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Open research questions in Hormonal and reproductive studies

223 gap statements mined from Hormonal and reproductive studies papers in our 7.9M-paper local library, which holds 1,264 papers on the topic — drawn mostly from each paper's own stated research gap, future-work, challenge and limitation notes, and its abstract. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one.

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What the literature leaves open

  • The current literature lacks a comprehensive understanding of the complex interplay between cortisol, DHEA, and their implications for health. There is a need to investigate the potential consequences of the age-related reduction in DHEA/S levels. The paper aims to address this gap by exploring the roles of cortisol and DHEA in the contexts of obesity, acute and chronic pain, aging, and age-related diseases.

    The Role of Cortisol and Dehydroepiandrosterone in Obesity, Pain, and Aging · 2025 · DOI

  • However, it remains unknown when testicular factors begin to exert their detrimental effects on mortality.

    Beneficial early, harmful later: age-dependent effects of testicular factors on male mortality · 2026 · DOI

  • Specifically, the effects of testosterone use on brain oestrogen synthase (aromatase), which maintains the balance between androgens and oestrogens, remain unexplored.

    Low‐dose testosterone administration and oestrogen synthase availability in the female brain: A pilot study · 2026 · DOI

  • The relationships between sex hormone levels and muscle composition in postmenopausal women remain underexplored.

    Exploring the Relationships between Sex Hormones and Abdominal Muscle Area and Radiodensity in Postmenopausal Women: Insights from the Multi-Ethnic Study of Atherosclerosis · 2025 · DOI

  • Testosterone has been implicated in mood regulation, yet its role in the development and treatment of depression remains unclear.

    Testosterone Concentration and Incident Depression in Older Men: A Longitudinal Cohort Study · 2025 · DOI

  • These findings warrant vigilance rather than contraindication, particularly in men with pre-existing risk factors. Erythrocytosis represents the most consistent adverse event of TRT. Hematocrit should be monitored regularly, and TRT should be reduced or temporarily withheld if hematocrit ≥ 54%.

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

  • Different GLP-1 RA agents, doses, and treatment durations were used across studies, and it remains unclear whether endocrine effects are class-wide or agent-specific. Nevertheless, current evidence remains limited, and GLP-1 receptor agonists should not be considered direct substitutes for TRT.

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

  • 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

  • The term 'functional hypogonadism' is controversial, as it may imply a pathological state requiring treatment. There is a need to improve adherence to guideline-recommended assessment and management of low testosterone. The importance of testicular examination in patients with hypergonadotrophic hypogonadism is often overlooked.

    Functional causes of low testosterone predominate in contemporary Australian endocrine referral practice: a two centre experience across 5 years · 2026 · DOI

  • IntroductionThe impact of testosterone therapy on hormone cycles, exercise capacity, and physiology of transmasculine individuals is not well understood.

    One year of testosterone therapy in a transmasculine amateur triathlete: changes in hormone cycles and exercise capacity · 2026 · DOI

  • Adrenal-derived 11-oxygenated C19 steroids (11-oxyandrogens) are relevant to several androgen-dependent pathologies, but data on their race/ethnic variations are lacking.

    Racial and Ethnic Differences in Classic and 11-Oxygenated Androgens in Men · 2026 · DOI

  • However, prospective studies evaluating whether hormone therapy improves sperm parameters and reproductive outcomes—either naturally or following intracytoplasmic sperm injection (ICSI)—in men with severe oligoasthenozoospermia or non-obstructive azoospermia (NOA) across APHRODITE groups are lacking.

    L26/P-051 Role of hormone therapy in infertile men with severe oligoasthenozoospermia and non-obstructive azoospermia according to the APHRODITE criteria: a prospective cohort study · 2026 · DOI

  • Study question Does hormone therapy guided by APHRODITE criteria improve ejaculated sperm parameters and surgical sperm retrieval rates? Does it enhance chances of natural or assisted conception? Summary answer Hormone therapy improved ejaculated sperm parameters and reduced the need for surgical sperm retrieval; effects on natural or assisted conception remain inconclusive.

    L26/P-051 Role of hormone therapy in infertile men with severe oligoasthenozoospermia and non-obstructive azoospermia according to the APHRODITE criteria: a prospective cohort study · 2026 · DOI

  • Sex differences in cardiovascular disease are well established, but the role of androgens and sex hormone–binding globulin (SHBG) remains unclear.

