Impact Of Sex Hormones Research Articles

The impact of sex hormones on metabolic syndrome: univariable and multivariable Mendelian randomization studies

BackgroundObservational studies have found associations between sex hormones and metabolic syndrome(Mets), but the causal relationships remains unclear. This study utilizes univariable and multivariable Mendelian randomization (MR) to elucidate the associations between sex hormones (including sex hormone-binding globulin(SHBG), estradiol(E2), testosterone(T)) and Mets and its subtypes (including waist circumference(WC), fasting blood glucose(FBG), high blood pressure(HBP), high-density lipoprotein(HDL-C), triglycerides(TG)).MethodsWe utilized summary data from large-scale genome-wide association studies. Univariable Mendelian randomization (UMVMR) analysis was primarily conducted using the inverse variance weighted method (IVW), with secondary analyses employing the weighted median, MR-Egger regression, simple mode method, and weighted mode method. Subsequently, multivariable Mendelian randomization (MVMR) was employed to assess the causal relationships between SHBG, T, E2, and MetS and its components: WC, FPG, HBP, HDL-C, and TG. Sensitivity analyses were conducted to assess result reliability.ResultsGenetically predicted SHBG was significantly negatively associated with MetS (UMVMR: β=-0.72; 95% CI = 0.41 to 0.57; P = 1.28e-17; MVMR: β=-0.60; 95% CI=-0.83 to -0.38; P < 0.001). Positive causal relationships were observed between SHBG and WC(MVMR: β = 0.10; 95% CI = 0.03 to 0.17; P = 0.01) and HDL-C (MVMR: β = 0.41; 95% CI = 0.21 to 0.60; P < 0.001), while negative causal relationships were found between SHBG and HBP (MVMR: β=-0.02; 95% CI=-0.04 to -0.00; P = 0.02), TG (MVMR: β=-0.48; 95% CI=-0.70 to -0.26; P < 0.001). Genetically predicted E2 exhibited a negative association with TG (MVMR: β=-1.49; 95% CI=-2.48 to -0.50; P = 0.003). Genetically predicted T was negatively associated with TG (MVMR: β=-0.36; 95% CI=-0.71 to -0.00; P = 0.049) and WC (MVMR: β=-0.13; 95% CI=-0.24 to -0.02; P = 0.02), with inconsistent sensitivity analyses. Additionally, No other causal associations were found.ConclusionOur study indicates that SHBG is a protective factor for MetS, potentially delaying its onset and progression through improvements in HBP and TG. Furthermore, T and E2 may improve TG levels, with T also reducing WC levels. Importantly, our study provides new insights for the prevention and treatment of MetS.

Postmenopausal Cognitive Function and Steroid Hormone Levels

Introduction: Most studies on the impact of sex hormones on the postmenopausal brain have focused on the lack of estrogen, with conflicting evidence. The influence of androgens on cognitive function is not well understood. This study aimed to assess the association between steroid hormones and cognitive function in postmenopausal women.

Sex-dependent interaction of PTGS2 with miR-146a as risk factor for melanoma and the impact of sex hormones in gene expression in skin cells.

Gender disparity in melanoma is a complex issue where sex hormones could be engaged. Differences in genetic variations are important in understanding the mechanisms of sex disparity in melanoma. Post-transcriptional regulation of prostaglandin-endoperoxide synthase (PTGS2) mRNA occurs through a complex interplay of specific trans-acting RNA-binding proteins and microRNAs. MiR-146a is a key player in melanoma, modulating immune responses and tumor microenvironment (TME). Polymorphisms in PTGS2 gene rs20415G<C and miR-146a gene rs2910164G>C have been associated with an increased risk of melanoma. Epistasis between polymorphisms rs20415G<C and rs2910164G>C was investigated by genotyping 453 melanoma patients and 382 control individuals. The effects of testosterone and 17β-estradiol were analyzed in keratinocytes and two melanoma cell lines. The rs2910164GG showed a higher risk in the presence of the genotype rs20417CC in the male population. Testosterone and 17β-estradiol act differently on PTGS2 and miR-146a expression, depending on the cell type. Testosterone augments PTGS2 gene expression in keratinocytes and miR-146a in melanoma cells. While 17β-estradiol only increases miR-146a expression in HaCaT cells. The present study indicates a sex-specific relation between miR-146a and PTGS2 polymorphisms with melanoma cancer risk. Testosterone and 17β-estradiol act differently on the expression of PTGS2 and miR-146a depending on the skin cell type.

