[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.

[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.

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.

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.

Imaging of membranous dysmenorrhea.

Membranous dysmenorrhea is an unusual clinical entity. It is characterized by the expulsion of huge fragments of endometrium during the menses, favored by hormonal abnormality or drug intake. This report describes a case with clinical, US, and MRI findings before the expulsion. Differential diagnoses are discussed.

Prostate cancer treated by anti-androgens: is sexual function preserved? EORTC Genitourinary Group. European Organization for Research and Treatment of Cancer.

This paper reports on results of the EORTC protocol 30892, an open, prospective, randomized study of 310 patients with previously untreated metastatic prostate cancer with favourable prognostic factors who were treated by either flutamide (FLU) or cyproterone acetate (CPA) monotherapy. The final analysis with regard to the main end points, time to progression and survival are still pending. Final results related to the evaluation of sexual functioning prior to and under treatment are reported here. Of 310 randomized patients 294 were eligible for evaluation within this side study. The median age was 71 years (range 48-85). Potential risk factors related to age, general health and prostate cancer were evaluated. For evaluation of sexual functions a five-item questionnaire was used which was administered by the investigator. The protocol allowed time dependent observations at 3-monthly follow-up visits. Sexual functioning was dependent on age but not on prostate cancer-related parameters. Sexual functions at entry were similar within the two treatment groups, spontaneous (nightly) erections and sexual activity were seen in 43-51% and 29-35% of cases. Under treatment, sexual functions under FLU and CPA declined slowly with median times of 12.9 and 5.8 months versus 13.7 and 8.9 months respectively for spontaneous erections and sexual activity. Eventually, with an average observation time in excess of 2 years, loss of spontaneous erections and of sexual activity occurred in 80% versus 92% and in 78% versus 88% of men under FLU versus CPA treatment respectively. None of these differences reached statistical significance. Maintenance of potency under treatment with FLU as reported in the literature is not confirmed in this study. However, loss of sexual functions under monotherapy with both antiandrogens is slow and 10-20% of men retain sexual activity after 2-6 years of treatment. This observation can be exploited in new treatment schemes and is likely to lead to improved quality of life. The advantage of FLU in time and total preservation of sexual functions is statistically not significant and must be balanced against the side effects of FLU and other pure antiandrogens, which may exceed those of CPA especially with respect to gynaecomastia. Hepatic toxicity may limit the long-term use of both drugs.

Cyproterone. A review of its pharmacology and therapeutic efficacy in prostate cancer.

Cyproterone (cyproterone acetate) is a steroidal antiandrogenic agent that inhibits the action of adrenal and testicular androgens on prostatic cells. Additionally, its progestogenic activity causes a centrally mediated reduction in testicular secretion of androgens. Studies have demonstrated the effectiveness of cyproterone monotherapy in patients with prostate cancer, and for those in whom orchiectomy is not an acceptable option cyproterone may be a useful alternative. In addition, the drug may be administered in combination with surgical or gonadotrophin-releasing hormone (GnRH) agonist-mediated castration to ensure ablation of adrenal androgens. However, the effectiveness of cyproterone in combination with these forms of testicular androgen deprivation remains to be fully established. Trials to date have not demonstrated prolonged survival in patients receiving the combination therapy. Importantly, however, cyproterone does prevent acute exacerbation of disease during initial treatment with a GnRH agonist. Furthermore, combination therapy tends to be associated with a lower incidence of hot flushes than GnRH agonist-mediated or surgical castration alone. Thus, cyproterone 200 mg/day has proven efficacy in preventing acute flare of disease and reducing the incidence of hot flushes associated with GnRH agonist therapy or orchiectomy. It may also facilitate maximal androgen deprivation in patients receiving GnRH agonist therapy. If this drug is used as monotherapy, dosages of 250 mg/day or greater will probably be required.