Cyproterone Acetate Research Articles

Effects of oral contraceptives on the quality of life of women with polycystic ovary syndrome: a crossover randomized controlled trial

Background and objectiveA limited number of studies have evaluated the effects of oral contraceptives (OCs) on the quality of life (QOL) of polycystic ovary syndrome (PCOS) patients. This study aimed to compare the effects of using OCs containing levonorgestrel (LNG) and those containing desogestrel (DSG), cyproterone acetate (CPA) or drospirenone (DRSP) for 6 months on the QOL with PCOS.MethodsIn this crossover randomized controlled 6-arm trial, 200 eligible patients with PCOS scheduled for OC therapy were randomly assigned to one of the 6 study arms. All 6 arms include two 6-month treatment periods, one period with OCs containing LNG, and the other with each of the 3 OCs containing DSG, CPA, or DRSP. Outcomes of interest were the total score of QOL and its domains, which were assessed using a specific and valid health-related quality of life questionnaire for PCOS, which is consisted of six domains, including psychosocial–emotional, self-image, fertility, sexual function, hirsutism, and obesity– menstrual disorders.ResultsFinally, a total of 88 patients were analyzed for this study. The results showed that use of OCs containing DSG, CPA, and DRSP for 3 months was not associated with significant differences in the total scores of QOL compared to those OCs containing LNG, whereas, after 6 months of treatment, patients treated with OCs containing CPA had more improvements in their total scores of QOL, in comparison to OCs containing LNG (P < 0.042). We found no significant differences in QoL domains, including psychosocial–emotional, self-image, fertility, sexual function, hirsutism, and obesity-menstrual disorders after 3–6 months of treatment with DSG, CPA, or DRSP, compared to LNG. The sequence and period effects were not significant in any of the analyses at 3 and 6 months of treatment. The carry-over effect was not significant for most outcomes assessed.ConclusionsThis crossover study demonstrated non-inferiority of OCs with newer generation progestins on different domains of QOL, in comparison with older compounds, although usage of products containing CPA was significantly associated with more improvement in total QOL of PCOS patients, compared to those containing LNG after 6-month of treatment.Trial registrationIRCT201702071281N2.

Hyperandrogenism, adrenal dysfunction, and hirsutism

Hyperandrogenism or hyperandrogenemia are medical conditions characterized by excessive levels of androgens in the periphery or systemically. Clinical manifestations of hyperandrogenism include hirsutism, seborrhea, acne, androgenetic alopecia, and virilization. Hirsutism, defined as excessive growth of terminal hair in women in amale-like pattern, is the most commonly used clinical diagnostic criterion of hyperandrogenism and is determined by using astandardized scoring system of hair growth. Acne and alopecia are further common androgenic skin changes and might be observed without hirsutism in some women. Clitoris hypertrophy, increase of muscle mass, irregular menstrual cycle, and metabolic syndrome can also accompany this condition. Among others polycystic ovary syndrome (PCOS), Cushing disease, and late-onset adrenogenital syndrome belong to the most frequent causes of hyperandrogenemia. Virilization is arelatively uncommon feature of hyperandrogenemia and its presence often suggests an androgen-producing tumor. Management of symptoms include the use of antiandrogens such as cyproterone acetate, spironolactone, and flutamide. Athorough history, afocused clinical examination and an interdisciplinary approach together with gynecologists and endocrinologists are extremely helpful in the diagnostic evaluation and therapy of patients with suspected hyperandrogenism.

Effects of adult male rat feminization treatments on brain morphology and metabolomic profile

Body feminization, as part of gender affirmation process of transgender women, decreases the volume of their cortical and subcortical brain structures. In this work, we implement a rat model of adult male feminization which reproduces the results in the human brain and allows for the longitudinal investigation of the underlying structural and metabolic determinants in the brain of adult male rats undergoing feminization treatments. Structural MRI and Diffusion Tensor Imaging (DTI) were used to non-invasively monitor in vivo cortical brain volume and white matter microstructure over 30 days in adult male rats receiving estradiol (E2), estradiol plus cyproterone acetate (CA), an androgen receptor blocker and antigonadotropic agent (E2 + CA), or vehicle (control). Ex vivo cerebral metabolic profiles were assessed by 1H High Resolution Magic Angle Spinning NMR (1H HRMAS) at the end of the treatments in samples from brain regions dissected after focused microwave fixation (5 kW). We found that; a) Groups receiving E2 and E2 + CA showed a generalized bilateral decrease in cortical volume; b) the E2 + CA and, to a lesser extent, the E2 groups maintained fractional anisotropy values over the experiment while these values decreased in the control group; c) E2 treatment produced increases in the relative concentration of brain metabolites, including glutamate and glutamine and d) the glutamine relative concentration and fractional anisotropy were negatively correlated with total cortical volume. These results reveal, for the first time to our knowledge, that the volumetric decreases observed in trans women under cross-sex hormone treatment can be reproduced in a rat model. Estrogens are more potent drivers of brain changes in male rats than anti-androgen treatment.

