ArticleThe Journal of clinical endocrinology and metabolism2021
Increased Burden of Rare Sequence Variants in GnRH-Associated Genes in Women With Hypothalamic Amenorrhea.
Article in The Journal of clinical endocrinology and metabolism, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 22 citations in OpenAlex.
- Does Depression Increase the Risk of Endometriosis? A Combined Population‑Based and Laboratory Study.International journal of women's health · 2026Article
- Synthesizing the latest guideline-based recommendations for the management of female hypogonadism.Archives of endocrinology and metabolism · 2025Review
- Shared Genetic Architecture Between Endometriosis and Psychiatric Conditions May Explain Comorbidity.medRxiv : the preprint server for health sciences · 2025Article
- [Endocrine and psychosomatic disorders in patients with amenorrhea].Problemy endokrinologii · 2024Review
- High Population Frequency ofJournal of the Endocrine Society · 2024Article
- Gene-environment interaction in functional hypothalamic amenorrhea.Frontiers in endocrinology · 2024Review
- Epigenetics of functional hypothalamic amenorrhea.Frontiers in endocrinology · 2022Review
- Clinical and biochemical discriminants between functional hypothalamic amenorrhoea (FHA) and polycystic ovary syndrome (PCOS).Clinical endocrinology · 2021Review
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Authors and funding
17 authors at 7 institutions in 3 countries.
Funding
Abstract
contextFunctional hypothalamic amenorrhea (HA) is a common, acquired form of hypogonadotropic hypogonadism that occurs in the setting of energy deficits and/or stress. Variability in individual susceptibility to these stressors, HA heritability, and previous identification of several rare sequence variants (RSVs) in genes associated with the rare disorder, isolated hypogonadotropic hypogonadism (IHH), in individuals with HA suggest a possible genetic contribution to HA susceptibility.
objectiveWe sought to determine whether the burden of RSVs in IHH-related genes is greater in women with HA than controls.
designWe compared patients with HA to control women.
settingThe study was conducted at secondary referral centers. PATIENTS AND OTHER
participantsWomen with HA (n = 106) and control women (ClinSeq study; n = 468).
interventionsWe performed exome sequencing in all patients and controls. MAIN OUTCOME MEASURE(S): The frequency of RSVs in 53 IHH-associated genes was determined using rare variant burden and association tests.
resultsRSVs were overrepresented in women with HA compared with controls (P = .007). Seventy-eight heterozygous RSVs in 33 genes were identified in 58 women with HA (36.8% of alleles) compared to 255 RSVs in 41 genes among 200 control women (27.2%).
conclusionsWomen with HA are enriched for RSVs in genes that cause IHH, suggesting that variation in genes associated with gonadotropin-releasing hormone neuronal ontogeny and function may be a major determinant of individual susceptibility to developing HA in the face of diet, exercise, and/or stress.
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