined in all participants at 0, 4, 8 h and 12 h on the day before drug intake. Specimens for hematological and biochemical analyses were also collected. RESULTS: A dose-dependent and statistically significant (P < 0.001) decrease in serum E2 concentrations was induced by MPV-2213ad. Lowest mean values were observed 8-12 h after drug administration and at 24 h the reductions were 10%, 34% and 69% from baseline in the 0.3-mg, 3-mg and 100-mg groups, compared with an 18% increase in the placebo group. Serum E2 concentrations returned to baseline within 4 days in all study subjects. A significant increase was observed in the serum concentrations of testosterone (P = 0.016), LH (P = 0.002) and FSH (P < 0.001) after administration of MPV-2213ad. Serum concentrations of cortisol and aldosterone were unaffected by MPV-2213ad. The drug was well tolerated. CONCLUSION: Single oral doses of MPV-2213ad, given to healthy male subjects, induced hormonal effects typical for a specific and selective inhibitor of the aromatase enzyme. Importantly, this study design with the determination of the diurnal rhythm in the levels of the corresponding hormones gives additional validity on the results.
Publication Types:
Clinical Trial
Clinical Trial, Phase I
Randomized Controlled Trial
PMID: 10206081 [PubMed - indexed for MEDLINE]
--------------------------------------------------------------------------------
8: Br J Clin Pharmacol. 1998 Feb;45(2):141-6. Related Articles, Links
Hormonal effects of MPV-2213ad, a new selective aromatase inhibitor, in healthy male subjects. A phase I study.
Ahokoski O, Irjala K, Huupponen R, Halonen K, Salminen E, Scheinin H.
Department of Pharmacology and Clinical Pharmacology, University of Turku, Turku University Central Hospital, Finland.
AIMS: A novel non-steroidal competitive inhibitor of the aromatase enzyme, MPV-2213ad, was entered into an open dose-escalation study. The objective of this study was to investigate the tolerability and efficiency of this new compound with assessment of the hormonal effects after study drug administration. METHODS: MPV-2213ad was given to 39 healthy male volunteers. Single increasing oral doses of 0.003, 0.03, 0.3, 3, 9, 30 and 100 mg were given to three subjects at each dose level, after which ten subjects received the 300 mg dose and eight subjects the highest 600 mg dose of MPV-2213ad. RESULTS: Serum oestradiol levels were suppressed by 58-65% when MPV-2213ad was given at doses between 0.3 and 30 mg. A reduction in serum oestradiol levels by 83% from baseline was achieved with the 300 mg dose. No additional decrease was seen with the highest dose. The suppression lasted longer with higher doses of MPV-2213ad. After the 300 and 600 mg doses serum oestradiol returned to baseline within 4 days. Marked increases in serum concentrations of testosterone, androstenedione, 17-OH-progesterone, LH and FSH were also observed at doses between 100 and 600 mg of MPV-2213ad. The drug was well-tolerated and the adverse events were mild or moderate including hot flushes, mild vertigo, nausea, acne and gastrointestinal discomfort. CONCLUSIONS: MPV-2213ad has a potent, dose-dependent inhibitory effect on serum oestradiol. It was selective for the aromatase enzyme with no signs of adreno-cortical suppression or haematological or biochemical toxicity.
Publication Types:
Clinical Trial
Clinical Trial, Phase I
PMID: 9491826 [PubMed - indexed for MEDLINE]
--------------------------------------------------------------------------------
9: Biopharm Drug Dispos. 1997 Aug;18(6):489-97. Related Articles, Links
Comparative bioavailability of letrozole under fed and fasting conditions in 12 healthy subjects after a 2.5 mg single oral administration.
Sioufi A, Sandrenan N, Godbillon J, Trunet P, Czendlik C, Howald H, Pfister C, Ezzet F.
Laboratoires Ciba-Geigy, Bioanalytics and Pharmacokinetics, Medical Department, Rueil-Malmaison, France.
