Combination of bone marrow mesenchymal stem cells and moxibustion restores cyclophosphamide-induced premature ovarian insufficiency by improving mitochondrial function and regulating mitophagy.

BACKGROUND: Premature ovarian insufficiency (POI) is a major cause of infertility. In this study, we aimed to investigate the effects of the combination of bone marrow mesenchymal stem cells (BMSCs) and moxibustion (BMSCs-MOX) on POI and evaluate the underlying mechanisms. METHODS: A POI rat model was established by injecting different doses of cyclophosphamide (Cy). The modeling of POI and the effects of the treatments were assessed by evaluating estrous cycle, serum hormone levels, ovarian weight, ovarian index, and ovarian histopathological analysis. The effects of moxibustion on BMSCs migration were evaluated by tracking DiR-labeled BMSCs and analyzing the expression of chemokines stromal cell-derived factor 1 (Sdf1) and chemokine receptor type 4 (Cxcr4). Mitochondrial function and mitophagy were assessed by measuring the levels of reactive oxygen species (ROS), mitochondrial membrane potential (MMP), ATP, and the mitophagy markers (Drp1, Pink1, and Parkin). Furthermore, the mitophagy inhibitor Mdivi-1 and the mitophagy activator CCCP were used to confirm the role of mitophagy in Cy-induced ovarian injury and the underlying mechanism of combination therapy. RESULTS: A suitable rat model of POI was established using Cy injection. Compared to moxibustion or BMSCs transplantation alone, BMSCs-MOX showed improved outcomes, such as reduced estrous cycle disorders, improved ovarian weight and index, normalized serum hormone levels, increased ovarian reserve, and reduced follicle atresia. Moxibustion enhanced Sdf1 and Cxcr4 expression, promoting BMSCs migration. BMSCs-MOX reduced ROS levels; upregulated MMP and ATP levels in ovarian granulosa cells (GCs); and downregulated Drp1, Pink1, and Parkin expression in ovarian tissues. Mdivi-1 significantly mitigated mitochondrial dysfunction in ovarian GCs and improved ovarian function. CCCP inhibited the ability of BMSCs-MOX treatment to regulate mitophagy and ameliorate Cy-induced ovarian injury. CONCLUSIONS: Moxibustion enhanced the migration and homing of BMSCs following transplantation and improves their ability to repair ovarian damage. The combination of BMSCs and moxibustion effectively reduced the excessive activation of mitophagy, which helped prevent mitochondrial damage, ultimately improving ovarian function. These findings provide a novel approach for the treatment of pathological ovarian aging and offer new insights into enhancing the efficacy of stem cell therapy for POI patients.

The therapeutic effect of Loranthus parasiticus lignan derivatives on collagen-induced arthritis in rats through the SHBG/NFκB pathway.

Lignan-rich beans, nuts, and various seeds are the main foods with antioxidative and hormone-modulating activities. Although the role of lignans in mediating hormone-dependent cancers and cardiovascular diseases is well characterized, the function of lignans in anti-arthritic activity and its underlying mechanisms remain unknown. Three new lignan derivatives, (-)-nortrachelogenin, trachelogenin, and matairesinol, were extracted from Loranthus parasiticus. After establishing the collagen-induced arthritis (CIA) model by intradermal injection of collagen, rats were treated with three new lignan derivatives ((-)-nortrachelogenin: 37%; trachelogenin: 27%; matairesinol: 25.7%) at a concentration of 50 mg/kg and 100 mg/kg, or methotrexate at 0.3 mg/kg. Mixed lignan derivatives significantly attenuated the immune responses in the joints of CIA rats, leading to lower levels of proinflammatory cytokines (IL-6 and TNF-α) and higher levels of free androgen in the serum compared to the CIA model. The results of molecular docking using AutoDock Vina showed that the lignan derivative (-)-nortrachelogenin was the most effective compound for binding to sex hormone-binding globulin (SHBG), thus inhibiting the activity of NFκB in LPS-stimulated macrophages. In this study, (-)-nortrachelogenin was identified as a novel natural lignan derivative with previously unrecognized anti-inflammatory activity. Its molecular mechanism appears related to the regulation of the NFκB/SHBG pathway. Our findings suggest that further application of sex hormone-like compounds in the treatment of rheumatoid arthritis and the potential clinical applications of (-)-nortrachelogenin are promising.

