Drveejay11
I am banned!
It does what Arimidex (Liquidex) and Femara CANNOT do.....keep your lipid profile in check.
http://www.fda.gov/cder/foi/label/1999/20753lbl.pdf
http://www.fda.gov/cder/foi/label/1999/20753lbl.pdf
WHY Aromasin should be your favorite anti-E
- Thread starter Drveejay11
- Start date
Nelson Montana
Community Veteran, Bodybuilding Author
This is questionable.
No anti-e drug is necessarily bad for your lipid profile. It's simply having too low of an estrogen level that is bad for the lipid count.
I'm on Hormone Replacement Therapy (HRT) which includes a non stop administration of 1/4 mg of A-dex, every 4 days and some herbals. This keeps my estro in the normal range and my cholesterol is 170 with a very favorable HDL count.
No anti-e drug is necessarily bad for your lipid profile. It's simply having too low of an estrogen level that is bad for the lipid count.
I'm on Hormone Replacement Therapy (HRT) which includes a non stop administration of 1/4 mg of A-dex, every 4 days and some herbals. This keeps my estro in the normal range and my cholesterol is 170 with a very favorable HDL count.
StoneColdNTO
Administrator
Clin Cancer Res. 2003 Jan;9(1 Pt 2):468S-72S. Related Articles, Links
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.
-----------------------------
Cancer. 2002 Nov 1;95(9):2006-16. Related Articles, Links
An overview of the pharmacology and pharmacokinetics of the newer generation aromatase inhibitors anastrozole, letrozole, and exemestane.
Buzdar AU, Robertson JF, Eiermann W, Nabholtz JM.
Department of Breast Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston 77030, USA. abuzdar@mdanderson.org
BACKGROUND: The newer generation, nonsteroidal aromatase inhibitors (AIs) anastrozole and letrozole have shown superior efficacy compared with tamoxifen as first-line treatments and compared with megestrol acetate as second-line therapy in postmenopausal women with advanced breast carcinoma. In an open-label, Phase II trial, it was reported that exemestane showed numerical superiority compared with tamoxifen for objective response and clinical benefit. Because these agents ultimately may be administered for periods of up to 5 years in the adjuvant setting, it is of increasing importance to assess their tolerability and pharmacologic profiles. METHODS: In the absence of data from direct clinical comparisons, the published literature was reviewed for the clinical pharmacology, pharmacokinetic characteristics, and selectivity profiles of anastrozole, letrozole, and exemestane. RESULTS: 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) were 41-48 hours, 2-4 days, and 27 hours, respectively. The time to steady-state plasma levels was 7 days for both anastrozole and exemestane and 60 days for letrozole. Androgenic side effects have been reported only with exemestane. Anastrozole treatment had no impact on plasma lipid levels, whereas both letrozole and exemestane had an unfavorable effect on plasma lipid levels. In indirect comparisons, anastrozole showed the highest degree of selectivity compared with letrozole and exemestane in terms of a lack of effect on adrenosteroidogenesis. CONCLUSIONS: All three AIs demonstrated clinical efficacy over preexisting treatments. However, there were differences in terms of pharmacokinetics and effects on lipid levels and adrenosteroidogenesis. The long-term clinical significance of these differences remains to be elucidated. Copyright 2002 American Cancer Society.
http://www.steroidology.com/forum/showthread.php?s=&threadid=6472
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.
-----------------------------
Cancer. 2002 Nov 1;95(9):2006-16. Related Articles, Links
An overview of the pharmacology and pharmacokinetics of the newer generation aromatase inhibitors anastrozole, letrozole, and exemestane.
Buzdar AU, Robertson JF, Eiermann W, Nabholtz JM.
