[h=1]Steroid Corner - Side Effects of Aromatase Inhibitors[/h][h=1][/h]Most bodybuilders who use anabolic-androgenic steroids (AAS) have used an aromatase inhibitor to prevent the otherwise inevitable estrogen excess that accompanies the use of supraphysiologic dosing of testosterone and other aromatizable AAS. Aromatase is an enzyme complex that converts androgens (such as AAS) into estrogens— female sex steroid hormones. The classic example is testosterone converting into estradiol. Many AAS convert into estrogenic metabolites. Those that are based on DHT, the 5-alpha-reduced form of testosterone, are protected from aromatization, as are those with certain other chemical modifications. Examples of AAS that do not aromatize include stanozolol, oxandrolone and nandrolone. Nandrolone can convert into estradiol, but through a separate enzyme pathway, and this happens to a much lesser degree.
If a cycle includes aromatizable AAS used in anabolic doses, and an aromatase inhibitor is not used, then estrogenic side effects can arise, including gynecomastia (“bitch tits”), mood disorders, etc. Clinical research has looked into the use of aromatase inhibitors as an option to testosterone replacement in older men, and to delay bone closure in adolescent boys who are short, to allow them to gain more height. Despite being used to treat or prevent a side effect, the use of aromatase inhibitors can precipitate adverse events of their own. Joint pain, osteoporosis and decreased libido have all been reported.
However, another adverse effect of aromatase inhibitors recently reported is worth considering, if the purpose of its use is to improve body composition or metabolic health.
Aromatase deficiency has been linked to increased insulin resistance, which is a precursor to type 2 diabetes. Animal studies have shown that an absence of aromatase in male rats increases insulin resistance as well as body fat, and “fatty liver” develops. These same effects are seen in men with the rare genetic absence of aromatase. When young, healthy men were given an aromatase inhibitor, they developed slightly increased body fat, particularly within the waist (i.e., intra-abdominal fat). This type of fat is associated with the development of metabolic syndrome, which includes insulin resistance.
A recently published paper looked at the effect of one milligram daily administration of anastrozole (aka Arimidex), compared to a placebo, each provided to all subjects for a period of six weeks per treatment.[SUP]1[/SUP] Rather than using the more convenient but less sensitive calculation of insulin sensitivity based upon fasting levels of glucose (blood sugar) and insulin, this study utilized a hyperinsulinemic euglycemic clamp, which means they administered insulin in excess and noted how much glucose needed to be given through an IV to maintain a normal blood glucose level. It is a very direct way of measuring what actually happens in response to insulin. In addition to watching how fast glucose was shuttled into tissues (primarily skeletal muscle), they also analyzed the production of glucose by the liver and stored fat release. The liver produces “new sugar” and fat cells release free fatty acids during periods of fasting, and these processes are turned off in people with good insulin sensitivity. Those with insulin resistance or type 2 diabetes do not shut down these processes as quickly or as completely. It is the inappropriately high blood sugar and free fatty acids that cause much of the pathology of type 2 diabetes, and promote further insulin resistance.
During the treatment with anastrozole, the expected changes were noted of an increase in LH (31.4%) and testosterone (20.5%), with a corresponding decrease in estradiol (41.3%). Body mass, composition (body fat percentage) and fasting levels of glucose, as well as glycerol (part of stored fat used to measure stored fat release) were not changed. However, it was noted that low concentrations of insulin were less effective at shuttling blood glucose into skeletal muscle and other insulin-sensitive tissue. When insulin concentration was higher, the response was no different between the groups. Another important finding was that leptin was decreased by 28 percent, despite no net loss of body fat. At first glance, this would be negative— as leptin induces satiety (fullness after eating) and increases calorie burning. When viewed with earlier findings that fat was “repartitioned” from the subcutaneous (under the skin) to intra-abdominal (including visceral fat), this may account for some of the insulin resistance seen with anastrozole, as well as the reduction in leptin, as this is preferentially made in subcutaneous fat. However, for those taking anastrozole for bodybuilding purposes, if diet and exercise were leading to overall fat loss and anastrozole shuttled fat away from the under the skin, this might enhance the physique appearance by making the skinfolds reduce even more.