Differential Endocrine and Metabolic Effects of Testosterone Suppressive Agents in Transgender Women

Suppression of testosterone secretion and/or action in transgender women using cyproterone acetate (CPA), spironolactone, or gonadotropin-releasing hormone analogues (GA) is achieved through various mechanisms. Our objective was to characterize possible differential effects of these compounds on metabolic and endocrine variables. We conducted a historic cohort study of transgender patients treated in a tertiary referral center. A longitudinal analysis of treatment naïve patients and a cross-sectional analysis of the whole cohort at the last visit was carried out. Among 126 transgender women (75 treatment-naïve), CPA was the predominant androgen suppressive therapy (70%), followed by spironolactone (17.6%), and GA (10.2%). Among those who were treatment-naïve, the increase in serum prolactin levels over baseline was greater at 3 months following CPA initiation (mean change 397 ± 335 mIU/L) than following spironolactone (20.1 ± 87 mIU/L) or GA initiation (64.6 ± 268 mIU/L; P = .0002). Prolactin levels remained higher in the CPA-treated group throughout follow-up, irrespective of estradiol levels, which were similar between the groups. A worse metabolic profile was associated with treatment with CPA than with spironolactone or GA. In the CPA compared to the spironolactone and GA groups, high-density lipoprotein-cholesterol levels were lower (47.1 ± 10.4, 54.4 ± 12.2, and 60.3 ± 13, respectively; P = .0076), while body mass index levels (24.3 ± 5, 21.7 ± 2.3, and 20.7±3.1 kg/m2; P = .03), and systolic (117 ± 12.1, 109 ± 12.2, and 105 ± 13.3mm Hg; P = .01) and diastolic (74 ± 9, 65.6 ± 5.5, and 65.4 ± 11 mm Hg; P = .0008) blood pressure levels were higher at the last visit. Treatment of transgender women with CPA was associated with hyperprolactinemia and a worse cardiovascular risk profile than treatment with spironolactone or GA. BMI = body mass index; CPA = cyproterone acetate; E2 = estradiol; FSH = follicle-stimulating hormone; GA = gonadotropin-releasing hormone analogues; LH = luteinizing hormone.

Early effects of androgen deprivation on bone and mineral homeostasis in adult men: a prospective cohort study.

Long-term androgen deprivation therapy (ADT) negatively influences bone. The short-term effects on bone and mineral homeostasis are less known. Therefore, we aimed to investigate the early effects of ADT on calcium/phosphate homeostasis and bone turnover. Prospective cohort study. Eugonadal adult, male sex offenders, who were referred for ADT to the endocrine outpatient clinic, received cyproterone acetate. Changes in blood markers of calcium/phosphate homeostasis and bone turnover between baseline and first follow-up visit were studied. Of 26 screened patients, 17 were included. The median age was 44 (range 20-75) years. The median time interval between baseline and first follow-up was 13 (6-27) weeks. Compared to baseline, an 81% decrease was observed for median total testosterone (to 3.4 nmol/L (0.4-12.2); P < 0.0001) and free testosterone (to 0.06 nmol/L (0.01-0.18); P < 0.0001). Median total estradiol decreased by 71% (to 17.6 pmol/L (4.7-35.6); P < 0.0001). Increased serum calcium (P < 0.0001) and phosphate (P = 0.0016) was observed, paralleled by decreased PTH (P = 0.0156) and 1,25-dihydroxyvitamin D3 (P = 0.0134). The stable calcium isotope ratio (δ44/42Ca) decreased (P = 0.0458), indicating net calcium loss from bone. Bone-specific alkaline phosphatase and osteocalcin decreased (P < 0.0001 and P = 0.0056, respectively), periostin tended to decrease (P = 0.0500), whereas sclerostin increased (P < 0.0001), indicating suppressed bone formation. Serum bone resorption markers (TRAP, CTX) were unaltered. In adult men, calcium release from the skeleton occurs early following sex steroid deprivation, reflecting early bone resorption. The increase of sclerostin and reduction of bone formation markers, without changes in resorption markers, suggests a dominant negative effect on bone formation in the acute phase.

