Peripheral Precocious Puberty due to Exogenous Estradiol in a 3-Year-Old Girl: A Case Report, European Society for Paediatric Endocrinology Introduction: Transdermal estrogen replacement therapy in girls with hypogonadism is well known for induction of the puberty. Sexual development due to exogenous exposure for sex steroids in food, environment or medication is known, but is rare and sparsely reported. We present a case of peripheral precocious puberty in a 3-year-old girl due to inadvertent exposure to an estradiol gel used by her father as gender affirming hormone therapy (GAHT).

Case description: A 3-year-old girl was referred to our pediatric outpatient clinic with breast development and vaginal discharge over a period of 6 months. The GAHT of her transgender father was estradiol spray 6.12 mg applied to both forearms daily. After 6 months this was changed to estradiol gel 3.75 mg daily for 7 months. The gel was manually applied to the chest, abdomen, shoulders, and thighs. The father reported skin to skin contact on a daily basis. A physical examination of the girl revealed a Tanner stage III for breast and Tanner stage I for pubic hair development. Height was 108.1 cm (+3,2 SD), weight 19.7 kg (+0,54 SD) and bone age advanced to 6.9 years (Greulich and Pyle). Pelvic ultrasound demonstrated increased size for age of both uterus and endometrium corresponding to Tanner stage III-IV. Estradiol was 0.04 nmol/l and GnRH stimulation test revealed a peak LH of 2.0 IU/l with a LH/FSH ratio of 0.77. MRI of the pituitary gland was normal. These clinical, radiologic and laboratory findings were consistent with a diagnosis of peripheral precocious puberty due to exogenous estradiol. The hormone therapy of the father was changed from a gel to a transdermal patch, and the girl experienced regression of breast development, normalization of growth velocity, pelvic ultrasound and GnRH stimulation test.

Conclusions: Exposure to exogenous estradiol can lead to precocious puberty in prepubertal girls. Transgender persons should be thoroughly informed of the risk of transmission of transdermal hormones and be advised to wash hands, use gloves and avoid skin contact shortly after hormone application. Patients with children must be warned of the risk and Gender Clinics should consider the possibility of prescribing alternative routes of administration such as tablets or patches in high-risk patients.