A reduction in long-term spatial memory persists after discontinuation of peripubertal GnRH agonist treatment in sheep#
Areas of the brain responsible for learning and memory develop during puberty. The study aimed to measure the impact of pubertal suppression on cognitive function in sheep. The researchers treated 25 male lambs with puberty blockers between ages eight and forty-five weeks (puberty onset in sheep averages ten weeks and is complete within one year). A group of thirty male lambs from the same litters served as the control group.
The researchers assessed spatial orientation and spatial learning performance at a maze task at forty-one, eighty-three and ninety-one weeks of age. They assessed long-term spatial memory at ninety-nine weeks of age.
There were no significant differences between the two groups for spatial orientation (time spent in the maze) and spatial learning (how quickly the animals were able to complete the maze in same day attempts). However, the treated group took 50% longer to complete the maze for the long-term spatial memory task. The latter result was statistically significant and demonstrated persisting impacts on cognitive function of puberty suppression after the researchers had discontinued blockers (emphasis added):
During the assessment of long-term spatial memory at 99 weeks of age, [treated] rams were found to be 1.5-fold slower than Controls in traversing the spatial maze...The maintenance of this difference in spatial performance, following the discontinuation of peripubertal GnRHa-treatment, demonstrated that the effects of peripubertal GnRHa on long-term spatial memory were not reversed and persisted into adulthood, despite the restoration of normal GnRH and gonadal steroid signaling. This result indicates that long-term spatial memory is dependent on changes that occurred during a critical window of development that is sensitive to alterations in GnRH signaling.
The researchers highlight the applicability of the results to children and adolescents and the possibility that pubertal suppression has impacts on other aspects of cognitive function (emphasis added):
...deficits in long-term spatial reference memory did not improve with exposure to endogenous testosterone and are likely permanently altered by the changes in GnRH signaling that occurred during the peripubertal period. In so doing, it identifies the peripubertal period as a critical window of development with regard to spatial memory, in which GnRH signaling is involved. The observation that peripubertal GnRHa-treatment is associated with permanent changes in brain development raises particular concerns about the cognitive changes associated with the prolonged use of GnRHa-treatment in children and adolescents.
Perturbations in GnRH signaling during this peripubertal period may also have long lasting effects on other brain areas and/or aspects of cognitive function.
Claims on the Ministry of Health website and in the New Zealand Guidelines that puberty blockers are "safe and fully reversible" are false. The study demonstrates that in sheep puberty is a critical window for the development of long-term spatial memory, amongst possible other cognitive functions. Suppressing normal puberty will likely have permanent negative impacts on cognitive function.