    Do Androgens and Sex Hormone–Binding Globulin Mediate Sex Differences in the Risk of Stroke and Myocardial Infarction? The KORA Study · 2026 · DOI

  • The effects of testosterone replacement therapy on broader symptom domains and metabolic biomarkers in women are not well understood. The therapeutic implications of testosterone replacement therapy in women, particularly beyond sexual function, remain undercharacterized.

    Testosterone Replacement Therapy in Women Is Associated with Improved Symptom Burden and Favorable Biomarker Changes: A Retrospective Observational Study · 2026 · DOI

  • Published trials have focused predominantly on sexual function, leaving gaps in understanding how testosterone replacement therapy (TRT) affects broader symptom domains and metabolic biomarkers in women.

    Testosterone Replacement Therapy in Women Is Associated with Improved Symptom Burden and Favorable Biomarker Changes: A Retrospective Observational Study · 2026 · DOI

  • Testosterone therapy (TT) is increasingly initiated outside classical hypogonadism, but long-term cardiovascular safety in this context remains uncertain.

    Off-label testosterone therapy is associated with higher long-term cardiovascular risk in men · 2026 · DOI

  • The influence of sex hormones on chronic liver disease (CLD) progression remains unclear, despite sex-related differences in disease susceptibility and outcomes.

    Association of testosterone and sex hormone–binding globulin with chronic liver disease outcomes across sex and menopausal status · 2026 · DOI

  • Hypogonadism is frequently observed in men living with human immunodeficiency virus (HIV), although its prevalence, etiology, and predictors remain incompletely understood.

    Hypogonadism in Cisgender Men Living With HIV: Prevalence, Clinical and Metabolic Features · 2026 · DOI

  • Testosterone replacement therapy (TRT) has been associated with a myriad of medical and postsurgical-related complications in orthopedic procedures, but its impact on PLF outcomes remains unclear.

    Testosterone Replacement Therapy in Posterior Lumbar Fusion Patients: A Propensity Score-Matched Analysis of Long-Term Outcomes · 2026 · DOI

  • Age-related declines in gonadal and cognitive function are commonly observed, but their relationship is still not completely understood.

    Cross-sectional and longitudinal associations between testosterone and cognitive performance in older people: results of the Berlin Aging Study II (BASE-II) · 2025 · 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

  • Despite its growing prevalence, no standardized treatment exists, and post-cycle therapy is often pursued through unsupervised use of selective oestrogen receptor modulators including clomiphene citrate (CC), human chorionic gonadotropin, and aromatase inhibitors.

    Clomiphene Citrate in off‐Label Post‐Cycle Therapy: Mechanisms, Efficacy and Diagnostic Challenges in Endocrine Recovery Following Anabolic Steroid Use · 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

Most-cited papers in Hormonal and reproductive studies

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Open questions raised by papers listed on this page include: (1) It remains unknown when testicular factors begin to exert their detrimental effects on mortality (“Beneficial early, harmful later: age-dependent effects of testicular factors on…”, 2026); (2) The effects of testosterone use on brain oestrogen synthase (aromatase), which maintains the balance between androgens and oestrogens, remain unexplored (“Low‐dose testosterone administration and oestrogen synthase availability in the…”, 2026); (3) The diagnosis of hypogonadism is challenging due to the lack of clear criteria (“Testosterone levels and symptoms of hypogonadism in Swedish men: a prospective…”, 2026); (4) Different GLP-1 RA agents, doses, and treatment durations were used across studies, and it remains unclear whether endocrine effects are class-wide or agent-specific (“Metabolic Reversal of Functional Hypogonadism? GLP-1 Receptor Agonists and Male…”, 2026); (5) There is a need to improve adherence to guideline-recommended assessment and management of low testosterone (“Functional causes of low testosterone predominate in contemporary Australian…”, 2026). 223 gap statements have been mined from Hormonal and reproductive studies papers in our 7.9M-paper local library, which holds 1,264 papers on the topic; the gaps come from whichever of those papers state one. They are mostly the research gaps the authors state and the papers' abstracts, plus future-work, limitations and challenges passages. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one, so you can read the original claim in context.

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