Cyclofenil for Raynaud's phenomenon in progressive systemic sclerosis.

OBJECTIVES: To assess the effects and toxicity of Cyclofenil versus placebo for the treatment of Raynaud's phenomenon (RP) in scleroderma. SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register, and Medline up to 1996 using the Cochrane Collaboration search strategy developed by Dickersin et al.(1994). Key words included: Raynaud's or Vasospasm, Scleroderma or Progressive Systematic Sclerosis or Connective Tissue Disease or Autoimmune Disease. Current Contents were searched up to and including April 7, 1997. All bibliographies of articles retrieved were searched and key experts in the area were contacted for additional and unpublished data. The initial search strategy included all languages. SELECTION CRITERIA: All randomized trials comparing cyclofenil versus placebo were eligible if they reported any clinical outcomes within the trial. DATA COLLECTION AND ANALYSIS: Data were abstracted independently by two reviewers (DF, AT). Peto's odds ratio (OR) was calculated for all dichotomous outcomes, and a weighted mean difference was calculated for all continuous outcomes. A fixed effects or random effects model was used if the data were homogeneous or heterogeneous respectively. MAIN RESULTS: One trial with 38 patients was included. There was a trend for Cyclofenil to demonstrate more improvement and more dropouts compared to placebo, but there were no statistically significant differences. REVIEWER'S CONCLUSIONS: Cyclofenil is not effective in the treatment of Raynaud's phenomenon secondary to scleroderma.

Effect of cyclofenil on hormonal dynamics, follicular development and cervical mucus in normal and oligomenorrhoeic women.

Cyclofenil is a triphenylethylene derivative, similar in structure to clomiphene citrate, which is used to induce ovulation in anovulatory women. The effects of cyclofenil on a group of 10 normal cyclic and 10 oligomenorrhoeic subjects were examined in a double blind controlled cross-over study. Both groups of women were administered either cyclofenil or, following a washout cycle, a placebo in two treatment cycles. Urinary oestrone and pregnanediol excretion were measured daily and ultrasound scans performed to assess follicular development. Frequent sampling of blood was performed on day 6 to study luteinizing hormone (LH) and follicle stimulating hormone (FSH) pulsatile release. Cervical mucus changes and sperm-cervical mucus interaction were studied after identification of the LH peak. There were no significant differences between cyclofenil and placebo cycles in the following: ovulation rates, daily urinary oestrone and pregnanediol excretion, the number or size of developing follicles, LH pulsatility (parameters studied: number of peaks, pulse interval, pulse amplitude, pulse area and mean nadir LH), mean FSH level on day 6, cervical mucus and sperm-cervical mucus interaction. In view of our inability to demonstrate an effect on any parameter of endocrine function in normal and oligomenorrhoeic women, these results throw doubt on the therapeutic value of cyclofenil in its present dosage and formulation.

Serum levels of aminoterminal type III procollagen peptide and hyaluronan predict mortality in systemic sclerosis.

Systemic sclerosis (SSc) is characterized by an excessive accumulation of collagen in skin and internal organs and increased serum concentrations of different connective tissue metabolites have been reported. In this study of 82 patients with SSc, serum concentrations of aminoterminal type III procollagen peptide (PIIINP), smaller PIIINP-related antigens (Fab PIIINP) and hyaluronan (HA) were increased as compared to healthy controls matched for age and sex. Patients with a shorter disease duration (less than 3 years) had higher serum levels of PIIINP and Fab PIIINP than patients with a longer disease duration. The highest serum concentrations of PIIINP and HA were seen in seven patients who died within 2 years.

Long-term evaluation of penicillamine or cyclofenil in systemic sclerosis. Results from a two-year randomized study.

In a two-year prospective therapeutic trial 13 patients with systemic sclerosis (SSc) were treated with penicillamine, 9 with cyclofenil, and 7 with neither. At entry skin involvement and esophageal, lung, heart, and kidney function did not differ significantly between the groups. Reevaluation after one and two years did not show any significant changes in skin, esophageal, heart, and kidney manifestations, while lung function had slightly improved in both drug-treatment groups. This study thus shows little overall effect of penicillamine and cyclofenil, although both drugs may arrest worsening of pulmonary dysfunction.

