Cyproterone Acetate Research Articles

Bone Mineral Density Increases in Trans Persons After 1 Year of Hormonal Treatment: A Multicenter Prospective Observational Study.

Sex steroids are important determinants of bone acquisition and bone homeostasis. Cross-sex hormonal treatment (CHT) in transgender persons can affect bone mineral density (BMD). The aim of this study was to investigate in a prospective observational multicenter study the first-year effects of CHT on BMD in transgender persons. A total of 231 transwomen and 199 transmen were included who completed the first year of CHT. Transwomen were treated with cyproterone acetate and oral or transdermal estradiol; transmen received transdermal or intramuscular testosterone. A dual-energy X-ray absorptiometry (DXA) was performed to measure lumbar spine (LS), total hip (TH), and femoral neck (FN) BMD before and after 1 year of CHT. In transwomen, an increase in LS (+3.67%, 95% confidence interval [CI] 3.20 to 4.13%, p < 0.001), TH (+0.97%, 95% CI 0.62 to 1.31%, p < 0.001), and FN (+1.86%, 95% CI 1.41 to 2.31%, p < 0.001) BMD was found. In transmen, TH BMD increased after 1 year of CHT (+1.04%, 95% CI 0.64 to 1.44%, p < 0.001). No changes were observed in FN BMD (-0.46%, 95% CI -1.07 to 0.16%, p = 0.144). The increase in LS BMD was larger in transmen aged ≥50 years (+4.32%, 95% CI 2.28 to 6.36%, p = 0.001) compared with transmen aged <50 years (+0.68%, 95% CI 0.19 to 1.17%, p = 0.007). In conclusion, BMD increased in transgender persons after 1 year of CHT. In transmen of postmenopausal age, the LS BMD increased more than in younger transmen, which may lead to the hypothesis that the increase in BMD in transmen is the result of the aromatization of testosterone to estradiol. © 2017 American Society for Bone and Mineral Research.

Consecutive Cyproterone Acetate and Estradiol Treatment in Late-Pubertal Transgender Female Adolescents

BackgroundCyproterone acetate (CA) is an antiandrogenic progestin commonly used in adult transwomen to suppress endogenous androgens, often in combination with estrogens to induce feminization. AimTo assess the (side) effects and biochemical changes of CA alone and in combination with estrogens in adolescent trans-girls. MethodsThis study was a retrospective analysis of clinical and biochemical data from 27 trans-girls who presented at Tanner stage G4 and were treated with CA monotherapy for at least 6 months (mean = 12 months) and then in combination with incremental doses of estrogens (CA + E; mean = 16 months). Statistical analysis of data included paired or unpaired Student t-test or Wilcoxon signed-ranks or Mann-Whitney U-test as appropriate. OutcomesAnthropometrics, reported beneficial and side effects, safety parameters, and hormone levels. ResultsPhysical changes included decrease of facial and non-facial hair growth. One third showed breast development under CA (Tanner stages B2–B3), which increased to Tanner stages B3 and B4 in 66.7% and 9.5% respectively, during CA + E. Reported side effects during CA and CA + E were breast tenderness, emotionality, fatigue, and flushes. No relevant weight changes were observed. Main safety parameters showed the following changes. Hemoglobin and hematocrit decreased and liver enzymes transiently and modestly increased during CA. Triglycerides and cholesterol levels slightly decreased during CA but returned to baseline during CA + E; glucose metabolism was unaffected. Relevant hormonal changes included a decrease in gonadotropins during CA + E and in total and free testosterone levels throughout treatment. Prolactin levels increased during CA and were restored during CA + E. Clinical ImplicationsCA produced modest feminizing effects in trans-girls and therefore might be a valuable alternative in situations in which gonadotropin-releasing hormone analogues are not the treatment of choice and/or are not reimbursed. Strengths and LimitationsThis is the first study to report on the effects of CA in the treatment of trans-girls and one of the few to report on the use of estrogens in this population. Limitations are the modest sample size and the retrospective nature of this study. ConclusionTreatment with CA in late-pubertal trans-girls overall was safe and well tolerated and induced mild clinical and biochemical feminizing changes. Rapid further feminization was observed with incremental doses of E.Tack LJW, Heyse R, Craen M, et al. Consecutive Cyproterone Acetate and Estradiol Treatment in Late-Pubertal Transgender Female Adolescents. J Sex Med 2017;14:747–757.

