The acceptability of a small intrauterine progestogen-releasing system for continuous combined hormone therapy in early postmenopausal women.

OBJECTIVE: To assess the acceptability, ease of insertion, tolerance and associated bleeding of a novel intrauterine progestogen-releasing system, combined with transdermal estradiol, in postmenopausal women. DESIGN: An open non-comparative study of 294 postmenopausal women with an intact uterus at 27 centers in six countries. METHOD: All subjects had requested treatment for menopausal symptoms and had received transdermal estradiol 50 microg/day by patch and an experimental intrauterine system (MLS) releasing levonorgestrel 10 microg/day. Details of the insertion were recorded and subsequent bleeding, side-effects and adverse events were documented on a daily diary. Endometrial thickness was measured by transvaginal ultrasound scan prior to insertion of the MLS and after 12 months. The study is of 3 years duration. This report summarizes the results after the first year. RESULTS: The median age of the subjects was 52.6 years (range 41.7-59.6 years), 90% were within 3-5 years of menopause and 78% had previously used hormone therapy (HT). The MLS was inserted at the first attempt in 297/294 (94%) subjects and was facilitated by dilatation of the cervical canal in 65 (22%) subjects. Local anesthesia was given to 30 (10%) subjects. Of the 17 with a failed first insertion, two subjects did not want a second attempt, in 14 a second attempt succeeded, facilitated by cervical dilatation in seven and local anesthetic in three subjects. There was one failed insertion. Investigators rated 80% of first insertions as easy, 14% as slightly difficult and 6% as very difficult. The second insertion was easy in 9/15 subjects, slightly difficult in 4/15 and very difficult in one (data from one subject missing). During insertion, 34% subjects had no pain, 49% said it was mild, in 15% it was moderate and in 2% the pain was severe. At 12 months, one MLS had been expelled. Spotting was the most common form of bleeding and this decreased from a median of 9 to 0 days at 4 months, although 10% of subjects continued to report spotting up to 12 months. Bleeding days were few and mainly in the first 2 months. At the end of month 11, 66.8% were amenorrheic and 87% non-bleeding. Only nine subjects discontinued because of bleeding. There was no correlation between the bleeding profiles and number of years since menopause, previous HT use or body mass index. The median endometrial thickness at entry to the study (without HT) was 2.6 mm and 3.4 mm at 12 months. Of the adverse events, after the pain associated with insertion, headache was the next most common at 13.3% and mastalgia was experienced by 7.8% of subjects. Overall, the dropout rate was low at 28 subjects (9.5%). There were favorable changes in the serum lipid profile consistent with the effects of estradiol and suggesting minimal attenuation by the intrauterine progestogen. Conclusion This interim report of a 3-year study has confirmed that the menopausal levonorgestrel intrauterine system is easy to insert and is well tolerated by postmenopausal women.

Intrauterine 10 microg and 20 microg levonorgestrel systems in postmenopausal women receiving oral oestrogen replacement therapy: clinical, endometrial and metabolic response.