[The sterile woman, the physician and time. Number of spontaneous pregnancies in patients with functional sterility]. / La femme stérile, le médecin et le temps. Taux de grossesses spontanées chez des patientes atteintes de stérilité fonctionnelle.

We analysed a one to eight year follow-up of the women remaining infertile after a double-blind study of cyclofenil versus placebo to determine the frequency of pregnancy occurring independently of treatment. Pregnancy occurred in 64 women, 25 during treatment, 39 without treatment. We evaluated the effect of age, cause and duration of infertility on the pregnancy rate. The cumulative pregnancy rates at 36 months after the beginning of the study was 92 per cent for anovulatory cycles, 55 per cent for luteal insufficiency, 69 per cent for cervical mucus insufficiency and 49 per cent for idiopathic infertility. Of the 213 women entering the study, pregnancy occurred in 111 women, 47 in 3 cycles by a placebo effect, 39 without any treatment and 25 during a cycle with treatment. We conclude that the rate of treatment-independent pregnancy is high among infertile couples and that the two main therapeutic factors are time and the doctor-patient relationship.

[Sterility from hormonal causes and unexplained sterility. Treatment with cyclofenil. Double-blind controlled study]. / Stérilités de cause hormonale et stérilités inexpliquées. Traitement par le cyclofénil. Etude contrôlée à double insu.

We treated 213 women during 3 cycles by cyclofenil versus placebo in a double-blind study. These women had infertility caused by ovulatory deficiencies, a cervical factor or idiopathic infertility. Twenty-six of the 114 women receiving cyclofenil became pregnant and 21 of the 99 receiving the placebo. The cumulative pregnancy rates were identical in the 2 groups: 22 per cent in 3 cycles. The authors insist on the importance of a good doctor-patient relationship and the role of the placebo effect in any treatment of infertility.

[Medium term treatment and prophylaxis of dysfunctional metrorrhagia in adolescence]. / Trattamento a medio termine e profilassi delle metrorragie disfunzionali della adolescenza.

The authors compared the therapeutic effectiveness of these different pharmacological methods of preventing dysfunctional menometrorrhagia in adolescents, which were: 1) chorionic gonadotropin, 2) cyclofenil, 3) ovariostatics. Therapy was given during 2 menstrual cycles, and effects were evaluated both during the treatment and for the succeeding 2 cycles. Parameters followed were: a) clinical recovery, b) persistence of spotting, c) effectiveness in inducing ovulation. The results were equally good both in treatment with ovariostatics and ovulation inducers. The latter proved however, more effective during follow-up. Side-effects were very rare, so much so that, in no case was it necessary to suspend treatment.

Ultrasonic assessment of ovulation in cyclofenil induced ovulatory cycles.

Graafian follicle growth was studied by ultrasound scanning during the peri-ovulatory period in 64 ovulatory cycles in 32 infertile patients on cyclofenil treatment, and compared with a control group of 32 patients with confirmed ovulatory cycles assessed on the basis of serum progesterone levels in the middle of the second half of the cycle. The mean maximum diameters of the leading follicles before ovulation were 21.9 +/- 0.6 (S.E.) mm and 24.4 +/- 0.5 (S.E.) mm, respectively for the cyclofenil group and the normal control group (P greater than 0.05). In 79% of the cyclofenil stimulated group and 83% of the spontaneous ovulation group, ultrasonic evidence of ovulation was present between 12 and 36 h after the initial increase in urine LH levels. Ultrasound scanning was found to be simple, and a quick method of monitoring graafian follicle development and ovulation on cyclofenil therapy and the cycles were comparable to the spontaneous ovulatory cycles as assessed on the basis of graafian follicle diameter, and the time of ovulation. Cervical score was not found to be useful to assess ovulation time in the cyclofenil treated group since 31.3% achieved a score of 10 or more on day -4, 93.8% within 24 h of ovulation and 24% on day 3 following the ovulation.