Prescription Appropriateness of Cyproterone Acetate/Ethinylestradiol in Primary Care: A Population-Based Study in Italy.

We evaluated the prescription appropriateness of cyproterone acetate in combination with ethinylestradiol (CPA/EE) in a primary care setting before and after the 2013 European Medicines Agency's (EMA) recommendation relating to the risk profile of CPA/EE. Data were obtained from the Health Search IMS Health Longitudinal Patient Database(HSD). We compared the results from 2011 to 2012 with the results of 2014, namely before and after the 2013 EMA recommendation, and investigated the burden of concurrent use of CPA/EE and other hormonal contraceptives (HCs) and the reported indication at the time of CPA/EE prescription. Overall, 1189 new users of CPA/EE were identified: 495 in 2011, 446 in 2012, and 261 in 2014. Concomitant use of CPA/EE and other HCs was found in 1% of cases in 2011-2012 and 2% of cases in 2014, while potential concomitant use was observed in 4% of cases in 2011 and 2% of cases in 2012 and 2014. A recent (within 365days) diagnosis of any hyperandrogenic condition was detected in 22 and 24% of CPA/EE users in 2011 and 2012, respectively, and in 24% of cases in 2014. The percentage of CPA/EE users with a recent acne diagnosis and/or treatment was 19, 21, and 18% in 2011, 2012, and 2014, respectively. Apart from an overall reduction in CPA/EE prescriptions in the HSD, no substantial difference was found in terms of the proportions of patients diagnosed with acne or other hyperandrogenic conditions and/or potential concomitant use of HCs before and after the EMA recommendation.

PD37-02 PHASE III STUDY OF INTERMITTENT MONOTHERAPY VERSUS CONTINUOUS COMBINED ANDROGEN DEPRIVATION

PD37-02 PHASE III STUDY OF INTERMITTENT MONOTHERAPY VERSUS CONTINUOUS COMBINED ANDROGEN DEPRIVATION

P-01-002 Prospective analysis: Mild elevation in serum prolactin in trans women is caused by cyproterone acetate

P-01-002 Prospective analysis: Mild elevation in serum prolactin in trans women is caused by cyproterone acetate

Cyproterone Acetate Enhances TRAIL‐induced Androgen‐independent Prostate Cancer Cell Apoptosis via Upregulation of Death Receptor 5

ObjectiveVirtually all prostate cancer deaths occur due to obtaining the castration‐resistant phenotype after prostate cancer cells escaped from the apoptosis and/or growth suppression initially induced by androgen receptor blockade. TNF‐related apoptosis‐inducing ligand (TRAIL) was an attractive cancer therapeutic agent due to its minimal toxicity to normal cells and remarkable apoptotic activity in tumor cells. However, most localized cancers including prostate cancer are resistant to TRAIL‐induced apoptosis, thereby creating a therapeutic challenge of inducing TRAIL sensitivity in cancer cells. Herein the effects of cyproterone acetate, an antiandrogen steroid, on the TRAIL‐induced apoptosis of androgen receptor‐negative prostate cancer cells are reported.MethodsCell apoptosis was assessed by both annexin V/propidium iodide labeling and poly (ADP‐ribose) polymerase cleavage assays. Changes of gene expression were determined by western blot and RT‐PCR assays. The effect of cyproterone acetate on the gene promoter activity was determined by luciferase reporter assay.ResultsCyproterone acetate dramatically increased the susceptibility of androgen receptor‐negative prostate cancer PC‐3 and DU145 cells to TRAIL‐induced apoptosis. Further investigation of the TRAIL‐induced apoptosis pathway revealed that cyproterone acetate exerted its effect by selectively increasing death receptor 5 (DR5) expression. Cyproterone acetate treatment increased DR5 gene promoter activity, which could be abolished by mutation of a consensus binding domain of transcription factor CCAAT‐enhancer‐binding protein homologous protein (CHOP) in the DR5 gene promoter. Cyproterone acetate increased CHOP expression by inducing endoplasmic reticulum (ER) stress / unfolded protein response (UPR) and siRNA silencing of CHOP significantly reduced cyproterone acetate ‐induced DR5 upregulation and TRAIL sensitivity in prostate cancer cells.ConclusionTogether, our study shows a novel effect of cyproterone acetate on prostate cancer cell apoptosis pathways and raises the possibility that a combination of TRAIL with cyproterone acetate could be a promising strategy for treating castration‐resistant prostate cancer.Support or Funding InformationThis work was supported by grants from the National Institutes of Health (5P20GM103489 and R01HL116849), Nebraska State LB595 research program.