Department of Breast Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston 77030, USA. abuzdar@mdanderson.org
BACKGROUND: The newer generation, nonsteroidal aromatase inhibitors (AIs) anastrozole and letrozole have shown superior efficacy compared with tamoxifen as first-line treatments and compared with megestrol acetate as second-line therapy in postmenopausal women with advanced breast carcinoma. In an open-label, Phase II trial, it was reported that exemestane showed numerical superiority compared with tamoxifen for objective response and clinical benefit. Because these agents ultimately may be administered for periods of up to 5 years in the adjuvant setting, it is of increasing importance to assess their tolerability and pharmacologic profiles. METHODS: In the absence of data from direct clinical comparisons, the published literature was reviewed for the clinical pharmacology, pharmacokinetic characteristics, and selectivity profiles of anastrozole, letrozole, and exemestane. RESULTS: 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) were 41-48 hours, 2-4 days, and 27 hours, respectively. The time to steady-state plasma levels was 7 days for both anastrozole and exemestane and 60 days for letrozole. Androgenic side effects have been reported only with exemestane. Anastrozole treatment had no impact on plasma lipid levels, whereas both letrozole and exemestane had an unfavorable effect on plasma lipid levels. In indirect comparisons, anastrozole showed the highest degree of selectivity compared with letrozole and exemestane in terms of a lack of effect on adrenosteroidogenesis. CONCLUSIONS: All three AIs demonstrated clinical efficacy over preexisting treatments. However, there were differences in terms of pharmacokinetics and effects on lipid levels and adrenosteroidogenesis. The long-term clinical significance of these differences remains to be elucidated. Copyright 2002 American Cancer Society.
http://www.steroidology.com/forum/showthread.php?s=&threadid=6472
StoneColdNTO
Administrator
Another interesting thread..........
http://www.healthandfitnesstalk.com/forum/showthread.php?s=&threadid=2714&highlight=cholesterol
http://www.healthandfitnesstalk.com/forum/showthread.php?s=&threadid=2714&highlight=cholesterol
The studies prior to 2004 showed mixed results. However the studies that were done recently have showed that arimidex and letrozole DO affect lipid profiles and Aromasin doesn't.
I had Arimidex trash my lipid panel and when I switched to letrozole it was the same deal. Now I use Aromasin and it's been fine the last year.
Ann Oncol. 2004 Feb;15(2):211-7. Related Articles, Links
The effect of exemestane on serum lipid profile in postmenopausal women with metastatic breast cancer: a companion study to EORTC Trial 10951, 'Randomized phase II study in first line hormonal treatment for metastatic breast cancer with exemestane or tamoxifen in postmenopausal patients'.
Atalay G, Dirix L, Biganzoli L, Beex L, Nooij M, Cameron D, Lohrisch C, Cufer T, Lobelle JP, Mattiaci MR, Piccart M, Paridaens R.
Jules Bordet Institute, Brussels, Belgium.
BACKGROUND: The impact of aromatase inhibitors (AIs) on non-cancer-related outcomes, which are known to be affected by oestrogens, has become increasingly important in postmenopausal women with hormone-dependent breast cancer. So far, data related to the effect of AIs on lipid profile in postmenopausal women is scarce. This study, as a companion substudy of an EORTC phase II trial (10951), evaluated the impact of exemestane, a steroidal aromatase inactivator, on the lipid profile of postmenopausal metastatic breast cancer (MBC) patients. PATIENTS AND METHODS: The EORTC trial 10951 randomised 122 postmenopausal breast cancer patients to exemestane (E) 25 mg (n = 62) or tamoxifen (T) 20 mg (n = 60) once daily as a first-line treatment in the metastatic setting. Exemestane showed promising results in all the primary efficacy end points of the trial (response rate, clinical benefit rate and response duration), and it was well tolerated with low incidence of serious toxicity. As a secondary end point of this phase II trial, serum triglycerides (TRG), high-density lipoprotein cholesterol (HDL), total cholesterol (TC), lipoprotein a (Lip a), and apolipoproteins (Apo) B and A1 were measured at baseline and while on therapy (at 8, 24 and 48 weeks) to assess the impact of exemestane and tamoxifen on serum lipid profiles. Of the 122 randomised patients, those who had baseline and at least one other lipid assessment are included in the present analysis. The patients who received concomitant drugs that could affect lipid profile are included only if these drugs were administered throughout the study treatment. Increase or decrease in lipid parameters within 20% of baseline were considered as non-significant and thus unchanged. RESULTS: Seventy-two patients (36 in both arms) were included in the statistical analysis. The majority of patients had abnormal TC and normal TRG, HDL, Apo A1, Apo B and Lip a levels at baseline. Neither exemestane nor tamoxifen had adverse effects on TC, HDL, Apo A1, Apo B or Lip a levels at 8, 24 and 48 weeks of treatment. Exemestane and tamoxifen had opposite effects on TRG levels: exemestane lowered while tamoxifen increased TRG levels over time. There were too few patients with normal baseline TC and abnormal TRG, HDL, Apo A1, Apo B and Lip a levels to allow for assessment of E's impact on these subsets. The atherogenic risk determined by Apo A1:Apo B and TC:HDL ratios remained unchanged throughout the treatment period in both the E and T arms. CONCLUSIONS: Overall, exemestane has no detrimental effect on cholesterol levels and the atherogenic indices, which are well-known risk factors for coronary artery disease. In addition, it has a beneficial effect on TRG levels. These data, coupled with E's excellent efficacy and tolerability, support further exploration of its potential in the metastatic, adjuvant and chemopreventive setting.
