Aromasin Study (on men)...Effects on Lipid Profile and IGF-1

[Jenetic]

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 Blood was withdrawn before and 24 h after the last dose of each treatment period.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.

 

[lartinos]

i love this stuff......wouldn't use anything else

 

[Guvna]

good post. k to ya.

 

[Goodfellow]

great

 

[b1ewsw32]

Great read dude!.....Check your PM's

B32

 

[bicepts101]

i know what ill be using next cycle...ldex doesnt work for me

 

[b1ewsw32]

I was just wondering? Since I know that Aromasin is a irreversible aromatase inhibitor(suicidal) and that new enzymes are formed eventually. Is it possible that with some kind of dysfunction/disposition that you could permanently supress conversion of T to E due to irreversible death of the aromatase enzymes.Similar to the need for HRT because of decreased sensitivity of the Leydig cells due to age or AAS abuse or possibly compromised piuitary or hypothalamus efficiency.
Would you have to take ERT. lol. or is the estrogen from the adrenal glands. ie. cholesterol>pregnenolone>DHEA>estrogen+testosterone be sufficient.

Jenetic,Huck,Ulter,Fonz or any member with experience or reasonable hypothesis please let me know what you think. Thanks.

B32

 

[ketogenic]

I believe its an aromatase inactavor not inhibitor. femara and arimidex are inhibitors.
keto

 

[brianzganjar]

I was just wondering? Since I know that Aromasin is a irreversible aromatase inhibitor(suicidal) and that new enzymes are formed eventually. Is it possible that with some kind of dysfunction/disposition that you could permanently supress conversion of T to E due to irreversible death of the aromatase enzymes.Similar to the need for HRT because of decreased sensitivity of the Leydig cells due to age or AAS abuse or possibly compromised piuitary or hypothalamus efficiency.
Would you have to take ERT. lol. or is the estrogen from the adrenal glands. ie. cholesterol>pregnenolone>DHEA>estrogen+testosterone be sufficient.

Jenetic,Huck,Ulter,Fonz or any member with experience or reasonable hypothesis please let me know what you think. Thanks.

B32

Aromasin binds to the aromatase protein molecule only, resulting in a distortion in its tree dimensional structure and it can no longer catalyze the conversion. It will not alter production of the enzyme. One would not ever have to go on ERT even if there were no aromatase production whatsoever. In elderly men with serum test levels <350 ng administration of arimidex increased test levels to youthful levels as you would expect but also estradiol levels remained in the normal male range despite total aromatase inactivity.


Leder BZ, Rohrer JL, Rubin SD, et al.
Effects of aromatase inhibition in elderly men with low or borderline-low serum testosterone levels.
J Clin Endocrinol Metab (United States), Mar 2004, 89(3) p1174-80

Concern over estradiol levels in genuine as you know due to the significant lipid abnormalities that occur and their subsequent acute affects on the liver which is often overly taxed to begin with.

 

[Jenetic]

Aromasin binds to the aromatase protein molecule only, resulting in a distortion in its tree dimensional structure and it can no longer catalyze the conversion. It will not alter production of the enzyme. One would not ever have to go on ERT even if there were no aromatase production whatsoever.

The first statement would make sense due to the fact that the CYP19 gene resposible for production of the P450 aromatase is unaffected, therefore it would not affect the production of the aromatase enzyme. A direct mutation of the CYP19 gene would be necessary for a loss in production to occur.

But to say that ERT would not be needed if the P450 aromatase was not in production whatsoever does not make much sense due to the fact that, in males, estrogens derive from circulating androgens. Aromatization of the C19 androgens, testosterone and androstenedione, to form estradiol and estrone, respectively, is the key step in estrogen biosynthesis, which is under the control of the aromatase enzyme.

 

[b1ewsw32]

The first statement would make sense due to the fact that the CYP19 gene resposible for production of the P450 aromatase is unaffected, therefore it would not affect the production of the aromatase enzyme. A direct mutation of the CYP19 gene would be necessary for a loss in production to occur.