OBJECTIVE: The clinical and endometrial efficacy and lipid response of two different doses of intrauterine levonorgestrel were assessed in comparison with sequential oral medroxyprogesterone acetate in postmenopausal women receiving continuous oral E2-valerate. DESIGN: One-year prospective multicentre randomised control trial. SETTING: Four outpatient clinics in Oulu, Helsinki and Jyväskylä, Finland. POPULATION: A total of 163 healthy volunteer postmenopausal women with climacteric complaints or already using hormone replacement therapy (HRT). INTERVENTIONS: Subjects were randomly allocated to receive a new intrauterine system releasing 10 microg of levonorgestrel daily or an established intrauterine system (Mirena) releasing 20 microg of levonorgestrel daily or sequential oral medroxyprogesterone acetate (5mg/day, 14/30 days). All three regimens were combined with an oral daily dose of 2mg of E2-valerate. MAIN OUTCOME MEASURES: Bleeding patterns were assessed by diaries kept by the subjects. Endometrial effects were evaluated by histologic biopsies taken at the baseline and after six and 12 months of therapy. Serum concentrations of total, HDL and LDL cholesterol, triglycerides and lipoprotein(a) were determined at the baseline and after six and 12 months of therapy. RESULTS: Insertion of the smaller 10 microg levonorgestrel system was easy in 70% and difficult in 4% and that of Mirena was easy in 46% and difficult in 21% of the subjects. After six months of therapy, 43 (95.6%) of the 47 subjects receiving 10 microg levonorgestrel and 54 (98.2%) of the 55 subjects receiving 20 microg levonorgestrel had no bleeding, while the sequential medroxyprogesterone acetate regimen produced typical cyclic withdrawal bleedings. Endometrial hyperplasia was not observed in any of the treatment groups during the 12-month study. After 12 months of therapy, strong endometrial suppression was found in 46/47 and 55/55 of the subjects receiving 10 microg and 20 microg of levonorgestrel, respectively, while the endometrium was proliferative in 18/47 of the subjects in the medroxyprogesterone acetate group. Serum total cholesterol decreased in all treatment groups. HDL cholesterol increased in women receiving medroxyprogesterone acetate or the smaller intrauterine dose of levonorgestrel. CONCLUSIONS: Both intrauterine doses of levonorgestrel provided good endometrial protection in postmenopausal women on oestrogen replacement therapy. The advantage of the 10 microg system with a smaller size is the easier insertion of the system and a minimal attenuation of the favourable effects of oral oestrogen on the serum lipid profile.

Intrauterine application of progestins in hormone replacement therapy: a review.

The intrauterine application of progestins as endometrial protection against hyperstimulation by estrogen replacement therapy has been investigated in clinical trials since the early 1990s and one product has become available for this indication. This review considers the available published and presented reports on intrauterine use of progestin to date. Reports of 19 studies were reviewed. These studies included both peri- and postmenopausal women (826 in total), treated with different types of estrogens administered via various routes. Progesterone was used in two small studies, while all other studies used different doses of levonorgestrel for periods ranging from 6 months to more than 5 years. Endometrial effects, bleeding profiles, systemic effects (symptoms and metabolic), as well as clinical experience, were considered and were comparable to other forms of continuous combined hormone replacement therapy (HRT). It is concluded that the current evidence supports complete endometrial protection and a good safety profile. The observed bleeding profiles appear favorable but have not yet been directly compared with other forms of continuous combined HRT. A favorable effect on serum lipids has been observed and also awaits direct comparative confirmation. Progestin-attributable side-effects, effects on bone and breast tissues and other systemic effects have not yet been studied. Acceptance by patients has been good, while insertion did not present undue problems for the investigating physicians. Retention of the studied intrauterine systems has been very good. Intrauterine use of progestins, especially levonorgestrel, by purpose-designed systems as part of combined HRT, is a new way of administration and carries good benefits, while some aspects require more clinical evidence.

The menopause, urinary incontinence and other symptoms of the genito-urinary tract.

In a study on incontinence and other symptoms of the genito-urinary tract in postmenopausal women covering their prevalence, consequences and predisposing factors, the prevalence of incontinence was found to be 26.4%. Daily incontinence was present in postmenopausal women more than twice as often as before the menopause (P < 0.05). The frequency of medical consultation for such incontinence was low; only 26.1% of the postmenopausal women had ever seen their doctor about it. Urgency, nocturia and dyspareunia were more prevalent in postmenopausal women, while vaginal itching and discharge were more frequent in premenopausal women (P < 0.05). The prevalence of incontinence and the other genito-urinary symptoms was higher after surgical than after natural menopause. Multivariate analysis showed the menopause to be the only factor that contributed significantly to the onset of incontinence (P < 0.001).

Urinary incontinence in women from 35 to 79 years of age: prevalence and consequences.