Melanoma and sex hormones: Pathogenesis, progressive disease and response to treatments.

Cutaneous melanoma represents the fifth tumor in terms of incidence in young adults, with a major involvement of males than females. Despite the significant changes in available effective treatments for cutaneous melanoma, there is still a proportion of patients that do not benefit long-term disease control with immune checkpoint inhibitors and/or BRAF/MEK inhibitors, and eventually develop progressive disease. In addition to the emerging biomarkers under investigation to understand resistance to treatments, recent studies resumed the role of sex hormones (estrogens, progesterone and androgens) in melanoma patients. In the last decades, the impact of sex hormones has been considered controversial in melanoma patients, but actual growing preclinical and clinical evidence underline the potential influence on melanoma cells' growth, tumor microenvironment, the immune system and consequently on the course of disease.This review will provide available insights on the role of sex hormones in melanoma pathogenesis, disease progression and response/resistance to systemic treatments. We will also offer an overview on the recent studies on the theme, describing the hormonal contribution to disease response and the interaction with targeted therapies and immune-checkpoint inhibitors in cutaneous melanoma patients, illustrating an insight into future research in this field.

Sex differences in blood pressure regulation and hypertension: renal, hemodynamic, and hormonal mechanisms.

The teleology of sex differences has been argued since at least as early as Aristotle's controversial Generation of Animals more than 300 years BC, which reflects the sex bias of the time to contemporary readers. Although the question "why are the sexes different" remains a topic of debate in the present day in metaphysics, the recent emphasis on sex comparison in research studies has led to the question "how are the sexes different" being addressed in health science through numerous observational studies in both health and disease susceptibility, including blood pressure regulation and hypertension. These efforts have resulted in better understanding of differences in males and females at the molecular level that partially explain their differences in vascular function and renal sodium handling and hence blood pressure and the consequential cardiovascular and kidney disease risks in hypertension. This review focuses on clinical studies comparing differences between men and women in blood pressure over the life span and response to dietary sodium and highlights experimental models investigating sexual dimorphism in the renin-angiotensin-aldosterone, vascular, sympathetic nervous, and immune systems, endothelin, the major renal sodium transporters/exchangers/channels, and the impact of sex hormones on these systems in blood pressure homeostasis. Understanding the mechanisms governing sex differences in blood pressure regulation could guide novel therapeutic approaches in a sex-specific manner to lower cardiovascular risks in hypertension and advance personalized medicine.

Genetic Correlation, Shared Loci, and Causal Association Between Sex Hormone-Binding Globulin and Bone Mineral Density: Insights From a Large-Scale Genomewide Cross-Trait Analysis.