Letrozole is a new non-steroidal inhibitor of the aromatase enzyme system. It is currently under development for the treatment of postmenopausal women with advanced breast cancer. To investigate the influence of food on the bioavailability of letrozole, 12 healthy male volunteers were treated under fed and fasted conditions with single oral doses of 2.5 mg letrozole in film-coated tablets. Plasma concentration profiles were determined. No significant difference in the extent of absorption (AUC or AUC0-8 h) was observed between the two treatments but the rate of letrozole absorption decreased slightly under fed conditions. However, in view of the half-life of about 2 d this small change in the absorption rate is not considered to be of clinical relevance for treatment with repeated administrations.
Publication Types:
Clinical Trial
Controlled Clinical Trial
PMID: 9267682 [PubMed - indexed for MEDLINE]
--------------------------------------------------------------------------------
10: J Steroid Biochem Mol Biol. 1996 Jul;58(4):439-45. Related Articles, Links
The preclinical pharmacology of "Arimidex" (anastrozole; ZD1033)--a potent, selective aromatase inhibitor.
Dukes M, Edwards PN, Large M, Smith IK, Boyle T.
Zeneca Pharmaceuticals, Alderly Park, Macclesfield, U.K.
Anastrozole is a comparatively simple, achiral benzyltriazole derivative, 2,2'-[5-(1H-1,2,4-triazol-1-ylmethyl)-1,3-phenylene]bis(2-++ +methylpropiononitrile), that inhibits human placental aromatase with an IC50 of 15 nM and elicits maximal activity in vivo in rats (inhibition of ovulation and androstenedione-induced uterine hypertrophy) and monkeys (lowering of plasma oestradiol) at 0.1 mg/kg p.o. At 30 times this dose, anastrozole does not elevate plasma 11-deoxycorticosterone in monkeys, and at 100 times this dose, does not affect plasma aldosterone levels or Na+/K+ excretion in rats, plasma K+ concentrations in dogs, or cause adrenal hypertrophy in rats or dogs. It therefore has no discernible effect on adrenocorticoid hormone synthesis in vivo at very large multiples of its maximally effective aromatase-inhibiting dose. At similar large multiples in rats it displays no oestrogenic, anti-oestrogenic, androgenic, anti-androgenic, progestogenic, glucocorticoid, antiglucocorticoid or mineralocorticoid activity. Anastrozole is thus a potent and highly selective aromatase inhibitor, with no intrinsic hormonal activities--a pharmacological profile particularly suitable for the treatment of breast cancer.
PMID: 8903429 [PubMed - indexed for MEDLINE]
--------------------------------------------------------------------------------
11: J Clin Endocrinol Metab. 1993 Aug;77(2):319-23. Related Articles, Links
Comment in:
J Clin Endocrinol Metab. 1993 Aug;77(2):316-8.
Open dose-finding study of a new potent and selective nonsteroidal aromatase inhibitor, CGS 20 267, in healthy male subjects.
Trunet PF, Mueller P, Bhatnagar AS, Dickes I, Monnet G, White G.
Research and Development Department, CIBA-GEIGY Limited, Basel, Switzerland.
The aim of this open, dose-finding study was to evaluate the effects of single dose CGS 20 267, a new oral nonsteroidal aromatase inhibitor, on the inhibition of estrogen production and also on the production of adrenal and testicular steroids in healthy male subjects. Nine dose levels ranging from 0.02-30 mg and placebo were tested, each dose being given to 3 subjects only. A total of 18 subjects were included; 12 of them received 2 single administration, the remaining 6 were exposed only once to one of the 2 highest dose levels. A reduction in serum estrogen levels when compared to baseline was already observed after 2 h, reaching maximum suppression between 10 and 48 h after administration. After 24 h, a suppression of estrone levels by 60-85% from baseline was achieved with all tested doses. A reduction in estradiol levels by about 30% from baseline was observed at the lowest dose (0.02 mg). This reduction was further enhanced dose dependently to a maximum of about 90% from baseline at 24 h after administration of the highest dose (30 mg). With the higher doses (10 and 30 mg), estrogen suppression was maintained up to 3 days. A dose-dependent increase of testosterone, LH, and FSH was observed and was most pronounced in the 10- and 30-mg dose groups, which can be considered as a consequence of the long-lasting aromatase inhibition achieved with these high doses. No effect on serum cortisol and aldosterone levels was observed up to the highest dose. No clinically relevant changes were observed in blood chemistry and hematology tests. The systemic and subjective tolerability of CGS 20 267 was good at all doses. This study has shown that CGS 20 267 is a well tolerated, potent, selective, and long-acting inhibitor of the aromatase enzyme after single administration.
