8665 Female Fertility In Patients With Classic And Non-Classic Congenital Adrenal Hyperplasia Under Modified-Release Hydrocortisone (MR-HC)
Authors: Tschaidse L , Nowotny H F , Auer M , Lottspeich C , Bidlingmaier M , Hawley J , Keevil B G , Reisch N 
Published: October 2024

Disclosure: L. Tschaidse: None. H.F. Nowotny: None. M. Auer: None. C. Lottspeich: None. M. Bidlingmaier: None. J. Hawley: None. B.G. Keevil: None. N. Reisch: None.

Background: Female patients with classic and non-classic (NC) CAH struggle with fertility, due to androgen excess, elevated progesterone and 17-hydroxyprogesterone (17OHP) levels, causing anovulation, impairment of endometrial development and menstrual irregularities. The typical approach to treating infertility often includes an increase in glucocorticoid (GC) dose. However, this poses a potential risk of side effects. Limited observational data on modified-release hydrocortisone (MR-HC), which better mimics the physiological diurnal rhythm of cortisol secretion, indicates improved fertility in 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: 21 adult female patients with CAH (14 classic; 5 NC) with a median (range) age of 33.0 (30.0) years, premenopausal and without hormonal contraception, were enrolled in this prospective, observational, single-centre study. The data collection took place before (conventional GC preparation) and after dose-equivalent switching the medication to MR-HC. In addition to clinical parameters such as menstrual cycle and desire to conceive, the collection of morning serum and daily saliva profiles was conducted, measuring progesterone, 17OHP, androstenedione (A4), testosterone, 11-ketotestosterone (11KT) as well as 11-hydroxyandrostenedione (11OHA4). Results: Before study inclusion, 4/21 patients had an irregular cycle, 5/21 were amenorrhoeic and 10/21 patients had a desire to have children. There was no difference in median (range) hydrocortisone dose equivalent before and after switching to MR-HC (25.0 (50.0) vs. 25.0 (30.0), p=.441). Median (range) morning serum concentrations between 8-10 am were not different before and after switch to MR-HC for progesterone (5.9 (55.5) vs. 5.0 (58.8), p=.823), 17OHP (5.9 (362.1) vs. 5.7 (73.7), p=.280), A4 (2.9 (25.6) vs. 2.5 (6.9), p=.106), testosterone (0.8 (3.5) vs. 0.7 (1.5), p=.063), 11KT (0.4 (7.4) vs. 0.2 (2.6), p=.242) and 11OHA4 (0.8 (12.9) vs. 0.9 (10.4), p=.231). Concerning saliva day profiles, we found a significantly lower median (range) 17OHP level in early morning saliva (43.0 (526.9) vs. 19.4 (264.3), p=.049). 5/9 patients with menstrual irregularities reported menstrual regularisation within and 5/10 patients with a desire to have children became pregnant after switching to MR-HC. Conclusion: Our preliminary data show clinical improvement in fecundity and fertility under MR-HC in both women with classic and NC CAH without a dose increase of glucocorticoids. Under MR-HC replacement lower 17OHP concentrations in early morning saliva reflect better hormonal control over night contributing to ovulatory cycle regulation and improved fertility.

Presentation: 6/1/2024