DeCure for Hypogonadotropic hypogonadism 1 with or without anosmia
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for hypogonadotropic hypogonadism 1 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 1 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 1 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 1968 report, two brothers and a half-sister related through the same mother were described with hypogonadotropic hypogonadism and anosmia. The mother did not have the full syndrome but her history suggested minor symptoms. X-linked inheritance was considered most compatible with the family distribution. The genetic defect was thought to affect the hypothalamus, linking olfaction and pituitary function. No gene was identified at that time.
A 1997 study noted that hypogonadotropic hypogonadism with anosmia is known as Kallmann’s syndrome, and the X-linked form had been mapped to chromosome Xp22.3 with several mutations described. In idiopathic hypogonadotropic hypogonadism without anosmia, the involved genes had not been characterised. The GnRH receptor gene was considered a candidate, but no abnormality of the GnRH gene itself had been found in several patients. No specific mutation in the GnRH receptor was reported in that abstract.
A 2018 study of 100 HIV-infected men found an overall prevalence of hypogonadism of 66%, with 30–35% reporting symptoms of hypoandrogenemia. Hypogonadotropic hypogonadism was present in 42% of patients. A significant association was found between prevalence of hypogonadism and level of immunodeficiency (P = 0.027), with prevalence increasing as CD4 counts decreased. Lower free testosterone and DHEAS levels were found in severe immunosuppression and correlated significantly with CD4 counts. 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), but no specific ART drug or combination correlated significantly with any sex hormone level. No treatment for hypogonadotropic hypogonadism itself was tested in this study.
What is still missing is a clear genetic or molecular target for the inherited form of hypogonadotropic hypogonadism with anosmia, and no trial has tested a drug aimed at the underlying defect. For the HIV-associated form, no intervention trial has addressed whether treating the hypogonadotropic hypogonadism improves outcomes, and patient stratification by CD4 count or ART regimen has not been used to guide such a trial. Funding for a randomised controlled trial of hormone replacement or a repurposed agent in either population has not been reported.
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 · 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.
Mediterranean Journal of Hematology and Infectious Diseases · 2016 · 0 citations · open access
REVIEW AND RECOMMENDATIONS ON MANAGEMENT OF ADULT FEMALE THALASSEMIA PATIEΝTS WITH HYPOGONADISM BASED ON LITERATURE REVIEW AND EXPERIENCE OF ICET-A NETWORK SPECIALISTS
AbstractBackground: Multi-transfused thalassemia major (TM) patients frequently develop severe endocrine complications, mainly due to iron overload, anemia and chronic liver disease, which require prompt diagnosis, treatment and follow-up by specialists.The most common endocrine complication documented is hypogonadotropic hypogonadism which increases with age and associated comorbidities. It is thus important for physicians to have a clear understanding of the pathophysiology and management of this disorder. Also to be aware of the side effects, contraindications and monitoring of sex steroid therapy. In this paper practical ICET-A recommendations for the management of hypogonadism in adult females with TM are addressed.Methods: In March 2015, the Coordinator of the International Network of Clinicians for Endocrinopathies in Thalassemia and Adolescent Medicine (ICET-A) conducted a two-step survey to assess the attitudes and practices of doctors in the ICET-A network taking care of adult female TM patients with hypogonadism. They were clinically characterized by the absence of pubertal development, or discontinuation or regression of the maturation of secondary sex characteristics, and biochemically by persistent low FSH, LH and estradiol levels. Recently a supplementary survey on adult female hypogonadism in TM was undertaken within the ICET-A network.Results: The completed questionnaires were returned by 16 of 27 specialists (59.2%) following 590 female TM patients over the age of 18 years; 315 patients (53.3%) had hypogonadism and only 245 (74.6%) were on hormone replacement therapy (HRT). Contraceptive oral pills (COC) were the first treatment choice in 11 centres (68.7%). A wide range of COCs were used with different progestin contents. In general, the patients’ compliance to treatment was reported as good in 81.2 % of centres. The frequency of required tests for follow-up HRT, in addition to the regular check-up for thalassemia, was variable in the participating centres.Conclusions: Doctors taking care of TM patients should have sound knowledge of the pathophysiology of hypogonadism in adult females with TM. They should know the potential effects of HRT including advantages and disadvantages of estrogen and progestins. Moreover, they should keep in consideration the emotional needs of these patients dreaming to attain a full pubertal development.Key words: Thalassemia, hypogonadism, hormone replacement therapy, benefits and disadvantages
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.
