今日の臨床サポート

避妊法、緊急避妊法

著者: 寺内公一 東京医科歯科大学 茨城県地域産科婦人科学講座

監修: 小林裕明 鹿児島大学大学院医歯学総合研究科生殖病態生理学

著者校正/監修レビュー済:2021/06/16
参考ガイドライン:
  1. 日本産科婦人科学会/日本産婦人科医会:産婦人科診療ガイドライン婦人科外来編2020
  1. 日本産科婦人科学会/日本女性医学学会:低用量経口避妊薬、低用量エストロゲン・プロゲスチン配合薬ガイドライン2020年度版
  1. 日本産科婦人科学会:緊急避妊法の適正使用に関する指針(平成28年度改訂版)
患者向け説明資料

概要・推奨   

  1. 低用量経口避妊薬(OC)、低用量エストロゲン・プロゲスチン配合薬(LEP)を処方するときには以下の説明を行う。
  1. OCは可逆的避妊法のなかで避妊効果において最も優れた方法の1つであり、安全性も高い。
  1. 月経困難症・過多月経の改善効果がある。
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薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、
著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適用の査定において保険適用及び保険適用外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適用の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
寺内公一 : 企業などが提供する寄付講座(キッコーマン株式会社)[2021年]
監修:小林裕明 : 講演料(中外製薬株式会社,アストラゼネカ株式会社),奨学(奨励)寄付など(中外製薬株式会社)[2021年]

改訂のポイント:
  1. 「産婦人科診療ガイドライン婦人科外来編2020」「低用量経口避妊薬、低用量エストロゲン・プロゲスチン配合薬ガイドライン2020年度版」「緊急避妊法の適正使用に関する指針(平成28年度改訂版)」に基づき文言の修正を行った。

まとめ

疾患情報(疫学・病態)  
  1. 避妊とは、妊娠を望まない場合、受胎を防ぐために薬剤や器具を使用し、または月経周期における排卵期の予測を行ったり、射精の方法を考慮して妊娠を防ぐ方法のことをいう。
  1. 避妊法には可逆的な方法と不可逆的な方法が存在する。
  1. 可逆的避妊法のうちで避妊効果が高いのが低用量経口避妊薬(OC)と子宮内避妊用具(IUD)・レボノルゲストレル放出子宮内システム(LNG-IUS)である。特にOCは安全性も高いことが明らかになっている[1][2]
  1. 不可逆的な避妊法としては卵管結紮や精管結紮が挙げられる。
  1. 緊急避妊とは、妊娠を望まない女性が、避妊を行わなかった、避妊法が不適切であった、性交を強要されたなど、妊娠に対して無防備な状況で行われた性交渉(Unprotected Sexual Intercourse、UPSI)後に妊娠の危険性を減少させる手段のことをいう。
  1. 緊急避妊法としては従来中用量ピルを用いたYuzpe法が行われていたが、レボノルゲストレル(ノルレボ錠)が2011年に緊急避妊薬として承認されたため、現在ではレボノルゲストレル単回投与法が経口薬を用いた唯一の緊急避妊法となった。
  1. レボノルゲストレル単回投与法はYuzpe法に比べて妊娠阻止率に優れており、悪心・嘔吐などの有害事象も少ない[3][4][5]
  1. 薬剤を服用しない緊急避妊法として、性交後120時間以内にIUDを挿入する方法もある[3][6]
 
パール指数
  1. パール指数とは100組のカップルが1年間その避妊法を行った際の妊娠例数と同義であるが、わが国で実施された臨床試験の成績によれば、OCのパール指数は0~0.59であり[1]、コンドーム、殺精子剤、リズム法等の避妊法と比較すると、避妊法のなかでは最も低いものの1つである。海外の報告では、OCを理想的に服用した場合の失敗率(パール指数:使用開始1年間の妊娠率)は0.3、一般的な服用(飲み忘れるリスク等も加味)の場合9である。
 
