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Progestin-associated meningioma is a rare complication of cyproterone acetate (CPA), an anti-androgen commonly prescribed in feminizing hormone therapy regimens for transgender and gender-diverse individuals. A dose-response association has been observed, particularly with longer-term exposure to doses ≥ 50 mg daily; however, the dose below which CPA use is safe remains unclear. We herein report the cases of 2 transgender women using CPA who developed meningioma. Novel aspects of our cases include: (i) the presence of symptomatic giant meningiomas (> 5 cm), including multiple meningiomas in one patient, requiring urgent surgical intervention; (ii) meningioma development with both high-dose, long duration and low-dose, shorter duration CPA; and (iii) the presence of a PIK3CA missense variant in one patient, which may play a role in the pathogenesis of progestin-associated meningioma. Our cases highlight the real-world risk of this likely underreported adverse effect and underscore the importance of clinician vigilance for neurological sequelae. We suggest using the lowest dose of CPA that maintains adequate androgen suppression, with consideration of alternative anti-androgens where appropriate. [ABSTRACT FROM AUTHOR]

Background Data regarding the effectiveness of low-dose cyproterone acetate (CPA) in testosterone suppression as feminizing hormone therapy (FHT) in individuals assigned male at birth (AMAB) are sparse. Aim To assess the effectiveness in testosterone suppression using low-dose CPA (<25 mg/day) compared to standard-dose CPA (25–50 mg/day) in FHT. Methods A retrospective cohort study of 59 individuals AMAB using CPA was done at a tertiary care center in Bangkok, Thailand between January 2014 and July 2022. Outcomes The main outcomes included a median time when the testosterone was suppressed (<50 ng/dL), the proportion of individuals AMAB who achieved the targeted testosterone level at 3 months, and the testosterone level at each follow-up. Changes in clinical data were assessed. Results Among 59 individuals AMAB, 37 initiated CPA with available testosterone levels at the 3-month follow-up. Twenty-two individuals AMAB started with low-dose CPA (12.5 mg/day), and 15 individuals AMAB started with standard-dose CPA. The median time to reach targeted testosterone was 3 months in both groups (adjusted hazard ratio 0.60, P  = .489). At 3 months, 72.7% of those on low-dose CPA and 86.7% of those on standard-dose CPA achieved targeted testosterone (adjusted relative risk 0.85, P  = .606). Testosterone levels at all follow-up visits were not significantly different. The standard dose group had higher high-density lipoprotein cholesterol (HDL-C) but lower low-density lipoprotein cholesterol (LDL-C) and alanine aminotransferase (ALT). Clinical Translation This study supports a paradigm shift toward using lower-dose CPA in FHT. Strengths and Limitations This is one of a few studies showing the effectiveness of low-dose CPA in testosterone suppression within 3 months. Limitations include a small sample size and missing data. Conclusions Testosterone suppression is comparable between CPA 12.5 mg/day and the standard dose in FHT. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract 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 β-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.

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 β-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. [ABSTRACT FROM AUTHOR]

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. • Differentiated/non-differentiated HepaRG™ cells show a benign/premalignant phenotype. • These cells may serve as in vitro model for human hepatocarcinogenesis. • Growth factors induced DNA replication in the cells; non-genotoxic carcinogens failed. • A similar reaction pattern is known from human hepatocytes. • HepaRG™ cells may be useful to predict non-genotoxic carcinogens. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction: Polycystic Ovary Syndrome (PCOS) is associated with hyperandrogenism and obesity. The present study was performed with aim to compare testosterone and dehydroepiandrosterone sulfate serum levels and anthropometric indices between patients with PCOS taking metformin and cyproterone compounds. Methods: This cross-sectional analytical study was conducted in 2022 was performed by reviewing the medical documents including age, body mass index (BMI), waist circumference (WC), waist-to-hip-ratio (WHR), waist-to-height ratio (WHtR), testosterone serum levels, and dehydroepiandrosterone sulfate before and after taking the drugs for 3 months. Two-hundred and twenty participants were divided in 4 groups (n=55 in each group) as follows: 1) taking metformin 500 mg daily, 2) taking cyproterone compound 2 mg daily, 3) taking metformin and cyproterone compound simultaneously, and 4) participants without PCOS as control. Data were analyzed by SPSS software (version 25) and paired T-test and ANOVA. P