Although the impact of sex hormones on bone metabolism is well-documented, effect of their primary modulator, sex hormone-binding globulin (SHBG), remains inconclusive. This study aims to elucidate the genetic overlap between SHBG and heel estimated bone mineral density (eBMD), a widely-accepted tool for osteoporosis management and fracture risk assessment. Using summary statistics from large-scale genomewide association studies conducted for SHBG (N = 370,125), SHBG adjusted for body mass index (SHBGa, N = 368,929), and eBMD (N = 426,824), a comprehensive genomewide cross-trait approach was performed to quantify global and local genetic correlations, identify pleiotropic loci, and infer causal associations. A significant overall inverse genetic correlation was found for SHBG and eBMD (rg = -0.11, p = 3.34 × 10-10 ), which was further supported by the significant local genetic correlations observed in 11 genomic regions. Cross-trait meta-analysis revealed 219 shared loci, of which seven were novel. Notably, four novel loci (rs6542680, rs8178616, rs147110934, and rs815625) were further demonstrated to colocalize. Mendelian randomization identified a robust causal effect of SHBG on eBMD (beta = -0.22, p = 3.04 × 10-13 ), with comparable effect sizes observed in both men (beta = -0.16, p = 1.99 × 10-6 ) and women (beta = -0.19, p = 2.73 × 10-9 ). Replacing SHBG with SHBGa, the observed genetic correlations, pleiotropic loci and causal associations did not change substantially. Our work reveals a shared genetic basis between SHBG and eBMD, substantiated by multiple pleiotropic loci and a robust causal relationship. Although SHBG has been implicated in preventing and screening aging-related diseases, our findings support its etiological role in osteoporosis. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

The Impact of Sex Hormones on Cognition and Treatment: A Review

Hormones serves as natural chemical triggers that regulate various processes within the human body, including growth, emotional states, and cognitive processing. Extensive research has been conducted to explore the correlation between hormonal effects and cognitive function; these studies have examined a variety of factors such as aging, pregnancy, post-natal states, emotions, and stress. This article focuses on the impact of hormonal changes on neuronal networks and the mechanisms underlying cognitive function. Hormones possess the ability to influence multiple processes in the human body, including emotions and cognition. The effects of hormones on cognitive function vary depending on the specific hormone involved. Furthermore, hormone levels that are too low or too high can lead to both positive and negative outcomes. Therefore, understanding the influence of sex hormones on cognition is a valuable endeavor.

Vocal and articulatory performance fluctuates across the menstrual cycle: Acoustic analysis of daily single participant speech data over three months

The impact of sex hormones on voice and speech has been observed across the menstrual cycle; however, the evidence remains mixed. Here, we investigated voice and articulatory performance as a function of the menstrual cycle over three months via an intensive longterm single case experimental design. A 17-yearold naturally cycling female who did not use oral/hormonal contraceptives gave a written consent to participate in the study over a period of three cycles (i.e., 90 days). Daily urine sample test strips were utilized to identify the onset of ovulation (via luteinizing hormone, LH). Daily voice and articulation tasks including a Maximum Phonation Time (MPT) task, a diadochokinesis (DDK) task were completed. A harmonic regression analysis showed a linear learning effect for DDK rate (p&amp;lt;.00001) with a fluctuation of values as a function of the menstrual cycle (p = 0.024). MPT showed a cyclic fluctuation (p = 0.028) but no linear learning effect. Linear and harmonic terms for fundamental frequency (measured from MPT recordings) showed no significant patterns. Understanding hormone driven variability in speech and voice helps to inform remediation strategies that aim to minimize the impact of speech motor and voice disorders across the lifespan.

1065P The impact of pre-treatment plasma sex hormones on the immune checkpoint inhibitors response in patients with metastatic non-small cell lung cancer

Immune checkpoint inhibitors (ICI) have changed the outcomes in metastatic non-small cell lung cancer (mNSCLC). The immune system partially determines the response to ICI. The impact of sex hormones on immune responses is well recognized in autoimmune disease and vaccine response. Little is known about the interplay between the sex hormones and the response to ICI in mNSCLC.

Testosterone Promotes the Intestinal Replication and Dissemination of Coxsackievirus B3 in an Oral Inoculation Mouse Model.

