In the field of obstetrics and gynecology, the levonorgestrel intrauterine delayed-release birth control system (IUS), or Mannorrhea, is not uncommonly used. It is a highly effective, safe, long-acting, and reversible method of contraception, in which levonorgestrel (52 mg/d) stored in a vertical tube is released quantitatively (20 μg/d) after IUS placement into the uterine cavity to provide contraception for up to 5 years. Mannorrhea results in low LNG concentration in the patient’s serum but high local concentration of LNG in the endometrium and adjacent tissues, which inhibits endometrial growth, causes glandular atrophy, thinning of the endometrium, interstitial metaplasia and inactive state, thus achieving contraception and reducing bleeding. The approved indications for use in China include contraception as well as excessive menstruation caused by non-organic pathologies, including adenomyosis, endometriosis, endometrial polyps, endometrial hyperplasia, and uterine fibroids. So let’s review the role of Manometrium in these diseases today. Contraception Differences from traditional IUDs: Mannorrhea contains the drug levonorgestrel, which is released regularly and is valid for 5 years; the material is plastic, not metal, and can be examined by MRI; levonorgestrel is a progestin, which can make the cervical mucus sticky and the endometrium thin, inhibiting the fertilization of the egg, and the contraceptive rate reaches 99.9%; levonorgestrel mainly works in the uterus, and is absorbed into the blood less, which does not Levonorgestrel works mainly in the uterus, is absorbed into the bloodstream, and does not inhibit the gonadal axis and affect ovulation. Because 20 μg of progestin is released in the uterus daily, only 0.2% (40 ng) enters the breast milk. Such a small dose will not affect breastfeeding and is relatively safe. Adenomyosis Adenomyosis (AM) is the presence of ectopic endometrial glands and mesenchyme in the myometrium and has a prevalence of 5-10%. Radical treatment remains hysterectomy, but is inappropriate for younger patients who have a requirement for uterine preservation. The 2015 Guidelines for the management of endometriosis state that levonorgestrel intrauterine delayed-release system (LNG-IUS) can be used to treat adenomyosis. Patients with a uterine cavity depth ≤ 9 cm can go directly to Mannorrhea; while patients with a cavity depth > 9 cm are first treated with gonadotropin-releasing hormone agonist (GnRH-a), which inhibits ovarian function by regulating gonadotropins in the pituitary gland, resulting in shrinkage and atrophy of the lesion and consequent recovery of uterine volume. Usually treatment with GnRH-a for 3-6 months is followed by the placement of Mannorrhea. The effect of Mannorrhea on adenomyosis is to reduce bleeding and relieve pain. The direct effect of intrauterine LNG on the endometrium causes endometrial metaplasia and atrophy, resulting in decreased bleeding, while LNG may affect the blood supply in the pelvis, resulting in relief of pelvic congestion and thus pain relief. Alternative treatment options currently available include oral contraceptives, progesterone, danazol, and GnRH-a, which may provide temporary relief but are prone to relapse after discontinuation and poor patient compliance. Other methods include endometrial ablation/excision, uterine artery embolization, and radiofrequency ablation. Prevention of recurrence after endometriosis EM is defined as the presence of endometrial tissue outside the body of the uterus. The main symptoms are lower abdominal pain, dysmenorrhea, painful intercourse, and infertility. The prevalence of EM is approximately 2-10% in women of childbearing age, 50% in infertile women, and 40%-60% in women with dysmenorrhea. The recurrence rate for patients treated with conservative surgery is 10%-15% within one year and up to 40%-50% within five years. In order to prevent recurrence, postoperative medication is required, including GnRH-a, Danazol, oral contraceptives, and progestin; GnRH-a, although effective, is more expensive and its long-term use will lead to side effects associated with low estrogen status, requiring hormone reversal and greatly affecting patient compliance. The long-term stable concentration of levonorgestrel in the endometrium can significantly inhibit endometrial proliferation and cause ectopic endometrium to degenerate, atrophy and shed; it may also inhibit local vascular regeneration, reduce pelvic vascular congestion, increase apoptosis and reduce macrophage activity in the peritoneal fluid. Uterine fibroids with menorrhagia The treatment of uterine fibroids with Mannedol is mainly aimed at improving severe uterine bleeding associated with uterine fibroids. However, whether it can reduce the size of the uterus and shrink the fibroids needs to be studied, and it may even encourage the growth of fibroids, so it should be used with caution. If the fibroids are large and bleeding is heavy, surgery should be considered first. Prevention of recurrence after hysteroscopy for endometrial polyps Endometrial polyps are formed by excessive proliferation of local endometrial tissue and are a common endometrial lesion in women. Clinical manifestations include abnormal uterine bleeding and infertility, etc. Some patients do not have any clinical symptoms and are only detected during ultrasonography. Endometrial polyps affect conception by interfering with embryonic implantation. Hysteroscopic surgery is the “gold standard” for the diagnosis and treatment of endometrial polyps. The recurrence rate after surgery is 6.2% to 29%. To prevent recurrence, oral COC and progesterone can be considered after surgery, but the prevention of recurrence is limited. The mechanism may be the inhibition of ER, PR and Ki-67 expression, which induces endometrial apoptosis and promotes endometrial atrophy. Endometrial hyperplasia Endometrial hyperplasia is a biological and morphological change of the endometrium due to prolonged estrogen stimulation without adequate progesterone antagonism. Among them, atypical endometrial hyperplasia is a lesion with a tendency to become cancerous and is a precancerous lesion. Young patients with fertility requirements and patients with a requirement for uterine preservation can be treated with high-dose progestin, which requires long-term oral administration and poor compliance, and there is no uniform protocol for progestin treatment of endometrial hyperplasia. The local high concentration of LNG directly applied to the endometrium by Mannorrhea can cause endometrial glandular atrophy, interstitial edema and metaplastic changes, mucosal thinning, epithelial inactivity, non-disintegrating phase, vascular inhibition, and inflammatory cell infiltration, etc., resulting in a smooth inhibition of endometrial overproliferation. The ACOG 2015 guidelines recommend oral progestin and LNG-IUS as the first choice for non-surgical treatment of endometrial intraepithelial neoplasia. Others Include people at high risk of endometrial hyperplasia, hyperplastic endometrium, menorrhagia, dysmenorrhea, etc. In addition to its contraceptive effects, its non-contraceptive applications are gradually being expanded in the clinical setting. The main side effects of Mannorrhea placement are vaginal spotting, amenorrhea, abdominal pain, back pain, weight gain, and IUD withdrawal. The rate of termination due to side effects was as high as 24% in the first year and 33% in the second year. Patients are fully informed of possible side effects before the procedure, for example, a small amount of vaginal bleeding is normal and does not cause anemia, and if the amount is high a combination of oral contraceptives is available. The side effects are treated symptomatically accordingly, and it is understood that there are no adverse effects on health in order to make the most of them.