Animal Study Found Puberty Blockers May Cause Depression — Decades After Doctors Began Administering To Children

A 2020 study was the first of its kind to use an animal model to examine the potential neurological and psychiatric effects of puberty-blocking drugs — 22 years after doctors began prescribing them to gender dysphoric adolescents on an experimental basis.

The results found that treatment with leuprolide, the drug used to suppress puberty, had “profound effects” of increased depression in female mice; in male mice, increased stress and a loss of interest in female mice were reported. 

“Our behavioral and neurobiological characterization reveals for the first time that chronic leuprolide treatment, starting after the onset of puberty, exerts sex-specific effects on social preference, despair-like behavior and hyponeophagia, neuroendocrine responses to mild stress, and hyperactivity of the [dentate gyrus], a crucial neurobiological regulator of stress responses in mice,” the paper reads.

In 1998, Dutch clinicians began using leuprolide (GnRH agonists) to suppress puberty as an intervention for pediatric gender dysphoria, and over the years published two studies on their use in this context. The problematic “Dutch protocol,” as it became known, was later adopted by the United States to form the bedrock of the “gender-affirming” model of care, which deploys the use of puberty blockers, cross-sex hormones, and surgeries to “affirm” minors in their chosen trans-identity.

While past studies on leuprolide treatment in animals looked at the physiological effects in the body, this placebo-controlled trial was the first to examine the neurobiological effects of leuprolide in the brain, using post-pubertal mice as a model for post-pubertal children with gender dysphoria. Mice and rats have long been used as model organisms for biomedical research because of their physiological, anatomical, and genetic similarity to humans.

The effects of GnRH agonists on brain function and mental health are not well understood,” the abstract read. “Here, we investigated the effects of leuprolide on reproductive function, social and affective behavior, cognition, and brain activity in a rodent model.”  

The study found that leuprolide treatment had sex-specific behavioral differences in male and female mice. For example, the puberty suppression drug affected the social behavior of male mice, but a change in social preference was not observed in female mice. The control group of male mice preferred the company of female mice, while the experimental group showed “a lack of interest in females and displayed no aggressive behavior toward other male mice.” 

Female mice treated with leuprolide had decreased appetite and spent more time immobile, both common indicators of despair-like behavior in animal models. When the researchers found increased neural activity in the brain region responsible for “mood and anxiety regulation, stress resilience and cognition” in female mice, it supported the observations made about their depressed behavior. Male mice treated with leuprolide showed increased neuroendocrine responses to stress. 

“In conclusion, we report that chronic leuprolide treatment in mice has profound effects on female behaviors that are commonly interpreted as depression-like, as well as on neural activity in the hippocampus—a brain region crucially involved in stress processing, depression, and cognition,” the discussion section read.

“While these mood-related effects are specific to females, leuprolide causes pronounced differences in locomotion and social preference in males and increases neuroendocrine responses to mild stress,” the researchers added.

“Our results in an animal model shed new light on the effects of chronic GnRHa treatment on behavioral, neuroendocrine, and neurobiological effects of a drug that is commonly used for many clinical conditions, and particularly to alleviate gender dysphoria in transgender youth,” the study concluded.

Dr. Claudia Gennari, an internist and researcher, believes the negative psychiatric outcomes found in this study have huge implications for pediatric gender medicine.

“This study was long overdue and should bring pause to clinicians treating children with puberty blockers because it shows sex-specific neuropsychological changes caused by this medication,” Gennari told The Daily Wire.  

“This strongly suggests GnRH agonists are not a ‘pause’ button at all and its use can cause negative effects on cognition, behavior, and coping skills,” she added.

Far from “completely safe and reversible” and “a pause button on puberty,” as proponents of “gender-affirming care” claim, the children who begin taking puberty blockers during the first signs of puberty and go on to take cross-sex hormones, which constitute the vast majority, will become sterilized and may never be able to achieve orgasm.

The New York Times investigated the deleterious effects that puberty blockers have on bone health, and published an article after reviewing the scientific literature and interviewing over 50 doctors and academic experts around the world. 

Puberty-blocking drugs are only FDA-approved for children for their use in treating central precocious puberty, a condition caused by pituitary gland dysfunction in which children begin to sexually mature before age 8 or 9. Doctors have prescribed puberty blockers off-label as a “treatment” for gender dysphoria in adolescents on an experimental basis. 

There are no long-term studies to support its use during this critical window of brain and body development, and they are not FDA-approved for their off-label use. They are, however, given out to children “like candy” to a “skyrocketing” number of new patients, according to a pediatric endocrinologist from Boston Children’s Hospital’s GeMS (Gender Management Service), which was the first clinic in the country to begin administering puberty blockers to children.

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