Targeting androgen receptor versus targeting androgens to suppress castration resistant prostate cancer

Prostate cancer (PCa) is the 2nd leading cause of cancer-related death among men in the United States and its progression is tightly associated with the androgen/androgen receptor (AR) signals. Men castrated before puberty (eunuchs) or men with inherited deficiency of type II 5α-reductase (with failure to convert testosterone to the more potent dihydrotestosterone) (DHT) do not develop PCa. To date, androgen deprivation therapy (ADT) with anti-androgen treatments to reduce or prevent androgens from binding to the AR remains the main therapeutic option for advanced PCa since its discovery by Huggins and Hodges in 1941. Multiple strategies related to surgical/chemical castration with combinations of various anti-androgens, including Cyproterone Acetate, Flutamide, Nilutamide, Bicalutamide (Casodex) and Enzalutamide, as well as some androgen synthesis blockers, including Abiraterone, have been used to control PCa progression. However, patients on ADT with anti-androgen treatment eventually develop resistance, which might be accompanied with the unwanted side effects of enhanced metastasis. New therapeutic approaches via directly targeting the AR with ASC-J9®, Cisplatin, EPI-001, Niclosamide, and VPC compounds as well as silencing AR with siRNAs or non-coding RNAs have been developed to further suppress PCa at the castration resistant stages.

The use of cyproterone acetate in a forensic psychiatric cohort of male sex offenders and its associations with sexual activity and sexual functioning.

BackgroundCyproterone acetate (CPA) is a steroidal anti-androgenic medication used in the field of psychiatry for the treatment of paraphilic disorders, hypersexuality, and inappropriate sexual behaviour which may be present in patients with disorders such as mild and major neurocognitive disorders. In the forensic psychiatric population, it is prescribed for these indications especially for patients with a history of committing a sexual offence or who are at moderate to high risk of recidivism.ObjectivesTo investigate the use of CPA in a forensic psychiatric cohort of male sex offenders and its associations with sexual activity and sexual functioning.MethodsSeventy-six forensic psychiatric patients from Weskoppies Hospital in Pretoria, South Africa, participated in the study which measured their sexual functioning. A specifically designed questionnaire was used to capture relevant background information. The use of CPA was studied. The Changes in Sexual Functioning Questionnaire, Male Clinical Version (CSFQ-M-C) was used to measure sexual functioning of participants. The CSFQ-M-C scores, and those of all its subscales, of participants on CPA were compared to those not on the drug. Relevant statistical analyses were performed.ResultsThirteen out of the 76 participants were being treated with CPA (17.11%). In total, 53.85% of the participants on CPA and 65.08% not on CPA had scores indicating the presence of sexual dysfunction. The total CSFQ-M-C scores for participants on CPA (mean = 40.54; median = 42) were not statistically significantly lower than those not on the drug (mean = 41.22; median = 41). More notable is that the use of CPA in this population was associated with lower levels of desire, frequency of and pleasure from sexual activity. There was an association between having intellectual disability and being treated with CPA.ConclusionThat all the participants were being treated with psychotropic medication could account for the high percentage of sexual dysfunction in any or all areas of sexual functioning and contribute to the small difference in CSFQ-M-C scores between the two groups. Only a tentative conclusion can be made that CPA may be more effective in decreasing levels of desire, frequency and pleasure related to sexual activity than other areas of sexual functioning. The indication for the use of CPA in this population should be assessed clinically according to patient circumstances and risk assessment.