One more thing... There is no evidence that short term disturbances in your lipid panel such as those that ocurr from a cycle have any affect on furture heart disease.
There is much debate about whether lipid panels are an accurate predictor of CAD in the first place, but there is no link to short term fluctuations at all.
So for us it's probably much ado about nothing.
I had Arimidex trash my lipid panel and when I switched to letrozole it was the same deal. Now I use Aromasin and it's been fine the last year.
Ann Oncol. 2004 Feb;15(2):211-7. Related Articles, Links
The effect of exemestane on serum lipid profile in postmenopausal women with metastatic breast cancer: a companion study to EORTC Trial 10951, 'Randomized phase II study in first line hormonal treatment for metastatic breast cancer with exemestane or tamoxifen in postmenopausal patients'.
Atalay G, Dirix L, Biganzoli L, Beex L, Nooij M, Cameron D, Lohrisch C, Cufer T, Lobelle JP, Mattiaci MR, Piccart M, Paridaens R.
Jules Bordet Institute, Brussels, Belgium.
BACKGROUND: The impact of aromatase inhibitors (AIs) on non-cancer-related outcomes, which are known to be affected by oestrogens, has become increasingly important in postmenopausal women with hormone-dependent breast cancer. So far, data related to the effect of AIs on lipid profile in postmenopausal women is scarce. This study, as a companion substudy of an EORTC phase II trial (10951), evaluated the impact of exemestane, a steroidal aromatase inactivator, on the lipid profile of postmenopausal metastatic breast cancer (MBC) patients. PATIENTS AND METHODS: The EORTC trial 10951 randomised 122 postmenopausal breast cancer patients to exemestane (E) 25 mg (n = 62) or tamoxifen (T) 20 mg (n = 60) once daily as a first-line treatment in the metastatic setting. Exemestane showed promising results in all the primary efficacy end points of the trial (response rate, clinical benefit rate and response duration), and it was well tolerated with low incidence of serious toxicity. As a secondary end point of this phase II trial, serum triglycerides (TRG), high-density lipoprotein cholesterol (HDL), total cholesterol (TC), lipoprotein a (Lip a), and apolipoproteins (Apo) B and A1 were measured at baseline and while on therapy (at 8, 24 and 48 weeks) to assess the impact of exemestane and tamoxifen on serum lipid profiles. Of the 122 randomised patients, those who had baseline and at least one other lipid assessment are included in the present analysis. The patients who received concomitant drugs that could affect lipid profile are included only if these drugs were administered throughout the study treatment. Increase or decrease in lipid parameters within 20% of baseline were considered as non-significant and thus unchanged. RESULTS: Seventy-two patients (36 in both arms) were included in the statistical analysis. The majority of patients had abnormal TC and normal TRG, HDL, Apo A1, Apo B and Lip a levels at baseline. Neither exemestane nor tamoxifen had adverse effects on TC, HDL, Apo A1, Apo B or Lip a levels at 8, 24 and 48 weeks of treatment. Exemestane and tamoxifen had opposite effects on TRG levels: exemestane lowered while tamoxifen increased TRG levels over time. There were too few patients with normal baseline TC and abnormal TRG, HDL, Apo A1, Apo B and Lip a levels to allow for assessment of E's impact on these subsets. The atherogenic risk determined by Apo A1:Apo B and TC:HDL ratios remained unchanged throughout the treatment period in both the E and T arms. CONCLUSIONS: Overall, exemestane has no detrimental effect on cholesterol levels and the atherogenic indices, which are well-known risk factors for coronary artery disease. In addition, it has a beneficial effect on TRG levels. These data, coupled with E's excellent efficacy and tolerability, support further exploration of its potential in the metastatic, adjuvant and chemopreventive setting.
