Combined oral contraceptives (COCs) are combined steroid hormone preparations containing estrogen and progestin for birth control. The first COC-Enovid was developed in 1960 and successfully marketed in the United States. After more than 50 years of development, COC has become one of the commonly used contraceptive methods worldwide, with a pregnancy rate of only 0.3 per 100 women per year when used correctly. However, in China, many clinicians often have some confusion when applying COC, especially in terms of long-term use, safety effects on reproductive function and offspring, and the risk of gynecologic malignancies, resulting in a low probability of recommending COC for contraception. COC mechanism of action COC is used to achieve fertility control through multiple actions such as suppression of ovulation, alteration of cervical mucus properties, change of endometrial morphology and function, and interference with fallopian tube function. 5 questions on the application of COC I. Is long-term use of COC harmful to the body and should it be intermittent? Currently, there is some clinical evidence and expert consensus that the safety risk associated with COC use is venous thromboembolism (VTE), including deep venous thrombosis and pulmonary embolism, and the increased risk of VTE occurs within 3-6 months after taking the drug and does not continue to increase with the duration of COC use. The risk of VTE also includes smoking, history of diabetes, obesity, hypertension, etc. Women with these risk factors should avoid using COCs. II. Can an unplanned pregnancy while taking COCs lead to fetal malformation or death? No. The use of COC before or during pregnancy does not increase the risk of fetal physical defects or death. Is it necessary to stop using COC for 3-6 months before pregnancy? No. The use of COC for contraception in women of childbearing age or the accidental use of COC during pregnancy will not cause teratogenicity in newborns. Moreover, the COC currently used in clinical practice is excreted or cleared within a short time after taking the drug. Ovulation can be resumed about 2 weeks after discontinuation of COC. Therefore, pregnancy can be considered after discontinuation of COC, without waiting for 3-6 months. Does the use of COC have any effect on fertility? The use of COC not only has no adverse effect on women’s reproductive function, but even has a significant protective effect, mainly through the following aspects of direct or indirect effects: 1, women adhere to and correct use of COC, the pregnancy rate in the first year is only 0.3 per 100 women years, can effectively avoid unwanted pregnancy and abortion, especially repeated abortion, which is the best protection for women’s reproductive function. 2. COC can effectively reduce the risk of pelvic inflammatory disease. The main mechanism is that COC can increase the viscosity of cervical mucus and stop the upward movement of pathogenic microorganisms in the lower reproductive tract. On the other hand, COC can inhibit the endometrium, reduce menstrual flow and decrease the risk of pelvic inflammatory disease due to menstrual blood reflux. Foreign observation shows that taking COC can reduce the incidence of pelvic inflammatory disease by 50% to 60%; not only that, among the pelvic inflammatory diseases diagnosed by laparoscopy, the degree of inflammatory reaction is mild in the pelvic inflammatory disease occurred during taking COC. 3, COC can effectively prevent the occurrence of ectopic pregnancy. The main mechanism is that COC can almost completely inhibit ovulation and can effectively interfere with fertilization.COC can reduce the incidence of ectopic pregnancy by 90%, and the literature reports that the incidence of ectopic pregnancy among COC users is only 0.005 per 1,000 woman-years, which is similar to that of women whose partners use vasectomy contraception, and much lower than that of women who use condoms, vaginal diaphragms, copper intrauterine devices and tubal sterilization.COC The strong contraceptive effect results in a very low incidence of ectopic pregnancy even when contraception fails. In addition to these direct effects, COC may protect reproductive function by reducing the risk of endometrial cancer and ovarian epithelial cancer (ovarian cancer). V. Does the use of COC increase the risk of gynecological malignancies and breast cancer? Whether long-term use of COC has an effect on the occurrence of common gynecological malignancies is a hot topic of research by scholars from various countries. Studies have found that women who have taken COC have significantly lower all-cause mortality; moreover, the mortality rate due to all malignant tumors (including colon cancer, rectal cancer, endometrial cancer and ovarian cancer, etc.) is also significantly lower. 1.COC and ovarian cancer: The incidence of ovarian cancer ranks 3rd among malignant tumors of female reproductive organs, and its pathogenesis is complex. 1 major factor may be related to the abnormal proliferation of ovarian surface epithelial cells caused by repeated ovulation of the ovary. It is now recognized that women taking COC have a reduced risk of ovarian cancer, and the earlier the age of the first dose and the longer the dose, the lower the risk of ovarian cancer, and the protective effect can still persist after stopping the drug. 2. COC and endometrial cancer: Endometrial cancer is one of the three common malignancies in gynecology, and most endometrial cancers are estrogen-dependent. The mechanism of COC in reducing the risk of endometrial cancer may be that COC inhibits the stimulation of the endometrium by estrogen secreted by the ovaries themselves, while the highly effective progestin component in COC can fully transform the endometrium and prevent excessive proliferation of the endometrium. The cyclical use of COC also enables the endometrium to shed and discharge periodically to protect the endometrium, thus reducing its probability of cancer. 3.COC and cervical cancer: cervical cancer is the most common malignant tumor of female reproductive organs in clinical practice. It is now recognized that persistent infection with high-risk HPV is the most important cause of the disease, and other factors related to the development of the disease include multiple sexual partners, first sexual intercourse <16 years old, early childbirth, multiple births, etc. However, the correlation between the use of COC and the risk of cervical cancer is still unclear. Currently, the more internationally recognized conclusion is that women infected with hpv who use coc for a long time have an increased risk of cervical cancer. 4.COC and breast cancer: Breast cancer is the most common female malignancy, and excessive use of exogenous estrogen is one of the high risk factors for the occurrence of breast cancer. A large number of studies in recent years have confirmed that taking COC does not increase the risk of breast cancer. In addition, women with a family history of breast cancer have not experienced a further increase in the incidence of breast cancer when taking COC. the WHO's Medical Criteria for the Selection of Contraceptive Methods states that COC does not increase the risk of breast cancer and is an appropriate contraceptive choice not only for women of reproductive age in general, but also for women with a family history of breast cancer; for women with a family history of breast cancer. IMPORTANT STATEMENT Regular breast examinations are required during use. It is important to clarify that COC is generally safe for healthy women of childbearing age to take for a long time without interruption; it has no adverse effects on reproductive function and has a protective effect; it can be used for pregnancy after discontinuation and is not teratogenic to the fetus even if taken during pregnancy; and it can reduce the risk of some gynecological malignancies and play a protective role. In conclusion, COC is a safe, efficient and reversible contraceptive method for healthy women of reproductive age that can be used for a long time.