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Open research questions in Hormonal and reproductive studies

104 unresolved questions extracted from the limitations and future-work sections of 612 Hormonal and reproductive studies papers in our library. Each links back to the study that raised it.

What the literature leaves open

  • Androgen abuse can lead to complex changes in the HPGA, making it challenging to diagnose and treat prolonged hypogonadism. The lack of standardized definition and diagnosis for prolonged post-androgen abuse hypogonadism complicates treatment and research. Undisclosed ongoing androgen abuse can make it difficult to exclude other causes of hypogonadism.

    Prolonged post-androgen abuse hypogonadism: potential mechanisms and a proposed standardized diagnosis · 2025 · DOI

  • further research into the pathophysiology and management of PPAAH, - examination of genetic predisposition to HPGA dysfunction in former androgen abusers, - investigation of the role of prolonged androgen activity in HPGA recovery

    Prolonged post-androgen abuse hypogonadism: potential mechanisms and a proposed standardized diagnosis · 2025 · DOI

  • Importance: The illicit use of anabolic androgenic steroids (AAS) is common among recreational athletes, yet studies on adverse cardiovascular outcomes, especially in female AAS users, are sparse.

    Illicit Anabolic Steroid Use and Cardiovascular Status in Men and Women · 2025 · DOI

  • Background: Long-term use of supraphysiologic doses of anabolic-androgenic steroids (AAS) has been associated with impaired visuospatial memory in young men but little is known about its cognitive effects in middle-aged men.

    A study of long-term supraphysiologic-dose anabolic-androgenic steroid use on cognitive function in middle-aged men · 2024 · DOI

  • Remnant cholesterol (RC) has emerged as a potential biomarker for cardiovascular risk, but its relationship with testosterone levels and TD has not been thoroughly investigated.

    The relationship between remnant cholesterol and the risk of testosterone deficiency in US adults: a cross-sectional study based on the NHANES database · 2024 · DOI

  • Background: Over the years, there has been extensive exploration of the association between testosterone and lipid profiles, yet the precise mechanisms underlying their interaction remain incompletely elucidated.

    Analysis of the association between testosterone and cardiovascular disease potential risk factor apolipoprotein B in adult males without cancer: national health and nutrition examination survey 2011-2016 · 2024 · DOI

  • BACKGROUND: The relationship of testosterone and estradiol concentrations with cognitive function among community-dwelling older men was inconclusive.

    Sex steroid and cognitive function among community-dwelling older men with or without vascular risk factors: a cross-sectional study · 2024 · DOI

  • Importance: Long-term use of anabolic androgenic steroids (AASs) is associated with a high risk of left ventricular hypertrophy, heart failure with reduced systolic function, and early sudden death, with the mechanism of progression being understudied.

    Coronary Microvascular Dysfunction Years After Cessation of Anabolic Androgenic Steroid Use · 2024 · DOI

  • There is a lack of awareness of the risks of anabolic steroid use among Sports Science students. The study highlights the need for targeted educational strategies to prevent AAS misuse.

    Public health awareness and safety of anabolic steroid use among Sports Science Students in Egypt · 2026 · DOI

  • There is a need for a conceptual framework to address muscle and bone loss in chronic disease and aging. Prior work has focused on lean mass alone rather than patient-centered outcomes.

    Clinical anabolism: a conceptual framework for preserving morphology and function in chronic disease, aging, and catabolic states · 2026 · DOI

  • Obesity is a major risk factor for male infertility due to its disruptive effects on the hypothalamic-pituitary-testicular axis. The effects of MBS on male fertility are not well understood. Small sample sizes and limited follow-up periods can limit the generalizability of study findings.

    The influence of different bariatric surgeries on male sex hormones and semen parameters among infertile obese male patients: an observational study · 2026 · DOI

  • The effects of MBS on male sex hormones and semen parameters in infertile men with obesity are not well understood. Prior studies have shown inconsistent evidence regarding the impact of obesity on conventional semen parameters.

    The influence of different bariatric surgeries on male sex hormones and semen parameters among infertile obese male patients: an observational study · 2026 · DOI

  • Small sample size of 12 patients. Non-randomized cohort study. Limited generalizability to other populations.

    Fractionated testosterone gel replacement therapy in clinical practice: A real-world exploratory clinical experience · 2026 · DOI

  • There remains a paucity of data regarding efficacy and long-term safety of testosterone replacement therapies. There is a need for a reliable reference range for female testosterone.

