Tumors consisting of smooth muscle and fibrous tissue of the uterine wall. It is the most common benign tumor in the female reproductive organs. It is generally believed that long-term massive and continuous estrogen stimulation is the main cause of this disease. It mostly occurs in the reproductive age and the tumor shrinks after menopause. According to the site of growth, the tumors are divided into uterine body fibroids and cervical fibroids, with the former being more common. The fibroids can be single or multiple. According to the relationship between the fibroid and the muscle wall, there are several types of fibroids as follows: ① Subplasma fibroids. The fibroids protrude from the surface of the uterus. ②Interstitial myomas. Myomas grow in the myometrium and are most common. (3) Submucosal leiomyoma. Myomas are located in the subendometrial layer and grow into the uterine cavity. Sometimes they may protrude from the cervical opening and are the cause of heavy menstrual flow and irregular bleeding. Due to impaired blood circulation, myomas can undergo degeneration, such as vitreous changes, cystic changes, red changes, and calcification. Very few myomas can also become malignant to sarcoma, which is mostly seen in older people and those with fast-growing myomas. The treatment of fibroids depends on the patient’s age, symptoms, location, size, growth rate, number of fibroids, deformation of the uterus, preservation of fertility and the patient’s wishes. There are several ways of treatment as follows.
I. Expectant therapy Small fibroids, no symptoms, no complications and no degeneration, no impact on health. Perimenopausal patients, no clinical symptoms, considering the possibility of myoma receding or shrinking after ovarian function decreases. All of the above cases can be treated with expectant therapy, i.e., regular follow-up observation (once every 3-6 months) in clinical and imaging terms. Their management will be decided based on the review. Usually, myomas regress naturally after menopause and therefore do not require surgical management. However, patients with leiomyosarcoma who are over 40 years old and may still have a few years to go before menopause may also be considered for surgery. However, conservative treatment with drugs can be given before surgery, and those with effective drugs can be treated without surgery for the time being. It should also be noted that postmenopausal women with leiomyosarcoma, a small number of patients with leiomyosarcoma does not shrink but increase in size, so follow-up should be strengthened.
There are many new advances in drug therapy.
(a) Indications for drug treatment 1. young people who require preservation of reproductive function. If the fibroids cause infertility or miscarriage at the reproductive age, drug therapy can make the fibroids shrink and promote conception and fetal survival.
2. Premenopausal women with fibroids that are not very large and with mild symptoms, who are exempted from surgery because of the atrophy of the uterus and menopause after the application of drugs.
3. Patients who have indications for surgery, but currently have contraindications that require treatment before surgery.
4. Patients with combined medical or surgical diseases are unable to perform surgery or unwilling to operate.
5. Before choosing drug treatment, it is advisable to perform diagnostic scraping and endometrial biopsy to exclude malignant changes, especially for menstrual disorders or increased menstrual flow. Scraping has both diagnostic and hemostatic effects.
The basis of drug treatment is that uterine fibroids are sex hormone-dependent tumors, so drugs that antagonize sex hormones are used for treatment. Newly applied are drugs that temporarily suppress the ovaries. Danazol and cotton wool are commonly used drugs in China. Other androgens, progestins and vitamin drugs are also used. Studies since 1983 have reported successful reduction of uterine smooth muscle tumors with the application of gonadotropin-releasing hormone analogs (GnRHa). Studies have shown that GnRHa indirectly reduces gonadotropin secretion at the pituitary level, thereby effectively suppressing ovarian function, a phenomenon known as “downregulation”.