Skin manifestations in adults with gender dysphoria on hormone treatment in the outpatient clinic of Hospital de San José, Bogotá-Colombia.

BACKGROUND: Comprehensive healthcare for patients with gender dysphoria includes access to gender-affirming hormone therapy. It may cause cutaneous and adnexal side effects, which often affect quality of life, are underdiagnosed, and do not receive timely treatment. The literature on this subject is scarce. The main objective was to identify skin manifestations secondary to hormone treatment in adults with gender dysphoria. METHODS: Observational, descriptive, cross-sectional study. A search was performed in the database of patients with gender dysphoria older than 18 years treated at the dermatology and/or endocrinology outpatient clinic of the Hospital de San José de Bogotá in the period 2015-2021. Medical records of patients on hormone therapy with skin manifestations were selected, while patients using other medications as possible triggers were excluded. RESULTS: In total, 85 patients were included, with a predominance of young transgender men (average age was 27 ± 9 years) in whom the main manifestation was acne (87%), followed by androgenetic alopecia and acanthosis nigricans. Transgender women presented more acne, androgenetic alopecia, hypertrichosis, seborrheic dermatitis, and melasma. The majority received treatment, mainly topical therapies. More than half of the patients were treated by the endocrinology and dermatology services. CONCLUSIONS: Skin manifestations in patients with gender dysphoria on hormone therapy are frequent, so they should be known and taken into account in the multidisciplinary approach to these patients, which should involve dermatologists. This is the first Colombian and Latin American study focused on documenting skin manifestations in patients with gender dysphoria undergoing hormone therapy.

Probiotic-fermented Qushi decoction alleviates reserpine-induced spleen deficiency syndrome by regulating spleen function and gut microbiota dysbiosis.

BACKGROUND: Spleen deficiency syndrome (SDS) is associated with elevated inflammatory factors and dysregulation of gastrointestinal motility hormones and intestinal microbiota. Qushi decoction (QD), a traditional formula, has not been reported using modern scientific research methods for changes in its probiotic fermented QD (FQD) composition and its potential mechanisms to alleviate SDS. Therefore, the aim of this study was to investigate the splenic protection of FQD in SDS rats by modulating gastrointestinal motility hormones and intestinal microbiota. RESULTS: The results showed that FQD increased total polysaccharides, total protein, total flavonoids and the other active ingredients compared to QD, effectively improved splenic inflammation and apoptosis in SDS rats, and modulated gastrointestinal motility hormones to alleviate diarrhea and other symptoms. In addition, the dysregulation of the gut microbiota was reversed by increasing the levels of Bifidobacterium and decreasing the levels of Escherichia-Shigella and Proteobacteria, which may be related to the regulation of bacterial metabolites to alleviate SDS. CONCLUSION: These results suggest that FQD is an effective formula for improving SDS. Our findings show that FQD beneficial to the implications for the treatment of SDS. © 2023 Society of Chemical Industry.

Role of tissue factor pathway inhibitor in hormone-induced venous thromboembolism.

ABSTRACT: Exposure to higher levels of steroid hormones, like that in pregnancy or during combined hormonal contraception, increases the risk of venous thromboembolism. Development of resistance to activated protein C (APC) thought to be the underlying pathomechanism of this prothrombotic state. This coagulation phenomena is largely to be explained by the hormone-induced impairment of the protein S/ tissue factor pathway inhibitor (TFPI) leading to a less efficient inactivation of factor Va and factor VIIIa by APC. APC resistance and decreased protein S/TFPI function were associated with the risk of first as well as recurrent venous thromboembolism. Preexisting disturbances in these pathways are likely to predispose to thrombosis during hormone exposure and can persist over years after the thrombosis event.Further studies are necessary to investigate the predictive value of forgoing APC resistance and decreased protein S/TFPI function or an excessive alteration in these parameters during hormone intake on the development of hormone-induced venous thromboembolism.

Hormone Therapy for the Primary Prevention of Chronic Conditions in Postmenopausal Persons: US Preventive Services Task Force Recommendation Statement.

