Gregory Pincus, a pioneer in the study of oral contraceptives and the true “father of the pill,” conducted a study in Puerto Rico in the late 1950s, using high doses of estrogen and progestin in his pill because he knew that his experiment could not risk pregnancy. In 1960, the first oral contraceptive pill – Enovid, was introduced to the United States and in 1961 to Europe. His first pill with high doses of steroids (containing 150 μg of estrogen – ethinyl estradiol) had a high contraceptive effect, but at that time his studies were not sufficiently aware of side effects. The history of contraceptive development is divided into two main trends: on the one hand, the reduction of estrogen doses, and on the other hand, the development of more selective progestin formulations to allow for lower progestin doses while maintaining their high efficiency, good cycle regulation, and low incidence of side effects. In order to reduce side effects, the dose of estrogen-ethinylestradiol in oral contraceptives has been gradually reduced from the initial 150 μg per pill to 20-35 μg, called low-dose contraceptives, and the latest ones are even as low as 15 μg. The reasons for reducing estrogen dose are as follows: estrogen dose is associated with thrombosis; estrogen dose is associated with the degree of alteration of the coagulation mechanism; many less serious but inconvenient side effects for the user, such as nausea, breast swelling, etc. side effects, such as nausea, breast tenderness, and vomiting, are mainly caused by estrogen. The decrease in estrogen dose is accompanied by a decrease in progestin dose, made possible by the production of highly effective progestins. Studies have found that progestin doses correlate with the incidence of arterial disease, and even at low doses, these older generations of progestins still have adverse effects on the cholesterol LDL, HDL balance. The above reasons have led to more research to develop new progestins that will improve the effects of OC on lipid metabolism. It has been shown that the stronger the androgenic effect of progestins, the greater the adverse effect on lipid metabolism. The progestin drospirenone in the new generation of oral contraceptives, euselenone, has a unique anti-salt corticosteroid and anti-androgen effect, both for weight control and for positive effects on heart lipids and blood pressure. In the 60 years since the introduction of oral contraceptives, researchers have conducted numerous studies on them. These studies have demonstrated that oral contraceptives have numerous non-contraceptive benefits —- many of which are related to ovulation suppression and cycle adjustment by the pill. As a result, doctors often prescribe the pill for non-contraceptive purposes and use oral contraceptives to treat conditions other than those for which they are indicated in their instructions. Oral contraceptives can be used to treat dysmenorrhea, abnormal uterine bleeding, dysfunctional uterine bleeding, polycystic ovary syndrome, acne and hirsutism. Oral contraceptives may also be used to prevent functional ovarian cysts, provide estrogen replacement therapy for patients with amenorrhea, and improve some symptoms associated with the menstrual cycle, including mood swings, headaches, and premenstrual tension syndrome. Primary dysmenorrhea The most common off-indication application of oral contraceptives is to improve menstrual disorders. Excessive menstrual flow, irregular menstruation and non-menstrual bleeding occur significantly less frequently in oral contraceptive pill users compared to non-users. Oral contraceptives also improve primary dysmenorrhea in most women and premenstrual tension in some women. Oral contraceptives for dysmenorrhea are particularly beneficial for adolescent girls. Dysmenorrhea is one of the most common symptoms in adolescent girls, with about 60% of girls experiencing these symptoms and an additional 14% unable to attend school as a result. Oral contraceptives should not be used as a first-line treatment for dysmenorrhea in adolescent girls who are not yet sexually active. For adolescent girls with significant dysmenorrhea, the first choice of treatment is still NSAIDs such as fenpropathrin, but if treatment is not effective or if the girl is still unable to attend school because of dysmenorrhea, oral contraceptives may be an option, unless there are contraindications to their use. The improvement in dysmenorrhea with oral contraceptives will also increase compliance with pill use. For adolescent girls with dysmenorrhea, who are sexually active and taking oral contraceptives, studies have shown that they are more likely to comply with their dosing regimen if their clinician indicates that one of the real benefits of taking oral contraceptives is relief of dysmenorrhea. Excessive and irregular menstruation Irregular uterine bleeding is often referred to as functional uterine bleeding ( DUB) when uterine bleeding due to organic disease such as fibroids has been excluded. Functional uterine bleeding is particularly common in adolescent girls and it is usually associated with anovulatory menstrual cycles due to immature feedback mechanisms of the HPO axis. DUB can also occur during the menopausal transition due to the decline of ovarian function and often presents with irregular menstrual cycles and prolonged bleeding. Excessive menstrual flow is a very common phenomenon and affects the quality of life of about 20% of women of childbearing age. Oral contraceptives can be used to treat excessive menstrual flow and non-menstrual bleeding, to restore the synchronization of the endometrium, and to prevent the long-term adverse consequences of non-ovulation leading to endometrial hyperplasia and even endometrial cancer. Inhibition of estrogen receptor synthesis by synthetic progestins in birth control pills can reduce endometrial activity and regulate menstrual flow. A recent review concluded that “if symptoms of irregular vaginal bleeding have persisted for a long time, the use of progestin alone does not stop the bleeding. The estrogen-pregnant combination of oral contraceptives is much more effective in stopping the bleeding. Oral contraceptives are a good option if the patient still has an active sex life.” A recent Cochrane Collaboration systematic review