Publication Types:
Clinical Trial
Controlled Clinical Trial
PMID: 8345034 [PubMed - indexed for MEDLINE]
The side effects of long term use are not really kown. Of more importance are the EFFECTS of these drugs -- namely HDL lowering, cholesterol elevations and bone resorption where apllicable. These effects can have long term detrimental effects on one's health.
For Ulter
Here are some studies done with aromatase inhibitors in males:
1. J Clin Endocrinol Metab. 2001 Oct;86(10):4887-94. Related Articles, Links
Inhibition of P450 aromatase enhances gonadotropin secretion in early and midpubertal boys: evidence for a pituitary site of action of endogenous E.
Wickman S, Dunkel L.
University of Helsinki, Hospital for Children and Adolescents, FIN-00029 Helsinki, Finland. [email protected]
In early pubertal boys, E concentrations are very low. We studied the role and site of action of endogenous E in the regulation of gonadotropin secretion in early and midpubertal boys by inhibiting the action of E with a potent and specific P450 aromatase inhibitor, letrozole. A total of 35 boys who were referred to us because of suspicion of delayed puberty were included in the study. The boys were in either early or midpuberty, and they composed 3 groups: 10 boys did not receive any treatment, 12 boys received T alone, and 13 boys received T and letrozole. In the untreated group during the 5-month follow-up, no changes were observed in 17beta-E2, T, basal gonadotropin, or inhibin B concentrations or in the GnRH-induced gonadotropin responses. In the T-treated group during the 5-month treatment, the T concentration increased by 55% (P < 0.05), and the 17beta-E2 concentration increased by 130% (P < 0.02). Concurrently, basal gonadotropin concentrations were suppressed, but the GnRH-induced gonadotropin responses and the inhibin B concentration remained unchanged. In the T- plus letrozole-treated group during the 5-month treatment, an increase in T concentration of 606% was observed (P < 0.001), but the 17beta-E2 concentration remained unchanged. The changes in the 17beta-E2 concentration within 5 months in the untreated and the T- plus letrozole-treated groups were different (P < 0.02), indicating significant inhibition of endogenous E synthesis during letrozole treatment. During the T plus letrozole treatment, basal gonadotropin concentration, the GnRH-induced LH response, and inhibin B concentration increased, and the GnRH-induced FSH response did not change significantly. Serum nocturnal gonadotropin pulses were determined in 5 boys treated with T and in 5 boys treated with T plus letrozole. In the T- plus letrozole-treated group, the nocturnal LH pulse amplitude increased, and the LH pulse frequency and interpulse interval remained unchanged. In conclusion, in early and midpubertal boys, suppression of the action of E by the P450 aromatase inhibitor increased LH concentration, LH pulse amplitude, and the GnRH-induced LH response, which indicates that in boys during early and midpuberty, endogenous E regulates LH secretion at the site of the pituitary.
PMID: 11600558 [PubMed - indexed for MEDLINE]
--------------------------------------------------------------------------------
2: J Clin Endocrinol Metab. 2001 Jun;86(6):2869-74. Related Articles, Links
The effect of aromatase inhibition on sex steroids, gonadotropins, and markers of bone turnover in older men.
