Home Body Building Supplements Do Sub-Q Testosterone Injections Cause High Estrogen? – T NATION+ – COMMUNITY

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

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


TRT and Subcutaneous Administration

Injecting testosterone subcutaneously versus intramuscularly has its benefits, but it might also have drawbacks. Here’s what you need to know.


The popularity of subcutaneous or sub-Q injections for testosterone replacement therapy (TRT) is on the uptick. Instead of injecting into the muscle – intramuscular or IM – you inject into the fatty layer just under the skin, usually in the butt or belly.

Proponents of sub-Q injection believe this method gives you more bang for your buck. The late Dr. John Crisler said that 80 mg of sub-Q testosterone has the effect of 100 mg of testosterone administered intramuscularly, and it leads to more stable T levels. And, of course, with sub-Q, there’s no muscle scarring, smaller needles, and less pain.

However, a few papers examined estrogen (estradiol or E2) levels after sub-Q testosterone administration. They are clearly elevated when compared to the intramuscular route. In men, high estrogen levels are associated with low libido, erectile dysfunction, infertility, mood swings, and low energy.

Study 1

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.

Study 2

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.

Study 3

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.

Why Does This Happen?

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.

What Should You Do?

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.

Take-Home Points

  • 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.

The natural T booster:

Biotest

References

References

  1. Kaminetsky JC, McCullough A, Hwang K, Jaffe JS, Wang C, Swerdloff RS. A 52-Week Study of Dose Adjusted Subcutaneous Testosterone Enanthate in Oil Self-Administered via Disposable Auto-Injector. J Urol. 2019 Mar;201(3):587-594. doi: 10.1016/j.juro.2018.09.057. PMID: 30296416.
  2. Kaminetsky J, Jaffe JS, Swerdloff RS. Pharmacokinetic Profile of Subcutaneous Testosterone Enanthate Delivered via a Novel, Prefilled Single-Use Autoinjector: A Phase II Study. Sex Med. 2015 Sep 17;3(4):269-79. doi: 10.1002/sm2.80. PMID: 26797061; PMCID: PMC4721027.
  3. Gittelman M, Jaffe JS, Kaminetsky JC. Safety of a New Subcutaneous Testosterone Enanthate Auto-Injector: Results of a 26-Week Study. J Sex Med. 2019 Nov;16(11):1741-1748. doi: 10.1016/j.jsxm.2019.08.013. Epub 2019 Sep 21. PMID: 31551193.
  4. Lakshman KM, Kaplan B, Travison TG, Basaria S, Knapp PE, Singh AB, LaValley MP, Mazer NA, Bhasin S. The effects of injected testosterone dose and age on the conversion of testosterone to estradiol and dihydrotestosterone in young and older men. J Clin Endocrinol Metab. 2010 Aug;95(8):3955-64. doi: 10.1210/jc.2010-0102. Epub 2010 Jun 9. PMID: 20534765; PMCID: PMC2913038.
  5. Longcope C, Pratt JH, Sub-Qhneider SH, Fineberg SE. Aromatization of androgens by musub-Qle and adipose tissue in vivo. J Clin Endocrinol Metab. 1978 Jan;46(1):146-52. doi: 10.1210/jcem-46-1-146. PMID: 752017.
  6. Ghanim H, Dhindsa S, Abuaysheh S, Batra M, Kuhadiya ND, Makdissi A, Chaudhuri A, Dandona P. Diminished androgen and estrogen receptors and aromatase levels in hypogonadal diabetic men: reversal with testosterone. Eur J Endocrinol. 2018 Mar;178(3):277-283. doi: 10.1530/EJE-17-0673. Epub 2018 Jan 16. PMID: 29339527.
  7. Frederiksen H, Johannsen TH, Andersen SE, Albrethsen J, Landersoe SK, Petersen JH, Andersen AN, Vestergaard ET, Sub-Qhorring ME, Linneberg A, Main KM, Andersson AM, Juul A. Sex-specific Estrogen Levels and Reference Intervals from Infancy to Late Adulthood Determined by LC-MS/MS. J Clin Endocrinol Metab. 2020 Mar 1;105(3):754–68. doi: 10.1210/clinem/dgz196. PMID: 31720688; PMCID: PMC7007877.
  8. Stanczyk FZ, Clarke NJ. Measurement of estradiol–challenges ahead. J Clin Endocrinol Metab. 2014 Jan;99(1):56-8. doi: 10.1210/jc.2013-2905. Epub 2013 Dec 20. PMID: 24178793.

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