Local hormonal status of tumor and adjacent tissues in patients with melanoma depending on their gender.

e22084 Background: Gender is an important independent prognostic factor for cutaneous melanoma incidence, and survival in women is better. The purpose of the study was to determine the content of sex steroids and prolactin in tumor, perifocal and resection line tissues in male and female patients with melanoma. Methods: The study included 13 men and 22 women with cutaneous melanoma (M) pT1-2N0M0. Levels of free testosterone (fT), estradiol (E2), estrone (E1), progesterone and prolactin were measured by ELISA in M, perifocal (P) and resection line (RL) tissues after surgical treatment. The average age of patients was in men 54±3.56 years (median age 53, 32-81), in women 65±2.67 years (median age 63, 39-82). Skin tissues obtained from 20 non-cancer patients after plastic surgery served as the control. Results: In M of women, levels of fT, E2 and E1 were elevated on average by 1.3 times, while in men fT was decreased by 1.7 times, and estrogens were increased – E2 by 1.7 and E1 by 3.7 times, compared to the corresponding control levels. In women, fT in P tissues was increased by 1.6 times, while parameters in RL were similar to control values. In men, fT in P and RL tissues was decreased by 3.8 and 2.3 times respectively, and E2 was increased by 1.6 and 1.3 times respectively. E1 in P tissues was decreased by 1.7 times, in RL – similar to control levels. Conclusions: M in patients of both genders has an altered hormonal profile characterized by hyperestrogenia, with the prevalence of E1 and androgen deficiency in men. The expansion of the “tumor field” due to changes in the hormonal profile of P and even RL tissues was established only in male patients with the same morphological prevalence of the process, which may be one of the reasons for the more aggressive tumor course.

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Sex steroids, sex-binding globulin, and prolactin in tissues of adenocarcinoma and esophageal squamous cell carcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.4_suppl.79 ◽

2017 ◽

Vol 35 (4_suppl) ◽

pp. 79-79

Author(s):

Oleg Ivanovich Kit ◽

Elena Mikhaylovna Frantsiyants ◽

Valeria Bandovkina ◽

Evgeniy N. Kolesnikov ◽

Roman E. Myagkov ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Sex Steroids ◽

Tumor Biology ◽

Free Testosterone ◽

Adenocarcinoma Of The Esophagus ◽

Esophageal Tumors ◽

Hormonal Content ◽

Resection Line

79 Background: Some researchers suggest that squamous cell carcinoma (SCC) and adenocarcinoma of the esophagus (ACE) are characterized by different pathogenesis, epidemiology and tumor biology, and therefore require different therapeutic strategies. The purpose of the study was to analyze local hormonal status in malignant esophageal tumors and surrounding tissues depending on the histogenesis. Methods: Levels of sex steroids – free testosterone (fT), estrone (E1), estriol (E3), prolactin (PRL) and sex steroid-binding globulin (SSBG) were studied by the standard ELISA methods in tumor tissue, perifocal zone and resection line of 39 patients aged 58-74 years: 27 SCC, 12 ACE, stage II, G2, pT1-2N1M0. Results: Differences were found in local hormonal content in all studied samples dependint on the tumor histotype. Levels of SSBG, PRL and E1 in ACE were higher than in SCC by 1.3, 3.3 and 1.4 times, respectively, while fT concentration was 2.4 times lower. Levels of PRL, E1 and E3 in perifocal zone of ACE compared to SCC were higher by 2.8, 3.3 and 3.1 times, and fT was 1.3 times lower. Resection line of ACE differed from that of SCC by higher tissue concentrations of SSBG – by 1.3 times, PRL – by 1.5 times, E1 – by 1.3 times, E3 – by 1.7 times and a lower level of fT – by 1.5 times. As a result, fT/E1 ratios in ACE and surrounding tissues were on average 3 times lower than in corresponding SCC samples. Conclusions: Levels of hormones in esophageal tumors and surrounding tissues depend on the histogenesis. ACE was characterized by hyperestrogenism in esophageal tissues along with a high prolactin concentration, while SCC – by hyperandrogenism with a low PRL level. Different pathogenesis of SCC and ACE was demonstrated by the fact that hormonal profile in both tumor and resection line depended on the tumor histology.

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Clinical Characteristics and Prognostic Implications of BRCA-associated Tumors in Males: A Pan-tumor Survey

10.21203/rs.3.rs-35299/v2 ◽

2020 ◽

Author(s):

Peng Sun ◽

Yue Li ◽

Xue Chao ◽

Jibin Li ◽

Rongzhen Luo ◽

...