Сучасне лікування гіперандрогенних станів у жінок репродуктивного віку

The objective: to study the effectiveness and safety of modern antiandrogen therapy in patients with polycystic ovary syndrome (PCOS). Materials and methods. Materials and methods. The first (main) study group included 39 patients with PCOS who received combination nonsteroidal antiandrogen therapy: antiandrogen drug containing flutamide (125 mg 3 times a day) and phyto drug Ovarimedin 1 capsule 2 times a day after meals for 6 months . The II (control) group included 37 patients who received a combination drug containing 35 μg of ethinylestradiol and 2 mg of cyproterone acetate for 6 months. Results. After the course of treatment, biphasic MC was preserved in 25 (64.1%) patients of group I, and in 14 (37.8%) of group II. In group I, before the treatment of stage III hirsutism was in 23 patients (58.9%), after treatment – in 6 patients (15.3%); II stage in 10 patients (25.6%) before treatment, after treatment – in 18 patients (46.1%); I stage was found in 6 patients before treatment (15.5%) and in 15 patients (38.6%) after treatment. In group II patients, stage ІІІ hirsutism was detected in 21 patients (56.7%) before treatment, and in 7 patients (18.9%) after treatment; II stage in 9 patients (24.3%) before treatment, after treatment – in 13 patients (35.1%); I stage was found in 7 patients before treatment (19.0%) and in 17 patients (45.9%) after treatment. Conclusions. Antiandrogenic nonsteroidal therapy with multicomponent herbal drug (Ovaremidine) and nonsteroidal antiandrogens may be recommended for the treatment of women with functional hyperandrogenism accompanied by hirsut syndrome, menstrual irregularities and / or infertility. Our study confirmed that the use of this therapy contributes to the effective treatment of hirsutism, the restoration of menstrual disorders and fertility in women. Differential algorithm for the treatment of hyperandrogenism of various etiologies, which can be recommended in the clinical practice of obstetricians and gynecologists. Keywords: hyperandrogenism, polycystic ovary syndrome (PCOS), menstrual cycle, infertility, hirsutism, phytotherapy.

Female gender and exogenous progesterone exposition as risk factors for spheno-orbital meningiomas.

The great heterogeneity of meningiomas is challenging and we need to distinguish relevant subgroups. Spheno-orbital osteomeningiomas (SOOM) constitute a clinically specific entity, with slow-growing benign osteo-meningiomatous tumors, which recur after surgery in one fourth of cases. Neurosurgical daily practice, supported by the literature, shows that the vast majority of patients with SOOM are women, and we explored whether their epidemiological and hormonal profiles suggest a progesterone influence. We retrospectively documented all radiologically and histologically confirmed cases of SOOM operated in 2005-2019 in our institution. We completed the clinical and hormone history by systematic telephone interviews. In the literature, SOOM occur significantly more often in women than other meningiomas (749/847, 86.4% versus 73.8%, p = 0.002). Among 175 cases, we included 124 patients, 93.5% were women, younger than men (51 ± 5 versus63 ± 8, p = 0.02). Women' meningiomas showed more progesterone receptors (96.4% versus 50%, p < 0.001). Exogenous hormonal intake, reliable in 82 cases, concerned 83.3% (64/78) of women, with frequent progesterone intake: 13 oestroprogestogenic treatment only, with old-generation progesterone analogs, 41 progesterone analogs (cyproterone acetate, nomegestrol acetate, chlormadinone, promegestone, etonogestrel, levonogestrel), 7 substitutive hormonal therapy for menopause, 3 others. Duration of treatment was 2-40years, median 10years. SOOM develop preferentially in women in their fifties, who often received progesterone analogs, and show progesterone receptors. Progesterone analogs are incriminated in skull base meningiomas, and this is the first report on the prevalence of exogenous hormone therapy specifically in SOOM. Whether SOOM reduce after treatment discontinuation, in particular the osteoma part, needs to be explored. Anti-progesterone treatments may represent an avenue for future research in soom.

Effects of oral contraceptives on serum concentrations of adipokines and adiposity indices of women with polycystic ovary syndrome: a randomized controlled trial.

