The Food and Drug Administration is warning of potential side effects in certain puberty-blocking drugs used in transgender treatments.

The FDA has added a warning to the labeling for gonadotropin-releasing hormone (GnRH) agonists such as Lupron.

GnRH agonists have several uses. Developed to treat certain types of cancer, GnRH agonists are also used to treat endometriosis, delay early puberty, and halt or eliminate puberty for pediatric patients who identify as transgender.

According to the Cleveland Clinic, GnRH agonists are also used to accomplish chemical castration, sometimes called medical castration.

According to the FDA, the warning will only apply to the GnRH agonists used in pediatric patients to delay or stop puberty. The warning informs users of the possibility of developing something called a pseudotumor cerebri.

According to Mayo Clinic, pseudotumor cerebri happens when there is increased pressure inside the skull “for no obvious reason.” Symptoms mimic those of a brain tumor. The increased intracranial pressure can cause swelling of the optic nerve and result in vision loss.

Through a study of several patients prescribed GnRH agonists, the FDA determined there was “a plausible association between GnRH agonist use and pseudotumor cerebri.”

Six cases were identified that supported a plausible association between GnRH agonist use and pseudotumor cerebri. All six cases were reported in females ages 5 to 12 years. Five were undergoing treatment for central precocious puberty and one for transgender care.

For years, patients who have been prescribed GnRH agonists have complained of adverse effects from the drugs.

In 2017, Stat News reported that several women experienced multiple adverse reactions to the drug after being prescribed it at a young age. Many women described bone disease, depression, mood swings, muscle spasms, seizures and other problems that developed in their 20s.

“A 20-year-old from South Carolina was diagnosed with osteopenia, a thinning of the bones, while a 25-year-old from Pennsylvania has osteoporosis and a cracked spine,” the article read. “A 26-year-old in Massachusetts needed a total hip replacement. A 25-year-old in Wisconsin has chronic pain and degenerative disc disease.”

In a 2011 article in The Journal of Pediatrics, research physicians found that even minor delays in puberty reduce children’s bone density.

While there are many GnRH agonist drugs used to delay puberty in pediatric patients, Lupron has the lion’s share of the market.

The only FDA-approved use of Lupron is to treat central precocious puberty, commonly called early puberty, defined by the FDA as occurring in boys younger than nine and girls younger than eight.

The FDA lists the side effects of Lupron as:

  • Injection site reactions such as pain, swelling, and abscess

  • Weight gain

  • Pain throughout body

  • Headache

  • Acne or red, itchy rash and white scales (seborrhea)

  • Serious skin rash (erythema multiforme)

  • Mood changes

  • Swelling of vagina (vaginitis), vaginal bleeding, and vaginal discharge

The Lupron website lists additional possible side effects, such as:

  • Crying

  • Irritability

  • Restlessness (impatience)

  • Anger

  • Acting aggressive

Off-label prescribing is a common practice, but some in the medical field have suggested caution when it comes to prescribing pediatric patients with GnRH agonists.

In a study for the American Academy of Pediatrics, Dr. Erica Eugster, an endocrinologist, wrote that GnRH agonists were mainly prescribed for off-label purposes.

There are dozens of groups and forums across social media with women describing their own adverse reactions to the drug. Facebook and Reddit have become havens for many who attempt to deal with the sometimes permanent effects of these drugs.

The fight over what has been called “gender-affirming” medical treatment has been a hot issue in Alabama in recent months.

In April, the Alabama Legislature passed the Vulnerable Child Compassion and Protection Act, which made it a felony punishable by up to 10 years in prison to perform surgeries or prescribe any transgender drugs to individuals under 19, including puberty blockers.

U.S. District Judge Liles Burke put a partial block on the law, allowing the ban on surgeries to stay in place but preventing the state from banning medications. Burke also removed any criminal penalties for those who prescribe or provide the medication.  

The case is currently being appealed to the Eleventh Circuit Court of Appeals by Alabama Attorney General Steve Marshall.

Marshall also led a 19-state brief to help Arkansas appeal a law that was nearly identical to Alabama’s.

“If anyone spent just a little bit of time with the scientific literature in this area, they would quickly learn that science is largely unsettled; nearly everyone agrees that far more research is needed; and the currently popular approach to care in the United States is not supported by well-researched evidence-based studies,” Marshall said in his brief.

“…Yet the evidence also shows that nearly all children whose gender dysphoria is treated with puberty blockers to ‘buy time’ will proceed to take cross-sex hormones and seek medical interventions with irreversible, life-long consequences such as infertility, loss of sexual function, increased risk of heart attack and stroke, bone density problems, risk of brain development issues, social harms from delayed puberty, and mental health concerns.”

Marshall’s office did not respond to inquiries if the FDA’s newest warning would be beneficial to the federal appeal.

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