Sex hormones play a major role throughout the body starting from gender differentiation in utero to senescence. While they are undoubtedly important for development and conservation of reproductive function, their importance has been shown in most systems by experimental and clinical models. While testosterone (T) is considered to be the most important androgen in circulation, it may either directly exert effects on target tissues or be metabolized by 5α-reductase into dihydrotestosterone (DHT) or aromatized to estradiol (E2). Differential effects of T and its metabolites are not well known and are a topic of scientific debate. These pleiotropic effects lead to variable phenotypes, clinical manifestations, and significance throughout life and may be more pronounced in some systems (such as bone and reproductive organs) or stages (such as puberty) than in others. This chapter focuses on the available clinical evidence of the androgen effects on several important systems.

Background/Objectives: Erectile dysfunction (ED) is a common sexual disorder in men, frequently linked to endothelial dysfunction affecting penile vasculature. Accumulating evidence suggests that vitamin D (VD) status may influence endothelial function and, consequently, erectile function. VD deficiency has also been associated with cardiovascular risk factors, which are well-known contributors to ED. Methods: A systematic review following PRISMA guidelines was conducted, analyzing studies from PubMed and Cochrane databases published between 2010 and 2025. Randomized controlled trials, observational studies, and pilot clinical trials examining the relationship between VD levels and ED in the general male population were included. Results: Out of 1335 identified articles, 10 studies met inclusion criteria, encompassing over 13,000 men. Observational studies consistently showed that men with moderate-to-severe or arteriogenic ED had significantly lower serum VD levels and poorer erectile function scores compared to those with mild ED. VD deficiency was independently associated with higher ED prevalence, irrespective of lifestyle, cardiovascular risk, or sex hormone levels. Although several observational studies suggested a potential optimal vitamin D threshold, definitive recommendations cannot be established due to the heterogeneity of available evidence and conflicting findings from randomized controlled trials. The latter demonstrated inconsistent effects of vitamin D supplementation on erectile dysfunction outcomes, with the largest trial reporting no significant reduction in disease prevalence. These findings underscore the critical need for rigorously designed trials targeting populations with severe VD deficiency and arteriogenic ED. Conclusions: This systematic review highlights an association between vitamin D status and erectile dysfunction, particularly in men with moderate-to-severe or arteriogenic ED. However, most of the evidence is derived from low-certainty observational studies. While observational data suggest potential benefits of adequate VD levels for sexual health, well-designed randomized controlled trials are essential to delineate causal relationships and potential for therapeutic efficacy.

Background/Objectives: The aim of this study was to identify systemic, metabolic, and host-related prognostic factors for long-term outcomes in patients with a diabetic foot ulcer (DFU). Methods: One hundred patients were selected from a high-risk cohort of 426 individuals with a DFU (January 2021–January 2023) based on predefined inclusion and exclusion criteria. Clinical, laboratory, and imaging data were collected. Outcomes were categorized as favorable (healing) or unfavorable (non-healing, re-ulceration, amputation, or death). Prognostic factors were analyzed using random forest and categorical boosting models, with SHAP values to determine the importance of individual predictors. Results: The median age of participants was 65 years (interquartile range [IQR], 57–69.25), and the median duration of diabetes was 18 years (IQR, 12–26). Over a mean 2.1-year follow-up, unfavorable outcomes occurred in 53% of the whole cohort and in 36% of survivors. The strongest predictors of poor prognosis were prior amputation, elevated inflammatory markers, reduced eGFR, and dyslipidemia. Triglycerides showed a U-shaped association with outcomes. A lower BMI and shorter diabetes duration paradoxically were also linked to poorer prognosis. Glycemic control, comorbidities, and local foot characteristics had limited predictive value. Conclusions: Long-term DFU prognosis is driven mainly by systemic and host-related factors rather than by ulcer characteristics alone. Inflammation, renal dysfunction, dyslipidemia—particularly triglycerides—and prior amputation were the strongest predictors of unfavorable outcomes.

In men, estrogens are derived largely from peripheral conversion of testosterone to estradiol and of androstenedione to estrone, with only a small contribution from the testes. While estrogens have long been considered female sex hormones, they have proven to be pivotal in many aspects of male physiology, as originally demonstrated by the clinical consequences of estrogen-deficient and estrogen-excess states in men. This article discusses recent advances in understanding of estrogen targets and effects.

