ArticleHuman reproduction open2026
Once-daily, late-night, modified-release hydrocortisone rapidly normalizes menstrual cyclicity in women with non-classic congenital adrenal hyperplasia.
Article in Human reproduction open, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
study questionDoes late-night, modified-release hydrocortisone (MR-HC) improve biochemical control and restore menstrual regularity in women with non-classic congenital adrenal hyperplasia (NCCAH)? SUMMARY ANSWER: Once-daily MR-HC substantially improved biochemical androgen control and rapidly restored menstrual cyclicity in women with NCCAH, including those with longstanding irregular cycles. WHAT IS KNOWN ALREADY: While pregnancy rates in women with NCCAH are generally comparable to those of the general population, time to conception is often prolonged and assisted reproductive techniques are frequently required. Optimizing adrenal androgen suppression through the superior pharmacokinetic profile of MR-HC may shorten this interval and reduce the need for fertility interventions. So far, MR-HC has not been tested in NCCAH. STUDY DESIGN SIZE DURATION: Prospective observational cohort study conducted between September 2021 and November 2025 at a tertiary referral center and European Reference Network (Endo-ERN) hub for congenital adrenal hyperplasia. Thirty women with NCCAH were enrolled and followed for a median of 22.5 months (interquartile range [IQR] 8.25-36.75), with up to five study visits. Only women with at least 3 months of follow-up were included in the analysis. PARTICIPANTS/MATERIALS SETTING
methodsThe cohort comprised 30 women with NCCAH. At initiation of MR-HC, 20 women transitioned from conventional glucocorticoid therapy, and 10 were treatment-naïve. Sixteen women had an active desire to conceive, while 15 presented with irregular menstrual cycles or secondary amenorrhea at baseline. MAIN RESULTS AND THE ROLE OF CHANCE: Among 14 evaluable women, ovulatory function, defined as return of regular menstrual cycles or conception, was restored in 13 (92.6%) of women within 6 months of MR-HC initiation. One woman with concomitant hypothalamic hypogonadism remained amenorrhoeic and commenced hormone replacement therapy. Cycle normalization occurred at a median MR-HC dose of 10 mg (IQR 10-15 mg), with all but one woman receiving a single bedtime dose. Among 16 women seeking pregnancy, ten conceived within a median of 2.65 months (IQR 2.0-12.4) compared to 8 months (IRQ 1.0-24.0) in a historic cohort of NCCAH women before the approval of MR-HC (not significant). Among those seeking pregnancy, 10 women had been attempting to conceive unsuccessfully for a median of 28.5 months (IQR 12-46) before. Six women did not become pregnant during follow-up (13.5 months; IQR 6.25-23). The hydrocortisone equivalent dose (HCeq) at the time of conception was significantly lower under MR-HC (10.0 mg (IQR 10-12.5) vs. 16.9 mg (IQR 15-25), LIMITATIONS REASONS FOR CAUTION: While the rapid normalization of, in part, long-standing menstrual irregularities was striking, the absence of a control group does not allow causal inferences, and the single-center design within a specialized tertiary setting may limit generalizability. WIDER IMPLICATIONS OF THE
findingsA single nightly dose of MR-HC appears sufficient to achieve hormonal control and subsequent menstrual-cycle restoration in most women with NCCAH and may improve time to conception. These findings support MR-HC as a promising therapeutic option in the management of NCCAH.
fundingThis work was supported by the Deutsche Forschungsgemeinschaft (Heisenberg Professorship 325768017, project 314061271 TRR205 to NR and FBCRC-1665 -515637292 to NR and UK). LT was supported by the LMU Munich funding scheme (FöFoLe) and by the IFCAH (International Fund Congenital Adrenal Hyperplasia) grant 2023. HN was supported by the Clinician Scientist Program RISE, supported by the Eva Luise und Horst Köhler Stiftung & Else Kröner-Fresenius-Stiftung (2019_KollegSE.03 to HN). DISCLOSURES: N.R. was Principal Investigator and consulted for Neurocrine Biosciences and Diurnal Ltd. L.T., M.K. A. und H.F.N. were Sub-Investigators for Neurocrine Biosciences and Diurnal Ltd. TRIAL REGISTRATION NUMBER: N/A.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.