Importance: Menopause is defined as the cessation of a person's menstrual cycle. It is defined retrospectively, 12 months after the final menstrual period. Perimenopause, or the menopausal transition, is the few-year time period preceding a person's final menstrual period and is characterized by increasing menstrual cycle length variability and periods of amenorrhea, and often symptoms such as vasomotor dysfunction. The prevalence and incidence of most chronic diseases (eg, cardiovascular disease, cancer, osteoporosis, and fracture) increase with age, and US persons who reach menopause are expected on average to live more than another 30 years. Objective: To update its 2017 recommendation, the US Preventive Services Task Force (USPSTF) commissioned a systematic review to evaluate the benefits and harms of systemic (ie, oral or transdermal) hormone therapy for the prevention of chronic conditions in postmenopausal persons and whether outcomes vary by age or by timing of intervention after menopause. Population: Asymptomatic postmenopausal persons who are considering hormone therapy for the primary prevention of chronic medical conditions. Evidence Assessment: The USPSTF concludes with moderate certainty that the use of combined estrogen and progestin for the primary prevention of chronic conditions in postmenopausal persons with an intact uterus has no net benefit. The USPSTF concludes with moderate certainty that the use of estrogen alone for the primary prevention of chronic conditions in postmenopausal persons who have had a hysterectomy has no net benefit. Recommendation: The USPSTF recommends against the use of combined estrogen and progestin for the primary prevention of chronic conditions in postmenopausal persons. (D recommendation) The USPSTF recommends against the use of estrogen alone for the primary prevention of chronic conditions in postmenopausal persons who have had a hysterectomy. (D recommendation).

Hormone Therapy for the Primary Prevention of Chronic Conditions in Postmenopausal Persons: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: It is uncertain whether hormone therapy should be used for the primary prevention of chronic conditions such as heart disease, osteoporosis, or some types of cancers. Objective: To update evidence for the US Preventive Services Task Force on the benefits and harms of hormone therapy in reducing risks for chronic conditions. Data Sources: PubMed/MEDLINE, Cochrane Library, EMBASE, and trial registries from January 1, 2016, through October 12, 2021; surveillance through July 2022. Study Selection: English-language randomized clinical trials and prospective cohort studies of fair or good quality. Data Extraction and Synthesis: Dual review of abstracts, full-text articles, and study quality; meta-analyses when at least 3 similar studies were available. Main Outcomes and Measures: Morbidity and mortality related to chronic conditions; health-related quality of life. Results: Twenty trials (N = 39 145) and 3 cohort studies (N = 1 155 410) were included. Participants using estrogen only compared with placebo had significantly lower risks for diabetes over 7.1 years (1050 vs 903 cases; 134 fewer [95% CI, 18-237]) and fractures over 7.2 years (1024 vs 1413 cases; 388 fewer [95% CI, 277-489]) per 10 000 persons. Risks per 10 000 persons were statistically significantly increased for gallbladder disease over 7.1 years (1113 vs 737 cases; 377 more [95% CI, 234-540]), stroke over 7.2 years (318 vs 239 cases; 79 more [95% CI, 15-159]), venous thromboembolism over 7.2 years (258 vs 181 cases; 77 more [95% CI, 19-153]), and urinary incontinence over 1 year (2331 vs 1446 cases; 885 more [95% CI, 659-1135]). Participants using estrogen plus progestin compared with placebo experienced significantly lower risks, per 10 000 persons, for colorectal cancer over 5.6 years (59 vs 93 cases; 34 fewer [95% CI, 9-51]), diabetes over 5.6 years (403 vs 482 cases; 78 fewer [95% CI, 15-133]), and fractures over 5 years (864 vs 1094 cases; 230 fewer [95% CI, 66-372]). Risks, per 10 000 persons, were significantly increased for invasive breast cancer (242 vs 191 cases; 51 more [95% CI, 6-106]), gallbladder disease (723 vs 463 cases; 260 more [95% CI, 169-364]), stroke (187 vs 135 cases; 52 more [95% CI, 12-104]), and venous thromboembolism (246 vs 126 cases; 120 more [95% CI, 68-185]) over 5.6 years; probable dementia (179 vs 91 cases; 88 more [95% CI, 15-212]) over 4.0 years; and urinary incontinence (1707 vs 1145 cases; 562 more [95% CI, 412-726]) over 1 year. Conclusions and Relevance: Use of hormone therapy in postmenopausal persons for the primary prevention of chronic conditions was associated with some benefits but also with an increased risk of harms.

Research Progress on Exosomes in Osteonecrosis of the Femoral Head.