Cyproterone acetate enhances TRAIL-induced androgen-independent prostate cancer cell apoptosis via up-regulation of death receptor 5

BackgroundVirtually all prostate cancer deaths occur due to obtaining the castration-resistant phenotype after prostate cancer cells escaped from apoptosis and/or growth suppression initially induced by androgen receptor blockade. TNF-related apoptosis-inducing ligand (TRAIL) was an attractive cancer therapeutic agent due to its minimal toxicity to normal cells and remarkable apoptotic activity in tumor cells. However, most localized cancers including prostate cancer are resistant to TRAIL-induced apoptosis, thereby creating a therapeutic challenge of inducing TRAIL sensitivity in cancer cells. Herein the effects of cyproterone acetate, an antiandrogen steroid, on the TRAIL-induced apoptosis of androgen receptor-negative prostate cancer cells are reported.MethodsCell apoptosis was assessed by both annexin V/propidium iodide labeling and poly (ADP-ribose) polymerase cleavage assays. Gene and protein expression changes were determined by quantitative real-time PCR and western blot assays. The effect of cyproterone acetate on gene promoter activity was determined by luciferase reporter assay.ResultsCyproterone acetate but not AR antagonist bicalutamide dramatically increased the susceptibility of androgen receptor-negative human prostate cancer PC-3 and DU145 cells to TRAIL-induced apoptosis but no effects on immortalized human prostate stromal PS30 cells and human embryonic kidney HEK293 cells. Further investigation of the TRAIL-induced apoptosis pathway revealed that cyproterone acetate exerted its effect by selectively increasing death receptor 5 (DR5) mRNA and protein expression. Cyproterone acetate treatment also increased DR5 gene promoter activity, which could be abolished by mutation of a consensus binding domain of transcription factor CCAAT-enhancer-binding protein homologous protein (CHOP) in the DR5 gene promoter. Cyproterone acetate increases CHOP expression in a concentration and time-dependent manner and endoplasmic reticulum stress reducer 4-phenylbutyrate could block cyproterone acetate-induced CHOP and DR5 up-regulation. More importantly, siRNA silencing of CHOP significantly reduced cyproterone acetate-induced DR5 up-regulation and TRAIL sensitivity in prostate cancer cells.ConclusionsOur study shows a novel effect of cyproterone acetate on apoptosis pathways in prostate cancer cells and raises the possibility that a combination of TRAIL with cyproterone acetate could be a promising strategy for treating castration-resistant prostate cancer.

Is a lower dose of cyproterone acetate as effective at testosterone suppression in transgender women as higher doses?

ABSTRACTObjective: The recommended dose of cyproterone acetate (CPA), an anti-androgen that is commonly used in the hormonal treatment of transgender women, is 50–100 mg daily. Our objective was to determine whether CPA at 25 mg daily would suppress total testosterone as effectively as 50 mg daily in transgender women.Methods: We conducted a retrospective cohort analysis of transgender women attending an endocrinology clinic between April 1, 2009, and June 30, 2015. We used a generalized linear mixed model to compare total testosterone between patients on CPA 25 mg versus CPA 50 mg or higher. In a subgroup of patients for which the CPA dose was decreased from 50 mg to 25 mg, we compared total testosterone levels before and after the decrease.Results: We divided the sixty-eight patients included in the study into 4 groups: group 1, CPA 25 mg (N =31); group 2, CPA 50 mg or higher (N = 19); group 3, CPA dose lowered from 50 mg to 25 mg (N = 15); group 4, CPA dose increased from 25 mg to 50 mg (N = 3). The mean total testosterone on treatment was 0.9 nmol/L (95% CI 0.7 to 1.1) in group 1 and 1.2 nmol/L (95% CI 0.9–1.5) in group 2 and were not significantly different (p = 0.087). In group 3, there was no significant difference between total testosterone levels before and after decreasing the dose of CPA from 50 mg to 25 mg, p = 0.86. Group 4 was excluded from analysis.Conclusions: We found that 25 mg of CPA daily was effective at suppressing testosterone levels to within normal female range when used in combination with recommended estrogen therapy in transgender women. Clinicians should consider using a lower dose of CPA in order to minimize potential adverse effects.

Impact of various progestins with or without transdermal testosterone on gonadotropin levels for non-invasive hormonal male contraception: a randomized clinical trial.