Background/Objectives: While it is known that Hashimoto’s thyroiditis (HT), goiter, thyroid nodules, and thyroid dysfunction may affect women’s reproductive health through hormonal and metabolic mechanisms, data are limited regarding the specific impacts on female sexual function. This study evaluated sexual function in women with thyroid disorders and examined its associations with thyroid function, age, menopausal status, and body mass index (BMI). Methods: A population-based survey was conducted in Kaunas, Lithuania, within the WHO MONICA framework. A random sample of 1569 women aged 25–69 years was included in the final analysis after applying the exclusion criteria. Anthropometric measurements were taken using standardized procedures, and the BMI was calculated. Sexual function was assessed using the 19-item Female Sexual Function Index (FSFI). Thyroid structure was evaluated by a team of trained physicians using ultrasound, while thyroid function was assessed via serum analysis (ELISA-based assays for TSH, fT4, and anti-TPO antibodies). Results: Of the 1569 women analyzed, 64.1% had sexual dysfunction (SD) (FSFI ≤ 26.55). Age and BMI showed significant negative correlations with all FSFI domains, with the strongest associations for arousal, lubrication, and total FSFI score (p < 0.01). SD was more prevalent among postmenopausal (43.6%) women than in premenopausal women (22.6%, p < 0.001) and increased with a higher BMI (p < 0.001). HT was found in 28.3% of participants. Compared with the reference group, women with HT were older, had higher BMI, higher TSH levels, and more hypothyroidism (p < 0.001). SD was more common in the HT group (71.7% vs. 64.2%, p < 0.001), with significantly lower lubrication and higher pain scores. In the multivariate analysis, only goiter remained an independent predictor of SD (p = 0.04). Conclusions: In conclusion, women with HT were older; had a higher BMI; and more frequently experienced SD, particularly reduced lubrication and increased pain, compared with the reference group. Although several thyroid conditions were associated with sexual dysfunction, only goiter remained an independent predictor after adjusting for age and BMI.

Abstract Background Acute Myocardial Infarction (AMI) represents a significant clinical challenge with diverse outcomes. Predicting patient-oriented composite endpoints (POCE) (all-cause death, any stroke, any AMI, or any revascularization) can significantly enhance post-AMI care. Incorporating clinical data with neuroendocrine biomarkers may offer improved prognostic capabilities. Objective To develop and validate a machine learning model to predict POCE in AMI patients, utilizing clinical parameters and neuroendocrine biomarkers. Methods There was prospective, observational, single-center study. Three approaches have been used to obtain the predictions for POCE event. First, as the dataset was imbalanced, an adaptive synthetic (ADASYN) sampling approach was used to generate synthetic instances, particularly focusing on those that are difficult-to-learn by using a weighted distribution. Then, random forest classifier (RF) was used to build a machine learning model to predict POCE. The model was tuned via a grid-search algorithm for optimal hyperparameters and validated using a 10-fold stratified cross-validation. Finally, the feature importance was determined by Shapley Additives, which measure the average marginal contribution of a feature value across all potential feature combinations. For the comparative purpose, the Gini index, which also shows the feature importance but in terms of mean decrease in impurity, was calculated. Results The study incorporated data from 315 patients, examining 47 variables and identifying 72 instances of POCE. After applying the ADASYN algorithm, the class distribution within the dataset was effectively equalized, facilitating the training of a robust RF model. Upon training with 252 instances, the model distinguished POCE with an accuracy of 83.8%, demonstrating a sensitivity of 80% and a specificity of 86%. During 10-fold cross-validation, the model's accuracy slightly dipped to 75%, with a sensitivity of 56% and specificity of 82%, indicating a balance between generalizability and overfitting. Testing mirrored these results, underscoring the model’s consistent performance. Notably, SHAP value analysis highlighted C-Reactive Protein (CRP) and alanine transaminase (ALT) as the most influential features, underscoring their significance in the context of AMI (Figure 1-2). The predictive power of each feature was further demonstrated by the mean decrease in Gini index (Figure 1-2). Conclusion Our study highlights the feasibility of employing machine learning to predict POCE post-AMI using an integrative dataset of clinical and neuroendocrine markers. The predictive model has the potential to revolutionize post-AMI care by allowing clinicians to identify high-risk patients early, tailor interventions, and allocate resources efficiently. Future research could explore the integration of this model into clinical workflows and its impact on patient outcomes.

It is considered that 1 in 10 adults worldwide have diabetes. Diabetic foot ulcers are some of the most common complications of diabetes, and they are associated with a high risk of lower-limb amputation and, as a result, reduced life expectancy. Timely detection and periodic ulcer monitoring can considerably decrease amputation rates. Recent research has demonstrated that computer vision can be used to identify foot ulcers and perform non-contact telemetry by using ulcer and tissue area segmentation. However, the applications are limited to controlled lighting conditions, and expert knowledge is required for dataset annotation. This paper reviews the latest publications on the use of artificial intelligence for ulcer area detection and segmentation. The PRISMA methodology was used to search for and select articles, and the selected articles were reviewed to collect quantitative and qualitative data. Qualitative data were used to describe the methodologies used in individual studies, while quantitative data were used for generalization in terms of dataset preparation and feature extraction. Publicly available datasets were accounted for, and methods for preprocessing, augmentation, and feature extraction were evaluated. It was concluded that public datasets can be used to form a bigger, more diverse datasets, and the prospects of wider image preprocessing and the adoption of augmentation require further research.