Osteonecrosis of the femoral head (ONFH) is a progressive disease that often necessitates hip replacement if hip preservation therapy fails. ONFH places a heavy economic burden and severe psychological pressure on patients. At present, ONFH is treated by either surgical or non-surgical methods. In clinical practice, stem cells combined with surgery has achieved some positive results, but many problems remain to be resolved. Exosomes are small vesicles of 30-150 nm, which are rich in various nucleic acids, proteins, and small molecules depending on the cells from which they are derived. A growing number of studies have found that exosomes play an important role in tissue damage repair. In comparison with stem cells, exosomes have lower immunogenicity. Also, exosomes can promote cell proliferation and inhibit tumor growth. In addition, exosomes can also be used as natural carriers of drugs. Many studies have shown that exosomes have therapeutic effects in hormone-induced ONFH. Exosomes have the effect of promoting vascular regeneration and show good application prospects in ONFH. Here, we present a review of studies on the application of exosomes in ONFH to provide a reference for future research.

Chrysin reduces inflammation and oxidative stress and improves ovarian function in D-gal-induced premature ovarian failure.

Premature ovarian failure (POF), a frequently occurring pathology. Chrysin has antioxidant, anti-inflammatory, anti-apoptotic and other pharmacological activities. This study was designed to detect the effect of Chrysin on POF. The establishment of POF was depended on the subcutaneous injection of D-gal (200 mg/kg/d). With the adoption of ELISA, the levels of hormones and release of inflammatory cytokines were assayed. The expression of MDA, GSH-px, SOD and ROS was evaluated with corresponding kits. In addition, the pathological changes of ovary and apoptosis of ovarian granulosa cells in D-gal-induced mice were detected using H&E staining and TUNEL, respectively. Moreover, the levels of FSH receptor and apoptosis-related proteins were measured with western blot. Finally, ERß expression was measured with RT-qPCR and western blot. In this study, we found that chrysin regulated the expression of hormones and weight of D-gal-induced mice. It was also found that chrysin inhibited the inflammation and oxidative stress in mice with D-gal induction. In addition, the number and advancement of follicle in D-gal-induced mice treated with chrysin revealed that chrysin could improve the ovarian function of mice with POF. Furthermore, chrysin exhibited inhibitory effects on the apoptosis of ovarian granulosa cells in D-gal-induced mice. More importantly, chrysin molecule targeted ERß and activated ERß expression in POF. Overall, Chrysin reduces inflammation and oxidative stress and improves ovarian function in D-gal-induced premature ovarian failure, suggesting that chrysin is valuable for the treatment of POF.

Carpal tunnel syndrome and tenosynovitis in women with breast cancer associated with hormone therapy: A multi-institutional analysis using a clinical data warehouse.

ABSTRACT: The study aims to evaluate the characteristics, treatments, and incidence rates of carpal tunnel syndrome (CTS) and tenosynovitis in women with breast cancer, according to the hormone therapy used. We retrospectively reviewed women with breast cancer identified from the clinical data warehouse of the six hospitals in Korea, from January 2015 to August 2020. Among them, patients with CTS or tenosynovitis were reviewed in terms of disease status and treatments. A total of 101 patients among a population of 15,504 met the study inclusion criteria, so their clinical data were analyzed. Aromatase inhibitor (AI) users frequently needed oral medication for CTS, and developed severe CTS which frequently required surgery. AI users presented with a higher incidence of CTS (1.3%) than patients without hormone therapy (0.4%), and tenosynovitis occurred at a higher rate in AI users (2.3%) compared to the tamoxifen (1.1%) and no hormone groups (0.5%). More than half of the CTS and tenosynovitis occurred within 12 months after hormone commencement. The incidence and disease characteristics of CTS and tenosynovitis differed among the groups depending on the type of hormone therapy received. Our findings will help clinicians understand clinical courses and treatments for CTS and tenosynovitis in breast cancer patients.

Occurrence of Dysgeusia in Patients Being Treated for Cancer.

