Cyproterone Acetate Research Articles

Use of high dose cyproterone acetate and risk of intracranial meningioma in women: cohort study

Abstract Objective To assess the risk of meningioma associated with use of high dose cyproterone acetate, a progestogen indicated for clinical hyperandrogenism. Design Observational cohort study. Setting Data from SNDS, the French administrative healthcare database, between 2007 and 2015. Participants 253 777 girls and women aged 7-70 years living in France who started cyproterone acetate between 2007 and 2014. Participants had at least one reimbursement for high dose cyproterone acetate and no history of meningioma or benign brain tumour, or long term disease status. Participants were considered to be exposed when they had received a cumulative dose of at least 3 g during the first six months (139 222 participants) and very slightly exposed (control group) when they had received a cumulative dose of less than 3 g (114 555 participants). 10 876 transgender participants (male to female) were included in an additional analysis. Main outcome measure Surgery (resection or decompression) or radiotherapy for one or more intracranial meningiomas. Results Overall, 69 meningiomas in the exposed group (during 289 544 person years of follow-up) and 20 meningiomas in the control group (during 439 949 person years of follow-up) were treated by surgery or radiotherapy. The incidence of meningioma in the two groups was 23.8 and 4.5 per 100 000 person years, respectively (crude relative risk 5.2, 95% confidence interval 3.2 to 8.6; adjusted hazard ratio 6.6, 95% confidence interval 4.0 to 11.1). The adjusted hazard ratio for a cumulative dose of cyproterone acetate of more than 60 g was 21.7 (10.8 to 43.5). After discontinuation of cyproterone acetate for one year, the risk of meningioma in the exposed group was 1.8-fold higher (1.0 to 3.2) than in the control group. In a complementary analysis, 463 women with meningioma were observed among 123 997 already using cyproterone acetate in 2006 (risk of 383 per 100 000 person years in the group with the highest exposure in terms of cumulative dose). Meningiomas located in the anterior skull base and middle skull base, particularly the medial third of the middle skull base, involving the spheno-orbital region, appeared to be specific to cyproterone acetate. An additional analysis of transgender participants showed a high risk of meningioma (three per 14 460 person years; 20.7 per 100 000 person years). Conclusions A strong dose-effect relation was observed between use of cyproterone acetate and risk of intracranial meningiomas. A noticeable reduction in risk was observed after discontinuation of treatment.

“THE EFFECT OF CYPROTERONE ACETATE AND ETHINYLESTRADIOL COMBINATION ON HYPERANDROGENIC AND OTHER SYMPTOMS IN PCOS”

INTRODUCTION- Polycystic ovarian syndrome (PCOS) is a common, heterogeneous disorder affecting 5-15% of women of reproducing age group and characterized by hyperandrogenic skin symptoms, (acne, Hirsutism and female pattern alopecia,) irregular menstrual bleeding, obesity, dysmenorrhea infertility, and increased risk of metabolic syndrome and endometrial cancer. MATERIAL AND METHOD-The present study was conducted in a private gynecological Clinic Shivpuri, (M.P.). After taking Consent women suffering from PCOS (Fullled the clinical and USG criteria of PCOS(Rotterdam criteria )) along with androgenic symptoms like acne, hirsutism and androgenetic alopecia with or without other symptoms like menstrual irregularities and dysmenorrhea were included in the study.. All patients then received a combination of ethenyl Estradiol (0.035mg) + Cyproterone acetate (2mg). The Patients were followed in the third month, Sixth month, and at about 1 year for improvement in various complaints RESULT- According to presenting symptoms the most common presenting symptom was acne 72.72%, followed by menstrual irregularities 68.18%, hirsutism 50%, alopecia 27.27%, and dysmenorrhea in 27.27%. In acne patients, 37.5% of patients showed improvement after 3 cycles of CPA/EE, 75% showed at 6 months and in 93.75%, improvement was seen at 12 months. In the case of alopecia (83.33%) patient showed improvement after >6 cycles. Patients with hirsutism showed no improvement after 3 months of therapy but 54.54% of the patients showed a change in texture after 6 months of therapy and 72.72% after 9-12 months of therapy. Patients with dysmenorrhea reported a decrease in pain after therapy. The acceptance of the treatment was very good. In 86.36% of patients, good tolerance of drug was seen and in only 3 patients adverse effects (headache and nausea) of the drug were there. All the patients were having good to moderate satisfaction with the therapy. CONCLUSION- Since androgen excess is the prime defect in polycystic ovarian disease, its reduction is the main therapeutic target for most women. Our study found that combined hormonal contraceptives containing ethenyl Estradiol (0.035mg) + Cyproterone acetate (2mg) in a 21/7 regimen had a positive effect in the treatment of acne, hirsutism, menstrual irregularity, and dysmenorrhea in PCOS patients.