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 Δ5,3β-HSD, 17β-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. [ABSTRACT FROM AUTHOR]

Introduction: Hirsutism is a condition characterized by excess hair growth on the face, chest, and/or back in women and it is often caused by an imbalance of hormones, such as androgens. OCPs prove to be effective in reducing hirsutism in patients with PCOS by inhibiting the production of androgens and decreasing the activity of androgen receptors. OCPs may have additional benefits for patients with PCOS, such as regulating menstrual cycles, improving fertility, and reducing the risk of endometrial cancer. However, OCPs may not be suitable for all women with PCOS. Methods: The study was conducted to investigate the effectiveness of these OCPs in reducing hirsutism in PCOS patients. In the study, 80 participants were included, 40 in the intervention group and 40 in the control group. The intervention group received a combination oral contraceptive pill containing cyproterone acetate and drosperinone (COCP) for a period of 6 months, while the control group received a placebo. Hirsutism was assessed at baseline and at the end of the 6-month treatment period using the Ferriman-Gallwey score. The primary outcome measure was the change in Ferriman-Gallwey score from baseline to the end of the treatment period. Results: The study found that OCPs containing cyproterone acetate and drosperinone were more effective in reducing hirsutism in patients with PCOS compared to OCPs containing levonorgestrel. Conclusion: It is important to note that OCPs may not be appropriate for all women with PCOS, therefore it's crucial to explore the risks and advantages with a healthcare professional before beginning therapy.

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. [ABSTRACT FROM AUTHOR]

Introduction: Hirsutism is a condition characterized by excess hair growth on the face, chest, and/or back in women and it is often caused by an imbalance of hormones, such as androgens. OCPs prove to be effective in reducing hirsutism in patients with PCOS by inhibiting the production of androgens and decreasing the activity of androgen receptors. OCPs may have additional benefits for patients with PCOS, such as regulating menstrual cycles, improving fertility, and reducing the risk of endometrial cancer. However, OCPs may not be suitable for all women with PCOS. Methods: The study was conducted to investigate the effectiveness of these OCPs in reducing hirsutism in PCOS patients. In the study, 80 participants were included, 40 in the intervention group and 40 in the control group. The intervention group received a combination oral contraceptive pill containing cyproterone acetate and drosperinone (COCP) for a period of 6 months, while the control group received a placebo. Hirsutism was assessed at baseline and at the end of the 6-month treatment period using the Ferriman-Gallwey score. The primary outcome measure was the change in Ferriman-Gallwey score from baseline to the end of the treatment period. Results: The mean age of participants was 27.4 years (SD ±5.3) and the majority had a BMI of 25.3 kg/m² (SD±4.5). The intervention group showed a significant reduction in the Ferriman-Gallwey score (-5.2, 95% CI -6.5 to -3.8), while the control group had a non-significant change (-1.9, 95% CI -3.3 to -0.5). Hormone levels showed changes. Patient satisfaction was high in the intervention group (90%). Statistical analysis revealed a significant difference in the Ferriman-Gallwey score (p < 0.05). The combination oral contraceptive pill effectively reduces hirsutism in PCOS patients. Conclusion: Our study demonstrates the significant reduction in hirsutism and high patient satisfaction with the COCP, highlighting its potential as a first-line treatment for women with PCOS, leading to improved well-being and quality of life. [ABSTRACT FROM AUTHOR]