Keyword(s):

Cutaneous Melanoma ◽

Brca Mutation ◽

Progression Free Survival ◽

Brca Mutations ◽

Male And Female ◽

Female Patients ◽

Male Patients ◽

Brca2 Mutations ◽

Prognostic Implications ◽

Associated Tumors

Abstract Background The BRCA mutation (BRCAm) in males has been reported to confer a higher risk for the development of various tumors. However, little is known about its clinicopathologic features and prognostic implications.Design We conducted a retrospective pan-tumor survey on 346 cases of BRCA-associated tumors in males. Comparative analyses were conducted among male and female patients with BRCAm (n=349), as well as in male patients without BRCAm (n=4577).Results Similar incidences of BRCAm (6.0 vs. 6.6%) and age at diagnosis of tumor (median, 65 vs. 60 years) were observed in male and female patients. Carcinomas of the lung, bladder, stomach, and cutaneous melanoma were the frequent tumors demonstrating BRCAm in males, of which the majority were stage II or III diseases with a higher frequency of BRCA2 mutations. Compared to that in the non-BRCAm group, cutaneous melanoma (16.3 vs. 5.0%), lung cancer (19.4 vs. 11.8%), bladder cancer (15.6 vs. 5.6%), and stomach cancer (11.9 vs. 5.5%) accounted for a higher proportion in the BRCAm group. Advanced disease and more mutation counts (median, 322 vs. 63 mutations) were also found in the BRCAm group. A total of 127 BRCA1 and 311 BRCA2 mutations were identified, of which 21.8% and 28.6% were deleterious, respectively. Frequent deleterious variants were identified in carcinomas of the breast (100.0%), colorectum (62.2%), prostate (43.3%), and stomach (42.9%). BRCA1 fusions with NF1, FAM134C, BECN1, or LSM12 and recurrent BRCA2 mutations at P606L/S, E832K/G, and T3033Lfs*29 were detected. Frameshift mutations in BRCA2 at N1784 (N1784Kfs*3, N1784Tfs*3) were frequently observed in both male and female patients. Compared with those in females, BRCA mutations in males were associated with decreased overall survival (OS) and progression-free survival (PFS). Male patients with deleterious BRCAm displayed increased OS compared with non-BRCAm carriers. The subgroup analysis demonstrated that BRCAm was associated with increased OS in gastric and bladder cancers, decreased PFS in prostate, esophageal, and head and neck cancers, and decreased OS in glioma/glioblastoma in males.Conclusion These findings provide an overview of the distinct characteristics and clinical outcomes of male patients with BRCA-associated tumors, suggesting the importance of further genetic BRCA testing in males.

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Clinical Characteristics and Prognostic Implications of BRCA-associated Tumors in Males: A Pan-tumor Survey

10.21203/rs.3.rs-35299/v3 ◽

2020 ◽

Author(s):

Peng Sun ◽

Yue Li ◽

Xue Chao ◽

Jibin Li ◽

Rongzhen Luo ◽

...

Keyword(s):

Cutaneous Melanoma ◽

Brca Mutation ◽

Progression Free Survival ◽

Brca Mutations ◽

Male And Female ◽

Female Patients ◽

Male Patients ◽

Brca2 Mutations ◽

Prognostic Implications ◽

Associated Tumors

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Clinical characteristics and prognostic implications of BRCA-associated tumors in males: a pan-tumor survey

BMC Cancer ◽

10.1186/s12885-020-07481-1 ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Peng Sun ◽

Yue Li ◽

Xue Chao ◽

Jibin Li ◽

Rongzhen Luo ◽

...

Keyword(s):

