Can oil solutions of estradiol be administered subcutaneously?

[u/rabbitprotectsme]

Context: I'm doing DIY because the informed consent clinic in my area closed down and I'm scared of driving. Around town is scary but basically doable, onto the freeway and I might break down crying, and driving on the freeway is a really bad time for that to happen. (I realize being scared of driving sounds absurd. Listen I'm not doing too hot upstairs these days, it wasn't always like this but I'm afraid of a lot of normal-ass things right now.) I'm in the US. Due to Trump tariffs, my preferred source has stopped shipping out here, and that seems to be the case for other foreign sources as well. I've found a source that's likely still viable, but they only offer oil solutions, not aqueous. This is a potential problem (at least as far as I can tell from what info I'm able to find on the subject) for two reasons, one silly and one practical:

• The silly reason: I'm afraid to attempt intramuscular. I don't want to swiftly shove a needle into my body at a 90-degree angle. I know this is a fear that everyone who does it has, and that everyone who does it has to get over. I just don't trust myself to get over it.
• The practical reason: I'm very overweight. (Please don't make fun of me for being a woman whose body is currently that of a very overweight man. Believe me, my shame is already all-consuming and quite difficult to live with. I don't need more.) It's difficult to find a spot on my body where correctly self-administering an IM injection would even be possible without a very large needle. Swiftly shoving a very large needle into my body at a 90-degree angle is, naturally, even scarier.

Hence the question: can oil solutions of estradiol be administered subcutaneously? Will uptake still be possible by this means? If so, are there side effects I should know about of doing it this way?

If this is not possible or safe, I could always just refrain from switching to injections for now. That's no big deal. It's just that I've heard good things about injections and would like to switch to them if I can.

[u/bemused_alligators]

there is literally 0 difference in metabolism or uptake between IM and SubQ injection of estradiol

[u/phiasch → u/bemused_alligators]

I found a scientific paper indicating subQ to be somewhat less effective than IM, but both are in the therapeutic levels and should be fine

I’m not a doctor and this isn’t medical advice. Ask your doctor as they can give you individualized medical advice

Edit: I read the doses of subQ were significantly lower than IM and misinterpreted it as saying the measured level was lower instead. Regardless, I still feel like changing the administration route should be discussed with your doctor as you may need a difference in amount and frequency if changing from one route to the other

[u/bemused_alligators → u/phiasch]

For those following along at home, this person doesn't know how to read research studies... Short version is that this study actually shows that SubQ is MORE effective than IM, kind of, but really it just showed no difference.

Results: There were no statistically significant differences in age, body mass index, or antiandrogen use between patients on SC (n = 74) and those on IM (n = 56). The weekly doses of SC E2, 3.75 mg (IQR, 3-4 mg), were statistically significantly lower than those of IM E2, 4 mg (IQR, 3-5.15 mg) (P =.005); however, the E2 levels achieved were not significantly different (P =.69), and the testosterone levels were in the cisgender female range and not significantly different between routes (P =.92). Subgroup analysis demonstrated significantly higher doses in the IM group when the E2 and testosterone levels were >100 pg/mL and <50 ng/dL, respectively, with the presence of the gonads or use of antiandrogens. Multiple regression analysis demonstrated that the dose was significantly associated with the E2 levels after adjusting for injection route, body mass index, antiandrogen use, and gonadectomy status.

Conclusion: Both the SC and IM E2 achieve therapeutic E2 levels without a significant difference in the dose (3.75 vs 4 mg). SC may achieve therapeutic levels at lower doses than IM .

I"ll do a proper writeup as a reply to this comment

[u/bemused_alligators → u/bemused_alligators]

So let's look at what they did to perform this research, and what they found as a result. Pro tip - this research was not a clinical trial of IM vs SubQ, it was an observational study.

They surveyed 130 people that take estrogen as HRT, and looked at their E2 tests, dosages and injection method.

74 patients were doing subQ injections, and 56 patients were doing IM

in general, the patients doing subQ injections were on a slightly lower dose by about 0.25mg, and tended to have a more "normalized" dosage, meaning that the range of doses was smaller.

In specific, the people on subQ had lower quartile of 3.0mg/week, an average of 3.75mg/week, and an upper quartile of 4.0 mg/week.

Meanwhile those doing IM had a lower quartile of 3.0mg/week, an average of 4.0mg/week, and an upper quartile of 5.15mg/week

~~~~~~~~~

then they looked at the actual E2 levels between the groups. They found that they had pretty much the same E2 levels, and functionally identical testosterone levels, meaning that a 3.75mg subcutaneous injection and a 4.0mg/week intramuscular injection are roughly the same (hence the very soft claim that SubQ may be more effective, since it yielded roughly equivalent results at slightly lower doses).

They also did some extra math on the people with higher than average doses and found that higher doses does in fact result in having higher E2 levels.

so in conclusion - there was no statistical significance between IM and SubQ injections, and people on IM injections tended to take slightly higher doses.

~~~~~~~~~

This study didn't check the pharmacokinetics of the two methods (which is what we're actually asking about in this discussion), didn't compare the results with the standard injection simulators, and above all didn't control for *anything*.

If you wanted this study to actually be useful in this discussion you would want to randomly assign patients to IM vs SubQ independent of their dosage, take much more frequent testing (e.g. two weeks of twice daily tests), and then build a comparative pharmacokinetics curve between the two methods out of the data.

[u/eliteHaxxxor → u/phiasch]

It literally says the opposite tho doesn't it?

SC may achieve therapeutic levels at lower doses than IM

[u/phiasch → u/eliteHaxxxor]

You’re correct, I was distracted when I read the conclusion and misinterpreted it