One more thing... There is no evidence that short term disturbances in your lipid panel such as those that ocurr from a cycle have any affect on furture heart disease.
There is much debate about whether lipid panels are an accurate predictor of CAD in the first place, but there is no link to short term fluctuations at all.
So for us it's probably much ado about nothing.
Drveejay11
I am banned!
ulter said:
Same here. With all the damn supps I would take alongside a-dex; it never mattered: wrecked lipid profile was always the result. With Aromasin....they barely changed on some cycles and actually improved during others.
It wins for me----hands down.
Drveejay11
I am banned!
ulter said:
Good eye.
StoneColdNTO
Administrator
Yes......but in essence, one should be more concerned about the actual steroids playing havoc with one's lipid profile, as opposed to what an Aromatase Inhibitor does to it.
Most steroids will effect it more than any Aromatase inhibitor (AI) ever will.
Most steroids will effect it more than any Aromatase inhibitor (AI) ever will.
hhajdo
Community Veteran
There's probably little difference between them in their effect on plasma lipids... Most of the studies we discussed were performed on postmenopausal women & can't be applied to healthy men because similar level of E suppression (90 %) can't be achieved....
In that study posted above most subjects already had abnormal total cholesterol, & 20 % variation was not considered significant... That study definitely doesn't prove that exemestane is superior... Also, the beneficial effect on triglycerides (which is thought to be due to exemestane's androgenic properties) wouldn't be noticed in presence of elevated androgen levels...
Here's an excerpt from a recent review:
The Oncologist, Vol. 9, No. 2, 126–136, April 2004
© 2004 AlphaMed Press
Aromatase Inhibitors for Breast Cancer in Postmenopausal Women
Susana M. Campos
Harvard Medical School, Dana-Farber Cancer Institute, Boston, Massachusetts, USA
..."Dewar and colleagues [49] report no significant lipid changes in postmenopausal women treated with anastrozole for fewer than 20 months. Wojtacki et al. [50] studied both anastrozole (n = 27) and letrozole (n = 3) in postmenopausal women for a median of 32 weeks. Their preliminary results suggest that neither anastrozole nor letrozole affect lipid metabolism. Harper-Wynne and coworkers [51] reported no negative effects on lipid metabolism after 3 months of treatment with letrozole. In contrast, in a study conducted in 20 postmenopausal women treated with letrozole at a dose of 2.5 mg daily for 16 weeks, there were significant increases in total cholesterol, low-density lipoprotein cholesterol, and Apo B levels [52]..."
In that study posted above most subjects already had abnormal total cholesterol, & 20 % variation was not considered significant... That study definitely doesn't prove that exemestane is superior... Also, the beneficial effect on triglycerides (which is thought to be due to exemestane's androgenic properties) wouldn't be noticed in presence of elevated androgen levels...
Here's an excerpt from a recent review:
The Oncologist, Vol. 9, No. 2, 126–136, April 2004
© 2004 AlphaMed Press
Aromatase Inhibitors for Breast Cancer in Postmenopausal Women
Susana M. Campos
Harvard Medical School, Dana-Farber Cancer Institute, Boston, Massachusetts, USA
..."Dewar and colleagues [49] report no significant lipid changes in postmenopausal women treated with anastrozole for fewer than 20 months. Wojtacki et al. [50] studied both anastrozole (n = 27) and letrozole (n = 3) in postmenopausal women for a median of 32 weeks. Their preliminary results suggest that neither anastrozole nor letrozole affect lipid metabolism. Harper-Wynne and coworkers [51] reported no negative effects on lipid metabolism after 3 months of treatment with letrozole. In contrast, in a study conducted in 20 postmenopausal women treated with letrozole at a dose of 2.5 mg daily for 16 weeks, there were significant increases in total cholesterol, low-density lipoprotein cholesterol, and Apo B levels [52]..."
