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

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.

  • Fiona@discuss.tchncs.de
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    25 minutes ago

    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.

  • Filetternavn@lemmy.blahaj.zone
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    14 hours ago

    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’d like to link to a much more complete analysis of the sublingual route of administration for estradiol that analyzes a wide variety of sources (including the one linked in this post) for those interested in a more accurate picture of the benefits and shortcomings of sublingual administration:

    An Exploration of Sublingual Estradiol as an Alternative to Oral Estradiol in Transfeminine People

  • dandelion@lemmy.blahaj.zone
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    11 hours ago

    Dysphoria did not significantly improve in either group, while sexual desire and function decreased at six months in both

    💀

      • dandelion@lemmy.blahaj.zone
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        6 hours ago

        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.

        • Of the Air (cele/celes)@lemmy.blahaj.zone
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          6 hours ago

          Thank you for explaining.

          Personally we do not think desire decreases completely, but in our own experience it has changed and made us wish for different functioning. Perhaps we always had that to some degree but the problem is that medical science is not really a place for many of us to feel congruent in our desires and functioning, that is why it is a problem for many trans femmes, we believe.

          As for functioning without the medical science currently able to provide us what we require, this can be true somewhat. However, it can be mitigated by alternative practices.

          • Selyle@lemmy.blahaj.zone
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            2 hours ago

            Personally, my desire pretty much disappeared… sometimes it super bothers me, especially since I know things need to stay engaged down there if I ever opt for certain surgeries. It’s not bothersome enough that I’ve seriously brought it up with my doctor, but I did ask to be prescribed progesterone to help as I’ve seen many anecdotes about it increasing sex drive and desire…zero change so far. I’d say it’s pretty nice for the most part as there’s this edge which is no longer there, buuuut I do sometimes miss actually feeling that type of desire. I have read that it just randomly returns eventually, so just doing my best to enjoy whatever this is for now 🤭

          • dandelion@lemmy.blahaj.zone
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            5 hours ago

            Estrogen increased desire significantly for me, but I personally wish it had decreased desire and functioning. I like the atrophy (esp. when I started to think of myself in normative terms as a woman), and I would prefer a much lower libido, I think I would (selfishly) be happy with no libido.

            Part of the problem with this study is that it has such a small sample size, dysphoria clearly decreases for many trans people when they take HRT and there are many, much larger and better studies showing this.

            I don’t really follow what you mean about medical science and congruence with desire and function, or what you mean by alternative practices.

            • Of the Air (cele/celes)@lemmy.blahaj.zone
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              5 hours ago

              We mean that medical science cannot give us certain body parts that would increase sexual functioning such a clitoris, certain glands nor ovaries, a womb etc (yet) and by alternative practises we mean kink or possibly certain cultural practises like tantra etc.