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Search Results (217)

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13 pages, 765 KB  
Article
Course of Testosterone Levels and Potential Biochemical Biomarkers of Androgenization with a Conservative Protocol of Androgen Hormone Therapy in Transgender Males
by Guillermo Velasco de Cos, María Teresa García Unzueta, Ana Moyano Martínez, Pedro Muñoz Cacho, Aurelia Villar Bonet, Armando Raul Guerra Ruiz, Bernardo A. Lavin-Gómez, Maialen Ormazabal Monterrubio and Luis Alberto Vázquez
J. Clin. Med. 2026, 15(16), 6498; https://doi.org/10.3390/jcm15166498 (registering DOI) - 21 Aug 2026
Viewed by 71
Abstract
Objectives: This study aimed to evaluate the hormonal, hematologic, and biochemical outcomes of a conservative protocol for androgen therapy for transgender males. Methods: This was an observational, prospective, and comparative study conducted in the gender identity clinic of a tertiary university hospital. [...] Read more.
Objectives: This study aimed to evaluate the hormonal, hematologic, and biochemical outcomes of a conservative protocol for androgen therapy for transgender males. Methods: This was an observational, prospective, and comparative study conducted in the gender identity clinic of a tertiary university hospital. Testosterone therapy consisted of testosterone cypionate administered intramuscularly every month at an initial dosage of 25 mg/month, which was increased to 50 mg/month at month 3, 100 mg/month at month 6, and 250 mg/month at month 9. Assessments consisted of a complete blood count, biochemical tests, urine analysis, and hormonal tests. We also administered the Transgender Congruence Scale (TCS) post hoc. Results: We recruited 40 transgender males with a mean (SD) age of 22.5 (8.4) years. Only changes in the hematocrit were statistically significant as early as month 9. There were no significant changes in the biochemical parameters related to cardiovascular risk, including serum lipids, over time. There was a significant increase in total, free, and bioavailable testosterone, while SHBG levels significantly decreased; the free androgen index, urine androstanediol glucuronide, androstenedione, and prostate-specific antigen as a marker of androgenization also significantly increased over time. Among the 20 evaluable individuals, 14 (70%) scored ≥4 on the appearance congruence subscale, and 16 (80%) scored ≥4 on the gender identity subscale of the TCS. Conclusions: Our results suggest that this conservative treatment paradigm with testosterone is associated with a reduced adverse impact on hematocrit and lipids but is sufficient to achieve the gender congruence and identity acceptance desired by transgender males. Full article
(This article belongs to the Section General Surgery)
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18 pages, 1570 KB  
Article
Non-Invasive Salivary Reproductive Endocrine Profiles in Gentoo Penguins
by Manuel De la Riva-Fraga, Gema Silvan, Carlos Barros-García, Juan Carlos Illera, Belen Crespo and Sara Caceres
Animals 2026, 16(16), 2622; https://doi.org/10.3390/ani16162622 - 21 Aug 2026
Viewed by 83
Abstract
Reproductive endocrine monitoring in penguins is fundamental for improving reproductive management, conservation programs, and welfare assessment, but most studies use serum, which requires handling and blood collection. We hypothesized that saliva, which reflects the free fraction of circulating steroids and can be repeatedly [...] Read more.
Reproductive endocrine monitoring in penguins is fundamental for improving reproductive management, conservation programs, and welfare assessment, but most studies use serum, which requires handling and blood collection. We hypothesized that saliva, which reflects the free fraction of circulating steroids and can be repeatedly collected with minimal disturbance, would be positively associated with serum concentrations, show hormone-specific reproductive temporal changes, and could be used as an alternative matrix for measuring steroid hormones in female gentoo penguins (Pygoscelis papua). Saliva from 21 females was collected every 3 days between 21 days before and 20 days after first egg-laying. Progesterone, 17β-estradiol, estrone sulfate, corticosterone, and testosterone were measured using competitive EIAs. Assay evaluation showed recoveries of 90.89–97.96% and intra- and inter-assay coefficients of variation <8%; paired serum–saliva analyses yielded r2 ≥ 0.858 for all hormones. Progesterone peaked in W−3 time window, 17β-estradiol in W−5, and estrone sulfate in W−4, with a decrease around egg-laying. These temporal patterns were consistent with endocrine changes associated with follicular growth, maturation, and oviposition. Saliva therefore appears to be a promising minimally invasive matrix for reproductive endocrine monitoring in female gentoo penguins, with potential future applications in welfare assessment and conservation breeding programs. Full article
(This article belongs to the Section Animal Reproduction)
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22 pages, 1544 KB  
Article
Influence of Vitamin E Intake on Sexual Function and Depressive Symptoms in Young Women with Euthyroid Autoimmune Thyroiditis Undergoing Vitamin D Therapy: A Pilot Study
by Robert Krysiak, Karolina Kowalcze, Johannes Ott, Giovanni Cangelosi, Simona Zaami and Bogusław Okopień
Int. J. Mol. Sci. 2026, 27(15), 6713; https://doi.org/10.3390/ijms27156713 - 27 Jul 2026
Viewed by 347
Abstract
Euthyroid autoimmune thyroiditis (Hashimoto’s disease) has been shown to negatively affect female sexual health; however, this adverse impact appears to be mitigated by vitamin D therapy. Emerging research suggests that vitamin E may reduce susceptibility to autoimmune thyroiditis and that supplementation could contribute [...] Read more.
