[Hypogonadism in men with inflammatory joint diseases: Frequency and clinical characteristics].

AIM: To study the frequency of hypogonadism (HG) in men with rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA) and to evaluate the impact of HG on the course of RA and and concomitant diseases. MATERIALS AND METHODS: A single-stage continuous study included 170 men with RA, 57 men with AS and 85 men with PsA, who were hospitalized at the Nasonova Research Institute of Rheumatology. Patients were assessed for total testosterone (ТS) levels and subsequently divided into subgroups with normal (>12 nmol/l) and reduced levels. An intergroup comparison was carried out on the main indicators used in clinical rheumatological practice to assess the stage, activity and other medical and demographic characteristics of rheumatic disease, as well as on concomitant conditions. The second stage of the study involved a pairwise intergroup comparison among patients with HG with RA, AS and PsA. RESULTS: The incidence of ТS deficiency among patients with RA was 24.1%, among patients with AS - 17.5%, and with PsA - 31.8%. In patients with RA, HG was associated with a significantly higher mean body mass index, higher fasting blood glucose and uric acid, higher erythrocyte sedimentation rate and anemia. Patients with AS with HG had significantly lower hemoglobin levels and more frequent anemia, as well as higher levels of C-reactive protein and erythrocyte sedimentation rate. In PsA, older age was observed in the androgen deficiency group, as well as higher body mass index and fasting glucose levels; obesity was more common. An intergroup comparison of quantitative and qualitative indicators between patients with androgen deficiency in all three rheumatic diseases (RDs) did not reveal significant differences in the average concentrations of ТS, luteinizing hormone, sex hormone binding globulin, experience of RD, laboratory markers of inflammatory activity, as well as glucose and uric acid. A similar incidence of diabetes mellitus, obesity and anemia was noted for all three nosologies. CONCLUSION: ТS levels and the presence of HG were not associated with the stage and activity of RD, but ТS deficiency was accompanied by higher laboratory indicators of inflammatory activity, lower hemoglobin values, and metabolic disorders. Patients with HG, regardless of nosology, had similar levels of sex hormones and indicators reflecting RD and concomitant conditions.

[Hypogonadism syndrome in men with inflammatory joint diseases: A review].

Most rheumatic diseases are characterized by sexual dimorphism both in prevalence and in the characteristics of the clinical course. Increased production of pro-inflammatory cytokines that accompanies inflammatory joint diseases may be accompanied by a decrease in the level of male sex hormones, and vice versa, the presence of hypogonadism in men increases the risk of developing certain rheumatic diseases. The review presents data on the relationship between testosterone deficiency and major inflammatory joint diseases, as well as the effect of testosterone replacement therapy on their manifestations.

[Features of steroidogenesis and arterial hypertension in men in different types of "physiological" male hyperandrogenism].

AIM: To reveal the peculiarities of steroidogenesis and arterial hypertension in «physiological¼ hyperandrogenism in men. MATERIALS AND METHODS: One-stage simultaneous study. The groups of men with hyperandrogenism caused by increased total testosterone (n=34) and those with hyperandrogenism caused by increased dihydrotestosterone (DHT) (n=66) were compared. In determining the type of hyperandrogenism and allocating patients to groups, DHT and total testosterone levels were determined by enhanced chemiluminescence. Subgroups of men with and without arterial hypertension were compared in the group of patients with hyperandrogenism due to an increase in total testosterone. Body mass index, waist circumference, systolic and diastolic blood pressure, pulse, and LH, SBHG, estradiol, blood multisteroid levels by isotope dilution liquid chromatography/tandem mass spectrometry, glucose, blood lipid spectrum, uric acid, creatinine, renin, potassium, sodium, and blood chloride were assessed in all patients. Patients with arterial hypertension additionally underwent daily BP monitoring, albuminuria assessment, electrocardiography, ocular fundus examination. The baseline threshold level of significance was p<0.05. For multiple comparisons, the p significance level was calculated using the Bonferroni correction. RESULTS: Statistically significant differences were found in the levels of 17-hydroxypregnenolone, 17-hydroxyprogesterone, and androstenedione, which were higher in men with elevated levels of total testosterone. No statistically significant differences in other laboratory parameters were found. No cases of increased blood pressure were detected in the group of men with elevated DHT. In the group of men with elevated total testosterone, 23,5% of men with arterial hypertension without targetorgan lesions were identified, while hyperandrogenism was associated with 17,6% of cases. Arterial hypertension associated with hyperandrogenism was characterized by a rise in blood pressure in the early morning hours. Estradiol levels, while remaining within normal limits, were statistically significantly lower in patients with arterial hypertension compared with men with elevated testosterone but without hypertension. CONCLUSION: No cases of arterial hypertension were observed in «physiological¼ hyperandrogenism due to elevated DHT levels, whereas its incidence in «physiological¼ hyperandrogenism due to elevated total testosterone was 23,5%. The features of steroidogenesis were increased production of 17-hydroxypregnenolone, 17-hydroxyprogesterone, and androstenedione in men with testosterone hyperandrogenism and decreased estradiol production in patients with arterial hypertension compared with patients without testosterone hyperandrogenism.