Taxel P, Kennedy DG, Fall PM, Willard AK, Clive JM, Raisz LG.
Division of Endocrinology and Metabolism, Center on Aging, University of Connecticut Health Center, Farmington, Connecticut 06030-1317, USA. [email protected]
There is evidence that estrogen decreases bone turnover in men as well as women. We therefore hypothesized that older men would show increased bone resorption in response to inhibition of the aromatase enzyme, which converts androgens to estrogen. Fifteen eugonadal men over 65 yr were treated for 9 weeks with 2.0 mg/day of anastrozole, an aromatase inhibitor. After 9 weeks of treatment, there were significant decreases in estradiol, estrone, and sex hormone-binding globulin levels by 29%, 73%, and 16%, respectively, and total testosterone increased significantly by 56%. Despite the limited decrease of estrogen and the increase in testosterone, C-telopeptide of type 1 collagen showed a progressive significant increase of 11%, 24%, and 33% (P for trend = 0.033) above baseline at 3, 6, and 9 weeks, respectively. N-telopeptide of type 1 collagen values were highly correlated with C-telopeptide of type 1 collagen, but the change in N-telopeptide of type 1 collagen was not statistically significant. Bone-specific alkaline phosphatase and N-terminal type I procollagen peptides showed significant decreases of 8% and 11% of baseline at 9 weeks. Osteocalcin decreased significantly by 30% at 18 weeks. We conclude that aromatase inhibition can reduce estrogen levels in older men, but this effect is limited, perhaps because of feedback stimulation of testosterone production, and that endogenous estrogen derived from aromatization of testosterone plays a role in bone metabolism of older men by limiting the rate of bone resorption.
PMID: 11397902 [PubMed - indexed for MEDLINE]
--------------------------------------------------------------------------------
3: J Clin Endocrinol Metab. 2000 Sep;85(9):3027-35. Related Articles, Links
Comment in:
J Clin Endocrinol Metab. 2000 Sep;85(9):3024-6.
Aromatase inhibition in the human male reveals a hypothalamic site of estrogen feedback.
Hayes FJ, Seminara SB, Decruz S, Boepple PA, Crowley WF Jr.
Department of Medicine and National Center for Infertility Research, Massachusetts General Hospital, Boston 02114, USA. [email protected]
The preponderance of evidence states that, in adult men, estradiol (E2) inhibits LH secretion by decreasing pulse amplitude and responsiveness to GnRH consistent with a pituitary site of action. However, this conclusion is based on studies that employed pharmacologic doses of sex steroids, used nonselective aromatase inhibitors, and/or were performed in normal (NL) men, a model in which endogenous counterregulatory adaptations to physiologic perturbations confound interpretation of the results. In addition, studies in which estrogen antagonists were administered to NL men demonstrated an increase in LH pulse frequency, suggesting a potential additional hypothalamic site of E2 feedback. To reconcile these conflicting data, we used a selective aromatase inhibitor, anastrozole, to examine the impact of E2 suppression on the hypothalamic-pituitary axis in the male. Parallel studies of NL men and men with idiopathic hypogonadotropic hypogonadism (IHH), whose pituitary-gonadal axis had been normalized with long-term GnRH therapy, were performed to permit precise localization of the site of E2 feedback. In this so-called tandem model, a hypothalamic site of action of sex steroids can thus be inferred whenever there is a difference in the gonadotropin responses of NL and IHH men to alterations in their sex steroid milieu. A selective GnRH antagonist was also used to provide a semiquantitative estimate of endogenous GnRH secretion before and after E2 suppression. Fourteen NL men and seven IHH