Euthyroid autoimmune thyroiditis (Hashimoto’s disease) has been shown to negatively affect female sexual health; however, this adverse impact appears to be mitigated by vitamin D therapy. Emerging research suggests that vitamin E may reduce susceptibility to autoimmune thyroiditis and that supplementation could contribute to improved sexual health outcomes. The present study aimed to investigate whether vitamin E status influences the effects of exogenous vitamin D on female sexual function and depressive symptoms in individuals with this condition. This pilot study included three cohorts of young women with Hashimoto’s disease, matched for age, thyroid antibody titers, and 25-hydroxyvitamin D levels, all exhibiting normal TSH and free thyroid hormone concentrations. The cohorts differed in vitamin E intake: below the recommended daily allowance (group 1), adequate intake (group 2), and high intake (exceeding 400 IU daily; group 3). All participants received vitamin D at a daily dose of 100 µg for six months. Serum hormone levels, thyroid antibody titers, and calculated indices of thyroid homeostasis were evaluated at enrollment and at the conclusion of the study. Female sexual function and depressive symptoms were also evaluated at both time points using validated instruments: the Female Sexual Function Index (FSFI) and the Beck Depression Inventory-II (BDI-II). At enrollment, group 2 scored higher than the other cohorts in the sexual desire and arousal domains. Vitamin D supplementation increased serum 25-hydroxyvitamin D in all groups. The decrease in antibody titers was most pronounced in group 2, and only in this group did vitamin D enhance thyroid secretory capacity and increase testosterone levels. In group 2, treatment led to improvements across all FSFI domains and the total score. In group 1, positive effects were limited to the lubrication and lack of pain/discomfort domains, whereas group 3 showed no changes in sexual function. Improvements in female sexual function correlated with vitamin E intake, reductions in antibody titers, and increases in testosterone levels. Significant improvements in depressive symptoms, as measured by the BDI-II, were observed exclusively in group 2. Adequate vitamin E intake is essential to achieve the full effects of vitamin D on female sexual function and mood in young euthyroid patients with Hashimoto’s disease. Full article
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28 pages, 874 KB  
Review
Selected Blood-Accessible Biomarkers in Prostate Cancer Radiotherapy: A PRISMA-ScR Timing-Window Framework Beyond PSA
by Miloš Grujić, Barbara Alicja Jereczek-Fossa, Ivan Jovanović, Marija Živković Radojević, Giulia Marvaso, Katarina Krasić, Katarina Janković, Marija Peulić, Federico Mastroleo, Łukasz Kuncman, Vladan Mutavdžić, Milica Mihajlović and Neda Milosavljević
Cancers 2026, 18(15), 2398; https://doi.org/10.3390/cancers18152398 - 25 Jul 2026
Viewed by 378
Abstract
Background: Blood-accessible biomarkers may support future personalization of prostate cancer radiotherapy, but their interpretation depends on sampling timing relative to radiotherapy, androgen deprivation therapy, and post-treatment recovery. We mapped clinical evidence for selected biomarker domains beyond prostate-specific antigen: γ-H2AX/DNA damage response, IL-6/inflammatory mediators, [...] Read more.
Background: Blood-accessible biomarkers may support future personalization of prostate cancer radiotherapy, but their interpretation depends on sampling timing relative to radiotherapy, androgen deprivation therapy, and post-treatment recovery. We mapped clinical evidence for selected biomarker domains beyond prostate-specific antigen: γ-H2AX/DNA damage response, IL-6/inflammatory mediators, testosterone/endocrine recovery and a prespecified galectin-1/3 immune–stromal domain evaluated as a potential evidence gap. Methods: We conducted a PRISMA-ScR scoping review of PubMed, Scopus, and Web of Science searched on 7 January 2026. Eligible original human studies evaluated soluble serum/plasma analytes or peripheral blood cell-based assays in prostate RT pathways. Data were charted by biomarker domain, treatment context, RT modality/fractionation, assay reporting, sampling schedule, and endpoint linkage. Results: Of 3499 records, 45 studies were included. No eligible study reported repeated circulating galectin-1/3 kinetics anchored to prostate radiotherapy, identifying a distinct clinical evidence gap. The remaining evidence was dominated by testosterone studies (n = 28), followed by IL-6/inflammatory mediators (n = 12) and γ-H2AX/DDR (n = 5). Testosterone studies were mapped as separate RT-only endocrine kinetics and ADT-anchored recovery streams. IL-6 studies mainly used during-RT or early post-RT sampling and linked trajectories to acute toxicity, fatigue, symptoms or inflammatory phenotypes; no included study directly validated serial IL-6/inflammatory trajectories against biochemical control, metastasis-free survival, or overall survival. γ-H2AX studies were characterized by ultra-acute, fraction-anchored sampling. Across domains, baseline definition and sampling timing limited interpretability more than assay platform alone. Conclusions: Evidence maturity was unequal across the selected domains. Testosterone provided the comparatively more developed longitudinal clinical literature, whereas IL-6/inflammatory mediators remained exploratory and were linked mainly to acute toxicity, fatigue, symptoms, and inflammatory phenotypes. γ-H2AX remained predominantly a translational and biodosimetry-oriented marker, while galectin-1/3 represented a hypothesis-generating clinical evidence gap. None of these biomarkers currently supports routine biomarker-guided prostate RT personalization. Future biomarker-embedded studies may benefit from domain-specific sampling considerations, explicit RT/systemic-therapy context stratification, standardized assay reporting, and clinically relevant endpoints. Full article
(This article belongs to the Special Issue Biomarkers of Urological Cancers)
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12 pages, 546 KB  
Article
Hormones, Sexual Function, and Dysfunctional Sexual Beliefs in Postmenopausal Women: A Cross-Sectional Study
by Clayton Peixoto, Melanie Navarro, Carolina Gomes Carrilho, Antonio José Grande, Antonio Egidio Nardi, Adriana Cardoso and André Barciela Veras
J. Pers. Med. 2026, 16(7), 394; https://doi.org/10.3390/jpm16070394 - 22 Jul 2026
Viewed by 773
Abstract
Background: Sexual function in postmenopausal women is influenced by both hormonal and psychological factors. This study investigates the associations between sex hormones, sexual function, and sexual beliefs in this population. Objective: This research seeks to assess the relationship between sex hormones, sexual function, [...] Read more.