[Androgenic status in men during COVID-19].

BACKGROUND: COVID-19 is a disease that has a negative systemic effect on the human body, including the male gonads. Therefore, the androgenic status in men with COVID-19 needs to be studied. AIM: To evaluate the levels of total testosterone, sex hormone binding globulin (SHBG) and free testosterone in men in the acute phase of COVID-19 and during convalescence. MATERIALS AND METHODS: A continuous dynamic prospective study of 70 men with moderate to severe COVID-19 at the age of 50[44; 64] years. During the study, the levels of total testosterone, SHBG were determined with further calculation of the level of free testosterone by Vermeullen. The data were collected twice - at the patient's hospitalization and at his discharge. The differences between the groups were considered statistically significant at p <0.05. RESULTS: At the time of hospitalization for COVID-19, hypogonadism syndrome was observed in 61 people - 87%. Patients with hypogonadism did not statistically significant differ in age and severity of COVID-19 disease compared to men without hypogonadism. Inpatient treatment lasting 12[10;14] days resulted in a statistically significant increase in the levels of total testosterone from 4,7[2,96;8,48] to 12,85[8,62;19,2] nmol/l, p<0,001; SHBG from 27,87[20,78;36,57] to 33,76[26,27;52,60] nmol/l, p<0,001 and free testosterone from 107[65;174] to 235[162;337] pmol/l, p<0,001. This led to the elimination of hypogonadism in 28 patients - 40%. Patients with persistent hypogonadism were statistically significantly older than men with normalized testosterone, there were no statistically significant differences in the initial levels of total testosterone, SHBG and free testosterone, and there were also no differences in the prevalence of severe COVID-19 (3,97[2,86;7,46] vs 4,26[2,93;5,96] nmol/l, p=0,100; 28,76[20,78;48,59] vs 24,63[18,85;31,70] nmol/l, р=0,994; 100[58;118] vs 96[64;143] pmol/l, p=0,522; 24 против 18%, p=0,754, respectively). CONCLUSION: COVID-19 has a pronounced negative effect on the production of testosterone in men, leading to the development of laboratoric hypogonadism, which is potentially reversible. The reversibility of laboratoric hypogonadism is typical for younger patients.

[Features of steroidogenesis in men with hypogonadism and type 2 diabetes].

