Endocrine Abstracts

Background: Women with classic and non-classic (NC) congenital adrenal hyperplasia (CAH) often struggle with fertility, due to androgen excess, elevated progesterone and 17-hydroxyprogesterone (17OHP) levels, causing anovulation, impaired endometrial development and menstrual irregularities. The typical approach to addressing infertility so far, often involves an increase in glucocorticoid (GC) doses, yet this strategy carries potential side effects. Limited observational data on modified-release hydrocortisone (MR-HC), which better replicates the natural diurnal cortisol rhythm, suggests improved fertility in both female and male patients with classic CAH. Therefore, the aim of this study was to investigate fertility in women with classic and non-classic CAH before and after switching to MR-HC.

Methods: A total of 28 adult female patients with CAH (18 classic; 10 NC), with a median (range) age of 32.0 (30.0) years, premenopausal, without hormonal contraception, participated in this prospective, observational, single-center study. The data collection took place before (using conventional GC preparation) and after a switch to MR-HC. Clinical parameters, along with morning serum and daily saliva profiles were collected, measuring progesterone, 17OHP, androstenedione (A4), testosterone and 11-oxygenated androgens.

Results: Prior to study inclusion, 7/28 patients had an irregular cycle, 3/28 were amenorrhoeic, and 14/28 desired pregnancy. After switch to MR-HC, the patients received a significantly lower mean (SD) hydrocortisone equivalent dose (26.3 (12.0) vs 23.1 (8.3), P=.038). Median (range) morning serum concentrations between 0800 and 0010 h showed no significant differences for progesterone, 17OHP, A4, testosterone, and 11-oxygenated androgens. However, in early morning saliva, median (range) 17OHP levels were significantly lower (67.3 (693.2) vs 28.1 (572.8), P=.006) after switching to MR-HC. Menstrual regularisation occurred in 6/10 patients with menstrual disturbance, and 8/14 patients desiring pregnancy became pregnant under MR-HC.

Conclusion: Our preliminary data indicate a clinical improvement in fecundity and fertility in women with classic and non-classic CAH under MR-HC, with even a slight decrease in GC dose. Lower 17OHP concentrations in early morning saliva suggest improved hormonal control overnight, contributing to regulated ovulatory cycles and enhanced fertility.