Background: Sexual function in postmenopausal women is influenced by both hormonal and psychological factors. This study investigates the associations between sex hormones, sexual function, and sexual beliefs in this population. Objective: This research seeks to assess the relationship between sex hormones, sexual function, and dysfunctional sexual beliefs in postmenopausal women. Methods: A cross-sectional study was conducted with 42 postmenopausal women aged 45–65 years. Instruments included the FSFI and SDBQ. Hormones assessed were testosterone, estradiol, progesterone, prolactin, DHEA, SHBG, and LH. Blood samples were collected in the morning and analyzed using chemiluminescence or radioimmunoassay. Pearson correlation tests were used, with Bonferroni adjustment applied to control for multiple comparisons. Results: Free testosterone was positively correlated with sexual desire and negatively associated with dysfunctional beliefs regarding sexual desire. Estradiol also showed a positive correlation with desire, while prolactin was negatively associated. No other FSFI domains showed significant hormonal associations. Conclusions: Findings suggest that testosterone may influence both sexual desire and the internalization of dysfunctional sexual beliefs in postmenopausal women, highlighting the interplay between biological and psychological dimensions of sexuality, which may be relevant for a more comprehensive clinical assessment of sexual function in this population. Full article
(This article belongs to the Special Issue Advancements in Psychiatry: Exploring New Horizons in Mental Health)
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16 pages, 2740 KB  
Article
A Randomized Double-Blind Placebo-Controlled Trial of a Botanical Formulation for Symptom Management in Male Climacteric Syndrome
by Da-In Choi, Jang Hee Hong, Gyuok Lee, Jaeyong Kim and Chul-Yung Choi
Medicina 2026, 62(7), 1334; https://doi.org/10.3390/medicina62071334 - 10 Jul 2026
Viewed by 468
Abstract
Background/Objectives: Male climacteric syndrome (MCS) affects quality of life through psychological, somatic, sexual, and endocrine-related symptoms. This study evaluated whether a botanical formulation containing Elaeagnus multiflora fruit and Cynanchum wilfordii extracts (EMF_CWW) improved MCS-related symptoms compared with placebo. Methods: We conducted a 12-week, [...] Read more.
Background/Objectives: Male climacteric syndrome (MCS) affects quality of life through psychological, somatic, sexual, and endocrine-related symptoms. This study evaluated whether a botanical formulation containing Elaeagnus multiflora fruit and Cynanchum wilfordii extracts (EMF_CWW) improved MCS-related symptoms compared with placebo. Methods: We conducted a 12-week, randomized, double-blind, placebo-controlled trial (Clinical Research Information Service registration: KCT0010695) in 70 men aged 45–75 years with MCS. Participants received EMF_CWW (1500 mg/day) or placebo. The primary outcome was the change in Aging Males’ Symptoms (AMS) total score from baseline to Week 12. Secondary outcomes included AMS subdomains, Androgen Deficiency in Aging Males (ADAM) positivity, hormonal parameters, lipid profile, and safety. Efficacy analyses were conducted in the per-protocol population (n = 64), and safety analyses were conducted in the safety population (n = 70). Results: EMF_CWW did not demonstrate superiority over placebo for the primary outcome. AMS total score decreased in both groups (treatment: −14.2 ± 12.5; placebo: −15.5 ± 12.3), with no significant between-group difference (p = 0.6726). AMS subdomains and ADAM positivity also improved in both groups without significant between-group differences. Free testosterone increased non-significantly in the treatment group (+0.8 ± 2.4 pg/mL; p = 0.0727) and significantly in the placebo group (+1.3 ± 2.6 pg/mL; p = 0.0076), with no between-group difference (p = 0.8720). No treatment-related serious adverse events were observed. Conclusions: EMF_CWW did not demonstrate efficacy superior to placebo for improving MCS-related symptoms or hormonal outcomes. The improvements observed in both groups highlight placebo responsiveness, regression to the mean, and symptom variability in MCS trials. No apparent short-term safety signal was observed; however, long-term safety cannot be concluded. Larger trials with standardized repeated morning testosterone measurements are required. Full article
(This article belongs to the Section Pharmacology)
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22 pages, 1330 KB  
Systematic Review
Vitamin D Supplementation, Total Testosterone, and Androgen Bioavailability Markers in Adult Men: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
by Loreto Paez-Allendes, Juan José Valenzuela-Fuenzalida, María P. Moya, Gustavo Oyanedel, Gloria Cifuentes-Suazo, Julio Figueroa-Puig, Mathias Orellana-Donoso, Eduardo Mateluna-Valls, Juan Jose Cabezas-Salgado, Juan Sanchis-Gimeno and Alejandro Bruna-Mejias
Nutrients 2026, 18(13), 2090; https://doi.org/10.3390/nu18132090 - 26 Jun 2026
Viewed by 2768
Abstract
Background: Vitamin D has traditionally been recognized for its role in calcium homeostasis and skeletal health, but vitamin D receptor expression and vitamin D-metabolizing enzymes have also been identified in extra-skeletal tissues, including components of the male reproductive tract. Observational evidence has suggested [...] Read more.
