LGBT Youth Consult

All about puberty blockers!

Publish date: September 18, 2020

While many transgender individuals develop their gender identity early on in life, medically there may not be any intervention until they hit puberty. For prepubertal children, providing a supportive environment and letting them explore gender expression with haircut, clothing, toys, name, and pronouns may be the main “interventions.” Ensure a safe bathroom and safe spaces at school (and home), and perhaps find an experienced therapist comfortable navigating gender concerns. Supporting the family supports the child and can make all the difference in the world. Often clinics specializing in gender care will see young children to provide this support and follow the child into puberty.

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Once puberty starts, however, medical interventions can be discussed and puberty blockers are a great place to start, given their reversibility. Having an understanding of how puberty blockers work, the side effects, and timing of blocker use is important to the average pediatric provider as you may see some of these children and be able to intervene by sending them to a specialist early!

How do puberty blockers work?

One of the first hormonal signals of puberty is the pulsatile release of gonadotropin-releasing hormone (GnRH) from the hypothalamus. GnRH stimulates the secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) from the anterior pituitary. LH and FSH then stimulate sex steroidogenesis (production of estradiol or testosterone) and gametogenesis in the gonads. The most common choice for puberty blockers are GnRH agonists, such as leuprolide (a series of shots) or histrelin (an implantable rod), which have been studied extensively for the treatment of children with central precocious puberty, and more recently gender dysphoria. Interestingly, these medicines actually stimulate gonadotropin release and the overproduction makes the gonadotropin receptors less sensitive.¹ Gradually the production of sex steroids decreases. One of the advantages of puberty blockers is that they are reversible – stop the medication and the effects wear off, allowing one to proceed with natal puberty if one so desires. Gender specialists always start with the most reversible intervention, especially at such a young age. Puberty blockers are like a pause button that gives everyone – patient, clinicians, therapists – time to process, explore, and ensure transition is the right path.

Sexual development should stop on puberty blockers. For those born with ovaries, breasts will not continue to develop and menses will not start if premenarchal or stop soon if postmenarchal. For those born with testicles, testicular and penile enlargement will not proceed, the voice will not deepen, hands will not grow in size, and an “Adam’s apple” will not develop. Preventing these changes may not only prevent future surgeries (mastectomy, tracheal shaving, etc.) but may also be lifesaving given the lack of development as secondary sex characteristics may not develop, thus avoiding telltale signs that one has transitioned physically, particularly for transwomen.

What are the side effects of puberty blockers?

Whenever an adolescent is started on puberty blockers, it is important to discuss both the main effects (i.e., cessation of puberty and sexual development) as well as the side effects. There are four main side effect areas that are important to cover: bone health and height, brain development, fertility, and surgical implications.

Bone health & height. Adolescence is an important time for growth. During adolescence, bones grow both in length, which determines an individual’s height, and in density, which can affect risk of osteoporosis later on in life. Sex steroids are an important factor for both of these issues. Estradiol is responsible for closure of the growth plates and, in general, those born with ovaries enter puberty earlier than those born with testicles, therefore they see higher rates of estradiol earlier, which causes cessation of growth, hence why females are typically shorter than males. Delaying these high levels of estrogen may give transmales (female to male individuals) more time to grow. Conversely, decreasing release of testosterone in transfemales (male to female individuals) and then introducing estradiol at higher levels earlier than they would experience with their natal puberty may stop transfemales from growing much taller than the average cisgender woman. Bone density also is a major concern as the sex steroids are very important for bone mass accretion.^1,2 Studies in transgender individuals using dual-energy x-ray absorptiometry show that, for transmale patients, z scores do decrease but they tend to catch up once gender-affirming hormones are started. For transfemale patients, the z scores don’t decrease as much but also don’t increase as much once estrogen is started.^1,3 It is for these reasons that the Endocrine Society guidelines recommend monitoring bone density both before and while on puberty blockers.^4,5
Brain development. Adolescence also is an important time for brain development, particularly the areas that focus on executive function. Studies comparing transgender patients on GnRH agonists noted no detrimental effects on higher-order cognitive process associated with a specific task meant to test executive function.⁶ Although not performed on transgender individuals, a study examining girls with central precocious puberty on GnRH agonists found no difference with the control group on auditory and visual memory, response inhibition, spatial ability, behavioral problems, or social competence.⁷
Fertility. Suspending puberty at an early Sexual Maturity Rating (such as stage 2 or 3) may make it difficult to harvest mature oocytes or spermatozoa, thus compromising long-term fertility, especially once they start on gender-affirming hormones. While some patients may choose to delay starting puberty blockers for the sake of cryopreservation, others may be in too much distress at their pubertal changes to wait. Fertility counseling is thus an important aspect of the discussion with transgender patients considering puberty blockers and/or gender-affirming hormones.
Surgical implications. The most common “bottom surgery” performed in transfemales is called penile inversion vaginoplasty, which uses the penile and scrotal skin to create a neovagina.⁸ However, one has to have enough penile and scrotal development for this surgery to be successful, which may mean waiting until a patient has reached Sexual Maturity Rating stage 4 before starting blockers. There are alternative surgical options, but one must discuss the risks and benefits of waiting to start blockers with the patient and family.

When can puberty blockers be started?

Patients must meet criteria for gender dysphoria with emergence or worsening with puberty.⁹ Any coexisting conditions (psychological, medical, social) that could interfere with treatment have to be addressed, and both the patient and their guardian must undergo informed consent for treatment.^4,5,10 Puberty blockers cannot be used until after puberty has started, so at least Sexual Maturity Rating stage 2. In the early stages of puberty, hormonally one will see LH rise followed by rise in estradiol and/or testosterone. Consideration for both the development of secondary sex characteristics and associated increased distress or dysphoria as well as surgical implications must be weighed in each individual case. The bottom line is that these medications can be life saving and are reversible, so if a patient and/or family decides to stop them, the effects will wear off and natal puberty will resume.

Dr. Lawlis is an assistant professor of pediatrics at the University of Oklahoma Health Sciences Center, Oklahoma City, and an adolescent medicine specialist at OU Children’s. She has no relevant financial disclosures. Email her at pdnews@mdedge.com.