|Aromatase inhibitors for steroids||Percentage change from baseline in bone-turnover markers and lipid profiles and percentage of baseline estrogen concentrations were also summarized by assessment time and treatment arm using descriptive statistics. A mixture of ethanol and water is used for the recrystallization process. Three basic study designs have been used in the current phase III studies of an aromatase inhibitor vs tamoxifen in the adjuvant setting. ISSN Aromatase inhibitors are candidates for future preventive agents. This study aimed to identify new biomarker s for aromatase inhibitor detection in sports using statistical analysis and adapt the model into ABP analysis. TT and JB-B have no competing interests.|
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|Steroids used for weight loss||What are the symptoms of high estrogen levels in men? Compared to the ABP biomarkers, these 3 new biomarkers take estrogen into account simultaneously, which makes the trend easier to be aromatase inhibitors for steroids. In addition, it converts the adrenally generated androstenedione into estrone and testosterone into estradiol in peripheral tissues, as well as in tumors. In the adjuvant setting, a recent Austrian study comparing tamoxifen with tamoxifen plus aminoglutethimide in 2, patients also failed to demonstrate any advantage to the combination regimen. Interestingly, some new biomarkers for ABP evaluation were obtained due to the effects of exogenous substances on various metabolic pathways.|
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|Aromatase inhibitors for steroids||The new ratio biomarkers fluctuated but not exceeding the reference limits in the remaining 3 female volunteers Appendix 3. Search all BMC articles Search. In our study, aromatase inhibitors for steroids data gathered by the AUC analysis demonstrate that exemestane might have a greater effect on bone formation compared with the nonsteroidal AIs, particularly PINP levels. The Oncologist. Arimidex may also be used illegally by bodybuilders to reduce side effects caused by high estrogen levels that occur from the aromatization of anabolic steroids. Subjects were evaluated at baseline and 2, 4, 8, innovagen steroids review, 16, 20, 24, and 36 follow-up weeks.|
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Baseline concentrations of lipids in the mITT population were similar among treatment groups Table 2. Overall, the percentage changes from baseline to week 12, 24, or 36 in all the lipid parameters monitored were similar between groups Table 5. Treatment-emergent adverse events were reported by 62 Most adverse events were mild to moderate in severity. Five subjects experienced serious adverse events two exemestane-, one anastrozole-, and two placebo-treated subjects , none of which were considered related to the study medication.
Two subjects one anastrozole- and one placebo-treated subject discontinued treatment owing to adverse events, neither of which was considered to be treatment related. The incidence of adverse events probably owing to estrogen reduction was comparable between treatment groups. The incidence of laboratory toxicities was comparable between active-treatment groups and the placebo group.
Most of the laboratory abnormalities were grade 1 mild , and none were considered an adverse event or clinically significant by the investigator. In postmenopausal women with early breast cancer, AIs offer significant benefit over standard treatment with tamoxifen for 5 years in terms of disease-free survival and, for anastrozole and exemestane, reduced contralateral breast cancer and time to recurrence [ 20 — 25 ].
Despite these encouraging results, the long-term clinical impact of AIs must be established because the aromatase enzyme has an important role in numerous normal physiological processes [ 26 ]. A key role of aromatase is local production of estrogens, which are essential for the maintenance of bone integrity [ 27 ].
There are, therefore, two important questions that must be addressed, as follows: will AIs accelerate the negative skeletal balance associated with the menopause; and if so, to what extent? Although several relatively short-term clinical studies suggest that AIs accelerate bone loss [ 2 , 4 — 6 , 8 ], to date there have been no comparative clinical studies.
Because preclinical data suggest that the steroidal AI exemestane might have different effects on bone compared with the nonsteroidal AIs [ 28 ], this study was designed to assess the effects of the different AIs by evaluating changes in bone biomarkers after short-term treatment 24 weeks.
This short-term study demonstrates differential effects of the AIs evaluated on bone-turnover markers. For the primary end point of the effect on markers of bone turnover at 24 weeks, markers of bone resorption were increased in all treatment groups, including placebo, but the magnitude of increase was noticeably lower for anastrozole compared with the other groups.