Possible Meningioma Comorbidity in Male Sickle Cell Cyproterone Acetate Recipients; Short Article

Despite the proven usefulness of cyproterone acetate in therapy for priapism, credible concerns arise over its effects on patients as scientific literature correlates it to development..

Innovative C2-symmetric testosterone and androstenedione dimers: Design, synthesis, biological evaluation on prostate cancer cell lines and binding study to recombinant CYP3A4.

The synthesis of two isomeric testosterone dimers and an androstenedione dimer is reported. The design takes advantage of an efficient transformation of testosterone leading to the synthesis of the key diene, 7α-(buta-1,3-dienyl)-4-androsten-17β-ol-3-one, through an elimination reaction. It was found that in some instances the same reaction led to partial epimerization of the 17β-hydroxyl group into the 17α-hydroxyl group. The specific orientation of the hydroxyl function was confirmed by NMR spectroscopy. Capitalizing on this unforeseen side reaction, several dimers were assembled using an olefin metathesis reaction with Hoveyda-Grubbs catalyst. This led to the formation of two isomeric testosterone dimers with 17α-OH or 17β-OH (14α and 14β) as well as an androstenedione dimer (14). The new dimers and their respective precursors were tested on androgen-dependent (LNCaP) and androgen independent (PC3 and DU145) prostate cancer cells. It was discovered that the most active dimer was made of the natural hormone testosterone (14β) with an average IC50 of 13.3μM. In LNCaP cells, 14β was ∼5 times more active than the antiandrogen drug cyproterone acetate (IC50 of 12.0μM vs. 59.6μM, respectively). At low concentrations (0.25-0.5μM), 14α and 14β were able to completely inhibit LNCaP cell growth induced by testosterone or dihydrotestosterone. Furthermore, cross-reactivity of androgen-based dimers with sterol-metabolizing cytochrome P450 3A4 was explored and the results are disclosed herein.

Intracranial Meningiomas Decrease in Volume on Magnetic Resonance Imaging After Discontinuing Progestin.

The behavior of meningiomas under influence of progestin therapy remains unclear. To investigate the relationship between growth kinetics of intracranial meningiomas and usage of the progestin cyproterone acetate (PCA). This study prospectively followed 108 women with 262 intracranial meningiomas and documented PCA use. A per-meningioma analysis was conducted. Changes in meningioma volumes over time, and meningioma growth velocities, were measured on magnetic resonance imaging (MRI) after stopping PCA treatment. Mean follow-up time was 30 (standard deviation [SD] 29) mo. Ten (4%) meningiomas were treated surgically at presentation. The other 252 meningiomas were followed after stopping PCA treatment. Overall, followed meningiomas decreased their volumes by 33% on average (SD 28%). A total of 188 (72%) meningiomas decreased, 51 (20%) meningiomas remained stable, and 13 (4%) increased in volume of which 3 (1%) were surgically treated because of radiological progression during follow-up after PCA withdrawal. In total, 239 of 262 (91%) meningiomas regressed or stabilized during follow-up. Subgroup analysis in 7 women with 19 meningiomas with follow-up before and after PCA withdrawal demonstrated that meningioma growth velocity changed statistically significantly (P=.02). Meningiomas grew (average velocity of 0.25 mm3/day) while patients were using PCA and shrank (average velocity of -0.54 mm3/day) after discontinuation of PCA. Ninety-one percent of intracranial meningiomas in female patients with long-term PCA use decrease or stabilize on MRI after stopping PCA treatment. Meningioma growth kinetics change significantly from growth during PCA usage to shrinkage after PCA withdrawal.