各種避妊法使用開始1年間の妊娠率[7]
  1. 避妊せず
  1. 1年間の妊娠率 85%
  1. ピル(OC)
  1. 理想的な使用:0.3%、一般的な使用:9%、1年間の継続率:67%
  1. コンドーム
  1. 理想的な使用:2%、一般的な使用:18%、1年間の継続率:43%
  1. 殺精子剤
  1. 理想的な使用:18%、一般的な使用:28%、1年間の継続率:42%
  1. ペッサリー
  1. 理想的な使用:6%、一般的な使用:12%、1年間の継続率:57%
  1. 薬物添加IUD
  1. 理想的な使用:0.2~0.6%、一般的な使用:0.2~0.8%、1年間の継続率:78~80%
  1. リズム法
  1. 理想的な使用:0.4~5%、一般的な使用:24%、1年間の継続率:47%
  1. 女性避妊手術
  1. 理想的な使用:0.5%、一般的な使用:0.5%、1年間の継続率:100%
  1. 男性避妊手術
  1. 理想的な使用:0.1%、一般的な使用:0.15%、1年間の継続率:100%
    *理想的な使用とは:選んだ避妊法を正しく続けて使用している場合である。また一般的な使用とは、飲み忘れを含め一般的に使用している場合である。
問診・診察のポイント  
  1. OCの服用禁忌となる疾患や病態を有していないか、あるいは慎重投与例に相当しないかを聴取する[8]
 
 
 
  1. 喫煙は有害事象の発症率を上昇させる報告が多いため、喫煙歴については特に十分な問診を行う[2]
  1. 不可逆的な避妊方法を選択する際には、特に慎重に説明し同意を得る。

今なら12か月分の料金で14ヶ月利用できます(個人契約、期間限定キャンペーン)

11月30日(火)までにお申込みいただくと、
通常12ヵ月の使用期間が2ヶ月延長となり、14ヵ月ご利用いただけるようになります。

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文献 

著者: Martin Vessey, Rosemary Painter, David Yeates
雑誌名: Lancet. 2003 Jul 19;362(9379):185-91. doi: 10.1016/S0140-6736(03)13907-4.
Abstract/Text BACKGROUND: As part of the Oxford Family Planning Association study, we compared mortality in relation to oral contraceptive use and smoking to highlight the differences between them from the perspective of public health.
METHODS: The study consisted of 17032 women, aged 25-39 years at entry, recruited between May 1, 1968, and July 31, 1974, who had used oral contraceptives, a diaphragm, or an intrauterine device. We assessed mortality from follow-up data recorded until Dec 31, 2000. The analysis is based on woman-years of observation.
FINDINGS: We analysed 889 deaths. Women who had ever used oral contraceptives had increased mortality from cervical cancer (rate ratio 7.2, 95% CI 1.1-303), and decreased mortality from other uterine (0.2, 0.0-0.8) and ovarian cancers (0.4, 0.2-0.7). Oral contraceptives had some adverse effect on deaths from ischaemic heart disease in women who smoked 15 or more cigarettes per day. For all causes of mortality, the rate ratio for death in women who ever used oral contraceptives was 0.89 (95% CI 0.77-1.02). By contrast, this rate ratio was 1.24 (1.03-1.49) in those who smoked one to 14 cigarettes per day, and 2.14 (1.81-2.53) in those who smoked 15 or more cigarettes per day.
INTERPRETATION: There was no harmful effect of oral contraceptive use on overall mortality. By contrast, death from all causes was more than twice as high in smokers of 15 or more cigarettes a day as in non-smokers. The harmful effect was already apparent in women aged 35-44 years.

PMID 12885478  Lancet. 2003 Jul 19;362(9379):185-91. doi: 10.1016/S014・・・
著者:
雑誌名: Lancet. 1998 Aug 8;352(9126):428-33.
Abstract/Text BACKGROUND: A previous randomised study suggested that the progestagen, levonorgestrel, given alone in two separate doses each of 0.75 mg caused nausea and vomiting in fewer women and might be more effective than the Yuzpe regimen of combined oral contraceptives for emergency contraception, although the difference was not significant. We compared these two regimens when started within 72 h of unprotected coitus.
METHODS: We enrolled in the double-blind, randomised trial 1998 women at 21 centres worldwide. Women with regular menses, not using hormonal contraception, and requesting emergency contraception after one unprotected coitus, received levonorgestrel (0.75 mg, repeated 12 h later) or the Yuzpe regimen (ethinyloestradiol 100 microg plus levonorgestrel 0.5 mg, repeated 12 h later).
FINDINGS: Outcome was unknown for 43 women (25 assigned levonorgestrel, 18 assigned Yuzpe regimen). Among the remaining 1955 women, the crude pregnancy rate was 1.1% (11/976) in the levonorgestrel group compared with 3.2% (31/979) in the Yuzpe regimen group. The crude relative risk of pregnancy for levonorgestrel compared with the Yuzpe regimen was 0.36 (95% CI 0.18-0.70). The proportion of pregnancies prevented (compared with the expected number without treatment) was 85% (74-93) with the levonorgestrel regimen and 57% (39-71) with the Yuzpe regimen. Nausea (23.1 vs 50.5%) and vomiting (5.6 vs 18.8%) were significantly less frequent with the levonorgestrel regimen than with the Yuzpe regimen (p<0.01). The efficacy of both treatments declined with increasing time since unprotected coitus (p=0.01).
INTERPRETATION: The levonorgestrel regimen was better tolerated and more effective than the current standard in hormonal emergency contraception. With either regimen, the earlier the treatment is given, the more effective it seems to be.

