Just throwing in my 2 cents. If anyone cares. There is definitely a lack of evidence to support the need for an AI on TRT. I for one also feel better without an AI while at a TRT dose, and I think @dbossa is correct regarding AI and TRT. Things get a little hairier when increasing exogenous testosterone above a TRT dose. There is just not enough research to say one way or the other. Anecdotally, when I increase my testosterone beyond TRT doses, I certainly need an AI or I get all sorts of estrogen related problems. There are so many guys on here on “TRT” but they’re really dosing way too high, putting free T and total T well above range. I expect those guys are the ones experiencing high E2 symptoms and “need” an AI.
Right now, there is some evidence that shows high E2 in older men increases mortality, however this was not a study evaluating testosterone to estrogen ratio, and not even on men on TRT. A long term study would need to be done to on TRT patients to see if this holds true for men with high levels of testosterone as well as estrogen.
Here is a well written explanation on the need (or not) for a AI.
https://journals.sagepub.com/doi/pdf/10.1177/1557988314539000
### Do We Need to Treat High E2 After TRT? Anastrozole
This study was not designed specifically to answer this question. A prospective, randomized controlled study would be needed over several years to understand if indeed high E2 after TRT may be beneficial or harmful. Currently, there are no national guidelines that are evidence based for treatment of high E2 after TRT. However, there was a high treatment rate for our group of patients at 30%. Based on interviews with select practitioners, we found that the reasons for the high rates of prescribing AI and SERM are partly patient pressure, practitioner confusion, and fear of the harmful effects of high E2 in long term. Some studies have indicated an association of high estrogens to higher rates of heart attacks, strokes, and prostate cancer (Basaria et al., 2013; Kristal et al., 2012; Lerchbaum et al., 2011). In one such study, higher estradiol levels in men were significantly associated with prevalent strokes, peripheral vascular disease, and carotid artery stenosis compared to lower estradiol levels. High levels of estradiol were also associated with all-cause and noncardiovascular mortality in a large cohort of older men referred to coronary angiography (Lerchbaum et al., 2011). These studies of association do not infer causality and as such should not be used for the basis for treatment of high estrogen. AI and SERM use may be justified for breast tenderness or gynecomastia. However, gynecomastia is rarely documented in problem list; this is an area of improvement for the practice.
In our study, high estradiol levels did not correlate with higher rates of low libido. On the other hand, low levels of E2 were associated with higher rates of low libido. The explanation could be that low E2 usually results from low testosterone levels, as E2 is aromatized from testosterone. Our study results parallel that of others (Finkelstein et al., 2013) suggesting a positive role of estradiol in human male libido functioning. There are limitations to our present study and we do declare that our results cannot be generalized. This is based on our methodology of assigning low libido as captured in the problem list. Providers may have not uniformly entered the ICD-9 diagnoses, and hence it may be possible that results may be overstated. The other limitation is that although 34,016 patients who presented to the Centers were screened, only 50% were eligible for treatment, based on inclusion and exclusion factors. The analysis was done on patients who presented to the Centers and were screened and not limited to those on treatment. The correlation of libido is definitely an area for further study.
The effects of estradiol on the human brain are unclear. Currently, there are no hormone markers within the brain to determine the association of levels of sex hormones with libido. In this study a presumption was made that serum estradiol reflects brain estradiol levels or activity. It may be possible that if serum estradiol level is low more estradiol is available for the brain, as it is shifted from the rest of the body to the brain. This hypothesis is given to support the results of our study, of not associating low libido to higher estradiol levels. In a previous study, positive emission tomography was used in an attempt to map areas of the brain involved in glucose metabolism after administration of testosterone. The brain stem and parietal lobes were highly metabolic, suggesting that these areas are involved in sexual processing (Tan, 2013). There are current arguments for an optimal T:E2 ratio for sexuality (Shabsigh et al., 2005), rather than the actual amounts, but studies are weakly powered.