（LHRH agonist (LHRH-A): GnRHa is a new type of anti-gynecological drug in recent years, after a large amount of continuous application of LHRH, the pituitary cell receptors are filled with hormones and cannot synthesize and release FSH and LH; in addition, LHRH has extra-pituitary effects, and after large doses are applied, the LHRH receptors on the ovaries are increased and the ovaries’ ability to produce estrogen and progesterone is reduced. In addition, LHRH has extra-pituitary effects. LHRH and LHRH-A are homologous and heterogeneous, but the latter is tens of times more active than the former. Usage: LHRH-A is mostly injected intramuscularly, but it can also be used for subcutaneous implantation or intranasal spray. 100-200 μg is injected intramuscularly from the first day of menstruation for 3 to 4 months. Its effect depends on the applied dose, the route of administration and the duration of the menstrual cycle. The average shrinkage of leiomyosarcoma after administration is 40 to 80%, with relief of symptoms and correction of anemia. The decrease in serum E2 was consistent with the reduction of leiomyoma, and there was no significant change in FSH and LH. The fibroids grew back soon after stopping the drug, suggesting that the effect of LHRH-A is transient and reversible. If used in perimenopause, natural menopause is achieved within a limited time. If used for those who preserve fertility, when myomas shrink and local blood flow decreases, thus reducing bleeding during surgery and narrowing the scope of surgery; or when myomas originally affected the fallopian tube opening and shrink after treatment to make the incompetent fallopian tubes open and improve the conception rate. In order to reduce the re-growth of fibroids after stopping the drug, the efficacy of LHRH-A can be maintained by sequential application of 200-500mg of megestrol acetate. The side effects are hot flashes, sweating, vaginal dryness or bleeding disorders. There may be osteoporosis due to the effect of low estrogen.
2. Danazol: It has a weak androgenic effect. Danazol inhibits the function of the thalamus and pituitary gland, causing the level of FSH and LH to decrease, thus inhibiting the production of ovarian steroids, or directly inhibiting the enzymes that produce ovarian steroids. As a result, the level of estrogen in the body decreases and the growth of the uterus is inhibited, the endometrium atrophies and menopause occurs. At the same time, the fibroids shrink and become smaller. However, in young people, menstruation can be restored after 6 weeks of discontinuation of the drug. Therefore, repeated application is needed. Dosage: 200mg orally 3 times a day for 6 months starting from the second day of menstruation. Side effects are hot flashes, sweating, weight gain, acne, and elevated SGPT in liver function (check liver function before and after medication). It can be recovered after 2-6 weeks of discontinuation.
3. cotton phenol: is a kind of double aldehyde naphthalene compound from cotton seeds, acting on the ovaries, no inhibition of the pituitary gland, the endometrium has a specific atrophy effect, and the endometrial receptors also have an inhibitory effect, the degenerative effect on the uterine muscle cells, resulting in pseudo-menopause and uterine atrophy. This drug is known as Chinese danazol, and is used to treat uterine fibroids with an efficiency of 93.7% for symptom improvement and 62.5% for fibroid shrinkage. Dosage: 20mg orally once a day for 2 months. After that, 20mg should be taken twice a week for 1 month. Then 1 time a week for 1 month for a total of 4 months. Since the side effect of cottonphenol is renal potassium excretion, it is necessary to pay attention to liver and kidney function and low potassium. Usually, 10% potassium citrate is added to the dose of cotton wool. Ovarian function will be restored after stopping the drug.
The first of these is the use of vitamins to treat uterine fibroids because it can reduce the sensitivity of the myometrium to estrogen, the neuroendocrine system has a regulatory role, so that the normalization of steroid hormone metabolism and promote the reduction of fibroids. 1980 the Soviet Union Палла дии reported to vit A-based, plus vit B, C, E and other comprehensive treatment of small fibroids, the effect of more than 80%, no side effects. Domestic Bao Yan also tried, the cure rate reached 71.6%, this method is suitable for small myomas. The method: vit A 150,000IU, from the fifteenth to twenty-sixth day of menstruation, daily oral. vit Bco1 tablet 3 times a day, from the fifth to fourteenth day of menstruation oral. vitc, 0.5, twice a day, from the twelfth to twenty-sixth day of menstruation oral. vit E 100mg, once a day, from the fourteenth to twenty-sixth day of menstruation oral, for a total of 6 months.
