DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for hypogonadotropic hypogonadism — screening already-approved drugs against its 32-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 maps to a 32-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
Structures already discussed alongside hypogonadotropic hypogonadism in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
Crystal structure of the neocarzinostatin 3Tes24 mutant — Testosterone has a real, experimentally solved structure in complex with this target (PDB 2CBO, 1.7 Å). This is the drug's own deposited structure, not a prediction, and confirms it is a structurally characterised molecule rather than an untested guess.
Loading structure…
helix sheet th2drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 2CBO · 1.7 Å · ligand Testosterone (TH2). Experimental structure, not a prediction.
What the evidence adds up to
In a 1996 open-label multicentre study of a testosterone transdermal system, men with hypogonadism showed more frequent nocturnal erections of longer duration and greater rigidity, and higher patient-reported sexual desire and weekly number of erections, when testosterone levels were normalised compared to a withdrawal period. A 2022 study of 95 hypogonadal men given 225 mg of oral testosterone undecanoate (TLANDO) twice daily for 24 days without dose adjustment found that 80% (95% CI 72–88%) achieved a mean 24-hour testosterone concentration in the eugonadal range, with mean steady-state Cavg of 476 ± 184 ng/dL from a baseline of 202 ± 74 ng/dL. A separate 2021 randomised trial of 321 hypogonadal men compared oral testosterone undecanoate (n=161) with testosterone gel (n=160) over one year, using the Psychosexual Daily Questionnaire; the abstract reports persistent improved sexual symptom scores but gives no numerical results for the comparison.
A 2023 randomised open-label study of 51 men with hypogonadotropic hypogonadism compared three gonadotropin regimens: human chorionic gonadotropin (hCG) alone, hCG plus human menopausal gonadotropin (HMG) from the start, and hCG alone followed by combination after six months. All groups had significant increases in mean testicular volume, with no clinically significant difference between groups, though the combination group had the highest increment. Serum testosterone rose significantly in all groups (p < 0.0001); the combination group reached the highest mean maximum level (710.4 ± 102.7 ng/dL), followed by the sequential group (636.0 ± 68.6 ng/dL, p = 0.031). Factors associated with lower testosterone included BMI > 30 kg/m², initial testicular volume < 5 mL, and therapy duration < 13 months. Prior exogenous testosterone did not affect final spermatogenesis.
A 2013 retrospective database analysis of 6,033 hypogonadal men found that 97 (1.6%) had profound hypogonadism (testosterone ≤ 50 ng/dL), and the most common identified cause was prior anabolic androgenic steroid use, accounting for 42 of those 97 (43%). In a follow-up survey of 382 men on testosterone therapy, 80 (20.9%) reported prior anabolic steroid exposure; men under 50 were more than ten times as likely to have such exposure than those over 50 (OR 10.16, 95% CI 4.90–21.08). A 2016 review notes that off-label therapies that modulate the hypothalamic–gonadal axis to raise endogenous testosterone exist but are not standard. A 2009 study of a fixed 2:1 combination of recombinant FSH and LH for ovulation induction in women with hypogonadotropic hypogonadism reports high efficiency and safety in phase II/III trials, but the abstract gives no specific response rates.
What remains missing is direct comparative effectiveness data between oral testosterone undecanoate and gonadotropin therapy for hypogonadotropic hypogonadism, particularly for fertility outcomes. The 2023 gonadotropin study had only 51 patients and no placebo arm. Long-term safety data for oral testosterone undecanoate beyond one year are not provided in these abstracts. No trial has stratified patients by prior anabolic steroid exposure or BMI to guide treatment choice.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
The Journal of Urology · 1996 · 159 citations
Improvement of Sexual Function in Testosterone Deficient Men Treated for 1 Year with a Permeation Enhanced Testosterone Transdermal System
AbstractPURPOSE: The effects of androgen replacement via a nonscrotal permeation enhanced testosterone transdermal system on the sexual function of men with hypogonadism were assessed. MATERIALS AND METHODS: An open label, multicenter study of testosterone supplementation and withdrawal was conducted with sexual function assessed by the Watts and Davidson questionnaires and RigiScan monitoring. RESULTS: When comparing results obtained during use of the testosterone transdermal system (with normalized testosterone levels) and during the androgen withdrawal period, nocturnal erections occurred more frequently with longer duration and greater rigidity, and patient assessments of sexual desire and weekly number of erections were higher. CONCLUSIONS: Sexual function improved significantly in men with hypogonadism treated with the testosterone transdermal system.
