EDUCATIONAL SESSION 1: HORMONAL CONTRACEPTION: EUROPEAN VERSUS ASIAN VIEW
ES01-1
Hormonal contraception: European view
Alfred O. Mueck
University Women’s Hospital, Tuebingen, Germany
The ‘First global conference on contraception, reproductive and sexual health, Copenhagen, Denmark (May 2013)’ will get an overview on the most important issues in the field of ‘Gynecological Endocrinology’ comparing for the first time worldwide the various countries as far as it can be achieved using, if possible, the same methods of assessment. ‘Hormonal Contraception’ seems to be an option for all countries to avoid unwanted pregnancies, however, there are large differences across the countries. Comparing with non-European countries some general aspects can be given, like much higher use of oral contraceptives (OC) (about 20–30%) compared to Japan or China (1–2%) or Russia (5%), and also higher use of reversible long-term contraception, in Europe 10% compared to less than 0.2% in China or Japan. However, within Europe there are differences between the countries, for example according to a large study across five European countries (France, Germany, Italy, Spain, UK) interviewing 12,000 randomly selected women, aged 15 to 49 years, by a standardised questionnaire, which addressed the current methods of contraception. The acceptance rate for the use of OC seems to be highest in France (up to 50%), lower in Germany and UK (about 30%), and lowest in Italy and Spain (ca. 20%) whereby the population of women aged 15 to 49 years is highest in Germany (about 20 million), compared to France and UK (about 15 million), somewhat lower in Italy and Spain (about 12 million), where also the starting age of OC is higher (over 20 years) compared to the other countries (first OC below 20 years). Despite different use and behaviour the awareness of side effects and risks are quite similar in the European countries which can be explained by the good communication in the scientific field. So in Europe it seems quite clear that the main risk of combined contraception is venous thrombosis which may not only depend on the estrogen but also on the progestogen component, whereas in countries like China there is almost no discussion about this issue. Similar is true for arterial risks like stroke and myocardial infarction which may be important in women having risk factors like smoking, obesity and hypertension. In contrast to, e.g., Asian countries much more discussion is seen in Europe on the beneficial or detrimental bone effects of hormonal contraception. However, with increasing use of hormones for contraception also in other countries, these main topics will become more and more similar across the world.
ES01-2
The role of the progestogen for the thromboembolic risk of hormonal contraceptives
Adolf Eduard Schindler
Institute for Medical Research and Education, Essen, Germany
Progestogens seem to play a role in thromboembolic risk, which comprises deep vein thrombosis and pulmonary embolism. For this, estrogen type and dose related activation of haemostasis (coagulation and fibrinolysis) is required. Progestogens as monotherapy in doses used for contraception are not associated with an increased thromboembolic risk.
Ethinylestradiol is far more thrombogenic compared with estradiol or estradiol valerate, since it affects to a greater extent liver metabolism in a dose-dependent manner. The changes in haemostasis induced by oral hormonal contraceptives seems to be related to the pattern of the partial effects of each progestogen. Androgens seems to have a profibrinolytic effect. Progestogens with partial androgenic effects seem to be related to the decreased metabolic effects expressed for instance by a lower SHBG- and CBG-levels, when used together with estrogen compared to estrogen alone.
Clinically, oral hormonal contraceptives with a progestogen having partial androgenic effect have a lower likelihood of a thromboembolic event than an oral hormonal contraceptive with an antiandrogenic progestogen, which leads to higher metabolic activity as expressed by the SHBG-levels and a more activated haemostatic system, which is in line with a higher thromboembolic risk.
