Throughout this profile, it has been clearly stated that the use of Arimidex (or any Aromatase Inhibitor) must be for the purpose of controlling estrogen, not eliminating it.
A reduction of estrogen in the body can cause negative changes and problems for the body, especially when estrogen is suppressed for extended periods using Aromatase Inhibitors.
Arimidex side effects are generally manageable and manifest mostly very differently in males than in females, as it has been previously demonstrated in this profile that females are more significantly affected due to their different endocrine physiology.
Side Effects Related to Estrogen Reduction
Almost all Arimidex side effects are a result of the reduction in total circulating estrogen levels in the body due to the inhibition of the aromatase enzyme.
The following are the main potential Arimidex side effects related to estrogen reduction.
Joint and Bone Pain
The use of Arimidex in postmenopausal breast cancer patients has been proven to increase the incidence of fractures[1].
However, this has been found to be attributable mostly to the fact that women generally respond more sensitively to the estrogen level reduction from Arimidex and the fact that this is generally a result of long-term Arimidex use.
In fact, estrogen is a crucial hormone in promoting and maintaining bone mineral content, thereby promoting bone strength.
This is why postmenopausal women are more likely to develop osteoporosis as they age, as their estrogen levels naturally decline.
In males, one study indicated that aromatase inhibition with Arimidex did not negatively affect kinetically measured bone calcium turnover or indirect indices of bone calcium turnover, at least in the short term[2].
Although no extreme changes in bone strength are seen with short-term use, many male users have reported increased bone and joint pain as a result of Arimidex use, where estrogen drops significantly below normal physiological levels.
This bone and joint pain always subsides upon cessation of Arimidex use or upon adjusting the Arimidex dosage to allow estrogen levels to return to normal physiological levels.
Fatigue
Similar to the bone and joint pain issue for anabolic steroid users who lower their estrogen levels too much, another commonly reported Arimidex side effect is persistent fatigue, which is also a common problem.
This is a result of estrogen levels dropping too low, as mentioned earlier.
Estrogen is well-known to play an important role in the proper function of the Central Nervous System (CNS), and a reduction of estrogen below normal physiological levels via Aromatase Inhibitors can cause chronic fatigue, a symptom that can only be properly remedied by restoring circulating estrogen levels back to normal.
Negative Impact on Cholesterol
This is a side effect common to all Aromatase Inhibitors, or any substance that reduces total circulating estrogen levels in the body.
Arimidex side effects are no exception, and this is perhaps one of the most important side effects to understand.
This side effect is also the reason why this profile has emphasized controlling estrogen levels rather than eliminating them.
Estrogen is known to play a very important role in the liver in producing favorable cholesterol levels (increasing the good cholesterol, HDL, and decreasing the bad cholesterol, LDL).
When estrogen levels drop below normal physiological levels, a shift in cholesterol occurs, where the good cholesterol (HDL) decreases and the bad cholesterol (LDL) increases, leading to an increased risk of Cardiovascular Disease (CVD).
There is even research showing that the use of 300mg per week of Testosterone Enanthate for 20 weeks without an Aromatase Inhibitor resulted in a 13% reduction in HDL cholesterol, and when the Testosterone dose was increased to 600mg per week, the HDL cholesterol reduction progressed further to 21%[3].
Thus, the data investigated shows a very clear increase in estrogen via aromatization and hepatic metabolism, which actually helps offset the negative cholesterol changes resulting from the use of supraphysiological amounts of anabolic steroids.
This makes sense, considering that estrogen itself is known to positively impact cholesterol levels.
Therefore, the use of Aromatase Inhibitors and their impact on cholesterol profiles is something that every user considering the addition of an Aromatase Inhibitor during a cycle or for PCT must always remember.
It is advisable to use the minimum dose of an Aromatase Inhibitor during a cycle for the purpose of controlling estrogen, rather than total estrogen level elimination.
The idea in this case is to keep estrogen levels within a normal range so that they do not skyrocket due to aromatization, while also preventing them from dropping to near-zero as a result of full Aromatase Inhibitor use.
Estrogen Rebound: This is one of the very important Arimidex side effects to understand.
It is a side effect generally seen with both Arimidex and Letrozole (Femara).
The third primary Aromatase Inhibitor, Aromasin (Exemestane), does not exhibit estrogen rebound.
This is because Arimidex and Letrozole are known as non-suicidal Aromatase Inhibitors.
Aromasin (Exemestane) is a suicidal Aromatase Inhibitor.
Suicidal Aromatase Inhibitors (e.g., Aromasin), when they bind to and inhibit the aromatase enzyme, indicate that the inhibited enzyme binds to the aromatase permanently, rendering the enzyme inactive forever.
The body will eventually produce more aromatase enzyme, but the currently bound enzyme remains bound indefinitely, posing no risk of estrogen rebound.
However, non-suicidal Aromatase Inhibitors like Arimidex and Letrozole bind to the aromatase enzyme for a limited time only, until the Aromatase Inhibitor becomes unbound due to natural metabolism or competition with other substrates.
If a non-suicidal Aromatase Inhibitor is discontinued too abruptly, the circulating inhibited aromatase enzymes that are not metabolized in the body become free again and begin aromatizing androgens into estrogen at a rapid rate.
Therefore, it is advisable to taper off Arimidex administration slowly, or when discontinuing, to slowly reduce the dosage amount and/or frequency of administration.
Medical References
[1] “Switching of postmenopausal women with endocrine-responsive early breast cancer to anastrozole after 2 years’ adjuvant tamoxifen: combined results of ABCSG trial 8 and ARNO 95 trial”. Jakesz R, Jonat W, Gnant M, Mittlboeck M, Menzel C, Samonigg H, Seifert M, Gademann G, Kaufmann M, Wolfgang J (2005). Lancet 366 (9484): 455–62. doi:10.1016/S0140-6736(05)67059-6. PMID 16084253.
[2] Estrogen suppression in males: metabolic effects. Mauras N; O’Brien KO; Klein KO; Hayes V. J Clin Endocrinol Metab 2000 Jul;85(7):2370-7 (ISSN: 0021-972X)
[3] Testosterone dose-response relationships in healthy young men. Bhasin S, Woodhouse L. et al. Am J Physiol Endocrinol Metab 281:E1172-81, 2001