We investigated the prevalence and the consequences of urinary incontinence in a group of 1299 women aged 35 to 79. Incontinence was present in 344 women (26.5%), in 5.9% the incontinence occurred at least once daily. The prevalence was highest in the younger age-groups and lowest between 65 and 69 years of age, thereafter it increased again. Almost half of the incontinent women used protective sanitary towels. In contrast to this, only 13.3% considered themselves handicapped by their symptoms, and only 28.2% had ever sought medical help, although the symptoms had been present for as long as 7.5 years on average. The major reason for not seeking medical help was that the symptoms were not considered to be so serious.

Contraception survey: Denmark 1988.

In 1988 a survey** was conducted in 1,033 women living in Denmark, whose ages ranged from 15 to 44 years. The main aims of the study were to identify the influence, if any, of demographic and socioeconomic factors on contraceptive use and to assess the women's knowledge of selected facts concerning their own fertility. The study's additional objectives were to gain insight into factors influencing communication on the subject of contraception, such as advice obtained from professional counsellors, general information dissemination and discussion between partners, and to investigate women's attitudes and opinions regarding contraceptive methods and their use. The results are discussed in relation to the findings of other studies on the use of contraceptives both worldwide and in a number of European countries. The Danish findings are also examined in the context of possible action to reduce the relatively high rate of legally induced abortions in Denmark.

PIP: A survey of 1033 Danish women aged 15-44 was aimed at analyzing the factors influencing contraceptive knowledge and practice. The survey was designed by the International Health Foundation of Geneva, based on 4-stage sampling and home interviews. The most common methods used were pill (29%), condom (24%), IUD (21%), and sterilization (11%). Condoms were used in addition to rhythm and withdrawal by 50%, 50% of diaphragm users, 10% of pill users, and smaller proportions of IUD users and sterilized men and women. Women not using any contraception were mainly teens. The more highly educated had higher use rates but lower prevalence of sterilization. Women changed methods primarily because of side effects of fear of side effects. Information was highly accurate came from doctors, reading and associates; but misconceptions on the cancer and infertility risks from pills were common. Reasons for having induced abortions were age 35, no steady partner, want no more children and contraceptive failure. While contraceptive education is food in Denmark, more efforts need to be made to reach young single women, perhaps with visits to clinics.

[Contraception in Austria]. / Kontrazeption in Osterreich.

952 sexual active women between 15 and 44 years were investigated for their contraceptive behaviour. In 42% the pill was the first choice followed by the condom in 16%. 18% of all sexual active women in this age group did not use any contraceptives. Therefore the rate of unplanned pregnancies was very high: 34% reported about such unplanned pregnancies in their history. The main sources for informations in contraception are the gynecologist and the partner, but not the parents or the newspapers. Nearly half of all women did not know how the pill really works and quite a lot has still the opinion that there are really harmful side effects of oral contraceptives.

PIP: 952 sexually active women between the ages of 15-44 were investigated concerning their contraceptive behavior. 42% used the pill as their method of choice, followed by the condom in 16%. 18% of all sexually active women in this age group did not use any contraceptives. Therefore, the rate of unplanned pregnancies was very high--34% reported such unplanned events in their histories. The main sources for information about contraception are the gynecologist and the sexual partner, rather than the parents or the newspaper. Nearly 1.2 of all women did not know how the pill works and many were still of the opinion that there are serious side effects associated with oral contraceptives. (author's modified)

[Fecundity, fertility, and sterility: assessment and controversy]. / Fertilite, fecondite et sterilite: evaluation et controverse.

The author reviews problems concerning infertility in developed countries. Topics covered include natural fertility, "demographic and social trends in family planning such as increasing maternal age at first childbirth, the increase of age-specific infertility rates through known ([adnexitis]), unknown (the environment) or debatable (induced abortion, certain contraceptive methods) causes, and the availability of highly developed techniques to assist conception. The actual prevalence of infertility is poorly documented and is either derived from demographic surveys or from hospital populations. To record the true prevalence of infertility, population-based surveys including infertility specialist confirmation of the etiology are needed. One survey of this type indicates a lifetime prevalence of 17% of couples." (SUMMARY IN ENG)

The effect of naftidrofuryl on intermittent claudication: a meta-analysis.

