Climodien (estradiol valerate 2 mg plus dienogest 2 mg) is safe and effective in the treatment of postmenopausal complaints.

OBJECTIVE: To evaluate the efficacy, safety and tolerability of continuous combined hormone replacement therapy (HRT) with Climodien (estradiol valerate 2 mg plus dienogest 2 mg). DESIGN: Open, multinational, multicenter, non-controlled phase III study. PARTICIPANTS: A total of 1501 women aged 52-65 years with postmenopausal symptoms of sufficient severity to require treatment. METHODS: Eligible patients were treated with Climodien for 12 treatment cycles (48 weeks), with assessments of efficacy, safety and tolerability (adverse events) at 8, 24 and 48 weeks. Efficacy was assessed using the Kupperman index. Safety assessments included endovaginal sonography, safety endometrial biopsies, mammography, physical and gynecological examination, vital signs, prothrombotic factors and routine laboratory safety parameters. RESULTS: The Kupperman index improved with increasing duration of treatment, accompanied by an improvement in self-reported patient well-being. Individual climacteric symptoms such as hot flushes and psychonervous disorders also improved. The most pronounced improvement was seen in women who had not previously used HRT. The incidence of breakthrough bleeding declined over time, resulting in complete amenorrhea in 86.2% of the patients after 12 cycles of treatment. Furthermore, total and low-density lipoprotein (LDL) cholesterol levels decreased and high-density lipoprotein (HDL) cholesterol levels increased. Decreases in alkaline phosphatase, pyridinoline and deoxypyridinoline demonstrated the inhibitory action of estradiol on bone resorption. Endometrial thickness remained almost constant, and the incidence of serious endometrial findings was similar to that in untreated women. CONCLUSIONS: Continuous combined estrogen-progestin therapy with Climodien is effective, safe and well tolerated in postmenopausal women, with a profile and incidence of adverse events consistent with those of existing HRT preparations.

[Preliminary evaluation of a histocytological association predicted in a single sample of uterine exploration via a modified pipette: Mark II pipette]. / Evaluation préliminaire d'une association histo-cytologique prélevée en un seul geste pour exploration endo-utérine par une pipelle modifiée: la pipelle Mark II.

The pipelle has become the sampling tool of choice for histological detection of endometrial adenocarcinoma. Some practitioners still prefer cytological sampling. The distal extremity of the pipelle has been modified to allow removal of both types of samples simultaneously. The aim of this preliminary study was to evaluate the feasibility of this method. A positive agreement between histological and cytological results was found in 10 out of the 12 cases examined, among which an adenocarcinoma was positively detected. A prospective study on larger size must confirm these first findings. The new modified pipelle (Pipelle Mark II) offers a possible approach for reduction of false negatives.

[The condom: a badly known method in 1995]. / Le preservatif: un produit mal connu en 1995.

PIP: The only contraceptive product that remained legal under French legislation of 1920 was the condom, which kept its place in the market because of its efficacy against venereal disease. Legislation of November 1987 governs manufacture, importation, marketing, and free distribution of condoms in France. Condoms sold in France must meet specific conditions for size, form, strength, packaging, and labeling. With 110 million units distributed in 1992, France represents 3.9% of the world market. The 61 approved brands of condoms are all imported. Only natural latex condoms are currently approved. Measures to increase condom use in France for AIDS prevention may focus on increasing accessibility or increasing acceptability. During the 1980s the principal factors limiting condom use were reported to be interference with sensation, interruption of coitus, the association of condoms with prostitution, and the negative attitude of physicians. The increased use of oral contraceptives, which largely replaced condoms in France, allowed men to disengage themselves from contraception. The decline of condom use has probably increased the difficulty of its reacceptance. Condoms are used primarily by young persons and those with multiple partners, but even in these groups usage should be increased. The efficacy of condoms must be evaluated in different ways. Condoms are impermeable to sperm and apparently to the AIDS virus, although apparently some smaller viruses are not barred. Neither the efficacy in vivo of spermicides used with condoms nor the greater efficacy of condoms with reservoirs have been demonstrated. Failure rates for condoms are very difficult to evaluate and depend greatly on motivation. Two recent studies of couples with one HIV seropositive and one seronegative partner indicate that systematic and correct condom use prevents HIV transmission.^ieng

A simple and inexpensive treatment of menopause: prophylaxis of postmenopausal bone loss.

