Although surgery is the first and best treatment for endometriosis (referred to as endometriosis), it is often difficult to remove all lesions and cannot remove lesions that are invisible to the naked eye, and postoperative recurrence is often inevitable. Therefore, pharmacological treatment still occupies an important position. Drug therapy can be divided into preoperative drugs or postoperative drugs. Preoperative medication is more commonly used for GnRH-a or pseudo-menopausal drugs, which can reduce lesions, shrink the uterus, reduce pelvic adhesions and congestion, and inhibit the generation of physiological ovarian cysts, which should be beneficial for laparoscopic surgery. However, due to the deepening understanding of evidence-based medicine in recent years and the emphasis on the importance of pre-treatment laparoscopic diagnosis, coupled with the fact that laparoscopic techniques have been widely used in clinical practice, often patients have undergone laparoscopic surgery while the diagnosis is clear, so preoperative drug therapy is not much used. Of course, if the doctor thinks that the diagnosis of endoheterosis is clear and the lesion is extensive or the pelvic adhesions are serious, the patient can be consulted and then treated with medication for 3 months before laparoscopic surgery. At present, most of the medication for endo is postoperative, and postoperative medication can reduce the residual lesions and delay the recurrence of endo. It is mainly suitable for those who have extensive ectopic lesions that have not been completely removed or those who have painful symptoms with no fertility requirements when the ectopic lesions are visually cleared. Evidence-based medical data published abroad suggest that a 6-month course of medication after conservative laparoscopic surgery is appropriate, and a 3-month course does not reduce the rate of pain recurrence. Patients who have cleared ectopic lesions as seen by the naked eye and who wish to have children in the near future may be encouraged to become pregnant as early as possible. The need for postoperative pharmacologic therapy for those with severe endoheterotrophy with fertility requirements remains controversial. Although pharmacologic therapy delays the timing of pregnancy in patients, it has also been reported that the chances of pregnancy will increase with aggressive fertility treatment. The drugs commonly used for the treatment of endometriosis are Danazol, Endometrium or Gestrinone, Gonadotropin-releasing-hormone analogus (GnRH-a), progestins and oral contraceptives. 1. Danazol is a derivative of 17-a – ethinyl testosterone, and therefore has some androgenic effects. Danazol can prevent the release of pituitary follicle stimulating hormone and luteinizing hormone, thus inhibiting follicular development and ovulation, and blood estrogen and progesterone levels drop significantly, which is not conducive to the growth and development of ectopic endometrium. The rise in blood androgen levels after danazol use, as well as the significant increase in free androgen levels due to the decrease in plasma sex hormone-binding globulin levels, is also one of the important mechanisms in its treatment of ectopic disease. Danazol has a direct inhibitory effect on the endometrium. After long-term use of danazol, the ectopic endometrium atrophied and even died. Studies have also shown that Danazol regulates the immune function of the body, inhibits the production of anti-endometrial antibodies in the body, and facilitates pregnancy after discontinuation of the drug. The maximum dosage is 800mg per day for six months. Common side effects include weight gain, acne, irritability, hot flashes, increased appetite, edema, breast reduction, headache, increased skin oil, vaginal dryness, muscle pain, dyslipidemia, and abnormal liver function. Rarely, increased hairiness, joint pain and low voice are seen. Menorrhagia is the effect of the drug, but many patients have a small amount of dripping bleeding, or breakthrough bleeding, which can be improved by increasing the dosage of the drug. Although side effects are more common, most of them are not serious and do not require discontinuation. The liver function should be checked monthly during the drug administration. For those with mildly elevated liver function, biphenyldiphenhydramine can be added to continue the medication. If liver function is occasionally too high, it is advisable to stop the drug and give liver-protective treatment in time. Liver function is usually normalized 2 weeks to 4 weeks after discontinuation. It is recommended to use instrumental contraception during the use of the drug and to stop the drug immediately if pregnancy is detected. Pregnancy should be tried after the formal resumption of menstruation after discontinuation of the drug for those who have fertility requirements. 