DeCure for Hypogonadotropic hypogonadism 9 with or without anosmia
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for hypogonadotropic hypogonadism 9 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 9 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 9 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
In a 1997 study of a family with hypogonadotropic hypogonadism, mutations in the gonadotropin-releasing hormone receptor were identified, but the abstract provides no sample size or quantitative outcomes. A 2019 case report describes a 25-year-old man with congenital severe hyposmia who later developed adult-onset isolated hypogonadotropic hypogonadism at age 48; next-generation sequencing revealed a rare heterozygous SPRY4 gene variant (c.158G>A, p.R53Q) not previously reported. The patient was started on testosterone replacement therapy. The authors note that genetic mutations are currently found in only 40% of IHH patients.
A 2002 study of a large consanguineous family with five affected siblings and a normal gonadotropin-releasing hormone receptor coding sequence found a homozygous 155-nucleotide deletion in the GPR54 gene, encompassing the splicing acceptor site of intron 4-exon 5 junction and part of exon 5. The deletion was absent or present on only one allele in unaffected family members. The abstract identifies GPR54 and possibly KiSS1 protein-derived peptide as playing a previously unsuspected role in the gonadotropic axis.
A 2018 study of 100 HIV-infected men found an overall prevalence of hypogonadism of 66%, with hypogonadotropic hypogonadism in 42% of patients. A significant association (P = 0.027) was found between prevalence of hypogonadism and level of immunodeficiency, with prevalence increasing as CD4 counts decreased. Mean free testosterone and FSH were significantly higher in patients on antiretroviral therapy than in those not on ART (P = 0.028 and P = 0.045, respectively), but no specific ART drug or combination correlated significantly with sex hormone levels.
A 2023 randomised open-label prospective study of 51 patients compared three gonadotropin therapy modalities: hCG alone, combination hCG and HMG, and sequential therapy (hCG then combination after six months). All modalities significantly increased mean testicular volume, but the combination group had the highest increment. The combination group achieved the highest mean maximum testosterone level (710.4±102.7 ng/dL), followed by the sequential group (636.0±68.6 ng/dL) (p = 0.031). Factors negatively affecting testosterone level included BMI > 30 kg/m², initial testicular volume < 5 mL, and duration of therapy < 13 months. Prior exogenous testosterone treatment had no effect on final spermatogenesis. What remains missing are larger, longer-term trials that stratify patients by genetic aetiology, and studies that address the 60% of IHH patients in whom no genetic mutation is currently found.
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 . . .
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.
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
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.
Management Outcomes in Males With Hypogonadotropic Hypogonadism Treated With Gonadotropins
AbstractBackground Hypogonadotropic hypogonadism is an important cause of male infertility and loss of secondary sexual characteristics. Gonadotropin replacement is mandatory for sexual function, bone health, and normal psychological status. This study is to compare the effectiveness of different gonadotropin therapy modalities in the management of male hypogonadism. Methods A randomized open-label prospective study of 51 patients attended the Faiha Specialized Diabetes, Endocrine and Metabolism Center (FDEMC) with hypogonadotropic hypogonadism, divided randomly into three groups. The first group was treated with human chorionic gonadotropin (hCG) alone, the second group was treated with a combination of both hCG and human menopausal gonadotropin (HMG), while the third group started with hCG alone then followed by combination therapy after six months. Results All modalities of therapy result in a significant increase in mean testicular volume although no clinically significant difference between the groups, but the combination group had the highest increment. The increment in serum testosterone level was statistically significant among the different groups of treatment (p-value < 0.0001). When comparing groups, a higher mean maximum testosterone level (710.4±102.7 ng/dL) was obtained with the combination group followed by the sequential group, with mean maximum testosterone levels (636.0±68.6 ng/dL) (p-value = 0.031). Factors negatively affecting testosterone level include BMI > 30 kg/m2, initial testicular volume < 5 mL, and duration of therapy < 13 months. Conclusions Induction of puberty using recombinant hCG alone is sufficient to induce secondary sexual characteristics, while for fertility issues combination from the start or sequential therapy has better for spermatogenesis. There was no effect of prior exogenous testosterone treatment on final spermatogenesis.
Problems of Endocrinology · 2014 · 4 citations · open access
The role of the genetic factors in pathogenesis of hypogonadotropic hypogonadism
AbstractModern diagnostics of hypogonadism is based on the results of X-ray and laboratory (biochemical) investigations that reveal the idiopathic form of the disease in the majority of the patients. However, the recent studies have demonstrated a number of genes, whose disturbed function may be responsible for the development of hypogonadism. This creates the prerequisites for the extension of diagnostics of hypogonadism by means of genotyping of the various forms of the pathology in question and thereby may facilitate the choice of the relevant treatment strategy. The present review is focused on the elucidation of the pathogenetic role of candidate genes involved in the development of isolated hypogonadotropic hypogonadism.
AbstractHypogonadotropic hypogonadism is defined as a deficiency of the pituitary secretion of follicle-stimulating hormone and luteinizing hormone, which results in the impairment of pubertal maturation and of reproductive function. In the absence of pituitary or hypothalamic anatomical lesions and of anosmia (Kallmann syndrome), hypogonadotropic hypogonadism is referred to as isolated hypogonadotropic hypogonadism (IHH). A limited number of IHH cases are due to loss-of-function mutations of the gonadotropin-releasing hormone receptor. To identify additional gene defects leading to IHH, a large consanguineous family with five affected siblings and with a normal gonadotropin-releasing hormone receptor coding sequence was studied. Homozygosity whole-genome mapping allowed the localization of a new locus within the short arm of chromosome 19 (19p13). Sequencing of several genes localized within this region showed that all affected siblings of the family carried a homozygous deletion of 155 nucleotides in the GPR54 gene. This deletion encompassed the splicing acceptor site of intron 4-exon 5 junction and part of exon 5. The deletion was absent or present on only one allele in unaffected family members. GPR54 has been initially identified as an orphan G protein-coupled receptor with 40% homology to galanin receptors. Recently, a 54-aa peptide derived from the KiSS1 protein was identified as a ligand of GPR54. The present study shows that loss of function of GPR54 is a cause of IHH, and it identifies GPR54 and possibly KiSS1 protein-derived peptide as playing a major and previously unsuspected role in the physiology of the gonadotropic axis.
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.