Relatively few women elect to receive classical hormone replacement therapy (HRT), and others discontinue treatment because of side-effects or fear of complications. This report presents the results of a long-term study of a low-dose step-down HRT protocol and discusses its potential benefits.

A comparison study of lipid and androgen metabolism with triphasic oral contraceptive formulations containing norgestimate or levonorgestrel.

The effects of norgestimate triphasic (Ortho Tri-Cyclen, Tri-Ciles) and levonorgestrel triphasic (Triphasi) formulations on lipid and androgen metabolism were assessed in a study of 66 healthy women treated through six menstrual cycles. Levels of the following were measured: cholesterol and its subfractions, triglycerides, carrier lipoproteins, estradiol, testosterone, and sex hormone binding globulin (SHBG). Comparison of baseline values with values after 3 and 6 months of treatment indicated that both regimens influenced lipid and androgen metabolism. There was a statistically significant between-regimen difference in levels of high-density lipoprotein, which were favorably increased with norgestimate triphasic but reduced with levonorgestrel triphasic. Related data on SHBG showed that plasma levels of this marker of estrogen/androgen balance were increased significantly more in the norgestimate triphasic group, providing additional evidence of low androgenicity. Both regimens inhibited follicular growth to the same extent, as evidenced by low mean levels of estradiol in all on-therapy cycles; and both decreased free testosterone. Side effects in both groups were minor and characteristic of those observed with low-dose oral contraceptive agents. The results of the study support the reported safety and positive effects of norgestimate on lipid and androgen metabolism, in comparison with a levonorgestrel-containing combined oral contraceptive.

PIP: The effects of norgestimate triphasic (Ortho Tri-Cyclen, Tri-Cilest) and levonorgestrel triphasic (Triphasil) formulations on lipid and androgen metabolism were assessed in a study of 66 healthy women who were treated through 6 menstrual cycles. Levels of the following were measured: cholesterol and its subfractions, triglycerides, carrier lipoproteins, estradiol, testosterone, and sex hormone binding globulin (SHBG). Comparison of baseline values after 3 and 6 months of treatment indicated that both regimens influenced lipid and androgen metabolism. There was a statistically significant between-regimen difference in the levels of high-density lipoprotein, which increased favorably with norgestimate triphasic but were reduced with levonorgestrel triphasic. Related data on SHBG showed that plasma levels of this marker of estrogen/androgen balance were increased significantly more in the norgestimate triphasic group, providing additional evidence of low androgenicity. Both regimens inhibited follicular growth to the same extent, as seen by low mean levels of estradiol in all of the on-therapy cycles. Both decreased free testosterone. Side effects in both groups were minor and characteristic of those observed with low-dose oral contraceptives (OCs). The results of the study support the reported safety and positive effects of norgestimate on lipid and androgen metabolism, in comparison with a levonorgestrel-containing combined OC.

[Study of the efficacy and tolerance of Iopamiron 370 compared to Telebrix Hystero in hysterosalpingography]. / Etude de l'efficacité et de la tolérance du Iopamiron 370 comparativement au Télébrix Hystéro au cours de l'hystérosalpingographie.

Hysterosalpingography is used to study the state of the uterine cavity as well as to analyse the patency of the tubes and the state of the tubal mucosa. It is difficult to find a contrast medium that has both the ideal qualities, be well tolerated and able to show fine pictures that have good contrasts, while at the same time are sufficiently viscous to allow up examination. The contrasts products that are used to carry out hysterosalpingography are often classed as viscous (Telebrix Hystero) and fluid (Iopamiron). This prospective randomised study compares local tolerance and efficiency of the two products. Fifty patients had Iopamiron and 48 Telebrix Hystero in July 1988 and February 1989. There was a statistical difference between the two groups which was significantly in favour of Iopamiron on the following features: Pain as noted on a questionnaire with steps of five points each (p = 0.02), Pain as described by the patient immediately after the examination on a visual analogue scale with p less than 0.01. Overall appreciation of the two products according to their tolerance and the efficiency of the products, which is to say the clearness of the pictures obtained with a p = 0.05.

The prevention of sexually transmitted diseases which affect fertility: methodological problems and initial results.