To compare the effects of oral contraceptives (OCs) with different progestins, including Levonorgestrel (LNG), Desogestrel (DSG), Cyproterone Acetate (CPA), and Drospirenone (DRSP) on adipokines levels and adiposity indices in women with polycystic ovary syndrome (PCOS). In this parallel randomized clinical trial, 120 women with PCOS randomly assigned to intervention with OCs containing LNG, DSG, CPA, or DRSP. Outcomes of interest, including serum concentrations of adiponectin, leptin, and resistin, and adiposity indices, i.e., body mass index (BMI), waist circumference (WC), obesity, central obesity, waist to hip ratio (WHR), waist to height ratio (WHtR), lipid accumulation product (LAP), a body shape index (ABSI), body roundness index (BRI), and visceral adiposity index (VAI), and lipid profiles were assessed at baseline, and 6months of treatment. This study showed no significant differences in serum concentrations of adipokines between the four study groups after 6months of treatment. Our results also showed that patients treated with various compounds of OC for 6months had no significant differences in their adiposity indices, except for LAP (p = 0.04), and VAI (p = 0.03). PCOS patients treated with OCs containing CPA had significantly a higher mean LAP, compared to those using products containing LNG. Besides, patients treated with OCs containing CPA had significantly a higher mean VAI, compared to those treated with OCs containing DRSP. This study demonstrated that OCs with low androgenic and antiandrogenic activities had identical effects on serum concentrations of adipokines, and adiposity indices, except LAP, and VAI parameters. IRCT20080929001281N3.

Effects of environmental steroid mixtures are regulated by individual steroid receptor signaling

Fish are exposed to steroids of different classes in contaminated waters, but their effects are not sufficiently understood. Here we employed an anti-sense technique using morpholino oligonucleotides to knockdown the glucocorticoid receptors (GRs, GRα and GRβ) and androgen receptor (AR) to investigate their role in physiological and transcriptional responses. To this end, zebrafish embryos were exposed to clobetasol propionate (CLO), androstenedione (A4) and mixtures containing different classes of steroids. CLO caused a decrease of spontaneous muscle contraction and increase of heart rate, as well as transcriptional induction of pepck1, fkbp5, sult2st3 and vitellogenin (vtg1) at 24 and/or 48 h post fertilization (hpf). Knockdown of GRs eliminated these effects, while knockdown of AR decreased the ar transcript but caused no expressional changes, except induction of sult2st3 after exposure to A4 at 24 hpf. Exposure to a mixture of 6 steroids comprising progesterone (P4) and three progestins, cyproterone acetate, dienogest, drospirenone, 17β-estradiol (E2) and CLO caused a significant induction of pepck1, sult2st3, vtg1 and per1a. Knockdown of GRs eliminated the physiological effects and the up-regulation of vtg1, sult2st3, pepck1, fkbp5 and per1a. Thus, as with CLO, responses in mixtures were regulated by GRs independently from the presence of other steroids. Exposure to a mixture comprising A4, CLO, E2 and P4 caused induction of vtg1, cyp19b, sult2st3 and fkbp5. Knockdown of AR had no effect, indicating that regulation of these genes occurred by the GRs and estrogen receptor (ER). Our findings show that in early embryos GRs cause vtg1 and sult2st3 induction in addition to known glucocorticoid target genes. Each steroid receptor regulated its own target genes in steroid mixtures independently from other steroids. However, enhanced expressional induction occurred for vtg1 and fkbp5 in steroid mixtures, indicating an interaction/cross-talk between GRs and ER. These findings have importance for the understanding of molecular effects of steroid mixtures.

P-06-13 Factors Other than Sex Steroid Levels Contribute to Sexual Desire in Transgender Women

The European Network for the Investigation of Gender Incongruence (ENIGI) investigated sexual desire scores in transgender women (TW). The prospective increase in sexual desire appears to be higher after gonadectomy. The contribution of serum steroid levels to sexual desire in transgender people are insufficiently explored. The current study assesses the role of testosterone (T), DHEAS, SHBG, free T before and after orchiectomy in TW. This prospective cohort study was part of the ENIGI study. Sex steroids, the Sexual Desire Inventory (SDI) questionnaire and self-rated sexual desire were assessed at baseline and each follow-up visit. Gender affirming hormones were initiated at baseline: estrogens (orally or transdermally) and anti-androgens (cyproterone acetate 25-50mg/day). After orchiectomy the anti-androgen were stopped. Data from 118 TW with ≥1 year of follow-up at the Ghent site were analyzed prospectively. Subgroup analyses were performed in TW who underwent orchiectomy (group A, n=85) versus TW who didn't (group B, n=33), at baseline, pre-operatively versus month 12 and post-operatively versus month 24.

