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Objective: Cyproterone acetate (CPA) and spironolactone (SPL) are different antiandrogens in gender-affirming hormone therapy (GAHT) for transgender women. Few studies have evaluated their efficacy and user satisfaction, especially among East Asians. This study aimed to evaluate these aspects in Chinese transgender women. Methods: Data were collected retrospectively from transgender women visiting the Peking University Third Hospital from 2012 to 2021. From 639 people identified as transgender women, 151 of them (80 using CPA and 71 using SPL, 16 to 40-year-old) under stable GAHT ≥6 months were enrolled. Total testosterone levels and visual analogue scale (VAS)-based satisfaction scores were evaluated. Results: No difference was observed in age between the CPA and SPL groups (median [IQR], 22 [20-24] years and 23 [20-26] years, respectively). The duration of GAHT was longer in CPA group than in SPL group (18 [10-32] months vs. 12 [8-21] months, p = 0.009). Total testosterone levels were significantly lower with CPA treatment (25 mg/d) than with SPL treatment (100 mg/d) (median [IQR]: 0.7 [0.7-2.1] nmol/L vs. 13.0 [6.0-17.8] nmol/L, p < 0.001). The proportion of total testosterone levels reaching the recommended range was significantly higher in CPA group than in SPL group (75.0% vs. 11.3%, p < 0.001). VAS-based satisfaction scores for erection decreased and figure feminization were higher in CPA group than in SPL group, which remained unchanged after adjusting for age, treatment duration, estradiol dose, and comorbid mental disorders (p < 0.05). The prolactin levels were higher in CPA group than in SPL group (18.9 [11.8-28.1] ng/ml vs. 11.8 [7.9-18.4] ng/ml, p < 0.001). No severe safety events were reported in both groups. Conclusion: In Chinese transgender women, CPA was more effective than SPL in lowering testosterone levels. Additionally, VAS scores indicated greater satisfaction with erection decreased and figure feminization using CPA compared to SPL.

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The most common type of alopecia in women is female androgenetic alopecia (FAGA), characterized by progressive hair loss in a patterned distribution. Many oral therapies, including spironolactone (an aldosterone antagonist), androgen receptor blockers (e.g., flutamide/bicalutamide), 5-alpha-reductase inhibitors (e.g., finasteride/dutasteride), and oral contraceptives, target the mechanism of androgen conversion and binding to its respective receptor and therefore could be administered for the treatment of FAGA. Despite significant advances in the oral treatment of FAGA, its management in patients with a history of gynecological malignancies, the most common cancers in women worldwide, may still be a concern. In this review, we focus on the safety of antiandrogens for the treatment of FAGA patients. For this purpose, a targeted literature review was conducted on PubMed, utilizing the relevant search terms. To sum up, spironolactone seems to be safe for the systemic treatment of FAGA, even in high-risk populations. However, a general uncertainty remains regarding the safety of other medications in patients with a history of gynecologic malignancies, and further studies are needed to evaluate their long-term safety in patients with FAGA and risk factors to establish an optimal risk assessment and treatment selection protocol.

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OBJECTIVE: This study aimed to investigate the curative effect of motherwort combined with ethinylestradiol-cyproterone acetate (EE/CPA) on dysfunctional uterine bleeding (DUB). METHODS: Atotal of 68 patients with DUB were divided into a single medication group (treated with EE/CPA) and a combination medication group(treated with motherwort and EE/CPA). The clinical efficacy, uterine hemodynamic parameters, sex hormone levels, coagulation index levels, blood routine test levels, and adverse reactions of patients were evaluated. RESULTS: After three months of treatment, total treatment response rate of the combination medication group was significantly higher than that of the single medication group. Decreased uterine volume, endometrial thickness and resistance index (RI), increased pulsatility index(PI), average flow rate, and uterine artery blood flow, as well asreduced follicle-stimulating hormone (FSH), luteinizing hormone (LH),estradiol (E2), progesterone (P), activated partial thromboplastin time (aPTT), prothrombin time (PT), fibrinogen (FIB), thrombin time(TT), platelet count (PLT), red blood cell (RBC), and hemoglobin (Hb)levels were witnessed in patients of the two groups. In thecombination medication group, there exhibited reduced uterine volume, endometrial thickness and RI, elevated PI, average flow rate, and uterine artery blood flow, reduced P, E2, FSH, LH, aPTT, PT, FIB, TT,PLT, RBC, and Hb levels in comparison to the single medication group. CONCLUSION: The combination of motherwort and EE/CPA is clinically effective in the treatment of DUB.

