Name and definition of adenomyosis
Adenomyosis is a benign condition in which the endometrial glands and mesenchyme invade the myometrium and was formerly called “intrinsic endometriosis”. In recent years, it has been found to have many differences from extrinsic endometriosis and has been classified as a separate uterine disease. Zhang Weiyang, Department of Obstetrics and Gynecology, Second Hospital of Jilin University
In 1860, Rokitansky was the first to mention the presence of endometrial glands in the myometrium as “cystic sarcoma-like glands”; in 1896, Von Recklinghausen defined it as “adenomas and cystic adenomas of the uterus and fallopian tubes”; In 1925 Frank first used the term “adenomyosis”; in 1972 Bird et al. described benign infiltration of the endometrium into the myometrium, producing diffuse uterine growth, which microscopically appears as hypertrophic hyperplasia of the myometrium surrounded by ectopic, nonmalignant endometrioid glands and mesenchyme; in 2000 Uduwela et al. concluded that adenomyosis is diagnosed when the glandular invasion exceeds 2.5 L of the endometrium-myometrium boundary or when the microinvasive adenomyoma exceeds >2.0 L of the subbasal lamina. This view is well established.
Adenomyosis and endometriosis
Adenomyosis differs from endometriosis in that the ectopic endometrium may appear outside the myometrium or may invade the plasma membrane and subplasma layer of the posterior wall of the uterus from the pelvic cavity from the outside to the inside, but is not attached to the surface endometrium and is not accompanied by hyperplasia or hypertrophy of the muscle tissue. Adenomyosis and endometriosis are not two forms of the same disease, but differ in etiology, pathogenesis, pathological changes and treatment modalities. There are some clinical similarities between adenomyosis and endometriosis, and they are not completely isolated from each other.
Adenomyosis and malignancy
Malignant transformation of adenomyosis is very rare and is mostly reported in isolated cases; mainly endometrioid adenocarcinoma, but not uterine sarcoma or carcinosarcoma has been reported; all cases of malignant transformation have an excellent prognosis after surgery.
Histopathologic criteria for the diagnosis of malignant changes in adenomyosis: (1) no malignant lesions exist in the orthotopic endometrium or pelvic area; (2) the cancer must be seen in the glandular epithelium from the adenomyosis area and not invaded or metastasized from other sites; (3) the interstitial endometrium must be seen around the cancerous lesion to support the evidence of adenomyosis.
Endometrial adenocarcinoma involving adenomyosis: there are mesenchymal cells of the endometrium around the focal gland separated from the surrounding myometrium; benign endometrial glands are seen near the cancerous gland, indicating that adenomyosis is partially involved; the involved lesion in the myometrium has a round and smooth shape; there is no pro-fibroplasia or interstitial laxity around the involved lesion and inflammatory reaction. The mechanism of endometrial adenocarcinoma involving adenomyosis: (1) the cancerous glands are directly extended from the orthotopic endometrial adenocarcinoma into the adenomyosis lesion; (2) ‘regional effect’, most scholars believe that the orthotopic endometrium and the focal endometrium of adenomyosis are affected by common carcinogenic factors to develop cancer in two places. Clinicopathological features of endometrial adenocarcinoma involving adenomyosis: ① patients often have a history of estrogen use ② tumors are mostly low grade ③ prognosis is excellent.
(b) Adenomyosis appears as a malignant lesion of ‘regional effect’, which does not affect the prognosis of endometrial cancer even if it appears in the deep myometrium, unlike the invasion of the myometrium by endometrial cancer.
It is very important to differentiate the malignant change of adenomyosis or endometrial adenocarcinoma involving adenomyosis from the invasion of real myometrium by endometrial cancer; a comprehensive and careful examination of the orthotopic endometrium must be done to determine the presence of cancer in the endometrium, and the malignant change of adenomyosis can be diagnosed only after the involvement of endometrial adenocarcinoma in adenomyosis has been excluded.
Clinical manifestations of adenomyosis
1, dysmenorrhea: the most common symptom; the incidence rate is 50%-70%; the main reason for consultation; the typical manifestation is secondary dysmenorrhea, which is progressively aggravated; the degree of dysmenorrhea is positively correlated with the depth of endometrial invasion to the myometrium and the density of endometrial interstitium and glands in the myometrium.