Pirmosios tarptautinės policistinių kiaušidžių sindromo diagnostikos ir gydymo gairės, kurių ruošime dalyvavo 6 pasaulio kontinentų įvairų specialybių eskpertai, apimančios tiek medicininius, tiek gyvensenos, psichologinius, socialinius aspektus, išleistos 2018 metais. 2023 metų rugpjūčio mėnesį buvo publikuotos atnaujintos rekomendacijos. Šių rekomomendacijų svarbiausi aspektai aptariami šioje apžvalgoje. Aprašomi stipresni įrodymai dėl širdies ir kraujagslių ligų, angliavandenių tolerancijos sutrikimo ir 2 tipo cukrinio diabeto, obstrukcinės miego apnėjos ir endometriumo vėžio rizikos šia liga sergančioms pacientėms. Pabrėžiamas būdinumas daugiau dėmesio skirti pacienčių psichologinei sveikatai. Taip pat aptariamas gyvensenos intervencijų būtinumas, medikamentinio gydymo efektyvumo įrodymų lygmuo. Pateikiama informacija apie naujus hirsutizmo gydymo būdus ir stipresnės rekomendacijos dėl nutukimo gydymo medikamentais ir bariatrinės chirurgijos. Aptariami nevaisingumo gydymo, esant policistinių kiaušidžių sindromui, principai. Policistinių kiaušidžių srityje būtini tolesni moksliniai tyrimai, nes daugelio gairėse pateikiamų įrodymų lygmuo yra žemas.

Transdermal testosterone administration delivers testosterone through the intact skin surface via a patch or a permeable membrane or directly on the skin as a gel or lotion. The subcutaneous tissues serve as a depot under the skin releasing small doses of testosterone into systemic circulation, thus achieving sustained "steady state" serum testosterone levels. There is usually a small peak of serum testosterone within the first few hours after application followed by levels within the physiological adult male range for 24 hours. In some preparations, depending on the time of application, serum testosterone profile mimics normal circadian variation observed in healthy younger men. Transdermal testosterone avoids first-pass metabolism by the liver and has less effect on the lipoproteins. For many hypogonadal men, transdermal testosterone is an attractive non-provider dependent and non-invasive way for testosterone replacement. The main problems of transdermal gels/lotions is the skin to skin transfer of testosterone to women and children on close skin contact and requirement that the gels must be applied over a large skin area. Despite these issues, transdermal testosterone is the most popular method of androgen replacement in some countries such as the United States.

Aprobavo Lietuvos sveikatos mokslų universiteto Medicinos akademijos Medicinos fakulteto taryba 2020 11 13, Protokolo Nr. 85 ir LSMU Leidybos komisija 2020-12-07, Protokolo Nr. 18/2020. Vilniaus universiteto Medicinos fakulteto Taryba 2020 11 10, Protokolo Nr. (1.2.)150000-TP-14-6

The aim of the present study was to determine associations of thyroid hormone levels and different metabolic parameters and anthropometric measurements with volume of nodular and nonnodular thyroid as well as with prevalence of goiter and thyroid nodules in middle-aged euthyroid subjects. Methods. The study consisted of 317 euthyroid subjects aged 48-49 from the Kaunas Cardiovascular Risk Cohort study. Thyroid-stimulating hormone (TSH), free thyroxine (FT4), and antithyroid peroxidase antibody (ATPO) levels, as well as anthropometric and metabolic parameters and smoking information, were evaluated. Results. In subjects with and without thyroid nodules, thyroid volume correlated with components of metabolic syndrome, body mass index (BMI), smoking, and TSH levels. In the nonnodular thyroid group, thyroid volume was also positively related to serum insulin and HOMA-IR, whereas a negative correlation between thyroid volume and leptin was identified in the nodular thyroid group. The goiter was identified in 12.3% of subjects. Female gender, thyroid nodules, smoking, BMI, and levels of TSH were independent predictors for goiter. Thyroid nodules were found in 31.2% of participants. Female gender, higher TSH levels, and thyroid volume were independent risk factors for thyroid nodules. Conclusions. Female gender, thyroid nodules, smoking, BMI, and TSH levels were identified as potential predictors of goiter. Female gender, TSH levels, and thyroid volume predicted the presence of thyroid nodules.