Sotos syndrome (SS) is characterized by overgrowth, distinctive facial appearance, and learning disability. It is caused by heterozygous mutations, including deletions of NSD1 located at chromosome 5q35. While advanced bone age can occur in some cases, precocious puberty (PP) has only been reported in three cases previously. Here, we reported a case of SS diagnosed in the infancy period with central PP. The discovery of potential factors that trigger puberty is one of the central mysteries of pubertal biology. Depot gonadotropinreleasing hormone analogs constitute the first-line therapy in central PP (CPP), which has proven to be both effective and safe. In our cases, leuprolide acetate at maximum dose was not successful in controlling pubertal progression, and cyproterone acetate (CPA) was added to therapy, with successful control of pubertal progression. In some specific syndromes with PP, such as SS, treatment can be challenging. CPA may be an asset for effective treatment.

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. [ABSTRACT FROM AUTHOR]

The article offers information on several articles published on medical topics. Topics discussed include American epidemiological study sought to note the factors long Covid risk, as well as the possibly preventive role of vaccination; increased risk with a hormone replacement therapy, but especially with high doses of acetate cyproterone, a progestogen with anti-androgen and issues related to sudden Infant Death Syndrome (SIDS).

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 β-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. [ABSTRACT FROM AUTHOR]

The antiprostatic activity of a new composition based on the sum of sesquiterpenoid alcohols esters of Ferula tenuisecta ferutinin, ferutin, teferin, tenuferidine and fertidine (the substance of the drug Ferulen - a phytoestrogenic drug) and cyproterone acetate, which has strong antigonadotropic properties and gestagenic activity, was studied. It has been established that the new composition has a pronounced antiprostatic effect in rats in oral administration, reduces the mass of adrenogendependent organs (ventral prostate, coagulating gland, seminal vesicles, and testes), and reduces the level of testosterone in the blood. In terms of antiprostatic activity, the new composition is not inferior to surgical castration. The influence of the composition on the biochemical parameters of experimental animals was studied. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background and purpose: A dose‐dependent association between the use of cyproterone acetate (CPA) and intracranial meningioma has been identified but data for other potent progestogens are scarce. The association was assessed between intracranial meningioma surgery and exposure to three potent progestogens: CPA (≥25 mg/day), nomegestrol acetate (NOMAC) (3.75–5 mg/day) and chlormadinone acetate (CMA) (2–10 mg/day). Methods: In this nationwide population‐based case–control study, cases underwent surgery for intracranial meningioma in France from 2009 to 2018. They were matched to five control subjects for sex, year of birth and area of residence. Progestogen exposure was defined as progestogen use within the year before surgery for cases or the same date for their controls. Results: In total, 25,216 cases were included (75% women, median age 58 years). Progestogen exposure was noted for 9.9% of cases (2497/25,216) and 1.9% (2382/126,080) of controls, with an odds ratio (OR) of 6.7 (95% confidence interval [CI] 6.3–7.1). The OR was 1.2 (1.0–1.4) for short‐term use (<1 year) and 9.5 (8.8–10.2) for prolonged use. A strong association was identified for prolonged use of CPA (OR = 22.7, 95% CI 19.5–26.4), NOMAC (OR = 6.5, 95% CI 5.8–7.2) and CMA (OR = 4.7, 95% CI 4.5–5.3). Progestogen exposure increased the risk of meningioma for all histological grades and anatomical sites, particularly for the anterior and middle skull base: OR = 35.7 (95% CI 26.5–48.2) and 23.9 (95% CI 17.8–32.2) for CPA. The estimated number of attributable cases was 2124 (95% CI 2028–2220) (212/year). Conclusion: A strong association between prolonged exposure to potent progestogens and surgery for meningioma was observed. The risk increased from CMA to NOMAC to CPA. Individuals should be informed of this risk. This study highlights a strong association between prolonged use of nomegestrol and chlormadinone acetate (two potent progestogens) and intracranial meningioma, although weaker than that of cyproterone acetate. The estimated number of cases was higher than 2000 in France over 10 years. [ABSTRACT FROM AUTHOR]