BACKGROUND: Type 2 diabetes mellitus (DM2) in men is associated with a high incidence of hypogonadism. Testosterone is a steroid hormone and one of the final metabolites of steroidogenesis, which causes interest in assessing the content of key steroid hormones, their precursors and metabolites in hypogonadal and eugonadal men with T2DM. AIMS: Assessment of the features of steroidogenesis in men with hypogonadism in T2DM using tandem mass spectrometry. MATERIALS AND METHODS: A full-design, cross-sectional, screening, single-center, non-interventional study included men with T2DM, who were he was treated in Endocrinology Research Centre, Moscow. The study was conducted from October 2021 to January 2022. Medical history assessment, physical examination with determination of body mass index (BMI), measurement of key steroid hormones, their precursors and metabolites by isotope dilution liquid chromatography/tandem mass spectrometry, glycated hemoglobin (HbA1c) were performed. The groups were compared using the Mann-Whitney U-test for quantitative indicators and χ² with Yates' correction for qualitative ones. Correlation analysis was performed by the Spearman correlation method. When determining the criterion of statistical significance, the Bonferroni correction was applied. RESULTS: Patients with hypogonadism had statistically significantly more pronounced obesity compared with eugonadal men. In a comparative analysis of patients, depending on the presence of hypogonadism, there were statistically significantly lower levels of androgen precursors 17-hydroxypregnenolone and 17-hydroxyprogesterone in hypogonadal men. At the same time, a positive statistically significant correlation was found between total testosterone and 17-hydroxyprogesterone. In addition, 17-hydroxyprogesterone, although to a lesser extent, but positively correlated with other androgens - androstenedione (r=0,328; p<0,001) and dehydroepiandrosterone (r=0,183; p=0,004). >< 0,001) and dehydroepiandrosterone (r=0,183; p=0,004). CONCLUSIONS: In this investigation the prevalence of male hypogonadism in type 2 diabetes, determined by high-precision tandem mass spectrometry, was 69,5%. There was no effect of the disease on the mineralocorticoid and glucocorticoid links of adrenal steroidogenesis. Hypogonadism was associated with decreased levels of a number of testosterone precursors. The most significant of them was 17-hydroxyprogesterone, which can be considered as a marker of testicular steroidogenesis.

[Features of hyperandrogenism in men].

BACKGROUND: Today the problem of hyperandrogenism in women is a widely studied and discussed while same issue in relation to men is barely raised. In clinical practice, hyperandrogenism can be the cause of a number of diseases. AIM: Provide characterization the variations of physiological hyperandrogenism in men. MATERIALS AND METHODS: Сontinuous cross-sectional study of 100 men with hyperandrogenism. The study assessed the volume and structure of the prostate, the volume of the testicles; the levels of luteinizing hormone (LH), total testosterone, sex hormone binding globulin (SHBG) were determined with further calculation of the level of free testosterone according to Vermeullen, and dihydrotestosterone (DHT). Based on the results of the analysis of the hormonal status of patients with hyperandrogenism, 4 groups of patients were formed: 1-patients with increased total testosterone and SHBG levels; 2-patients with elevated total testosterone levels and normal SHBG levels; 3-patients with an increased level of total testosterone, DHT with a normal level of SHBG; 4-patients with an increased level of DHT with normal levels of total testosterone and SHBG. The difference between groups of patients was determined, a p-value <0.05 was considered statistically significant. RESULTS: The age and volume of the prostate in group 1 patients were statistically significantly higher than in the other groups. This group, despite the high level of total testosterone, was not characterized by complaints of acne. Group 2 patients complained of acne more often, but the prevalence of this symptom even in this group was statistically significantly lower than in group 3 patients. At the same time, the frequency of occurrence of alopecia was statistically significantly lower in group 2 than in patients of both groups 3 and 4. Patients of group 3 had the most striking clinical manifestations of hyperandrogenism. Group 4 was characterized by alopecia. CONCLUSION: An increase of androgen levels can be detected at any age. At the same time, in men of the older age group, an increase in the level of total testosterone may be due to an increase in the secretion of SHBG and not be accompanied by an increase in the level of free testosterone. In young patients, the clinical manifestations of hyperandrogenism may differ: patients with elevated DHT levels are characterized by androgenic alopecia; acne is common in men with elevated total and free testosterone levels, and increased DHT exacerbates the problem.

[Effect of transderrmal testosterone on the quality of life of men with androgen deficiency and chronic prostatitis in routine clinical practice].