2, excessive menstruation: the main manifestation is prolonged menstruation and increased menstrual flow; the incidence is 40%-70%; myometrial lesions affect the contraction of uterine fibers, and the open blood sinuses cannot be closed during menstruation; the thickening of the uterine wall increases the area of the uterine cavity; the endometrial hyperplasia is excessive due to the influence of estrogen and progesterone.
3, infertility: combined with endometriosis: non-specific inflammation affects the egg collection and transport function of the fallopian tubes, and serious adhesions may cause local mechanical obstruction; a large number of cytokines are produced to affect sperm activity, follicle development and oocyte division. The lesion is located in the uterine horn and can cause obstruction in the interstitial part of the fallopian tube; combined with uterine fibroids.
4, decreased libido, sexual frigidity, painful intercourse: pain caused by local lesions stimulated by intercourse; painful intercourse makes the patient refuse to have intercourse psychologically and physiologically, showing decreased libido and sexual frigidity.
5, uterine enlargement: generally does not exceed the size of 3 months of pregnancy; diffuse uterus is uniformly spherical enlargement; uterine size and texture change with the menstrual cycle, the uterus increases during or before menstruation, and then gradually shrinks; uterine enlargement exceeds the size of 3 months of pregnancy, surface irregularities are often combined with fibroids.
Diagnosis of adenomyosis – medical history
(1) Prevalent in women aged 40-49 years; (2) history of previous pregnancy and delivery and uterine operations; (3) dysmenorrhea; (4) menstrual disorders; (5) other: painful intercourse, pelvic pain, infertility, anemia, etc.; (6) no clinical symptoms.
Diagnosis of adenomyosis – Auxiliary tests
①Ultrasound diagnosis
TAS imaging features: uterus enlargement, full morphology, regular envelope, diffuse or limited thickening of the muscle wall, inhomogeneous echogenicity with poorly defined surrounding normal tissues, some of them showing stellate strong echogenicity, posterior fenestrated acoustic shadow, and small dark areas may be scattered. Most of the thickening of the posterior wall is predominant, and the endothelial line is anteriorly shifted in an arch shape.
Color multispectral imaging (CDFI): there is abundant stellate blood flow signal in the wall lesion with unclear border, and the surrounding blood flow signal is not abundant and irregular; while there is abundant blood flow in the myometrium with radiolucent or branching blood flow signal. Pulsed multispectral (PD): low-velocity high-resistance arterial flow or venous low-velocity flow.
Magnetic resonance imaging (MRI):
The MRI signal of the normal uterus has the following characteristics on T2W1: a distinct high signal in the endometrium, a slightly high signal in the myometrium, and a low signal in the binding band located between the two.
The MRI features of adenomyosis are: the uterus is enlarged and the contour is shiny; the endometrial margin on the adenomyoma side is often irregular and serrated; the changes in the binding zone are diagnostically specific. The thickening of the union zone is one of the main differences between the MRI signs of adenomyosis and fibroids. The binding zone is a superficial subendometrial layer that appears as a narrow band-like low signal around the endometrium on MRI signal. The diagnostic criteria are inconsistent, ranging from 5 to 12 mm. A diagnostic criterion of >12 mm has a sensitivity of 93% and a specificity of 91%.
MRI features of adenomyosis: endometrial tissue in the myometrium is high signal on T1W1 and T2W1 when there is periodic bleeding; adenomyoma without envelope; cystic adenomyosis: high signal cystic lesion on T2W1 with low signal intensity area in the cyst wall.
(iii) CA125
CA125 is a surface antigen derived from the epithelial cells of the corpora cavernosa and is a high molecular protein, mainly found in the endometrium, cervical epithelium, fallopian tubes and peritoneum; Krasnieki et al. found that ectopic endometrium in adenomyosis has a strong function in secreting CA125; serum CA125 >35KU/L is a positive criterion; serum CA125 test is useful for the diagnosis of adenomyosis. The serum CA125 test has significance for the diagnosis of adenomyosis.
Differential diagnosis of uterine adenomyosis
Uterine fibroids; pregnancy; endometrial cancer; uterine sarcoma; uterine hypertrophy; dysfunctional uterine bleeding; extrinsic endometriosis; pelvic stasis.