PMID 9708750  Lancet. 1998 Aug 8;352(9126):428-33.
著者: L Cheng, A M Gülmezoglu, E Ezcurra, P F Van Look
雑誌名: Cochrane Database Syst Rev. 2000;(2):CD001324. doi: 10.1002/14651858.CD001324.
Abstract/Text OBJECTIVES: To determine which emergency contraceptive method following unprotected intercourse is the most effective, safe and convenient for use in preventing pregnancy.
SEARCH STRATEGY: The search strategy included electronic searches of the Cochrane Controlled Trials Register, Popline, Chinese biomedical databases and HRP emergency contraception database. In addition, references of retrieved papers were searched and researchers in the field and two pharmaceutical companies were contacted.
SELECTION CRITERIA: Randomized or quasi-randomized studies including women attending services for emergency contraception following a single act of unprotected intercourse were eligible.
DATA COLLECTION AND ANALYSIS: Data on outcomes and trial characteristics were extracted in duplicate by two reviewers. Results were expressed as relative risk using a fixed-effects model with 95 % confidence interval.
MAIN RESULTS: Fifteen trials were included in the review. The majority (8/15) of the trials were conducted in China. Most comparisons between different interventions included one or two trials although some trials were appropriately sized with power calculations. Levonorgestrel appears to be more effective than Yuzpe regimen (2 trials, RR: 0.51, 95 % CI: 0.31-0.84) and causes less side-effects (RR: 0.80, 95 % CI: 0.76 to 0.84). Levonorgestrel was less effective than locally manufactured mifepristone in a single, large Chinese study (RR: 2.17, 95 % CI: 1.00 to 4.77). Effectiveness of different doses of mifepristone seem to be similar but the frequency of delay in onset of the subsequent menstrual period increases with increased dose.
REVIEWER'S CONCLUSIONS: Levonorgestrel and mifepristone seem to offer the highest efficacy with an acceptable side-effect profile. One disadvantage of mifepristone is that it causes delays in onset of subsequent menses which may induce anxiety. However, this seems to be dose-related and low doses of mifepristone minimise this side-effect without compromising effectiveness. Future studies should compare the effectiveness of mifepristone with levonorgestrel.

PMID 10796776  Cochrane Database Syst Rev. 2000;(2):CD001324. doi: 10.・・・
著者: M Luerti, A Tonta, P Ferla, R Molla, F Santini
雑誌名: Contraception. 1986 Jan;33(1):61-8.
Abstract/Text Five-hundred-thirty-eight patients received a complete follow-up to the first menses after post-coital contraception (PCC). Hormonal contraception (pill) was used in 436 women and mechanical contraception (IUD) was used in 102 women. No pregnancies were observed in the IUD group, while 8 pregnancies were found in the hormonal group. A comparative evaluation of the effectiveness and side effects of the two methods was made. The usefulness of PCC after an unprotected intercourse in order to avoid a pregnancy is confirmed.

PMID 3956207  Contraception. 1986 Jan;33(1):61-8.
著者: James Trussell
雑誌名: Contraception. 2011 May;83(5):397-404. doi: 10.1016/j.contraception.2011.01.021. Epub 2011 Mar 12.
Abstract/Text This review provides an update of previous estimates of first-year probabilities of contraceptive failure for all methods of contraception available in the United States. Estimates are provided of probabilities of failure during typical use (which includes both incorrect and inconsistent use) and during perfect use (correct and consistent use). The difference between these two probabilities reveals the consequences of imperfect use; it depends both on how unforgiving of imperfect use a method is and on how hard it is to use that method perfectly. These revisions reflect new research on contraceptive failure both during perfect use and during typical use.

