[Efficacy and metabolic safety of long-term treatment with ethinyl oestradiol/cyproterone and desogestrel/ethinyl oestradiol tablets in women with polycystic ovary syndrome].

OBJECTIVE: To evaluate the efficacy and metabolic safety of long-term treatment with ethinyl oestradiol/cyproteroneand desogestrel/ethinyl oestradiol tablets in women with polycystic ovary syndrome (PCOS). METHODS: Women with PCOSfrom West China Second Hospital of Sichuan University enrolled between September, 2011 and August, 2013 were randomlyallocated to receive either ethinyl oestradiol/cyproterone tablets (Group A, n=355) or desogestrel/ethinyl oestradiol tablets(Group B, n=357) for a prospective observation period of 6 months. Women with insulin resistance also received metformin. Atbaseline, 3 months, and 6 months, the patients were evaluated for menstruation, acne score, body mass index (BMI), waist-tohip ratio (WHR), plasma levels of sex hormones, fasting blood glucose (FPG), HOMA-insulin resistance index (HOMA-IR), serum lipid, ovarian volume, and the number of ovarian follicles. RESULTS: All the patients had a regular menstrual cycle aftertreatments. Testosterone level, acne score, LH/FSH, ovarian volume, and the number of follicles decreased significantly afterthe treatments without significant differences between the two groups. Significant increases were noted in TG, TCh, LDL, HDL, and AIP, and HDL level in group A as compared with group B (P < 0.001). FPG decreased in both groups, and wassignificantly lower in group B at 6 months (P < 0.05). BMI and WHR decreased in all the patients with insulin resistance aftercombination treatment with metformin (P < 0.05), but increased significantly in patients without insulin resistance (P < 0.05). Ingroup A, HOMA- IR significantly increased in patientswithout insulin resistance at 3 months (P < 0.05), whereas asignificant increase was not observed until 6 months ingroup B (P < 0.05). CONCLUSIONS: Both ethinyl oestradiol/cyproterone tablets and desogestrel/ethinyl oestradioltablets can relieve the symptoms of PCOS, but it isadvisable to assess the risk of cardiovascular diseasebefore the treatments.

Pills-related severe adverse events: A case report in Taiwan.

OBJECTIVE: To review and evaluate the potential adverse effects of these oral contraceptives (OCP) to overweight women. CASE REPORT: A 19-year-old college student, with a body mass index (BMI) of 35.2 kg/m(2), who received 2 months of OCP containing cyproterone and ethinyl estradiol for polycystic ovary syndrome (PCOS)-related menstrual problems was complicated with a thromboembolism-related life-threatened disease. After intensive care, including the use of an extracorporeal membrane oxygenation system, thrombolytic treatment, anticoagulant, and inferior vena filter, she recovered well without significant sequelae. CONCLUSION: This case illustrates the risk of using OCPs, especially for those containing cyproterone and ethinyl estradiol components, as a treatment for menstrual problems in young women with PCOS and a high BMI.

Ethinylestradiol + cyproterone: back in France for acne and hirsutism, despite frequent off-label prescription.

Following a European review, products containing the ethinylestradiol + cyproterone combination are back on the French market for women with acne (as second-line treatment) or hirsutism. Yet experience has shown that frequent off-label prescription of this combination for contraceptive purposes exposes many women to an unjustified risk of thromboembolism.

Combined oral contraceptives: venous thrombosis.

BACKGROUND: Combined oral contraceptive (COC) use has been associated with venous thrombosis (VT) (i.e., deep venous thrombosis and pulmonary embolism). The VT risk has been evaluated for many estrogen doses and progestagen types contained in COC but no comprehensive comparison involving commonly used COC is available. OBJECTIVES: To provide a comprehensive overview of the risk of venous thrombosis in women using different combined oral contraceptives. SEARCH METHODS: Electronic databases (Pubmed, Embase, Web of Science, Cochrane, CINAHL, Academic Search Premier and ScienceDirect) were searched in 22 April 2013 for eligible studies, without language restrictions. SELECTION CRITERIA: We selected studies including healthy women taking COC with VT as outcome. DATA COLLECTION AND ANALYSIS: The primary outcome of interest was a fatal or non-fatal first event of venous thrombosis with the main focus on deep venous thrombosis or pulmonary embolism. Publications with at least 10 events in total were eligible. The network meta-analysis was performed using an extension of frequentist random effects models for mixed multiple treatment comparisons. Unadjusted relative risks with 95% confidence intervals were reported.Two independent reviewers extracted data from selected studies. MAIN RESULTS: 3110 publications were retrieved through a search strategy; 25 publications reporting on 26 studies were included. Incidence of venous thrombosis in non-users from two included cohorts was 0.19 and 0.37 per 1 000 person years, in line with previously reported incidences of 0,16 per 1 000 person years. Use of combined oral contraceptives increased the risk of venous thrombosis compared with non-use (relative risk 3.5, 95% confidence interval 2.9 to 4.3). The relative risk of venous thrombosis for combined oral contraceptives with 30-35 µg ethinylestradiol and gestodene, desogestrel, cyproterone acetate, or drospirenone were similar and about 50-80% higher than for combined oral contraceptives with levonorgestrel. A dose related effect of ethinylestradiol was observed for gestodene, desogestrel, and levonorgestrel, with higher doses being associated with higher thrombosis risk. AUTHORS' CONCLUSIONS: All combined oral contraceptives investigated in this analysis were associated with an increased risk of venous thrombosis. The effect size depended both on the progestogen used and the dose of ethinylestradiol. Risk of venous thrombosis for combined oral contraceptives with 30-35 µg ethinylestradiol and gestodene, desogestrel, cyproterone acetate and drospirenone were similar, and about 50-80% higher than with levonorgestrel. The combined oral contraceptive with the lowest possible dose of ethinylestradiol and good compliance should be prescribed-that is, 30 µg ethinylestradiol with levonorgestrel.

