Hormonal Contraception: Asian View. Hormonal Contraception: Asian View: focused on Chinese View. Prof.Dr.Xiangyan Ruan, MD.PhD

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Asian View Prof.Dr.Xiangyan Ruan, MD.PhD Beijing Obstetrics & Gynecology Hospital, Capital Medical University (China) WHO Collaborative Centre - Director of Dept. of Gynecological Endocrinology & & - Fertility Protection Centre,Beijing,China Asian View: focused on Chinese View Xiangyan Ruan, MD.Phd.Prof. Beijing Obstetrics & Gynecology Hospital, Capital Medical University (China) WHO Collaborative Centre - Director of Dept. of Gynecological Endocrinology with main importance for clinical practice Contraception compared to rate of induced abortions to prevent unwanted pregnancies in China (2010) - Number of women in reproductive age in China: 363 Million women - 50.3% of these women take no conception methods - only 12.3% women take conception methods every time - eight ten Million induced abortions to prevent unwandted pregnancies every year in China! Urgent need for more education Urgent need for more contraception China Government, Health Authorities, Data 2010 1

In Asia and Europe the same percentage of induced abortion: Need for contraception all over the world to prevent unwanted pregnancies Singh S, Sedgh G, Hussain R. Unintended pregnancy: worldwide levels, trends, and outcomes. Stud Fam Plann. 2010 Dec; 41(4): 241-50. Singh S, Sedgh G, Hussain R. Unintended pregnancy: worldwide levels, trends, and outcomes. Stud Fam Plann. 2010 Dec; 41(4): 241-50. Contraception in Asia: Large differences between China and Japan, but in both countries < 2% Italy** 18% 24% 33% 19% 5% USA*** 22% 1 8% 39% 19% Germany 16% 14% 1 7% 18% 34% Japan 15% 37% China 38% 10% 2% Russia 34% 33% 45% 5% 45% n.a. 22% 8% 3% Sources: *female and male sterilizations: **Pan European FC Study 2003 ***Advance data: Use of contraception and use of family planning services in the United States 1982-2002 Contraception in China Changes over the last 30 years Importance of Long acting reversible methods (Percentage of Women in Reproductive age) - non-hormonal constant about 50% still small and further ongoing increase - small increase of LNG- (Mirena available since??? years), however, still less than 0.2% Use about 100,000 Mirena/year, about 50% for contraception 50% for treatment such as Heavy Menstrual Bleeding (HMB) - Importance of injections: less than 0.2% (despite DMPA is available since 30 years) - Importance of implants: less than 0.2% (despite Implanon is available since > 10 years) Contraception in China Changes over the last 30 years Importance of contraceptive pills - containing levonorgestrel or desogestrel available since 20-30 years - Availability of other : Ethinyl Estradiol/Drospirenone (Yasmin) since two years Ethinyl Estradiol/Cyproterone acetate for symptoms of hyperandrogenism, especially in PCOS - still no progestin-only pills available (exception levonorgestrel as emergency contraception) - since launch of Yasmin (2010), small increase, but still less than 2% of women in reproductive age - In specialized Women's hospitals more than 95% of COC is used for problems in Gyn.Endocrinology (like bleedings, PCOS etc), but not for contraception China Government, Health Authorities, Data 2010 China Government, Health Authorities, Data 2010 2

