How Does HRT Induce Puberty in Children With 46,XY DSD?

If your child’s gonads were removed or do not produce enough hormones, they will go through puberty with the help of hormone replacement therapy (HRT). A pediatric endocrinologist will start them on a pubertal induction protocol, which involves giving very low, gradually increasing doses of either estrogen or testosterone ^[1][2]. By slowly increasing the hormone levels over two to three years, the medical team closely approximates typical pubertal timing, helping your child develop physically and emotionally ^[3][4].

Timing and Decision Making

There is no single “right” time to start puberty. While hormone therapy is often considered around ages 11 to 12, the exact timing is highly individualized ^[1][5]. It depends on your child’s specific 46,XY DSD diagnosis, their overall growth, and, most importantly, their affirmed gender identity and readiness. The decision should be a collaborative process involving you, your child, and a multidisciplinary team (a group of different specialists working together, such as endocrinologists, urologists, and psychologists) ^[6].

How Pubertal Induction Works

The goal of pubertal induction is not to rush development, but to guide the body through a gradual transition over 2 to 3 years before settling into a long-term maintenance dose. The specific hormones used will depend on your child’s gender identity and the physical changes they desire.

Estrogen-Based Puberty

If an estrogen-based puberty is desired, the endocrinologist will prescribe estrogen to promote feminizing changes like breast development. This is often given as a transdermal patch (placed on the skin) or an oral pill, starting at a very low dose ^[7][8]. Over several years, the dose is slowly increased ^[3].

If your child has a uterus, a second hormone called a progestogen is usually added 12 to 24 months after starting estrogen, or after their first instance of breakthrough bleeding (unexpected vaginal bleeding) ^[9][10]. The main purpose of the progestogen is to protect the uterine lining and create predictable bleeding ^[3]. Children without a uterus do not need a progestogen for this purpose and will not have menstrual bleeding.

Testosterone-Based Puberty

If a testosterone-based puberty is desired, your child will receive testosterone to promote masculinizing secondary sex characteristics (physical traits that develop during puberty, such as a deepening voice, facial hair, and increased muscle mass) ^[11][4]. Keep in mind that some changes, like voice deepening, are permanent.

Testosterone is most commonly given via injections or transdermal gels ^[2][12]. While oral testosterone exists, certain forms are rarely used in adolescents due to how they are processed by the liver. The dose starts very low and is increased step-by-step. Keep in mind that individual response to testosterone varies by diagnosis; for example, if the body’s androgen receptors do not respond fully to hormones, the virilizing effects will be milder ^[13].

Why A Gradual Approach?

Starting with a low dose and escalating slowly is crucial for your child’s health. This gradual approach provides several key benefits:

• Healthy Skeletal Development: Sex hormones are essential for building bone mass. A slow increase supports healthy bone mineralization and balances growth with the eventual fusion of the growth plates ^[4][14]. It does not guarantee a specific adult height, but it supports healthy skeletal development.
• Physical Development: A gradual escalation ensures that physical changes happen at a steady pace, allowing the body time to adjust ^[15].
• Psychological Adjustment: Going through puberty as a process rather than a sudden event allows the care team to respond to your child’s emotional needs, giving them time to adjust to their changing body ^[1].

Long-Term Care, Monitoring, and Safety

Pubertal induction is a 2- to 3-year process, but if your child’s gonads have been removed, they will require lifelong hormone replacement therapy at an adult maintenance dose to stay healthy ^[16]. Do not stop or change hormone doses without speaking to your care team.

During the induction process, the medical team will monitor several factors to ensure safety and progress:

• Physical changes: Tracking height, weight, blood pressure, and pubertal development ^[17].
• Bone health: Checking bone age (an X-ray of the hand that estimates skeletal maturity, not actual bone strength) ^[18]. If your child has been without hormones for a long time, a DXA scan may be used to measure actual bone density ^[18].
• Lab work: Monitoring hormone levels. For those on testosterone, tests will likely include checking red blood cell counts (hematocrit) and liver function, as testosterone can affect these ^[19].

Possible Side Effects: As with any natural or induced puberty, hormone shifts can cause side effects. Estrogen may cause breast tenderness, headaches, or mood changes. Testosterone can cause acne, mood shifts, and increased red blood cell counts. Speak to your doctor if side effects become unmanageable.

Fertility: It is important to know that while HRT induces physical changes, it does not restore gonadal function or fertility ^[20]. Depending on the diagnosis and anatomy, fertility preservation and reproductive counseling should be discussed with the medical team before starting HRT ^[21][6].

Because puberty can be complex to navigate, ongoing support from a DSD-informed mental health professional is an essential part of care, helping your child discuss their identity, body changes, and future goals ^[6][22].