Although several progestins have been tested for hormonal male contraception, the effects of dosage and nature of various progestins on gonadotropin suppression combined with and without additional testosterone has not been performed in a comparative trial. The aim of this study was to evaluate the differential impact of four oral or transdermal progestins on the suppression of gonadotropins in healthy men: oral: cyproterone acetate (CPA), levonorgestrel (LNG), norethisterone acetate (NETA), and transdermal: Nestorone® (NES), all in combination with transdermal testosterone (T). Randomized clinical trial testing was performed with four progestins at two doses each. After a 2-week progestin-only treatment, transdermal T was added for further 4weeks and was followed by a 3-week recovery period. Progestin-dose per day: CPA 10mg/20mg, NES 2mg/3mg/dose e.g. 200/300μg/day absorbed, NETA 5mg/10mg, LNG 120μg/240μg. From an andrology outpatient clinic, 56 healthy men aged 18-50years, with body mass index ≤33kg × m-2 were included in the study. Serum concentrations of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were studied. Secondary outcome measure included were serum testosterone concentrations, sperm concentrations, and safety parameters. Intergroup comparisons demonstrated that CPA and LNG had the strongest effect on LH/FSH suppression. Nevertheless, every substance showed significant inhibitory effects on gonadotropin secretion, especially in combination with transdermal T. A decrease in hematocrit and insulin sensitivity as well as cholesterol subfractions and triglycerides was uniformly seen for every group. The combination of oral or transdermal progestins with a transdermal testosterone preparation is able to suppress gonadotropins. Further dose titration studies with sperm suppression as an end-point should be conducted to determine the lowest effective dose for hormonal male contraception.

What is the rate of venous thromboembolism (VTE) in women taking combined oral contraceptives (COCs)?

EVIDENCE-BASED ANSWER The rate of VTE in women taking COCs is approximately 0.06% per year. Third-generation and newer progestins (norgestimate, desogestrel, gestodene, drospirenone, and cyproterone acetate) are associated with greater risk of VTE (about 0.1% per year) (SOR: B, consistent findings from cohort studies).

Protective effect of Chuquiraga spinosa extract on N-methyl-nitrosourea (NMU) induced prostate cancer in rats.

BackgroundThe main objective was to evaluate the possible protective effect of Chuquiraga spinosa extract on N-methyl nitrosourea (NMU)-induced prostate cancer in rats and DU-145 cell line.Materials and methodsProstate carcinogenesis was induced in 30 male Holtzman rats by providing cyproterone acetate, testosterone, and NMU. The tumors were monitored and hematological and biochemical parameters and frequency of micronucleated polychromatic erythrocytes were recorded. The cell line was assessed by a cytotoxicity assay.ResultsOral administration of C. spinosa extract significantly lowered superoxide dismutase malondialdehyde, NO, C-reactive protein, and prostate-specific antigen levels (all P < 0.01 compared with Inductor Group). There was a significant decrease in the frequency of micronucleated polychromatic erythrocytes (P < 0.05). C. spinosa presented a selectivity index of 17.24 in the cytotoxicity assay.ConclusionsConsidering its anti-inflammatory, antioxidant, and antigenotoxic effects, and important variations on biochemical and hematological parameters, including prostate-specific antigen of C. spinosa extract, we conclude that it has a protective effect on NMU-induced prostate cancer in rats and cytotoxicity in the DU-145 cell line.

Male contraceptive efficacy of poly herbal formulation, contracept-TM, composed of aqueous extracts of Terminalia chebula fruit and Musa balbisiana seed in rat

Context: Terminalia chebula Retz (Combretaceae) and Musa balbisiana Colla (Musaceae) have a traditional reputation as a male contraceptive.Objective: To determine the hypo-testicular activity of aqueous extracts of Terminalia chebula (fruit) and Musa balbisiana (seed) separately, and in composite manner at the ratio of 1:1 named as ‘Contracept-TM’ compared to cyproterone acetate (CPA), for developing a polyherbal contraceptive.Materials and methods: The separate extract of above said plants or ‘Contracept-TM’ at the dose of 40 mg/100 g body weight of rat/day or CPA at 2 mg/100 g body weight of rat/day was administered for 28 days. Spermiological, androgenic and oxidative stress sensors, LD50 and ED50/100 g body weight values were measured.Results: Treatment of individual, ‘Contracept-TM’ or CPA resulted significant decrease in the count of spermatogonia A (36.36–49.09%), pre-leptotene spermatocyte (19.11–55.30%), mid-pachytene spermatocyte (28.65–47.28%) and step 7 spermatid (29.65–51.59%). Activities of testicular Δ5, 3β (21.25–48.02%),17β-hydroxysteroid dehydrogenases (29.75–55.08%), catalase (19.06–43.29%) and peroxidase (30.76–62.82%), levels of testosterone (28.15–63.44%), testicular cholesterol (19.61–49.33%), conjugated diene (29.69–84.99%) and thiobarbituric acid reactive substances (41.25–86.73%) were elevated compare to the control. The ED50 and LD50 values were 40 mg and 5.8 g (T. chebula), 48 mg and 6.3 g (M. bulbisiana), 40 mg and 6.0 g (‘Contracept-TM’), respectively.Discussion and conclusion: The said spermiological and androgenic sensors’ levels were decreased significantly by ‘Contracept-TM’ than its constitutional individual plant extract and it may be comparable to standard anti-testicular drug like CPA. So, it may be concluded that above polyherbal formulation is potent for inducing hypo-testicular activity.

