Cyproterone Acetate Research Articles

Further data against the use of cyproterone acetate in gender affirming hormone therapy regimens.

Further data against the use of cyproterone acetate in gender affirming hormone therapy regimens.

5065 Cyproterone Acetate Versus Spironolactone In Transgender Women Commencing Estradiol: A Randomized Controlled Trial

Abstract Disclosure: L.M. Angus: Advisory Board Member; Self; Kirin Brewery. Speaker; Self; Kirin Brewery. S. Leemaqz: None. A. Kasielska-Trojan: None. M. Mikołajczyk: None. J. Doery: None. J.D. Zajac: None. A.S. Cheung: None. Background: Transgender women commonly use cyproterone acetate or spironolactone as anti-androgens with estradiol to assist with feminization. However, the optimal anti-androgen is unclear. We aimed to assess the effect of these anti-androgens on breast development and hypothesized that cyproterone acetate would result in greater breast development than spironolactone due to greater androgen receptor antagonism and suppression of serum total testosterone. Design: Double-blind, randomised controlled trial Methods: Transgender women newly commencing estradiol were randomized to spironolactone 100mg daily or cyproterone acetate 12.5mg daily for six months. The primary outcome was measurement of breast development via breast chest distance with secondary outcomes of estimated breast volume using the BreastIdea Volume Estimator application and serum total testosterone using LCMS. Results: Fifty-five participants were included in per protocol analysis (cyproterone acetate group n=28, spironolactone group n=27). Baseline age, body mass index, breast indices, serum estradiol and serum total testosterone were comparable. At six months, the mean (standard deviation) breast chest distance was 9.2cm (3.0) in the cyproterone group versus 8.3cm (2.7) in the spironolactone group (p=0.27). The mean (SD) estimated breast volume was 190.25 mL (158.60) in the cyproterone acetate group and 157.84mL (112.03) in the spironolactone group (p=0.39) with significant inter-individual variation (range 20.27 - 787.77 mL). The mean (SD) serum total testosterone was 1.48 nmol/L (3.45) in the cyproterone acetate group and 4.29 nmol/L (5.44) in the spironolactone group (p=0.04). Serum estradiol levels were comparable. Use of cyproterone acetate was associated with mild hyperprolactinaemia and spironolactone with an increase in serum urea and creatinine. Conclusions: Choice of anti-androgen should be individualised based on clinician and patient preference, with consideration of associated side effects. Further research is needed to optimise breast development in transgender women. Presentation: 6/3/2024

8614 Low Dose Sublingual Estradiol Decreases Protein S, Generating a Potentially Pro-thrombotic Profile: Interim Results of a Controlled Prospective Pilot Study of Treatment-Naïve Trans Women