Enteroviruses initiate infection in the gastrointestinal tract, and sex is often a biological variable that impacts pathogenesis. Previous data suggest that sex hormones can influence the intestinal replication of Coxsackievirus B3 (CVB3), an enterovirus in the Picornaviridae family. However, the specific sex hormone(s) that regulates intestinal CVB3 replication is poorly understood. To determine if testosterone promotes intestinal CVB3 replication, we orally inoculated male and female Ifnar-/- mice that were treated with either placebo or testosterone-filled capsules. Following oral inoculation, we found that the testosterone-treated male and female mice shed significantly more CVB3 in their feces than did the placebo-treated mice, indicating that testosterone enhances intestinal replication. Similarly, testosterone enhanced viral dissemination in both sexes, as we observed higher viral loads in peripheral tissues following infection. Further, the testosterone-treated male mice also had a higher mortality rate than did the testosterone-depleted male mice. Finally, we observed that testosterone significantly affected the immune response to CVB3. We found that testosterone broadly increased proinflammatory cytokines and chemokines while decreasing the number of splenic B cells and dendritic cells following CVB3 infection. Moreover, while testosterone did not affect the early CD4 T cell response to CVB3, testosterone reduced the activation of CD8 T cells. These data indicate that testosterone can promote intestinal CVB3 replication and dissemination while also impacting the subsequent viral immune response. IMPORTANCE Biological sex plays a significant role in the outcomes of various infections and diseases. The impact of sex hormones on the intestinal replication and dissemination of Coxsackievirus B3 remains poorly understood. Using an oral inoculation model, we found that testosterone enhances CVB3 shedding and dissemination in male and female mice. Further, testosterone can alter the immune response to CVB3. This work highlights the role of testosterone in CVB3 pathogenesis and suggests that sex hormones can impact the replication and dissemination of enteric viruses.

What is the impact of sex hormones on the pathogenesis of rheumatoid arthritis?

Rheumatoid arthritis (RA) is the most common inflammatory rheumatic disease and has a female predominance of around 3:1. The relationship between sex hormones and RA has been of great interest to researchers ever since Philip Hench's observations in the 1930's regarding spontaneous disease amelioration in pregnancy. Extensive basic scientific work has demonstrated the immunomodulatory actions of sex hormones but this therapeutic potential has not to date resulted in successful clinical trials in RA. Epidemiological data regarding both endogenous and exogenous hormonal factors are inconsistent, but declining estrogen and/or progesterone levels in the menopause and post-partum appear to increase the risk and severity of RA. This review assimilates basic scientific, epidemiological and clinical trial data to provide an overview of the current understanding of the relationship between sex hormones and RA, focusing on estrogen, progesterone and androgens.

The impact of pre-treatment plasma sex hormones on the immune checkpoint inhibitors response to metastatic non-small cell lung cancer.

e21088 Background: Immune checkpoint inhibitors (ICI) have changed the outcomes in metastatic non-small cell lung cancer (mNSCLC). The immune system partially determines the response to ICI. The impact of sex hormones on immune responses is well recognized in autoimmune disease and vaccine response. Little is known about the interplay between the sex hormones and the response to ICI in mNSCLC. Methods: This prospective, observational study included patients with mNSCLC at Moffitt Cancer Center who received ICI as monotherapy or combination with chemotherapy. Plasma was collected before the first ICI infusion. Extraction and detection of the hormones were optimized by modifying the previous method. Hormone levels were measured using ultra-high-performance liquid chromatography high-resolution mass spectrometry (UHPLC-HRMS). Estrogens included propyl pyrazole triol (PPT), 17β-estradiol (E2), and S-equol. Androgens included 5-androstenediol, 3β-androstenediol (3β-diol), and dehydroepiandrosterone (DHEA).Patients were divided based on clinical benefits, defined as a complete or partial response or stable disease for at least 12 months. Categorical variables were compared using the Chi-square test or Fischer exact test; continuous variables were compared using the Mann-Whitney U test. Results: Sixty-one patients were included and 50.8% were female. The median age was 67 years. Twenty-eight patients had clinical benefits from ICI. Patients in the clinical benefit group had higher BMI. The clinical benefit group had significantly lower androgen levels but no difference in estrogen levels. The median DHEA level was 3.7 ng/ml in the clinical benefit group and 9.6 ng/ml in the group without (p &lt; 0.001). The 5-Androstenediol was also lower in the clinical benefits group (table I). When normalized to the age/sex-adjusted reference range, the difference of DHEA and 5-androstenediol was retained (p &lt; 0.001 and 0.014, respectively). 3β-diol was below the limit of detection. Conclusions: The serum DHEA and 5-androstenediol levels were lower in mNSCLC patients who benefited from ICI, regardless of sex. Larger studies are needed to confirm the role of pre-treatment androgens levels as negative biomarkers for ICI response. [Table: see text]