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OBJECTIVE: Polycystic ovary syndrome (PCOS) is widely reported among young females, and anti-androgens are used for treating hirsutism and acne in these patients. The protective effects of myo-inositol, oral contraceptives, and insulin sensitizers have been reported on the periodontium and high-sensitivity C-reactive protein (hsCRP) levels in PCOS females. However, cyproterone acetate/ethinyl estradiol (CPA/EE) has not yet been studied. This cross-sectional study explores the periodontal status and systemic inflammation in PCOS women on CPA/EE drug combination compared to females not on medication. METHOD AND MATERIALS: A total of 150 participants were enrolled into three groups: 50 newly diagnosed PCOS females not on medication (N-PCOS); 50 PCOS females consuming CPA/EE combination for the last 6 months (PCOS+CPA/EE); and 50 systemically healthy females (control group). Anthropometric, biochemical, periodontal parameters, and health-related quality of life questionnaires were recorded. RESULTS: N-PCOS and PCOS+CPA/EE groups showed a nonsignificant difference in hsCRP levels, Gingival Index, bleeding on probing, waist circumference, and waist-hip ratio (P > .05). Gingival thickness and keratinized tissue width were significantly greater in the PCOS+CPA/EE than the N-PCOS group (P ≤ .05); however, these were comparable with the control group (P > .05). Regression analysis showed significant association of bleeding on probing with Gingival Index, clinical attachment level, and hsCRP (P ≤ .05). CONCLUSIONS: CPA/EE combination does not influence the periodontal and systemic inflammatory status in PCOS females, as similar levels of local and systemic inflammation were observed in CPA/EE consumers compared with PCOS females not on medication. However, it might play a role in increasing gingival thickness and keratinized tissue width in these patients.

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BACKGROUND: Individuals whose gender identity differs from the biological sex and the social norms are defined as transgender. Sometimes transgender undergo gender affirming hormone therapy, which lasts for the entire life making essential to evaluate its potential long-term effects. Moreover, transgender can represent a susceptible sub-group of population and specific attention is needed in risk assessment, including the development of targeted animal models. Aim of the study is the implementation of a rodent demasculinizing-feminizing model through the setting of appropriate dose of hormone therapy and the selection of specific biomarkers to evaluate the sex transition. Specific attention is paid to thyroid homeostasis due to the close link with reproductive functions. Four male adult rats/group were subcutaneously exposed to three doses plus control of ß-estradiol valerate plus cyproterone acetate at: 0.045 + 0.2 (low), 0.09 + 0.2 (medium) and 0.18 + 0.2 (high) mg/dose, five times/week. The doses were selected considering the most recent recommendations for transgender woman. Sperm count, histopathological analysis (testis, liver, thyroid), testosterone, estradiol, triiodothyronine and thyroid-stimulating hormone serum levels and gene expression of sex dimorphic CYP450 were evaluated. RESULTS: The doses induced feminizing-demasculinizing effects: decreased testosterone serum levels at the corresponding cisgender, increased estradiol, impairment of male reproductive function and reversal of sex-specific CYP liver expression. However, the medium and high doses induced marked liver toxicity and the low dose is considered the best choice, also for long-term studies in risk assessment. The alterations of thyroid indicated follicular cell hypertrophy supported by increased thyroid-stimulating hormone serum levels at the higher doses. CONCLUSIONS: The implementation of animal models that mimic the effects of gender affirming hormone therapy is essential for supporting clinical studies in transgender people and filling data gap in order to ensure an appropriate risk assessment and a more accurate, personalized care for transgender people.

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The South American weakly electric fish, Gymnotus omarorum, displays territorial aggression year-round in both sexes. To examine the role of rapid androgen modulation in non-breeding aggression, we administered acetate cyproterone (CPA), a potent inhibitor of androgen receptors, to both male and females, just before staged agonistic interactions. Wild-caught fish were injected with CPA and, 30 min later, paired in intrasexual dyads. We then recorded the agonistic behavior which encompasses both locomotor displays and emission of social electric signals. We found that CPA had no discernible impact on the levels of aggression or the motivation to engage in aggressive behavior for either sex. However, CPA specifically decreased the expression of social electric signals in both males and female dyads. The effect was status-dependent as it only affected subordinate electrocommunication behavior, the emission of brief interruptions in their electric signaling ("offs"). This study is the first demonstration of a direct and rapid androgen effect mediated via androgen receptors on non-breeding aggression. Elucidating the mechanisms involved in non-breeding aggression in this teleost model allows us to better understand potentially conserved or convergent neuroendocrine mechanisms underlying aggression in vertebrates.