But to say that ERT would not be needed if the P450 aromatase was not in production whatsoever does not make much sense due to the fact that, in males, estrogens derive from circulating androgens. Aromatization of the C19 androgens, testosterone and androstenedione, to form estradiol and estrone, respectively, is the key step in estrogen biosynthesis, which is under the control of the aromatase enzyme.

OK...excellent. So the CYP19 gene can never be affected by aromasin and therefore will always be able to synthesize more aromatase enzymes.

As far as ERT is concerned, I agree as brianz failed to realize that despite having"normal" detectable e levels is not the issue as libido,lipid,bone and neurological problems can still ensue because estrogen levels are an individual matter and what's optimum may very from one person to another. It's just like free testosterone levels being within "normal limits" but it's usually low normal and the individual feels like shit. Once HRT brings patient to the higher normal parameters then psycological and physiological benefits become apperant.

This study came to mind.....


Role of oestrogen in male sexual behaviour: insights from the natural model of aromatase deficiency.

Carani C, Rochira V, Faustini-Fustini M, Balestrieri A, Granata AR.

Chair of Endocrinology, Department of Internal Medicine, University of Modena, Italy.

OBJECTIVE: In order to evaluate the role of oestrogens on human male sexual behaviour, the gender-identity, psychosexual orientation and sexual activity of a man with a congenital lack of oestradiol resulting from an inactivating mutation of the aromatase P450 gene was investigated. The psychosexual and sexual behavioural evaluations were performed before and during testosterone treatment and before oestradiol treatment, during three phases of different dosages of oestradiol treatment. DESIGN: The study was performed before (phase A) and during (phase B) testosterone enanthate treatment (250 mg i.m. every 10 days, for 6 months), during testosterone withdrawal (phase C), and during each of the following transdermal oestradiol treatments: 50 microg twice a week for 6 months (phase D); 25 microg twice a week for 9 months (phase E), and 12.5 microg twice a week for 9 months (phase F). MEASUREMENTS: Sexual behaviour was investigated by a sexological interview and by a 2-month self-reported daily diary performed during each phase of the protocol study. Furthermore, during each oestradiol treatment (phase C, D, E and F), a study of depression, anxiety trait and sexual behaviour was performed by the Beck Depression Inventory (BDI), the Spielberger Trait Anxiety Inventory (STAI) and the Golombok-Rust Inventory of Sexual Satisfaction (GRISS), respectively. Sexual orientation and gender-identity were evaluated by the BEM Sex Role Inventory (BSRI). Serum testosterone and oestradiol were measured during each phase of the study. RESULTS: Before oestradiol treatment (phase C), serum oestradiol was undetectable, while it rose to 356.1, 88.1 and 55.1 pmol/l during phases D, E and F, respectively. Before any oestradiol treatment, during phase D, phase E and phase F serum testosterone was 18.13, 0.72, 14.3 and 18.51 nmol/l, respectively. The patient's gender-identity as assessed by BSRI and by the sexological interview was clearly male. The psychosexual orientation evaluated by BSRI, by the sexological interview and by the analysis of the self-filled diary was heterosexual. Relevant modification of the patient's sexual behaviour occurred only during oestrogen treatment. This was more evident during both phase E and phase F, and concerned the behavioural parameters with an increase of libido, frequency of sexual intercourse, masturbation and erotic fantasies. A reduction of BDI and STAI scores was detected during the oestrogen phases. CONCLUSIONS: The study of the sexual behaviour in this man with aromatase deficiency suggests that oestrogens in humans do not affect gender-identity and sexual orientation but could have a role in male sexual activity.

B32

 

[Jenetic]

Thanks for the reference.

 

[VictorBR]

bump , lots of good info here


Victor

 

[Davs]

If you are a man you don't want more estgrogen than a man should have as determined bynature. Otherwse you are talking transgender. Who cares if your libido increases.

 

[b1ewsw32]

If you are a man you don't want more estgrogen than a man should have as determined bynature. Otherwse you are talking transgender. Who cares if your libido increases.

So it seems that "Aromasin is the king of anti-e's" is the general consensus of most members.

Other then no effects on the lipids,lack of effect on circulating levels of IGF, and no detrimental effects on libido. Is there any other beneficial effects of aromasin compared to other anti-e's?
We know for the most part that cost is not one of them. LOL.

B32