296P Efficiency of intermittent androgen blockade in patients with advanced prostate cancer

Background One of the methods to prevent the development of hormone-resistant prostate cancer (PC) is intermittent androgen blockade (IAB). The concept of IAB is in a temporary androgen blockade, in which stem tumor cells are partially preserved. When a certain response is achieved, antiandrogen therapy is stopped to allow the growth of new clones of androgen-sensible cancer cells. Then treatment is resumed. The mechanism of this method is based on the activity of the remaining stem tumor cells, which cause the growth of androgen-dependent colony, receptive to re-hormonal treatment. Methods The study included 235 patients with advanced prostate cancer who were treated at the City Cancer Center, Tashkent city. Patients were divided into 2 groups: group 1(n = 49) - patients underwent surgical castration; group 2(n = 186) - patients received combined hormone therapy. All patients from group 2 were treated in the mode of intermittent therapy with - LHRH agonist - goserelin acetate 3.6 mg in the form of a depot injection 1 time per month and the injection form of cyproterone acetate 300 mg 2 times a month in combination with bisphosphonates. Results The study included 235 patients with advanced prostate adenocarcinoma. In group1 (n=49),wherepatientsreceivedorchiectomy,theaverageageofpatientswas 77.0861.12years.In18patients(36.766.88%) theprevalenceoftumorprocesswas T2NxMx,26patients(53.167.12%)-T3NxMx,5patients(10.264.32)-T3NxMx.19 patients (38.7 6 6.96%) were detected to have skeletal bone metastases, retroperitoneal and iliac lymph nodes. Conclusions The results of our research confirm the effectiveness of hormone therapy IAB in comparison with the traditional method of surgical castration. Our certain methods of selecting the optimal mode of hormonal therapy, depending on prognostic factors has led to improved health outcomes and quality of life of patients with advanced prostate cancer. Herewith, determination of the period of the second cycle start of hormone therapy is decided individually for each patient based on the PSA level before treatment and on the extent of tumor spread, dynamics of clinical symptoms, tolerance to androgen blockade. Legal entity responsible for the study Yusupov Sherali Khasanovich Funding Tashkent city oncology dispanser Disclosure All authors have declared no conflicts of interest.

Attenuation of the cyproterone acetate-induced testicular hypofunction by a novel nutraceutical lycopene: a genomic approach.

This study was designed to explore the cyproterone acetate (CPA)-induced andrological hypofunction and its correction by oral administration of lycopene. In this concern, spermatogenic, biochemical, histological and genomic profiles were studied. Cyproterone acetate administration for 1month helped to develop infertile model rats. A significant recovery was noted in sperm motility, sperm count, sperm viability, hypo-osmotic swelling tail-coiled spermatozoa; activities of testicular ∆5 , 3β-hydroxysteroid dehydrogenase (HSD), 17β-HSD, catalase (CAT) and superoxide dismutase (SOD); and levels of conjugated diene (CD), malondialdehyde (MDA), testicular cholesterol and serum testosterone after the administration of lycopene at 1.5mg/0.5ml Tween-80/100g body weight/day for last 1month to infertile model rats. Simultaneously, qRT-PCR study of Bax, Bcl-2, caspase-3, ∆5 , 3β-HSD and 17β-HSD genes in testicular tissue showed a significant rectification towards the control in CPA-pre-treated cum CPA-lycopene-cotreated rats. Side-by-side histological and histometric studies showed a significant correction in qualitative analysis of spermatogenesis and seminiferous tubular diameter (STD) in CPA-pre-treated cum CPA-lycopene-cotreated rats. Lycopene showed outstanding efficacy in the management of CPA-induced testicular hypofunction with special reference to correction in oxidative stress-induced testicular apoptosis at genomic level.

