Variability of response to early puberty induction demonstrated by transverse uterine diameter measurement and a novel method of 3D breast imaging

Clin Endocrinol (Oxf). 2022 Jul;97(1):91-99. doi: 10.1111/cen.14740. Epub 2022 Apr 22.

Abstract

Objective: Induction of puberty with exogenous oestrogen results in considerable variability in final uterine and breast volumes. We set out to quantify the variability of these two outcome measures with a view to establishing monitoring methods that could be used to individualise treatment protocols.

Design: A prospective observational study.

Participants: Sixteen participants with pubertal delay and primary amenorrhoea, due to hypogonadism were recruited from paediatric gynaecology and endocrinology clinics at University College London Hospital. A standardised protocol of transdermal 17β oestradiol (17βE) was used (Evorel™), with a starting dose of 12.5 mcg increasing to 25 mcg (patch changed twice weekly) after 4 months. Follow up was every 2 months for a total of 8 months.

Measurements: Uterine dimensions using ultrasound, oestradiol concentrations and breast development assessed by both Tanner staging and 3D photographic imaging.

Results: After 8 months of treatment, the changes in oestradiol concentrations (0-174 pmol), uterine volume growth (4.4-16.4 ml) and breast volume (1.76-140.1 ml) varied greatly between individuals. Of uterine parameters, transverse uterine diameter was most closely associated with serum oestradiol levels at 8 months (beta standardised coefficient = 0.80, p = .001). Change in breast volume was associated with age of treatment initiation (beta standardised coefficient 0.55 p = .04).

Conclusions: We demonstrate variation in response to exogenous oestrogen, emphasising the necessity for individualised dose titration. In the absence of sensitive oestradiol assays, uterine transverse measurements may be used as a surrogate marker of oestrogen sensitivity to guide early dose adjustment. 3D breast imaging may provide a quantitative assessment of breast development to complement Tanner breast staging.

Trial registration: ClinicalTrials.gov NCT02871986.

Keywords: breast; imaging; induction; oestradiol; puberty; uterus.

Publication types

  • Observational Study

MeSH terms

  • Child
  • Estradiol
  • Estrogens
  • Female
  • Humans
  • Puberty / physiology
  • Puberty, Precocious*
  • Uterus* / diagnostic imaging

Substances

  • Estrogens
  • Estradiol

Associated data

  • ClinicalTrials.gov/NCT02871986