What to Know About Supprelin (Histrelin Implant)

A Puberty Blocking Implant for Precocious Puberty & Transgender Youth

In This Article

Supprelin is a long-acting implant used for the treatment of precocious puberty, or early puberty. Supprelin is also used as a puberty blocker for transgender youth who want to delay puberty in their assigned sex. The Supprelin implant is inserted under the skin of the upper arm. In theory, it only remains effective for slightly longer than a year, but some researchers suggest that it can be left in place for up to two years to reduce costs. When the implant is no longer effective, it can be replaced or removed, if the youth has reached an age where it is appropriate for them to go through puberty. Supprelin implants can be used consecutively for many years in a row.

Supprelin implants contain histrelin acetate. Histrelin is what is known as a gonadotropin-releasing hormone (GnRH) agonist. That means it activates the gonadotropin receptors in the pituitary gland. GnRH stimulation of the pituitary during adolescence and adulthood is what leads to the production of the sex hormones—estrogen and testosterone—by the gonads (ovaries or testes).

While it sounds counter-intuitive to stimulate the pituitary, normal GnRH stimulation happens in pulses. In contrast, GnRH agonist stimulation of the pituitary by Supprelin is constant. This leads to an initial surge of hormones being released (which can be blocked by other drugs). The pituitary then quickly becomes less sensitive to GnRH. After just a week or two, it stops sending the signals that cause the gonads to release sex hormones. This effectively turns off puberty. GnRH agonists are also used to treat certain hormone-sensitive cancers, such as prostate cancer.

Like Supprelin, Vantas is a long-lasting implant that releases histrelin. However, Vantas use in children is off-label, as it is only approved for use in adults.

Stand in line, it’s the kid’s turn now
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Uses

Supprelin implants are FDA-approved for the treatment of central precocious puberty. Supprelin has been approved for use in individuals 2 years of age and older.

Off-Label Use of Supprelin in Transgender Youth

Supprelin implants are widely used as a puberty blocker for transgender youth who have not yet completed puberty in their assigned sex. Use of puberty blockers has been shown to improve the overall health and well-being of transgender youth. Puberty blockers have also been shown to reduce the risk of suicidal ideation. As such, many professional organizations recommend that transgender youth be routinely offered access to puberty blockers.

For transgender youth, puberty blockers help reduce gender dysphoria. They do this by helping youth avoid physical changes that would increase their gender dysphoria. For example, a young transgender man who is given puberty blockers at the start of puberty would not develop breasts. A young transgender woman would not grow an Adam's apple or experience male pattern hair growth on her chest or other body parts.

Transgender youth who are able to start puberty blockers and then go onto gender-affirming hormone therapy undergo only a single puberty in their affirmed gender. Because of this, they are more physically similar to cisgender individuals of their affirmed gender than individuals who first go through puberty in their assigned sex. This can make it easier for them to move through the world without being misgendered. On the flip side, prompt use of puberty blockers can make fertility preservation more difficult or even impossible. That can be an issue for individuals who want to have genetic offspring in the future. However, research suggests that few transgender individuals regret their choice to transition without preserving their fertility, even those who are disappointed not to have had children.

Before Taking

Before a child or adolescent is put on Supprelin, their doctor will want to evaluate how hormones are affecting their body. This not only allows the doctor to determine the stage of puberty that the child is in, but to be certain what is causing the early or otherwise unwanted puberty. Blood tests will be used to measure the child's amount of sex steroids and other hormones. Their bone age will likely be measured, as bone is responsive to sex hormones as well. In fact, the ways in which bones respond to sex hormones is why men are generally taller than women. It is also why individuals with untreated central precocious puberty are shorter than average.

Precautions and Contraindications for Supprelin Use

Supprelin should not be used in individuals who are pregnant. The hormone changes induced by Supprelin increase the risk of pregnancy loss. Supprelin should also not be used in people who are hypersensitive to GnRH or GnRH agonists.

Individuals considering starting on Supprelin should be aware that there may be an initial increase in the concentration of sex hormones in the blood. This means that for individuals assigned female, there would be an increase in estradiol, and there would be an increase in testosterone for those assigned male. This increase is largest during the first week and sex hormone production should subside completely within four weeks. The surge of hormones would not be expected in someone transitioning from another GnRH agonist onto Supprelin.