An Experience of Treating Stuttering Priapism

Priapism is a clinical manifestation of disordered erection physiology and results from a combination of disturbances involving the regulatory mechanisms governing penile tumescence and detumescence. I present here a case of stuttering priapism and its treatment for over 20 years. Antiandrogens were main stay of the treatment and helped to improve his symptoms and preserved his function. Over these 20 years other treatment options are available and antiandrogens are no longer first line treatment agents for such patients. I’ll also review the newer options for treatment of this condition. Keywords: Stuttering priapism; Antiandrogen; Cyproterone acetate.

Effects of antiandrogenic progestins, chlormadinone and cyproterone acetate, and the estrogen 17α-ethinylestradiol (EE2), and their mixtures: Transactivation with human and rainbowfish hormone receptors and transcriptional effects in zebrafish (Danio rerio) eleuthero-embryos

Synthetic progestins act as endocrine disrupters in fish but their risk to the environment is not sufficiently known. Here, we focused on an unexplored antiandrogenic progestin, chlormadinone acetate (CMA), and the antiandrogenic progestin cyproterone acetate (CPA). The aim was to evaluate whether their in vitro interaction with human and rainbowfish (Melanotaenia fluviatilis) sex hormone receptors is similar. Furthermore, we investigated their activity in zebrafish (Danio rerio) eleuthero-embryos.First, we studied agonistic and antagonistic activities of CMA, CPA, and 17α-ethinylestradiol (EE2), in recombinant yeast expressing either the human progesterone (PGR), androgen (AR), or estrogen receptor. The same compounds were also investigated in vitro in a stable transfection cell system expressing rainbowfish nuclear steroid receptors. For human receptors, both progestins exhibited progestogenic, androgenic and antiestrogenic activity with no antiandrogenic or estrogenic activity. In contrast, interactions with rainbowfish receptors showed no progestogenic, but antiandrogenic, antiglucocorticoid, and some antiestrogenic activity. Thus, interaction with and transactivation of human and rainbowfish PGR and AR were distinctly different.Second, we analyzed transcriptional alterations in zebrafish eleuthero‐embryos at 96 and 144h post fertilization after exposure to CPA, CMA, EE2, and binary mixtures of CMA and CPA with EE2, mimicking the use in oral contraceptives. CMA led to slight down-regulation of the ar transcript, while CPA down-regulated ar and pgr transcripts. EE2 exposure resulted in significant transcriptional alterations of several genes, including esr1, pgr, vtg1, cyp19b, and gonadotropins (fshb, lhb). The mixture activity of CMA and EE2 followed the independent action model, while CPA and EE2 mixtures showed additive action in transcriptional alterations.Third, we analyzed the interactions of binary mixtures of CMA and CPA, and of CMA and EE2 for their joint activity in vitro and in eleuthero-embryos. Both mixtures behaved according to the concentration addition model in their in vitro interaction with human and rainbowfish receptors, often showing antagonism. In zebrafish eleuthero-embryos, binary mixtures of CMA and EE2 showed the same expression patterns as EE2 alone, indicating an independent action in vivo.Our study demonstrates that CMA and CPA interact distinctly with human and rainbowfish receptors, suggesting that activities of these and possibly additional environmental steroids determined with yeast expressing human receptors cannot simply be translated to fish. The lack of agonistic activities of both progestins to rainbowfish PGR and AR is the probable reason for the low activity found in zebrafish eleuthero-embryos.

Hormonal therapies for acne

Acne is a common, worldwide problem that is usually multifactorial in etiology, but androgens may play a pivotal role in the development and severity of acne. Endocrinopathies, such as polycystic ovarian syndrome, ovarian tumors, or adrenal hyperplasia or tumors, may be detected in some patients with acne, especially if acne is sudden in onset, associated with hirsutism or menstrual irregularities, or associated with cushingoid facies, acanthosis nigricans, patterned hair loss, or deepened voice. In these instances, serum-free and total testosterone, dehydroepiandrosterone, luteinizing hormone, and follicle stimulating hormone should be tested. Appropriate referral and long-term follow-up is warranted in patients diagnosed with an endocrinopathy. Hormonal therapies for acne include systemic medications with various mechanisms: androgen receptor blockers, adrenal androgen production blockers, or ovarian androgen production blockers. Androgen receptor blockers include spironolactone, cyproterone acetate, chlormadinone, and flutamide; adrenal androgen production blockers include glucocorticoids; and ovarian production blockers include gonadotropin-releasing agonists and oral contraceptives. Practical guidelines are shared for the practicing physician treating hormonally related acne.