Copyright © 2011 Elsevier Inc. All rights reserved.
PMID 21477680  Contraception. 2011 May;83(5):397-404. doi: 10.1016/j.c・・・
著者: Yana Vinogradova, Carol Coupland, Julia Hippisley-Cox
雑誌名: BMJ. 2015 May 26;350:h2135. doi: 10.1136/bmj.h2135. Epub 2015 May 26.
Abstract/Text OBJECTIVE: To investigate the association between use of combined oral contraceptives and risk of venous thromboembolism, taking the type of progestogen into account.
DESIGN: Two nested case-control studies.
SETTING: General practices in the United Kingdom contributing to the Clinical Practice Research Datalink (CPRD; 618 practices) and QResearch primary care database (722 practices).
PARTICIPANTS: Women aged 15-49 years with a first diagnosis of venous thromboembolism in 2001-13, each matched with up to five controls by age, practice, and calendar year.
MAIN OUTCOME MEASURES: Odds ratios for incident venous thromboembolism and use of combined oral contraceptives in the previous year, adjusted for smoking status, alcohol consumption, ethnic group, body mass index, comorbidities, and other contraceptive drugs. Results were combined across the two datasets.
RESULTS: 5062 cases of venous thromboembolism from CPRD and 5500 from QResearch were analysed. Current exposure to any combined oral contraceptive was associated with an increased risk of venous thromboembolism (adjusted odds ratio 2.97, 95% confidence interval 2.78 to 3.17) compared with no exposure in the previous year. Corresponding risks associated with current exposure to desogestrel (4.28, 3.66 to 5.01), gestodene (3.64, 3.00 to 4.43), drospirenone (4.12, 3.43 to 4.96), and cyproterone (4.27, 3.57 to 5.11) were significantly higher than those for second generation contraceptives levonorgestrel (2.38, 2.18 to 2.59) and norethisterone (2.56, 2.15 to 3.06), and for norgestimate (2.53, 2.17 to 2.96). The number of extra cases of venous thromboembolism per year per 10,000 treated women was lowest for levonorgestrel (6, 95% confidence interval 5 to 7) and norgestimate (6, 5 to 8), and highest for desogestrel (14, 11 to 17) and cyproterone (14, 11 to 17).
CONCLUSIONS: In these population based, case-control studies using two large primary care databases, risks of venous thromboembolism associated with combined oral contraceptives were, with the exception of norgestimate, higher for newer drug preparations than for second generation drugs.

© Vinogradova et al 2015.
PMID 26013557  BMJ. 2015 May 26;350:h2135. doi: 10.1136/bmj.h2135. Epu・・・
著者: Philip C Hannaford, Sivasubramaniam Selvaraj, Alison M Elliott, Valerie Angus, Lisa Iversen, Amanda J Lee
雑誌名: BMJ. 2007 Sep 29;335(7621):651. doi: 10.1136/bmj.39289.649410.55. Epub 2007 Sep 11.
Abstract/Text OBJECTIVE: To examine the absolute risks or benefits on cancer associated with oral contraception, using incident data.
DESIGN: Inception cohort study.
SETTING: Royal College of General Practitioners' oral contraception study.
PARTICIPANTS: Directly standardised data from the Royal College of General Practitioners' oral contraception study.
MAIN OUTCOME MEASURES: Adjusted relative risks between never and ever users of oral contraceptives for different types of cancer, main gynaecological cancers combined, and any cancer. Standardisation variables were age, smoking, parity, social class, and (for the general practitioner observation dataset) hormone replacement therapy. Subgroup analyses examined whether the relative risks changed with user characteristics, duration of oral contraception usage, and time since last use of oral contraception.
RESULTS: The main dataset contained about 339,000 woman years of observation for never users and 744,000 woman years for ever users. Compared with never users ever users had statistically significant lower rates of cancers of the large bowel or rectum, uterine body, and ovaries, tumours of unknown site, and other malignancies; main gynaecological cancers combined; and any cancer. The relative risk for any cancer in the smaller general practitioner observation dataset was not significantly reduced. Statistically significant trends of increasing risk of cervical and central nervous system or pituitary cancer, and decreasing risk of uterine body and ovarian malignancies, were seen with increasing duration of oral contraceptive use. Reduced relative risk estimates were observed for ovarian and uterine body cancer many years after stopping oral contraception, although some were not statistically significant. The estimated absolute rate reduction of any cancer among ever users was 45 or 10 per 100,000 woman years, depending on whether the main or general practitioner observation dataset was used.
CONCLUSION: In this UK cohort, oral contraception was not associated with an overall increased risk of cancer; indeed it may even produce a net public health gain. The balance of cancer risks and benefits, however, may vary internationally, depending on patterns of oral contraception usage and the incidence of different cancers.