Background: Vitamin D has traditionally been recognized for its role in calcium homeostasis and skeletal health, but vitamin D receptor expression and vitamin D-metabolizing enzymes have also been identified in extra-skeletal tissues, including components of the male reproductive tract. Observational evidence has suggested associations between vitamin D status and androgen-related markers; however, whether vitamin D supplementation has a measurable effect on androgen bioavailability remains uncertain. Objective: This systematic review and meta-analysis evaluated the effects of vitamin D supplementation on total testosterone (TT) and androgen bioavailability markers in adult men, including sex hormone-binding globulin (SHBG), free androgen index (FAI), calculated free testosterone (calculated FT), and bioactive testosterone (BAT) where methodologically compatible. Methods: The review was registered in PROSPERO (CRD420261365005) and conducted according to PRISMA 2020 and Cochrane methodological guidance. Searches were conducted from database inception to April 2026 in PubMed, Web of Science, Scopus, ClinicalTrials.gov, and the WHO ICTRP. Embase was initially planned but was not searched because institutional access was unavailable; this amendment was made before screening, extraction, risk-of-bias assessment, and synthesis. Records were deduplicated in Zotero, screened in a structured matrix, and converted from report-level records into independent comparison-level datasets where appropriate. Meta-analyses used random-effects REML models with Hartung–Knapp adjustment. Results: The official search set comprised 2854 records, of which 703 duplicates were removed, leaving 2151 records for title and abstract screening. The full-text screening file was reconciled to 162 PRISMA-countable reports/records: 135 reports were assessed, 27 reports could not be assessed because the full text was unavailable or had not been obtained for review, and 27 reports/studies were retained for qualitative synthesis. Eighteen reports were considered candidate sources for quantitative synthesis and were operationalized into 21 comparison-level records. The primary TT model included 11 comparisons and showed no clear effect of vitamin D supplementation on final TT (MD 0.47 nmol/L, 95% CI −0.50 to 1.44; I2 = 24.1%). No clear effects were observed for SHBG (MD 0.27 nmol/L, 95% CI −2.14 to 2.68), FAI (MD −0.37, 95% CI −4.28 to 3.55), calculated FT sensitivity evidence (MD −0.0096 nmol/L, 95% CI −0.0525 to 0.0332), or BAT exploratory evidence (MD −0.47 nmol/L, 95% CI −1.77 to 0.83). GRADE certainty was low for TT, SHBG, and FAI, and very low for calculated FT and BAT. Conclusions: Current randomized evidence does not demonstrate a statistically clear or reproducible effect of vitamin D supplementation on total testosterone or androgen bioavailability markers in adult men. GRADE certainty was low for total testosterone, SHBG, and FAI, and very low for calculated free testosterone and bioactive testosterone. Because directly measured and calculated free testosterone are not analytically equivalent, free testosterone was not pooled as a primary outcome; method-compatible calculated FT was handled as sensitivity evidence and BAT as exploratory evidence. Full article
(This article belongs to the Special Issue Vitamins and Human Health: 3rd Edition)
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36 pages, 7032 KB  
Article
Limitations of Molecular Docking in Predicting the Selectivity of Selective Androgen Receptor Modulators (SARMs): A Comparative Study of YK11 and Ostarine Across Five Nuclear Receptors
by Kaloyan Mihalev, Ivelin Iliev, Nadya Agova, Nikolay Toshev and Svetlana Georgieva
Int. J. Mol. Sci. 2026, 27(13), 5765; https://doi.org/10.3390/ijms27135765 - 26 Jun 2026
Viewed by 982
Abstract
Selective androgen receptor modulators (SARMs) are commonly described as tissue-selective anabolic agents, yet the extent to which this selectivity is reflected at the level of receptor-binding energetics remains uncertain. This study evaluated the receptor interaction profiles of the steroidal SARM YK11 and the [...] Read more.