Sexually transmitted diseases and their consequences for fertility are currently a major preoccupation in public health. A joint research project is being carried out in France to develop an STD prevention program and then to implement it experimentally to evaluate its efficiency. It includes 2 phases: a feasibility phase, currently concluded, and an active phase, a community randomized trial. The aim of the feasibility phase was to test the research methods and tools and to act as a basis for the design of the prevention program. It measured the incidence of discharge (men and women) at a one-year interval and patient characteristics. Participating physicians were GPs in a French administrative department near Paris. Between the two measurements, information and sensitization actions were carried out in the same department among health professionals and the general public. The results show that the incidence of discharge (chosen here as indicators of STDs) in daily general medical practice is low, of the order of 6 cases per 1000 consultations. The community randomized trial will now be conducted in 6 French administrative departments, randomly divided into 3 treated departments, benefiting from a prevention campaign, and 3 controls, where no actions will be undertaken, and its results will be used in a national STD prevention campaign.

PIP: The complications of sexually transmitted diseases -- epididymitis in men and pelvic inflammatory disease in women -- result in 12,000 cases of infertility a year in France. It is therefore necessary to implement a program for the prevention of sexually transmitted diseases in France. The 1st step in such a program must be a feasibility study to determine the level of participation of general practitioners and the suitability of the questionnaires. The feasibility study was carried out in 2 steps, one in 1984 and a similar one in 1985. In each year, during a 4-week period, 57 participating doctors filled out questionnaires for each patient consulting for leucorrhea or urethral discharge. During the year between the studies, information brochures on sexually transmitted diseases were produced for doctors and the public. In 1984, the physicians noted 154 cases of leucorrhea and urethral discharge; in 1985, they noted 121 cases, an average of 6 cases/1000 patients. Of the 275 cases, 141 were in men, 134 in women. Only 4% of the men and 9% of the women were under 20, indicating that young patients go to a free health clinic rather than to private practitioners. Over 1/2 of the men, but only 1/5 of the women had multiple sexual partners, and 1/2 the patients were consulting for a recurrence. Bacteriological screening showed that the commonest organisms in the male infections were Gonococcus and Chlamydia trachomatis, while in women mycoses were more prevalent. The feasibility study showed that general practitioners cooperated and that the quality of the data was good. The 2nd phase of the study, a community randomized trial, is currently being conducted in 6 French administrative departments, 3 for treatment and 3 to act as controls. In each department 50 physicians are participating. All available information will be disseminated in the 3 treatment departments for 3 months after beginning the experiment.

[Sexually transmitted diseases in free sexual practice. Epidemiological aspects]. / Les maladies sexuellement transmissibles en pratique libérale. Aspects épidémiologiques.

One of the major public health preoccupations at present is the incidence of sexually transmissible diseases and their consequences for fertility. At present there is a programme of combined research by the National Institute of Health and the Medical Research (INSERM U 292) and the Director-General of Health (DGS) and the French Committee for Education in Health Matters (CFES). The object of the exercise is to produce a programme for preventing sexually transmissible diseases and then to put in into action in order to find out how practical it is. The programme consists of two phases, the first which has already been completed was to assess how practical the exercise is, and the second phase which is the active pursuit of the enquiry in a random attempt to change things, and this started in November 1986. The first phase tried to test the methods and see whether they were useful forms of research, and also to serve as a base for the programme of prevention. This consists in looking twice a year at the incidence of discharges in men and in women and the characteristics of the patients who are affected. The consultants were a representative sample of general practitioners who work in the Hauts-de-Seine Department. They gave the information voluntarily. There were two measures carried out in the same region of France. The first was informing the public and making the professionals aware of the situation.(ABSTRACT TRUNCATED AT 250 WORDS)

Community prevention of STDs and their complications: methodological issues.