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Purpose: Chronic gender-affirming hormone therapy (GAHT) with sublingual estradiol (SLE) has not been studied. We aimed to compare GAHT with SLE only, to combined oral (CO) estradiol and cyproterone acetate, in treatment-naive trans women. Methods: Twenty-two trans women enrolled into either the CO arm or the SLE-only arm (0.5 mg four times daily) in this 6-month prospective study. Anthropometric and laboratory variables were collected at baseline and 3 and 6 months. At the study beginning and end, body composition was measured by dual-energy X-ray absorptiometry and bioelectrical impedance, and gender dysphoria, sexual desire, and function were assessed by validated questionnaires. Results: Subjects in the SLE were older, 26.3±5.8 years versus 20.1±2.3 years, p=0.006. All anthropometric, body composition, and laboratory variables were identical at baseline. Although dysphoria appeared greater, and sexual function lower at baseline in the CO group, this canceled out after age adjustment. Both treatments induced similar biochemical and hormonal changes. Creatinine, hemoglobin and cholesterol decreased significantly, while testosterone was suppressed to the same level in both groups: 3.22 [1.47-5.0] nmol/L in the SLE group and 2.41 [0.55-8.5] nmol/L in the CO, p=0.65. Significant changes in body composition toward a more feminine body were noted in both groups. Dysphoria did not significantly improve in either group, while sexual desire and function decreased at six months in both, p<0.001. Conclusions: Both treatments achieved similar clinical changes. At this stage, SLE, which repeatedly induces alarming excursions of serum estradiol throughout the day, appears to offer no advantage over the CO approach.

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The risks of meningioma associated with the use of cyproterone acetate at high doses (25 to 100 mg/day) have been known since 2007. Recently, two additional molecules have been incriminated: nomegestrol acetate and chlormadinone acetate. The higher the cumulative dose and the longer the treatment duration, the bigger the risk of meningioma (12-fold after 5 years of treatment for nomegestrol acetate, and 7-fold after 3.5 years of treatment for chlormadinone acetate). Nevertheless, these medications have many indications that demonstrate their importance in the daily practice of the general practitioner, of the gynecologist and of the reproductive endocrinologist. Therefore, caution is required when introducing a powerful progestin that is incriminated in the long term at high doses. If the benefit/risk balance favours the initiation of progestin therapy, it is recommended to use the minimal effective dose and to limit the duration of use. Clinical and brain imaging monitoring should also be performed. Finally, if a meningioma develops on progestin, it is recommended that any medication containing a progesterone agonist be suspended.

Les risques de méningiome liés à la consommation de l'acétate de cyprotérone à de fortes doses (25 à 100 mg/jour) sont connus depuis 2007. Récemment, deux molécules supplémentaires ont été incriminées : l'acétate de nomégestrol et l'acétate de chlormadinone. Le risque de développer un méningiome est d'autant plus important que la dose cumulée est grande et que la prescription se prolonge dans le temps (risque multiplié par 12 à partir de 5 ans de traitement pour l'acétate de nomégestrol, et multiplié par 7 à partir de 3,5 ans de traitement par acétate de chlormadinone). Néanmoins, ces médications possèdent de nombreuses indications témoignant de leur importance dans la pratique quotidienne du médecin généraliste, du gynécologue et de l'endocrinologue de la reproduction. Dès lors, la vigilance est de mise lors de l'introduction d'un progestatif puissant incriminé à long terme et à haute dose. Si la balance bénéfices/risques plaide en faveur de l'instauration d'un traitement par progestatif, il est recommandé d'utiliser la dose minimale efficace et d'en limiter la durée d'utilisation. Une surveillance clinique et par imagerie cérébrale systématique est vivement recommandée. Enfin, en cas de détection d'un méningiome, il est recommandé de suspendre toute médication contenant un agoniste de la progestérone.

