Evidence mapPaperPMID 41206002Full record

SynthesisThe Journal of clinical endocrinology and metabolism2026

Reversal of Congenital Hypogonadotropic Hypogonadism.

Andrew A Dwyer, Maria Stamou

Abstract readSystematic Review
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

2 authors.

Andrew A DwyerWilliam F. Connell School of Nursing, Boston College, Chestnut Hill, MA 02467, USA.ORCID 0000-0002-7023-6794
Maria StamouP50 Massachusetts General Hospital-Harvard Center for Reproductive Medicine, Boston, MA 02114, USA.ORCID 0000-0001-5992-2120

Funding

Elucidating the Role of the FGFR1 Signaling Pathway in the Intersection of Reproduction and MetabolismK23HD117006 · MASSACHUSETTS GENERAL HOSPITAL · 2025 to 2025
$171k
National Institute of Child Health and Human 1P50HD104224-01National Institutes of Health Eunice Kennedy ShriverNICHD NIH HHS K23 HD117006
6 · The paper itself

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.

Indexed as

Hormone Replacement TherapyHypogonadismExtracellular Matrix ProteinsGonadotropin-Releasing HormoneHumansHypothalamo-Hypophyseal SystemMaleNerve Tissue ProteinsTestosteroneANOS1 protein, humanExtracellular Matrix ProteinsGonadotropin-Releasing HormoneNerve Tissue ProteinsTestosteronegeneticsKallmann syndromepubertyreproduction

Identifiers

PMID41206002
PMCPMC12819876

What Socratic holds

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Registered trials

None linked

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.