DeCure for Hypogonadotropic hypogonadism 12 with or without anosmia
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for hypogonadotropic hypogonadism 12 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 12 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 12 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
gonadotropin releasing hormone 1 (GNRH1) — GNRH1 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 4D5M · 0.85 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
In two brothers and a half-sister related through the same mother, hypogonadotropic hypogonadism with anosmia was observed; the mother did not have the full syndrome but her history suggested minor symptoms. X-linked inheritance was considered most compatible with that familial distribution. The genetic defect was thought to directly or indirectly affect the hypothalamus, which has associations with both olfaction and pituitary function. A separate 1972 report described a 58-year-old male with anosmia and primary testicular failure who secreted elevated levels of gonadotrophin, indicating that in hypogonadotropic hypogonadism with anosmia (Kallmann’s syndrome) the hypogonadotrophism is not the result of anosmia alone, and that other, probably hypothalamic, factors are involved. That patient phenotypically resembled Klinefelter’s syndrome but no chromosomal abnormality was detected; hypergonadotrophic hypogonadism associated with anosmia had not previously been reported.
In a 2018 study of 100 HIV-infected men, the overall prevalence of hypogonadism was 66%, and 30–35% of patients had symptoms of hypoandrogenemia. Hypogonadotropic hypogonadism was found in 42% of patients. A significant association (P = 0.027) was found between the prevalence of hypogonadism and the level of immunodeficiency, with prevalence increasing as CD4 counts decreased. Lower levels of free testosterone and dehydroepiandrosterone sulfate were found in cases of severe immunosuppression, with a statistically significant correlation with CD4 counts. Correlation of other sex hormones (luteinising hormone, follicle-stimulating hormone, prolactin) with CD4 counts was not statistically significant. Mean free testosterone and follicle-stimulating hormone were significantly higher in patients on antiretroviral therapy than in those not on it (P = 0.028 and P = 0.045, respectively), but no specific antiretroviral drug or combination had a significant correlation with levels of any sex hormone.
A 2024 review states that hypogonadotropic hypogonadism is a relatively rare cause of nonobstructive azoospermia, but that it can be corrected with medical therapy in three quarters of cases. Congenital forms may be anosmic (Kallmann syndrome) or normosmic; acquired forms occur after pubertal development. Gonadotropin-releasing hormone or gonadotropin replacement therapy is the mainstay of drug therapy and offers excellent results, although a small but significant proportion of patients do not achieve sufficient responses.
What is still missing is prospective data on which patients with congenital hypogonadotropic hypogonadism fail to respond to gonadotropin therapy and why, and whether the association with immunodeficiency in HIV-infected men represents a distinct mechanism that might be reversible with immune restoration. No randomised trial has stratified patients by anosmia status or by genetic defect to predict treatment response.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
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.
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.
European Journal of Endocrinology · 1972 · 6 citations
HYPERGONADOTROPHIC HYPOGONADISM WITH ANOSMIA
AbstractABSTRACT A 58 year old male with anosmia and primary testicular failure is described. The presence of anosmia did not preclude the secretion of elevated levels of gonadotrophin suggesting that in hypogonadotrophic hypogonadism with anosmia (Kallmann's syndrome) the hypogonadotrophism is not the result of anosmia alone, but that other, probably hypothalamic, factors are involved. The patient described phenotypically resembled Klinefelter's syndrome, but no chromosomal abnormality was detected. To our knowledge, hypergonadotrophic hypogonadism associated with anosmia has not previously been reported, and thus may represent a heretofore unrecognized clinical entity.
Asian Journal of Andrology · 2024 · 3 citations · open access
Hypogonadotropic hypogonadism as a cause of NOA and its treatment
AbstractABSTRACT: Hypogonadotropic hypogonadism (HH) represents a relatively rare cause of nonobstructive azoospermia (NOA), but its knowledge is crucial for the clinical andrologists, as it represents a condition that can be corrected with medical therapy in 3 quarters of cases. There are forms of congenital HH, whether or not associated with an absent sense of smell (anosmic HH or Kallmann syndrome, and normosmic HH, respectively), and forms of acquired HH. In congenital HH, complete absence of pubertal development is characteristic. On the other hand, if the deficit occurs after the time of pubertal development, as in acquired HH patients, infertility and typical symptoms of late-onset hypogonadism are the main reasons for seeking medical assistance. Gonadotropin-releasing hormone (GnRH) or gonadotropin replacement therapy is the mainstay of drug therapy and offers excellent results, although a small but significant proportion of patients do not achieve sufficient responses.
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.