Abstract Disclosure: S. Bar On: None. I. Yaish: None. M. Barzilai: None. Y. Greenman: None. G. Gindis: None. Y. Moshe: None. K.M. Tordjman: None. Background: Sublingual estradiol (SLE) for gender-affirming hormone therapy (GAHT) of transgender women (TW) might obviate the need for an anti-androgen, and mitigate pro-coagulant changes. We recently showed that 2 mg E, divided into 4 daily sublingual doses, offers no clinical advantage over the same dose given orally in combination with cyproterone acetate (CPA)1. Furthermore, we showed that after each sublingual administration, serum estradiol (sE2) peaked to levels, the likes of which are achieved only during induction of ovulation with gonadotrophins. Hypothesis and Aim: Given the exceedingly high peak sE2 measured under SLE-GAHT, we hypothesized it could lead to partial acquired Protein S deficiency, a recognized pro-thrombotic state and risk factor for venous thromboembolic events (VTE). Our aim was to assess the hemostatic system under SLE in comparison with the standard combined oral (CO) approach. Design and Methods: In this ongoing open label study, treatment-naïve TW are assigned in a 1:1 ratio (15 in each arm) to either standard CO (2 mg E2 with 10 mg CPA once daily), or to SLE with 2 mg sublingual estradiol divided into 4 daily dose for 6 months (6M). An extensive battery of hemostatic biomarkers, including free Protein S antigen (fPS), are assessed at baseline (BL) and at 6M. Results: We herein report on 27 subjects (15 CO/12 SLE) who initiated treatment, 17 of whom have already completed it. The median age of the cohort is 20 y (IQR 19-27; range 18-42]. There were no BL differences between the groups. At 6M, none of the hemostatic markers differed between the groups except for fPS, which was significantly lower in the SLE group 79.7%±11.6% vs. 104.6%±5.6%, P=0.039. By paired comparisons for the entire group, fPS decreased from 104%.2±5.2% at BL to 95.8%±5.9% at 6M, P=0.003. This was entirely accounted for by the change in the SLE group, in which fPS went down from 95.7%±10.3% to 79.7%±11.6%, P<0.001; with some values reaching the fPS deficiency range. In contrast, fPS, remained unchanged under CO 108.9%±5.7% and 104.5%±5.2%, at BL and 6M respectively, P=0.153. Conclusions: The most notable interim finding was a clinically significant decrease in fPS under low dose SLE. Given the extreme peaks of sE2 we previously reported with this protocol, an acquired deficiency of this natural anti-coagulant was expected. These preliminary findings support our hypothesis, and raise the concern that GAHT of TW with chronic SLE might carry an increased long-term risk for VTE. 1 Yaish I, Gindis G, Greenman Y, et al. Sublingual Estradiol Offers no Apparent Advantage Over Combined Oral Estradiol and Cyproterone Acetate for Gender-Affirming Hormone Therapy of Treatment-Naive Trans Women: Results of a Prospective Pilot Study. Transgend Health. 2023;8(6):485-493. Published 2023 Dec 13. doi:10.1089/trgh.2023.0022 Presentation: 6/2/2024

8614 Low Dose Sublingual Estradiol Decreases Protein S, Generating a Potentially Pro-thrombotic Profile: Interim Results of a Controlled Prospective Pilot Study of Treatment-Naïve Trans Women

Abstract Disclosure: S. Bar On: None. I. Yaish: None. M. Barzilai: None. Y. Greenman: None. G. Gindis: None. Y. Moshe: None. K.M. Tordjman: None. Background: Sublingual estradiol (SLE) for gender-affirming hormone therapy (GAHT) of transgender women (TW) might obviate the need for an anti-androgen, and mitigate pro-coagulant changes. We recently showed that 2 mg E, divided into 4 daily sublingual doses, offers no clinical advantage over the same dose given orally in combination with cyproterone acetate (CPA)[1]. Furthermore, we showed that after each sublingual administration, serum estradiol (sE2) peaked to levels, the likes of which are achieved only during induction of ovulation with gonadotrophins. Hypothesis and Aim: Given the exceedingly high peak sE2 measured under SLE-GAHT, we hypothesized it could lead to partial acquired Protein S deficiency, a recognized pro-thrombotic state and risk factor for venous thromboembolic events (VTE). Our aim was to assess the hemostatic system under SLE in comparison with the standard combined oral (CO) approach. Design and Methods: In this ongoing open label study, treatment-naïve TW are assigned in a 1:1 ratio (15 in each arm) to either standard CO (2 mg E2 with 10 mg CPA once daily), or to SLE with 2 mg sublingual estradiol divided into 4 daily dose for 6 months (6M). An extensive battery of hemostatic biomarkers, including free Protein S antigen (fPS), are assessed at baseline (BL) and at 6M. Results: We herein report on 27 subjects (15 CO/12 SLE) who initiated treatment, 17 of whom have already completed it. The median age of the cohort is 20 y (IQR 19-27; range 18-42]. There were no BL differences between the groups. At 6M, none of the hemostatic markers differed between the groups except for fPS, which was significantly lower in the SLE group 79.7%±11.6% vs. 104.6%±5.6%, P=0.039. By paired comparisons for the entire group, fPS decreased from 104%.2±5.2% at BL to 95.8%±5.9% at 6M, P=0.003. This was entirely accounted for by the change in the SLE group, in which fPS went down from 95.7%±10.3% to 79.7%±11.6%, P<0.001; with some values reaching the fPS deficiency range. In contrast, fPS, remained unchanged under CO 108.9%±5.7% and 104.5%±5.2%, at BL and 6M respectively, P=0.153. Conclusions: The most notable interim finding was a clinically significant decrease in fPS under low dose SLE. Given the extreme peaks of sE2 we previously reported with this protocol, an acquired deficiency of this natural anti-coagulant was expected. These preliminary findings support our hypothesis, and raise the concern that GAHT of TW with chronic SLE might carry an increased long-term risk for VTE. [1] Yaish I, Gindis G, Greenman Y, et al. Sublingual Estradiol Offers no Apparent Advantage Over Combined Oral Estradiol and Cyproterone Acetate for Gender-Affirming Hormone Therapy of Treatment-Naive Trans Women: Results of a Prospective Pilot Study. Transgend Health. 2023;8(6): 485-493. Published 2023 Dec 13. doi:10.1089/trgh.2023.0022 Presentation: 6/2/2024