Does Coronavirus Disease 2019 Kill More Elderly Men than Women Due to Different Hormonal Milieu.

Preliminary data depicts a much greater prevalence and high case-fatality rate in advanced age males as compared to age-matched women with severe acute respiratory syndrome-coronavirus-2 infections with high morbidity, mortality, high referral, and admission to intensive care unit with severe sequelae. However, the literature search revealed both for and against studies in this context. Thus, at present, in light of the mixed studies, it cannot be established whether low testosterone levels in aging hypogonadal males create a permissive environment for severe response to coronavirus disease 2019 (COVID-19) infection and can it increase the morbidity or mortality, or on the contrary if the virus inhibits androgen formation. Hence, it is highly warranted to establish the said hypothesis by conducting large statistically powered clinical studies in future. Further, it is highly indicated that impact of sex hormones and gender on the incidence and case fatality of the disease and hormones as a treatment according to sex and gender for COVID requires further scientific research by the research community before it is actually recommended to mitigate the COVID-19 disease course among elderly men and women at large.

Androgen receptor and immune cell PD-L1 expression in bladder tumors predicts disease recurrence and survival.

The impact of sex hormones on cancer immunotherapy remains controversial. Androgens, via the androgen receptor (AR), may impact the success of immune checkpoint blockade. This study characterizes AR and programmed death ligand-1 (PD-L1) expression in bladder tumors with long clinical follow-up. AR and PD-L1 expression was analyzed using immunohistochemistry on 143 transurethral resection (TUR) and 203 radical cystectomy (RC) specimens. Descriptive statistics and survival analyses assessed the relationship of AR and PD-L1 staining with clinical outcomes of tumor recurrence, progression, and overall survival. AR expression was observed in a higher proportion of TUR than RC specimens (59% vs 35%, p < 0.001). High immune cell (IC) PD-L1 expression was associated with higher stage and grade. Patients with the combination of an absence of AR expression and the highest (> 10%) IC PD-L1 expression in TUR tumors had an increased risk of recurrence and progression. In RC specimens, the expression of AR increased the risk of local recurrence (adjusted hazard ratio (HR) 2.09, 95% CI 0.98-4.45), which was even higher among patients who also had IC PD-L1 expression (HR 4.16, 95% CI 1.28-13.52). For 28 paired metastatic lymph nodes among RC patients, tumor cell PD-L1 expression was significantly correlated (r = 0.48, p = 0.01), while no relationship with IC PD-L1 expression was observed. The expression of AR and its relationship to clinical outcomes appears to vary between non-muscle invasive and muscle-invasive bladder cancer. Our results support the role of IC PD-L1 expression as an independent risk factor for bladder cancer outcomes.

Adult vernal keratoconjunctivitis.

Vernal keratoconjunctivitis (VKC) is a rare chronic self-limiting allergic inflammatory disease of the ocular surface mostly affecting young boys in their first decade of life. In the last few years a new clinical entity of VKC has been described: adult VKC. Two variants have been identified according to clinical onset: early (childhood VKC persisting beyond puberty) and late onset (arising de novo in adults) adult VKC. Several epidemiologic studies on VKC have been published from single tertiary centers but while the age distribution of VKC patients does show a small percentage of adults with the disease, detailed analysis on this small subset of adult VKC cases is lacking. In this review we describe pathogenesis, clinical features, diagnostic alternatives, and therapeutic alternatives of this highly invalidating disease. Adult variants of VKC have same clinical manifestations of classic form, but show higher inflammatory response and increased risk of chronic fibrotic sequelae. Adult VKC research could provide insights on the impact of sex hormones in the pathogenesis of allergic diseases and on the mechanisms of inflammation and fibrosis, which cause potentially vision threatening sequelae. The present review will highlight the recent developments in our understanding of this uncommon entity.