Anabolic Steroid Induced Hypogonadism in Young Men
AbstractPURPOSE: The use of anabolic androgenic steroids has not been traditionally discussed in mainstream medicine. With the increased diagnosis of hypogonadism a heterogeneous population of men is now being evaluated. In this larger patient population the existence of anabolic steroid induced hypogonadism, whether transient or permanent, should now be considered. MATERIALS AND METHODS: We performed an initial retrospective database analysis of all 6,033 patients who sought treatment for hypogonadism from 2005 to 2010. An anonymous survey was subsequently distributed in 2012 to established patients undergoing testosterone replacement therapy. RESULTS: Profound hypogonadism, defined as testosterone 50 ng/dl or less, was identified in 97 men (1.6%) in the large retrospective cohort initially reviewed. The most common etiology was prior anabolic androgenic steroid exposure, which was identified in 42 men (43%). Because of this surprising data, we performed an anonymous followup survey of our current hypogonadal population of 382 men with a mean±SD age of 49.2±13.0 years. This identified 80 patients (20.9%) with a mean age of 40.4±8.4 years who had prior anabolic androgenic steroid exposure. Hypogonadal men younger than 50 years were greater than 10 times more likely to have prior anabolic androgenic steroid exposure than men older than 50 years (OR 10.16, 95% CI 4.90-21.08). Prior anabolic androgenic steroid use significantly correlated negatively with education level (ρ=-0.160, p=0.002) and number of children (ρ=-0.281, p<0.0001). CONCLUSIONS: Prior anabolic androgenic steroid use is common in young men who seek treatment for symptomatic hypogonadism and anabolic steroid induced hypogonadism is the most common etiology of profound hypogonadism. These findings suggest that it is necessary to refocus the approach to evaluation and treatment paradigms in young hypogonadal men.
Treatment of Hypogonadism: Current and Future Therapies
AbstractThe treatment of hypogonadism in men is of great interest to both patients and providers. There are a number of testosterone formulations currently available and several additional formulations under development. In addition, there are some lesser-used alternative therapies for the management of male hypogonadism, which may have advantages for certain patient groups. The future of hypogonadism therapy may lie in the development of selective androgen receptor modulators that allow the benefits of androgens whilst minimizing unwanted side effects.
A new oral testosterone (TLANDO) treatment regimen without dose titration requirement for male hypogonadism
AbstractBACKGROUND: Male hypogonadism (testosterone level < 300 ng/dl) is a clinical syndrome that results from failure of the testis to produce physiological levels of testosterone. Most marketed testosterone replacement therapy products often require multiple dose adjustment clinic visits to achieve the desired, eugonadal testosterone levels. OBJECTIVE: To evaluate the efficacy and safety of a novel oral testosterone undecanoate therapy for the treatment of hypogonadism. MATERIAL AND METHODS: Ninety-five (N = 95) hypogonadal men were enrolled in this open-label, single-arm, multicenter study in the United States (NCT03242590). Subjects received 225 mg of oral testosterone undecanoate (TLANDO) twice a day for 24 days without dose adjustment. Primary efficacy was percentages of subjects who achieved mean 24-h testosterone levels within the eugonadal range and secondary efficacies were evaluated based on the upper limit of lab normal range of testosterone concentration. RESULTS: . The baseline mean total testosterone values were below the normal range (202 ± 74 ng/dl). Post-treatment with 450 mg testosterone undecanoate daily dose without dose adjustment, 80% of subjects (95% confidence interval of 72%-88%) achieved a testosterone Cavg in the normal range and restored testosterone levels to mean testosterone Cavg of 476 ± 184 ng/dl at steady state. Testosterone restoration was comparable to other approved testosterone replacement therapy products. TLANDO was well tolerated with no deaths, no drug-related serious adverse events, and no hepatic adverse events. DISCUSSION AND CONCLUSIONS: TLANDO restored testosterone levels to the normal range in the majority of hypogonadal males. This new oral testosterone replacement therapy can provide an option for no-titration oral testosterone replacement therapy. This therapy has the potential to improve patient compliance in testosterone replacement therapy.