12480 REMS Technology For The Bone Health Assessment After Hormonal Therapy In Transgender Subjects

Abstract Disclosure: F.A. Lombardi*: None. A. Russo: None. P. Pisani*: None. C. Stomaci*: None. F. Conversano*: None. R. Franchini*: None. M. Di Paola*: None. V. Racanelli*: None. S. Casciaro: None. Introduction: Sex steroid hormones play crucial roles in bone metabolism and the musculoskeletal system. These hormones interact with specific nuclear receptors, such as estrogen and androgen receptors, which are expressed in bone tissue. This interaction regulates the ongoing process of bone remodeling and induces positive effects on bone health.In this regard, it is crucial to examine the long-term impact of gender affirming hormone therapy (GAHT) on bone metabolism. Radiofrequency Echographic Multi-spectrometry (REMS) is a radiation-free technology for assessing bone mineral density (BMD) and fracture risk prediction by the analysis of the reference axial sites: lumbar spine (LS) and femoral neck (FN). REMS has been widely validated in comparison with Dual Energy X-ray Absorptiometry (DXA), showing good accuracy and precision (>90%), thereby representing a valid technology to monitor bone health status (BHS) in a short-term period. In this context, the goal of this preliminary clinical study was to track the bone health of transgender subjects for one year after starting treatment, using REMS, in order to comprehend the effects of GAHT on BHS. Methods: 7 transgender patients were recruited at Endocrinology Unit of Internal Medicine Department of Santa Chiara Hospital Trento (Italy). Among them were 4 individuals assigned male at birth (AMAB) undergoing therapy with oestradiol valerate 2 g/day and cyproterone acetate 25 mg/day, as well as 3 individuals assigned female at birth (AFAB) undergoing therapy with testosterone 25 mg/day. Before starting GAHT, patients underwent LS-DXA scan, followed by monitoring of BHS by REMS technology after 12 months from the start of treatment. Results: The results show an increase of T-score values in AMAB (-0,3 ± 0,3 REMS vs -1,8 ± 1,8 DXA) after estrogen treatment starting, and no effect on bone in AFAB subjects after GAHT (0.5 ± 0.4 REMS vs 0.9 ± 0.4 DXA); this is due to:-the protective effect of estrogen therapy in AMAB subjects against bone loss;-the combined effect of the decrease of estrogen together with the increase of testosterone in AFAB ones. Conclusions In summary, these initial findings indicate that REMS could be appropriate for monitoring the bone health status of these individuals, confirming the anticipated beneficial effects of estrogen therapy on bone loss in AMAB individuals. The limitation of the study is the lack of REMS data at the beginning of the treatment, but the possibility of carrying out the technique in subsequent evaluation times will allow us to evaluate the change in bone mass during hormonal reaffirmation therapy and compare it with the progress of the measurements obtained with DXA data ones. Presentation: 6/2/2024