Organ of hearing and balance in peri- and postmenopausal women. Effects of hormone replacement therapy on hearing and balance in peri- and post-menopausal women: The current state of knowledge.

Sensory-neural hearing loss in people over 50 - senile deafness - is currently an increasing problem due to the growing proportion of the elderly people in the population. We can find a number of worldwide publications on hearing loss and dizziness in peri-menopausal women, but the data is inconsistent. Reports describing the influence of sex hormones on the ear and its aging are similarly controversial. This review attempts to summarize the current state of knowledge regarding hearing and balance in women during menopause, based on recent studies in this field. It describes the possible causes of hearing and balance impairment in post-menopausal women other than the mere physiological aging of the ear. The review concludes that impairment of hearing and balance is significantly related to osteoporosis, which results from estrogen deficiency during menopause. It also presents the results of studies on the impact of hormone replacement therapy (HRT) and of particular hormonal components of HRT on hearing and balance. The European population is aging, so accurate knowledge about the effects of HRT on hearing and balance is crucial in the context of improving the quality of life of elderly women through appropriate qualification for hormone substitution therapy. Further detailed and extensive study is necessary to verify the impact of sex hormones on hearing in post-menopausal women, taking into account the type of HRT used, serum hormone levels and the presence or absence of osteoporosis.

An Insight into the Sex Differences in COVID-19 Patients: What are the Possible Causes?

Studies have reported a sex bias in case fatalities of COVID-19 patients. Moreover, it is observed that men have a higher risk of developing a severe form of the disease compared to women, highlighting the importance of disaggregated data of male and female COVID-19 patients. On the other hand, other factors (eg, hormonal levels and immune functions) also need to be addressed due to the effects of sex differences on the outcomes of COVID-19 patients. An insight into the underlying causes of sex differences in COVID-19 patients may provide an opportunity for better care of the patients or prevention of the disease. The current study reviews the reports concerning with the sex differences in COVID-19 patients. It is explained how sex can affect angiotensin converting enzyme-2 (ACE2), that is a key component for the pathogenesis of COVID-19, and summarized the gender differences in immune responses and how sex hormones are involved in immune processes. Furthermore, the available data about the impact of sex hormones on the immune functions of COVID-19 cases are looked into.

Brain Sex Differences Related to Gender Identity Development: Genes or Hormones?

The complex process of sexual differentiation is known to be influenced by biological and environmental determinants. The present review has the aim of summarizing the most relevant studies on the biological basis of sexual development, and in particular, it focuses on the impact of sex hormones and genetic background on the development of sexual differentiation and gender identity. The authors conducted a search of published studies on Medline (from January 1948 to December 2019). The evidence suggests that the sexual dimorphic brain could be the anatomical substrate of psychosexual development, on which gonadal hormones may have a shaping role during prenatal and pubertal periods. Additionally, according to several heritability studies, genetic components may have a role, but a promising candidate gene has not been identified. Even though growing evidence underlines the primary role of biological factors on psychosexual development, further studies are necessary to better explain their complex interactions.