The cautionary value of this study is primarily for men not using AAS who might be considering an aromatase inhibitor to boost testosterone. While studies with letrozole revealed more pronounced testosterone boosting, and improved insulin sensitivity using less accurate measures, this may be an effect of the greater rise in testosterone.[SUP]2,3[/SUP] Other aromatase inhibition studies have shown no effect on insulin sensitivity. Further, letrozole is more active inside the cells than anastrozole, so its effects on skeletal muscle or other tissue metabolism may have greater impact. Men are protected from the more deleterious changes seen in post-menopausal women, as this class of aromatase inhibitor is a competitive inhibitor. This means that if there is little testosterone (such as in older women), then the drug is able to beat out most testosterone from being converted into estradiol. If there is a greater, or even supraphysiologically HUGE amount of androgens, then the aromatase inhibitor has much less of an effect. It is like a deputy at a quiet, small-town bank, keeping people inside those velvet-roped lines, as compared to mall security guard holding back a ravaging hoard on Black Friday.
Thus, it appears that people with low testosterone may need to be wary of using aromatase inhibitors, due to a number of potential metabolic effects— unless they respond vigorously, as happened in the letrozole studies. For the AAS-using bodybuilder/athlete, aromatase inhibitors are often a necessary adjunct to combat aromatization of supraphysiologic concentrations of testosterone and other aromatizable AAS. This study should serve to reinforce the need to be supervised and monitored for potential harm when using this or any drug.
References:
1. Gibb FW, Horner NZM, et al. Aromatase inhibition reduces insulin sensitivity in healthy men. J Clin Endocr Metab. March 7, 2016. [Epub, ahead of print]
2. Lapauw B, T'Sjoen G, et al. Short-term aromatase inhibition: effects on glucose metabolism and serum leptin levels in young and elderly men. Eur J Endocrinol 2009;160:397-402.
[FONT="]3. Lapauw B, Ouwens M, et al. Sex steroids affect triglyceride handling, glucose-dependent insulinotropic polypeptide, and insulin sensitivity: a 1-week randomized clinical trial in healthy young men. Diabetes Care 2010;33:1831-3.[/FONT]
If a cycle includes aromatizable AAS used in anabolic doses, and an aromatase inhibitor is not used, then estrogenic side effects can arise, including gynecomastia (“bitch tits”), mood disorders, etc. Clinical research has looked into the use of aromatase inhibitors as an option to testosterone replacement in older men, and to delay bone closure in adolescent boys who are short, to allow them to gain more height. Despite being used to treat or prevent a side effect, the use of aromatase inhibitors can precipitate adverse events of their own. Joint pain, osteoporosis and decreased libido have all been reported.
However, another adverse effect of aromatase inhibitors recently reported is worth considering, if the purpose of its use is to improve body composition or metabolic health.
Aromatase deficiency has been linked to increased insulin resistance, which is a precursor to type 2 diabetes. Animal studies have shown that an absence of aromatase in male rats increases insulin resistance as well as body fat, and “fatty liver” develops. These same effects are seen in men with the rare genetic absence of aromatase. When young, healthy men were given an aromatase inhibitor, they developed slightly increased body fat, particularly within the waist (i.e., intra-abdominal fat). This type of fat is associated with the development of metabolic syndrome, which includes insulin resistance.
