Are puberty blockers fully reversible?

Question

Multiple sources claim that puberty blockers function like a pause button. To name a few:

Using puberty blockers is like hitting a pause button

St. Louis Children's Hospital

“The really wonderful feature of puberty blockers is that they are a fully reversible medication,” Roberts says.

MSN factcheck

it’s more like a pause. If we stop the medicine, puberty can restart,” says Dr. Cartaya. She adds that once it begins again, the body will go through puberty that’s associated with the sex assigned at birth.

Cleveland Clinic

However NHS is no longer supporting prior positions, quoting an article

Newly published short-term outcomes research suggests that the effects of puberty blockers, specifically in relation to bone-mass density and height, are not as “fully reversible” as the clinic once promised.

Are puberty blockers reversible*?
If so, to what degree?

Edit 3.11.2022: mayoclinic.org claims

Use of GnRH analogues might also have long-term effects on:
Growth spurts
Bone growth and density
Future fertility — depending on when pubertal blockers are started

* To those who wish to quibble about meaning of reversible. I mean something to spirit of 'continue developing (and arriving to result) in the pathway, which would occur without the action/medication taken.' Are people put on blockers losing some biological function or do they suffer something that can't be reversed?

Answer 1

The closest I've found to an indication that they are not reversible is the NHS statement that

Little is known about the long-term side effects of hormone or puberty blockers in children with gender dysphoria.

Although GIDS advises this is a physically reversible treatment if stopped, it is not known what the psychological effects may be.

It's also not known whether hormone blockers affect the development of the teenage brain or children's bones. Side effects may also include hot flushes, fatigue and mood alterations.

So basically, they say that it does seem that the delayed puberty resumes normally, but there may be physical and mental side effects from the delay. Depending on your point of view, you could see that as reasonable caution, implying unsubstantiated danger, or weasel-wording just in case it turns out there are notable side effects in the future.

The specific study that you mention notes an increase in Bone Mineral Density and Bone Mineral Content at the 24 month mark, but not at the 36 month mark, which to me suggests that there is some difference when the blockers are present compared to their baseline figures, but that it went back to normal.

44 patients had data at 12 months follow-up, 24 at 24 months and 14 at 36 months. All had normal karyotype and endocrinology consistent with birth-registered sex. All achieved suppression of gonadotropins by 6 months. At the end of the study one ceased GnRHa and 43 (98%) elected to start cross-sex hormones.

There was no change from baseline in spine BMD at 12 months nor in hip BMD at 24 and 36 months, but at 24 months lumbar spine BMC and BMD were higher than at baseline (BMC +6.0 (95% CI: 4.0, 7.9); BMD +0.05 (0.03, 0.07)). There were no changes from baseline to 12 or 24 months in CBCL or YSR total t-scores or for CBCL or YSR self-harm indices, nor for CBCL total t-score or self-harm index at 36 months. Most participants reported positive or a mixture of positive and negative life changes on GnRHa. Anticipated adverse events were common.

Of note to me, despite the study being cited as a reasoning for believing the changes are not reversible, it does not seem to show a lasting effect at the 36 month mark, and it does not study the actual effects of ceasing to use the puberty blockers, so the question of reversibility is not addressed.