Do Sub-Q Testosterone Injections Cause High Estrogen? – T NATION+ – COMMUNITY

In a 52-week study of 150 men who qualified for TRT, subjects self-administered either 50, 75, or 100 mg of testosterone enanthate weekly via sub-Q auto-injection (1). This was after a 6-week period where all subjects received 75 mg per week, after which the dose was titrated up or down. After 12 weeks, blood was drawn and analyzed at various times after the last injection.

Interestingly, average estrogen concentrations were 46.3 pg/ml, while the peak plasma concentration was 64.2 pg/ml. The authors also reported an estrogen-to-total testosterone ratio of 0.93%. Confusingly, they didn’t bother to report these data by dose, so it’s unclear what dose these values reflect. The reference range for estrogen was 10-50 pg/ml.

A 100 mg dose of testosterone enanthate given sub-Q produced testosterone concentrations greater than 50% of those seen with 200 mg of testosterone enanthate given IM. But the estrogen concentrations were essentially the same, reflecting a skewed conversion to estrogen.

In a 6-week study of 39 men, subjects self-administered either 50 or 100 mg of testosterone enanthate weekly via sub-Q or a 200 mg dose of testosterone enanthate IM (2). Blood was again drawn after 6 weeks and evaluated. Here, the average estrogen levels were 25.6, 48.3, and 50.0 pg/ml, respectively. The ratio for estrogen to total testosterone was 0.0063, 0.0055. and 0.0032, respectively.

Once again, these data demonstrate a skewed conversion of testosterone to estrogen. The estrogen to total testosterone ratio for sub-Q administration was nearly twice that of IM.

In a 26-week study of 133 men, a subgroup of subjects self-administered 75 mg of testosterone enanthate weekly via sub-Q (3). Blood was drawn after 1, 6, and 12 weeks. Again, once steady-state estrogen levels are reached around week 6, these values are, on average, beyond the reference range of 10-50 pg/ml.

It’s difficult to say why sub-Q administration leads to greater estrogen levels than the IM route. However, we can rule out the notion that higher total amounts of testosterone are available because the area under the curve (AUC) values for total T are fairly linear between the two routes, confirming they have similar bioavailability (2).

It’s also unlikely that the higher dose of IM testosterone (comparing a 100 mg dose sub-Q vs. a 200 mg dose IM) results in saturation of the aromatase enzyme (4).

Adipose tissue (fat) is a major site of aromatase activity in men, especially considering its relative activity compared to muscle (almost two-fold greater). So this is probably the main factor. (5).

This also fits with the data demonstrating that sub-Q administration produces an estrogen-to-total testosterone ratio around two-fold greater compared to IM. While skeletal muscle occupies a greater amount of body mass compared to fat, we’re only concerned with its relative activity because this is a localized administration.

Some limited evidence suggests that exogenous testosterone administration may increase aromatase expression in adipose tissue (6). However, the enzyme wouldn’t be saturated, leaving aromatase available to continue binding to and catalyzing the formation of testosterone to estrogen. Even if aromatase expression were increased, if more substrate (testosterone) isn’t available, this shouldn’t make any difference.

If your estrogen levels are regularly monitored as part of your TRT blood work and are in the normal range, there’s no need to change anything. While relative estrogen levels do appear higher, there was substantial variation with some individuals going over the normal reference range in these studies. Others were well below it.

If you’re just starting TRT and using sub-Q, check your estrogen levels once you’ve been using it for at least 6 weeks and see where they are. If they’re elevated well beyond the normal range, talk to your doc about adjusting the dose or using an alternative route of administration. Potentially, you might need a very low dose of an aromatase inhibitor. You may also want to consider free estrogen levels.

• Sub-Q testosterone administration can increase estrogen blood levels compared to IM.
• There is substantial variation: not all individuals will have values out of the normal reference range.
• The main factor contributing to this is likely the aromatase activity in fat compared to skeletal muscle.
• Have your estrogen (estradiol or E2) levels checked after using sub-Q administration for at least 6 weeks.
• If estrogen is too high, talk to your physician about switching routes, dose, or taking a very low dose of an aromatase inhibitor.
• If you feel fine and your estrogen levels are within the normal range or close to it, there’s no need to change anything unless your doc feels differently.

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