DeCure for Hypogonadotropic hypogonadism 6 with or without anosmia
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for hypogonadotropic hypogonadism 6 with or without anosmia — screening already-approved drugs against its 1-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleHypogonadotropic hypogonadism 6 with or without anosmia maps to a 1-gene Open Targets module — the target space DeCure's AI scientist screens approved drugs against.
DeCure.ai methodSignature reversal (LINCS) plus network proximity (STRING) rank already-approved drugs likely to perturb this module — the same engine that produces DeCure.ai's repurposing hypotheses.
Repurposing thesisScreening approved medicines against this disease module, then publishing the evidence for the strongest candidate. Known pharmacology and human exposure data make the first question sharper — they do not establish safety or efficacy in a new indication.
Research record
01
ResearchComing soon
Candidate research + dossier — target rationale, drug-repurposing thesis and evidence pack.proof: Published dossier + on-chain hash
02
ValidationComing soon
In-vitro biological validation at a contract research org (CRO).proof: CRO contract + in-vitro report
03
Peer review & paperComing soon
Peer-reviewed paper published open-access (preprint + journal).proof: DOI + open-access link + on-chain hash
Current lead
No approved-drug candidate for hypogonadotropic hypogonadism 6 with or without anosmia is corroborated in the literature DeepSearch retrieved. Some conditions are managed with non-pharmacological care — a device, surgery or physical therapy — rather than a medicine; that may be the case here, or the literature we found may simply be too sparse yet to support a drug-repurposing angle.
Molecular view
fibroblast growth factor 8 (FGF8) — FGF8 is one of the genes genetically linked to this disease in Open Targets — shown as context, not as a drug target we're pursuing: no approved-drug candidate for this disease is yet corroborated in the literature we found.
Loading structure…
helix sheet apo structuredrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 2FDB · 2.28 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
A 1997 study identified mutations in the gonadotropin-releasing hormone receptor gene in a family with hypogonadotropic hypogonadism, but noted that no abnormality of the GnRH gene itself had been found in several patients with the idiopathic form. Earlier reports from 1966 and 1968 described familial cases of hypogonadotropic hypogonadism with anosmia, with one proposing X-linked inheritance and another suggesting an autosomal mode based on an affected father. A 1970 paper reported that a patient with Kallmann’s syndrome did not show a rise in luteinizing or follicle-stimulating hormone after six weeks of clomiphene citrate.
A 2018 study of 100 HIV-infected men found an overall hypogonadism prevalence of 66%, with 42% having hypogonadotropic hypogonadism. Lower free testosterone and DHEAS levels correlated significantly with lower CD4 counts, and the prevalence of hypogonadism increased as immunodeficiency worsened. Mean free testosterone and FSH were significantly higher in patients on antiretroviral therapy than in those not on it, but no specific drug or combination correlated with hormone levels.
A 2022 case report described a 27-year-old man with known hypogonadotropic hypogonadism who presented with bilateral subtrochanteric insufficiency fractures of the femur that had been present for a considerable time. The authors noted that most proximal femur insufficiency fractures in the literature were associated with prolonged alendronate therapy or post-bariatric surgery, making this an uncommon presentation.
What is still missing is any controlled trial of a drug specifically for hypogonadotropic hypogonadism 6 with or without anosmia. The 1970 clomiphene failure is a single case. No genetic stratification beyond the GnRH receptor mutation has been linked to a treatment response. No funding for a dedicated trial in this rare condition is evident.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
New England Journal of Medicine · 1997 · 529 citations · open access
A Family with Hypogonadotropic Hypogonadism and Mutations in the Gonadotropin-Releasing Hormone Receptor
AbstractHypogonadotropic hypogonadism is often associated with anosmia in a condition known as Kallmann's syndrome. The gene for the X-linked form of Kallmann's syndrome has been mapped to chromosome Xp22.3,1 and several mutations have been described.2–4 In idiopathic hypogonadotropic hypogonadism there is no anosmia, and the involved genes have not been characterized. One possible candidate is the gene for gonadotropin-releasing hormone (GnRH), especially since hypogonadal mice with the deletion of this gene have been identified.5 However, no abnormality of the gene for GnRH has been found in several patients with idiopathic hypogonadotropic hypogonadism.6–9 The gene for the GnRH receptor . . .
The Journal of Clinical Endocrinology & Metabolism · 1970 · 29 citations
Hypogonadotropic Hypogonadism with Anosmia (Kallmann's Syndrome) Unresponsive to Clomiphene Citrate
AbstractA patient with hypogonadotropic hypogonadism and anosmia (Kallmann's syndrome) is reported. Plasma levels of pituitary follicle stimulating and luteinizing hormones, as determined by radioimmunoassay, were low, and did not rise following administration of clomiphene citrate for 6 weeks. Anosmia in the father supports an autosomal mode of inheritance in this case.