2. Endometrium or Pregnant Trienone (Trienogonadone). It is a derivative of 19 norethindrone, and its mechanism of action is similar to danazol, which also has some androgenic effects. Trienogonadione can block the release of pituitary follicle stimulating hormone and luteinizing hormone, thus inhibiting follicular development and ovulation, and blood estrogen and progesterone levels are significantly decreased. The rise in blood androgen level is not obvious after trienogonadione use, but the free androgen level also increases due to the decrease in plasma sex hormone binding globulin level, which may also be one of the mechanisms for the treatment of ectopic disorders. There is also a direct inhibitory effect on the endometrium. After long-term use, the ectopic endometrium atrophies and even dies. Start taking 2.5mg each time within the first day of menstruation – 5 days, twice a week for six months. The incidence of adverse reactions is similar to that of Danazol, but to a lesser extent, and the precautions are the same as those for Danazol. 3.GnRH-a. It is currently recognized as the most effective drug for the treatment of endometriosis, with a prescribed course of treatment of six months, and is the most commonly used drug in developed countries, and its clinical application in China has increased significantly in recent years. The main difference between them and natural GnRH is that the 6th amino acid (glycine) is replaced by serine or leucine or D-tryptophan, and the 10th amino acid also undergoes some changes, and the resulting drugs are triptorelin, leuprolide acetede and goserelin respectively. goserelin.) The chemical structure is altered so that the biological activity is 80-100 times higher than that of the natural hormones. Under normal conditions, the hypothalamus secretes GnRH in a pulsatile manner. With GnRH-a, the drug continues to act on the pituitary gland and binds to GnRH receptors in the pituitary gland, which continuously occupy GnRH receptors and move into the cells, resulting in a lack of GnRH receptors in the cell membrane and a loss of rhythmic secretion of FSH and LH from the pituitary gland, thus inhibiting follicular development and ovulation. The blood estrogen level reaches the menopausal level after 21 days of the first injection, and after long-term use, the ectopic endometrium atrophies and even dies. Subcutaneous injection (goserelin implant, 3.6 mg/stem) or subcutaneous injection (leuprolide acetate, 3.75 mg/stem) or intramuscular injection (treprostinil, 3.75 mg/stem) into the lower abdomen from the first day of menstruation to the fifth day of menstruation, every 4 weeks for a total of 6 injections for 6 months. Change the injection site each time. Do not rub the injection site. Dosage adjustment is generally not necessary. A transient increase in blood estrogen levels may cause a transient increase in pain and breast tenderness within 2 weeks of administration. Subsequent side effects are mainly menopause-like symptoms caused by low estrogen, such as hot flashes, sweating, irritability, headache, insomnia, vaginal dryness, change in libido, depression, and breast reduction. Androgenic effects such as acne, increased skin oil, edema, hirsutism and voice changes are rare. It has been reported that it can cause rash, which is mostly mild and does not affect the treatment. Patients tend to be amenorrheic from the 2nd month after drug administration, and may have a small amount of drenching bleeding. Weight gain is not significant. There is generally no effect on blood lipids and liver function. Long-term use of the drug may cause bone calcium loss, but does not increase the risk of fracture, and can gradually recover after discontinuation of the drug. During the use of the drug, it is advisable to use instrumental contraception, and pregnancy should be discontinued immediately. Pregnancy should be attempted after the formal resumption of menstruation after discontinuation of the drug for those with fertility requirements. According to the doctrine of “estrogen window” required for the treatment of endometriosis, serum E2 level should be 30pg/ml to 50pg/ml, which is ideal for patients after GnRH-a injection. Therefore, nowadays, it is mostly advocated to start supplementation with small doses of estrogen and progestin from the second to third month of medication, which is known as “add-back therapy”, such as taking premarin 0.3mg-0.625mg and progesterone 2-5mg per day, or Levi’s 1.25 mg-2.5mg per day, which can prevent bone loss and It reduces the side effects of low estrogen without reducing the efficacy of the treatment for endometriosis. When GnRH-a has been used for more than 6 months, it is necessary to administer “anti-additive therapy”. The duration of GnRH-a use can be safely extended to 1 year or even 5 years with “anti-additive therapy”. The intensity of pituitary inhibition varies between GnRH-a, and the short-acting domestic GnRH-a Alarelin is less potent and does not require “reverse add-on therapy” during treatment. Since the current dose of GnRH-a may be too high, there have been several reports from abroad on the use of “draw-back therapy”, which is