There are no known drug interactions for Supprelin, but taking this medication may affect the results of blood tests looking at the products of the pituitary gland and the gonads. These include sex hormones but also hormones such as insulin-like growth factor-1 (IGF-1) and dehydroepiandrosterone (DHEA).

Other GnRH Agonists

GnRH agonists are also used to treat other hormone-sensitive conditions such as endometriosis, prostate cancer, and uterine fibroids. There are a number of drugs in this class.

GnRH Agonists
Generic Name Brand Names Route of Administration
leuprolide Lupron, Eligard, Lupron Depot, Viadur intramuscular or subcutaneous injection; implant
goserelin Zoladex long-acting sub-cutaneous injection
nafarelin Synarel nasal spray
triptorelin Trelstar, Trelstar Depot, Trelstar LA, Triptodur (many others outside the U.S.) intramuscular injection

Dosage

Supprelin is a long-lasting implant that contains 50 milligrams (mg) of histrelin acetate. It releases approximately 65 micrograms (mcg) of histrelin acetate per day for 12 months. In contrast, the Vantas implant also contains 50 mg of histrelin acetate and releases approximately 50 mcg per day for 12 months.

Supprelin can be inserted under either local anesthetic in a doctor's office or under general anesthetic in an operating room. After 12 months of use, the implant should either be removed or replaced. The implant is designed to last for a few weeks over 12 months in order to allow for flexibility with doctors' appointments, if the implant needs to be replaced.

After Supprelin is inserted, a patient will be instructed not to get their arm wet for 24 hours. They will also be advised to avoid heavy use of the arm for one week. This allows the incision time to fully heal and may reduce the risk of issues with the implant.

Side Effects

Serious side effects of Supprelin are rare. The most common side effects of Supprelin are reactions around the place where the implant is inserted. Implant site side effects include bruising, swelling, and pain. These should go away on their own and do not require treatment. However, severe pain or redness should be reported to your doctor. Some people also experience scarring at the implant site. In rare cases, the implant may break or start to come through the skin on its own.

Severe Side Effects of Supprelin

Although severe side effects are rare, there have been reports of patients experiencing convulsions on GnRH agonists, including Supprelin. These have primarily occurred in individuals with underlying neurological disorders, such as epilepsy. They have also occurred in individuals who are taking other drugs that increase the risk of convulsions. However, some convulsions have been reported in individuals with no other risk factors.

Individuals who have undiagnosed medical conditions affected by GnRH signaling may experience flareups associated with Supprelin implantation. These could be severe.

Warnings and Interactions

Supprelin should not be used in individuals who are pregnant or in those under 2 years of age. It should be used only with caution in patients with a history of seizures, cerebrovascular disease, or medications that increase the risk of convulsions.

People taking Supprelin or other GnRH agonists, and their caregivers, should be aware that some people experience an increase in psychiatric symptoms on these drugs including:

  • Crying
  • Irritability
  • Impatience
  • Anger
  • Aggression
  • Depression

If you, or your child, experiences worrisome mood changes, it is important to discuss these with your doctor.

The interaction of Supprelin with other drugs has not been studied. Drug interactions for other GnRH agonists have also not been reported.

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  2. Lopez CM, Solomon D, Boulware SD, Christison-lagay ER. Trends in the use of puberty blockers among transgender children in the United States. J Pediatr Endocrinol Metab. 2018;31(6):665-670. doi:10.1515/jpem-2018-0048

  3. Turban JL, King D, Carswell JM, Keuroghlian AS. Pubertal suppression for transgender youth and risk of suicidal ideation. Pediatrics. 2020. doi:10.1542/peds.2019-1725

  4. Cheng PJ, Pastuszak AW, Myers JB, Goodwin IA, Hotaling JM. Fertility concerns of the transgender patientTransl Androl Urol. 2019;8(3):209–218. doi:10.21037/tau.2019.05.09

  5. Endo Pharmaceuticals Inc. Supprelin LA (histrelin acetate implant ) package insert. Updated 2019.

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