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Many xenobiotics are non-genotoxic carcinogens (NGC) in rodent liver. Their mode of action (MoA) and health risks for humans are unclear and no in-vitro tests are available to predict NGC. Human HepaRG™ cells in the differentiated (d-HepaRG) and non-differentiated state (nd-HepaRG) were studied as new approach methodology (NAM) for NGC. Cell-biological assays were performed with d-/nd-HepaRG and human hepatoma/hepatocarcinoma cell lines to characterize the benign/malignant phenotype. Reaction of d-/nd-HepaRG to several liver growth factors and NGC (phenobarbital, PB; cyproterone acetate, CPA; WY-14643) was compared to unaltered and premalignant rat hepatocytes in ex-vivo culture. Enzyme induction by NGC was checked by RT-qPCR/oligo-arrays. Growth, anchorage-independency, migration, clonogenicity, and in-vivo tumorigenicity of nd-HepaRG ranged between benign d-HepaRG and malignant hepatoma/hepatocarcinoma cells. All growth factors elevated DNA replication of d-/nd-HepaRG cells, similarly to unaltered/premalignant rat hepatocytes. NGC induced their prototypical enzymes in the rat and human cells, but elicited a growth response only in the unaltered/premalignant rat hepatocytes and not in human d-/nd-HepaRG cells. To conclude, a benign/premalignant phenotype of d-/nd-HepaRG cells and a reactivity towards several hepatic growth factors and NGC, as known from human hepatocytes, are essential components for an in-vitro model for early stage human hepatocarcinogenesis.The potential value as new approach methodology (NAM) for NGC is discussed.

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Androgenetic alopecia (AGA) is the most common nonscarring alopecia and is characterised by distinct gradual patterned hair loss. AGA is mediated by genetic predisposition and excessive follicular sensitivity to androgens, mainly in males, leading to the progressive conversion of scalp terminal hair into vellus hair. Although highly prevalent, it is not fatal but may have a severe psychosocial impact, especially on females and younger males. Significant advances have been made in understanding AGA's epidemiology and pathophysiology, but only 2 drugs remain approved by the FDA - finasteride and minoxidil. Prolonged use of these drugs, is a prerequisite for enhanced treatment response. However, this leads to poor medication adherence and adverse effects from extended use eg, the "postfinasteride syndrome" which persists beyond stopping the drug. Hence, there is a need for research on more effective alternative treatments for AGA, with fewer side effects. This paper reviewed recent advances in AGA pathophysiology and its treatment options. The recently characterized structure of type 2, 5-alpha reductase holds significance in comprehending present and prospective treatments of AGA.

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OBJECTIVE: To compare between different combined oral contraceptive pills (COCPs) as part of the update of the International Evidence-Based Guidelines on the Assessment and Management of polycystic ovary syndrome (PCOS). DESIGN: A systematic review and meta-analysis was performed, Prospero CRD42022345640. METHODS: MEDLINE, EMBASE, All EBM, CINAHL, and PsycINFO was searched on July, 8, 2022, for studies including women with PCOS, comparing 2 different COCPs in randomized controlled trials. RESULTS: A total of 1660 studies were identified, and 19 randomized controlled trials (RCTs) were included.Fourth-generation COCP resulted in lower body mass index (BMI) (mean difference [MD] 1.17 kg/m2 [95% confidence interval {CI} 0.33; 2.02]) and testosterone (MD 0.60 nmol/L [95% CI 0.13; 1.07]) compared with third-generation agents, but no difference was seen in hirsutism.Ethinyl estradiol (EE)/cyproterone acetate (CPA) was better in reducing hirsutism as well as biochemical hyperandrogenism (testosterone [MD 0.38 nmol/L {95% CI 0.33-0.43}]) and BMI (MD 0.62 kg/m2 [95% CI 0.05-1.20]) compared with conventional COCPs.There was no difference in hirsutism between high and low EE doses. No evidence regarding natural estrogens in COCP was identified. CONCLUSION: With current evidence, combined regimens containing an antiandrogen (EE/CPA) may be better compared with conventional COCPs in reducing hyperandrogenism, but EE/CPA will not be recommended as a first-line COCP treatment by the pending PCOS guideline update, due to higher venous thrombotic events (VTE) risk in the general population. Later-generation progestins offer theoretical benefits, but better evidence on clinical outcomes is needed in women with PCOS. TRIAL REGISTRATION: The protocol for the systematic review was registered prospectively in Prospero, CRD42022345640.