Postgraduate Medical Journal · 1966 · 14 citations · open access
Hypogonadism and life-long anosmia
AbstractJournal Article Hypogonadism and life-long anosmia Get access T D R Hockaday, MA, BM, BSc (Oxon), MRCP (Lond) T D R Hockaday, MA, BM, BSc (Oxon), MRCP (Lond) Lecturer in Medicine Department of the Regius Professor of Medicine, Radcliffe Infirmary, Oxford Search for other works by this author on: Oxford Academic Google Scholar Postgraduate Medical Journal, Volume 42, Issue 491, September 1966, Pages 572–574, https://doi.org/10.1136/pgmj.42.491.572 Published: 01 September 1966
Archives of Internal Medicine · 1968 · 14 citations
Familial hypogonadotropic hypogonadism with anosmia
AbstractHypogonadotropic hypogonadism with anosmia has been found in two brothers and a half sister, who are related through the same mother. Although the mother does not have the full syndrome, her history suggests she may have minor symptoms of the syndrome. X-linked inheritance seems most compatible with the familial distributions. Differences of this syndrome from other inherited hypogonadal conditions are discussed. The genetic defect is thought to directly or indirectly affect the hypothalamus which has associations with both olfaction and pituitary function. The importance of testing for anosmia in patients with abnormality in sexual development is noted.
Indian Journal of Endocrinology and Metabolism · 2018 · 12 citations · open access
Sex hormone profile in human immunodeficiency virus-infected men and it's correlation with CD4 cell counts
AbstractBackground: In human immunodeficiency virus (HIV)-infected men, hypogonadism is the most common endocrinological disorder, and most cases of hypogonadism are secondary. The aim of this study was to find out the hormonal abnormalities in HIV-infected males and it's correlation with CD4 cell counts. Materials and Methods: One hundred HIV-infected male patients were evaluated in the Department of Medicine, Postgraduate Institute of Medical Education and Research and Dr. Ram Manohar Lohia Hospital, New Delhi, India, over a period of 12 months from September 2014 to August 2015 using history, physical examination, routine baseline investigations, and CD4 counts. Free testosterone, dehydroepiandrosterone sulfate (DHEAS), luteinizing hormone (LH), follicle-stimulating hormone (FSH), and prolactin were measured using an overnight fasting sample. Patients were divided into three groups on the basis of CD4 counts (Group A: CD4 counts ≥350/mm3, Group B: CD4 counts between 200 and 349/mm3, and Group C: CD4 counts <200/mm3). Data were analyzed using Student's t-test, ANOVA test, Chi-square test, and Pearson's test and P ≤ 0.05 was considered statistically significant. Results: In 100 HIV-infected males, overall prevalence of hypogonadism was found to be 66%, and 30%–35% patients had symptoms of hypoandrogenemia. Hypogonadotropic hypogonadism was found in 42% of patients. A significant association (P = 0.027) was found between prevalence of hypogonadism and the level of immunodeficiency with an increase in the prevalence of hypogonadism as CD4 counts decreased. Lower levels of free testosterone and DHEAS were found in cases of severe immunosuppression with a statistically significant correlation with CD4 counts. Correlation of other sex hormones (LH, FSH, and prolactin) with CD4 counts not statistically significant. Mean free testosterone and FSH were found to be significantly higher in patients on antiretroviral therapy (ART) than in those not on ART (P = 0.028 and P = 0.045, respectively), but no specific ART drug or their drug combination was found to have a significant correlation with levels of any sex hormone. Conclusion: Hypogonadism (hypogonadotropic hypogonadism) was found to be a common endocrinological disorder in HIV-infected male population, seen more commonly in association with low CD4 counts.
Journal of Musculoskeletal Surgery and Research · 2022 · 1 citations · open access
Uncommon presentation of bilateral subtrochanteric insufficiency fractures in young male associated with hypogonadism: A case report
AbstractHypogonadism in men is a well-recognized cause of secondary osteoporosis. It is characterized by insufficient production of androgen, testosterone, and sperms. Testosterone deficiency is the key factor for insufficiency fractures in men, resulting from normal loading on an osteoporotic bone. In this report, we are presenting a case of a 27-year-old male known to have hypogonadotropic hypogonadism, who suffered from both femoral atraumatic subtrochanteric fractures that had been existing for a considerable time. The fractures interfered with the patient’s walking and daily activity. It is worth reporting this case because most of the proximal femur insufficiency fractures mentioned in the literature correlated with prolonged alendronate therapy or were post-bariatric surgery.
Disease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works (targeted per-candidate search), resolved on OpenAlex.
DeCure is a research and publication project, not medical advice and not a treatment. "DeCure for X" describes a research goal, not a claim that a cure exists. Backing a cure is a contribution to fund the research — it is not an investment, and confers no yield, royalty, equity or IP ownership. Papers are published open-access by the DeCure.ai DAO.