The aims of this study were to assess the presence of dysgeusia in patients receiving anticancer therapy and to explore possible factors influencing its occurrence. A total of 242 adult patients with histological diagnoses of malignant neoplasia and undergoing all types of anticancer treatment were included in the analysis. Data were collected from May 2019 to November 2019 at the Unit of Medical Oncology of Careggi University Hospital, Florence, Italy. Dysgeusia was assessed using the Chemotherapy-induced Taste Alteration Scale (CiTAS), while treatment-related symptoms were assessed using the Common Terminology Criteria for Adverse Events (CTCAE). Patients were aged 68 ± 13 years, mostly males (65%). A large proportion of them was undergoing chemotherapy (42.2%), while the others were receiving immunotherapy (20.7%), hormone therapy (15.5%), targeted therapy (12.8%), or a combination of them. Overall, 21.5% of patients reported dysgeusia, 17.4% nausea, 10.7% dysosmia, 9.9% xerostomia, 4.5% mucositis, and only 3.7% vomiting. The targeted therapy showed the greatest adverse effects, followed by chemotherapy, immunotherapy, and hormone therapy. When patients with dysgeusia were analyzed, phantogeusia and parageusia was the most affected dimension of gustatory disorders. Significant differences (p < 0.05) in CiTAS scores were found according to treatment-related symptoms for nausea and mucositis.

Histologic Findings in Surgical Pathology Specimens From Individuals Taking Feminizing Hormone Therapy for the Purpose of Gender Transition.

CONTEXT.­: Transgender women experience health disparities in all areas of medicine. Within surgical pathology, knowledge gaps relating to the concepts of transgender care exist. Medical transition for transgender women and transfeminine persons may involve hormone therapy and/or surgery to feminize the body. Understanding the common histologic changes in specimens from feminizing surgeries, as well as other specimens from patients on feminizing hormone therapy, will aid surgical pathologists in providing better care to this unique patient population. OBJECTIVE.­: To summarize histologic findings in surgical pathology specimens from transgender women taking feminizing hormones. DATA SOURCES.­: A systematic review of the OVID Medline and PubMed databases was performed to identify all studies describing histologic findings in surgical pathology specimens from transgender women from 1946 to 2019. CONCLUSIONS.­: Much of the literature to date describing histologic findings in transgender women comes from the examination of genitourinary specimens removed during feminizing surgeries. Common benign changes associated with feminizing hormone therapy include the development of acini and lobules in the breast, testicular tubular changes, and squamous metaplasia of the prostate and urethra. Neoplastic cases include breast adenocarcinoma and fibroepithelial lesions, testicular germ cell tumors, prostatic adenocarcinoma, anal squamous cell carcinoma, pituitary adenomas, and meningiomas. Additional studies assessing the findings in other organ systems as well as population-based studies assessing rates of neoplasia are needed. However, future research relies on engagement within the surgical pathology community as well as collaboration with clinicians and patients to achieve optimal results.

Risk of Venous Thromboembolism in Transgender People Undergoing Hormone Feminizing Therapy: A Prevalence Meta-Analysis and Meta-Regression Study.

Background: Although venous thromboembolism (VTE) is a recognized side effect of some formulations of estrogen therapy, its impact in transgender people remains uncertain. The aim of this study was to define pooled prevalence estimate and correlates of VTE in Assigned Males at Birth (AMAB) trans people undergoing gender affirming hormone therapy. Methods: A thorough search of MEDLINE, COCHRANE LIBRARY, SCOPUS and WEB OF SCIENCE databases was carried out to identify suitable studies. Quality of the articles was scored using the Assessment Tool for Prevalence Studies. Data were combined using random effects models and the between-study heterogeneity was assessed by the Cochrane's Q and I2. Results: The eighteen studies included gave information about 11,542 AMAB undergoing gender affirming hormone therapy. The pooled prevalence of VTE was 2% (95%CI:1-3%), with a large heterogeneity (I2 = 89.18%, P<0.0001). Trim-and-fill adjustment for publication bias produced a negligible effect on the pooled estimate. At the meta-regression analysis, a higher prevalence of VTE was significantly associated with an older age (S=0.0063; 95%CI:0.0022,0.0104, P=0.0027) and a longer length of estrogen therapy (S=0.0011; 95%CI:0.0006,0.0016, P<0.0001). When, according to the meta-regression results, the analysis was restricted to series with a mean age ≥37.5 years, the prevalence estimate for VTE increased up to 3% (95%CI:0-5%), but with persistence of a large heterogeneity (I2 = 88,2%, P<0.0001); studies on younger participants (<37.5 years) collectively produced a pooled VTE prevalence estimate of 0% (95%CI:0-2%) with no heterogeneity (I2 = 0%, P=0.97). Prevalence estimate for VTE in series with a mean length of estrogen therapy ≥53 months was 1% (95%CI:0-3%), with persistent significant heterogeneity (I2 = 84,8%, P=0.0006); studies on participants subjected to a shorter length of estrogen therapy (<53 months), collectively produced a pooled VTE prevalence estimate of 0% (95%CI:0-3%) with no heterogeneity (I2 = 0%, P=0.76). Conclusions: The overall rate of VTE in AMAB trans people undergoing gender affirming hormone therapy was 2%. In AMAB population with <37.5 years undergoing estrogen therapy for less than 53 months, the risk of VTE appears to be negligible. Further studies are warranted to assess whether different types and administration routes of estrogen therapy could decrease the VTE risk in AMAB trans people over 37.5 years subjected to long-term therapy. Systematic Review Registration: [https://www.crd.york.ac.uk/PROSPERO/], identifier [CRD42021229916].