ES01-3
Hormonal contraception: Asian view
Xiangyan Ruan
Beijing Obstetrics & Gynecology Hospital, Capital Medical University, Beijing, China
An ‘Asian View’ on contraception depends primarily on the frequency of different use of the available methods to avoid unwanted pregnancy. In some respects such a view comparing with other countries can be given because, for example, the use of oral contraceptives (OC) is much higher in Western compared to Asian countries – about 20 to 30% in USA and Europe, compared to 1 to 2% in China and Japan. This might reflect different opinions of the prescribing doctors and users on the benefits and risks of OC, but perhaps even more the difference depends on reasons without medical background like the different strategies of pharmaceutical companies to be active in the various countries. But there are also large differences comparing between the Asian countries, for example, the much higher use of Intrauterine Devices (mostly copper IUD) in China (about 30%) compared to Japan (about 5%). Likewise also the use comparing other nonhormonal contraception is very different – condoms less than 10% in China compared to about 50% in Japan, female sterilisation more frequent in China (about 30%) compared to Japan (about 5%). According to the lower use of hormonal methods in Asia compared to Western countries there are also different opinions about risks and benefits of hormonal contraception, but it seems to be impossible to give a view of Asia in general. However, we are able to answer some crucial questions on the basis of our own experience in our hospital (one million out- and emergency patients/year) and especially derived from our experience in our Department of Gynecological Endocrinology (up to 80,000 outpatients/year). Comparing with Europe we can answer some main questions on the use of hormones as follows: The risk of venous thrombosis seems to be lower in China, at least there is not much discussion on this. There is some discussion about the risk of breast cancer. Using OC our patients mostly fear weight gain and bleeding problems. Chinese doctors are aware of the non- contraceptive benefits of OC like in PCOS and signs of hirsutism. However, China needs more information about all the benefits of OC (use in 2010 only 1.3%) and of hormonal long acting methods like hormonal injections and implants (use less than 0.2%, compared to European countries about 10%). Also there is a need for more information about the hormonal IUD, use in China is less than 0.2%, about 100,000/year, 50% for contraception, 50% for bleeding problems.
EDUCATIONAL SESSION 2: LONG-ACTING REVERSIBLE CONTRACEPTION (LARC)
ES02-2
Long acting reversible contraception and repeat abortion
Anna Glasier1,2
1University of Edinburgh, Scotland, UK, 2University of London School of Hygiene and Tropical Medicine, London, UK
It is now well recognised that women who choose to use an intrauterine or implantable contraceptive after having an abortion are significantly less likely to return for a repeat abortion than women who choose other methods – including injectables. In many countries LARC may seldom be chosen for a variety of reasons including cost, lack of appropriately skilled or enthusiastic providers and unfamiliarity with or negative perceptions of these methods among potential users. Recent research has demonstrated that these barriers can be overcome.
LARC methods are more likely to be chosen if made available at the time of the abortion. As we move increasingly towards medical abortion being done, or at least completed, at home, the opportunity for immediate initiation of these methods is lost and we need to think of innovative ways to improve access to delayed insertion of implants and intrauterine contraceptives.
ES02-3
Safety of LARC quick start
Sharon Cameron
NHS Lothian, Edinburgh, UK
In recent years there has been a trend towards a ‘quick start’ of contraception, that is, initiation of contraception at any time in the menstrual cycle, rather than waiting for the next period to start.
The most effective methods of contraception are the long acting reversible (LARC) methods; namely the intrauterine system (IUS), intrauterine device (IUD), implant and injectable. However, there remains considerable controversy about quick-starting LARC methods for women who are postpartum or post abortion.
In addition to being more convenient for the women and avoiding an extra visit to the contraceptive provider, quick-starting LARC at these times has the potential to prevent more unintended pregnancies for more women. However, concerns remain about possible increased risks associated with quick-starting LARC at these times, and this is reflected in the differing guidelines between countries (WHO, US, UK) on medical eligibility criteria for use of LARC post-abortion and postpartum. However, new evidence has been emerging on the safety of LARC methods postpartum and post abortion that will support future clinical guidance and practice in these areas.
There is good observational data that immediate commencement of an IUD or IUS or implant post abortion significantly reduces the likelihood of a further abortion within the next few years. Although some studies have reported higher expulsion rates of an IUD/IUS with immediate insertion, there is no evidence that perforation or infection rates differ and continuation rates are higher than with delayed insertion. Furthermore, women who quick start an IUS post abortion have reduced days of bleeding.
There are a growing number of studies that demonstrate that insertion of an IUD or IUS postpartum (after vaginal birth or at caesarean section) is practical and safe (even in developed countries). Although expulsion rates are higher with immediate postpartum insertion of an IUD/IUS, overall complication rates are low. There is also evidence to suggest that quick start of the implant in young mothers is associated with reduced risk of another birth within 12 months, and that delay in insertion is a barrier to uptake of the method.