A recently published paper looked at the effect of one milligram daily administration of anastrozole (aka Arimidex), compared to a placebo, each provided to all subjects for a period of six weeks per treatment.[SUP]1[/SUP] Rather than using the more convenient but less sensitive calculation of insulin sensitivity based upon fasting levels of glucose (blood sugar) and insulin, this study utilized a hyperinsulinemic euglycemic clamp, which means they administered insulin in excess and noted how much glucose needed to be given through an IV to maintain a normal blood glucose level. It is a very direct way of measuring what actually happens in response to insulin. In addition to watching how fast glucose was shuttled into tissues (primarily skeletal muscle), they also analyzed the production of glucose by the liver and stored fat release. The liver produces “new sugar” and fat cells release free fatty acids during periods of fasting, and these processes are turned off in people with good insulin sensitivity. Those with insulin resistance or type 2 diabetes do not shut down these processes as quickly or as completely. It is the inappropriately high blood sugar and free fatty acids that cause much of the pathology of type 2 diabetes, and promote further insulin resistance.
During the treatment with anastrozole, the expected changes were noted of an increase in LH (31.4%) and testosterone (20.5%), with a corresponding decrease in estradiol (41.3%). Body mass, composition (body fat percentage) and fasting levels of glucose, as well as glycerol (part of stored fat used to measure stored fat release) were not changed. However, it was noted that low concentrations of insulin were less effective at shuttling blood glucose into skeletal muscle and other insulin-sensitive tissue. When insulin concentration was higher, the response was no different between the groups. Another important finding was that leptin was decreased by 28 percent, despite no net loss of body fat. At first glance, this would be negative— as leptin induces satiety (fullness after eating) and increases calorie burning. When viewed with earlier findings that fat was “repartitioned” from the subcutaneous (under the skin) to intra-abdominal (including visceral fat), this may account for some of the insulin resistance seen with anastrozole, as well as the reduction in leptin, as this is preferentially made in subcutaneous fat. However, for those taking anastrozole for bodybuilding purposes, if diet and exercise were leading to overall fat loss and anastrozole shuttled fat away from the under the skin, this might enhance the physique appearance by making the skinfolds reduce even more.
The cautionary value of this study is primarily for men not using AAS who might be considering an aromatase inhibitor to boost testosterone. While studies with letrozole revealed more pronounced testosterone boosting, and improved insulin sensitivity using less accurate measures, this may be an effect of the greater rise in testosterone.[SUP]2,3[/SUP] Other aromatase inhibition studies have shown no effect on insulin sensitivity. Further, letrozole is more active inside the cells than anastrozole, so its effects on skeletal muscle or other tissue metabolism may have greater impact. Men are protected from the more deleterious changes seen in post-menopausal women, as this class of aromatase inhibitor is a competitive inhibitor. This means that if there is little testosterone (such as in older women), then the drug is able to beat out most testosterone from being converted into estradiol. If there is a greater, or even supraphysiologically HUGE amount of androgens, then the aromatase inhibitor has much less of an effect. It is like a deputy at a quiet, small-town bank, keeping people inside those velvet-roped lines, as compared to mall security guard holding back a ravaging hoard on Black Friday.
Thus, it appears that people with low testosterone may need to be wary of using aromatase inhibitors, due to a number of potential metabolic effects— unless they respond vigorously, as happened in the letrozole studies. For the AAS-using bodybuilder/athlete, aromatase inhibitors are often a necessary adjunct to combat aromatization of supraphysiologic concentrations of testosterone and other aromatizable AAS. This study should serve to reinforce the need to be supervised and monitored for potential harm when using this or any drug.
References:
1. Gibb FW, Horner NZM, et al. Aromatase inhibition reduces insulin sensitivity in healthy men. J Clin Endocr Metab. March 7, 2016. [Epub, ahead of print]
2. Lapauw B, T'Sjoen G, et al. Short-term aromatase inhibition: effects on glucose metabolism and serum leptin levels in young and elderly men. Eur J Endocrinol 2009;160:397-402.
[FONT="]3. Lapauw B, Ouwens M, et al. Sex steroids affect triglyceride handling, glucose-dependent insulinotropic polypeptide, and insulin sensitivity: a 1-week randomized clinical trial in healthy young men. Diabetes Care 2010;33:1831-3.[/FONT]