The effect of short-term use of finasteride versus cyproterone acetate on perioperative blood loss with monopolar transurethral resection of prostate

BackgroundPerioperative 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.MethodsThis 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.ResultsOur 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 < 0.0001), respectively, significant decrease in post-operative Hb and HCT value in finasteride and control groups in comparison with CPA group (p < 0.01), significant increase in specimen weight in CPA group compared to other groups (p < 0.01), and there was also significant decrease in microvascular density in CPA group in comparison with other groups (p < 0.01).ConclusionCyproterone acetate is more effective than finasteride in decreasing perioperative bleeding with TURP by decreasing microvascular density of the prostate.

The influence of testosterone suppression on HER2 immunoexpression in prostatic neoplastic tissue.

During initial risk assessments, the metastatic potential of prostate cancer (PCa) may not be fully considered. The tumor's multicentric origin, which is associated with genetic mutations, may explain existing treatment limitations. Investigating human epidermal growth factor receptor 2 (HER2) expression in patients with different stages of PCa may therefore increase understanding of the mechanisms associated with the development of castration resistance. The present study examined the association between HER2 expression and the histologic features of PCa subjected to radical prostatectomy (RP) and evaluated the role of testosterone suppression in HER2 expression. In group 1, specimens from individuals who underwent RP without prior neoadjuvant androgen deprivation therapy (ADT) were included (n=42). In group 2 (PCa with ADT), specimens from individuals who underwent RP and received neoadjuvant cyproterone acetate during distinct periods (200 mg daily for 1-24 months) were included (n=150; cohort derived from a previous study). Immunohistochemical expression of HER2 was associated with prognostic factors such as perineural invasion, extra-prostatic disease, T stage, serum prostate-specific antigen (PSA), angiolymphatic invasion and surgical margins. Univariate regression analysis indicated that perineural invasion, PSA, International Society of Urological Pathology, angiolymphatic invasion, margin, T stage and neoadjuvant ADT was associated with HER2 expression. Ordinal regression analysis indicated a significant effect of neoadjuvant ADT alone on HER2 expression (P<0.001). In addition, regression analysis indicated a significant effect of neoadjuvant ADT alone on HER2 expression (odd ratio=0.01; 95% CI, 0.00, 0.02; P<0.001). HER2 was expressed in PCa samples but was not associated with known prognostic factors. The use of short-acting ADT and the consequent blockage of testosterone effect may suppress the expression of HER2 in PCa cells.

Anti-Androgenic Effects Comparison Between Cyproterone Acetate and Spironolactone in Transgender Women: A Randomized Controlled Trial