AIM: To evaluate the effect of Androgel on the quality of life of patients with androgen deficiency (hypogonadism) and chronic prostatitis in everyday practice. MATERIALS AND METHODS: This open multicenter observational non-interventional study comprised 401 men with testosterone deficiency and chronic prostatitis who were treated with topical applications of 1% testosterone gel of (Androgel) at a dose of 50 or 100 mg in routine clinical practice for three months. The primary endpoint was the health related quality of life. Also, the patients filled out AMS, I-PSS, NIH-CPSI questionnaires to assess the quality of life related to chronic prostatitis, lower urinary tract symptoms, and aging. Secondary endpoints included changes in the overall score of the International Index of Erectile Function (IIEF-5), changes in body weight and waist circumference, the reasons for treatment discontinuation and any adverse events that occurred during treatment. RESULTS: Mean total testosterone levels at baseline and three months were 9.5 (95% CI 9.2-9.7) nmol/L and 16.5 (95% CI 16.1-16.9) nmol/l (p<0.001), respectively. There were statistically significant (p<0.001) differences in scores on all questionnaires. Mean scores at baseline and at three months for AMS, IIEF-5, I-PSS, NIH-CPSI questionnaires were 44.6 (95% CI 43.2-45.9) and 25.8 (95% CI 24.8-26.7); 12.7 (95% CI 12.2-13.2) and 19.3 (95% CI, 18.8-19.8); 14.5 (95% CI 13.7-15.3) and 5.6 (95% CI 5.2-6.1); 27.8 (95% CI 26,5-29.1) and 10.0 (95% CI 9.1-10.9), respectively. There were positive changes in body weight and waist circumference: at baseline and three months these parameters were 95 (95% CI 93.6-96.3) and 91.4 (95% CI 90.1-92.7) kg and 102.9 (95% CI 101.8-104.1) and 98.3 (95% CI 97.3-99.3) cm, respectively. No clinically significant adverse events were observed during follow-up. CONCLUSIONS: Transdermal therapy with 1% testosterone gel (Androgel) is highly effective and safe in the management of androgen deficiency (hypogonadism). Its use in patients with chronic prostatitis and hypogonadism results in an improvement in low urinary tract symptoms, symptoms of chronic prostatitis, alleviates pelvic pain and thus leads to significant improvements in the quality of life.

[Stimulation of a spermatogenesis in men at a pathospermia and infertility].

THE PURPOSE: to investigate of the methods of treatment, directed on increase in quantity of spermatozoa in an ejaculate. MATHERIALS AND METHODS: for this purpose used clomifene and combinations of recombinant FSH with chorionic gonadotrophin (HCG) in 60 men with infertility. RESULTS: Efficiency of monotherapy by clomiphene was higher and made 20% for conception, and 63% for oligoteratozoospermia. Efficiency of the combined therapy of HCG in combination with recombinant FSH was 40% for conception, and 87% for oligoteratozoospermia. The efficiency of the combined therapy by recombinant FSH and HCG in cases of the previous inefficiency monotherapy HCG and clomifene for oligoteratozoospermia made 65%. SUMMARY: The combined therapy of HCG in combination with recombinant FSH is al most effective. At the same time the studied types of the stimulating therapy are safe and don't lead to development of side effects.

[Nebido in the treatment of hypogonadism syndrome and its complications in men].

The article presents original experience with use of undecanoate (nebido, BayerHealthcare Pharmaceuticals, Germany) in androgenic testosteron replacement therapy in males with hypogonadism. Prospective studies of nebido efficacy were made in males with vein-occlusive erectile dysfunction (n = 20), chronic pelvic pain syndrome (n = 77), metabolic syndrome (n = 170). Retrospective studies assessed efficacy of nebido monotherapy in patients with erectile dysfunction and hypogonadism (n = 34), hematological and urological safety of the drug (n = 40). Laboratory monitoring was performed in all the studies according to ISSAM recommendations. The patients were not included in contraindications to androgenic therapy. Nebido treatment significantly improved libido and erectile function, efficacy of phosphodiesterase of type 5 inhibiors used in moderate and severe erectile dysfunction. Depressive, asthenic, pain symptoms declined in males with chronic pelvic pain. Body fat reduced in metabolic syndrome with alleviation of its other components. Insignificant rise of hemoglobin level and packed cell volume was observed in some patients while a PSA level increase was clinically significant in 10% patients who had initial PSA > 2.5 ng/ml and acromegalia. Also, nebido depressed production of gonadotropins and spermatogenesis. Thus, nebido is highly effective in sexual dysfunction and other somatic disorders caused by hypogonadism. Nebido does not induce severe side effects, but clinically significant rise of PSA level requires treatment discontinuation and more careful urological examination. In view of nebido ability to suppress spermatogenesis, the drug should not be used in reproductively active men.

