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On Delaying Puberty

Photo: Pituitary gland, by Athikhun.suw, CC BY-SA 4.0 , via Wikimedia Commons.

Author’s note: This is Part Four of a seven-part series about transgenderism. Nothing in the series is intended to disparage any transgender person, any gender non-conforming person, or any person attracted to members of the same sex. I write as a developmental biologist (Berkeley PhD), and I focus on evidence pertaining to transgender treatments for children.

WARNING: Parts of this series contain explicit language. Reader discretion is advised.

Currently, in the U.S. and the Netherlands, about 95 percent of girls start puberty between 8 and 13. About 95 percent of boys begin puberty between 9 and 14. But about 5 percent of healthy girls and boys start puberty a little sooner or a little later.

In girls, the first noticeable sign of puberty is an increase in the size of the breasts. In boys, it is an increase in the size of the testicles. Pubic hair usually starts to grow, as well. In the mid 20th century, British pediatrician James Tanner divided puberty into five stages. Tanner stage 1 is pre-puberty. Stage 2 is the start of puberty. And stage 5 is sexual maturity.

Puberty begins when the base of the brain starts producing gonadotropin-releasing hormone (GnRH). This stimulates the pituitary gland just below the brain. The pituitary then produces hormones that stimulate the ovaries in girls and the testicles in boys. 

Precocious Puberty

Some girls reach Tanner stage 2 before the age of 8. Some boys reach Tanner stage 2 before the age of 9. They might be among the few children who start normal puberty slightly earlier than most. Or they may start much sooner because of “precocious puberty.” This pathological condition can cause significant medical and emotional problems.

The most common cause of precocious puberty is premature production of GnRH. In 1981, American physician William Crowley pioneered the treatment of precocious puberty. Paradoxically, he administered GnRH to children suffering from it. The excess GnRH over-stimulates the pituitary gland. The pituitary then becomes de-sensitized and stops producing gonadotropins. As a result, the ovaries and testicles stop developing. They may even revert to their pre-puberty state.

When affected children reach the age at which normal puberty would start, the GnRH treatment is stopped. Their development resumes, and puberty proceeds pretty much as though nothing had happened. So in cases of precocious puberty, GnRH appears to be a fully reversible “puberty blocker.”

Puberty Blockers and Short Stature

From 1993 to 1996, a controlled experiment in the Netherlands focused on normal children with short stature. Before puberty, growth hormone (GH) can help such children. But once puberty begins the ends of their long bones begin to fuse. This reduces the final gain in height. In the experiment, an artificial GnRH analog (GnRHa) was administered to delay puberty. It was hoped that GH could then continue to work.

With parental consent 24 girls and 12 boys were enrolled. All the children were experiencing early (but not precocious) puberty. All had reached Tanner stage 2. All the girls were eleven or under, and all the boys were twelve or under. 

Half of the 36 children were randomly assigned to receive treatment. The other half received no treatment. Children in the treatment group received daily injections of GH and monthly injections of GnRHa. Treatment was stopped after three years.

The research team did long-term follow-up on 32 of the 36 participants. After treatment stopped, all of the treated children went through normal puberty. By the time the girls were 18 or the boys were 19 they had all reached sexual maturity. 

Treated children experienced an average height gain of about two inches. But they suffered through three years of frequent injections with very expensive drugs. The research team concluded in 2007 that the suffering and expense were not worth it. “We therefore do not recommend this treatment regimen in general.”

Note that none of the children in this study wanted to transition to the other sex. All stopped taking GnRHa within (or close to) the normal range of puberty onset. At that point they were probably no further behind in their sexual development than some of their untreated peers. 

So puberty blockers in this experiment were fully reversible.

Gender Dysphoria and Puberty Blockers

In 1960, John Money and sexologist Richard Green described five young boys with feminine behavior. Money and Green called this “incongruous gender role.” The term has now been largely replaced by “gender dysphoria.”

The 2013 edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) defines gender dysphoria in children (302.6). It is “a marked incongruence between one’s experienced/expressed gender and assigned gender, of at least 6 months’ duration.” It is accompanied by “a strong desire to be of the other gender or an insistence that one is the other gender.” And, “the condition is associated with clinically significant distress or impairment.” Note that gender dysphoria is listed as a mental disorder.

Ironically, “Brenda” Reimer fit this description, because “her” assigned sex was different from “her” biological sex. But in most cases, “assigned sex” means biological sex.

Among transgender advocates, the gold standard for treating gender dysphoria is the Dutch Protocol. The Protocol has four stages. The first is beginning the transition to the other sex psychologically and socially. The second is receiving a puberty blocker upon reaching Tanner stage 2. The third is receiving cross-sex hormones at 16. The fourth is undergoing transgender surgery after reaching the age of 18. In other words, the Dutch Protocol for treating a mental disorder is social and physical.

Stage 4 is irreversible. Stage 3 is also irreversible, since (among other things) boys will develop breasts and girls will develop facial hair and deeper voices. But the Protocol emphasizes that stage 2 (puberty suppression) is fully reversible. “The suppression of puberty using GnRHa is a reversible phase of treatment… It can be considered as ‘buying time’ to allow for an open exploration of the [sex reassignment] wish.” 

An excellent resource on this topic is a 2017 article by pediatrician Paul Hruz and psychiatrists Lawrence Mayer and Paul McHugh. The article is “Growing Pains,” and it was published online by The New Atlantis.

In 2017 the Endocrine Society recommended puberty blockers for children with gender dysphoria. The Society claimed its authors “used the best available evidence” to arrive at their recommendations.

The “best available evidence” is the focus of Part Five in this series.