Therapeutic and skincare products used in hirsutism and hypertrichosis

Introduction. Hirsutism is a disorder manifested by excessive hair growth in the telogen phase in androgen-dependent areas: on the face, lower back, thighs and breasts in women with hormonal disorders. Hypertrichosis is excessive hair covering the entire skin surface or limited to certain areas of the skin, independent of androgens. It may occur in both men and women and is not limited to androgen-dependent areas. Hormonal disorders are not observed in hypertrichosis. It may be genetically determined or caused by medications taken by the patient: minoxidil or cyclosporine A. Hypertrichosis most often occurs on the arms and lower legs. Aim. The aim of the study was to identify the therapeutic and skincare products used in hirsutism and hypertrichosis available on the Polish market. Material and methods. In 2022 and 2023, therapeutic and skincare products used in hirsutism and hypertrichosis available in 10 randomly selected pharmacies and 10 drugstores in the Lubelskie Voivodeship in Poland were analyzed. Results. Together 53 therapeutic and skincare products used in hirsutism and hypertrichosis were found. The therapeutic products were available with doctor’s prescription only (Rp.), while the skincare products were available without prescription, like cosmetics. In the analyzed preparations for hirsutism, the most frequently used active substances are dienogest and cyproterone acetate. Conclusion. The most commonly used form of drugs in hirsutism are tablets, and in hypertrichosis – foams that facilitate the removal of unwanted hair. The new promising formulas for treatment of hirsutism and hypertrichosis contain eflornithine, acyclovir, licorice and vitamin D. Keywords: hirsutism, hypertrichosis, skincare products, therapeutic products.

P194 VERY LOW-DOSE CYPROTERONE ACETATE (12.5 MG/DAY) IS EFFECTIVE AS ANDROGEN BLOCKER; WELL TOLERATED AND NOT ASSOCIATED WITH HYPERTENSION DEVELOPMENT IN YOUNG FEMALE TRANSGENDER PEOPLE

Background and Objective: Cyproterone acetate (CPA) has serious adverse effects (hyperprolactinemia, obesity, depression, thrombogenesis, liver toxicity, meningioma…) but the optimal dose has not been established. CPA is associated with a high risk of hypertension development, even with doses as low as 25 mg/day. We sought to establish if a very low CPA dose (12.5 mg/day) is effective as antiandrogen, its side effect profile, and if it is associated with hypertension development. Methods: Consecutive non-orchidectomized transgender women <30 years were offered CPA 12.5 mg/day instead of the regular 50-100 mg/day dose, along with estradiol (individually titrated); CPA dose was increased to 25 (eventually 50) mg/day if plasma testosterone was >2 nmol/L or there was clinical hyperandrogenism. Body weight, blood pressure, AST, ALT, GGT, prolactin, FSH, LH, estradiol and testosterone were monitored. A matched group of patients with LHRH agonist as antiandrogen plus estradiol served as control. Hypertension was diagnosed according to the current ESH guidelines. All patients gave informed consent. Results: 39 patients were recruited, median follow-up was 2.3 years. 32 were maintained on CPA 12.5 mg/day, two increased to 25 mg/day, one to 50 mg/day, two withdrew due to gender-affirming surgery; one was lost to follow-up. There were no serious side effects or related withdrawals. The control group included 35 patients without significant differences at baseline. Suppression of testosterone, LH and FSH were effective and comparable with the control group but a moderate increase in prolactin was observed (26±12 to 38±22 ng/mL, p=0.034). Neither group had changes in liver enzymes. Blood pressure and body weight did not increase significantly in either group; the incidence of hypertension was low in both groups (1 patient each). Conclusions: Very low-dose CPA was effective and well tolerated as antiandrogen in a large majority of our patients. While CPA is reportedly associated with a striking dose-dependent increase in the incidence of hypertension in the 25-100 mg/day dose-range, the 12.5 mg/day dose appears to be safer.

Effectiveness of low dose cyproterone acetate compared to standard dose in feminizing hormone treatment: a single institutional retrospective pilot study.

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. To assess the effectiveness in testosterone suppression using low-dose CPA (<25mg/day) compared to standard-dose CPA (25-50mg/day) in FHT. 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. The main outcomes included a median time when the testosterone was suppressed (<50ng/dL), the proportion of individuals AMAB who achieved the targeted testosterone level at 3months, and the testosterone level at each follow-up. Changes in clinical data were assessed. 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 (12.5mg/day), and 15 individuals AMAB started with standard-dose CPA. The median time to reach targeted testosterone was 3months in both groups (adjusted hazard ratio 0.60, P = .489). At 3months, 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). This study supports a paradigm shift toward using lower-dose CPA in FHT. This is one of a few studies showing the effectiveness of low-dose CPA in testosterone suppression within 3months. Limitations include a small sample size and missing data. Testosterone suppression is comparable between CPA 12.5mg/day and the standard dose in FHT.

