Puberty Blocker, Leuprolide, Reduces Sex Differences in Rough-and-Tumble Play and Anxiety-like Behavior in Juvenile Rats

Endocrinology. 2024 Mar 29;165(5):bqae046. doi: 10.1210/endocr/bqae046.


We examined the effect of the puberty blocker, leuprolide acetate, on sex differences in juvenile rough-and-tumble play behavior and anxiety-like behavior in adolescent male and female rats. We also evaluated leuprolide treatment on gonadal and pituitary hormone levels and activity-regulated cytoskeleton-protein messenger RNA levels within the adolescent amygdala, a region important both for rough-and-tumble play and anxiety-like behavior. Our findings suggest that leuprolide treatment lowered anxiety-like behavior during adolescent development, suggesting that the maturation of gonadotropin-releasing hormone systems may be linked to increased anxiety. These data provide a potential new model to understand the emergence of increased anxiety triggered around puberty. Leuprolide also reduced masculinized levels of rough-and-tumble play behavior, lowered follicle-stimulating hormone, and produced a consistent pattern of reducing or halting sex differences of hormone levels, including testosterone, growth hormone, thyrotropin, and corticosterone levels. Therefore, leuprolide treatment not only pauses sexual development of peripheral tissues, but also reduces sex differences in hormones, brain, and behavior, allowing for better harmonization of these systems following gender-affirming hormone treatment. These data contribute to the intended use of puberty blockers in stopping sex differences from developing further with the potential benefit of lowering anxiety-like behavior.

Keywords: GnRH; adolescent; behavior; leuprolide; puberty blockers.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Amygdala / drug effects
  • Amygdala / metabolism
  • Animals
  • Anxiety* / drug therapy
  • Behavior, Animal* / drug effects
  • Corticosterone / blood
  • Female
  • Leuprolide* / pharmacology
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Sex Characteristics
  • Sexual Maturation* / drug effects
  • Testosterone / blood


  • Leuprolide
  • Corticosterone
  • Testosterone