SAT-227 Long-Term Outcomes of Two Siblings with X-Linked Congenital Adrenal Hypoplasia Due to a Mutation in NR0B1 (DAX1) Gene: Reproductive and Neuropsychiatric Aspects

Background: X-linked congenital adrenal hypoplasia (CAH) is a rare disease caused by mutations in the NR0B1 (DAX-1) gene. Non-classical manifestations have been described, including late-onset adrenal insufficiency (AI) and gonadotropin-independent precocious puberty (GIPP). We report long-term endocrine and neuropsychiatric outcomes of two siblings with CAH due to mutation in NR0B1.Case report: A 2-yr-old boy was referred due to progressive clinical signs of puberty since 6 months of age. At the age of 3 yr, AI was diagnosed, and the molecular analysis revealed a mutation in the NR0B1 (p.Cys65Leufs*6). Glucocorticoid replacement resulted in reduced testicular volume and decreased testosterone levels. At 11 yr, cyproterone acetate was indicated due to pubertal progression and bone age advancement. At 17 yr the patient had incomplete sexual development and no pubarche. Testosterone levels declined, despite pubertal levels of basal and GnRH-stimulated gonadotropin levels, indicating partial hypogonadotropic hypogonadism. Adult height was 156 cm (SDS: -2.7) within his target height of 161 cm (SDS: -2.1). This patient also presented a psychiatric diagnosis of mood disorder and attention-deficit/hyperactivity disorder (ADHD), and was under methylphenidate, topiramate and sertraline. Both the patient and his mother had SNP array performed, which excluded contiguous gene syndrome. His younger brother also harbored the same mutation in the NR0B1, confirmed shortly after birth. AI was diagnosed with 1 month of age. Cortisone acetate and fludrocortisone were initiated. At 11 months of age, he presented signs of pubertal development with an elevated ACTH and testosterone levels with suppressed gonadotropins, confirming the diagnosis of GIPP. He was treated with cyproterone acetate. At 8 yr, a pubertal response to the GnRH test was detected, and leuprorelin was added. At 9 yr, due to the low growth velocity and advanced bone age, rhGH was started. However, this patient presented a poor compliance and severe obesity (BMI 33 kg/m2). Treatment for GIPP and secondary CPP was stopped at 10 yr, with bone age of 13.5 yr and height of 151 cm (SDS: - 2.3). The diagnosis of ADHD and autism spectrum disorder was made after neuropsychiatric assessment and the patient received treatment with methylphenidate and sertraline. Conclusion: Pubertal development of patients with CAH due to NR0B1 mutations can be heterogeneous. However, the intriguing neuropsychiatric features in two siblings may suggest a role of NR0B1 in neuropsychological development or other still unknown underlying genetic defect.

SUN-042 Low Dose Cyproterone Acetate for the Treatment of Transgender Women - a Retrospective Study

Introduction: Transgender women with intact gonads receive lifelong hormonal treatment in order to suppress physiologic androgen production. Cyproterone acetate (CA) is the most comon antiandrogenic drug prescribed for this indication in Europe, with a dose range between 25-100 mg/day. Aim: To assess the effectiveness and safety of low dose (<20 mg/day), compared with high dose (>50 mg/day) CA treatment. Methods: Historical cohort study of transgender women treated in our department between January 2000 and October 2018. Results: There were 42 transgender women in the low dose group (LDG) and 32 in the high dose group (HDG). Age (27.9 ± 1.6 vs.28.9 ± 1.7 years) and follow up time (16.2 ± 2.2 vs. 20.1 ± 2.1 months) were similar in the LDG and HDG, respectively. At the last available visit, testosterone levels were effectively and similarly suppressed in both treatment groups (0.6 ± 0.1 vs 0.8 ± 0.3 nmol/l; p=0.37, for LDG and HDG respectively). Prolactin (659 ± 64 vs 486 ± 42 mIU/ml, p=0.02), LDL cholesterol (96.1 ± 5 vs 78.5 ± 4 mg/dl, p= 0.02) and triglycerides (93.3 ± 9 vs 69 ± 5 mg/dl; p=0.02) were higher in the HDG compared with LDG respectively. Side effects were common in the HDG (four cases of increased liver enzymes, one case of pulmonary embolism and one case of sudden death). Conclusion: We show for the first time that anti-androgenic treatment of transgender women with low dose CA is as effective as high dose treatment, but safer. We suggest incorporation of this observation in future guidelines.

MON-393 Evaluation of Bone Mass in Transgender Women After Gender Affirming Surgery - a Pilot Study