Sotos syndrome (SS) is characterized by overgrowth, distinctive facial appearance, and learning disability. It is caused by heterozygous mutations, including deletions of NSD1 located at chromosome 5q35. While advanced bone age can occur in some cases, precocious puberty (PP) has only been reported in three cases previously. Here, we reported a case of SS diagnosed in the infancy period with central PP. The discovery of potential factors that trigger puberty is one of the central mysteries of pubertal biology. Depot gonadotropinreleasing hormone analogs constitute the first-line therapy in central PP (CPP), which has proven to be both effective and safe. In our cases, leuprolide acetate at maximum dose was not successful in controlling pubertal progression, and cyproterone acetate (CPA) was added to therapy, with successful control of pubertal progression. In some specific syndromes with PP, such as SS, treatment can be challenging. CPA may be an asset for effective treatment. [ABSTRACT FROM AUTHOR]

Introduction. About 10–20% of patients among women of reproductive age suffer from signs and symptoms of androgen excess in hyperandrogenism. Its skin symptoms may include hirsutism, acne, seborrhea and alopecia.Aim. To assess the effect of cyproterone acetate on skin symptoms of hyperandrogenism and improvement in the patients’ quality of life after treatment.Materials and methods. The study included 120 patients with skin symptoms of hyperandrogenism. The patients ranged in age from 18 to 35 years. The inclusion criteria were the main complaints of the patients as follows: acne, hirsutism and alopecia. The patients underwent a comprehensive clinical and laboratory examination. The drug of choice for the treatment of androgendependent dermatopathies was cyproterone acetate at a dose of 50–100 mg daily.Results and discussion. All patients were divided into three groups: 44 (37%) patients with hirsutism, 55 (53%) with acne, 12 (10%) with alopecia. Moreover, 32 (27%) patients had a mix of symptoms at the same time. Such patients were assigned to one of the groups depending on the predominant complaint. All patients were prescribed cyproterone acetate at a dose of 50-100 mg once daily, depending on the severity of symptoms from day 1 to day 10 of the menstrual cycle, and 54 (52%) patients were prescribed cyproterone acetate 20 mg and ethinyl estradiol 35 mg from day 1 to day 21 of the menstrual cycle. The study showed stabilization of the psychoemotional state, relief of anxiety, depressive disorders, enhancement of self-esteem and sociability, and improvement of the quality of life in its various manifestations in the majority of patients after the treatment.Сonclusion. When assessed using the dermatology life quality index questionnaires, all patients reported the stabilization of the psychoemotional state and the improvement in the quality of life after the treatment. The anxiety and depressive disorders decreased in 109 (91%) patients, which favourably influenced various areas of quality of life, enhanced self-esteem and sociability with a positive effect on personal relationships.

Abstract Background Perioperative bleeding is the most common complication related to transurethral resection of prostate; the aim of the study was to compare the effect of pre-operative use of finasteride versus cyproterone acetate (CPA) on blood loss with monopolar TURP. Methods This prospective randomized controlled study was conducted on (60) patients with BPH underwent monopolar TURP between July 2019 and July 2020. Patients were distributed into three equal groups; CPA group: 20 patients received cyproterone acetate 50 mg tab BID for two weeks before TURP, finasteride group: 20 patients received single daily dose of finasteride 5 mg for two weeks before TURP, control group: 20 patients received no treatment before TURP, all patients underwent monopolar TURP, and then histopathological examination of the resected tissues was done with assessment of the microvascular density of the prostate. Results Our study showed that there was significant decrease in intraoperative blood loss and operative time in CPA and finasteride groups in comparison with control group (p = 0.0012) (p