A retrospective statistical comparison of the changes in PINP levels showed a statistically greater increase for exemestane treatment compared with the other AIs or placebo at week 24, but this statistical comparison must be interpreted in light of its retrospective nature and the potential lack of sufficient power of this small study.
Following discontinuation of treatment at 24 weeks, the levels of markers of bone resorption S-CTx and U-CTx remained elevated or continued to increase from baseline to week 36 in patients receiving letrozole, anastrozole, or placebo; by contrast, the levels of markers of bone resorption tended to decline towards baseline at week 36 following discontinuation of exemestane at week The effect of exemestane withdrawal for 3 and 6 months has been studied in postmenopausal women following 2 years' treatment [ 29 ].
After exemestane withdrawal, bone-resorption markers returned to, or below, baseline values within 6 months, with the exception of the S-CTx concentration. For markers of bone formation for example, BAP, PINP, and osteocalcin , a successive decrease in values at 3 and 6 months after terminating therapy was recorded; however, the levels of all markers of bone formation remained elevated at 6 months compared with the baseline value. The results of the current study, described after 12 weeks of exemestane withdrawal, are consistent with these observations.
These findings could be further assessed by correlating BMD measurements and fracture data to changes in bone biomarkers in a large confirmatory trial. The primary benefit of the use of biochemical markers is their ability to reflect small changes in bone formation or resorption before such changes are detectable radiologically [ 30 ].
Although bone-turnover data are typically reported at discrete time points, we suggest that assessing data over time using the AUC method might be more illustrative of the true impact of interventions. This technique avoids the oversimplification associated with reporting a value at a single point in time, which might lead to incorrect inferences. Instead, the AUC provides a view of the whole spectrum of values because results are depicted over time [ 19 , 30 , 31 ].
In our study, the data gathered by the AUC analysis demonstrate that exemestane might have a greater effect on bone formation compared with the nonsteroidal AIs, particularly PINP levels. By contrast, letrozole, the more potent of the two nonsteroidal agents [ 32 , 33 ], demonstrated the greatest impact on bone resorption, which continued to be significantly elevated 3 months after discontinuation of treatment.
Thus, this short-term study suggests there are differences between steroidal and nonsteroidal AIs; however, the results from this exploratory, short-term study must be replicated by a larger controlled trial of longer duration. The basis for the hypothesized difference in the effects of nonsteroidal AIs and the steroidal aromatase inactivator exemestane is the steroidal structure of exemestane and the androgenic activity of its primary metabolite, hydroexemestane [ 18 ].
Both androgens and estrogens have a role in skeletal development and maintenance in women [ 27 ]. However, estrogens reduce bone resorption, whereas androgens stimulate bone formation and are thought to be effective in reducing fracture risk [ 34 ]. In fact, regardless of estrogen status, perimenopausal women with higher androgen concentrations have a slower rate of bone loss compared with women who have lower concentrations [ 35 ], and administration of low doses of oral androgen in combination with estrogen results in higher concentrations of bone-formation markers than treatment with estrogen alone in postmenopausal women [ 36 ].
On the basis of its pharmacologic characteristics, these findings support the hypothesis that exemestane might have differential effects on bone compared with nonsteroidal AIs. When the bone-marker data were analyzed for the mITT population data not shown , the results were similar to those observed in the evaluable population. The mITT population included all subjects who received at least one dose of study medication and had baseline and week 12 assessments at least.
Therefore, unlike the evaluable population, the mITT population included the five patients who did not demonstrate estrogen suppression following treatment with an AI. Because third-generation AIs provide consistent suppression of estrogen synthesis in postmenopausal women, it is our impression that these five subjects had poor or inconsistent compliance and were, therefore, not evaluable for the purpose of our study because our analysis was designed to demonstrate the potentially unique response of bone biomarkers to AIs in the presence of effective suppression of estrogens.
We did not report the BMD or fracture rate because of the relatively short duration of our study. BMD is directly related to fracture risk and, therefore, often used to diagnose osteoporosis. However, the BMD must be monitored for several years, not months, to be useful for determination of fracture risk, and changes in BMD do not correlate linearly to fracture risk reduction.
