UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.

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.

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

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

OBJECTIVE: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: Most TGD patients achieve target testosterone levels within 9 months of GAHT initiation. Adverse effects of GAHT are rare, and are usually mild.

BACKGROUND: Cyproterone acetate (CPA) is a synthetic progesterone derivative introduced in the 1970s and prescribed as antiandrogenic therapy for inoperable prostate cancer, sexual deviations in men, and signs of androgenization in women. In 2020, the CPA summary of product characteristics (SmPC) was revised to include an updated special warning and precaution about (1) the risk of meningioma with increasing cumulative dose and (2) contraindication in patients with meningioma or history of meningioma. A Direct Healthcare Professional Communication (DHPC) was distributed. The European Medicine Agency\'s Pharmacovigilance Risk Assessment Committee requested that marketing authorization holders in Europe conduct a survey to assess physicians\' knowledge of the updated key safety information. The primary objective of this study was to measure physicians\' awareness (i.e., did they receive and review the revised SmPC and DHPC) and level of knowledge and understanding of the key safety information pertaining to the restricted use of CPA monotherapy because of the risk of meningioma.
METHODS: This cross-sectional web-based survey was administered to dermatologists, endocrinologists, gynecologists, urologists, oncologists, psychiatrists, and general practitioners in France, Germany, Poland, Spain, and the Netherlands who had prescribed CPA monotherapy in the previous 12 months to assess awareness of the risk of meningioma associated with CPA monotherapy.
RESULTS: Of the 613 physicians who participated, 85% correctly indicated that CPA monotherapy should be prescribed with the lowest effective dose, 75% correctly indicated that the risk of meningioma increases with increasing cumulative CPA monotherapy doses, and 73% correctly indicated that treatment with CPA-containing products must be stopped permanently if a patient is diagnosed with meningioma. Overall, 40% of physicians reported having received the DHPC, and 42% reported having received the revised SmPC.
CONCLUSIONS: Despite low recall of receipt of the updated SmPC and DHPC, most physicians surveyed are aware of the meningioma risk and actions to mitigate the risk.

UNASSIGNED: Comparison of hormonal, metabolic and inflammatory markers of glutathione with metformin and Diane-35 in a rat model of PCOS induced by dehydroepiandrosterone.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.

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.
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.
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.

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

UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.