SynthesisThe Journal of clinical endocrinology and metabolism2026
Reversal of Congenital Hypogonadotropic Hypogonadism.
Synthesis in The Journal of clinical endocrinology and metabolism, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
What it found
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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
1 citing paper in PubMed.
- Reversible congenital hypogonadotropic hypogonadism: keys for clinical management.Archives of endocrinology and metabolism · 2026Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors.
Funding
Abstract
contextCongenital genetic disorders have been traditionally considered to be lifelong. An exception to this long-held view is the reversal of congenital hypogonadotropic hypogonadism (CHH). Approximately 10% of male individuals with CHH undergo reversal with sustained hypothalamic-pituitary-gonadal (HPG) axis activation and/or fertility after discontinuing hormonal treatment. EVIDENCE ACQUISITION: We conducted a structured, systematic literature search to identify relevant articles published on reversal of CHH in males (up to 2025). This mini-review provides a concise overview and synthesizes findings to inform clinical management of CHH. EVIDENCE SYNTHESIS: We identified 31 articles reporting reversal of CHH in males, including cases of severe GnRH deficiency and individuals harboring pathogenic variants in CHH genes. Reversal is distinct from delayed puberty, and olfactory phenotype (ie, anosmia) does not predict HPG axis recovery. In males, reversal universally occurs after achieving normal serum testosterone levels on hormone therapy. Testicular growth on testosterone replacement is a hallmark of HPG axis activation-yet reversal is not always lasting. Cases exist on a continuum from normosmic individuals with severe GnRH deficiency to milder cases with partial spontaneous puberty (Pasqualini syndrome subtype). Pathogenic variants in GNRHR favor reversal while ANOS1 variants virtually exclude HPG axis recovery.
conclusionThe reversal phenomenon in males has expanded our understanding of the regulation of human reproduction-yet precise mechanism(s) have yet to be elucidated. Clinicians can use clinical signs and genetic testing to identify patients who may benefit from close surveillance of reversal. Insights from reversal of CHH reversal have helped shape the first tailored approach managing CHH.
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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 Socratic graph.