Further studies on quick start of LARC post abortion and postpartum are required including data on bleeding patterns with injectable or implant when initiated at these times.
EDUCATIONAL SESSION 3: EMERGENCY CONTRACEPTION
ES03-1
Levonorgestrel (LNG) – development of hormonal methods of emergency contraception
Pak Chung Ho
University of Hong Kong, Hong Kong, China
Emergency contraception is a method of contraception used after an unprotected intercourse, or in the case of failure of the barrier method or in the case of rape. The first hormonal method for emergency contraception consisted of high doses of oestrogens which caused a lot of gastrointestinal side effects like nausea and vomiting. This was replaced by the Yuzpe regimen which consisted of two doses of combined oral contraceptive pills taken 12 hours apart. Each dose contained 100 mcg of ethinyl oestradiol and 50 mcg of levonorgestrel. However, the incidence of gastrointestinal side effects is still high. As we believed that oestrogen is the main cause for the nausea and vomiting, we conducted a randomised clinical trial comparing the efficacy and side effects of Yuzpe regimen with those of two doses of 0.75 mg levonorgestrel taken12 hours apart. The results showed that the incidence of side effects was significantly lower in the levonorgestrel group. The pregnancy rate was also lower in the levonorgestrel group but the difference was not statistically significant. Subsequent multicentre studies confirmed that two doses of 0.75 mg of levonorgestrel taken 12 hours apart is more effective and better tolerated than the Yuzpe regimen and that a single dose of 1.5 mg of levonorgestrel is as effective as two doses of 0.75 mg of levonorgestrel taken 12 hours apart with no significant difference in the incidence of side effects. The single dose regimen is more convenient. Mifepristone, an antiprogestin has been shown to be more effective than the Yuzpe regimen and the incidence of gastrointestinal side effects is also less frequent. A WHO multicentre study showed that mifepristone is as effective as levonorgestrel. As mifepristone is not available in many countries, levonorgestrel became the drug of choice for emergency contraception. Levonorgestrel probably acts by its effect on ovulation. The failure rate of levonorgestrel is usually higher in those women with a longer coitus-treatment interval, further acts of intercourse in the same cycle or high BMI. Therefore, women should be advised to take the emergency contraceptive pills as soon as possible after intercourse and to refrain from further acts of intercourse in the same cycle.
ES03-2
Ulipristal acetate (UPA) vs levonorgestrel (LNG) and quick start of contraception
Sharon Cameron1, Kristina Gemzell Danielsson2, Christine Klipping3, Lucy Michie4, Cecilia Berger5, Delphine Levy6, Jean Louis Abitbol6
1NHS Lothian, Edinburgh, UK, 2Karolinska Institutet, Stockholm, Sweden, 3the Netherlands, 4Chalmers Sexual Health Centre, Edinburgh, UK, 5Sweden, 6HRA Pharma, France
Background: Ulipristal acetate (UPA) is a progesterone receptor modulator that is available for emergency contraception (EC) and can be taken up to 120 hours after unprotected intercourse. A meta-analysis of clinical trials comparing UPA with levonorgestrel (LNG) for EC demonstrated that UPA has higher efficacy than LNG. Since further unprotected sex after EC is associated with a significantly increased risk of pregnancy, it is important that women establish an effective method of ongoing contraception immediately after EC. This is often termed ‘quick-start’. Given the fact that UPA is a progesterone receptor modulator, there is theoretical concern that it might alter the effectiveness of progestogen containing contraception. A study was therefore designed to determine if UPA (30 mg) would impact the efficacy of a commonly prescribed combined oral contraceptive (COC) containing 30 µg ethinylestradiol and 150 µg levonorgestrel initiated immediately afterwards.
Methods: UPA or placebo was administered when the dominant follicle was > 13 mm. COC was started on the following day and continued for 21 days. Follicular growth, monitored by ultrasound, and hormonal measurements were performed three times a week before and during treatment. The primary endpoint was time to ovarian quiescence defined by a Hoogland score ≤ 3.