Selective androgen receptor modulators (SARMs) are commonly described as tissue-selective anabolic agents, yet the extent to which this selectivity is reflected at the level of receptor-binding energetics remains uncertain. This study evaluated the receptor interaction profiles of the steroidal SARM YK11 and the nonsteroidal SARM ostarine across five steroid hormone nuclear receptors. Flexible molecular docking was performed with AutoDock 4.2 against the androgen (AR), estrogen (ER), progesterone (PR), glucocorticoid (GR), and mineralocorticoid (MR) receptors, using testosterone, estradiol, progesterone, cortisol, and aldosterone as endogenous reference ligands. Binding free energy, docking-derived inhibition constants, intermolecular interaction energies, conformational sampling, and two-dimensional interaction maps were analyzed. Ostarine showed favorable binding across all receptor systems, with binding energies ranging from −10.42 to −12.05 kcal/mol and no pronounced energetic preference for the androgen receptor. YK11 displayed stronger predicted binding, particularly toward the glucocorticoid, progesterone, and androgen receptors, with a docking energy trend of GR > PR > AR > MR > ER. Interaction analysis revealed conserved polar anchoring residues across receptor pockets, together with scaffold-specific contacts that may explain cross-receptor compatibility. These findings indicate that, within the AutoDock 4.2 flexible docking framework applied in this study, docking-derived binding energies primarily describe thermodynamic compatibility with nuclear receptor ligand-binding domains and should not be interpreted as direct predictors of functional SARM tissue selectivity. The observed discordance between predicted receptor affinity and the established tissue-selective pharmacology of ostarine highlights the need for caution when using single-method docking workflows to infer selectivity among closely related steroid hormone receptors. The novelty of this study lies in demonstrating, using a defined AutoDock 4.2-based comparative protocol, that receptor-binding energetics alone do not recapitulate the functional tissue-selective behavior attributed to SARMs. Full article
(This article belongs to the Special Issue Molecular Docking Method and Application)
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15 pages, 446 KB  
Article
Weight Reduction via Lifestyle Intervention Improves Androgen Levels and Glucose Metabolism in Women of Reproductive Age with Hyperandrogenism: A Real-World Observational Study
by Yang Yang, Zheng Liu and Jing Zhang
J. Clin. Med. 2026, 15(12), 4795; https://doi.org/10.3390/jcm15124795 - 20 Jun 2026
Viewed by 404
Abstract
Background/Objectives: Weight loss achieved through lifestyle interventions has been demonstrated to improve the clinical prognosis of female hyperandrogenism. However, the interplay between such interventions, androgens, and glucose–lipid metabolism remains heterogeneous. This study evaluated the effects of lifestyle-induced weight loss on glucose and [...] Read more.
Background/Objectives: Weight loss achieved through lifestyle interventions has been demonstrated to improve the clinical prognosis of female hyperandrogenism. However, the interplay between such interventions, androgens, and glucose–lipid metabolism remains heterogeneous. This study evaluated the effects of lifestyle-induced weight loss on glucose and lipid metabolism and androgen levels in Chinese women of reproductive age with hyperandrogenism and examined the association between the degree of weight loss and changes in androgen levels, glucose and lipid metabolism, exercise capacity, and dietary patterns. Methods: This observational study, based on real-world clinical settings, collected medical records of women of reproductive age with hyperandrogenism who underwent weight-loss interventions between July 2023 and September 2025. Correlation analysis employed Spearman’s rank correlation coefficient, whilst pre- and post-weight-loss comparisons utilised paired t-tests or Wilcoxon signed-rank tests. Results: After a follow-up of 6 to 7 months, a total of 66 participants achieved a mean weight loss of 5.67 ± 4.27 kg. Statistically significant reductions were observed in testosterone (0.40 ± 0.10 vs. 0.30 ± 0.10 ng/mL, p < 0.001), androstenedione (p < 0.001), and the free androgen index (p < 0.001). Glucose metabolism showed statistically significant improvement, with decreases in HOMA-IR (p = 0.040), fasting glucose (p = 0.001), and fasting/2 h postprandial insulin (p < 0.001). However, lipid profiles showed no statistically significant changes. Multiple linear regression revealed that change in testosterone was independently and inversely associated with change in apolipoprotein A1 (β = −0.496, p = 0.008), while change in dehydroepiandrosterone sulfate was inversely associated with change in fasting insulin (β = −0.357, p = 0.032). A non-linear, inverted U-shaped relationship was found between weight loss magnitude and change in sex hormone-binding globulin, with moderate weight loss (5–10%) yielding the greatest increase (p = 0.044). Marked weight loss (≥10%) was associated with the lowest follow-up fasting insulin levels (p = 0.039). Conclusions: Weight loss achieved through lifestyle interventions is associated with improvements in androgen levels and glucose metabolism, though its impact on lipid metabolism remains limited. The degree of improvement in insulin sensitivity correlates more strongly with the magnitude of weight reduction. Full article
(This article belongs to the Section Endocrinology & Metabolism)
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14 pages, 2386 KB  
Article
Testosterone in Relapsing–Remitting Multiple Sclerosis: A Case–Control Study
by Iwona Rościszewska-Żukowska, Małgorzata Popiel, Adam Perenc, Julia Rudnicka-Czerwiec, Ilona Malska and Halina Bartosik-Psujek
J. Clin. Med. 2026, 15(12), 4401; https://doi.org/10.3390/jcm15124401 - 6 Jun 2026
Viewed by 487
Abstract
Background/Objectives: This study aimed to evaluate the prevalence of hypogonadism in men with RRMS (relapsing–remitting multiple sclerosis) who are undergoing treatment with disease-modifying therapies (DMTs) and its association with clinical and magnetic resonance imaging (MRI) parameters. Methods: A total of 126 [...] Read more.