WHO grade II progestin-related meningiomas have been reported in recent series but we found no previous study describing their long-term outcome. Our study aimed to evaluate patients operated on for high-grade intracranial meningioma and who underwent long-term exposure to high dose of cyproterone acetate, nomegestrol acetate, and chlormadinone acetate. Our study retrospectively included 9 patients with high-grade progestin-related intracranial meningioma between December 2006 and September 2021. In each patient, clinico-radiological follow-up was performed every 6 months after diagnosis and treatment withdrawal recommendation. The mean progestative exposure was 11.4 years. Edema existence or absence of cleft sign on MRI were the key factors for surgical indication. All patients underwent surgery. Adjuvant radiotherapy was indicated in 1 patient, and Gamma Knife radiosurgery was proposed in 2 other patients for a second location of meningioma. Six patients harbored a grade II chordoid meningioma subtype with 100% PR expression and 3 patients a grade II atypical meningioma subtype with lower PR expression. The mean follow-up was 8.1 years and none of the 9 patients presented with a recurrence. Patients with grade II progestin-related meningiomas have less tumor recurrence after surgery than patients with sporadic grade II meningiomas, especially after progestin withdrawal. The presence/appearance of peri-meningioma edema and the absence of cleft sign before volumetric change should suggest the existence of an underlying WHO grade II meningiomas. In these cases, surgical resection may immediately be considered and adjuvant radiotherapy should be reserved for proven recurrence cases. [ABSTRACT FROM AUTHOR]

Objective: Comparison of hormonal, metabolic and inflammatory markers of glutathione with metformin and Diane-35 in a rat model of PCOS induced by dehydroepiandrosterone., Methods: Twenty-five female rats were randomized into four groups. Group 1 was administered a subcutaneous dose of 0.2 ml saline/day. Group 2 was given 0.2 ml of 1% carboxymethyl cellulose (CMC)/day orally for 28 days. A PCOS model was established with DHEA in rats. Group 3 was given 4.5 mg/kg/day of Diane-35 orally dissolved in 1% CMC for 28 days. Group 4 was given 300 mg/kg/day of metformin orally dissolved in 1 ml of saline for 28 days, and Group 5 was administered 100 mg/kg of glutathione intraperitoneally on days 35, 42, and 49. On day 56, the rats were sacrificed. Serum markers and follicle count were examined., Results: Serum IL-6, hs-CRP, insulin, testosterone, SHBG, and MDA values were significantly lower in the glutathione group than in the PCOS group ( p  = 0.0006, p  = 0.023, p  = 0.0082, p  = 0.0007, p  = 0.0048, and p  < 0.0001, respectively).The number of all follicles was similar between the control and glutathione groups ( p  < 0.05). When we compared the other groups with the PCOS group, the number of primary, secondary, atretic, and cystic follicles was significantly lower in the metformin and glutathione groups. The number of primordial and antral follicles was significantly higher than in the PCOS group., Conclusions: Glutathione plays anti-inflammatory and antioxidant roles, similar to metformin, by lowering serum IL-6, insulin, testosterone, CRP, and MDA levels; decreasing atretic/cystic follicle count; and improving antral follicle count and folliculogenesis in PCOS patients.

Meningiomas are common intracranial tumors with a female predominance. Their etiology is still poorly documented. The role of sexual hormones has long been evoked, and data have been conflicting across studies. However, a dose-dependent relationship between the incidence and growth of meningiomas and hormonal treatment with the progestin cyproterone acetate (CPA) has recently been established. CPA-associated meningiomas seem to be mainly located in the anterior and middle skull base, are more likely to be multiple, may harbor P1K3CA mutations in up to one-third of cases, and are more common with a longer duration of treatment. A similar but lower risk of meningiomas has been recently reported with the use of chlormadinone acetate and nomegestrol acetate as progestin treatments. Concerning hormonal replacement therapy (HRT) in menopausal patients, evidence from epidemiological studies seem to favor an increased risk of meningiomas in treated patients although a recent study failed to show an increased growth of meningiomas in HRT treated vs nontreated patients. Until larger studies are available, it seems wise to recommend avoiding HRT in patients with meningiomas. Evidence from published data does not seem to support an increased risk of meningiomas with oral contraceptive oral contraceptive (OR) use. Data are too scarce to conclude on fertility treatments. Based on studies demonstrating the expression of hormonal receptors in meningiomas, therapies targeting these receptors have been tried but have failed to show an overall favorable clinical outcome in meningioma treatment. [ABSTRACT FROM AUTHOR]

