Formestane's Effect on Cholesterol

[Ichidan]

Does formestane and ATD have the same negative effects on cholesterol levels as other AIs such as Aridmidex?

 

[same_old]

i believe those effects are a direct result of low E2...if so, any stronger AI has the potential to do it...certainly ATD. i never felt that (oral) formestane was super potent as an AI, though.

i have a "knee test" for AIs...if my knees start to ache while using an AI, i know it's restricting E2 too much. letro does it in about 3 days @ 1mg ED. AT (6OXO) takes much longer and much higher doses. formestane barely does it at all. aromasin (which is supposedly much better for lipids) seems to inhibit aromastase a very small amount, as compared to the others.

perhaps there is another dimension of the E2-joint lubrication-cholesterol relationship that i dont know....but i have not read anything definitive on the subject (not to say it doesnt exist)

so my answer is: i have no idea.

sorry!

 

[bioman]

Yes, ATD will crash lipids and is a fairly potent AI. I also strongly suspect that it has androgenic activity and that we do not know the full extent of it's role in PCT..ie whether it's suppressive or not.

 

[same_old]

Yes, ATD will crash lipids and is a fairly potent AI. I also strongly suspect that it has androgenic activity and that we do not know the full extent of it's role in post cycle therapy..ie whether it's suppressive or not.

you meant formestane right?

 

[Ichidan]

The effects of formestane or ATD, i am curious how either one effects cholesterol levels

 

[Sonicology]

Whilst you are correct that type II AI's (letro and adex) will hurt lipids, the studies I have seen suggest that type I AI's (specifically exemestane, although probably also ATD due to their structural similarity) actually have a positive effect upon lipids;

Anti-aromatase agents in the treatment and prevention of breast cancer.

Goss P.

Breast Cancer Prevention Program at the Princess Margaret Hospital, Toronto, Ontario, Canada. [email protected]

Anti-aromatase agents now have a central role in the management of breast cancer in postmenopausal women; they are superior to megestrol acetate as second-line therapy and to tamoxifen for initial therapy of metastatic disease. They also are highly active as neoadjuvant therapy. Two classes of anti-aromatase agents are available: steroidal (eg, exemestane) and nonsteroidal (eg, anastrozole, letrozole). Although both types of agents act on the aromatase enzyme, they do so by different mechanisms and have different effects on cellular aromatase activity. Nonsteroidal agents are associated with increased aromatase enzyme content and steroidal agents are associated with decreased content. The increase in aromatase content seen with the nonsteroidal agents may in part explain the development of resistance with these agents and the ability of the steroidal agent exemestane to induce a response when nonsteroidal agents fail. Because the anti-aromatase agents almost completely eliminate endogenous estrogen production, they not only affect breast cancer tissues, but also may alter the function of other estrogen-responsive tissues. However, preclinical data show that the steroidal agent exemestane may actually improve bone and lipid metabolism. In addition, no increase in clinical fracture rate has been noted in women treated with exemestane in metastatic trials; the fracture risk has not yet been studied following prolonged exposure in healthy women. Exemestane associated beneficial effects on these end organs may be due to the steroidal nature of both the parent compound and its principal metabolite, 17-hydroexemestane. Similar benefits have not been reported with nonsteroidal antiaromatase agents. Based on their excellent activity in the metastatic setting, anti-aromatase agents are now being evaluated in the adjuvant setting and in pilot studies for chemoprevention. These studies will provide long-term data in healthy women and will help to differentiate anti-aromatase agents, in terms of their efficacy in the treatment of breast cancer and their effects on end organs.

Entrez PubMed

Effects of the steroidal aromatase inhibitor exemestane and the nonsteroidal aromatase inhibitor letrozole on bone and lipid metabolism in ovariectomized rats.

Goss PE, Qi S, Cheung AM, Hu H, Mendes M, Pritzker KP.