PIP: Sexually transmitted diseases (STD) remain significant public health problems due to their increasing incidence and longterm sequelae. Prevention of STD is an important public health goal. However, there are several methodological problems encountered by such programs. Correct determination of the incidence of STD is hampered by difficulties sampling populations and uncertainty in defining the diseases in question. Random population surveys are invalidated by low response rates. Registry of all STD cases is difficult due to the large number of institutions operating independently, and the number of patients who treat themselves without coming in contact with physicians. A solution may be to determine the incidence among patients approaching primary care physicians and extrapolating to the general population. This method has been validated in 3 French studies. Defining what constitutes a sexually transmitted disease is essential for accurate statistics. Physicians participating in surveys should be provided with checklists of diagnoses included and with standards for accurate diagnosis. A program to prevent STD is currently being tested in 6 French regions. Interventions include dissemination of information concerning STD to high risk groups via mass media, and to physicians, free medical tests and consultations and examination of prostitutes. The incidence of STD before and after intervention will be determined by visits to randomly selected physicians. Effects will be compared to control areas without the intervention. Possible sources of bias include other factors that may affect the number of non-STD visits, inability to detect effects on mild cases that do not present to physicians, and insufficient numbers of cases to arrive at statistical significance. A preliminary study was completed, demonstrating the feasibility of this study design.^ieng

[Do's and don'ts in treating amenorrhea in women taking the minipill]. / Faites...Ne Faites pas...devant une absence de regles en cours de traitement par minipilule.

PIP: 3 conditions may be responsible for absence of menstruation in women taking the minipill: pregnancy, extrauterine pregnancy, or endometrial atrophy which is the most frequent cause but should be treated only after the other 2 possibilities are excluded. The most frequent cause of pregnancy while taking minipills is error in pill consumption due to forgetting, but malabsorption due to vomiting less than 2 hours after taking the pill or an interaction with some other medication may be responsible. The possibility of extrauterine pregnancy should be systematically considered, and the possibility that a micropill and not a minipill is involved should be ruled out. With a sequential minipill contraceptive efficacy does not reach 100% but iatrogenic amenorrhea is infrequent because of the strong dose of ethinyl estradiol. In the case of a preexisting amenorrhea that does not respond to the estrogen or progestin dose, a prolactin adenoma may be suspected. After 2 consecutive beta tests of pregnancy 8 days apart have been negative, it may be concluded that endometrial atrophy is the cause of the amenorrhea. Unprotected sexual relations should be avoided and the patient should be given a fast-acting combined oral contraceptive such as Lutestral to induce bleeding, after which the minipill can be resumed. If unprotected intercourse occurs there is a risk of pregnancy since amenorrhea and anovulation are not synonymous. A morning after pill can be used if the unprotected sexual relations occurred within the last 72 hours. If a pill was forgotten or probably forgotten before the emenorrhea, the most prudent attitude would be to consider the pill to have been ineffective during the preceding 21 days and to test for pregnancy. Unprotected intercourse should be avoided, a fast-acting combination pill should be prescribed to induce bleeding, and the minipill should then be resumed. Amenorrhea in the 1st month of use after an abortion is not significant. This secondary effect of the minipill should be explained to the patient to avoid unnecessary worry.^ieng

[Dos...don'ts...in the case of unexplained high temperature in an IUD user (author's transl)]. / Faites...ne faites pas...devant une fievre inexpliquee chez une femme porteuse de D.I.U.

PIP: Fever, like metrorrhagia or pelvic pain, should be a danger signal alerting women with IUDs to seek medical attention without delay. If the temperature is elevated and the clinical signs suggest salpingitis or pelvic infalmmation, the patient should be hospitalized to obtain a diagnostic and therapeutic laparoscopy, intravenous polyantibiotic treatment, and bed rest. A temperature of about 38 degrees Celsius associated with metrorrhagia suggests salpingitis, regardless of other clinical findings, particularly if the patient is under 25, has had several sexual partners, is nulliparous, or is an insulin-dependent diabetic. The diagnosis should be confirmed by laparoscopy. If a virus or flu is as likely to be the cause as a gynecological infection, blood tests and assay of sedimentation rates should be obtained; over 10,000 polynuclear forms, mainly neutrophils, and a sedimentation rate elevated beyond that expected by the fever are significant in diagnosis. A sonogram can be used to rule out endometrial or tubal infection. If doubt persists, the IUD should be removed and a careful laparoscopy performed to assess the extent and nature of lesions. If the IUD is removed, effective replacement contraception should be prescribed. The physician should not ignore a fever in a patient using an IUD, and should be available for consultation immediately. Removal of the device without further treatment is insufficient in case of gynecological infection because of the danger posed to subsequent fertility. The IUD should not be removed without a short and intensive antibiotic treatment. The possibility of a partner with urethritis should not be ignored, and the fever should not be attributed to vaginitis, even if it is a severe case. The possibility of a pregnancy with the device in place should be ruled out. If the strings are not visible, a sonogram should be obtained to locate the device. In diagnosing febrile patients, the possibility of appendicitis and pyelonephritis should also be considered.^ieng

[Modes of action of IUDs]. / Les mecanismes d'action du sterilet.

