Nocturnal Application of Transdermal Estradiol Patches Produces Levels of Estradiol That Mimic Those Seen at the Onset of Spontaneous Puberty in Girls

The objective of pubertal induction in children with hypogonadism is to mimic spontaneous puberty in terms of physical and psychological development. In a clinical observation study, we induced puberty in 15 girls with hyper- or hypogonadotropic hypogonadism using low doses of transdermal estradiol patches attached only during the night and compared the estradiol concentrations obtained with those in healthy girls. Pubertal induction was started between the ages of 12.3 and 18.1 yr. A transdermal matrix patch of 17β-estradiol (25 μg/24 h; Evorel, Janssen Pharmaceuticals-Cilag) was cut into pieces corresponding to 3.1, 4.2, or 6.2 μg/24 h initially and attached to the buttock. After 4–14 months, the dose was increased gradually. Serum 17β-estradiol concentrations were measured every 2 h by RIA (detection limit, 6.0 pmol/L; 1.6 pg/mL).

The results show that it is possible to mimic the spontaneous levels as well as the diurnal pattern of serum 17β-estradiol in early puberty, by cutting a transdermal 17β-estradiol matrix patch and attaching a part of it, corresponding to 0.08–0.12 μg estradiol/kg BW, to the buttock nocturnally. In most of the girls, breast development occurred within 3–6 months of the start of treatment.