3w ago

Sublingual Estradiol Offers No Apparent Advantage Over Combined Oral Estradiol and Cyproterone Acetate

pubmed.ncbi.nlm.nih.gov Sublingual Estradiol Offers No Apparent Advantage Over Combined Oral Estradiol and Cyproterone Acetate for Gender-Affirming Hormone Therapy of Treatment-Naive Trans Women: Results of a Prospective Pilot Study - PubMed

Both treatments achieved similar clinical changes. At this stage, SLE, which repeatedly induces alarming excursions of serum estradiol throughout the day, appears to offer no advantage over the CO approach.

Sublingual Estradiol Offers No Apparent Advantage Over Combined Oral Estradiol and Cyproterone Acetate for Gender-Affirming Hormone Therapy of Treatment-Naive Trans Women: Results of a Prospective Pilot Study - PubMed

Abstract

Purpose: Chronic gender-affirming hormone therapy (GAHT) with sublingual estradiol (SLE) has not been studied. We aimed to compare GAHT with SLE only, to combined oral (CO) estradiol and cyproterone acetate, in treatment-naive trans women.

Methods: Twenty-two trans women enrolled into either the CO arm or the SLE-only arm (0.5 mg four times daily) in this 6-month prospective study. Anthropometric and laboratory variables were collected at baseline and 3 and 6 months. At the study beginning and end, body composition was measured by dual-energy X-ray absorptiometry and bioelectrical impedance, and gender dysphoria, sexual desire, and function were assessed by validated questionnaires.

Results: Subjects in the SLE were older, 26.3±5.8 years versus 20.1±2.3 years, p=0.006. All anthropometric, body composition, and laboratory variables were identical at baseline. Although dysphoria appeared greater, and sexual function lower at baseline in the CO group, this canceled out after age adjustment. Both treatments induced similar biochemical and hormonal changes. Creatinine, hemoglobin and cholesterol decreased significantly, while testosterone was suppressed to the same level in both groups: 3.22 [1.47-5.0] nmol/L in the SLE group and 2.41 [0.55-8.5] nmol/L in the CO, p=0.65. Significant changes in body composition toward a more feminine body were noted in both groups. Dysphoria did not significantly improve in either group, while sexual desire and function decreased at six months in both, p<0.001.

Conclusions: Both treatments achieved similar clinical changes. At this stage, SLE, which repeatedly induces alarming excursions of serum estradiol throughout the day, appears to offer no advantage over the CO approach.

16 comments

I think this conclusion is incredibly naïve given the dramatically increased bioavailability and significantly decreased side effects that sublingual administration has over oral estradiol. Flooding the liver through oral administration results in strain that is significantly reduced by sublingual administration, and the increased bioavailability alone accounted for comparable testosterone suppression without an anti-androgen at the same daily dosage. So on top of the decrease in liver damage by moving away from oral administration, this approach also does not account for the side effects of the anti-androgen. The miniscule sample size doesn't do any favors to this study, either. The supposed "alarming excursions of serum estradiol" is solved simply by adjusting the dosage and spreading it out into more frequent doses throughout the day. It seems they did split the dosage into 4 doses for sublingual administration, but they are providing the same daily dosage despite significantly increased bioavailability of the sublingual route (which also accounts for the testosterone suppression). Additionally, a dosage of only 2mg of estradiol daily via oral administration is quite low for trans women.
I have a lot of problems with the conclusions of this study.
- I think the conclusion is accurate given what the researchers found from what they measured during the study.
  The results of any experimental study are be limited to the scope of the experiment, and the conclusion must be as well. This is science working as it does.
  Everything you say about HRT is accurate as far as I'm aware, but those are only arguments you can make from meta-analyses that take into account the results of many studies.
  Don't take the findings of single experimental studies conclusively. This study is a report on what was found with around 20 specific trans women over a 6 month period. This is published by scientists for other scientists, to direct, refute, or confirm other research. Read all expiriments in that light.

The main reason I hear people stating in favor of sublingual is that it is better for the liver, which those guys didn’t even study and wouldn’t have been able to with those sample sizes either…
And reducing CPA-intake is a pretty good reason to switch to SL in its own right, so this is all really non-convincing.

Dysphoria did not significantly improve in either group, while sexual desire and function decreased at six months in both
💀
- Why the skull?
  
  Sexual desire & function decreasing is commonly seen as a negative thing, and dysphoria not improving is clearly negative - so I am attempting a kind of sympathetic humor at the unfortunate irony of a treatment being unsuccessful. It makes me sound monstrous, now that I have to explain it.

16 comments