PMID 17855280  BMJ. 2007 Sep 29;335(7621):651. doi: 10.1136/bmj.39289.・・・
著者: Susan L Hendrix, Nancy J Alexander
雑誌名: Contraception. 2002 Dec;66(6):393-9.
Abstract/Text This randomized, double-blind, placebo-controlled exploratory study examined the efficacy and safety of a low-dose oral contraceptive (Mircette), desogestrel/ethinyl estradiol [DSG/EE] and ethinyl estradiol [EE]) in relieving the symptoms of dysmenorrhea. Twenty-three clinics in the United States enrolled 77 women (age < or =32 years) with primary dysmenorrhea documented for at least four consecutive cycles. Forty participants received DSG/EE&EE and 37 received placebo for four consecutive 28-day cycles. The intensity of menstrual-related distress was measured with the Menstrual Distress Questionnaire (MDQ). Patient diaries were used to assess number of school/work days missed as well as the use of rescue medication. Participants receiving DSG/EE&EE recorded reduced menstrual pain severity, lower total MDQ scores, and significantly less menstrual cramping. No significant change in bloating, anxiety, loneliness, weight gain, or acne was reported. The DSG/EE&EE formulation shows promise for the treatment of primary dysmenorrhea and was well tolerated by the participants in this study.

Copyright 2002 Elsevier Science Inc.
PMID 12499030  Contraception. 2002 Dec;66(6):393-9.
著者: I S Fraser, G McCarron
雑誌名: Aust N Z J Obstet Gynaecol. 1991 Feb;31(1):66-70.
Abstract/Text A series of 45 ovulatory women with a complaint of menorrhagia were randomized into 3 treatment groups, before receiving therapy with mefenamic acid in 2 cycles and 1 of 3 other agents in 2 cycles: naproxen (group 1; n = 14), a low dose monophasic combined oral contraceptive (group 2; n = 12) or low dose danazol (group 3; n = 12). Menstrual blood loss was measured in 2-4 control cycles and during therapy. Mefenamic acid reduced measured blood loss by 20%; 38%; and 39% in groups 1-3 respectively. Naproxen reduced blood loss by 12%; the oral contraceptive by 43%; and danazol by 49%. There was no statistically significant difference in blood loss reduction (mean of 2 cycles) between any of the treatments, although women on danazol experienced a dramatic and highly significant further reduction in blood loss after the first treatment cycle (p less than 0.003). These were all effective therapies in a majority of women, but some 'non-responders' were seen in each group. The 'non-responders' had a significantly lower pretreatment blood loss than responders. Several women in group 1 showed anomalous responses to prostaglandin inhibitors with consistent and substantial exacerbation of menorrhagia during therapy. A number of reasonable therapies exist for the medical treatment of menorrhagia, but because none is suitable for everyone management needs to be individualized for each patient.

PMID 1872778  Aust N Z J Obstet Gynaecol. 1991 Feb;31(1):66-70.
著者: Collaborative Group on Epidemiological Studies of Ovarian Cancer, V Beral, R Doll, C Hermon, R Peto, G Reeves
雑誌名: Lancet. 2008 Jan 26;371(9609):303-14. doi: 10.1016/S0140-6736(08)60167-1.
Abstract/Text BACKGROUND: Oral contraceptives were introduced almost 50 years ago, and over 100 million women currently use them. Oral contraceptives can reduce the risk of ovarian cancer, but the eventual public-health effects of this reduction will depend on how long the protection lasts after use ceases. We aimed to assess these effects.
METHODS: Individual data for 23,257 women with ovarian cancer (cases) and 87,303 without ovarian cancer (controls) from 45 epidemiological studies in 21 countries were checked and analysed centrally. The relative risk of ovarian cancer in relation to oral contraceptive use was estimated, stratifying by study, age, parity, and hysterectomy.
FINDINGS: Overall 7308 (31%) cases and 32,717 (37%) controls had ever used oral contraceptives, for average durations among users of 4.4 and 5.0 years, respectively. The median year of cancer diagnosis was 1993, when cases were aged an average of 56 years. The longer that women had used oral contraceptives, the greater the reduction in ovarian cancer risk (p<0.0001). This reduction in risk persisted for more than 30 years after oral contraceptive use had ceased but became somewhat attenuated over time-the proportional risk reductions per 5 years of use were 29% (95% CI 23-34%) for use that had ceased less than 10 years previously, 19% (14-24%) for use that had ceased 10-19 years previously, and 15% (9-21%) for use that had ceased 20-29 years previously. Use during the 1960s, 1970s, and 1980s was associated with similar proportional risk reductions, although typical oestrogen doses in the 1960s were more than double those in the 1980s. The incidence of mucinous tumours (12% of the total) seemed little affected by oral contraceptives, but otherwise the proportional risk reduction did not vary much between different histological types. In high-income countries, 10 years use of oral contraceptives was estimated to reduce ovarian cancer incidence before age 75 from 1.2 to 0.8 per 100 users and mortality from 0.7 to 0.5 per 100; for every 5000 woman-years of use, about two ovarian cancers and one death from the disease before age 75 are prevented.
INTERPRETATION: Use of oral contraceptives confers long-term protection against ovarian cancer. These findings suggest that oral contraceptives have already prevented some 200,000 ovarian cancers and 100,000 deaths from the disease, and that over the next few decades the number of cancers prevented will rise to at least 30,000 per year.