Translational Andrology and Urology · 2016 · 12 citations · open access
Off label therapies for testosterone replacement
AbstractThe incidence of hypogonadism has been steadily increasing over the last few years. Exogenous testosterone has been the standard treatment for hypogonadal men, but is associated with suppression of spermatogenesis as well as other possible adverse effects. There are other medications, currently considered "off label" for androgen replenishment, that exert their effect through modulation of the hypothalamic-gonadal axis. These medications increase endogenous testosterone levels and offer a different therapeutic approach. This review will focus on these alternative (off-label) therapies for androgen replacement in men.
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.
Recombinant human FSH and recombinant human LH in a 2:1 ratio combination: a new tool for ovulation induction
AbstractHypogonadotrophic hypogonadism is a dysfunction characterized by the lack of gonadotrophin production and, therefore, attenuated or stopped gonadal action, which leads to anovulation and subsequent infertility. A new fixed combination of recombinant human FSH and recombinant human LH in a 2:1 ratio has recently been developed. Pharmacological studies show bioequivalence with the parameters of the separated compounds. Phase II/III studies have demonstrated high efficiency and safety for inducing ovulation in these patients. Studies analyzing the potential role of recombinant human luteinizing hormone supplement in normovulatory patients following ovarian stimulation for IVF–embryo transfer under pituitary downregulation, suggest a benefit in patients over 35 years old and/or with low response to stimulation with recombinant human follicle-stimulating hormone administered alone. However, further studies are needed to further analyze this issue.
The Journal of Sexual Medicine · 2021 · 1 citations
026 Hypogonadal Men Treated with an Oral Testosterone Undecanoate had Persistent Improved Sexual Symptom Scores Over One Year
AbstractMale hypogonadism is defined by a low serum testosterone (T) concentration (e.g., < 300 ng/dL) and associated symptoms. A novel oral testosterone undecanoate (TU) formulation1 now offers hypogonadal men in the U.S. a new treatment option compared to long-standing T replacement products (e.g., intramuscular or subcutaneous injections (T-esters), subcutaneous T pellets, transdermal T-gels, buccal T patch or a nasal T-gel). To determine the change in sexual functioning and well-being, as measured by the Psychosexual Daily Questionnaire (PDQ)2, in hypogonadal men after treatment with an oral TU for one year. Hypogonadal men, 18-65 y/o, were recruited into a one year, randomized, multi-center trial. Patients were randomized to either oral TU (n=161) or T-gel (n=160). Hypogonadism was defined as two morning T concentrations < 300 ng/dL with accompanying symptoms. The starting dose of oral TU was 316 mg, BID, and was adjusted to the eugonadal range (300 to 1000 ng/dL) at two pre-defined time points (D45 and D105) based on serum T levels. Patients were instructed to complete the PDQ for 7 consecutive days prior to their study visits on D0 (baseline; BL), D30, D90, D180, D270, and D365. Safety measures included physical examination, vital signs, fasting clinical laboratory analyses, and prostate measures.
Disease module: DeepOracle (Open Targets). Approved indication: ChEMBL drug_indication (max_phase=4). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works, 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.