Spironolactone and cyproterone acetate are commonly used in feminizing hormone therapy to achieve the goal of female range testosterone level; however, the data on the efficacy comparing between these two anti-androgens are scarce. To compare the anti-androgenic effects between spironolactone and cyproterone acetate as the component of feminizing hormone therapy among transgender women population. The study was single-blinded randomized controlled trial involved 52 transgender women from two transgender health clinics. Each participant received oral estradiol valerate 4 mg/day combined with anti-androgen, spironolactone 100 mg/day or cyproterone acetate 25 mg/day, depending on which group they were randomized to. Clinical and biochemical variables were obtained at baseline and at 12 weeks of feminizing hormone therapy. The change of testosterone level from baseline. Other changes including free testosterone, estradiol, prolactin and lipid profile after the therapy. After a 12 weeks of feminizing hormone therapy, the change of testosterone level in the cyproterone acetate group [558.0 ng/dL (IQR 352.0 to 783.3)] was significantly higher than the spironolactone group [226.2 ng/dL (IQR,-4.3 to 480.1)](p value <0.001). Testosterone and calculated free testosterone in the cyproterone acetate group were significantly lower than the spironolactone group. Consequently, a proportion of the participants who achieved the female range testosterone (<50 ng/dL) was significantly higher in cyproterone acetate group (90%) compared to the spironolactone group (19%). Serious adverse effects observed in cyproterone acetate users were drug-induced liver injury and asymptomatic hyperprolactinemia. The data on the differences between the two anti-androgen could be benefit for the transgender health-care providers in medication selection and adverse-effects counseling. The study design was randomized controlled trial and controlled the estrogen component by prescribed the same type and dose for each participant. However, the study was suffered from the confound feminizing effects from previous hormone therapy and the high drop-out rate. For feminizing hormone therapy, cyproterone acetate had a higher testosterone suppression efficacy than spironolactone. Burinkul S, Panyakhamlerd K, Suwan A, et al. Anti-Andorgenic Effects Comparison Between Cyproterone Acetate and Spironolactone in Transgender Women: A Randomized Controlled Trial. J Sex Med 2021;18:1299-1307.

Nonylphenol and cyproterone acetate effects in the liver and gonads of Lithobates catesbeianus (Anura) tadpoles and juveniles.

Environmental pollution plays an important role in amphibian population decline. Contamination with endocrine disrupting chemicals (EDCs) is particularly worrying due to their capacity to adversely affect organisms at low doses. We hypothesized that exposure to EDCs such as 4-nonylphenol (NP) and cyproterone acetate (CPA) could trigger responses in the liver and gonads, due to toxic and endocrine disrupting effects. Growth rate may also be impaired by contamination. We investigated sublethal effects of a 28-day exposure to three different concentrations of NP and CPA on liver pigmentation, gonadal morphology, body mass, and length of tadpoles and juveniles Lithobates catesbeianus. Liver pigmentation and the gonadal morphologies of treated tadpoles did not differ from control, but growth rate was impaired by both pollutants. Juveniles treated with 10 μg/L NP and 0.025 and 0.25 ng/L CPA displayed increased liver melanin pigmentation, but gonadal morphologies, sex ratios, and body mass were not affected after treatments. The increase in liver pigmentation may be related to defensive, cytoprotective role of melanomacrophages. The decreased growth rate in tadpoles indicates toxic effects of NP and CPA. Thus, contamination with NP and CPA remains a concern and sublethal effects of different dosages of the compounds on native species should be determined.

Structure-based virtual screening of CYP1A1 inhibitors: towards rapid tier-one assessment of potential developmental toxicants

Cytochrome P450 1A1 (CYP1A1) metabolizes estrogens, melatonin, and other key endogenous signaling molecules critical for embryonic/fetal development. The enzyme has increasing expression during pregnancy, and its inhibition or knockout increases embryonic/fetal lethality and/or developmental problems. Here, we present a virtual screening model for CYP1A1 inhibitors based on the orthosteric and predicted allosteric sites of the enzyme. Using 1001 reference compounds with CYP1A1 activity data, we optimized the decision thresholds of our model and classified the training compounds with 68.3% balanced accuracy (91.0% sensitivity and 45.7% specificity). We applied our final model to 11 known CYP1A1 orthosteric binders and related compounds, and found that our ranking of the known orthosteric binders generally agrees with the relative activity of CYP1A1 in metabolizing these compounds. We also applied the model to 22 new test compounds with unknown/unclear CYP1A1 inhibitory activity, and predicted 16 of them are CYP1A1 inhibitors. The CYP1A1 potency and modes of inhibition of these 22 compounds were experimentally determined. We confirmed that most predicted inhibitors, including drugs contraindicated during pregnancy (amiodarone, bicalutamide, cyproterone acetate, ketoconazole, and tamoxifen) and environmental agents suspected to be endocrine disruptors (bisphenol A, diethyl and dibutyl phthalates, and zearalenone), are indeed potent inhibitors of CYP1A1. Our results suggest that virtual screening may be used as a rapid tier-one method to screen for potential CYP1A1 inhibitors, and flag them out for further experimental evaluations.