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Infertility affects 15% of global population. This study was designed to search out the most effective dose of chloroform fraction of hydro-ethanolic extract of Hygrophila auriculata seed to ameliorate cyproterone acetate (CPA)-treated male subfertility. The rats were made subfertile by CPA at the dose of 2.5 mg/100gm body weight for 45 days. The male subfertility represented by low sperm concentration, less motile, less viable, and less hypo osmotic tail swelled spermatozoa in CPA-treated group. Serum LH, FSH, and testosterone levels were significantly decreased in CPA-treated group in respect to control. Androgenic key enzyme Δ5,3ß-HSD, 17ß-HSD activities and gene expression pattern were also decreased significantly in respect to control. These antispermatogenic and antiandrogenic activities of CPA were significantly recovered after the treatment of Hygrophila auriculata at the dose of 2.5 mg, 5mg, and 10 mg/100gm body weight. CPA also generate oxidative free radical that indicated by altered catalase, superoxide dismutase, and peroxidase activities and protein expression pattern along with conjugated diene and thiobarbituric acid reactive substance levels in testis. Expression pattern of Bax and Bcl2 genes were deviated from control after CPA treatment. Significant diminution of body weight, organo-somatic indices, and SGOT, SGPT activities were observed in CPA-treated group. All these biomarkers significantly recovered towards control after the treatment of Hygrophila auriculata at different doses. More significant recovery was observed in 5 mg and 10 mg of chloroform fraction-treated group and 5 mg dose, i.e., the minimum therapeutic dose to recover the CPA-induced subfertility.

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OBJECTIVE: Numerous studies have confirmed a strong association between progestins and meningiomas and the regression and/or stabilization of meningiomas after discontinuation of treatment. Osteomeningiomas represent a small subgroup of meningiomas that appear to be more common among progestin-related meningiomas. However, the specificity of the behavior of this subset of meningiomas after discontinuation of progestin has not yet been assessed. METHODS: Thirty-six patients (mean age 49.5 years) who presented with at least one progestin-related osteomeningioma (48 tumors total) were identified from a prospectively collected database of patients and had been referred to our department for meningioma and had documented use of cyproterone acetate, nomegestrol acetate, and/or chlormadinone acetate. Hormonal treatment was stopped at the time of diagnosis for all the patients, and the clinical and radiological evolution of this subgroup of tumors was evaluated. RESULTS: For half of the 36 patients, treatment was prescribed for signs of hyperandrogenism, such as hirsutism, alopecia, or acne. Most lesions were spheno-orbital (35.4%) or frontal (31.2%). Although the tissular part of the meningioma shrank in 77.1% of cases, the osseous part exhibited discordant behavior with 81.3% showing volume progression. The combination of estrogens, as well as the prolonged duration of progestin treatment, seems to increase the risk of progression of the osseous part after treatment discontinuation (p = 0.02 and p = 0.028, respectively). No patient required surgical treatment at diagnosis or during the study. CONCLUSIONS: These results show that while the soft intracranial part of progestin-related osteomeningioma tumor is the most likely to regress after treatment discontinuation, the bony part is more likely to increase in volume. These findings suggest the need for careful follow-up of these patients, especially those with tumors near the optical apparatus.

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OBJECTIVE: To investigate the effects of letrozole combined with ethinylestradiol and cyproterone acetate tablets on serum sex hormones and lipid metabolism in patients with polycystic ovary syndrome (PCOS). METHODS: Clinical data of 152 PCOS patients in the First Affiliated Hospital of Guangxi University of Chinese Medicine from May 2019 to June 2021 were collected for a retrospective analysis. Among the patients, 73 treated with ethinylestradiol and cyproterone acetate tablets alone were seen as control group (CG), and the rest 79 with letrozole combined with ethinylestradiol and cyproterone acetate tablets were seen as observation group (OG). The treatment efficacy was observed, and the adverse reactions in the course of treatment were counted. The levels of luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone (T), estrogen (E2), total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL) and low-density lipoprotein (LDL) were compared before and after treatment. The number of mature follicles, ovulation rate and pregnancy rate were assessed. Multivariate logistic regression analysis was used to detect the independent risk factors of ineffective efficacy. RESULTS: After the treatment, the total efficacy rate of the OG was higher than that of the CG (P<0.05); moreover, the levels of TC, TG, LDL, FSH, LH and T in OG were lower while HDL and E2 were higher (all P<0.05) than those of the CG. Also, the number of mature follicles, ovulation rate and pregnancy rate were higher in OG than those in the CG (all P<0.05). There was no obvious difference in the incidence of adverse reactions between the groups (P>0.05). Higher fasting glucose, higher Ferriman-Gallway hair score, single drug treatment regimen, higher systolic blood pressure, and lower E2 before treatment were independent risk factors for ineffective treatment efficacy. CONCLUSION: Letrozole combined with ethinylestradiol and cyproterone acetate tablets can enhance the treatment efficiency of PCOS and improve serum sex hormones and lipid metabolism in PCOS patients.

