Modified-Release Hydrocortisone for Female Fertility in Congenital Adrenal Hyperplasia

Women with classic congenital adrenal hyperplasia (CAH) suffer from reduced fecundity and fertility. This study aimed to assess fertility outcomes following treatment with modified-release hydrocortisone (MRHC), which more closely replicates the physiological circadian cortisol rhythm.

In this prospective case series, eight women with classic CAH and either menstrual irregularities or an unfulfilled desire to have children despite conventional GC therapy for a median duration of four years, including assisted reproduction, were switched to MRHC. Hormonal parameters, including morning serum progesterone, 17-hydroxyprogesterone (17OHP), androstenedione, testosterone, as well as daily salivary 17OHP profiles, were assessed before and after the switch. Clinical outcomes included menstrual cycle regularity and pregnancy.

Descriptive analysis of morning serum samples indicate lower median concentrations of progesterone (0.9 vs. 2.1 ng/mL [2.9 vs. 6.7 nmol/l]), 17OHP (49.0 vs. 131.5 ng/dl [1.5 vs. 4.0 nmol/l]), androstenedione (76.0 vs. 261.0 ng/dL [2.7 vs. 9.1 nmol/l]), and testosterone (27.0 vs. 63.0 ng/dL [0.9 vs. 2.2 nmol/l]) after switching to MRHC with a lower median hydrocortisone dose equivalent (HDE) (30.0 v. 32.5 mg/d). Salivary 17OHP profiles showed a trend towards lower median AUC (183.9 vs. 676.5 pg×t(n)/mL) and lower concentrations across all time points. Regular menstrual cycles were restored in all patients. All five women seeking pregnancy conceived within a median of 9.8 months. Two unintended pregnancies occurred. Outcomes included six healthy live births and one early miscarriage.

MRHC improved hormonal control and was associated with restoration of menstrual cyclicity and high rates of spontaneous conception with a lower HDE. Circadian optimization of GC therapy by MRHC may represent a paradigm shift in fertility management in females with CAH.