PMID 18294997  Lancet. 2008 Jan 26;371(9609):303-14. doi: 10.1016/S014・・・
著者: Collaborative Group on Epidemiological Studies on Endometrial Cancer
雑誌名: Lancet Oncol. 2015 Sep;16(9):1061-1070. doi: 10.1016/S1470-2045(15)00212-0. Epub 2015 Aug 4.
Abstract/Text BACKGROUND: Oral contraceptives are known to reduce the incidence rate of endometrial cancer, but it is uncertain how long this effect lasts after use ceases, or whether it is modified by other factors.
METHODS: Individual participant datasets were sought from principal investigators and provided centrally for 27 276 women with endometrial cancer (cases) and 115 743 without endometrial cancer (controls) from 36 epidemiological studies. The relative risks (RRs) of endometrial cancer associated with oral contraceptive use were estimated using logistic regression, stratified by study, age, parity, body-mass index, smoking, and use of menopausal hormone therapy.
FINDINGS: The median age of cases was 63 years (IQR 57-68) and the median year of cancer diagnosis was 2001 (IQR 1994-2005). 9459 (35%) of 27 276 cases and 45 625 (39%) of 115 743 controls had ever used oral contraceptives, for median durations of 3·0 years (IQR 1-7) and 4·4 years (IQR 2-9), respectively. The longer that women had used oral contraceptives, the greater the reduction in risk of endometrial cancer; every 5 years of use was associated with a risk ratio of 0·76 (95% CI 0·73-0·78; p<0·0001). This reduction in risk persisted for more than 30 years after oral contraceptive use had ceased, with no apparent decrease between the RRs for use during the 1960s, 1970s, and 1980s, despite higher oestrogen doses in pills used in the early years. However, the reduction in risk associated with ever having used oral contraceptives differed by tumour type, being stronger for carcinomas (RR 0·69, 95% CI 0·66-0·71) than sarcomas (0·83, 0·67-1·04; case-case comparison: p=0·02). In high-income countries, 10 years use of oral contraceptives was estimated to reduce the absolute risk of endometrial cancer arising before age 75 years from 2·3 to 1·3 per 100 women.
INTERPRETATION: Use of oral contraceptives confers long-term protection against endometrial cancer. These results suggest that, in developed countries, about 400 000 cases of endometrial cancer before the age of 75 years have been prevented over the past 50 years (1965-2014) by oral contraceptives, including 200 000 in the past decade (2005-14).
FUNDING: Medical Research Council, Cancer Research UK.

Copyright © 2015 Elsevier Ltd. All rights reserved.
PMID 26254030  Lancet Oncol. 2015 Sep;16(9):1061-1070. doi: 10.1016/S1・・・
著者: Jennifer M Gierisch, Remy R Coeytaux, Rachel Peragallo Urrutia, Laura J Havrilesky, Patricia G Moorman, William J Lowery, Michaela Dinan, Amanda J McBroom, Vic Hasselblad, Gillian D Sanders, Evan R Myers
雑誌名: Cancer Epidemiol Biomarkers Prev. 2013 Nov;22(11):1931-43. doi: 10.1158/1055-9965.EPI-13-0298. Epub 2013 Sep 6.
Abstract/Text Oral contraceptives may influence the risk of certain cancers. As part of the AHRQ Evidence Report, Oral Contraceptive Use for the Primary Prevention of Ovarian Cancer, we conducted a systematic review to estimate associations between oral contraceptive use and breast, cervical, colorectal, and endometrial cancer incidence. We searched PubMed, Embase, and Cochrane Database of Systematic Reviews. Study inclusion criteria were women taking oral contraceptives for contraception or ovarian cancer prevention; includes comparison group with no oral contraceptive use; study reports quantitative associations between oral contraceptive exposure and relevant cancers; controlled study or pooled patient-level meta-analyses; sample size for nonrandomized studies ≥100; peer-reviewed, English-language; published from January 1, 2000 forward. Random-effects meta-analyses were conducted by estimating pooled ORs with 95% confidence intervals (CIs). We included 44 breast, 12 cervical, 11 colorectal, and 9 endometrial cancers studies. Breast cancer incidence was slightly but significantly increased in users (OR, 1.08; CI, 1.00-1.17); results show a higher risk associated with more recent use of oral contraceptives. Risk of cervical cancer was increased with duration of oral contraceptive use in women with human papillomavirus infection; heterogeneity prevented meta-analysis. Colorectal cancer (OR, 0.86; CI, 0.79-0.95) and endometrial cancer incidences (OR, 0.57; CI, 0.43-0.77) were significantly reduced by oral contraceptive use. Compared with never use, ever use of oral contraceptives is significantly associated with decreases in colorectal and endometrial cancers and increases in breast cancers. Although elevated breast cancer risk was small, relatively high incidence of breast cancers means that oral contraceptives may contribute to a substantial number of cases.