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BACKGROUND: Individuals convicted of a sexual offense (ICSO) can be treated with testosterone-lowering medication (TLM) in order to support the control of paraphilic sexual fantasies and to decrease the risk of sexual recidivism. However, due to partly severe side effects, TLM should not be a lifelong treatment. AIM: The aim of the current study was to further evaluate the Change or Stop Testosterone-Lowering Medication (COSTLow)-R Scale in forensic outpatient aftercare practice. The scale was developed to assist forensic professionals in deciding on whether to change or stop TLM treatment in ICSO. METHODS: The COSTLow-R Scale was applied retrospectively in a forensic-psychiatric outpatient institution in Hesse, Germany, on 60 ICSO. TLM was terminated in 24 patients (40%). Moreover, 10 forensic professionals of the institution as well as an experienced working group within the institution focusing on the treatment of ICSO, qualitatively evaluated the COSTLow-R Scale by participating in an open designed survey. OUTCOMES: The COSTLow-R Scale ratings as assessed by forensic professionals were collected. In addition, a survey was performed among these professionals about the usefulness of the scale and their practical experiences with it. RESULTS: A binary logistic regression analysis was conducted to ascertain the predictive power of the scale regarding the stopping of TLM. Three items of the COSTLow-R Scale significantly predicted stopping decisions: the possibility of psychotherapy before TLM treatment, psychopathic traits, and a substantial decrease of paraphilic severity. Thus, a decision towards stopping TLM was more likely for patients who showed greater treatment readiness before starting TLM, lower psychopathy scores, and a higher decrease of paraphilic severity. The forensic professionals described the scale as a good and structured tool that displays which aspects are important to consider during TLM treatment decisions. CLINICAL IMPLICATIONS: The COSTLow-R Scale provides structure to the decision of whether to change or stop TLM and should thus be implemented in the forensic treatment process of patients with TLM more frequently. STRENGTHS AND LIMITATIONS: Although the small sample size limits generalizability of the findings, the present study was conducted directly in a forensic outpatient practice and, therefore, has high external validity and a strong impact on the life and health of patients treated with TLM. CONCLUSION: The results indicate that the COSTLow-R Scale can be a useful instrument facilitating the TLM decision-making process by providing a structured compendium of criteria. Further research is still needed to evaluate the scale and to provide additional evidence for the results of the current study.

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Transgender (TG) describes individuals whose gender identity differs from the social norms. TG people undergoing gender-affirming hormone therapy (HT) may be considered a sub-group of the population susceptible to environmental contaminants for their targets and modes of action. The aim of this study is to set appropriate HT doses and identify specific biomarkers to implement TG animal models. Four adult rats/group/sex were subcutaneously exposed to three doses of HT (plus control) selected starting from available data. The demasculinizing-feminizing models (dMF) were ß-estradiol plus cyproterone acetate, at 0.09 + 0.33, 0.09 + 0.93 and 0.18 + 0.33 mg, respectively, five times/week. The defeminizing-masculinizing models (dFM) were testosterone (T) at 0.45, 0.95 and 2.05 mg, two times/week. Clitoral gain and sperm count, histopathological analysis of reproductive organs and liver, hormone serum levels and gene expression of sex-dimorphic CYP450 were evaluated. In the dMF model, the selected doses-leading to T serum levels at the range of the corresponding cisgender-induced strong general toxicity and cannot be used in long-term studies. In the dFM model, 0.45 mg of T represents the correct dose. In addition, the endpoints selected are considered suitable and reliable to implement the animal model. The sex-specific CYP expression is a suitable biomarker to set proper (de)masculinizing/(de)feminizing HT and to implement TG animal models.