Estrogen deficiency is classically associated with bone loss in both men and women. In transgender women, after being submitted to gender-affirming surgery (GAS), the main goal of hormone therapy (HT) is to maintain the female phenotype and prevent the consequences of the orchiectomy-related hypogonadal state. The aim of this study was to evaluate the impact of GAS on bone mass in transgender women. A total of 142 trans women attending the outpatient Gender Identity Program were sequentially enrolled. Patients aged < 20 and > 60 years (n=15), with gluteal silicone prosthesis (n=26) and without FSH dosage after surgery (n=9) were excluded. Anthropometric evaluation, laboratory tests and dual-energy X-ray absorptiometry (DXA) were performed in all patients during the follow-up. In women undergoing CAS (CAS-Y), DXA was performed at least 12 months after surgery and with estrogen therapy. In the other women (CAS-N), tests were performed after at least 3 months of standardized treatment (estradiol plus spironolactone or cyproterone acetate). Patients with testosterone values still above the reference for women were not excluded as long as they were on regular HT. Ninety two trans women were included. Among them, 30 had performed CAS, and had DXA assessment performed 37 months (21-78) after surgery. The mean age and BMI were 37 years (33 - 46) and 24.9 kg/m² (23.1 - 27.5) in patients CAS - Y and 30 years (24 - 36) and 24.3 kg/m² (21.5 - 28.5) in patients CAS - N. Trans women CAS-Y were significantly older (p=0.000). No difference was observed regarding estradiol levels between the groups [105.7pmol/L (48.4-207.8) and 147.5 pmol/L (71.9-284.5), p=0.622]. Free androgen index (FAI) was significantly higher [0.45 (0.17 - 1.63) and 4.47 (0.70 - 36.4), p=0.002] and FSH significantly lower [60.4mIU/ml (37.9 - 75.6) and 2.6mIU/ml (0.6 - 4.4), p=0.000] in trans women CAS - N. BMD (g/cm²) and Z-score of lumbar spine, femoral neck and total femur did not differ significantly between the groups. Considering all participants, the lumbar spine BMD was negatively correlated with FSH levels (r=-0.343, p=0.005), which remained significant even after adjustments for FAI. When only CAS - Y trans women were considered, a negative correlation was found between FSH levels and lumbar spine (r=-0.598, p=0.001) and hip (r=-0.404, p=0.033) BMD. In a multiple regression model adjusted for age and surgery, women with FSH > 35 mIU/ml presented a prevalence rate ratio of 11.79 for low bone mass (p=0.040, IC 95% 1.19 - 124.39). The results of this pilot study in trans women show no difference in bone mass according to GAS status. However, long-term elevated FSH levels observed in some post GAS - trans women, even on HT, presented a negative association with bone mass. Further studies with greater sample sizes are needed to confirm the impact of GAS on bone mass and fracture risk.

SUN-004 Case Study: A 17-year-old Girl with HAIR-AN Syndrome, T2DM and Primary Amenorrhea

Introduction: HAIR-AN syndrome is a sub-type of polycystic ovarian syndrome which consists of virilization, insulin resistance and acanthosis nigricans. It may be associated with menstrual irregularity, and hyperandrogenic features such as hirsutism and masculinization. Aim: We report an adolescent girl with HAIR-AN syndrome, T2DM, a very high testosterone level (male range) and primary amenorrhea Case report: A 17-year-old female who had been investigated by pediatric endocrinology since the age of 13 because of hyperpigmentation which was proven to be acanthosis nigricans on skin biopsy. The patient was found to have insulin resistance with initially normal glucose level. She has hirsutism and hypertrichosis. There is no similar condition in her family, she has three siblings all are well. She developed T2DM with at the age of 14. She was started on Metformin 2 gram daily and them pioglitazone 30 mg was added when she was 16 years. She never had menarche. The clinical examination revealed an adolescent girl with normal BP 106/68 mmHg, and BMI 19.6kg/m2. She scored 24 onFerriman-Gallwey hirsutism scoring system. She had severe acanthosis nigricans on both axillae. She also had back and upper limbs hyperpigmentation.Lab tests revealed normal thyroid function tests, prolactin, cortisol, DHEA-S, and 17 hydroxy progesterone. Fasting glucose 7.2, insulin 123 μU/ml (2.6-24.9), c-peptide 964, HbA1c 8.2%. Total testosterone 24.61 nmol/L (0.069-2.715), SHBG 184.9 nmol/L, and Free testosterone index 13.31 (0.51-6.53). Her LH 8.9 and FSH 4.7.Radiological investigations revealed polycystic ovaries on pelvic ultrasound. MRI abdomen showed normal adrenals, and mildly enlarged ovaries with peripherally located follicles consistent with polycystic ovarian syndrome. The patient was started in Diane-35 (cyproterone acetate and ethinyl estradiol) oral pills. She started to have menarche three months after using Diane-35. Her Total testosterone had dropped from 24.61 to 1.69 nmol/L (0.069-2.715), SHBG 579 nmol/L, and Free testosterone index 0.29 (0.51-6.53). She reported that the hirsutism is getting less than before starting the treatment.Conclusion: Primary amenorrhea might be a manifestation of in HAIR-AN syndrome due to sever hyperandrogenism. The management of such condition is challenging. In addition to controlling the metabolic parameters, combined oral pills with antiandrogen effect might be effective.