Gender Incongruence: Prevalence and Therapeutic Options Among Transsexuals Belonging to a Single Center.

This study aimed to describe characteristics and treatment choices among AMABs (Assigned Male At Birth) and AFABs (Assigned Female At Birth) transgenders enrolled from March 2021 to July 2023 at the PTA S. Giorgio of the ASP3-Catania. A total of 145 patients were studied, and there was no prevalence of AMAB/AFAB. At first observation for AMABs, the age was 26 years and 25 years for AFABs, with 11 AMAB/AFAB declared as "non-binary" (average age 17 years). In AMAB/AFAB, we evaluated hormonal treatment, efficacy, and dosage/hormonal levels. In AMABs, oral estradiol valerate (4 mg/day) or transdermal estradiol in gel (2 mg/day) + oral cyproterone acetate (25 mg/day) for both estrogenic formulations were used. Testosterone (TE), LH, FSH, and PRL at baseline and during chronic treatment were measured. In AFABs, we used injectable TE (250 mg/3-4 weeks or 1 g/12-16 weeks) or transdermal TE (60- 80 mg/day). In these patients, we analyzed blood count, LH, FSH, and TE. Hematocrit, hemoglobin, and red blood cell count showed a modest elevation after 4-6 months of treatment. About 32% of AFABs complained of transient uterine bleeding, but no hypertension or ovarian pathology was detected. In AMABs, despite the short observation period, no patient showed an increased risk of myocardial infarction and ischemic stroke. Among AFABs, no increased risk of cardiovascular or cerebrovascular disease was observed. Furthermore, given the complexity of the phenomenon, the integration between the different professional figures who require specific and qualified skills is fundamental.</p>.

P-105 Gender affirming hormone therapy affects the spermatogonial cell compartment in transwomen

Abstract Study question What are the specific changes under gender affirming hormone therapy (GAHT) in the spermatogonial cell compartment in testicular tissues of transwomen? Summary answer GAHT has a negative effect on the most undifferentiated PIWIL4+ spermatogonia potentially leading to reduced chances for fertility preservation in transwomen. What is known already Transwomen take GAHT to achieve transition between the gender assigned at birth and their gender identity. GAHT leads to a reduction of the most advanced germ cells and a reduction of MAGEA4 positive spermatogonia (pan spermatogonial marker). Single-cell RNA sequencing studies identified spermatogonial subpopulations based on the expression of the marker genes PIWIL4, FGFR3, NANOS3, GFRA1, KIT, UTF1. PIWIL4+ cells are considered the origin of germ cell differentiation (state 0). State 1 and 2 spermatogonia are characterized by expression of GFRA1 and KIT, respectively. Study design, size, duration On the day of gender affirming surgery (GAS) testicular tissues and blood samples were collected of 25 age matched trans women (mean 28.1 yr), who underwent comparable GAHT regimens (10 or 12.5 mg cyproterone acetate and estrogens) between 2013 and 2018. 8 adult cis men (mean 34.5 yr) with complete spermatogenesis served as controls. Age, start and type of GAHT were assessed using a questionnaire. This study was approved by the local ethics committee. Participants/materials, setting, methods We performed immunohistochemical stainings to evaluate the expression of spermatogonial markers (MAGEA4, UTF1, PIWIL4, FGFR3, NANOS3, GFRA1) in Bouin’s-fixed testicular tissue sections. For each marker the number of positive cells per round tubular cross-section was determined in 25 round tubules. The spermatogonial proliferation rate was evaluated using immunofluorescence co-stainings for GFRA1/MIKI67/MAGEA4 and KIT/MKI67/MAGEA4. We scored 400 MAGEA4+ cells per individual and determined the proportion of GFRA1+/KIT+. MKI67+ cells among the GFRA1+/KIT+ were evaluated. Main results and the role of chance The number of MAGEA4+ spermatogonia and the proportion of PIWIL4+ spermatogonia within the MAGEA4+ spermatogonia were reduced in transwomen compared to controls (p &amp;lt; 0.001). In contrast, the relative proportion of UTF1+, FGFR3+ and NANOS3+ spermatogonia was comparable. The number of spermatogonia per tubule correlated negatively with the age at start of GAHT (p &amp;lt; 0.01) and the age on the day of GAS (p &amp;lt; 0.001). The treatment duration correlated negatively with the proportion of PIWIL4+ (p &amp;lt; 0.01) and NANOS3+ spermatogonia (p &amp;lt; 0.05). The immunofluorescence stainings in transwomen revealed a similar ratio of proliferating KI67+ spermatogonia, both within the GFRA1+ and KIT+ cells, compared to controls. These results show the negative effects of the GAHT itself on the population of spermatogonia as well as the individual susceptibility depending on age-related factors. These results have the potential to better define the chances for fertility preservation under GAHT. Limitations, reasons for caution Transwomen are a very heterogeneous patient group varying in age, different GAHT, different treatment durations, intake of co-medications and possible pre-existing medical conditions. Hence, testicular size and histological appearance of transwomen’s testes are heterogeneous. Wider implications of the findings Transwomen, who wish to have own biological children, have to be counseled with regard to fertility preservation, best before initiation of GAHT, in order to avoid adverse effects on spermatogonia. Individual counselling has to take place with regard to fertility preservation. Trial registration number 2012-555-f-S