Breast Cancer Prevention Program, Princess Margaret Hospital, University Health Network, University of Toronto, Ontario, Canada. [email protected]

PURPOSE: Exemestane (EXE) and letrozole (LET) are third-generation aromatase inhibitors currently prescribed for postmenopausal hormone-dependent breast cancer. The impact on end organs of estrogen depletion in menopausal women is of significant clinical importance. We studied the effects of EXE, its principal metabolite, 17-hydroexemestane (17-H-EXE), and LET on bone and lipid metabolism in ovariectomized (OVX) rats. EXPERIMENTAL DESIGN: OVX rats were treated by weekly intramuscular injection for 16 weeks with 20, 50, and 100 mg/kg EXE, 20 mg/kg 17-H-EXE, and daily oral gavage of 1 mg/kg LET. At the end of the treatment period, bone mineral density (BMD), the bone resorption marker serum pyridinoline, the bone formation marker serum osteocalcin, bone mechanical properties, histomorphometry, and serum lipid concentrations were determined. RESULTS: Lumbar vertebral and femoral BMD, bending strength of the femur, compressive strength of the fifth lumbar vertebra, and trabecular bone volume were significantly higher in OVX animals given EXE and 17-H-EXE than in OVX controls. EXE and 17-H-EXE significantly reduced an ovariectomy-induced increase in serum pyridinoline and serum osteocalcin. EXE and 17-H-EXE given to OVX rats caused significant reductions of serum cholesterol and low-density lipoprotein cholesterol. In contrast, OVX rats treated with LET had BMD, bone biomarkers, mechanical failure properties, and lipid levels similar to those of OVX controls. CONCLUSIONS: EXE and 17-H-EXE significantly prevent bone loss, enhance bone mechanical strength, and lower serum cholesterol and low-density lipoprotein levels in OVX rats. These protective effects on end-organ function are not seen with the nonsteroidal inhibitor LET.

Entrez PubMed

The steroidal aromatase inhibitor exemestane prevents bone loss in ovariectomized rats.

Goss PE, Qi S, Josse RG, Pritzker KP, Mendes M, Hu H, Waldman SD, Grynpas MD.

Department of Medical Oncology, Princess Margaret Hospital, Toronto, Ontario, Canada M5G 2M9. [email protected]

The irreversible steroidal aromatase inhibitor exemestane (EXE) is one of three third generation aromatase inhibitors currently prescribed for advanced breast cancer in postmenopausal women. Its principal mechanism of action is to reduce estrogen by inhibiting its synthesis. In addition to its efficacy against breast cancer, its effects on other organs are important, especially when given to women with good-prognosis breast cancer or potentially to healthy women at increased risk of developing breast cancer. The purpose of this study was to evaluate the effects of EXE on bone and lipid metabolism in ovariectomized (OVX) rats. Ten-month-old Sprague-Dawley female rats were sorted into intact controls, intact + EXE, OVX controls, and OVX + EXE groups, and treated by weekly intramuscular injection with vehicle or 100 mg/kg EXE for 16 weeks. The bone mineral density (BMD), mechanical testing, histomorphometry, bone resorption marker-serum pyridinoline (PYD), and bone formation marker-serum osteocalcin (OC) were used to determine the effects of treatment on bone. In addition, total serum cholesterol, triglyceride, high-density lipoprotein (HDL), and low-density lipoprotein (LDL) were determined. BMD of the lumbar spine and femur were 11% and 7%, respectively, higher in OVX animals given EXE than in OVX controls (all Ps<0.001). Significant increases in the bending strength and toughness of the femora as well as the compressive strength and elastic modulus of the vertebrae were observed in OVX rats given EXE (all Ps<0.02 vs. OVX controls). Trabecular bone volume (BV) was significantly higher in OVX rats treated with EXE than in OVX controls (P<0.0001). In OVX animals, EXE reduced the OVX-induced increase of serum PYD by 96% (P<0.0001), and the OVX-induced increase of serum OC was completely prevented by treatment with EXE. In OVX animals, EXE resulted in a 28% reduction of serum cholesterol (P<0.0001) and reduced LDL by 64% compared with OVX controls (P<0.0001). The positive results of EXE on bone and lipid metabolism in the OVX rat model merit further investigation of the effects of EXE in postmenopausal women.

Entrez PubMed

 

[Ichidan]

Great Stuff!

 

[natiels]

Whilst you are correct that type II AI's (letro and adex) will hurt lipids, the studies I have seen suggest that type I AI's (specifically exemestane, although probably also ATD due to their structural similarity) actually have a positive effect upon lipids;

Yep. 6oxo has been shown to improve lipids in short runs. From what I recall when Rebound XT (ATD) first came out DS was saying steroidal AIs like RXT improve lipids.