SAT-LB92 Sex Hormones Therapy Differentially Modulates HDL Function in Transgender Individuals

Background/aim: The main proposed atheroprotective function of high-density lipoproteins (HDL) lays on their role to promote macrophage cholesterol efflux. An insightful way to learn more about the effects of sex hormones on HDL function is to study changes during hormone therapy. The present study was aimed at evaluating the effects of exogenous sex hormones administration on HDL cholesterol efflux capacity (CEC) within transgender individuals. CEC estimates the ability of HDL to remove cholesterol from cells, i.e. the initial step in reverse cholesterol transport. Subjects/Methods: Transmen were treated with testosterone gel, a mix of testosterone esters once every three weeks) or testosterone undecanoate once every twelve weeks, whereas transwomen were treated with either oral estradiol valerate or a transdermal application of estradiol (patches). Cyproterone acetate was prescribed as a testosterone-blocking agent to all transwomen. HDL function was evaluated by a radioisotopic technique. Hormone levels, lipids and HDL function were evaluated after one year of follow-up. Results: In transmen (n= 15), testosterone markedly increased (+ 97%; p < 0.0001), whereas luteinizing hormone (LH) decreased significantly (- 64%; p = 0.049). Total cholesterol and low-density lipoprotein cholesterol (LDL-C) were not affected by testosterone treatment, whilst triglycerides (TG) were raised (+ 11.76%; p = 0.0078) and HDL-C reduced (- 19.6%, p=0.0103). Concerning HDL CEC, only the aqueous diffusion process was lowered (- 9.8%; p = 0.0032), an effect directly correlated with HDL-C changes (r = 0.6242, p = 0.0002). Total-, ATP-binding cassette transporter (ABCA1)-, and ABCG1-mediated CEC were not affected by testosterone treatment. In transwomen (n= 15), estradiol levels were raised (+200%, p=0.013) whereas LH and testosterone significantly reduced, i.e. - 97% for both. Relative to lipids, estradiol supplementation reduced total cholesterol (- 10.7%, p=0.0017), HDL-C (- 14.3%, p = 0.0024) and LDL-C (- 10.9%, p = 0.0058). Total HDL CEC decreased (- 11%, p=0.0001) with a specific decrement in CEC mediated by the ATP-binding cassette transporter (ABCA1) (-24%, p = 0.0003) and aqueous diffusion (-4.7%, p = 0.0014). This last was associated to a reduction in HDL-C (r = 0.4084, p = 0.0251). Conversely, the drop in ABCA1 and total CEC did not associate to reductions in HDL-C levels. Conclusions: In transmen, testosterone supplementation was associated with a reduction in aqueous diffusion-mediated CEC, an effect potentially dependent to HDL-C changes. In transwomen, estrogen significantly decreased HDL function (CEC), independent of HDL-C levels changes.

New Insights into Expression of Hormonal Receptors by Meningiomas

Meningiomas have a female predilection, which is even stronger for spinal than for intracranial meningiomas. The relationship between meningiomas and endogenous or exogenous sex hormones such as cyproterone acetate (CPA) is well documented, yet their underlying mechanism remains unknown. Clarification of the expression profile of hormonal receptors by meningiomas would help us to better understand their hormonal susceptibility. We used tissue microarray and immunohistochemistry to determine the receptor status of the 3 main sex hormones: androgen (AR), estrogen, and progesterone (PR) in 30 intracranial meningiomas, 30 spinal meningiomas, and 30 meningiomas developed on CPA. AR status was positive in 73% of meningiomas in the intracranial group, 87% of meningiomas in the CPA group, and in all meningiomas in the spinal group. Estrogen status was positive in only 7% of meningiomas in the intracranial group and in only 3% of meningiomas in the CPA group but in 30% of meningiomas in the spinal group. PR status was positive in 90% of meningiomas in the intracranial group, in 97% of meningiomas in the CPA group, and in 87% of meningiomas in the spinal group. These specific hormonal receptor statuses based on immunoreactive score were reflected on staining intensities. Furthermore, AR and PR expression was correlated in each group. Our study shows that intracranial meningiomas, spinal meningiomas, and meningiomas developed on CPA express specific hormonal receptor patterns. This result invites the scientific community to review the potential role of AR in the unbalanced sex ratio of meningiomas.