©2013 AACR.
PMID 24014598  Cancer Epidemiol Biomarkers Prev. 2013 Nov;22(11):1931-・・・
著者: International Collaboration of Epidemiological Studies of Cervical Cancer, Paul Appleby, Valerie Beral, Amy Berrington de González, Didier Colin, Silvia Franceschi, Adrian Goodhill, Jane Green, Julian Peto, Martyn Plummer, Siân Sweetland
雑誌名: Lancet. 2007 Nov 10;370(9599):1609-21. doi: 10.1016/S0140-6736(07)61684-5.
Abstract/Text BACKGROUND: Combined oral contraceptives are classified by the International Agency for Research on Cancer as a cause of cervical cancer. As the incidence of cervical cancer increases with age, the public-health implications of this association depend largely on the persistence of effects long after use of oral contraceptives has ceased. Information from 24 studies worldwide is pooled here to investigate the association between cervical carcinoma and pattern of oral contraceptive use.
METHODS: Individual data for 16,573 women with cervical cancer and 35,509 without cervical cancer were reanalysed centrally. Relative risks of cervical cancer were estimated by conditional logistic regression, stratifying by study, age, number of sexual partners, age at first intercourse, parity, smoking, and screening.
FINDINGS: Among current users of oral contraceptives the risk of invasive cervical cancer increased with increasing duration of use (relative risk for 5 or more years' use versus never use, 1.90 [95% CI 1.69-2.13]). The risk declined after use ceased, and by 10 or more years had returned to that of never users. A similar pattern of risk was seen both for invasive and in-situ cancer, and in women who tested positive for high-risk human papillomavirus. Relative risk did not vary substantially between women with different characteristics.
INTERPRETATION: The relative risk of cervical cancer is increased in current users of oral contraceptives and declines after use ceases. 10 years' use of oral contraceptives from around age 20 to 30 years is estimated to increase the cumulative incidence of invasive cervical cancer by age 50 from 7.3 to 8.3 per 1000 in less developed countries and from 3.8 to 4.5 per 1000 in more developed countries.

PMID 17993361  Lancet. 2007 Nov 10;370(9599):1609-21. doi: 10.1016/S01・・・
著者: M F Gallo, D A Grimes, K F Schulz, F M Helmerhorst
雑誌名: Cochrane Database Syst Rev. 2003;(2):CD003987. doi: 10.1002/14651858.CD003998.
Abstract/Text BACKGROUND: Weight gain is often attributed as a side effect of combination hormonal contraceptive, and many women and clinicians believe that an association exists. Concern about weight gain can limit the use of this highly effective method of contraception by deterring the initiation of its use and causing early discontinuation among users. Nevertheless, a causal relationship between combination contraceptives and weight gain has not been established.
OBJECTIVES: The aim of the review was to evaluate the association between combination contraceptive use and changes in weight.
SEARCH STRATEGY: We searched the computerized databases MEDLINE, Popline, CENTRAL, EMBASE, and LILACS for studies of combination contraceptives. We also wrote to known investigators and manufacturers to request information about other published or unpublished trials not discovered in our search.
SELECTION CRITERIA: All English-language, randomized controlled trials at least three treatment cycles in duration that compared a combination contraceptive to a placebo or with a combination contraceptive that differed in drug, dosage, regimen, and/or study length were eligible.
DATA COLLECTION AND ANALYSIS: All titles and abstracts located in the literature searches were assessed. Data were entered and analyzed with RevMan 4.1, and a second reviewer verified the data entered. Depending on the data available, the weighted mean difference using a fixed effects model with 95% confidence intervals was calculated for the mean change in weight between baseline and post-treatment measurements or the Peto odds ratio with 95% confidence intervals was calculated using the proportion of women who gained or lost more than a specified amount of weight.
MAIN RESULTS: The three placebo-controlled, randomized trials did not find evidence supporting a causal association between combination oral contraceptives or a combination skin patch and weight gain. Most comparisons of different combination contraceptives showed no substantial difference in weight. In addition, discontinuation of combination contraceptives because of weight gain did not differ between groups where this was studied.
REVIEWER'S CONCLUSIONS: Available evidence is insufficient to determine the effect of combination contraceptives on weight, but no large effect is evident.