Results: Seventy-six women received UPA (n = 37) or placebo (n = 39), followed by COC. Quiescence was reached in 47/76 subjects (62%), 24 in the UPA group and 23 in the placebo group. Median time to quiescence was 5 days for UPA and 6 for placebo. The cumulated distribution of time to quiescence was similar in both groups and all had reached quiescence after 14 days of COC. Thirty percent of women ovulated in both groups. In the UPA group, no ovulation occurred before 5 days. A further 3 women ovulated within 12 days of UPA intake. In the placebo group, 5/12 of ovulations occurred before 5 days and all women had ovulated by day 8 of COC. Follicle diameter at the time of treatment initiation and use of COC in the previous cycle were significant covariates in competing risk regression analyses.
Conclusion: UPA for EC followed by quickstart of a COC does not appear to impact the ability of the COC to induce ovarian quiescence. This suggests that UPA should not impact upon the efficacy of the COC.
ES03-3
Copper-intrauterine devices for emergency contraception
Linan Cheng
Shanghai Institute of Planned Parenthood Research, Shanghai, China
Emergency contraception (EC) refers to use of a drug or device as an emergency method to prevent pregnancy after unprotected intercourse. The first report of using the copper-intrauterine device (Cu-IUD) for EC was in 1976 by Dr Lippes. From 1979 to 2011, there were 42 studies (7034subjects) published in English or Chinese, with a defined population of women who presented for EC and were provided with Cu-IUDs. The data collected from six countries identifies the use of eight different types of Cu-IUDs. The Cu-IUDs were inserted between two and ten or more days after intercourse; the majority of insertions (74%) occurred within 5 days of intercourse. The pregnancy rate among these studies (excluding one outlier) was 0.09%.
There has been very strong evidence to confirm that the Cu-IUD is a highly effective method of contraception after unprotected intercourse. Because they are safe for the majority of women, highly effective, and cost-effective when left in place as ongoing contraception, whenever clinically feasible. It is highly accepted by both parous women and nulliparous women. Cu-IUDs should be included in the range of emergency contraception options offered to patients presenting after unprotected intercourse.
ES03-4
High hopes versus harsh realities: The population Impact of ECPs
James Trussell1,2
1Princeton University, Princeton, NJ, USA, 2The Hull York Medical School, Hull, UK
Despite early hopes that widespread use of emergency contraceptive pills (ECPs) could prevent half of all unintended pregnancies and abortions in the United States each year, most studies designed to assess this have not shown that increased access to ECPs lowers pregnancy or abortion rates. Fifteen studies, conducted between 1998 and 2011, compared increased access to ECPs to standard access. In most studies, women were assigned either to an advance provision group (in which women were given a supply of ECPs for later use should the need arise) or to a standard provision group (in which women obtain ECPs from a clinic in the regular way). In all but one of these studies, there was no significant difference in pregnancy rates between the intervention and control groups. The exception is a new study, conducted in Egypt, of women using the Lactational Amenorrhea Method. In this study, women given ECPs in advance were significantly less likely to become pregnant than those in the control group; the authors suggest that uptake of ongoing contraception in Egypt is typically quite high, and that women in this study used EC to protect themselves until they could obtain a more effective method of ongoing contraception. Some explanations for the overall disappointing results include methodological flaws in the studies (although some of the studies were well-designed), a theoretical increase in risk-taking when access to ECPs is improved (although this is unsupported by most evidence), the relatively low efficacy of ECPs (the precise efficacy of ECPs is difficult to measure and is not precisely known), and insufficient use of ECPs to cover all acts of unprotected intercourse (clearly and consistently shown to be a problem). Although it is disappointing that a population-level impact has not been demonstrated, ECPs can be effective for individuals and are a very important option for women who need a second chance to prevent pregnancy after sex has occurred. EC advocates are cautioned not to oversell ECPs by implying that they will reduce unintended pregnancy or abortion rates or be cost-effective; rather, the emphasis should be placed on efficacy for individuals and each woman's right to all available options to prevent pregnancy. The best emergency contraceptive option is the copper IUD, which is over 99% effective, does not lose efficacy among women of higher BMI, and provides at least 5 to 10 years of excellent ongoing contraception.