    Redefining testosterone reference ranges for adult females · 2026 · DOI

  • We acknowledge that this study has some limitations that may affect the interpretation of the results. Samples were collected remotely, resulting in a 24–72 h lag between col- lection and assay, however serum stability of a least 3 days has been previously verified [50, 51]. The sample is a self- selected convenience sample of test purchasers, which likely results in a dual bias: overrepresenting individuals of higher socioeconomic status and those who are symp- tomatic or experiencing fertility difficulties. Given the strict exclusion criteria applied, this cohort likely represents a well-screened population actively engaged in reproductive health monitoring. Consequently, the findings may not be generalisable to the broader population. The current exclu- sion criteria focused on self-reported hirsutism and PCOS diagnosis. However, acne and female pattern hair loss are also key clinical features of hyperandrogenism. The poten- tial inclusion of individuals with T-related acne or hair loss, but without hirsutism or a PCOS diagnosis, represents a limitation, as this may slightly inflate the upper quantiles. We acknowledge that insulin resistance is a common meta- bolic factor that can influence T [52]. Whilst we did not have direct biochemical measurements of insulin sensitivity for this cohort, we excluded participants with a history of Type 1 or 2 diabetes. The number of individuals reporting this condition was negligible, and as the final reference cohort was restricted to those with a normal BMI and regular men- strual cycles, the impact of undiagnosed insulin resistance is likely minimal. Further, self-reported data may lead to erroneous report- ing of medical history. The reference cohort was predomi- nantly white (white = 83.7%, Asian = 5.5%, Black = 1.8% Mixed = 4.8%, Other = 4.2%). Future studies should expand this model into more diverse populations.

    Redefining testosterone reference ranges for adult females · 2026 · DOI

  • The study is limited to FAERS data, which may not be representative of all patients taking Vamorolone. The study uses a conservative consensus framework, which may lead to false negatives.

    Post-marketing safety surveillance and signal characterization of the novel dissociative steroid Vamorolone in Duchenne muscular dystrophy: a comparative disproportionality analysis based on FAERS data · 2026 · DOI

  • There is a need for a comprehensive evaluation of the post-marketing safety profile of Vamorolone. There is a lack of comparative studies evaluating the safety profile of Vamorolone against traditional glucocorticoids.

    Post-marketing safety surveillance and signal characterization of the novel dissociative steroid Vamorolone in Duchenne muscular dystrophy: a comparative disproportionality analysis based on FAERS data · 2026 · DOI

  • The limitations of prior work, including small sample sizes and conflicting results. The challenge of capturing rare thromboembolic events and assessing the applicability of findings to the oldest and most vulnerable patients. The need for careful risk-benefit evaluation, particularly in men with pre-existing risk factors.

    Testosterone replacement therapy and cardiovascular safety in older men: lessons from TRAVERSE and beyond · 2026 · DOI

  • The cardiovascular safety of testosterone replacement therapy in older men has been debated for over a decade due to limited and conflicting evidence. Prior work has been limited by small sample sizes and inadequate control for confounding variables.

    Testosterone replacement therapy and cardiovascular safety in older men: lessons from TRAVERSE and beyond · 2026 · DOI

  • The biological pathways connecting adiposity to diabetes are not fully understood. The role of testosterone in the relationship between body fat percentage and diabetes mellitus risk is not well established.

    The mediating role of testosterone in the relationship between body fat percentage and diabetes mellitus risk · 2026 · DOI

  • The diagnosis of hypogonadism is challenging due to the lack of clear criteria. The spectrum of symptoms attributable to testosterone deficiency is not well established.

    Testosterone levels and symptoms of hypogonadism in Swedish men: a prospective study from the Vara – Skövde cohort · 2026 · DOI

  • The diagnosis of hypogonadism and the spectrum of symptoms attributable to testosterone deficiency are debated. Prior studies have reported only weak correlations between reported symptoms and biochemical testosterone levels.

    Testosterone levels and symptoms of hypogonadism in Swedish men: a prospective study from the Vara – Skövde cohort · 2026 · DOI

  • The certainty of evidence was limited by reliance on observational data, short follow-up durations, and the lack of testosterone and reproductive outcomes as primary endpoints in most studies. Heterogeneity in study design and incomplete adjustment for metabolic confounders limited the overall certainty of evidence.

    Metabolic Reversal of Functional Hypogonadism? GLP-1 Receptor Agonists and Male Reproductive Endocrinology—A Systematic Review · 2026 · DOI

  • The variability of stressors and individual responses. The complex interplay of multiple neuroendocrine systems. Methodological challenges in assessing subjective stress experiences.

    The effect of stress on testosterone and sexual function · 2026 · DOI

  • Conclusion This literature review demonstrates that RIs for HPG-axis hormones show significant changes during mini-puberty and puberty, although data using appropriate analytical methods, using sufficient sample sizes and reporting on age categories, Tanner stage and menstrual cycle phase are scarce.

    A literature overview of age- and Tanner stage-specific reference intervals for sex hormones for children aged 0 – 18 years · 2026 · DOI

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104 open questions have been extracted from the limitations and future-work passages of 612 Hormonal and reproductive studies papers in our library. Each one below links back to the study that raised it, so you can read the original claim in context.

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