men were studied. In Exp 1, nine NL and seven IHH men received anastrozole (10 mg/day po x 7 days). Blood samples were drawn daily between 0800 and 1000 h in the NL men and immediately before a GnRH bolus dose in the IHH men. In Exp 2, blood was drawn (every 10 min x 12 h) from nine NL men at baseline and on day 7 of anastrozole. In a subset of five NL men, 5 microg/kg of the Nal-Glu GnRH antagonist was administered on completion of frequent blood sampling, then sampling continued every 20 min for a further 8 h. Anastrozole suppressed E2 equivalently in the NL (136 +/- 10 to 52 +/-2 pmol/L, P < 0.005) and IHH men (118 +/- 23 to 60 +/- 5 pmol/L, P < 0.005). Testosterone levels rose significantly (P < 0.005), with a mean increase of 53 +/- 6% in NL vs. 56 +/- 7% in IHH men. Despite these similar changes in sex steroids, the increase in gonadotropins was greater in NL than in IHH men (100 +/- 9 vs. 58 +/- 6% for LH, P = 0.07; and 85 +/- 6 vs. 41 +/- 4% for FSH, P < 0.002). Frequent sampling studies in the NL men demonstrated that this rise in mean LH levels, after aromatase blockade, reflected an increase in both LH pulse frequency (10.2 +/- 0.9 to 14.0 +/- 1.0 pulses/24 h, P < 0.05) and pulse amplitude (5.7 +/- 0.7 to 8.4 +/- 0.7 IU/L, P < 0.001). Percent LH inhibition after acute GnRH receptor blockade was similar at baseline and after E2 suppression (69.2 +/- 2.4 vs. 70 +/- 1.9%), suggesting that there was no change in the quantity of endogenous GnRH secreted. From these data, we conclude that in the human male, estrogen has dual sites of negative feedback, acting at the hypothalamus to decrease GnRH pulse frequency and at the pituitary to decrease responsiveness to GnRH.
Publication Types:
Clinical Trial
PMID: 10999781 [PubMed - indexed for MEDLINE]
--------------------------------------------------------------------------------
4: J Clin Endocrinol Metab. 2000 Jul;85(7):2370-7. Related Articles, Links
Comment in:
J Clin Endocrinol Metab. 2001 Apr;86(4):1836-8.
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. [email protected]
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.
Publication Types:
Clinical Trial
PMID: 10902781 [PubMed - indexed for MEDLINE]
--------------------------------------------------------------------------------
5: Endocr Relat Cancer. 1999 Jun;6(2):181-5. Related Articles, Links
Drug and hormone interactions of aromatase inhibitors.
Dowsett M.
Academic Department of Biochemistry, The Royal Marsden NHS Trust, London, UK.
The clinical development of aromatase inhibitors has been largely confined to postmenopausal breast cancer patients and strongly guided by pharmacological data. Comparative oestrogen suppression has been helpful in circumstances in which at least one of the comparitors has caused substantially non-maximal aromatase inhibition. However, the triazole inhibitors, letrozole and anastrozole, and the steroidal inhibitor, exemestane, all cause >95% inhibition. Comparisons between these drugs therefore require more sensitive approaches such as the direct measurement of enzyme activity by isotopic means. None of these three agents has significant effects on other endocrine pathways at its clinically applied doses. Pharmacokinetic analyses of the combination of tamoxifen and letrozole have revealed that these drugs interact, resulting in letrozole concentrations approximately 35-40% lower than when letrozole is used alone.
Publication Types:
Review
Review, Tutorial
PMID: 10731107 [PubMed - indexed for MEDLINE]
--------------------------------------------------------------------------------
6: Eur J Endocrinol. 2000 Feb;142(2):164-9. Related Articles, Links
Acute inhibition of oestrogen biosynthesis does not affect serum leptin levels in young men.
Luukkaa V, Rouru J, Ahokoski O, Scheinin H, Irjala K, Huupponen R.