Purpose: The long-term use of cyproterone acetate (CPA) is associated with an increased risk of developing intracranial meningiomas. CPA discontinuation most often induces a stabilization or regression of the tumor. The underlying biological mechanisms as well as the reasons why some meningiomas still grow after CPA discontinuation remain unknown. We reported a series of patients presenting CPA-induced meningiomatosis with opposed tumor evolutions following CPA discontinuation, highlighting the underlying histological and genetic features. Methods: Patients presenting several meningiomas with opposite tumor evolution (coexistence of growing and shrinking tumors) following CPA discontinuation were identified. Clinical and radiological data were reviewed. A retrospective volumetric analysis of the meningiomas was performed. All the growing meningiomas were operated. Each operated tumor was characterized by histological and genetic analyses. Results: Four women with multiple meningiomas and opposite tumor volume evolutions after CPA discontinuation were identified. Histopathological analysis characterized the convexity and tentorial tumors which continued to grow after CPA discontinuation as fibroblastic meningiomas. The decreasing skull base tumor was characterized as a fibroblastic meningioma with increased fibrosis and a widespread collagen formation. The two growing skull base meningiomas were identified as meningothelial and transitional meningiomas. The molecular characterization found two NF2 mutations among the growing meningiomas and a PIK3CA mutation in the skull base tumor which decreased. Conclusion: To our knowledge, this is the first report describing an atypical tumor evolution of CPA-associated meningiomas after CPA discontinuation. The underlying biological mechanisms explaining this observation and especially the close relationship between mutational landscapes and embryologic origins of the meninges in CPA-related meningiomas as well as their clonal origin require further research. [ABSTRACT FROM AUTHOR]

Abstract Introduction The management of recurrent ischemic priapism is unclear in contemporary practice. Yet, if left untreated, the condition may evolve into an acute ischemic priapism and in some cases result in erectile dysfunction. This report documents the results of successful management of recurrent ischemic priapism using cyproterone acetate in a 30-year-old Saudi man with sickle cell anemia as a comorbidity. Case presentation A 30-year-old Saudi man denoted visited the emergency room with a painful erection which had lasted for more than four hours. The patient has sickle cell anemia and a family history of sickle cell disease. He is married and has two children. His first priapism case occurred when he was 7 years old. At the age of 15, the condition recurred, and the patient’s doctor prescribed cyproterone acetate 50 mg twice daily for 5 days. The doctor had told him that whenever he was experiencing priapism, he should adhere to this regimen for 5 days. The doctor could not find any guidelines for the prescription of cyproterone acetate. Conclusion Priapism cases represent a significant challenge in therapeutic management because of the elevated risk of structural damage to the penis. The fact that there lacks a clinically approved standard approach to managing the condition make it difficult for physicians to effectively manage the condition. Management of the condition is further complicated by existence of comorbidities such as sickle cell anemia. This patient’s case demonstrates that cyproterone acetate prescription is a great preventative strategy that limits priapism recurrences.

The use of antiandrogens is gaining significance in dermatology practice these days. Though once considered a domain of endocrinologists and gynecologists, these drugs now constitute an important category while treating a number of dermatologic conditions. A thorough knowledge of these drugs, as well as their applications in dermatology would therefore be of immense value for the practicing dermatologist. This review will throw a bird's eye view on the salient aspects of these drugs and their importance in those conditions, where their usage in applicable.

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 β-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.