Transgender healthcare: metabolic outcomes and cardiovascular risk.

Transgender identity is often associated with gender dysphoria and minority stress. Gender-affirming hormone treatment (GAHT) includes masculinising or feminising treatment and is expected to be lifelong in most cases. Sex and sex hormones have a differential effect on metabolism and CVD in cisgender people, and sex hormone replacement in hypogonadism is associated with higher vascular risk, especially in ageing individuals. Using narrative review methods, we present evidence regarding metabolic and cardiovascular outcomes during GAHT and propose recommendations for follow-up and monitoring of metabolic and cardiovascular risk markers during GAHT. Available data show no increased risk for type 2 diabetes in transgender cohorts, but masculinising GAHT increases lean body mass and feminising GAHT is associated with higher fat mass and insulin resistance. The risk of CVD is increased in transgender cohorts, especially during feminising GAHT. Masculinising GAHT is associated with a more adverse lipid profile, higher haematocrit and increased BP, while feminising GAHT is associated with pro-coagulant changes and lower HDL-cholesterol. Assigned male sex at birth, higher age at initiation of GAHT and use of cyproterone acetate are separate risk factors for adverse CVD markers. Metabolic and CVD outcomes may improve during gender-affirming care due to a reduction in minority stress, improved lifestyle and closer surveillance leading to optimised preventive medication (e.g. statins). GAHT should be individualised according to individual risk factors (i.e. drug, dose and form of administration); furthermore, doctors need to discuss lifestyle and preventive medications in order to modify metabolic and CVD risk during GAHT. Follow-up programmes must address the usual cardiovascular risk markers but should consider that biological age and sex may influence individual risk profiling including mental health, lifestyle and novel cardiovascular risk markers during GAHT.

Re: "Sublingual Estradiol Offers No Apparent Advantage Over Combined Oral Estradiol and Cyproterone Acetate for Gender-Affirming Hormone Therapy of Treatment-Naive Trans Women: Results of a Prospective Pilot Study" by Yaish et al.

Re: "Sublingual Estradiol Offers No Apparent Advantage Over Combined Oral Estradiol and Cyproterone Acetate for Gender-Affirming Hormone Therapy of Treatment-Naive Trans Women: Results of a Prospective Pilot Study" by Yaish et al.