A meta-analysis was performed on four clinical trials, conducted during 1980-1989 in France (two trials) and in the Federal Republic of Germany (two trials). Altogether, 596 patients with peripheral arterial occlusive disease (Fontaine's classification stage II) entered these four multicenter studies. Four hundred fifty-two patients completed the trials, 241 were treated with 600 mg naftidrofuryl orally per day and 211 were given a placebo. The studies were of a double-blind parallel design and lasted for 3 or 6 months. Inclusion and exclusion criteria were comparable, as were the experimental methods used. Occasionally, differences in study design and methods were observed. Risk factors were recorded in three of the four studies. The outcome criterion of pain-free walking distance was studied for the four trials together and showed a significant improvement in the active drug tested group, following both 3- and 6-month duration of treatment. The type of treatment, the severity of the disease, the existence of blood lipid disorders, and smoking were found to be the predictive factors associated with the evolution of pain-free walking distance during 3 months. The meta-analysis confirms the beneficial effect of naftidrofuryl in treating peripheral arterial occlusive disease.

Contraception in Sweden.

In 1987, a survey of contraceptive use, knowledge and attitudes was conducted in Sweden by the International Health Foundation (IHF) as part of a multi-country study that has so far involved six other countries in Europe. The women involved, who were aged 15-44, completed a standard questionnaire. The overall percentage use of contraceptive methods, especially the reliable ones, was found to be high (95%). Oral contraception was the most frequently used method, followed by barrier methods and the intrauterine device (IUD). Contraceptive methods were chosen or abandoned mainly because of health reasons and better reliability. Knowledge of fertility proved to be generally good. Medical methods such as oral contraceptives and IUDs were associated with health hazards. In the case of the pill, fears of cardiovascular risks, thrombosis and cancer were widespread, while infection risk and menorrhagia were the most frequently quoted perceived disadvantages of the IUD. Indeed, these two methods suffer from a very negative image among Swedish users.

PIP: In Sweden, contraceptive behavior is a product of many determinants such as motivation and communication and perception of advantages and disadvantages. Other determinants identified by the International Health Foundation survey included the knowledge of fertility and the perception of the reliability, safety and disturbance of a method choice. The survey found that contraceptive use is high among Swedish women. This is most likely as a result of both cultural traditions and family planning and public sexual education. The 3 most prevalent methods were oral contraceptives, barrier methods and the IUD. Socioeconomic factors were more important than psychological factors in method choice. Although both oral contraceptives and IUDs are highly prominent among choices, a large portion of the survey's participants not only recognized but feared the disadvantages of oral contraceptives such as cardiovascular risks and thrombosis and also those of the IUD such as the risk of infection and menorrhagia. Reliability and concern for health were 2 of the most important factors in choosing a method. Sweden enjoys high levels of contraceptive awareness and use. To further enhance the general understanding and use of the IUD and oral contraceptives, more information needs to be provided to users.

A survey of contraception in five west European countries.

In 1984 and 1985, a survey was conducted of 7696 women aged 15-44 living in Italy, France, Great Britain, Spain and the Federal Republic of Germany. The aim of the study was to examine the use of contraceptive methods, the differences in contraceptive use, knowledge of fertility, communication about contraception, motives for choice and the perceptions held by women regarding contraceptive methods, particularly oral contraception. The results show important differences between the countries studied.

