ESPE Abstracts (2014) 82 P-D-1-3-95

Sex Development

Ovarian Development and Hormonal Feedback Mechanism in a 46XX Patient with cyp19a1 Deficiency Under Low Dose Estrogen Replacement

Marie-Anne Burckhardta, Verena Obmannb, Marco Jannera & Primus E Mullisa


aPaediatric Endocrinology, Diabetology and Metabolism, University Children’s Hospital, Inselspital, Bern, Switzerland; bDepartment of Diagnostic, Interventional and Paediatric Radiology, Inselspital, Bern, Switzerland

Background: Ovarian and uterine development in relation to hormonal feedback mechanisms (E2, LH, FSH, and inhibin) has rarely been studied. Therefore, the age specific and longitudinally adequate replacement dose of estradiol to achieve normal maturation in terms of ovarian and uterine development during infancy, childhood and adolescence remains not well known. However, aromatase deficiency offers an excellent model to study the relevant estradiol dose needed to achieve a normal maturation so important for a natural development such as puberty, growth and bones.

Objective and methods: We studied the impact of oral 17β-estradiol treatment on ovarian and uterine development in relation to FSH and inhibin B in the long-term follow-up of a girl compound heterozygote for two point mutations within the CYP19A1 gene (1).

Results: At the beginning (early childhood) low doses of oral 17β-estradiol (starting with 0.1 mg daily) were given. In the follow-up doses were adequately increased to ensure normal height velocity and bone age maturation. During prepuberty, this treatment resulted in an almost normal development of ovarian volume and both number and size of follicles. Only at the beginning of puberty we found a minimal increase of ovarian volume compared to literature, normalizing when gestagen replacement was added in late puberty (Figure 1). Regarding hormonal feedback mechanism of the ovaries, inhibin B levels were in the upper normal range. On the contrary, low dose of estradiol replacement was not sufficient to achieve physiological gonadotropin levels in late prepuberty and puberty.

Conclusion: In summary, this girl suffering from a complete aromatase deficiency provides an excellent model of how ovarian and uterine development in relation to E2, LH, FSH and inhibin feedback progresses from infancy to adolescence. In addition, the estradiol doses to use can be deduced from this experiment of nature, which may help to treat our patients in a more appropriate way.

Figure 1 Ovarian and uterine development compared to literature (2).

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