Contraception in China: Changes over the years (Percentage of Women in Reproductive Age) Own experience in clinical practice during the last 10 years Importance and use of contraception in China - it is difficult to get more detailled figures for China regarding different types of contraception, especially for - My own view is based on experience in one of the largest (may be the largest) departments of Gyn. Endocrinology in China, which was founded 10 years ago as the first in China Own view is somehow different from average use, because: - we see more patients with preexisting diseases - we are particularly good informed by the companies of new activities, of new substances launched and coming soon - we are involved in studies for contraception, particularly also using new types of - we see many patiens: every day > 3,000 outpatients in Beijing OB/GYN- Hospital, about 500/day in our department, increasing every year China Government Health Authorities Data 2010 About 70,000 outpatients 2012 in our Department of Gyn.Endocrinology Beijing OB/GYN Hospital, Capital Medical University, China Own experience in clinical practice during the last 10 years Importance and use of contraception in China - in future we can expect an increase of the use of caused by more informations to the women via media, internet etc. (in our department > 30% of contraceptive methods used; all over China average use only about 1.5%)) - however, Chinese women often prefer as long-acting method, and non-hormonal s are free in China (family planning policy) - more use of injections can not be expected, especially because Chinese women do not like it. - at least in the near future also more use of implants can not be expected Main reason are bleeding problems observed during launch of Implanon, without information and education about this problem - the use of Mirena is well assessed by experts, but it is too expensive and more education about benefits and problems (bleedings) is needed Own experience in clinical practice during the last 10 years Importance of non-contraceptive benefits in China - Chinese gynecologists are well informed about the benefits to treat symptoms of hyperandrogenism like acne and hirsutism. For these symptoms almost exclusively only Diane 35 has the indication. - There is only very little discussion about other non-contraceptive benefits with the exception of experts in the field of hormones (exception: COC are often used for bleeding problems!) - the benefits of long-cycle treatment using COC are not known, Until now no use of this form of treatment (we started just now in our department, especially in women with PCOS). 3

Own experience in clinical practice during the last 10 years Importance of non-contraceptive benefits in China - An exception for the importance of non-contraceptive benefits also in China may be the use of contraceptive pills in PCOS in specialized centres. - In our department about 180 women with PCOS/day whereby almost exclusively Diane is used *) 1) to treat symptoms of hyperandrogenism 2) to treat hyperandrogenism, which can treat the PCOS (in China this is a labelled indication for Diane!) 3) to increase fertility in women with PCOS who want to get pregnancy (use for three months) Benefits for the use of COC with special importance in women with PCOS (if not wanting fertility) Contraceptive Reduction Pregnancy > 99 Deaths at birth > 90 Abortions > 90 (spontaneous/induced) Extrauterinal Pregnancy > 90 modified according Rabe T, Runnerbaum B. Fertility Control Update 2000 Springer New York, pp. 99-120 Noncontraceptive Reduction Cycle disturbances 25-50 Dysmenorrhea 25-50 Anemia 25 Acne, Hirsutismus 10-50 Pelvic inflammation 50 Rheumatoid arthritis 50 Benign Breast Disease 25-50 Benign ovarial tumours 25 Ovarial follicle cysts 25 Ovarial carcinoma 50 Endometrium carcinoma 50 Colon/Rectal carcinoma 50 Benefits for the use of COC with special importance in women with PCOS (without wanting fertility) Contraceptive Reduction Pregnancy > 99 Deaths at birth > 90 Abortions > 90 (spontaneous/induced) Extrauterinal Pregnancy > 90 In addition COC like Diane can decrease hyperandrogenism which is a main factor in the pathophysiology of PCOS! modified according Rabe T, Runnerbaum B. Fertility Control Update 2000 Springer New York, pp. 99-120 Noncontraceptive Reduction Cycle disturbances 25-50 Dysmenorrhea 25-50 Anemia 25 Acne, Hirsutismus 10-50 Pelvic inflammation 50 Rheumatoid arthritis 50 Benign Breast Disease 25-50 Benign ovarial tumours 25 Ovarial follicle cysts 25 Ovarial carcinoma 50 Endometrium carcinoma 50 Colon/Rectal carcinoma 50 with main importance for clinical practice Own experience during endocrinological education of gynecologists over the last 10 years in China Assessement of main risks using COC 1) Venous thromboembolism (VTE): only little discussion, induced not by Chinese gynecologists but by the BAYER company (giving us information about the controversial studies) VTEs are very rare in China, genetic alteration of clotting factors very rare Since 2 months discussion about CPA, caused by information of BAYER company; labelling perhaps will be changed. 2) Stroke: Risk largely not known (exception experts) need for more education in risk factors (smoking, hypertension, obesity etc.) 3) Myocardial Infarction: risk largely not known (exception experts) 4) Risk of Bone loss and fractures: risk largely not known (exception experts) 5) Cervical cancer: risk well known, no problem in practice (annually cervical smear, vaccination only available in Hongkong) Own experience during endocrinological education of gynecologists over the last 10 years Assessement of side effects using COC in China 1) Weight gain: very often observed in clinical practice greatest fear of the gynecologists and of the women 2) Irregular bleedings/spotting: problems not with COC, but with progestin-only (, implant) Bleeding problems caused by ovarian cysts 3) loss of libido: perhaps important, but no data available others like headache, migraine, mood changes, breast tenderness, acne not really a problem! 6) Breast cancer: more than 50% of gynecologists growing awareness and fear 4