PMID 12804496  Cochrane Database Syst Rev. 2003;(2):CD003987. doi: 10.・・・
著者: Anne R Davis, Robin Kroll, Barbara Soltes, Nan Zhang, Gary S Grubb, Ginger D Constantine
雑誌名: Fertil Steril. 2008 May;89(5):1059-1063. doi: 10.1016/j.fertnstert.2007.05.012. Epub 2007 Jul 20.
Abstract/Text OBJECTIVE: To evaluate the time to return to spontaneous menses in women after 1 year of daily continuous levonorgestrel (LNG) 90 microg/ethinyl E(2) (EE) 20 microg.
DESIGN: Observational study.
SETTING: Gynecologic and primary care practices.
PATIENT(S): Women aged 18-49 years with a history of regular menstrual cycles. After participation in an open-label, continuous oral contraceptive (OC) trial for at least 6 months, participants agreed to enroll in a separate study of the return to menses or pregnancy.
INTERVENTION(S): None.
MAIN OUTCOME MEASURE(S): Time to return to spontaneous menses or pregnancy.
RESULT(S): The 198 subjects had a mean age of 30.4 +/- 6.6 years with 72% white, 13% Hispanic, and 7% African American. The mean duration of continuous LNG/EE treatment before enrollment was 349 +/- 41 days. Of the 187 (94%) subjects who completed this study, 181 returned to spontaneous menses and 4 became pregnant within 90 days after the last dose of LNG 90 microg/EE 20 microg. The median time to return to menses in the completer population was 32 days, and the incidence of spontaneous menses or pregnancy at day < or = 90 was 98.9%. The duration of amenorrhea during continuous LNG/EE use before stopping treatment was unrelated to the time to the return to menses.
CONCLUSIONS: Spontaneous menses or pregnancy occurred in 98.9% of women after cessation of continuous LNG/EE.

PMID 17658522  Fertil Steril. 2008 May;89(5):1059-1063. doi: 10.1016/j・・・
著者: G Zuliani, U F Colombo, R Molla
雑誌名: Eur J Obstet Gynecol Reprod Biol. 1990 Dec;37(3):253-60. doi: 10.1016/0028-2243(90)90032-v.
Abstract/Text The ethinylestradiol-norgestrel combination (EE-NG) for postcoital contraception, as described by Yuzpe, has been shown to be an effective method but with frequent side effects. To overcome the problem of adverse effects a new approach using danazol was proposed, but the efficacy and acceptability of this treatment have not yet been tested in large studies. In a 5-year period at the AIECS Family Planning Centre in Milan we treated 2448 women requesting postcoital contraception using Yuzpe's regimen and two danazol regimens (800 mg/1200 mg). The patients' acceptability for danazol treatment was higher than for Yuzpe's regimen due to fewer, milder and shorter side effects. Nine pregnancies occurred in the EE-NG group (2.21%), 17 in the 800 mg group (1.71%) and 6 in the 1200 mg group (0.82%). Our study shows a statistically significant efficacy against expected pregnancy rates both with Yuzpe's regimen and with danazol. The 1200 mg danazol treatment seems to be more effective and can be considered a valid alternative to the EE-NG combination for hormonal postcoital contraception.

PMID 2227068  Eur J Obstet Gynecol Reprod Biol. 1990 Dec;37(3):253-60・・・
著者: A A Yuzpe, W J Lancee
雑誌名: Fertil Steril. 1977 Sep;28(9):932-6.
Abstract/Text Six hundred and eight women were treated with 200 microgram of ethinylestradiol and 2 mg of dl-norgestrel, administered in two divided doses, as a postcoital contraceptive. Criteria for entry into the study included definite unprotected coital exposure within the previous 72 hours and the absence of any contraindications to the use of estrogen/progestin-containing compounds. Women with coital exposures outside of the 72-hours-to-treatment time frame were excluded. Four hundred and sixty-four of the patients were cycling regularly and, of these, 152 were exposed at midcycle. Only one patient became pregnant as a result of probable method failure as compared with the minimal estimated number of 12 to 30 pregnancies.

PMID 892044  Fertil Steril. 1977 Sep;28(9):932-6.

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