Cutaneous Melanoma ◽

Brca Mutation ◽

Progression Free Survival ◽

Brca Mutations ◽

Male And Female ◽

Female Patients ◽

Male Patients ◽

Brca2 Mutations ◽

Prognostic Implications ◽

Associated Tumors

Abstract Background The BRCA mutation (BRCAm) in males has been reported to confer a higher risk for the development of various tumors. However, little is known about its clinicopathologic features and prognostic implications. Design We conducted a retrospective pan-tumor survey on 346 cases of BRCA-associated tumors in males. Comparative analyses were conducted among male and female patients with BRCAm (n = 349), as well as in male patients without BRCAm (n = 4577). Results Similar incidences of BRCAm (6.0 vs. 6.6%) and age at diagnosis of tumor (median, 65 vs. 60 years) were observed in male and female patients. Carcinomas of the lung, bladder, stomach, and cutaneous melanoma were the frequent tumors demonstrating BRCAm in males, of which the majority were stage II or III diseases with a higher frequency of BRCA2 mutations. Compared to that in the non-BRCAm group, cutaneous melanoma (16.3 vs. 5.0%), lung cancer (19.4 vs. 11.8%), bladder cancer (15.6 vs. 5.6%), and stomach cancer (11.9 vs. 5.5%) accounted for a higher proportion in the BRCAm group. Advanced disease and more mutation counts (median, 322 vs. 63 mutations) were also found in the BRCAm group. A total of 127 BRCA1 and 311 BRCA2 mutations were identified, of which 21.8 and 28.6% were deleterious, respectively. Frequent deleterious variants were identified in carcinomas of the breast (100.0%), colorectum (62.2%), prostate (43.3%), and stomach (42.9%). BRCA1 fusions with NF1, FAM134C, BECN1, or LSM12 and recurrent BRCA2 mutations at P606L/S, E832K/G, and T3033Lfs*29 were detected. Frameshift mutations in BRCA2 at N1784 (N1784Kfs*3, N1784Tfs*3) were frequently observed in both male and female patients. Compared with those in females, BRCA mutations in males were associated with decreased overall survival (OS) and progression-free survival (PFS). Male patients with deleterious BRCAm displayed increased OS compared with non-BRCAm carriers. The subgroup analysis demonstrated that BRCAm was associated with increased OS in gastric and bladder cancers, decreased PFS in prostate, esophageal, and head and neck cancers, and decreased OS in glioma/glioblastoma in males. Conclusion These findings provide an overview of the distinct characteristics and clinical outcomes of male patients with BRCA-associated tumors, suggesting the importance of further genetic BRCA testing in males.

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Clinical Characteristics and Prognostic Implications of BRCA-associated Tumors in Males: A Pan-tumor Survey

10.21203/rs.3.rs-35299/v4 ◽

2020 ◽

Author(s):

Peng Sun ◽

Yue Li ◽

Xue Chao ◽

Jibin Li ◽

Rongzhen Luo ◽

...

Keyword(s):

Cutaneous Melanoma ◽

Brca Mutation ◽

Progression Free Survival ◽

Brca Mutations ◽

Male And Female ◽

Female Patients ◽

Male Patients ◽

Brca2 Mutations ◽

Prognostic Implications ◽

Associated Tumors

Abstract Background The BRCA mutation (BRCAm) in males has been reported to confer a higher risk for the development of various tumors. However, little is known about its clinicopathologic features and prognostic implications. Design We conducted a retrospective pan-tumor survey on 346 cases of BRCA-associated tumors in males. Comparative analyses were conducted among male and female patients with BRCAm (n=349), as well as in male patients without BRCAm (n=4577). Results Similar incidences of BRCAm (6.0 vs. 6.6%) and age at diagnosis of tumor (median, 65 vs. 60 years) were observed in male and female patients. Carcinomas of the lung, bladder, stomach, and cutaneous melanoma were the frequent tumors demonstrating BRCAm in males, of which the majority were stage II or III diseases with a higher frequency of BRCA2 mutations. Compared to that in the non-BRCAm group, cutaneous melanoma (16.3 vs. 5.0%), lung cancer (19.4 vs. 11.8%), bladder cancer (15.6 vs. 5.6%), and stomach cancer (11.9 vs. 5.5%) accounted for a higher proportion in the BRCAm group. Advanced disease and more mutation counts (median, 322 vs. 63 mutations) were also found in the BRCAm group. A total of 127 BRCA1 and 311 BRCA2 mutations were identified, of which 21.8% and 28.6% were deleterious, respectively. Frequent deleterious variants were identified in carcinomas of the breast (100.0%), colorectum (62.2%), prostate (43.3%), and stomach (42.9%). BRCA1 fusions with NF1, FAM134C, BECN1, or LSM12 and recurrent BRCA2 mutations at P606L/S, E832K/G, and T3033Lfs*29 were detected. Frameshift mutations in BRCA2 at N1784 (N1784Kfs*3, N1784Tfs*3) were frequently observed in both male and female patients. Compared with those in females, BRCA mutations in males were associated with decreased overall survival (OS) and progression-free survival (PFS). Male patients with deleterious BRCAm displayed increased OS compared with non-BRCAm carriers. The subgroup analysis demonstrated that BRCAm was associated with increased OS in gastric and bladder cancers, decreased PFS in prostate, esophageal, and head and neck cancers, and decreased OS in glioma/glioblastoma in males. Conclusion These findings provide an overview of the distinct characteristics and clinical outcomes of male patients with BRCA-associated tumors, suggesting the importance of further genetic BRCA testing in males.