Department of Pharmacology, University of Turku, and Clinical Pharmacology Unit, Turku University Central Hospital, FIN-20520 Turku, Finland. [email protected]
OBJECTIVE: Leptin plays an important role in the regulation of reproduction. To explore the contribution of oestradiol to serum leptin levels in men, we measured the concentrations of serum leptin and insulin after inhibition of oestrogen biosynthesis by selective blockade of the aromatase enzyme. DESIGN: The study had a double-blind parallel group design. METHODS: The aromatase inhibitor, MPV 2213ad, was given to eight healthy male volunteers as a single dose of 100mg. Eight men received placebo. Serum leptin and insulin were determined from blood samples collected at 0800h, 1600h and 2000h both on the actual test day (day 0) and on the previous day (day -1), and from single blood samples taken in the morning of days 1, 2, 4 and 7. Changes in serum leptin were correlated with those seen in serum oestradiol, testosterone, LH, FSH, cortisol and aldosterone, which were determined earlier. RESULTS: After the aromatase inhibitor administration, mean serum oestradiol concentration was reduced by 74% from the baseline compared with a 19% reduction in the placebo group (P for difference <0.001), and returned to pre-treatment levels within four days. Despite marked changes in serum oestradiol and sustained elevations in serum testosterone, LH and FSH concentrations, serum leptin concentrations were similar in the group receiving the aromatase inhibitor and in the placebo group. We found a weak correlation between serum oestradiol and leptin, which could not be reproduced when the percentage changes in these variables were analysed. CONCLUSION: Marked short-term reduction in serum oestradiol concentration has no effect on serum leptin levels in young men.
Publication Types:
Clinical Trial
Randomized Controlled Trial
PMID: 10664525 [PubMed - indexed for MEDLINE]
--------------------------------------------------------------------------------
7: Eur J Clin Pharmacol. 1999 Mar;55(1):27-34. Related Articles, Links
A double-blind study of MPV-2213ad, a novel aromatase inhibitor, in healthy male subjects.
Ahokoski O, Irjala K, Huhtala S, Salminen E, Scheinin H, Huupponen R.
Department of Pharmacology and Clinical Pharmacology, University of Turku, Turku University Central Hospital, Finland. [email protected]
OBJECTIVE: Novel aromatase inhibitors are developed with requirements of high potency and selectivity for the aromatase enzyme. The hormonal effects of a new, non-steroidal competitive inhibitor of the aromatase enzyme, MPV-2213ad, were investigated in this study. METHODS: The study was conducted as a double-blind, placebo controlled phase I study, where 32 healthy male volunteers were randomized to receive a single oral dose of either 0.3, 3 or 100 mg of MPV-2213ad or placebo. Serum concentrations of estradiol (E2), testosterone, follicle stimulating hormone (FSH), luteinizing hormone (LH), cortisol and aldosterone were determined from samples taken 0, 4, 8 h and 12 h during the day of drug administration and 1, 2, 4 and 7 days after drug intake. The individual diurnal variation of circulating hormone concentrations was determined in all participants at 0, 4, 8 h and 12 h on the day before drug intake. Specimens for hematological and biochemical analyses were also collected. RESULTS: A dose-dependent and statistically significant (P < 0.001) decrease in serum E2 concentrations was induced by MPV-2213ad. Lowest mean values were observed 8-12 h after drug administration and at 24 h the reductions were 10%, 34% and 69% from baseline in the 0.3-mg, 3-mg and 100-mg groups, compared with an 18% increase in the placebo group. Serum E2 concentrations returned to baseline within 4 days in all study subjects. A significant increase was observed in the serum concentrations of testosterone (P = 0.016), LH (P = 0.002) and FSH (P < 0.001) after administration of MPV-2213ad. Serum concentrations of cortisol and aldosterone were unaffected by MPV-2213ad. The drug was well tolerated. CONCLUSION: Single oral doses of MPV-2213ad, given to healthy male subjects, induced hormonal effects typical for a specific and selective inhibitor of the aromatase enzyme. Importantly, this study design with the determination of the diurnal rhythm in the levels of the corresponding hormones gives additional validity on the results.
