DeCure for Hypogonadotropic hypogonadism 5 with or without anosmia
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for hypogonadotropic hypogonadism 5 with or without anosmia — screening already-approved drugs against its 2-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 5 with or without anosmia maps to a 2-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 5 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.
What the evidence adds up to
A 1968 report described two brothers and a half-sister with hypogonadotropic hypogonadism and anosmia, all related through the same mother, and proposed X-linked inheritance as the most likely pattern. In 1997, a family with hypogonadotropic hypogonadism and mutations in the GnRH receptor was reported; the abstract notes that no abnormality of the GnRH gene itself had been found in several patients with idiopathic hypogonadotropic hypogonadism at that time. A 2019 case report identified a rare heterozygous variant in the SPRY4 gene (c.158G>A, p.R53Q) in a 48-year-old man who had congenital severe hyposmia but completed normal puberty, and only later developed adult-onset isolated hypogonadotropic hypogonadism. The authors state that genetic mutations are currently found in only 40% of IHH patients.
A separate 2018 study of 100 HIV-infected men found an overall prevalence of hypogonadism of 66%, with hypogonadotropic hypogonadism specifically in 42% of patients. Lower free testosterone and DHEAS levels correlated significantly with lower CD4 counts, and the prevalence of hypogonadism increased as CD4 counts decreased (P = 0.027). Mean free testosterone and FSH were significantly higher in patients on antiretroviral therapy than in those not on it, but no specific drug or drug combination correlated with any sex hormone level.
The 2019 case report concludes that in patients with apparently isolated congenital anosmia, genetic analysis can guide follow-up because IHH can manifest later in adulthood. The 1968 paper notes the importance of testing for anosmia in patients with abnormal sexual development. The 1997 abstract states that the genes involved in idiopathic hypogonadotropic hypogonadism without anosmia had not been characterised at that time.
What is still missing is a molecular diagnosis for the majority of IHH patients — mutations are found in only 40% — and a clear understanding of modifying genes and acquired environmental factors that determine whether and when the condition manifests. The HIV study is observational and does not test any intervention for hypogonadotropic hypogonadism itself. No trial has prospectively tested whether early genetic screening in anosmic individuals alters long-term outcomes, and no therapy beyond testosterone replacement is evaluated in these abstracts.
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 . . .
Archives of Internal Medicine · 1968 · 72 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.
Frontiers in Endocrinology · 2019 · 14 citations · open access
A Rare SPRY4 Gene Mutation Is Associated With Anosmia and Adult-Onset Isolated Hypogonadotropic Hypogonadism
AbstractBackground. Isolated hypogonadotropic hypogonadism (IHH) is a rare, clinically heterogeneous condition, caused by the deficient secretion or action of gonadotropin releasing hormone (GnRH). It can manifest with absent or incomplete sexual maturation, or as infertility at adult-age; in a half of cases, IHH is associated with hypo/anosmia (Kallmann syndrome). Although a growing number of genes are being related to this disease, genetic mutations are currently found only in 40% of IHH patients. Case description. Severe congenital hyposmia was diagnosed in a 25-year-old Caucasian man. The patient had no history of neonatal cryptorchidism or micropenis and had gone through and completed physiological puberty; past medical history and physical examination were unremarkable. Olfactory structures appeared hypoplasic on neuroradiological imaging, while hypothalamus, pituitary gland and stalk were normal; testosterone levels, functioning of GnRH-gonadotropin axis and other pituitary hormones’ secretion were unaffected at the time of first referral. At the age of 48, the patient returned to our clinic for sexual complaints, and the finding of low testosterone levels with inappropriately normal gonadotropin levels led to the diagnosis of hypogonadotropic hypogonadism. GnRH test was consistent with hypothalamic origin of the defect. Next generation sequencing was then performed revealing a rare heterozygous allelic variant in SPRY4 gene (c.158G>A, p.R53Q). The biological and clinical effects of this gene variant had never been reported before. A diagnosis of Kallmann syndrome was finally established, and the patient was started on testosterone replacement therapy. Conclusion. This case describes the clinical phenotype associated with a rare SPRY4 gene allelic variant, consisting in congenital severe smell defect and adult-onset IHH; in patients with apparently isolated congenital anosmia genetic analysis can be valuable to guide follow up, since IHH can manifest later in adulthood. Characterization of other modifying genes and acquired environmental factors is needed for a better understanding of the physiopathology and clinical manifestations of this disease.
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.
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.