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The application value of serum 25(OH)D3, uric acid, triglyceride, and homeostasis model assessment of insulin resistance in male patients with hyperuricemia combined with hypogonadism

BMC Endocrine Disorders ◽

10.1186/s12902-021-00765-y ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Qun Zhang ◽

Wei Chen ◽

Canqin Yun ◽

Juan Wang

Keyword(s):

Insulin Resistance ◽

Logistic Regression ◽

Uric Acid ◽

Free Testosterone ◽

Normal Group ◽

Model Assessment ◽

Homeostasis Model Assessment ◽

Alcoholic Fatty Liver ◽

Male Patients ◽

Function Group

Abstract Background The purpose of this study was to investigate the application value of serum 25(OH)D3, uric acid, triglyceride (TG), and homeostasis model assessment of insulin resistance (HOMA-IR) in male patients with hyperuricemia combined with hypogonadism. Methods From August 2018 to August 2020, a total of 198 male patients with primary hyperuricemia were prospectively enrolled in our hospital for inpatient treatment in the department of Metabolism and Endocrinology. They are divided into normal gonadal function group (normal group, n = 117) and hypogonadal function group (hypogonadism group, n = 81), according to free testosterone (FT) level, International Index of Erectile Function (IIEF-5), and androgen deficiency in the aging male (ADAM) questionnaires. Laboratory indexes were compared between two groups. Multivariate logistic regression was applied to analyze the influencing factors of hypogonadism. Results Among the 198 hyperuricemia patients, 40.91 % were hypogonadism. Compared with the normal group, the BMI, waist circumference (WC), and the prevalence of non-alcoholic fatty liver disease (NAFLD), hyperlipidemia (HLP), and obesity (OB) in the hypogonadism group were higher, and the difference was statistically significant (P < 0.05, respectively). The levels of fasting plasma glucose (FPG), fasting insulin (FINS), homeostasis model assessment of insulin resistance (HOMA-IR), triacylglycerol (TG), serum uric acid (SUA), alanine transaminase (ALT) of hypogonadism group were higher than those of normal group, while the levels of TT, FT, E2, 25(OH)D3 of hypogonadism group were lower than those of normal group (P < 0.05, respectively). Pearson’s linear correlation was used to analyze the correlation between the indicators with significant differences in general data and laboratory indicators and hypogonadism. BMI, WC, HOMA-IR, TG, SUA, TT, FT, 25(OH)D3, E2 were positively correlated with hypogonadism (r = 0.556, 0.139, 0.473, 0.143, 0.134, 0.462, 0.419, 0.572, 0.601, P = 0.012, 0.027, 0.018, 0.019, 0.028, 0.029, 0.030, 0.009, 0.003, respectively). Taking the above indicators as independent variables and hypogonadism as the dependent variable, logistic regression analysis found that the risk factors for hypogonadism were SUA, WC, BMI, HOMA-IR, TG, TT, FT, E2, and 25(OH) D3. Conclusions Serum 25(OH)D3, SUA, HOMA-IR, TG levels were positively correlated with male hyperuricemia patients with hypogonadism. They have important application value in the diagnosis of male hyperuricemia patients with hypogonadism.

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Androgen Deficiency And Insulin Resistance in Obese Male Patients

Journal of Men s Health ◽

10.1016/j.jomh.2010.09.064 ◽

2010 ◽

Vol 7 (3) ◽

pp. 300-301

Author(s):

Sh. Janjgava ◽

E. Giorgadze ◽

K. Asatiani ◽

M. Amashukeli ◽

L. Uchava ◽

...

Keyword(s):

Insulin Resistance ◽

Androgen Deficiency ◽

Male Patients ◽

Obese Male

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Sex steroids regulate pro- and anti-inflammatory cytokine release by macrophages after trauma-hemorrhage

AJP Cell Physiology ◽

10.1152/ajpcell.1999.277.1.c35 ◽

1999 ◽

Vol 277 (1) ◽

pp. C35-C42 ◽

Cited By ~ 116

Author(s):

Martin K. Angele ◽

Markus W. Knöferl ◽

Martin G. Schwacha ◽

Alfred Ayala ◽

William G. Cioffi ◽

...