Publication Types:
Clinical Trial
Clinical Trial, Phase I
Randomized Controlled Trial
PMID: 10206081 [PubMed - indexed for MEDLINE]
--------------------------------------------------------------------------------
8: Br J Clin Pharmacol. 1998 Feb;45(2):141-6. Related Articles, Links
Hormonal effects of MPV-2213ad, a new selective aromatase inhibitor, in healthy male subjects. A phase I study.
Ahokoski O, Irjala K, Huupponen R, Halonen K, Salminen E, Scheinin H.
Department of Pharmacology and Clinical Pharmacology, University of Turku, Turku University Central Hospital, Finland.
AIMS: A novel non-steroidal competitive inhibitor of the aromatase enzyme, MPV-2213ad, was entered into an open dose-escalation study. The objective of this study was to investigate the tolerability and efficiency of this new compound with assessment of the hormonal effects after study drug administration. METHODS: MPV-2213ad was given to 39 healthy male volunteers. Single increasing oral doses of 0.003, 0.03, 0.3, 3, 9, 30 and 100 mg were given to three subjects at each dose level, after which ten subjects received the 300 mg dose and eight subjects the highest 600 mg dose of MPV-2213ad. RESULTS: Serum oestradiol levels were suppressed by 58-65% when MPV-2213ad was given at doses between 0.3 and 30 mg. A reduction in serum oestradiol levels by 83% from baseline was achieved with the 300 mg dose. No additional decrease was seen with the highest dose. The suppression lasted longer with higher doses of MPV-2213ad. After the 300 and 600 mg doses serum oestradiol returned to baseline within 4 days. Marked increases in serum concentrations of testosterone, androstenedione, 17-OH-progesterone, LH and FSH were also observed at doses between 100 and 600 mg of MPV-2213ad. The drug was well-tolerated and the adverse events were mild or moderate including hot flushes, mild vertigo, nausea, acne and gastrointestinal discomfort. CONCLUSIONS: MPV-2213ad has a potent, dose-dependent inhibitory effect on serum oestradiol. It was selective for the aromatase enzyme with no signs of adreno-cortical suppression or haematological or biochemical toxicity.
Publication Types:
Clinical Trial
Clinical Trial, Phase I
PMID: 9491826 [PubMed - indexed for MEDLINE]
--------------------------------------------------------------------------------
9: Biopharm Drug Dispos. 1997 Aug;18(6):489-97. Related Articles, Links
Comparative bioavailability of letrozole under fed and fasting conditions in 12 healthy subjects after a 2.5 mg single oral administration.
Sioufi A, Sandrenan N, Godbillon J, Trunet P, Czendlik C, Howald H, Pfister C, Ezzet F.
Laboratoires Ciba-Geigy, Bioanalytics and Pharmacokinetics, Medical Department, Rueil-Malmaison, France.
Letrozole is a new non-steroidal inhibitor of the aromatase enzyme system. It is currently under development for the treatment of postmenopausal women with advanced breast cancer. To investigate the influence of food on the bioavailability of letrozole, 12 healthy male volunteers were treated under fed and fasted conditions with single oral doses of 2.5 mg letrozole in film-coated tablets. Plasma concentration profiles were determined. No significant difference in the extent of absorption (AUC or AUC0-8 h) was observed between the two treatments but the rate of letrozole absorption decreased slightly under fed conditions. However, in view of the half-life of about 2 d this small change in the absorption rate is not considered to be of clinical relevance for treatment with repeated administrations.
Publication Types:
Clinical Trial
Controlled Clinical Trial
PMID: 9267682 [PubMed - indexed for MEDLINE]
--------------------------------------------------------------------------------
10: J Steroid Biochem Mol Biol. 1996 Jul;58(4):439-45. Related Articles, Links
The preclinical pharmacology of "Arimidex" (anastrozole; ZD1033)--a potent, selective aromatase inhibitor.
Dukes M, Edwards PN, Large M, Smith IK, Boyle T.