Yes that's true StoneCold, AS has a greater impact but everything should be considered IF you're going to consider it at all. I will say this for the 100th time and I get a lot of grief for posting it, there is virtually NO evidence that short term flucuations in lipid profiles contribute to or are an indicator for future CAD. Whether it's caused by AI's or AS doesn't make any difference. Most people cycle for 12 weeks or less and that's just not enough time to cause CAD or contibute to it. Because if it did there would be thousands of body builders from the 70's and 80's dropping dead or becoming seriously ill by now of CAD and that's just not the case. I realize it's anecdotal but come on, there are 10's of thousands of people who used steroids 25-30 years ago and that demographic would have been exposed by now by the medical profession if they weren't living long healthy lives. They would love to point to them and say, "see what a health risk steroids are", " this will happen to you", etc. NONE of the people I know from 20-25 years ago who did pretty hefty cycles has any health problems today, not a single one out of a couple hundred.
Aromasin surpressed male estrogen as much as 76% in this study and still didn't affect the plasma lipids. So it looks like it does do for men what it does for women and the results can be applied to men afterall.
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
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.
Abbreviations: AUC, Area under the curve; CBC, cell blood count; HDL, high density lipoprotein; LDL, low density lipoprotein; PK, pharmacokinetic.
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
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.
Abbreviations: AUC, Area under the curve; CBC, cell blood count; HDL, high density lipoprotein; LDL, low density lipoprotein; PK, pharmacokinetic.
Drveejay11
I am banned!
Governor said:
A little more for ya
Aromasin Study (on men)...Effects on Lipid Profile and IGF-1
--------------------------------------------------------------------------------
I've seen a lot of questions on Aromasin lately. This study on men should clearify the issues.
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
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.
Abbreviations: AUC, Area under the curve; CBC, cell blood count; HDL, high density lipoprotein; LDL, low density lipoprotein; PK, pharmacokinetic.
hhajdo
Community Veteran
I didn't see that one before, thanks for posting it.
The average estradiol suppression was about 38 %, and it peaked @ 62 ± 14%.
This is comparable to what is usually achieved when 1-2 mg of anastrozole is administered ED, and the effect on plasma lipids is similar as I said earlier...
38% is not comparable to >90 % which is usually seen in studies on postmenopausal women.
Here are a few examples in which anastrozole was used:
http://jcem.endojournals.org/cgi/content-nw/full/86/6/2869/T3
In this study (which lasted 10 times longer than the exemestane study) 15 men were treated with 2 mg of anastrozole ED for 9 weeks.
After 9 weeks their HDL decreased only slightly from 54 ± 3 to 50 ± 2 mg/dl... 50 mg/dl is average normal HDL ... LDL decreased also...
---------------
http://jcem.endojournals.org/cgi/content/full/85/7/2370
In this one eight young males were treated with 1 mg of anastrozole ED for 10 weeks.
"...Anastrozole treatment was well tolerated by all subjects. Glucose and insulin concentrations remained unchanged during these studies, as did plasma lipid concentrations, blood chemistries, and cell blood counts... "
This shows that there's little difference between them in their effect on cholesterol, and that their effect is not significant when compared to what only 6 mg of stanozolol does after 2 weeks of use:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=9284885
...we treated these two men and two controls with the oral androgen stanozolol (6 mg/d) for 2 weeks. Consistent with other reports, HL activity increased a mean of 277% in controls with a concomitant decrease in HDL cholesterol (49%), HDL2 cholesterol (90%), HDL3 cholesterol (16%), and apo A-I (41%) and no change in apo A-II.....
Since elevated androgen levels negatively affect cholesterol, increased estradiol is beneficial since it was shown that it may attenuate atherogenesis...
PNAS | March 19, 2002 | vol. 99 | no. 6 | 4055-4060
Testosterone attenuates expression of vascular cell adhesion molecule-1 by conversion to estradiol by aromatase in endothelial cells: Implications in atherosclerosis
..."Men are twice as likely as women to die from coronary artery disease, probably because men lack the protection afforded by endogenous or exogenous estrogens ..."
IMO, aromatase inhibitors are overused and may negatively affect health in the long term.
The average estradiol suppression was about 38 %, and it peaked @ 62 ± 14%.
This is comparable to what is usually achieved when 1-2 mg of anastrozole is administered ED, and the effect on plasma lipids is similar as I said earlier...
38% is not comparable to >90 % which is usually seen in studies on postmenopausal women.