Low-Dose Cyproterone Acetate Treatment for Transgender Women

BackgroundTransgender women with intact gonads receive lifelong hormonal treatment to suppress physiologic androgen production, the optimal efficacious and safe cyproterone acetate (CPA) dose has not been established. AimTo assess the effectiveness and safety of low-dose (10–20 mg/day) compared with high-dose (50–100 mg/day) CPA treatment. MethodsWe conducted a historical cohort study of transgender women treated at a tertiary center for transgender health. Outcome MeasuresSerum levels of testosterone, estradiol, prolactin, gonadotrophins, liver enzymes, and lipids. ResultsThere were 38 transgender women in the low-dose group and 26 in the high-dose group. Age (median 24.9 years, interquartile range [IQR] 21–30 vs 25 years, IQR 19–35) and follow-up time (median 12 months, IQR 6–23 vs 15 months, IQR 12–36) were similar in the low- and high-dose groups, respectively. Serum gonadotropins and testosterone were suppressed to a similar level at all time points in both groups. Prolactin levels increased significantly in both groups, however, with a more substantial increase in the high- vs the low-dose group (804 ± 121 vs 398 ± 69 mIU/ml at 12 months, respectively, P = .004). Total cholesterol, high-density lipoprotein, low-density lipoprotein, and triglyceride levels were not significantly affected by the dose. Clinical ImplicationsWe suggest an adjustment of current clinical practice guidelines to recommend lower doses of CPA for the treatment of transgender women. Strengths & LimitationsThis is the first demonstration that low-dose CPA treatment of transgender women is effective. Limitations include a relatively small sample and retrospective study design. ConclusionLow-dose CPA treatment of transgender women is as effective as high-dose treatment and possibly safer.Zohar NE, Sofer Y, Yaish I, et al. Low-Dose Cyproterone Acetate Treatment for Transgender Women. J Sex Med 2021;18:1292–1298.

The consequences of living longer-Effects of an experimentally extended velvet antler phase on the histomorphology of antler bone in fallow deer (Dama dama).

Antlers are periodically regenerated paired cranial appendages of male deer (both sexes in reindeer) that constitute the fastest‐growing bones in the animal kingdom. The annual antler cycle of male deer is linked to testicular activity and largely controlled by seasonal fluctuations of testosterone concentrations in their blood. We studied the effects of an experimental doubling (to eight months) of the velvet antler phase, during which the antlers are covered by skin (velvet), on the histomorphology of antler bone in three adult fallow bucks. Extension of the velvet antler phase in the experimental animals had been caused by administration of the antiandrogen cyproterone acetate (CPA). The distal portions of the antlers from two of the CPA‐treated bucks exhibited partial sequestration of the antler cortex, with the separation plane typically located along the border between cortex and spongiosa. It is hypothesized that this was caused by cortical necrosis due to severe ischemia during later stages of the extended velvet antler phase. In places, new cancellous bone had been deposited on the resorption surface of the spongiosa, indicating a regeneration process. Normal fallow deer antlers (“controls”) from this and a previous study, that is, antlers with a timespan of about four months between onset of new antler growth and velvet shedding, exhibited no or only minor bone remodeling and still contained remnants of calcified cartilage in their distal portions. In contrast, the antlers of the three CPA‐treated bucks showed evidence (secondary osteons and resorption cavities) of marked bone remodeling along their entire length and lacked remnants of calcified cartilage. Our results underscore that the typical histological features of antler bone reflect its short‐lived nature. Antlers are not mechanically loaded during the velvet stage, and it is presently unclear what triggered remodeling activity in the antlers whose lifespan had been experimentally extended.