Keyword(s):

Immune Responses ◽

Peritoneal Macrophage ◽

Kupffer Cell ◽

Sex Steroids ◽

Sham Operation ◽

Male And Female ◽

Splenic Macrophage ◽

Female Sex ◽

17Β Estradiol ◽

Tissue Trauma

Studies indicate that macrophage immune responses in males are depressed after trauma-hemorrhage, whereas they are enhanced in females under such conditions. Nonetheless, the involvement of male and female sex steroids in this gender-dependent dimorphic immune response after trauma-hemorrhage remains unclear. To study this, male C3H/HeN mice were castrated and treated with pellets containing either vehicle, 5α-dihydrotestosterone (DHT), 17β-estradiol, or a combination of both steroid hormones for 14 days before soft tissue trauma (i.e., laparotomy) and hemorrhagic shock (35 ± 5 mmHg for 90 min followed by adequate fluid resuscitation) or a sham operation. Twenty-four hours later the animals were killed, plasma was obtained, and Kupffer cell and splenic and peritoneal macrophage cultures were established. For DHT-treated mice, we observed significantly decreased releases of the proinflammatory cytokines interleukin 1β (IL-1β) and IL-6 by splenic macrophage (−50 and −57%, respectively) and peritoneal macrophage (−51 and −52%, respectively) cultures after trauma-hemorrhage compared with releases by cultures of cells from mice subjected to a sham operation; in contrast, responses of splenic and peritoneal macrophage cultures from other groups subjected to trauma-hemorrhage did not change significantly. In addition, only DHT-treated animals exhibited increased Kupffer cell IL-6 release (+634%). The release of IL-10 in DHT-treated hemorrhaged animals was increased compared with that in sham-operated animals but was decreased in estrogen-treated mice under such conditions. These results suggest that male and female sex steroids exhibit divergent immunomodulatory properties with respect to cell-mediated immune responses after trauma-hemorrhage.

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Sex-Disaggregated Data on Clinical Characteristics and Outcomes of Hospitalized Patients With COVID-19: A Retrospective Study

Frontiers in Cellular and Infection Microbiology ◽

10.3389/fcimb.2021.680422 ◽

2021 ◽

Vol 11 ◽

Author(s):

Mengdie Wang ◽

Nan Jiang ◽

Changjun Li ◽

Jing Wang ◽

Heping Yang ◽

...

Keyword(s):

Logistic Regression ◽

Regression Analysis ◽

Logistic Regression Analysis ◽

Clinical Characteristics ◽

Random Effect ◽

Hospitalized Patients ◽

Male And Female ◽

Female Patients ◽

Disease Outcomes ◽

Male Patients

BackgroundSex and gender are crucial variables in coronavirus disease 2019 (COVID-19). We sought to provide information on differences in clinical characteristics and outcomes between male and female patients and to explore the effect of estrogen in disease outcomes in patients with COVID-19.MethodIn this retrospective, multi-center study, we included all confirmed cases of COVID-19 admitted to four hospitals in Hubei province, China from Dec 31, 2019 to Mar 31, 2020. Cases were confirmed by real-time RT-PCR and were analyzed for demographic, clinical, laboratory and radiographic parameters. Random-effect logistic regression analysis was used to assess the association between sex and disease outcomes.ResultsA total of 2501 hospitalized patients with COVID-19 were included in the present study. The clinical manifestations of male and female patients with COVID-19 were similar, while male patients have more comorbidities than female patients. In terms of laboratory findings, compared with female patients, male patients were more likely to have lymphopenia, thrombocytopenia, inflammatory response, hypoproteinemia, and extrapulmonary organ damage. Random-effect logistic regression analysis indicated that male patients were more likely to progress into severe type, and prone to ARDS, secondary bacterial infection, and death than females. However, there was no significant difference in disease outcomes between postmenopausal and premenopausal females after propensity score matching (PSM) by age.ConclusionsMale patients, especially those age-matched with postmenopausal females, are more likely to have poor outcomes. Sex-specific differences in clinical characteristics and outcomes do exist in patients with COVID-19, but estrogen may not be the primary cause. Further studies are needed to explore the causes of the differences in disease outcomes between the sexes.

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