Efficacy of Topical Finasteride 0.5% vs 17α-Estradiol 0.05% in the Treatment of Postmenopausal Female Pattern Hair Loss: A Retrospective, Single-Blind Study of 119 Patients

Female pattern hair loss (FPHL) is a common form of scalp hair loss that occurs in 38% of females. Currently, minoxidil solution is the only therapy approved by the US Food and Drug Administration, but many other treatments are used, including cyproterone acetate, spironolactone, topical 17α-estradiol, and prostaglandin analogs. Systemic finasteride has been considered a treatment option in women even though its teratogenic effects tend to limit its prescription. Recently, topical finasteride has been evaluated to limit the side effect profile of the drug. The objective of the present study is to compare retrospectively the efficacy of topical 0.05% 17α-estradiol solution and a 0.5% finasteride lotion in the treatment of FPHL. We enrolled 119 postmenopausal female patients. The first group comprised 69 women treated with finasteride 0.5% and minoxidil 2%. The second group included 50 women treated with 17α-estradiol 0.05% and minoxidil 2%. At baseline and at 6- and 12- to 18-month follow-up, global photographs were systematically taken. Three operators blind to the prescribed treatment evaluated photographs using a 7-point scale. One-way analysis of variance and unpaired Student t tests were performed to analyze 7-point scale scores. The improvement was statistically significant from 6 months to 12-18 months, both for finasteride (P < 0.005) and 17α-estradiol (P < 0.05). The efficacy of topical finasteride was significantly greater than that of 17α-estradiol solution, both at the 6-month (P < 0.05) and at the 12- to 18-month follow-up (P < 0.005). In general, the highest improvement was observed after 12-18 months of treatment with topical finasteride therapy. Topical finasteride 0.5% in combination with minoxidil 2% could represent a valid therapeutic option for the treatment of postmenopausal FPHL, showing higher efficacy than topical 17α-estradiol with minoxidil 2% both at 6-month and 12- to 18-month follow-up.

Symptomatic progestin-associated atypical grade II meningioma. A first case report

BackgroundLong-term use of high-dose progestin is known to promote the development of meningioma. Atypical meningioma in a patient under progestin has not previously been reported. Case reportA 53-year-old right-handed woman presented with focal onset seizures, without impaired consciousness. Medical history featured endometriosis, treated successively by cyproterone acetate 25mg/day for 2 months then 50mg/day for 101 months, and chlormadinone acetate 5mg/day for 68 months then 10mg/day for 83 months. Brain MRI revealed multiple extra-axial lesions suggestive of left central meningioma associated with anterior skull base meningiomatosis. Surgical resection of the left central meningioma was achieved and progestin was withdrawn. Neuropathology diagnosed grade II atypical meningioma. Close clinical and imaging monitoring was implemented without adjuvant oncological treatment. At 25 months, imaging follow-up showed no recurrence of the left central meningioma and a significant regression of all other lesions, except for the right frontal lesion. ConclusionsNeurosurgeons should be aware of the possible aggressiveness of meningioma in patients under progestin, and particularly those treated by different types of progestin over a long period of time without interruption. This may require systematic close monitoring, to adapt neurosurgical management.

Sorption and desorption of seven steroidal synthetic progestins in five agricultural soil-water systems.

Manure fertilization and wastewater irrigation can introduce the biologically potent synthetic progestins into agricultural soils, causing endocrine disruption in organisms of nearby surface waters. Therefore, this study investigated the sorption and desorption potential of etonogestrel, medroxyprogesterone, gestodene, norgestrel, cyproterone acetate, levonorgestrel, and dienogest in five agricultural soil-water systems. Sorption data were well-described by the linear sorption model. In most batch systems, cyproterone acetate exhibited the highest affinities for soils, followed by etonogestrel, medroxyprogesterone, levonorgestrel, gestodene, norgestrel, and dienogest. The sorption magnitudes (logKoc or logKd) were significantly correlated with the progestin hydrophobicities (R2=0.72-0.86, p<0.05). The Kd values of the progestins were also significantly correlated with organic carbon content and pore volumes of the soils (R2=0.68-0.98, p<0.05). In addition, 0.5M urea resulted in 3-19% decreases in Kd values of the progestins. Taken together, these data indicated that hydrophobic partitioning interaction, hydrogen bonding interaction, and pore filling were the sorption mechanisms for the progestins in soil-water systems. No significant desorption hysteresis was observed for the progestins, indicating that they can be readily desorbed under rainfall or irrigation events. Based on the sorption and desorption data, we estimated the dynamic transport of the progestins in conventional agricultural management systems, and predicted the concentrations of the progestins as a function of soil-sorbed concentration, water-soil ratio, and dilution factor of receiving waters. This study will improve the understanding of the risks posed by the progestins under field-scale hydrological conditions.

Spironolactone for treatment of female pattern hair loss

Spironolactone for treatment of female pattern hair loss