5. Androgens: To counteract estrogen, control uterine bleeding (excessive menstruation) and prolong menstrual cycle. How to use: Methyltestosterone 10mg, sublingual, once daily for 3 months. Or testosterone propionate is injected intramuscularly once daily at 25mg for 8 to 10 days starting 4 to 7 days after menstruation clears to obtain hemostatic effect. Long-acting male hormone is testosterone phenylacetate, which is 3 times stronger than testosterone propionate, 150mg injected 1 to 2 times a month. Generally, masculinization does not occur, and even if it does, the symptoms disappear naturally after stopping the drug. Androgen application is advisable within 6 months, if further use is needed, it should be stopped after 1 to 2 months. Long-term administration at the above doses is mostly free of side effects. It can make near-menopausal women enter menopause and stop bleeding. The use of androgens not only stops the growth of leiomyosarcoma, but also makes the leiomyosarcoma degenerate and shrink to a smaller size in 1/3 to 1/2 of patients. Because androgens cause water and salt retention, they should be used with caution or contraindicated in patients with heart failure, liver cirrhosis, chronic nephritis and swelling. Since some scholars believe that the occurrence of leiomyosarcoma may also be related to androgens, some tend not to use androgens.
6. progestin: progestin is to some extent an antagonist of estrogen and can inhibit its action, so some scholars use progestin to treat uterine fibroids with persistent follicles. Commonly used progestins include: methandrostenolone (androprogesterone), gynecomastia tablets (methandrostenolone), gynecomastia tablets (norethindrone), etc. Pseudopregnancy therapy can be performed in cycles or continuous treatment according to the patient’s specific situation to denature and soften the fibroids. However, it is not suitable for long-term application because it can increase the size of the tumor and irregular uterine bleeding. Methandrostenolone: Cycle therapy is 4mg orally daily from the sixth to the twenty-fifth day of menstruation. Continuous therapy: 4mg orally 3 times a day in the first week, 8mg twice a day in the second week. Later 10mg, 2 times a day. All continue to be applied for 3-6 months. It is also useful to take 10mg, 3 times a day for 3 months. Gynecomastia tablets: Cycle therapy is 5-10mg orally daily from the sixth to twenty-fifth day of menstruation or from the sixteenth to twenty-fifth day. Continuous therapy is 5mg once a day for the first week and 10mg once a day for the second week. Later 10mg twice a day. All applied for 3 to 6 months.
7. triamcinolone acetonide (tamoxifin, TMX): TMX is a bisphenoxy derivative, a non-steroidal anti-estrogen drug. TMX acts first on the pituitary gland and then on the ovaries, and also has a direct effect on the ovaries. tmx is more effective in ER positivity. Dosage: 10mg, 3 times a day orally for 3 months. Side effects include mild hot flashes, nausea, sweating, delayed menstruation, etc.
8. Trienolone (R2323): nemestran, a 19-nortestosterone derivative, has strong anti-estrogenic effects, which inhibits the secretion of FSH and LH from the pituitary gland, causing the estrogen level in the body to drop and the uterus to shrink, and is mainly used for the treatment of uterine fibroids. Dosage: 5mg, 3 times a week, vaginally placed, long-term application is advisable to prevent rebound enlargement of the uterus. The first 6 months of treatment showed good efficacy with significant uterine shrinkage. Side effects are acne, hot flashes, weight gain.
9. Mifepristone 10mg qd 3 months In the bleeding period of myoma patients with heavy bleeding, uterine contraction drugs or oral or intramuscular injection of hemostatic drugs are available. Such as motherwort fluid infusion, motherwort cream, oxytocin, ergotoxine, etc. Hemostatic drugs include gynecologic hemorrhage, triptolide tablets, hemostatic minerals, hemostatic aromatic acid, hemostatic cyclic acid, 6-aminoacetic acid, etc. Calcium can excite the uterine muscle tone and increase the coagulation properties of blood, and can also be tried. For example, 5-10ml of 10% calcium gluconate can be injected or 30-35ml of 5% calcium chloride can be used for enema.