Leukocyte Profile of Tadpoles and Juveniles of Lithobates catesbeianus Shaw, 1802 (Anura) and the Effects of Nonylphenol and Cyproterone Acetate

Amphibians are threatened with extinction worldwide, and one of the global causes is environmental pollution. Several toxicants can interfere with their immune system, making them more susceptible to disease, which also contributes to their decline. The contaminants 4-nonylphenol (NP), a detergent with estrogenic properties, and cyproterone acetate (CPA), an anti-androgenic medicine, are known to impair the immune system of some vertebrates, but the effects are understudied in anurans. In this study, we evaluated the effects of NP (at 1, 10, and 100 µg/L) and CPA (at 0.025, 0.25, and 2.5 ng/L) on leukocyte count in tadpoles and juveniles of Lithobates catesbeianus. We analyzed lymphocytes, neutrophils, basophils, eosinophils, monocytes, and thrombocytes in a proportional count and made comparisons between the groups. The experiments lasted 28 d, and the conditions were almost identical for both stages (varying only the volume of water). The tadpoles showed decreased lymphocytes and increased neutrophils at 1 µg/L NP and increased eosinophils at the two highest doses of CPA. The juveniles showed reduced neutrophils in all treatments with both compounds and increased thrombocytes (except at 2.5 ng/L CPA). Also, all dosages of CPA increased basophils. Although the life-stages had different response patterns, our study showed that NP and CPA altered the proportion of leukocytes on blood stream in both stages, probably as a response against the negative effects of the compounds, which might make the animals more susceptible to diseases and contribute to their decline.

Serum and intratesticular inhibin B, AMH, and spermatogonial numbers in trans women at gender-confirming surgery: An observational study.

Anti-Müllerian hormone and inhibin B are produced by Sertoli cells. Anti-Müllerian hormone secretion indicates an immature Sertoli cell state. Inhibin B serves as a marker of male fertility. Identification of markers reflecting the presence of germ cells is of particular relevance in trans persons undergoing gender-affirming hormone therapy in order to offer individualized fertility preservation methods. Serum and intratesticular inhibin B and anti-Müllerian hormone values were assessed and related to clinical features, laboratory values, and germ cell numbers. Twenty-two trans women from three clinics were included. As gender-affirming hormone therapy, 10-12.5mg of cyproterone acetate plus estrogens were administered. Height, weight, age, medication, and treatment duration were inquired by questionnaires. Serum luteinizing hormone, follicle-stimulating hormone, testosterone, and estradiol were measured by immuno-assays. Serum and intratesticular inhibin B and anti-Müllerian hormone were measured by commercially available ELISAs. Spermatogonia were quantified as spermatogonia per cubic millimeter testicular tissue applying a morphometric analysis of two independent testicular cross-sections per individual after MAGEA4 immunostaining. Patients with high inhibin B levels presented with a higher number of spermatogonia (*p<0.05). Furthermore, mean serum inhibin B was associated with low age (*p<0.05), low follicle-stimulating hormone (*p<0.05), and low testosterone (*p<0.05). Serum anti-Müllerian hormone, however, was not related to spermatogonial numbers. It correlated with high testosterone (*p<0.05) and high follicle-stimulating hormone (*p<0.05) only. High intratesticular inhibin B was accompanied by high luteinizing hormone (*p<0.05), high follicle-stimulating hormone (**p<0.01), and high testosterone levels (**p<0.01). Higher the intratesticular anti-Müllerian hormone levels, the longer gender-affirming hormone therapy was administered (*p<0.05). Serum inhibin B levels indicate the presence of spermatogonia, whereas anti-Müllerian hormone seems not to be a reliable marker concerning germ cell abundance.

Toward a Lowest Effective Dose of Cyproterone Acetate in Trans Women: Results From the ENIGI Study.