PIP: There are between 14-17 million women in the world, excluding China, who wear an IUD, or about 3-5% of all married women younger than 45. Studies on the mode of action of IUDs have been conducted mostly on laboratory animals; they show that ovulation and fecundation are not inhibited by the presence of an IUD. Contrary to what was generally believed, the latest studies have shown that the principle mode of action of the IUD is not its anti-implantation effect, but it depends on the adjustment inside the uterine cavity between the size of the uterine cavity itself, and the size and shape of the device. Endometrial modifications caused by IUDs include inflammatory phenomena, and inhibition of endometrial maturation. Moreover, copper IUDs act directly on spermatozoa and on endometrial steroid receptors. It is still not clear what role prostaglandins play in the mechanism of action of IUDs. Incidence of ectopic pregnancy is not greater in IUD wearers than in women who do not use contraception. Follicle stimulating hormone and luteinizing hormone levels also are comparable in IUD wearers and in nonwearers. IUD wearers have a shorter luteal phase, which entails an earlier menstrual bleeding due to the antifibrinolytic action of the IUD; progesterone levels are identical in users and in nonusers of IUDs.^ieng

[Do's and don'ts in the case of a request for voluntary abortion in a nine-week pregnancy]. / Devant une demande d'IVG a neuf semianes de grossesse: faites...ne faites pas....

PIP: This brief article outlines the duties of a doctor when requested to perform legal abortion in France. If the doctor does not do abortions, he/she should: 1) immediately inform the patient; 2) provide her with names and addresses of colleagues who do or of the proper places where to obtain information; 3) determine exactly the duration of pregnancy; and 4) give the woman a signed certificate confirming the consultation, as by law. If the doctor is willing to perform the abortion he/she should: 1) inform the patient about the cost of the operation; 2) immediately decide the day of the operation; 3) arrange for social counseling, as prescribed by law; 4) discuss contraceptive methods; 5) take all the necessary preoperative tests; and 6) ask for written consent of parents if the patient is an unwed minor, and for certificate of residence if the patient is a foreigner.^ieng

[When a pill has been forgotten (author's transl)]. / Devant un oublie de pilule.

PIP: It is not unusual that a woman panics when she has forgotten her pill or pills. In that case she will immediately call her doctor who is then forced to conduct a consultation over the phone. Questions should be brief, simple and clear, and so should be the therapeutic attitude. A gynecological clinical examination is usually not necessary, nor is any drug prescription. A doctor must be informed about the type and number of pills not taken, and if there have been any sexual relations in the meantime. It is usually necessary to counsel the patient to take contraceptive precautions till the next menstrual period, to keep an accurate chart of her body temperature, and, if there have been sexual relations, it may be necessary to prescribe administration of a type of morning after pill, such as Stediril. All paramedical personnel, and not only doctors, should be trained and ready to give counseling of this nature.^ieng

[What has contraception changed in France?]. / Qu'est-ce que la contraception a change en France.

PIP: In France 36% of women in fertile age use contraception; 27% utilize the pill, 9% the IUD, and 7% mechanical contraception. Contraception has revolutionized the traditional rapport doctor-patient, especially for those physicians belonging to the generation before the pill. Some of them have little by little changed attitude, and initiated a dialogue with their patients; some have not modernized their techniques, and not modified their rapport with patients. Contraception has changed the morals of French society and the traditional husband-wife relation, where the husband had always been the master. Other advantages of contraception are the fact that it allows, by constant surveillance of contraception users, the early detection of hypertension and of breast cancer, and that it has brought into evidence the existence, and the cure, of certain sexual problems.^ieng

[For or against I.U.D.'s in nullipara (author's transl)]. / Pour ou contre le sterilet chez la nullipare.

PIP: Contraception with an IUD can be indicated for a nulliparous woman only when there is a definite contraindication to hormonal contraception. A careful examination of possible contraindications is even more important in a nulliparous patient, since complications of a severe case of infection could lead to sterility. The patient must be regularly seen by her doctor; age over 40 would also be an indication for this type of contraception.^ieng