BACKGROUND:Novel male-based contraceptives are needed to broaden family planning choices. A progestin, Nestorone® (Nes) gel, plus a testosterone (T) gel suppresses sperm concentrations to levels associated with effective contraception in normal men. However, administration of two gels on different parts of the body daily is impractical.OBJECTIVE:Compare the effectiveness of daily application of a single, combined 8.3 mg Nes-62.5 mg T gel (Nes-T) vs. 62.7 mg T gel to suppress serum FSH and LH concentrations to ≤1.0 IU/L (a threshold associated with suppression of sperm concentrations to ≤1 million and effective contraception) and to compare the pharmacokinetics of serum Nes and T concentrations between the gel groups.DESIGN:We conducted a 28-day, double-blind, controlled trial of 44 healthy men randomized to daily Nes-T or T gel with measurement of hormones at baseline, treatment, and recovery and during 24-h pharmacokinetic studies on days 1 and 28 of treatment.RESULTS:Of the subjects who met pre-defined inclusion criteria, 84% of the Nes-T group suppressed serum gonadotropin concentrations to ≤1.0 IU/L at days 21-28 vs. 16.7% in the T group (p < 0.001). On day 1, Nes concentrations rose significantly above baseline by 2 h and continued to rise up to 24 h after Nes-T gel application. Nes concentrations were not detectable in the T group. Serum total T concentrations rose and were significantly higher in the T gel group compared to the Nes-T group at 24 h on day 1 and days 11, 14, and 21 (p < 0.01). There were no serious adverse events in either group. About 80% of the subjects reported satisfaction with both gels.CONCLUSION:Daily Nes-T gel effectively and safely suppresses serum gonadotropins and is acceptable to most men. It should be studied further in efficacy trials of hormonal male contraception.

Diabetes mellitus (DM) is a rapidly increasing problem in health care worldwide: recent forecast indicates that the number of DM patients will rise to 640 million by 2040. Vascular damage is associated with severe complications, including cardiac neuropathy and limb amputation. Therefore, early prediction of diabetic vascular damage using advanced technologies is an important challenge because timely preventive and therapeutic measures could diminish the risk of development and burden of complications. The aim of the article is to provide a review of the initial stages of vascular damage and main mechanisms for development, as well as appropriate modern technologies for prediction and diagnosis. The manuscript provides an overview of interrelated vascular damage mechanisms influenced by diabetes, along with a review of possible technologies for early prediction and diagnosis. A comparative analysis of technologies appropriate for particular issues of prediction is summarised in the discussion.

Aprobavo Lietuvos sveikatos mokslų universiteto Medicinos akademijos Medicinos fakulteto taryba 2019-10-23 Protokolo Nr. 72/2019 ir LSMU Leidybos komisija 2019-11-06 Protokolo Nr. 22/2019

Context: Dimethandrolone (DMA) has androgenic and progestational activity. Single oral doses of DMA undecanoate (DMAU) were well tolerated and reversibly suppressed serum LH and testosterone (T) in men. Objective: Assess safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of oral DMAU. Design: Double-blind, randomized, placebo-controlled study. Setting: Two academic medical centers. Participants: Healthy men (18 to 50 years). Interventions: One hundred men received DMAU [0, 100, 200, or 400 mg, formulated in castor oil/ benzyl benzoate (C) or powder (P)] for 28 days. Subjects underwent 24-hour PK sampling on days 1 and 28 and twice weekly ambulatory visits throughout treatment. Main Outcome Measures: Primary outcomes were safety and tolerability parameters (vitals, laboratory data, mood, and sexual function scores) and adverse events. Secondary outcomes were drug PK profiles and PD effects (serum LH, FSH, and sex hormones). Results: Eighty-two subjects completed the study and were included in the analysis. There were no serious adverse events. No clinically significant changes developed in safety laboratory parameters. A significant dose effect was seen for weight, hematocrit, high-density lipoprotein cholesterol, corrected QT interval, and sexual desire. Serum 24-hour average concentrations of DMAU and DMA showed dose-related increases (P < 0.001). All six subjects in the P400 group and 12 of 13 subjects in the C400 group achieved marked suppression of LH and FSH (<1.0 IU/L) and serum T (<50 ng/dL). Conclusions: Daily oral administration of DMAU for 28 days in healthy men is well tolerated. Doses of.200 mg markedly suppress serum T, LH, and FSH. These results support further testing of DMAU as a male contraceptive.

Cardiovascular disease (CVD) is the most significant prognostic factor in individuals with type 2 diabetes (T2D). However, a significant number of individuals may develop CVD that does not present with the classic angina-related or heart failure symptoms. In these cases, CVD may seem to be silent' or asymptomatic', but may be more accurately characterised as unrecognised diabetic cardiac impairment. An initial step to raise awareness of unrecognised CVD in individuals with T2D would be to reach a consensus regarding the terminology used to describe this phenomenon. By standardising the terminologies, and agreeing on the implementation of an efficient screening program, it is anticipated that patients will receive an earlier diagnosis and appropriate and timely treatment. Given the availability of anti-diabetic medications that have been shown to concomitantly reduce CV risk and mortality, it is imperative to improve early identification and initiate treatment as soon as possible in order to enable as many patients with T2D as possible to benefit.