ContextCyproterone acetate (CPA) is a competitive inhibitor of the androgen receptor and exerts negative hypothalamic feedback. It is often used in combination with estrogens in trans women to achieve feminization. However, CPA has been associated with side effects such as changes in liver enzyme concentrations and increases in prolactin concentrations. The question is whether the testosterone-lowering effect, as well as these side effects, are dose dependent.ObjectiveTo assess the lowest effective dose of CPA in trans women to prevent side effects.MethodsThis longitudinal study, conducted at gender identity centers in Amsterdam, Ghent, and Florence, is part of the European Network for the Investigation of Gender Incongruence (ENIGI), a multicenter prospective cohort study. Participants were trans women (n = 882) using estrogens only or in combination with 10, 25, 50, or 100 mg CPA daily. The primary outcome measure was the concentration of testosterone at 3 and/or 12 months of hormone therapy.ResultsUsing estrogens only (without CPA) led to testosterone concentrations of 5.5 nmol/L (standard error of the mean [SEM] 0.3). All doses of CPA resulted in testosterone concentrations below the predefined threshold of suppression of 2 nmol/L (10 mg, 0.9 nmol/L, SEM 0.7; 25 mg, 0.9 nmol/L, SEM 0.1; 50mg, 1.1 nmol/L, SEM 0.1; 100 mg, 0.9 nmol/L, SEM 0.7). Higher prolactin and lower high-density lipoprotein concentrations were observed with increasing doses of CPA. No differences in liver enzyme concentrations were found between the doses.ConclusionCompared with higher doses of CPA, a daily dose of 10 mg is equally effective in lowering testosterone concentrations in trans women, while showing fewer side effects.

Chinese herbal medicine for subfertile women with polycystic ovarian syndrome.

Chinese herbal medicine for subfertile women with polycystic ovarian syndrome.

MANAGEMENT OF ENDOCRINE DISEASE: Optimal feminizing hormone treatment in transgender people.

Transgender women are assigned male at birth but identified as women. The incidence of gender dysphoria is estimated to be around 1% of the population. Gender dysphoria may be associated with depression and low quality of life, which in most cases improves during gender-affirming hormonal treatment (GAHT). Feminizing hormonal treatment for transgender women or gender non-binary people typically includes natural estrogen (estradiol). Additional testosterone-blocking treatment is often needed to ensure the suppression of the pituitary-gonadal axis and may include cyproterone acetate, a gonadotropin-releasing hormone agonist (GnRH-a), or spironolactone. The health risks of cyproterone acetate as anti-androgen treatment are debated and randomized protocols with other anti-androgen treatments are requested. Orchiectomy is performed in some transgender women after various duration of GAHT. Currently, natural progesterone is not recommended as part of GAHT due to limited knowledge on the balance between risks and benefits. In the present article, we discuss evidence regarding established and upcoming feminizing treatment for adult transgender women or gender non-binary people seeking feminization. Data on study populations with transgender women are put into a wider context of literature regarding the effects of sex steroid hormones in cisgender study populations. Relevant follow-up and monitoring during feminizing treatment is debated. The review has a special focus on the pharmacotherapy of feminizing hormonal therapy.

Contraceptive progestins with androgenic properties stimulate breast epithelial cell proliferation

Hormonal contraception exposes women to synthetic progesterone receptor (PR) agonists, progestins, and transiently increases breast cancer risk. How progesterone and progestins affect the breast epithelium is poorly understood because we lack adequate models to study this. We hypothesized that individual progestins differentially affect breast epithelial cell proliferation and hence breast cancer risk. Using mouse mammary tissue ex vivo, we show that testosterone‐related progestins induce the PR target and mediator of PR signaling‐induced cell proliferation receptor activator of NF‐κB ligand (Rankl), whereas progestins with anti‐androgenic properties in reporter assays do not. We develop intraductal xenografts of human breast epithelial cells from 36 women, show they remain hormone‐responsive and that progesterone and the androgenic progestins, desogestrel, gestodene, and levonorgestrel, promote proliferation but the anti‐androgenic, chlormadinone, and cyproterone acetate, do not. Prolonged exposure to androgenic progestins elicits hyperproliferation with cytologic changes. Androgen receptor inhibition interferes with PR agonist‐ and levonorgestrel‐induced RANKL expression and reduces levonorgestrel‐driven cell proliferation. Thus, different progestins have distinct biological activities in the breast epithelium to be considered for more informed choices in hormonal contraception.