Here are a few examples in which anastrozole was used:
http://jcem.endojournals.org/cgi/content-nw/full/86/6/2869/T3
In this study (which lasted 10 times longer than the exemestane study) 15 men were treated with 2 mg of anastrozole ED for 9 weeks.
After 9 weeks their HDL decreased only slightly from 54 ± 3 to 50 ± 2 mg/dl... 50 mg/dl is average normal HDL ... LDL decreased also...
---------------
http://jcem.endojournals.org/cgi/content/full/85/7/2370
In this one eight young males were treated with 1 mg of anastrozole ED for 10 weeks.
"...Anastrozole treatment was well tolerated by all subjects. Glucose and insulin concentrations remained unchanged during these studies, as did plasma lipid concentrations, blood chemistries, and cell blood counts... "
This shows that there's little difference between them in their effect on cholesterol, and that their effect is not significant when compared to what only 6 mg of stanozolol does after 2 weeks of use:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=9284885
...we treated these two men and two controls with the oral androgen stanozolol (6 mg/d) for 2 weeks. Consistent with other reports, HL activity increased a mean of 277% in controls with a concomitant decrease in HDL cholesterol (49%), HDL2 cholesterol (90%), HDL3 cholesterol (16%), and apo A-I (41%) and no change in apo A-II.....
Since elevated androgen levels negatively affect cholesterol, increased estradiol is beneficial since it was shown that it may attenuate atherogenesis...
PNAS | March 19, 2002 | vol. 99 | no. 6 | 4055-4060
Testosterone attenuates expression of vascular cell adhesion molecule-1 by conversion to estradiol by aromatase in endothelial cells: Implications in atherosclerosis
..."Men are twice as likely as women to die from coronary artery disease, probably because men lack the protection afforded by endogenous or exogenous estrogens ..."
IMO, aromatase inhibitors are overused and may negatively affect health in the long term.
Yes the average was 38% but it did take out 76% in some subjects so it's possible. Admittedly though it does this better in women.
I am not and the others posting over the years are not a study. But I have had and others posting have had their lipids trashed by Arimidex a few years back. And it doesn't happen with Aromasin, at least for me and those posting about it.
P.S. I didn't find it, I saw it posted somewhere else. But I immediately knew where I wanted to copy it to.
I am not and the others posting over the years are not a study. But I have had and others posting have had their lipids trashed by Arimidex a few years back. And it doesn't happen with Aromasin, at least for me and those posting about it.
P.S. I didn't find it, I saw it posted somewhere else. But I immediately knew where I wanted to copy it to.
einstein1905
Banned
Lots of good info here. Studies are great, obviously, but you can almost always find a study to contradict any study.
What's important to me here is that adex and letro (class II AIs), inhibit aromatase via competitive inhibition, exemestane (a class I AI) does the very same thing, although via irreversible binding to aromatase. Adex and letro are in a perpetual bind and release state, which also allows for substrate to bind aromatase while unoccupied by the AI.
The fact is that they both affect the exact same mechanism at the exact same step, and they all lower systemic estrogen levels. Even though studies, thus far, are showing no drop in HDL, you have to ask yourself how this could be so. Ultimately, it's the decreased systemic estrogen levels that reduce HDL, so anything that reduces estrogen, reduces HDL. I can't explain why the studies thus far haven't shown this, but it just doesn't make sense to me.
exemestane is androgen-like, which will have other effects in the body, like lowered SHBG, but this still doesn't explain why the studies are showing no lipid impact. if anyone has any ideas, I'm all ears.
What's important to me here is that adex and letro (class II AIs), inhibit aromatase via competitive inhibition, exemestane (a class I AI) does the very same thing, although via irreversible binding to aromatase. Adex and letro are in a perpetual bind and release state, which also allows for substrate to bind aromatase while unoccupied by the AI.
The fact is that they both affect the exact same mechanism at the exact same step, and they all lower systemic estrogen levels. Even though studies, thus far, are showing no drop in HDL, you have to ask yourself how this could be so. Ultimately, it's the decreased systemic estrogen levels that reduce HDL, so anything that reduces estrogen, reduces HDL. I can't explain why the studies thus far haven't shown this, but it just doesn't make sense to me.
exemestane is androgen-like, which will have other effects in the body, like lowered SHBG, but this still doesn't explain why the studies are showing no lipid impact. if anyone has any ideas, I'm all ears.
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