[Sexual function rehabilitation of men with pituitary tumors].

A prospective trial of the methods of sexual rehabilitation of 31 men with pituitary tumors has shown that therapy with testosterone and chorionic gonadotropin effectively corrects hypogonadism and sexual disorders. In insufficient efficacy normalization of sexual function is achieved with tadalafil. Both methods of treatment had no negative effect on the size of the prostatic gland and PSA level except 2 patients with somatotropinoma on testosterone. In the course of chorionic gonadotropin treatment pituitary tumor increased in size in 3 patients.

[Sexual and reproductive function in males with somatotropinoma].

The examination of 72 males with somatotropinoma has found that 65% of such patients have hypogonadism which is essential in pathogenesis of sexual dysfunction and spermatogenetic disorders. However, hypogonadism in males with somatotropinoma does not provoke sexual dysfunction in most the cases. High production of somatotropic hormone and insulin-like growth factor 1 in somatotropinoma leads to prostatic hyperplasia which is not accompanied with a rise of a PSA level and symptoms of infravesical obstruction.

[Treatment of erectile dysfunction of neurogenic genesis with inhibitors of phosphodiesterase of type 5 in patients with diabetes mellitus].

We performed a pilot study of PDE-5 inhibitors efficacy in the treatment of diabetic genital neuropathy. A total of 16 diabetic males (type 1 diabetes mellitus) having erectile dysfunction with symptoms of genital neuropathy entered the trial. These patients received tadalafil for 3 months. The results were assessed with sexological questionnaires and dynamics of genital neuropathy symptoms. Tadalafil treatment was found effective.

[Gender-specific features of hyperprolactinemia syndrome].

The objective of the present work was to study specific clinical features of hyperprolactinemia in men and women. A total of 148 men and 138 women with hyperprolactinemia of tumorous and non-tumorous etiology were examined. Analysis of medical histories demonstrated that the period between the appearance of the first clinical symptoms and the establishment of diagnosis of hyperprolactinemia in men was longer than in women. The frequency, size, and invasiveness of macroprolactinomas were also different in the two sexes. Prolactin-secreting pituitary tumours in men showed more aggressive growth than in women. All the patients included in the study were examined for the measurement of monomeric prolactin (PRL) by separation of individual fractions in the precipitation reaction with 25% polyethyleneglycol. Macroprolactinemia occurred more frequently in women than in men. Total and monomeric PRL levels were higher in men with hyperprolactinemia of tumorous origin compared with women.

[Hematological and urological aspects of the safety of androgen substitution therapy using long-acting testosterone undecanoate in patients with hypogonadism].

The objective of this work was to evaluate hematological and urological safety of androgen substitution therapy by retrospective analysis of 40 medical histories of patients with hypogonadism. It was shown that treatment with testosterone undecanoate resulted in a significant increase of hemoglobin concentration and packed cell volume that did not however cause serious adverse events and did not require withdrawal of therapy. No statistically significant changes in prostate size or prostate specific antigen (PSA) level were documented in patients receiving androgen therapy. Clinically significant elevation of PSA was apparent in 12.5% of the patients in whom its initial level exceeded 2.5 ng/ml and also in patients with acromegaly. To conclude, the data obtained in this study point out to hematological and urological safety of androgen substitution therapy.