Chinese herbal medicine for subfertile women with polycystic ovarian syndrome.

Polycystic ovarian syndrome (PCOS) is one of the most common reproductive endocrinology abnormalities, and affects 5% to 10% of women of reproductive age. Western medicines, such as oral contraceptives, insulin sensitizers and laparoscopic ovarian drilling (LOD), have been used to treat PCOS. Recently, many studies have been published that consider Chinese herbal medicine (CHM) as an alternative treatment for women with PCOS. To assess the efficacy and safety of CHM for subfertile women with PCOS. We searched sources, including the following databases, from inception to 9 June 2016: the Cochrane Gynaecology and Fertility Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Allied and Complementary Medicine (AMED), PsycINFO, Chinese National Knowledge Infrastructure (CNKI), VIP, Wanfang and trial registries. In addition, we searched the reference lists of included trials and contacted experts in the field to locate trials. Randomized controlled trials (RCTs) that considered the use of CHM for the treatment of subfertile women with PCOS. Two review authors independently screened appropriate trials for inclusion, assessed the risk of bias in included studies and extracted data. We contacted primary study authors for additional information. We conducted meta-analyses. We used the odds ratios (ORs) to report dichotomous data, with 95% confidence intervals (CI). We assessed the quality of the evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methods. We included five RCTs with 414 participants. The comparisons in the included trials were as follows: CHM versus clomiphene, CHM plus clomiphene versus clomiphene (with or without ethinyloestradiol cyproterone acetate (CEA)), CHM plus follicle aspiration plus ovulation induction versus follicle aspiration plus ovulation induction alone, and CHM plus laparoscopic ovarian drilling (LOD) versus LOD alone. The overall quality of the evidence for most comparisons was very low.None of the included studies reported live birth rate, and only one study reported data on adverse events.When CHM was compared with clomiphene (with or without LOD in both arms), there was no evidence of a difference between the groups in pregnancy rates (odds ratio (OR) 1.98, 95% confidence interval (CI) 0.78 to 5.06; two studies, 90 participants, I² statistic = 0%, very low quality evidence). No study reported data on adverse events. When CHM plus clomiphene was compared with clomiphene (with or without CEA), there was low quality evidence of a higher pregnancy rate in the CHM plus clomiphene group (OR 2.62, 95% CI 1.65 to 4.14; three RCTs, 300 women, I² statistic = 0%,low quality evidence). No data were reported on adverse events.When CHM with follicle aspiration and ovulation induction was compared with follicle aspiration and ovulation induction alone, there was no evidence of a difference between the groups in pregnancy rates (OR 1.60, 95% CI 0.46 to 5.52; one study, 44 women, very low quality evidence), severe luteinized unruptured follicle syndrome (LUFS) (OR 0.60, 95% CI 0.06 to 6.14; one study, 44 women, very low quality evidence), ovarian hyperstimulation syndrome (OHSS) (OR 0.16, 95% CI 0.00 to 8.19; one study, 44 women, very low quality evidence) or multiple pregnancy (OR 0.60, 95% CI 0.06 to 6.14; one study, 44 women, very low quality evidence).When CHM with LOD was compared with LOD alone, there was no evidence of a difference between the groups in rates of pregnancy (OR 3.50, 95% CI 0.72 to 17.09; one study, 30 women, very low quality evidence), No data were reported on adverse events.There was no evidence of a difference between any of the comparison groups for any other outcomes. The quality of the evidence for all other comparisons and outcomes was very low. The main limitations in the evidence were failure to report live birth or adverse events, failure to describe study methods in adequate detail and imprecision due to very low event rates and wide CIs. There is insufficient evidence to support the use of CHM for women with PCOS and subfertility. No data are available on live birth, and there is no consistent evidence to indicate that CHM influences fertility outcomes. However there is very limited low quality evidence to suggest that the addition of CHM to clomiphene may improve pregnancy rates. There is insufficient evidence on adverse effects to indicate whether CHM is safe.