Background/Objectives: This study aimed to evaluate the prevalence of hypogonadism in men with RRMS (relapsing–remitting multiple sclerosis) who are undergoing treatment with disease-modifying therapies (DMTs) and its association with clinical and magnetic resonance imaging (MRI) parameters. Methods: A total of 126 male patients with RRMS, aged 18–67 years, receiving DMTs and a group of 35 age- and BMI-matched healthy individuals were enrolled. Clinical and demographic data were collected, including neurological disability (EDSS, T25FW, 9-HTP, SDMT), and MRI findings. Symptoms of androgen deficiency and depression were assessed using ADAM questionnaire and Beck Depression Inventory, while quality of life was evaluated using MSIS-29. Serum total testosterone (TT), sex hormone-binding globulin (SHBG), and free testosterone (fT) were measured in two stored morning blood samples. Results: A total of 118 (93.6%) MS patients (median age of 38.8 y) had normal TT levels; only 2 (1.6%) MS patients and 2 (5.7%) healthy controls had below-normal levels. Meanwhile, low fT levels were observed in 53 (43.7%) MS patients and 12 (34.3%) controls. However, the fT level was significantly lower in the MS patients under 38 years of age than in control individuals (p = 0.015). Only depression from all concomitant diseases was more prevalent in MS patients with low fT (p = 0.016). There was no correlation between low fT and clinical (EDSS, T25FT, SDMT) and MRI (new T2 and new Gd+ lesions) parameters but a longer disease duration and a higher total number of steroid treatments were associated with below-normal fT levels (p = 0.048 and p = 0.003, respectively). Change of DMT and current and previous DMT type did not correlate with low fT. Patients with low fT levels had a higher median score on the BDI (8.00; IQR: 3.00–12.50 vs. 5.00; IQR: 1.00–10.50) (p = 0.034) and the higher median ADAM questionnaire score (4.00 [IQR: 2.00–7.50] vs. 2.00 [IQR: 0.00–6.00]) (p = 0.034). Only a longer duration of MS (11.83 years) exhibited a significant positive correlation with the risk of a low fT level (OR = 1.19, CI 95%: 1.06–1.35, p = 0.004) in multivariate logistic analysis. Conclusions: Total testosterone level was normal in most male RRMS patients; however, low free testosterone level was observed, in particular in younger MS patients. Depression was more prevalent in patients with low fT but longer duration was a significant risk factor for a low fT level. Full article
(This article belongs to the Section Clinical Neurology)
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21 pages, 2337 KB  
Review
Effects of Intermittent Fasting on Male and Female Reproductive Hormones, Fertility, and Sexual Function: A Comprehensive Review with Emphasis on the Existing Evidence Gap in Women
by Sandro La Vignera and Rosita A. Condorelli
Nutrients 2026, 18(11), 1817; https://doi.org/10.3390/nu18111817 - 4 Jun 2026
Cited by 2 | Viewed by 3905
Abstract
Intermittent fasting (IF) has emerged as a popular dietary intervention with potential metabolic and endocrine benefits. However, its effects on sexual function and reproductive health remain incompletely understood. This comprehensive review synthesizes current evidence from human clinical trials and animal studies examining the [...] Read more.
Intermittent fasting (IF) has emerged as a popular dietary intervention with potential metabolic and endocrine benefits. However, its effects on sexual function and reproductive health remain incompletely understood. This comprehensive review synthesizes current evidence from human clinical trials and animal studies examining the impact of various IF protocols—including time-restricted eating (TRE), alternate-day fasting (ADF), and Ramadan fasting—on male and female sexual function, reproductive hormones, and fertility outcomes. In males, limited human data suggest preserved erectile function but reduced sexual desire during Ramadan fasting, with neutral effects on testosterone in obese adults undergoing TRE. Animal studies demonstrate context-dependent effects, with IF protecting against high-fat diet-induced reproductive dysfunction while potentially impairing spermatogenesis under prolonged energy restriction. In females, IF shows promise for improving hyperandrogenism and menstrual regularity in polycystic ovary syndrome (PCOS), mediated by enhanced insulin sensitivity and reduced free androgen index. However, direct measurements of female sexual function domains (libido, arousal, lubrication, orgasm) are largely absent from the literature. Mechanistic pathways involve modulation of the hypothalamic–pituitary–gonadal (HPG) axis, insulin–adipokine signaling, sex hormone-binding globulin (SHBG), and oxidative stress pathways. Evidence quality is limited by small sample sizes, heterogeneous protocols, short follow-up periods, and predominance of animal data. While IF may offer reproductive benefits in metabolically compromised populations, particularly women with PCOS, caution is warranted in young, lean, or energy-deficient individuals. Future research should employ standardized IF protocols, validated sexual function instruments, and long-term fertility endpoints to establish evidence-based clinical recommendations. Full article
(This article belongs to the Special Issue Nutrition for Endocrine Conditions: Tailoring Dietary Approaches)
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26 pages, 2325 KB  
Article
Vitamin E Intake Modulates the Effect of Selenomethionine on Sexual Function and Depressive Symptoms in Reproductive-Age Women with Euthyroid Autoimmune Thyroiditis: A Pilot Study
by Robert Krysiak, Karolina Kowalcze, Johannes Ott, Giovanni Cangelosi, Simona Zaami and Bogusław Okopień
Antioxidants 2026, 15(5), 549; https://doi.org/10.3390/antiox15050549 - 26 Apr 2026
Viewed by 1229
Abstract
Oxidative stress appears to be implicated in both the initiation and progression of autoimmune thyroiditis. Selenomethionine, which exhibits antioxidant properties, has been shown to reduce thyroid antibody titers in patients with autoimmune thyroiditis. Recent evidence suggests that vitamin E, a fat-soluble antioxidant, may [...] Read more.