Moreover, BMD is only one factor contributing to bone strength and fracture risk. Bone strength is determined by bone quantity that is to say, density and size and bone quality that is to say, microarchitecture and macroarchitecture, material properties, and turnover [ 37 ].
In mechanical terms, the load-bearing capacity or quality of bone is determined by ultimate force strength , resilience, stiffness, and toughness, and the overall quality of bone is affected by the rate of bone turnover [ 38 ].
Although BMD is considered a good diagnostic tool for identifying osteoporosis in untreated patients, emerging data suggest that biochemical markers of bone turnover might also be accurate predictors of treatment-induced bone changes [ 37 , 38 ]. Ultimately, adverse effects on bone metabolism are among the most serious concerns when considering the long-term use of AIs in postmenopausal women. Although measures such as exercise, calcium and vitamin D supplementation, and bisphosphonate administration are being used to alleviate this risk, a finding that exemestane might be superior to other third-generation AIs, in terms of its effects on bone metabolism, could have clinical significance.
For this reason, two large ongoing trials are of particular interest: the CAN-NCIC-MA27 study and its companion study, evaluating BMD in postmenopausal women who have primary breast cancer that is treated using exemestane or anastrozole, and the Femara Anastrozole Clinical Evaluation study, a comparison of letrozole with anastrozole in the treatment of postmenopausal women with hormone-receptor-positive and node-positive breast cancer.
These studies should help determine the relative differences in the risk of bone loss with long-term use of the different AIs. Our data support the hypothesis that a mild androgenic effect on bone can be exerted by the steroidal AI exemestane.
Our study shows a qualitative difference in the concentration of the bone-formation marker PINP in a short-term, week treatment period, but it involved a small number of women and these findings need confirmation by a larger trial. It is also important to note that all AIs are associated with bone loss, and only long-term comparative clinical studies monitoring fracture outcome will determine the relative effects of the different AIs on fracture risk.
Changes in the levels of bone-resorption markers are more sensitive in predicting subsequent fracture risk than changes in the levels of bone-formation markers, thus limiting the interpretation of our short-term findings [ 39 ]. However, because androgens affect bone quality and quantity [ 40 , 41 ], the use of surrogate markers, such as BMD, to assess bone effects of AIs might not provide a clear indication of comparative fracture risk.
Bone-quality studies using bone biopsies and histomorphometry might prove valuable for assessing the early effects of exemestane on bone quality. In recent years, use of the third-generation AIs anastrozole, letrozole, and exemestane has resulted in improved clinical outcomes for postmenopausal patients with early breast cancer. However, because of their estrogen-lowering effect, AIs might increase the risk of osteoporosis and fractures in some patients.
Preclinical studies have suggested that exemestane a steroidal aromatase inactivator might have differential effects on bone compared with the nonsteroidal AIs anastrozole and letrozole. In our study, exemestane was the only AI that significantly increased serum levels of PINP, a marker of bone formation, at 24 weeks in healthy postmenopausal women.
These data need confirmation by a larger comparative trial. Whether these observations correlate to a decreased relative risk of osteoporosis and fractures compared with nonsteroidal AIs in patients receiving long-term adjuvant treatment for early breast cancer requires further study. J Bone Miner Res. Ann Oncol. Google Scholar. Breast Cancer Res Treat. J Bone Miner Metab. Cancer Epidemiol Biomarkers Prev. J Clin Oncol. Clin Cancer Res.
Article PubMed Google Scholar. McCloskey E: Effects of third-generation aromatase inhibitors on bone. Eur J Cancer. CAS Google Scholar. Arimidex Tamoxifen Alone or in Combination Trialists' Group: Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early breast cancer: first results of the ATAC randomized trial. Obstet Gynecol. The ATAC Arimidex, Tamoxifen Alone or in Combination Trialists' Group: Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early-stage breast cancer.