Main problem in China: No time to give extended counselling (3,000 outpatients/day in our hospital; 500/day in our department!) Breast Cancer Collaboration project Germany - China J Sexual Medicine 2010; 7: 2139-2148 Contraception 2010; 82: 155-159 1,096 German medical students using COC different types of contraception The same study now will be performed in Beijing OB/GYN Hospital using the validated Female Sexual Function Index (FSFI score) aim: 10,000 Chinese women Leading causes of death in view of the women PR1-membrane-bound high expressed in patients with breast cancer, mediating progestin-effects via cross-talk with other cell components Old age () /don t know (16%) Actual causes of death among US women Heart disease (18%) Smoking () Stress (2%) Ovarian cancer (9%) Progesterone Receptor 1 Membrane-bound Progesterone mpr cancer (13%) Cell membrane PAIRBP1 Lung cancer (2%) Heart disease (45%) ERK1/2? PR/PGR Breast cancer (39%) (25%) Pneumonia (4%) COPD (4%) Cell nucleus Ovarian cancer (<2%) Breast cancer (4%) Lung cancer (5%) cancer (1) http://www.keepstudy.org/why_keeps/keeps_causedeath.pdf Mueck AO, Xiangyan Ruan. Edwards et al., Journal of Steroid Biochemistry & Molecular Biology 83 (2003) 173 186 Horm Mol Biol Clin Invest 2011; 5: 105-116 5

Hormonal contraception: Asian View Conclusion - Induced abortion rate to prevent unwanted pregnancies similar to Europe (although large differences between the countries) - Most frequently used is non-hormonal (50%), almost no change since 30 years; COC since 20 y. less than 2%, slowly increasing - Because of the low use of COC, the risks are not well known in China, only little discussion about VTE (this risk is in general low in China) - By far most important side effects weight gain and bleedings. Increasing fear of risk of breast cancer (gynecologists and women) - With increasing use of COC and LNG- more bleeding problems More education especially needed: - benefits of long-acting contraception like LNG- - differences between - use and benefits of long-cycle regimen using - non-contraceptive benefits of COC - options to treat bleeding problems Educational Session 1 Europe/China European vs. Asian View Europe contracepgon methods rates 40,0% 35,0% China concepgon methods rates 35,5% 50,0% 45,0% 30,0% 25,0% Asian View 43,7% 40,2% 40,0% 24,9% 35,0% 22,5% 30,0% 20,0% Beijing, China 25,0% 15,0% 10,0% 15,0% 8,2% 5,7% 5,0% <3.0% 0,0% condom vaso Tubal ligati ligation on Injectio n and implant 9,2% 10,0% 4, 5,0% 0,6% XIANGYAN RUAN 20,0% 2,0% 0,0% others vaso Tubal ligati condom ligation on 0,5% 0,2% others Injectio n and implant Tuebingen, Germany Thank you for your attention! 6