Oxidative stress appears to be implicated in both the initiation and progression of autoimmune thyroiditis. Selenomethionine, which exhibits antioxidant properties, has been shown to reduce thyroid antibody titers in patients with autoimmune thyroiditis. Recent evidence suggests that vitamin E, a fat-soluble antioxidant, may protect against the development of autoimmune thyroiditis, and that its supplementation has been associated with improvements in female sexual function. The objective of the present pilot study was to determine whether vitamin E intake modulates the effects of selenomethionine on female sexual function and depressive symptoms in individuals with thyroid autoimmunity. The study enrolled three groups of reproductive-age women with euthyroid autoimmune thyroiditis, with 26 participants in each group. The groups were matched for age, thyroid peroxidase antibody titers, and TSH levels and differed according to vitamin E intake: adequate intake (group A), low intake (group B), and high intake (group C). All participants received selenomethionine supplementation (200 µg/day) for six months. Antibody titers and hormone levels were measured, and participants completed questionnaires assessing female sexual function (FSFI) and depressive symptoms (BDI-II). At baseline, no differences in biochemical outcomes were observed between the groups, except for testosterone levels. The study groups differed in sexual desire and arousal domain scores, which were higher in group A than in the other two groups. Total FSFI scores, the remaining FSFI domain scores, and BDI-II scores did not differ between groups at baseline. Across all groups, selenomethionine reduced thyroid peroxidase and thyroglobulin antibody titers and increased SPINA-GD and the ratio of free triiodothyronine to free thyroxine; however, the effects on antibody titers were most pronounced in group A. An increase in SPINA-GT and testosterone levels following selenomethionine supplementation was observed only in group A. In this group, selenomethionine also led to significant improvements in total FSFI scores and all individual domain scores. In contrast, in the remaining groups, the effects of supplementation were limited to increases in domain scores for lubrication, sexual satisfaction, and pain. A treatment-related reduction in total BDI-II scores was observed exclusively in women with adequate vitamin E intake. These findings suggest, for the first time, that dietary intake of a natural antioxidant may influence the effects of exogenous selenomethionine on sexual function and depressive symptoms in reproductive-age women with euthyroid autoimmune thyroiditis. Full article
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17 pages, 823 KB  
Article
Testosterone Replacement Therapy in Women Is Associated with Improved Symptom Burden and Favorable Biomarker Changes: A Retrospective Observational Study
by Carter W. Elggren, Charles H. Iverson, Madeline D. Morris, Ella F. Cooper-Leavitt, Genevieve Parker, Andrew W. Richardson, Asher P. Reynolds, Paul M. Cortes, Benjamin T. Bikman and Paul R. Reynolds
J. Pers. Med. 2026, 16(5), 231; https://doi.org/10.3390/jpm16050231 - 22 Apr 2026
Viewed by 8427
Abstract
Background: Testosterone is the most abundant biologically active sex steroid in women, yet the therapeutic implications of its age-related decline remain undercharacterized. Published trials have focused predominantly on sexual function, leaving gaps in understanding how testosterone replacement therapy (TRT) affects broader symptom [...] Read more.
Background: Testosterone is the most abundant biologically active sex steroid in women, yet the therapeutic implications of its age-related decline remain undercharacterized. 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. Objective: To investigate whether individualized, biomarker-guided TRT in women is associated with improvements across multiple symptom domains and favorable hormonal, hematologic, and cardiometabolic biomarker changes, and to examine whether symptomatic benefit varies with treatment duration. Methods: In this retrospective observational study, women (n = 332; ages 27 to 78; mean 45.7 ± 7.1 years) receiving TRT as part of routine clinical care through a telehealth-based platform completed a structured survey at a single post-treatment time point assessing eight symptom domains: energy/fatigue, memory, concentration, irritability, depression, anhedonia, sexual interest, and relationship satisfaction. Respondents were stratified by TRT duration (1 month to >12 months) and a subset (n = 120) underwent paired biomarker assessment at baseline and 12 weeks for total testosterone, free testosterone, SHBG, hemoglobin, and triglycerides. Results: Improvement was reported across all eight domains, with energy/fatigue showing the strongest response (84.3% improved). Depression, irritability, anhedonia, and sexual interest each exceeded 65% improvement. Cognitive domains showed a delayed trajectory, with meaningful gains emerging at 4 to 6 months. Quality of life improvement was reported by 89.7%, with significant improvement rising from 5.4% at 1 month to 51.5% at greater than 12 months. Energy/fatigue (64.2%) and mood (49.7%) ranked above sexual desire (41.3%) as self-identified areas of greatest benefit. All five biomarkers changed favorably: total testosterone +151.8% (d = 3.60), free testosterone +216.7% (d = 3.01), hemoglobin +5.5% (d = 2.03), SHBG −13.3% (d = 1.57), and triglycerides −12.6% (d = 1.28). Conclusions: Individualized TRT in women was associated with broad symptomatic improvement spanning energy/fatigue, depression, irritability, anhedonia, cognitive function, and sexual interest, with duration-dependent gains and favorable biomarker changes across all five markers assessed. These findings suggest that the value of testosterone in women extends beyond sexual function and supports the need for larger controlled trials with extended follow-up. Full article
(This article belongs to the Section Disease Biomarkers)
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20 pages, 2552 KB  
Article
Impact of Orchiectomy on Oxidative Stress-Induced Neurodegeneration in the Male Rat Retina: A Proteomic Analysis
by Khadiza Zaman, Ammar Kapic, Vien Nguyen and Katalin Prokai-Tatrai
Antioxidants 2026, 15(4), 479; https://doi.org/10.3390/antiox15040479 - 12 Apr 2026
Cited by 3 | Viewed by 1007
Abstract
Elevated oxidative stress (OS) is a primary driver of ocular neurodegeneration, worsening with age-related declines in gonadal hormones. While the loss of endogenous 17β-estradiol (E2) is a recognized risk factor for retinal degeneration in females, the impact of testosterone depletion in males remains [...] Read more.