[The enigma of quaternary prevention in Primary Care. When and when not to do it (presentation of two cases)]. / El enigma de la prevención cuaternaria en atención primaria. Cuándo hacer y cuándo no hacer (a propósito de 2 casos).

Quaternary prevention has been commonly defined with the "primum non nocere" of classical texts by many authors. The daily life of our primary care consultations are full of patients in which we wondered if we try to obtain the benefit of our intervention will exceed the damage we cause him to intervene. Patients with multiple comorbidities, polypharmacy and complex are common in our consultations and it is becoming more difficult to move the balance of our actions, diagnostic or therapeutic benefit to the side. Through 2 cases often move to the reflection of this problem. Quaternary prevention must also be present in our daily activities.

A long-term follow-up study of mortality in transsexuals receiving treatment with cross-sex hormones.

OBJECTIVE: Adverse effects of long-term cross-sex hormone administration to transsexuals are not well documented. We assessed mortality rates in transsexual subjects receiving long-term cross-sex hormones. DESIGN: A cohort study with a median follow-up of 18.5 years at a university gender clinic. Methods Mortality data and the standardized mortality rate were compared with the general population in 966 male-to-female (MtF) and 365 female-to-male (FtM) transsexuals, who started cross-sex hormones before July 1, 1997. Follow-up was at least 1 year. MtF transsexuals received treatment with different high-dose estrogen regimens and cyproterone acetate 100 mg/day. FtM transsexuals received parenteral/oral testosterone esters or testosterone gel. After surgical sex reassignment, hormonal treatment was continued with lower doses. RESULTS: In the MtF group, total mortality was 51% higher than in the general population, mainly from increased mortality rates due to suicide, acquired immunodeficiency syndrome, cardiovascular disease, drug abuse, and unknown cause. No increase was observed in total cancer mortality, but lung and hematological cancer mortality rates were elevated. Current, but not past ethinyl estradiol use was associated with an independent threefold increased risk of cardiovascular death. In FtM transsexuals, total mortality and cause-specific mortality were not significantly different from those of the general population. CONCLUSIONS: The increased mortality in hormone-treated MtF transsexuals was mainly due to non-hormone-related causes, but ethinyl estradiol may increase the risk of cardiovascular death. In the FtM transsexuals, use of testosterone in doses used for hypogonadal men seemed safe.

Alteration of cardiovascular risk parameters in women with polycystic ovary syndrome who were prescribed to ethinyl estradiol-cyproterone acetate.

PURPOSE: We aimed to evaluate the alteration of cardiovascular and metabolic risk parameters of polycystic ovary syndrome (PCOS) patients after a 6-month treatment with an oral contraceptive (OC) containing cyproterone acetate (CPA). METHODS: Forty women with PCOS were evaluated at baseline and after treatment with an OC. Carotid intima-media thickness (CIMT), brachial artery flow-mediated dilatation (FMD), nitrate-mediated dilatation (NMD), high sensitive (hs)-CRP, lipid levels, index of glucose sensitivity, and homeostasis model assessment of insulin resistance index (HOMA) were assessed. RESULTS: Mean CIMT was significantly elevated (0.03 ± 0.01 mm) (p < 0.05). There was a tendency of reduction in FMD, which was significant among overweight patients (p < 0.05). Total cholesterol, low-density lipid (LDL), and triglyceride levels were significantly elevated (p < 0.05). CONCLUSION: CIMT as an indicator of early atherosclerosis and FMD as a finding of endothelial dysfunction seem to be deteriorated especially in overweight PCOS patients who were prescribed to OC containing cyproterone acetate for 6 months.