Hormonal influences on meningioma risk in women

Summary Meningiomas have been linked to endogenous and exogenous hormones, but the exact mechanisms are unclear. A review of 23 studies (1958–2018) found no significant association between menarche age and meningioma risk. Most contraceptives showed no link, though some specific types indicated high risk. Pregnancy might be protective while breastfeeding over 6 months showed a protective effect in one study. Postmenopausal status increased risk in two studies. Hormone replacement therapy (HRT) results were inconsistent, with some studies indicating increased risk, particularly with long-term use. High cumulative doses of cyproterone acetate (CPA) were significantly associated with increased risk. Overall, hormonal factors’ role in meningioma development varies, with specific hormones and high doses of CPA posing significant risks, suggesting the need for further research.

The Toxic Effects on the Testis of Flutamide vs. Bicalutamide vs. Cyproterone Acetate: An Experimental Rat Study

The aim of this study was to investigate the toxic effects on the rat testis of flutamide, bicalutamide, and cyproterone acetate using histopathological methods. Twenty-four male Sprague-Dawley rats were randomly divided into four groups, control (Group 1), flutamide (Group 2), bicalutamide (Group 3), and cyproterone acetate (Group 4). Physiological saline solution or anti-androgens were administered via oral gavage for 14 days. At the end of the study, the testes were harvested for histological toxic effect scoring. The mean histopathology scores were 0 in Group 1, 0.33 ± 0.81 in Group 2, 1.66 ± 1.36 in Group 3, and 2.93 ± 0.98 in Group 4. The histopathology score in Group 4 was significantly higher than that in Group 1 (p = 0.002), but was not significantly different to those in groups 2 and 3 (p = 0.317 and p = 0.028, respectively). No significant difference was also observed between the other groups. Cyproterone acetate, a steroidal antiandrogen, resulted in significant impairment of testis histology relative to the non-steroidal antiandrogens flutamide and bicalutamide. A non-steroidal agent such as flutamide or bicalutamide should therefore be selected if antiandrogen therapy is to be initiated for reasons such as acne, hirsutism, and paraphilias, particularly in young males.

Aphrodisiac and androgenic effects of the aqueous extract of the roots of Vepris afzelii on cyproterone acetate-induced hypogonadism in rat.

This work aimed to evaluate the effects of the aqueous extract of Vepris afzelii roots on a rat model of hypogonadism. Phytochemical screening and acute toxicity of the extract were performed using different procedures. Hypogonadism was induced orally in adult Wistar rats using cyproterone acetate (30 mg/kg) for ten days. Besides six normal rats (10 ml/kg of distilled water, normal control), 30 hypogonadal rats were subdivided into five groups of six animals each, receiving for 14 days: distilled water (10 ml/kg, hypogonadal control), testosterone (4 mg/kg/3days) and the extract of V. afzelii (100, 200 and 400 mg/kg). Sexual behavior, sperm parameters, testes function and structure were assessed. Compared to the normal controls, significant (p = 0.0000) increases in mount (24 ± 0.94 seconds vs. 1200 ± 00 seconds) and intromission (49.16 ± 10.85 seconds vs. 1200 ± 00 seconds) latencies, and post-ejaculatory interval (381.72 ± 37.55 seconds vs. 1200 ± 00 seconds) were observed in all groups receiving cyproterone acetate on day 0. Total inhibitions of mounts (63.50 ± 8.91 vs. 00 ± 00), intromissions (36.66 ± 3.51 vs. 00 ± 00) (p = 0.0000), ejaculations (2.83 ± 00 vs. 00 ± 00, p = 0.0002) frequencies and mean copulatory interval (627.30 ± 81.80 vs. 00 ± 00, p = 0.0000) were also observed in these groups. Moreover, decreases in daily sperm production (2.65 ± 0.19 vs. 1.17 ± 0.08, p = 0.0498), percentage of sperm mobility (78.64 ± 8.41 vs. 10.12 ± 2.32), serum testosterone level (8.39 ± 0.63 ng/dl vs. 1.68 ± 0.19 ng/dl), diameter of seminiferous tubules (111.97 ± 0.51 µm vs. 94.51 ± 0.57 µm) and height of germinal epithelium (46.58 ± 0.34 µm vs. 33.74 ± 0.66 µm) (p = 0.0000) associated with increases in sperm transit (3.13 ± 0.45 vs. 11.07 ± 1.45, p = 0.0000) were also observed in these groups. Interestingly, compared to hypogonadal control and day 0, the administration of V. afzelii extract induced significant (p = 0.0000) improvements in all these altered parameters with 400 mg/kg being the most active dose. These results, attributed to saponins, flavonoids, polyphenols and triterpenes detected in this plant's extract confirm its traditional usage and could be useful for the management of patients suffering from hypogonadism.