Hormonally Induced Hepatocellular Carcinoma in Diabetic Wild Type and Carbohydrate Responsive Element Binding Protein Knockout Mice.

OBJECTIVE: In the rat, the pancreatic islet transplantation model is an established method to induce hepatocellular carcinomas (HCC), due to insulin-mediated metabolic and molecular alterations like increased glycolysis and de novo lipogenesis and the oncogenic AKT/mTOR pathway including upregulation of the transcription factor Carbohydrate-response element-binding protein (ChREBP). ChREBP could therefore represent an essential oncogenic co-factor during hormonally induced hepatocarcinogenesis. METHODS: Pancreatic islet transplantation was implemented in diabetic C57Bl/6J (wild type, WT) and ChREBP-knockout (KO) mice for 6 and 12 months. Liver tissue was examined using histology, immunohistochemistry, electron microscopy and Western blot analysis. Finally, we performed NGS-based transcriptome analysis between WT and KO liver tumor tissues. RESULTS: Three hepatocellular carcinomas were detectable after 6 and 12 months in diabetic transplanted WT mice, but only one in a KO mouse after 12 months. Pre-neoplastic clear cell foci (CCF) were also present in liver acini downstream of the islets in WT and KO mice. In KO tumors, glycolysis, de novo lipogenesis and AKT/mTOR signalling were strongly downregulated compared to WT lesions. Extrafocal liver tissue of diabetic, transplanted KO mice revealed less glycogen storage and proliferative activity than WT mice. From transcriptome analysis, we identified a set of transcripts pertaining to metabolic, oncogenic and immunogenic pathways that are differentially expressed between tumors of WT and KO mice. Of 315 metabolism-associated genes, we observed 199 genes that displayed upregulation in the tumor of WT mice, whereas 116 transcripts showed their downregulated expression in KO mice tumor. CONCLUSIONS: The pancreatic islet transplantation model is a suitable method to study hormonally induced hepatocarcinogenesis also in mice, allowing combination with gene knockout models. Our data indicate that deletion of ChREBP delays insulin-induced hepatocarcinogenesis, suggesting a combined oncogenic and lipogenic function of ChREBP along AKT/mTOR-mediated proliferation of hepatocytes and induction of hepatocellular carcinoma.

Impact of Hormonal Therapies for Treatment of Hormone-Dependent Cancers (Breast and Prostate) on the Cardiovascular System: Effects and Modifications: A Scientific Statement From the American Heart Association.

Cardiovascular disease and cancer are the leading causes of death in the United States, and hormone-dependent cancers (breast and prostate cancer) are the most common noncutaneous malignancies in women and men, respectively. The hormonal (endocrine-related) therapies that serve as a backbone for treatment of both cancers improve survival but also increase cardiovascular morbidity and mortality among survivors. This consensus statement describes the risks associated with specific hormonal therapies used to treat breast and prostate cancer and provides an evidence-based approach to prevent and detect adverse cardiovascular outcomes. Areas of uncertainty are highlighted, including the cardiovascular effects of different durations of hormonal therapy, the cardiovascular risks associated with combinations of newer generations of more intensive hormonal treatments, and the specific cardiovascular risks that affect individuals of various races/ethnicities. Finally, there is an emphasis on the use of a multidisciplinary approach to the implementation of lifestyle and pharmacological strategies for management and risk reduction both during and after active treatment.