Article Google Scholar. N Engl J Med. J Natl Cancer Inst. Goss PE: Risks versus benefits in the clinical application of aromatase inhibitors. Endocr Relat Cancer. Compston JE: Sex steroids and bone. Physiol Rev. Clin Lab. Clin Chem. J Steroid Biochem Mol Biol. J Clin Endocrinol Metab. A prospective study of pre-, peri-, and postmenopausal women.
J Clin Invest. Cefalu CA: Is bone mineral density predictive of fracture risk reduction?. Curr Med Res Opin. Felsenberg D, Boonen S: The bone quality framework: determinants of bone strength and their interrelationships, and implications for osteoporosis management. Clin Ther. J Br Menopause Soc. Notelovitz M: Androgen effects on bone and muscle. Fertil Steril. Mayo Clin Proc. Download references. This study was sponsored by Pharmacia, Inc.
Pfizer Inc. You can also search for this author in PubMed Google Scholar. Correspondence to Paul E Goss. TT and JB-B have no competing interests. The article processing charge assessed by the journal was paid by Pfizer Inc. PEG conceived of the study, participated in its design, and helped to draft the manuscript. PH participated in the design of the study. PA conducted the statistical analysis. MS and PA participated in data analysis, data interpretation, and drafting of the manuscript.
TT and JB-B were the principal investigators responsible for all clinical aspects of this study. All authors read and approved the final manuscript. Reprints and Permissions. Goss, P. Effects of steroidal and nonsteroidal aromatase inhibitors on markers of bone turnover in healthy postmenopausal women. Breast Cancer Res 9, R52 Download citation.
Received : 21 December Revised : 13 July Accepted : 10 August Published : 10 August Skip to main content. Search all BMC articles Search. Download PDF. Abstract Introduction In contrast to nonsteroidal aromatase inhibitors, the steroidal aromatase inactivator exemestane does not have detrimental effects on bone in animal models.
Methods Changes in the concentrations of bone-turnover markers, estrogens, and lipids were assessed after daily administration of exemestane 25 mg , letrozole 2. Conclusion Exemestane increased serum levels of the bone-formation marker PINP after 24 weeks, suggesting a specific bone-formation effect related to its androgenic structure.
Introduction Aromatase inhibitors AIs , which potently suppress estrogen synthesis in postmenopausal women, are increasingly used in the treatment of early-stage breast cancer to prevent disease recurrence. Materials and methods This randomized, single-blind, placebo-controlled exploratory study investigated the effect of low plasma estrogen levels, induced by AIs, on markers of bone turnover in 80 healthy postmenopausal women during 24 weeks of outpatient treatment using exemestane, letrozole, anastrozole, or placebo.
Patient selection and treatment Healthy postmenopausal volunteers between 50 and 75 years of age were enrolled. Ask your doctor which type of non-hormonal birth control would be best for you, as well as how long you should use this type of birth control after you stop taking an aromatase inhibitor. A number of studies have compared aromatase inhibitors with tamoxifen to see which type of medicine was more effective in treating early-stage, hormone-receptor-positive breast cancer in postmenopausal women.
Based on the results, most doctors recommend that after initial treatment surgery and possibly chemotherapy and radiation therapy :. Aromatase inhibitors tend to cause fewer serious side effects than tamoxifen, such as blood clots, stroke, and endometrial cancer. But aromatase inhibitors can cause more heart problems , more bone loss osteoporosis , and more broken bones than tamoxifen, at least for the first few years of treatment.
If you and your doctor are considering an aromatase inhibitor as part of your treatment plan, you may want to ask your doctor about having a bone density test to see if a bone strengthening medicine might be necessary while you're taking the aromatase inhibitor. The most common side effects of aromatase inhibitors are joint stiffness or joint pain. If you're experiencing side effects from taking one aromatase inhibitor medicine, tell your doctor.
You may be able to take a different medicine. Arimidex and Femara have similar chemical structures, while Aromasin has a different structure. Ashish Khanna, M. Create a profile for better recommendations. Breast implant illness BII is a term that some women and doctors use to refer to a wide range Sign up for emails about breast cancer news, virtual events, and more. Subscribe to our podcast for conversations on the issues that matter most.
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