PIP: A survey was conducted in 1984 and 1985 of 7696 women aged 15-44 and living in Italy, France, Great Britain, Spain, and the Federal Republic of Germany with several objectives: to obtain new information on contraceptive use and the various contraceptive methods available in these 5 countries; to detect the influence, if any, of demographic and socioeconomic factors on contraceptive use; to assess the women's level of knowledge of selected facts relating to their own fertility; to gain insight into elements influencing communication of the subject of contraception; and to learn the attitudes and opinions of the women about contraceptive methods and their use. 1-stage cluster sampling was the basic sampling method used in all 5 countries, with variations adopted to deal with characteristics unique to individual countries. Refusal rates were low: 9% for Italy, 10% for France, 7% for Great Britain, 12% for Spain, and 11% for the Federal Republic of Germany. Women not using contraception or depending on less reliable methods such as rhythm or withdrawal represented 67% (Italy), 36% (France), 14% (Great Britain), 42% (Spain), and 43% (Federal Republic of Germany) of those sampled. Barrier methods were quite popular in Italy, Spain, and Great Britain but not in West Germany or France. The use of the IUD seems to have become a southern European practice, the method being most widely used in Spain, and also in France and Italy especially in comparison with other studies. Oral contraceptive (OC) use remained at a high level in Great Britain, France, and West Germany. All countries showed similar variations in practice with age and desire for future children. Education was still an important factor affecting attitudes and practice in Italy and Spain but not (any longer) in the other 3 countries. The role of the general practitioner at the gynecologist as sources of information varied from 1 country to another according to the health care system, but the use of family planning institutions, available in all 5 countries, was disappointing (except in Great Britain), especially since such institutions often were established specifically to provide services to high risk groups. Health reasons were the primary motivation for changing contraceptive method, with reliability following well behind. General perceptions of contraceptive method showed a marked consistency among all 5 countries and in all groups.

The menopause viewed in relation to other life events--a study performed in Belgium.

In order to study the impact of the menopause and hysterectomy in relation to other life events, a study was carried out in Belgium in a random sample of 510 women over 18 yr of age. It was found that these 2 life events are not perceived as being important. Comparison of the findings with those of an earlier unpublished study performed by the International Health Foundation on the same subject indicates that there has been a decrease in the perceived severity of the 2 life events. This could mean that, in the intervening period, socioeconomic status and emotional problems have acquired greater importance, although the change in attitudes might also be partly explained by the fact that the respondents were younger.

A survey of family planning in the Philippines.

PIP: A multicenter survey of 400 married Filipino women 15-40 years of age conducted in 1986 by Family Health International and the International Health Foundation provided valuable information on contraceptive use in the Philippines, as well as factors influencing such practices. The respondents, who were drawn from 10 urban communities in Metro Manila and 10 rural communities in Nueva Ecija Province, averaged 31.5 years of age and had a mean number of 2.9 children. 32% of respondents indicated they desired another child. 225 women (56%) reported they were using no method of contraception. 59 (14%) were protected from pregnancy by tubal sterilization or vasectomy. 77 women (19%) were oral contraceptive (OC) users, and 8 (2%) were IUD users. Only 1 respondent was using a long-acting contraceptive. 3 women used spermicides, 21 (5%) used condoms, 25 (6%) practiced rhythm, and 30 (3%) of the women's husbands practiced withdrawal. Overall, 27% of contraceptive users in this sample used more than 1 method. 26% had been using a contraceptive method for 1-3 years and another 46% for more than 3 years, indicating consistent acceptance of family planning. A sequential trend of nonuse, OC use, and finally sterilization was observed. OC use was highest among women in their late 20s with 2-3 children. Urban-rural residence and socioeconomic factors had little impact on OC use. An encouraging finding was that only 25% of respondents believed that the pill poses important health risks and 61% were aware that pregnancy and childbirth involve greater health risks than OC use. This finding is in opposition to the extremely high levels of misinformation about the dangers of OC use identified in other surveys in developing countries and probably reflects the fact that 77% of women in the present study reported receiving advice on contraception from family planning professionals.^ieng

Contraceptive behaviour of women aged over 35.