It should not be forgotten that when vaginal bleeding hemostatic drugs are not effective, diagnostic scraping is not only helpful for diagnosis, but also for hemostasis.
Those who have anemia should correct it, take vitamins, iron or blood transfusion.
Where drug treatment fails, those who cannot reduce symptoms but worsen or those suspected of malignant change should be treated surgically.
Third, surgical treatment Myoma patients, the age of uterine adnexal resection, used to be set at 45 years old or above. Now it seems to be practical, especially according to the progress of gynecological endocrinology, the age of ovarian preservation is generally defined as 50 years old (the average age of menopause is 49.5 years old), that is, those who are within 50 years old and can preserve their ovaries should be preserved. Alternatively, normal ovaries of those who are not menopausal after the age of 50 should also be preserved, without drawing a line by age. The reason is that normal postmenopausal ovaries still have some endocrine function and will work for another 5 to 10 years. Retaining the ovaries helps to implicitly determine the vegetative nerves, regulate metabolism and facilitate the transition to old age. The uterus also has an endocrine role and is a target organ for the ovaries, which should not be removed casually. Usually, the age of hysterectomy is set at 45 years or older, and myomectomy is recommended for those under 45 years of age, especially for those under 40 years of age. If the adnexa can be preserved bilaterally, it is better to preserve both sides than only one side. The incidence of ovarian cancer is 0.15% if the ovaries are preserved, which is not higher than that of the uncircumcised uterus.
(a) Myomectomy: This is an operation to remove the fibroids from the uterus and preserve the uterus. It is mainly used for those under 45 years old, especially those under 40 years old. This procedure is not only for infertile women who have no children, but also for those who have children, have large fibroids larger than 6 cm in diameter, have heavy menstrual flow, have symptoms of pressure, have submucosal fibroids, and have fast-growing fibroids. For the sake of physical and psychological health, they should also be removed. As for the number of fibroids, it is usually limited to 15 or less. There are cases where the number of fibroids is more than 100 or more and the child is born. There are four types of surgical procedures: laparoscopic, transvaginal, transabdominal, and transhysteroscopic (submucosal fibroids). Excision is contraindicated in cases of malignant fibroids with severe pelvic adhesions, such as tuberculosis or endometriosis, or in cases of highly suspicious cervical cytology. For myomectomy, preoperative pathological examination of the endometrium is preferable to exclude precancerous or cancerous endometrial lesions. Intraoperative attention should be paid to whether the fibroids are malignant, and rapid biopsy should be performed when there is suspicion.
Those who are not pregnant after myomectomy should use contraception for 1 to 2 years; later pregnancy should be alerted to uterine rupture and placental implantation, and elective cesarean section should be performed at full term. The possibility of recurrence after myomectomy should be checked regularly.
(B) Hysterectomy: If the patient’s symptoms cannot be improved by expectant therapy or drug therapy, and the patient needs surgery and is not eligible for myomectomy, hysterectomy is appropriate. Hysterectomy can be performed laparoscopically, transabdominally and transvaginally.
Large submucosal fibroids causing bleeding and severe anemia are usually treated with blood transfusion to improve the body condition before surgery (simple myomectomy or hysterectomy). However, in remote rural areas where there is a lack of blood supply, the bleeding does not stop, it is not advisable to move and walk, the cervical opening is wide, and the fibroids are protruding outside the cervical opening or near the vaginal opening, the fibroids should be removed vaginally, which often helps to stop the bleeding and correct the general condition.
Total hysterectomy is generally recommended, especially in cases with cervical hypertrophy, laceration or severe erosion. However, if the patient’s general condition is poor and technical conditions are limited, only subtotal hysterectomy can be performed, and the incidence of stump cancer only accounts for about 1-4%. However, regular checkups are still appropriate after surgery.
Other treatment modalities 1.Uterine fibroid embolization 2.Coagulation knife treatment 3.Ultrasound focus treatment