Impact of Distinct Antiandrogen Exposures on the Plasma Metabolome in Feminizing Gender-affirming Hormone Therapy.

The plasma metabolome is a functional readout of metabolic activity and is associated with phenotypes exhibiting sexual dimorphism, such as cardiovascular disease. Sex hormones are thought to play a key role in driving sexual dimorphism. Gender-affirming hormone therapy (GAHT) is a cornerstone of transgender care, but longitudinal changes in the plasma metabolome with feminizing GAHT have not been described. Blood samples were collected at baseline and after 3 and 6 months of GAHT from transgender women (n = 53). Participants were randomized to different anti-androgens, cyproterone acetate or spironolactone. Nuclear magnetic resonance-based metabolomics was used to measure 249 metabolic biomarkers in plasma. Additionally, we used metabolic biomarker data from an unrelated cohort of children and their parents (n = 3748) to identify sex- and age-related metabolite patterns. We identified 43 metabolic biomarkers altered after 6 months in both anti-androgen groups, most belonging to the very low- or low-density lipoprotein subclasses, with all but 1 showing a decrease. We observed a cyproterone acetate-specific decrease in glutamine, glycine, and alanine levels. Notably, of the metabolic biomarkers exhibiting the most abundant "sex- and age-related" pattern (higher in assigned female children and lower in assigned female adults, relative to assigned males), 80% were significantly lowered after GAHT, reflecting a shift toward the adult female profile. Our results suggest an anti-atherogenic signature in the plasma metabolome after the first 6 months of feminizing GAHT, with cyproterone acetate also reducing specific plasma amino acids. This study provides novel insight into the metabolic changes occurring across feminizing GAHT.

Effect of Feminizing Hormone Therapy on QTc Interval

This secondary analysis of a randomized clinical trial investigates the effect of spironolactone and cyproterone acetate hormone therapy on the QT interval corrected for heart rate among transgender women and nonbinary or transfeminine individuals.

Use of progestogens and the risk of intracranial meningioma: national case-control study

ABSTRACTObjectiveTo assess the risk of intracranial meningioma associated with the use of selected progestogens.DesignNational case-control study.SettingFrench National Health Data System (ie, Système National des Données de Santé).ParticipantsOf 108 366 women...

The efficacy of and user satisfaction with different antiandrogens in Chinese transgender women

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.

Effects of gender affirming hormone treatment in transgender individuals - a retrospective cohort study.

Gender affirming hormone treatment (GAHT) results in measurable changes to anthropomorphic, biochemical and hormonal variables that are important to patients and their health care professionals to guide treatment. This study sought to quantify changes which occur in response to initiation of GAHT. We performed a retrospective cohort study of outcomes in transgender and gender diverse (TGD) patients starting GAHT. The primary outcome was proportion of patients and time required to achieve optimal hormone levels after commencement of GAHT. Additional analyses were performed to assess whether clinical and biochemical factors were associated with likelihood of achieving target hormone levels. 345 patients were included. Among 154 transmasculine individuals, 116 (75%) achieved a testosterone level >10 nmol/L during follow-up at a median of 4-months (IQR 4-9). No clinical or biochemical factors were significantly associated with likelihood of reaching therapeutic testosterone concentrations in transmen. Among 191 transfeminine individuals, 131 (72%) achieved a testosterone level <2.0 nmol/L during follow-up at a median of 4-months (IQR 3-9). Factors associated with increased likelihood of testosterone suppression were use of subdermal estradiol implants as well as cyproterone acetate as an androgen antagonist. Changes in differing directions were observed during repeated measures of lipids, liver function, and blood count between transmasculine and transfeminine individuals, reflecting the important effects of testosterone and estradiol on biochemical tests ordered as part of routine clinical care. Most TGD patients achieve target testosterone levels within 9 months of GAHT initiation. Adverse effects of GAHT are rare, and are usually mild.