to halve the current dose of GnRH-a, in patients receiving “draw-back therapy”. The blood estrogen level of patients receiving “draw-back therapy” is exactly within the “window” required for the treatment of endometriosis, and the efficacy is the same as that of the full dose, with reduced symptoms of low estrogen and reduced bone loss. 4.Progestin drugs. Commonly used drugs include norethindrone (gynecomastia tablets), megestrol (gynecomastia tablets), and progesterone, etc. Progesterone drugs can feedback inhibit the hypothalamic-pituitary-ovarian axis and lower estrogen levels in the body by inhibiting ovulation. In addition, they can also act directly on the ectopic endometrium, causing excessive metaplasia and then atrophy and necrosis. The dose of progesterone should be taken from the 1st day of menstruation – within 5 days, each time between 5mg – 10mg in one dose, subject to amenorrhea, and the dosage can be adjusted appropriately. Progesterone is available as a long-acting injection (Depo-Provera), one injection (150mg) every 3 months, and the duration of treatment is usually 6 months. It can be extended to 9 months for severe cases. The side effects of norethindrone are similar to those of danazol, and sometimes there are gastrointestinal symptoms such as nausea and vomiting. Androgenic side effects of megestrol and androprogesterone are less severe. Liver function should be checked regularly during medication. Breakthrough bleeding is more common during progestogen therapy, and does not need to be treated when the amount is small. Pseudopregnancy therapy is now used sparingly. 5.Compound estrogen and progestin. For oral contraceptive drugs. Newer drugs such as compounded disoproxil (Marvelon) with milder side effects are being promoted and are gradually replacing false pregnancy therapy. It is taken from the first day of menstruation to the fifth day, one or two tablets each time for six months. The dosage is adjusted according to amenorrhea. Common side effects are mainly nausea and vomiting, which will gradually decrease or disappear as the dosing time increases. There is also weight gain and liver function impairment. There are adverse effects on blood lipid metabolism. In addition, because the estrogen and progesterone in the pill will stimulate the growth of fibroids, so use with caution if you have fibroids. 6.Other drugs. In recent years, the literature has reported that other drugs used to treat endometriosis include Tamoxifen (Tamoxifen, TMX), mifepristone, intrauterine device containing drugs (LNG-IUS, Manuel), aromatase inhibitors, GnRH antagonists and cyclooxygenase-2 inhibitors, etc. However, they are all in the research and development stage and have not yet been approved by the State Food and Drug Administration (SFDA). Drug Administration (SFDA) approval. Tamoxifen can be used for patients with dysmenorrhea by taking 10 mg twice or three times a day from day 1 to day 5 of the menstrual cycle. Adverse effects include flushing, nausea and vomiting, and weight gain. Some patients may experience menstrual disorders, such as frequent or incomplete menstruation. Patients with uterine fibroids may experience rapid growth of fibroids and symptoms. Functional ovarian cysts may also develop during the course of the drug. Long-term use of large doses (more than 30 mg per day) may cause endometrial polyps, excessive endometrial hyperplasia or even malignant changes, which is worth noting. It is also possible that ovarian chocolate cysts may increase in size during administration. Mifepristone for the treatment of endometriosis has been reported in China in recent years, and is considered to have a high amenorrhea rate, mild side effects and satisfactory pain control. The dosage is 10mg – 25mg per day for 3 – 6 months. Treatment of endometriosis with LNG-IUS resulted in significant improvement of dysmenorrhea, painful intercourse and pelvic pain symptoms and reduction of ectopic nodules in patients with moderate to severe endometriosis. Immediate placement of LNG-IUS after conservative laparoscopic surgery for moderate to severe endometriosis significantly reduced the recurrence rate of pain. There are also case reports of successful treatment of postmenopausal endometriosis with the aromatase inhibitor anastrozole (anastrozole). The treatment of endometriosis with cetrorelix (Cetrotide), a GnRH antagonist, was first reported in Germany. 15 patients were treated with subcutaneous cetrorelix at 3 mg once a week for 8 weeks, and their symptoms resolved during the treatment period. The second laparoscopy confirmed the regression of the ectopic lesions in 9 of 15 cases, and the stage of endoheterosis decreased from a mean of stage III before treatment to stage II after treatment. Compared with GnRH-a, GnRH antagonists do not have the “ignition effect” of a transient increase in blood estradiol levels after treatment, and their effect should be more rapid, but the exact efficacy needs to be compared with GnRH-a before a conclusion can be drawn.