ESPE Abstracts

Background: At present, treatment of „classic" congenital adrenal hyperplasia (21-hydroxylase-deficiency, 21OHD) consists of glucocorticoid and mineralocorticoid replacement. However, often androgen excess and its negative metabolic impact are difficult to control without accepting glucocorticoid overtreatment, especially in adolescence. In healthy subjects oral contraceptives (containing ethinylestradiol) increase cortisol binding capacity and free cortisol, while prolonging half-life of unbound cortisol and reducing its clearance. Intake of combined contraceptives (ethinylestradiol/progestin) in healthy women leads to decreased androgen levels by inhibition of ovarian and adrenal androgen synthesis and by an increase of sex hormone binding globulin (SHBG).

Therefore we aimed to investigate the effect of contraceptives in female adolescents with 21OHD on androgen levels in a pilot study.

Methods: Retrospective chart analysis. Laboratory data of female adolescents with confirmed 21OHD under glucocorticoid and mineralocorticoid treatment were reviewed before and after introducing an oral or transdermal contraceptive: Serum 17-OH-progesterone-, androstendione-, DHEA-, DHEA-S- and free testosterone-values were measured basally and 3-6 months after introduction of the contraceptives.

Results: So far, five adolescents with available data sets could be identified in our centre. Mean age was 15.5 years [range 14.2 – 17.2]. Four patients took hydrocortisone, prednisolone and fludrocortisone as their long-term medication, one patient hydrocortisone and fludrocortisone. The oral contraceptives (4 patients) contained ethinylestradiol 0.03-0.035 mg or cyclic (1, 2 and 3 mg) estradiol valerat and either levonorgestrel, cyproteronacetat, dienogest or destogestrel. The transdermal preparation consisted of ethinylestradiol 0.6 mg and norelgestromin 6 mg. Comparing laboratory values basal to values under treatment with contraceptives a significant decrease of androgens androstendione, DHEA, free testosterone (all P <0.05) was observed. No difference was seen for 17-OH-progesterone or DHEA-S. Treatment regimen changes for hydrocortisone were thus executed in two patients.

Conclusion: In this pilot study in five young females with classic CAH due to 21OHD, we saw a significant reduction in serum androgens after introduction of contraceptives. We therefore plan to confirm this promising result in a larger multi-centre cohort study with a prospective design looking at clinical and biochemical parameters under use of contraceptives. Steroids will be measured from serum and urine by mass spectrometric methods, and hydrocortisone needs calculated. Markers of metabolic syndrome will also be assessed.