Associaçäo do ciclofenil e cinarizina no tratamento da síndrome climatérica / Combination of cyclophenyl and cinnarizine in the treatment of climateric syndrome

Foram avaliadas 30 pacientes com síndrome climatérica tratadas com associaçäo de ciclofenil e cinarizina. O controle de eficácia foi efetuado através do índice de Kuppermann, antes e após o tratamento. Os resultados favoráveis da associaçäo medicamentosa induzem-nos a afirmar a validade deste tratamento na síndrome do climatério

Estudo clínico e laboratorial da síndrome climatérica com medicaçäo näo estrogênica / Clinical and laboratorial study of climacteric syndrome with non-strogenic administration

Trinta pacientes pós-menopáusicas pertencentes à Secçäo de Climatério da Clínica Ginecológica da Faculdade de Medicina da Universidade de Säo Paulo (Serviço Prof. CARLOS ALBERTO SALVATORE), submeteram-se a estudo "duplo-cego" com ciclofenil associado a benzodiazepínico e placebo. Todas tinham pelo menos 12 meses de amenorréia. Apreciaçäo dos resultados baseou-se no IMK na dosagem de FSH, LH, Prl e Estradiol 17 B na colpocitologia hormonal. A administraçäo de 400mg de ciclofenil e 10mg de dizepam foi suficiente para diminuir os sinais e sintomas mais característicos da Síndrome do Climatério, com quanto näo alterassem as concentraçöes sanguíneas hormonais e tampouco modificassem os índices de eosinofilia e cariopicnose

Evaluation by integrated thermography of the beneficial effect of cyclofenil in severe subcutaneous arterial insufficiency.

Integrated thermographic measurements were made in a patient suffering from a complex syndrome which included scleroderma, Osler-Weber-Rendu disease and a marked atherosclerotic circulatory insufficiency. A new anti-estrogenic drug, cyclofenil, elicited a rapid and prolonged curative effect against the entire syndrome. The circulatory amelioration was registered periodically by integrated thermography of the face and both hands. This method enables temperature distribution functions to be calculated and seems to hold considerable promise for the evaluation of circulatory changes and in particular those changes evoked by therapeutic agents.

[Induction of ovulation in 1985]. / L'induction de l'ovulation en 1985.

There are many methods that can be used to induce ovulation when there is a fault in ovulation in patients who have normal prolactin levels. These are: Bringing the weight to a normal level. Giving Clomiphene. Giving Tamoxifen. Giving cyclofenil and bromocriptine, which really have no more effect than giving a placebo. Giving gonadotrophins in a classical way. This is very useful where there is hypogonadic amenorrhoea but much less useful when the failure of ovulation occurs with normal gonadic function. It is accompanied by a risk of multiple pregnancies and of hyperstimulation, which should be monitored by ultrasound very strictly so that it cannot become too serious. The use of purified FSH which theoretically should be more adequate, at least in cases where the gonadic function is normal in spite of failure of ovulation. Pulsatile administration of LHRH, which in cases of hypothalamic amenorrhoea carries less total risk than giving gonadotrophins. Finally, wedge resection of the ovaries which is reversed for polycystic ovaries that are larger than normal in size, and allied methods. The first choice for hypogonadic hypothalamic amenorrhoea would seem to be the LHRH pump; and for failure of ovulation with normal gonadic function Clomiphene or Tamoxifen. When anti-oestrogens fail to correct these latter cases one can choose according to the case between gonadotrophins, choosing if possible pure FSH, and/or wedge resection. In the last resort in these cases the LHRH pump can be used. The frequent failure of these methods show that perhaps it is possible to create a hypogonadotrophic hypogonadism by giving agonists for a long time or antagonists to LHRH in such a way that a second attempt can be made to induce ovulation using gonadotrophins in better conditions of efficacy and safety.

Treatment of primary hyperparathyroidism with cyclofenil--a synthetic stilbestrol derivative with minimal feminizing effects.

In eight patients with primary hyperparathyroidism (HPT) the laboratory effects of cyclofenil, which is a synthetic stilbestrol derivative with weak feminizing effects, were studied over a period of 5-13 weeks. In all the patients there were during treatment clear reductions of the serum calcium levels as well as the urinary excretions of calcium and hydroxyproline. These findings are in accordance with earlier reports that oestrogens reduce bone resorption mediated by parathyroid hormone. It has previously been demonstrated that cyclofenil can be given, on other indications, for several years to both male and female patients without oestrogenic side-effects. This pilot study, therefore, indicates that treatment with cyclofenil might be of value in some cases of primary HPT where surgery is not considered.