Zeneca Pharmaceuticals, Alderly Park, Macclesfield, U.K.
Anastrozole is a comparatively simple, achiral benzyltriazole derivative, 2,2'-[5-(1H-1,2,4-triazol-1-ylmethyl)-1,3-phenylene]bis(2-++ +methylpropiononitrile), that inhibits human placental aromatase with an IC50 of 15 nM and elicits maximal activity in vivo in rats (inhibition of ovulation and androstenedione-induced uterine hypertrophy) and monkeys (lowering of plasma oestradiol) at 0.1 mg/kg p.o. At 30 times this dose, anastrozole does not elevate plasma 11-deoxycorticosterone in monkeys, and at 100 times this dose, does not affect plasma aldosterone levels or Na+/K+ excretion in rats, plasma K+ concentrations in dogs, or cause adrenal hypertrophy in rats or dogs. It therefore has no discernible effect on adrenocorticoid hormone synthesis in vivo at very large multiples of its maximally effective aromatase-inhibiting dose. At similar large multiples in rats it displays no oestrogenic, anti-oestrogenic, androgenic, anti-androgenic, progestogenic, glucocorticoid, antiglucocorticoid or mineralocorticoid activity. Anastrozole is thus a potent and highly selective aromatase inhibitor, with no intrinsic hormonal activities--a pharmacological profile particularly suitable for the treatment of breast cancer.
PMID: 8903429 [PubMed - indexed for MEDLINE]
--------------------------------------------------------------------------------
11: J Clin Endocrinol Metab. 1993 Aug;77(2):319-23. Related Articles, Links
Comment in:
J Clin Endocrinol Metab. 1993 Aug;77(2):316-8.
Open dose-finding study of a new potent and selective nonsteroidal aromatase inhibitor, CGS 20 267, in healthy male subjects.
Trunet PF, Mueller P, Bhatnagar AS, Dickes I, Monnet G, White G.
Research and Development Department, CIBA-GEIGY Limited, Basel, Switzerland.
The aim of this open, dose-finding study was to evaluate the effects of single dose CGS 20 267, a new oral nonsteroidal aromatase inhibitor, on the inhibition of estrogen production and also on the production of adrenal and testicular steroids in healthy male subjects. Nine dose levels ranging from 0.02-30 mg and placebo were tested, each dose being given to 3 subjects only. A total of 18 subjects were included; 12 of them received 2 single administration, the remaining 6 were exposed only once to one of the 2 highest dose levels. A reduction in serum estrogen levels when compared to baseline was already observed after 2 h, reaching maximum suppression between 10 and 48 h after administration. After 24 h, a suppression of estrone levels by 60-85% from baseline was achieved with all tested doses. A reduction in estradiol levels by about 30% from baseline was observed at the lowest dose (0.02 mg). This reduction was further enhanced dose dependently to a maximum of about 90% from baseline at 24 h after administration of the highest dose (30 mg). With the higher doses (10 and 30 mg), estrogen suppression was maintained up to 3 days. A dose-dependent increase of testosterone, LH, and FSH was observed and was most pronounced in the 10- and 30-mg dose groups, which can be considered as a consequence of the long-lasting aromatase inhibition achieved with these high doses. No effect on serum cortisol and aldosterone levels was observed up to the highest dose. No clinically relevant changes were observed in blood chemistry and hematology tests. The systemic and subjective tolerability of CGS 20 267 was good at all doses. This study has shown that CGS 20 267 is a well tolerated, potent, selective, and long-acting inhibitor of the aromatase enzyme after single administration.
Publication Types:
Clinical Trial
Controlled Clinical Trial
PMID: 8345034 [PubMed - indexed for MEDLINE]
OXANDRIN said:
Why do people care which one is the most powerful mg to mg? You have to look at the effective dose.
Besides, no amount of armidex will come close to 2.5mg of femera ... at least according to macro, and same thing with aromasin (I think).
So femera is the most "powerful" one mg to mg.
-sk