similarly described the benefits of oral contraceptives for excessive periods, which are now being treated with a number of drugs, including prostaglandin synthase inhibitors, antifibrinolytic drugs, oral contraceptive pills (OCPs) and other hormones. Objective data show that taking OCPs can result in a significant reduction in menstrual flow, at least in the short term, and when taken periodically, OCPs can cause the thinner endometrium to shed periodically and inhibit ovulation. This method provides both good cycle regulation and reliable contraception, making oral contraceptives the most acceptable long-term treatment option for some women with excessive menstruation. Studies in the literature have shown that oral contraceptives can reduce menstrual flow by up to 53%. Therefore, oral contraceptives are very effective for women with irregular and heavy periods. Studies have shown that all oral contraceptives —- including low-dose oral contraceptives —- containing 20 micrograms of ethinyl estradiol can reduce the number of days that a period lasts and the amount of menstruation. Oral contraceptives are currently the main treatment for heavy periods for women of all ages and may also be used in patients with certain blood disorders. The treatment regimen of oral contraceptives for DUB depends on the severity of the bleeding. For acute bleeding symptoms, especially heavy vaginal bleeding with anemia, the U.S. guidelines for abnormal uterine bleeding recommend a combination oral contraceptive regimen with a higher dose of 35 μg of ethinyl estradiol, which can be used up to 3-4 pills per day. Once bleeding has stopped, the higher dose regimen can be discontinued, or tapered until it is discontinued for withdrawal bleeding. After the acute bleeding is controlled, the patient can use the standard dose oral contraceptive regimen. For symptoms that are not associated with slightly less anemic bleeding, the use of 1-2 pills per day of oral contraceptives can be successful. Polycystic ovary syndrome Oral contraceptives have been used to treat symptoms of hyperandrogenism, such as polycystic ovary syndrome (PCOS). Characteristics of polycystic ovary syndrome include a history of chronic non-ovulatory bleeding with laboratory indicators of high androgen levels such as elevated serum androgen levels and or hyperinsulinemia. clinical features of PCOS often include acne, hirsutism, infertility, insulin resistance, and obesity. Women with PCOS usually do not have estrogen counteracted by progesterone and therefore have a higher risk of developing endometrial cancer. They also have a higher risk of developing diabetes. The primary goal of PCOS treatment is to improve symptoms and also to reduce the risk of sequelae of PCOS. The most commonly used methods are ovulation induction for infertility, oral contraceptives and progestins for irregular periods, oral contraceptives and/or Advil for hyperandrogenemia and hirsutism, and for PCOS-induced acne. Acne Oral contraceptives can treat acne and hirsutism in women. This is because it inhibits the metabolism of ovarian, adrenal and peripheral androgens, resulting in a decrease in free testosterone. The American College of Obstetricians and Gynecologists summarizes its benefits for hirsutism this way: “The main method of pharmacological treatment (of hirsutism) is the use of a low-dose combination of oral contraceptives, which effectively suppresses ovarian function and reduces ovarian production of androgens. Moreover, the estrogen in oral contraceptives stimulates the synthesis of sex hormone binding globulin (SHBG) in the liver, which increases the level of bound androgens, thereby decreasing its bioavailability.” Countless studies have reported improvements in acne with various oral contraceptives. Endometriosis Endometriosis affects about 15-20% of women of childbearing age and it causes chronic pelvic pain, dysmenorrhea, painful intercourse and infertility. Endometriosis is an abnormal immune response and clinical discomfort caused by endometrial tissue growing in the abdomen and pelvis when the endometrium peels off for menstruation. Therefore, oral contraceptives and other birth control methods that can alter the flow of menstrual blood can improve the symptoms of endometriosis by affecting the growth of the endometrium. A recent Cochrane Collaboration review summarized data on the association between oral contraceptive use and pain associated with endometriosis. The researchers found that “there are fewer data on the use of oral contraceptives for endometriosis; however, these data support their use as a first-line treatment option in daily therapy, and it provides an acceptable long-term treatment option to address the painful symptoms of endometriosis.” Diet- or exercise-induced amenorrhea Oral contraceptives can supplement the estrogen needed by patients with amenorrhea due to estrogen deficiency. The disorder is common among women with eating disorders or who engage in endurance sports, such as running. Many adolescent girls either have an eating disorder or have had such problems that their bodies do not produce enough estrogen. Likewise, some athletes are underweight relative to their height, especially among women who are involved in gymnastics or track and field, and girls who practice barre usually have amenorrhea with estrogen deficiency. Oral contraceptives can be prescribed for these women to supplement estrogen. PMS Oral contraceptives can improve many disorders associated with the menstrual cycle, including headaches, mood changes, etc. Dramatic changes in estradiol and progesterone serum levels during the menstrual cycle trigger these symptoms. In contrast, women taking monophasic oral contraceptives have relatively stable hormone levels throughout their cycle, thereby reducing or avoiding the occurrence of these symptoms. There are currently many public misconceptions about the use of oral contraceptives, which are associated with significant side effects and weight gain, whereas the progestin in the new generation of oral contraceptives, Eusebio, counteracts water and sodium retention and does not increase weight. And for non-smoking women, long-term oral contraceptives do not increase the risk of coronary heart disease and reduce the risk of endometrial and ovarian cancers.