The Effects of Salvia miltiorrhiza on Reproduction and Metabolism in Women with Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis.

Objective Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age. As a traditional medicine, Salvia miltiorrhiza (S. miltiorrhiza) has been widely used in the treatment of many gynecological diseases, but the efficacy of S. miltiorrhiza in women with PCOS has not been assessed. The purpose of this systematic review and meta-analysis was to evaluate the effectiveness and safety of S. miltiorrhiza in women with PCOS. Methods We conducted searches in PubMed, Embase, the Cochrane Library, the China National Knowledge Infrastructure, the Wanfang Database, the Chinese Scientific Journal Database, and the Chinese BioMedical database from inception to December 23, 2020, to identify studies that met the inclusion criteria. The quality of the evidence was estimated using the Cochrane Reviewer Handbook 5.0.0, and the meta-analysis was performed using RevMan 5.3.5 software. Results Six randomized controlled trials (RCTs) involving 390 patients with PCOS were included. The studies suggested that S. miltiorrhiza extract combined with letrozole (LET) was more effective in improving pregnancy rate (RR: 2.60, 95% CI: 1.06 to 6.39, P=0.04) compared to LET alone. S. miltiorrhiza extract was associated with decreased fasting blood glucose (MD: –0.25, 95% CI: –0.37 to –0.13, P < 0.0001), fasting insulin (MD: –1.16, 95% CI: –1.74 to –0.58, P < 0.0001), total cholesterol (TC) (MD: –0.58, 95% CI: –0.72 to –0.43, P < 0.00001), and triglycerides (TG) (MD: –0.31, 95% CI: –0.35 to –0.26, P < 0.00001) compared with placebo, but not with improvements in body mass index or waist-to-hip ratio (MD: –1.41, 95% CI: –4.81 to 2.00, P=0.42; MD: –0.02, 95% CI: –0.05 to 0.01, P=0.16, respectively). There was a significant difference between S. miltiorrhiza extract combined with cyproterone acetate (CPA) and CPA alone in terms of decreasing TC (MD: –0.77, 95% CI: –0.89 to –0.65, P < 0.00001), TG (MD: –0.43, 95% CI: –0.65 to –0.20, P < 0.0001), and low-density lipoprotein cholesterol (MD: –0.49, 95% CI: –0.66 to –0.33, P < 0.00001) and increasing high-density lipoprotein cholesterol (MD: 0.30, 95% CI: 0.20, 0.40, P < 0.00001). In addition, S. miltiorrhiza extract also decreased testosterone, follicle-stimulating hormone, and luteinizing hormone. The studies did not mention any adverse events with S. miltiorrhiza extract. Conclusion The current studies indicate that S. miltiorrhiza has beneficial effects on reproduction and glucose and lipid metabolism in patients with PCOS, and it is generally safe for clinical application. However, more prospective RCTs with large samples, multiple centers, and longer intervention duration are needed in the future to obtain more reliable conclusions.

First case of cyproterone acetate induced multiple meningiomas in identical female twins: A case report

Meningiomas are the most common tumors of the central nervous system. Most meningiomas are benign and occur mainly in middle-aged women. Only a few cases of meningiomas in identical twins have been reported. Cyproterone acetate (Androcur® Bayer Healthcare SAS) (CPA) is an antiandrogenic progestin used to treat female hirsutism in some countries including France. We report a case of identical twin sisters who developed multiple, atypically located meningiomas in the setting of long-term CPA use. Eighteen-month follow-up showed spontaneous decrease of meningiomas after cessation of CPA. This case illustrates CPA's ability to induce development of atypically located meningiomas that differ even between identical twins, confirms benefit of surgical abstention, and raises questions regarding security of use of CPA.