Cyproterone to treat aggressivity in dementia: a clinical case and systematic review.

Aggressivity is a common problem in the management of elderly patients with dementia. Medications currently used to diminish aggressive behaviour in dementia can have problematic side effects. We present a case and systematic review of the current knowledge about the use of cyproterone acetate to treat aggressivity (excluding hypersexuality related behaviours) in dementia. An 82-year-old man required psychiatric inpatient admission due to agitation and aggressivity and was diagnosed with Alzheimer's disease. After failed trials of atypical antipsychotics (quetiapine 100 mg/day and risperidone 1 mg/day), drugs for dementia (memantine 20 mg/day and rivastigmine 9 mg/day) and benzodiazepines (lorazepam 0.5-1 mg prn) he was started on cyproterone acetate titrated up to 50 mg twice daily. After two weeks he was calmer and did not express aggressivity. Two months later he was discharged to a community placement where he subsequently remained settled on cyproterone. We reviewed literature on the use of cyproterone in aggressivity (excluding hypersexuality) associated with dementia. We searched the main medical databases including articles in English, Spanish, French and Italian. Only one randomized double-blind trial was found, comparing cyproterone with haloperidol (n = 27). Cyproterone was more effective controlling aggressivity and had lower incidence of side effects. In the one uncontrolled naturalistic observational study identified (n = 19), cyproterone was associated with significant reductions in aggressivity without causing major side effects. Further literature was limited to theoretical discussions. Despite there being evidence to support our observations of a useful role for cyproterone in aggressivity in dementia, further studies are needed to establish the efficacy and safety of this therapeutic option.

Unusually high alanine aminotransferase to aspartate aminotransferase ratio in a patient with cyproterone-induced icteric hepatitis.

A 70-year-old man with prostatic adenocarcinoma received cyproterone acetate 200 mg per day. Three months later, mild fatigue and anorexia with elevation of the alanine aminotransferase (ALT) level to 1311 U/L, total bilirubin level to 14 mg/dL and prothrombin time of 15/11.9 seconds developed. At that time the aspartate aminotransferase (AST) level was only 82 U/L. Viral hepatitis and autoimmune markers were all negative. This hepatitis resolved quickly after cyproterone therapy was discontinued. One and a half years later, the patient was prescribed cyproterone 100 mg daily at another hospital where staff were unaware of his previous history. General malaise, upper abdominal pain and jaundice developed two months later. Laboratory studies at emergency room revealed an AST of 245 U/L, ALT of 255 U/L, total bilirubin of 8.2 mg/dL, amylase of 6055 U/L, prothrombin time of 15.2/11.1 seconds and platelet count of 68000 cells/mL. Although cyproterone was discontinued, the patient died of multiple organ failure 20 days after admission. This case report presents a rare situation with marked elevation of the ALT level without AST level elevation. This finding suggests that cyproterone may induce specific damage to the plasma membrane, and the mitochondria are not involved in the initial stage.

Abrupt regression of a meningioma after discontinuation of cyproterone treatment.

The multiplicity of meningiomas or abrupt lesion growth in patients treated with cyproterone acetate suggests that this progestative treatment may promote lesion growth. We report the rapid regression of an incidental meningioma after discontinuation of a 10-year cyproterone acetate treatment. This unique observation suggests that conservative management of meningiomas may be the best option among users of high doses of cyproterone acetate, given that spontaneous regression may occur after hormonal treatment discontinuation.

Comparison of effects of 3 mg drospirenone plus 20 µg ethinyl estradiol alone or combined with metformin or cyproterone acetate on classic metabolic cardiovascular risk factors in nonobese women with polycystic ovary syndrome.