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In order to assess the risk of hypertension development, we performed a retrospective analysis of the clinical records of consecutive transgender patients who began gender-affirming hormonal therapy in our Outpatient Gender Identity Clinic with <30 years of age and had a follow-up >5 years. 149 transgender women treated with estradiol and 153 transgender men treated with testosterone were included; 129 of the transgender women received also androgen blockers (54 spironolactone, 49 cyproterone acetate and 26 LHRH agonists). The annual incidence of hypertension in young transgender men (1.18%) seemed comparable to that of the general population. In young transgender women, it seemed higher (2.14%); we found that the choice of androgen blocker had a remarkable effect, with a highly significant increase in patients treated with cyproterone acetate (4.90%) vs. the rest (0.80%); the adjusted hazard-ratio was 0.227 (p = 0.001). Correlation, logistic regression and mediation analyses were performed for the associations of the available clinical variables with the increase in systolic blood pressure and the onset of hypertension, but besides the use of cyproterone acetate, only the ponderal gain was found significant (Spearman's r: 0.361, p < 0.001); with a 36.7% mediation effect (31.2-42.3%). Cyproterone acetate has additional known risks, such as meningioma; although we cannot conclusively prove that it has a role in the development of hypertension, we conclude that the use of cyproterone acetate for this indication should be reconsidered.

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Combined oral contraceptives (containing synthetic forms of estradiol and progestins) are one of the most commonly used drugs among females. However, their effects on the gut-brain axis have not been investigated to a great extent despite clear evidence that suggest bi-directional interactions between the gut microbiome and endogenous sex hormones. Moreover, oral contraceptives are prescribed during adolescence, a critical period of development during which several brain structures and systems, such as hypothalamic-pituitary-gonadal axis, undergo maturation. Considering that oral contraceptives could impact the developing adolescent brain and that these effects may be mediated by the gut-brain axis, further research investigating the effects of oral contraceptives on the gut-brain axis is imperative. This article briefly reviews evidence from animal and human studies on the effects of combined oral contraceptives on the brain and the gut microbiota particularly during adolescence.

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Herein, a novel homemade electrical device was designed, including two pieces of external neodymium magnets, providing a reciprocating magnetic field to introduce a magnetic-assisted dispersive pipette-tip micro solid-phase extraction. To evaluate the performance efficiency of the proposed method, a novel magnetic calcined GO/SiO2@Co-Fe nanocube sorbent was synthesized, filled into the pipette-tip, exposed to the reciprocating magnetic field, and applied for the preconcentration of some hormone therapy drugs in human biological matrices. The effective adsorption and desorption parameters were optimized using a rotatable central composite design and one-variable-at-a-time approaches. Under the optimized conditions, the target analytes' detection limits were found to be below 0.02 ng mL-1. Moreover, the calibration curves were linear in the range of 0.03-500.00 ng mL-1 (R2 > 0.9966), with RSDs% less than 7.8 %. Eventually, the established method was applied to extract the analytes from breast milk samples, followed by LC-ESI-MS/MS analysis.

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PURPOSE: To report the results of systematic meningioma screening program implemented by French authorities in patients exposed to progestin therapies (cyproterone (CPA), nomegestrol (NA), and chlormadinone (CMA) acetate). METHODS: We conducted a prospective monocentric study on patients who, between September 2018 and April 2021, underwent standardized MRI (injection of gadolinium, then a T2 axial FLAIR and a 3D-T1 gradient-echo sequence) for meningioma screening. RESULTS: Of the 210 included patients, 15 (7.1%) had at least one meningioma; seven (7/15, 47%) had multiple meningiomas. Meningiomas were more frequent in older patients and after exposure to CPA (13/103, 13%) compared to NA (1/22, 4%) or CMA (1/85, 1%; P = 0.005). After CPA exposure, meningiomas were associated with longer treatment duration (median = 20 vs 7 years, P = 0.001) and higher cumulative dose (median = 91 g vs. 62 g, P = 0.014). Similarly, their multiplicity was associated with higher dose of CPA (median = 244 g vs 61 g, P = 0.027). Most meningiomas were ≤ 1 cm3 (44/58, 76%) and were convexity meningiomas (36/58, 62%). At diagnosis, patients were non-symptomatic, and all were managed conservatively. Among 14 patients with meningioma who stopped progestin exposure, meningioma burden decreased in 11 (79%) cases with no case of progression during MR follow-up. CONCLUSION: Systematic MR screening in progestin-exposed patients uncovers small and multiple meningiomas, which can be managed conservatively, decreasing in size after progestin discontinuation. The high rate of meningiomas after CPA exposure reinforces the need for systematic screening. For NA and CMA, further studies are needed to identify patients most likely to benefit from screening.

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