Perioperative Transgender Hormone Management: Avoiding Venous Thromboembolism and Other Complications.

SUMMARY: This review discusses the current evidence regarding perioperative hormone therapy for transgender individuals, with an emphasis on strategies to reduce the risk of perioperative venous thromboembolism. Historically, surgeons routinely discontinued estrogen therapy in the perioperative period with the goal of reducing the risk of venous thromboembolism. However, abrupt estrogen cessation may also lead to adverse emotional and physiologic effects, including an exacerbation of one's gender dysphoria. The data on the relationship of feminizing hormones and venous thromboembolism in the perioperative setting are largely based on extrapolation of hormone regimens that are no longer in use and may not accurately reflect the actual risk of venous thromboembolism. Future studies will allow surgeons to engage in evidence-based, patient-centered, informed consent while also minimizing the risk of complications, such as venous thromboembolism.

Increased obstetric and neonatal risks in artificial cycles for frozen embryo transfers?

RESEARCH QUESTION: What are the obstetric and neonatal risks for women conceiving via frozen-thawed embryo transfer (FET) during a modified natural cycle compared with an artificial cycle method. DESIGN: A follow-up study to the ANTARCTICA randomized controlled trial (RCT) (NTR 1586) conducted in the Netherlands, which showed that modified natural cycle FET (NC-FET) was non-inferior to artificial cycle FET (AC-FET) in terms of live birth rates. The current study collected data on obstetric and neonatal outcomes of 98 women who had a singleton live birth. The main outcome was birthweight; additional outcomes included hypertensive disorder of pregnancy, premature birth, gestational diabetes, obstetric haemorrhage and neonatal outcomes including Apgar scores and admission to the neonatal ward or the neonatal intensive care unit and congenital anomalies. RESULTS: Data from 82 out of 98 women were analysed according to the per protocol principle. There was no significant difference in the birthweights of children born between groups (mean difference -124 g [-363 g to 114 g]; P = 0.30). Women who conceived by modified NC-FET have a decreased risk of hypertensive disorders of pregnancy compared with AC-FET (relative risk 0.27; 95% CI 0.08-0.94; P = 0.031). Other outcomes, such as rates of premature birth, gestational diabetes or obstetric haemorrhage and neonatal outcomes, were not significantly different. CONCLUSIONS: The interpretation is that modified NC-FET is the preferred treatment in women with ovulatory cycles undergoing FET when the increased risk of obstetrical complications and potential neonatal complications in AC-FET are considered.

No significant long-term complications from inadvertent exposure to gonadotropin-releasing hormone agonist during early pregnancy in mothers and offspring: a retrospective analysis.

BACKGROUND: Administration of gonadotropin-releasing hormone agonist (GnRH-a) in the luteal phase is commonly used for pituitary suppression during in vitro fertilisation (IVF). There is an ineluctable risk of inadvertent exposure of spontaneous pregnancy to GnRH-a. However, little is known about the pregnancy complications and repregnancy outcomes of the affected women and the neurodevelopmental outcomes of the GnRH-a-exposed children. METHODS: Retrospective analysis was used to determine obstetric and repregnancy outcomes after natural conception in 114 women who naturally conceived while receiving GnRH-a during their early pregnancy over the past 17 years. The GnRH-a-exposed children were evaluated to determine their neonatal characteristics and long-term neurodevelopmental outcomes. The outcomes were compared to those of relevant age-matched control groups. RESULTS: Sixty-five women had 66 live births. The neonatal health outcomes and the incidence of maternal complications were similar in the GnRH-a-exposed and control groups. Thirty-one GnRH-a-exposed children, aged 2-8 years, were available for investigation of neurodevelopment. Except for one case of autism spectrum disorder, the full-scale intelligence quotient score was within the normal range and similar to that of the control group. Most mothers with successful pregnancies and about one-third of the women who had spontaneous abortions were subsequently able to conceive naturally again. IVF is recommended for repregnancy in women who have experienced ectopic pregnancies. CONCLUSIONS: Accidental exposure to GnRH-a in early pregnancy might be safe. Reproductive treatment suggestions for repregnancy should be made with consideration of the outcomes of the previously GnRH-a-exposed spontaneous pregnancy.