Elevated oxidative stress (OS) is a primary driver of ocular neurodegeneration, worsening with age-related declines in gonadal hormones. While the loss of endogenous 17β-estradiol (E2) is a recognized risk factor for retinal degeneration in females, the impact of testosterone depletion in males remains poorly understood. To address this knowledge gap, we employed mass spectrometry-based proteomics and bioinformatic pipelines to characterize retinal protein shifts triggered by orchiectomy (ORX) in the Brown Norway rat. Proteins from ORX and intact retinas were analyzed via a discovery-driven approach using nanoflow liquid chromatography–tandem mass spectrometry with data-independent acquisition. Ingenuity Pathway Analysis® of differentially expressed proteins (DEPs) revealed nearly 300 significantly regulated canonical pathways, many associated with OS, free radical detoxification, mitochondrial dysfunction and ophthalmic disease. A selected panel of DEPs was verified by protein-targeted data extraction. Notably, pathway analysis revealed the prominence of estrogen receptor signaling over androgen receptor signaling in the retina, despite the loss of male sex hormones following ORX. These findings indicate that E2-mediated pathways play a more significant role in male retinal protection than previously recognized. Our study provides the first proteomics-based evidence of the male rat retina’s heightened susceptibility to ORX-associated OS, identifying potential targets for treating sex hormone deprivation-associated retinal neurodegeneration. Full article
(This article belongs to the Special Issue Role of Oxidative Stress in Eye Diseases)
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10 pages, 463 KB  
Article
Evaluation of the Effects of COVID-19 Infection and COVID-19 mRNA Vaccine on Ovarian Reserve
by Zafer Basibuyuk, Ceren Cebi Basibuyuk, Seyma Okumus, Mahmut Oncul and Kutsiye Pelin Ocal
J. Clin. Med. 2026, 15(7), 2614; https://doi.org/10.3390/jcm15072614 - 29 Mar 2026
Viewed by 1043
Abstract
Objectives: This study aimed to investigate whether COVID-19 infection or COVID-19 mRNA vaccination affects ovarian reserve and reproductive hormone profiles in reproductive-aged women. Methods: This retrospective longitudinal (before–after observational) single-center study included women aged 16–44 years who presented to a tertiary [...] Read more.
Objectives: This study aimed to investigate whether COVID-19 infection or COVID-19 mRNA vaccination affects ovarian reserve and reproductive hormone profiles in reproductive-aged women. Methods: This retrospective longitudinal (before–after observational) single-center study included women aged 16–44 years who presented to a tertiary center between January 2021 and September 2023. Participants either had a confirmed COVID-19 infection by a positive polymerase chain reaction (PCR) test or had received two doses of a COVID-19 mRNA vaccine without prior infection. Women with available ovarian reserve parameters within six months of infection or vaccination were included. Anti-Müllerian hormone (AMH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), prolactin (PRL), thyroid-stimulating hormone (TSH), total testosterone, and free testosterone levels were evaluated at baseline and reassessed six months later. Menstrual cycle characteristics were recorded. Parametric and non-parametric statistical tests were applied as appropriate. Results: No statistically significant differences were observed in AMH, FSH, LH, E2, PRL, TSH, total testosterone, or free testosterone levels before and after COVID-19 infection or vaccination (all p > 0.05). Comparisons between infection and vaccination groups across age subgroups (<25, 25–35, ≥35 years) revealed no significant differences in ovarian reserve parameters. Menstrual irregularities were reported in 38.0% of women following infection and 18.6% following vaccination. All reported menstrual changes were transient and resolved within six months. Conclusions: COVID-19 infection and mRNA vaccination were not associated with detrimental effects on ovarian reserve or reproductive hormone profiles. Although transient menstrual irregularities were observed, no long-term adverse reproductive impact was detected. Larger prospective studies are warranted to confirm these findings. Full article
(This article belongs to the Section Obstetrics & Gynecology)
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