Impact of Sex Hormones, Postmenopausal Hormone Therapy and Risk Factors on Development of Abdominal Aortic Aneurysm in Women: A Population-based Prospective Study in Norway: A Hunt Study

Introduction - Women develop abdominal aortic aneurysms (AAA) five to ten years later than men (1,2). The delay in AAA development may be secondary to a protection from estrogens (3,4). The aim of the present study was to evaluate the impact of risk factors associated with AAA development in women, including postmenopausal hormone therapy. This has previously been investigated in small cohorts with limited information. Methods - In a total cohort of 106,000 individuals from the Norwegian Nord-Trøndelag Health Study (HUNT), 20,024 postmenopausal women were identified, of which 201 developed AAAs during a median follow-up of 18 years (1995-2014, i.e. 295,554 person-years). The data is based on questionnaires, physical measurements, medical records and blood samples. A multivariable Cox regression model was constructed, where the final adjusted model included the following variables: smoking (current, past, never), body mass index, coronary heart disease, diabetes, hypertension and postmenopausal hormone therapy. Multiple imputation was performed for missing data (n=50 data sets). Serum estradiol concentrations were compared between women who later did or did not develop AAAs. Median time from blood sample collection to AAA diagnosis was seven years. Results - Mean age at AAA diagnosis was 77 (59 -100) years. 28% of the cohort reported ever use of postmenopausal hormone therapy. In the multivariable analysis, a notable Hazard ratio (HR) of 0.58 was observed for current use of hormone therapy, but the result was not statistically significant (95% CI 0.29-1.16, p=0.12). Women who reported current smoking had a more than ten-fold risk for developing AAA during follow-up (HR 10.9 (7.4-16.1)). Positive associations were also found for hypertension (HR 2.0 (1.4-3.0)) and coronary heart disease (HR 2.2 (1.6-3.2)). There was no substantial difference in estradiol concentrations between women with and without AAA (p=0.06). Conclusion - Postmenopausal hormone therapy is of less clinical importance compared to the strong associations observed between smoking, hypertension coronary heart disease and AAA development in women. These findings were supported by measured estradiol concentrations.

The impact of sex hormones on genital wound healing in mice: a comparative study

The effects estrogen and testosterone have on penile wound healing are still uncertain. This study evaluated the effects of these hormones on the wound healing process of penile and non-penile skin in wild-type (Mus musculusspecies) 4-5-week-old mice. Seventy wild-type Mus musculusspecies were randomly assigned to four groupscontrol (n=17), 1-week post-operative topical estrogen (n=18), 1-week pre-operative testosterone (n=17), and immediate post-operative testosterone (n=18). Incisions were made on the ventrum of the penis and dorsal neck skin. On post-operative day 3, 7, and 14, incision sites were harvested. Evaluation was performed grossly for postsurgical penile edema and histologically for inflammatory cell concentration, presence of fibrinopurulent materials and distribution of collagen-fibroblastic cells. Each treatment group was compared at the three post-operative time points using the Fisher-Freeman--Halton exact test. CD34 and androgen receptor immunohistostaining was performed for between-group differences to assess microvascular density or vasodilatation and androgen receptor upregulation. In this study, the experiment noted significant penile edema on post-operative day 7 in the testosterone groups, whereas less edema in the estrogen group (P=0.010; Figure). On histologic evaluation of the penile wounds, a significantly increased inflammatory cell concentration was noted for both pre-operative and post-operative testosterone groups on post-operative day 14 (P=0.023). The estrogen group revealed significantly increased fibrinopurulent material on the 3rd and 7th post-operative days (P=0.045 and P=0.005, respectively). No significant between-group differences in the collagen-fibroblastic distribution were noted over the three-time phases. On histologic evaluation of the skin wounds, no significant differences were noted between the groups for inflammatory cell concentration and presence of fibrinopurulent materials. However, compared with the testosterone treatment groups, a significant higher collagen-fibroblast distribution was noted in the estrogen groups on post-operative day 3 and 14 (P=0.001 and P=0.044,respectively). Sex hormones, when given peri-operatively, may affect the wound healing process in mice. Testosterone appears to stimulate a prolonged inflammatory effect on penile wounds. Conversely, estrogen induces a fibrinopurulent congregation early in the penile wound healing process. For general skin healing, estrogen induces earlier collagen and fibroblast distribution, whereas testosterone has a delayed effect. The findings of this study should be further investigated in larger animal model with longer follow-up period.