PIP: The contraceptive use of women in the 35-39 and 40-44 age groups living in Italy, France, Great Britain, Spain, the Federal Republic of Germany (FRG), Austria, and Sweden is examined. Data were derived from 7 national surveys carried out between 1984 and 1987 by the International Health Foundation. A total of 9876 women aged 15-44 were administered a questionnaire containing questions on demographic information, socioeconomic factors, sexual activity, fertility, as well as current, past, and factor contraceptive use. Postponement of pregnancy while not using contraceptives was highest among women aged 35-39 in Italy (45%) and Sweden (23%). In Italy 30% of exposed women aged 15-44 used no method vs. 5% in Sweden. A higher rate of women aged 35-39 and 40-44 used no contraceptive or relied on rhythm and withdrawal in Italy (60% and 84%) and Spain (40% and 52%) than in Great Britain (17% and 13%) and Sweden (12% and 21%). A substantial percentage of French (25%) and Swedish (31%) women aged 35-39 were using IUDs. Male sterilization exceeded female sterilization only in the FRG (13% vs. 11%) and Austria (7.5% vs. 2.5%). Health and reliability were the most often cited reasons for future changing of contraceptive methods of exposed women aged 35-44. Among alleged advantages and disadvantages reliability, good for sex life, and unsafe for health scored highest. The pill was favored mostly by young women and couples, older women used it less and had more negative opinions about its health effects. Most rumors lacked scientific basis, therefore better education of the public is recommended.^ieng

Epidemiology of contraception with steroids in Western Europe.

A study of contraceptive practice, essential knowledge and communication concerning contraception as well as the related perceptions was conducted among women aged 15-44 in Italy, France, Great Britain, Spain and the Federal Republic of Germany in the years 1984 and 1985. The pattern of contraceptive use and its differential varied strongly between countries. Knowledge, information and communications were observed to be different to a similar degree. Motives for changing contraceptive methods were largely inspired by concern for health and, to a lesser degree, reliability. Perceptions of contraceptive methods were found to be reasonably well in concurrence with reality, with the important exception of the perceptions of the health hazards of the pill which were largely overestimated, giving oral contraception and injustified bad image where effects on health are concerned.

PIP: This study of contraceptive practices among 8544 exposed women 15-44 years (excluding pregnant, infertile, and sexually inactive women) in 1984 and 1985 in Italy, France, Great Britain, Spain, and the Federal Republic of Germany was conducted by the International Health Foundation. Nonuse of contraceptives was high in all countries except Great Britain. Peak use was at 25 years with Great Britain showing a lower peak age. Pill use decreased with increasing age except for German women who maintained a high rate. In Italy and France, higher education meant higher contraceptive use. Religious practice had no or little effect on use, and all methods were considered acceptable based on moral and religious considerations. Contraceptive information from gynecologists was widespread except for Great Britain where the general practitioner and family planning clinic personnel were the information sources. The partner's [reference was the most important influence method choice in Italy, Spain, and Germany while professional sources were most important in France and Great Britain. Media was another influence in Great Britain, France, and Italy. Past change in method or future planned change was influenced by reliability and health issues. Health concerns were an important reason for change in all countries. Correct knowledge of the Pill's mode of action was low in France even though use was high, and the reverse was true in Italy and Span; Germany and Great Britain had high knowledge and use. All countries showed that the perception of pill use was overestimated. Perceptions of method reliability indicated that all countries found the pill to be reliable except in Great Britain. As a health hazard, the IUD, sterilization, and the pill were found to be doubtful except in Great Britain where sterilization was considered safe, and France considered the pill dangerous. In all countries the pill received the lowest score on health safety. The perception was that the pill caused no disturbance in sex life, while barrier methods did and rhythm was considered to be moderately or highly disturbing of sex life. Further investigations of the perceptions of the safety of the pill suggested that misinformation abounds and although positive effects were noted, future use will be related to health concerns.