OBJECTIVE: To evaluate the effects of a pill with drospirenone (3 mg) plus ethinyl E(2) (20 µg) (DRP/20EE) alone or associated with metformin or cyproterone acetate (CPA) on some metabolic cardiovascular risk factors in women with polycystic ovary syndrome (PCOS). DESIGN: Randomized, open-label clinical trial. SETTING: Academic medical clinic. PATIENT(S): Forty-eight hirsute women with PCOS. INTERVENTION(S): Patients were randomized to treatment with DRP/20EE or with DRP/20EE plus metformin (1,500 mg/d) or with DRP/20EE plus CPA (12.5 mg/d, 10 days per cycle) for 6 months. MAIN OUTCOME MEASURE(S): Blood pressure, lipid profile, and indexes of glucose tolerance and insulin sensitivity were assessed before and after 6 months of treatment. RESULT(S): Body mass index and blood pressure were not modified by any treatment. Treatment with DRP/EE20 did not change the lipid profile; DRP/EE20 plus metformin significantly increased high-density lipoprotein cholesterol concentrations; DRP/EE20 plus CPA significantly increased triglycerides and total cholesterol. The area under the curve for insulin was significantly decreased by DRP/EE20 and DRP/EE20 plus metformin, but it was significantly increased by DRP/EE20 plus CPA. Treatment with DRP/EE20 plus CPA significantly increased the homeostasis model assessment of insulin resistance index and significantly reduced the glucose to insulin ratio index. Treatment with DRP/EE20 significantly increased the glucose to insulin ratio index. CONCLUSION(S): Treatment with DRP/EE20 improved insulin sensitivity in hirsute women with PCOS, with no deterioration of lipid profile. This effect was not ameliorated by the addition of metformin. The positive metabolic effects of DRP are abolished by the concomitant use of CPA.

Antiaggressive effect of cyproterone versus haloperidol in Alzheimer's disease: a randomized double-blind pilot study.

OBJECTIVE: Alzheimer's disease (AD) is commonly accompanied by aggressive behavior. In the elderly, effective and safe antiaggressive treatment is lacking. Risks of antipsychotics in this population demand therapeutic alternatives. This randomized, double-blind, pilot trial examined the efficacy and safety of cyproterone in the treatment of agitated AD. METHOD: The subjects were 27 elderly patients referred to the University Hospital of Guadalajara Psychogeriatric Clinic diagnosed with AD and associated aggressive behavior (mean Staff Observation Aggression Scale [SOAS] score >or=2). Each patient underwent a 15-day washout for psychotropics and then was randomly assigned to receive stable doses of either cyproterone (100 mg/day) or haloperidol (2 mg/day) for 90 days. The primary outcome measure was the SOAS score. This trial was conducted between October 27, 1993, and March 24, 1998. RESULTS: Of the 27 patients, 19 (70.4%) were women, and the mean age was 80.7 years. The trial was completed by 24 (88.9%) of the subjects (13 in the cyproterone group and 11 in the haloperidol group for 90 days). Three patients (11.1%) dropped out, all after adverse effects in the haloperidol group. Baseline aggression level in the sample was mild (mean SOAS score of 4.48 [SD = 2.04]). Efficacy analyses for all intent-to-treat patients showed that 9 (69.2%) in the cyproterone group achieved complete elimination of aggression at endpoint, in contrast to 2 patients (14.2%) in the haloperidol group (p = .012). Ten patients (71.4%) taking haloperidol had adverse events, compared with 4 (30.7%) taking cyproterone (p = .035). CONCLUSION: Cyproterone showed significantly better efficacy and safety than haloperidol in controlling mild aggression associated with AD. Additional research is needed to confirm if these results can be ratified in a larger study and generalized to patients whose aggression is more severe.

El papel de los gestágenos en los anticonceptivos hormonales orales / The role of gestagens in oral hormonal contraceptives

El papel de los gestágenos en los anticonceptivos hormonales orales está en relación directa con los efectos secundarios y el impacto sobre el metabolismo. En la última década se han desarrollado cinco nuevos gestágenos con alta potencia progestogénica y sin actividad androgénica. Es necesario desarrollar y utilizar gestágenos más selectivos para que la píldora sea usada con seguridad y confianza, para aumentar el cumplimiento y así disminuir el número de embarazos no deseados

The role of gestagens in oral hormonal contraceptives was directly related to secondary effects and metabolic impact. In the last decade five new gestagens have been developed, each presenting high progestogenic potency and absent androgenic activity. It is necesary to develop more selective gestagens to reduce secondary effects in order to get a safe and confident use of contraceptive pill, to increase compliance and to decrease the number of unwanted pregnancies

Venous thrombosis with cyproterone.

Do not use cyproterone-based pills as first-line oral contraceptive.

Risk of venous thromboembolism with cyproterone or levonorgestrel contraceptives.

Results of studies have shown that there is an excess risk of venous thromboembolism in users of oral contraceptives containing cyproterone compared with those containing levonorgestrel. We did a case-control study, in which we assessed the risk of idiopathic venous thromboembolism in women taking combined low-dose oestrogen oral contraceptives containing cyproterone (n=24401) or levonorgestrel (n=75000). We compared the 26 women in this population who had idiopathic venous thromboembolism with 144 matched controls. 12 individuals and 30 controls were taking contraceptives that contained cyproterone. Our results suggest that risk of venous thromboembolism is increased four-fold in women taking contraceptives containing cyproterone by comparison with those exposed to levonorgestrel.