Late-Onset Puberty Induction by Transdermal Estrogen in Turner Syndrome Girls—A Longitudinal Study

Abstract

ObjectiveEstrogen replacement therapy (ERT) for Turner syndrome (TS) is a widely discussed topic; however, the optimal model of ERT for patients with delayed diagnosis and/or initiation of therapy is still unclear, mainly due to insufficient data. We present the results of a prospective observational single-center study in which the efficacy of late-onset puberty induction by one-regimen transdermal ERT in TS girls was evaluated.MethodsThe analysis encompassed 49 TS girls (63.3% with 45,X) with hypergonadotropic hypogonadism in whom unified transdermal ERT protocol was used for puberty induction (first two months 12.5 μg/24 h, thereafter 25.0 μg/24 h until breakthrough bleeding). Clinical visits for examination and therapy modification took place every 3–6 months. Transabdominal pelvic ultrasound examinations were performed at least twice: at the beginning and at the end of follow-up.ResultsThe mean (SD) age at ERT induction was 15.1 (1.3) years. The duration of follow-up was 2.4 (1.1) years. Half of all the patients had at least B2 after 0.57 years, B3 after 1.1 years, B4 after 1.97 years, and menarche after 1.82 years from ERT initiation. With earlier initiation of ERT (≤14 years), B2 (p = 0.059) was achieved faster and B4 (p = 0.018) significantly slower than with the later start of ERT. Thirty-four (94.4%) patients had at least stage B3 at menarche. The karyotype, initial weight, and body mass index had no impact on puberty tempo during ERT. The uterine volume increased significantly during ERT in all the study group (p < 0.0001), and in half of the patients, the increase was at least 12.4-fold. It did not correlate with the duration of treatment (p = 0.84) or the dose of estradiol per kilogram (p = 0.78), nor did it depend on karyotype (p = 0.71) or age at ERT initiation (p = 0.28). There were no differences in ΔhSDS during ERT (p = 0.63) between the two age groups (ERT ≤14 and >14 years).ConclusionThe presented easy-to-use fixed-dose regimen for late-onset puberty induction allowed for a satisfactory rate of achieving subsequent puberty stages and did not influence the growth potential.

Uterine Development During Induced Puberty in Girls with Turner Syndrome

“…Compared to the participants in the aforementioned study, our patients started ERT earlier (mean age 12.9 years), and although they were younger at the final evaluation (mean age 16.1 versus 24 years), they achieved better uterine development: all but two (95%) attained a mature uterine configuration with FCR>1, and 61% had a final UV above the 5th percentile of the reference group. In a study by Gawlik et al (2), which involved girls with TS with late-onset ERT (mean age 15.1 years), the initial UV was comparable with our results, but the final UV seemed to be significantly smaller than that in our subjects (10 vs 30 cm 3 ). Considering the postulated existence of an optimal time window for uterine development in adolescence, we can assume that in our patients, we probably applied ERT closer to this optimal window; nevertheless, we found no correlation between age at the onset of ERT and final uterine size.…”

Reduced uterine volume after induction of puberty in women with hypogonadism

“…Although some uterine growth is detectable as early as the age of 6 years, the majority occurs during puberty and continues beyond the time of menarche and full breast development. 6,7 Most research has focused only on girls with Turner syndrome which forms a large subgroup of hypogonadism, but in this instance, comparison with normal reference ranges may not be valid. Without oestrogen exposure, the uterus fails to grow and may be described as hypoplastic, 3,4 often being apparently absent on imaging.…”

“…5 Induction of puberty with exogenous oestradiol aims to mimic normal physiology, but there are little data on how successful the process is in terms of uterine size. 6,7 Most research has focused only on girls with Turner syndrome which forms a large subgroup of hypogonadism, but in this instance, comparison with normal reference ranges may not be valid. Moreover, there is no standardisation of uterine measurements or their attainment and no consensus for the normal reference size for the uterus.…”

Turner Syndrome with Isochromosome Xq

“…She had estrogen replacement therapy (ERT) which was recommended to initiate and maintain pubertal development, which is a standard of care in patients with TS. 12 Ultrasound examination of the thyroid revealed diffuse parenchyma. Growth hormone and insulin level were normal range.…”