Treatment of adenomyosis
The treatment of adenomyosis is diversified; hysterectomy is not the only effective treatment for adenomyosis; the choice of treatment should take into account the patient’s age, fertility requirements, severity, location and extent of the lesion, as well as the patient’s wishes and hospital conditions and technical equipment; the combined application of treatment methods.
Treatment of adenomyosis – general principles
1, for young patients with fertility requirements, dysmenorrhea and insignificant uterine enlargement, expectant therapy can be chosen.
2, the uterus enlargement is obvious, the clinical symptoms are serious, affecting normal life and workers, according to different situations to choose the program. ①Younger patients with or without fertility requirements: simple medication, conservative surgery with medication; no fertility requirements can be surgically removed from the uterus. ②Operation is the mainstay for those who are older. ③ Near menopause can be expected therapy or surgery.
Conservative treatment of adenomyosis
the purpose of conservative treatment is to preserve the patient’s reproductive function; conservative treatment cannot achieve the purpose of curing the disease
conservative treatment is indicated for young, fertile and near-menopausal patients, or middle-aged patients who are determined to preserve the uterus
conservative treatment includes expectant treatment, pharmacological treatment, and conservative surgery combined with pharmacological treatment
Conservative treatment of adenomyosis – expectant therapy
Indications: 1 Patients without symptoms; 2 Mild symptoms or predominantly dysmenorrhea with insignificant menstrual changes and uterine enlargement; 3 Near menopausal patients
Methods: 1 patients with insignificant symptoms regular examination v3-6 monthsw, symptomatic treatment; 2 patients with fertility requirements assisted reproductive technology early pregnancy.
Pharmacological treatment of adenomyosis
Indications for pharmacological treatment: 1 patients young with fertility requirements; 2 perimenopausal patients; 3 patients with a strong desire to preserve the uterus.
Types of drug therapy: 1 gonadotropin-releasing hormone agonists 2 mifepristone; 3 androgenic derivatives; 4 oral contraceptives with indomethacin
Pharmacological treatment of adenomyosis – GnRH-a
The gonadotropin-releasing hormone agonist vGnRH-aw is considered the most effective drug for patients with adenomyosis with infertility. The drug is used to cause a low estrogenic state in the body and temporary amenorrhea, which acts as a temporary drug depot for therapeutic purposes.
Drug mechanism: 1 GnRH-a is a synthetic 10-peptide compound, a long-acting gonadotropin-releasing hormone agonist, similar in action to natural GnRH, but with strong affinity for GnRH receptors, good stability to peptidase decomposition, long half-life, and about 100 times the potency of GnRH; 2 GnRH- a can promote the secretion of LH and FSH by pituitary cells, and long-term application has a down-regulating effect on the pituitary gland. Long-term application of GnRH-a continuously down-regulates GnRH receptors and inhibits the secretion of pituitary gonadotropins, thereby inhibiting ovarian function and reducing estrogen levels, ultimately leading to a persistent low estrogen state in the body.
Usage and dosage: 1 leuprorelin vleuprorelin inhibitor w3.75mg/stem, 1 subcutaneous injection on the 1st day of menstruation, 1 injection every 28 days, 3-6 times; 2 goserelin vgoserelin norad w3.6mg/stem, usage as before; 3 tryptorelin v daphylline tryptorelinw3.75mg/stem, intramuscular injection, as before.
Efficacy: GnRH-a can effectively control the symptoms of adenomyosis and improve the pregnancy rate; induce amenorrhea in perimenopausal women; continuous use of uterine shrinkage, patients with amenorrhea and disappearance of dysmenorrhea.
Adverse effects: hot flashes, night sweats, vaginal dryness, decreased libido, breast tenderness, insomnia, depression, irritability and fatigue due to low estrogen status. Usually disappears within a short period of time after discontinuation of the drug; the use of GnRH-a bone conversion is significantly accelerated, resulting in faster bone loss and osteoporosis.
Reactive additive therapy: serum E2 level of patients with 30-50 pg/ml after medication is more desirable, and mostly advocate supplementation with small doses of estrogen and progestin from the 2nd to 3rd month of medication.
Pharmacological treatment of adenomyosis – Mifepristone
Mifepristone is an anti-progesterone drug that acts at the receptor level and has five times the affinity of progesterone for its progesterone receptor. It can replace progesterone in the body to compete with the receptor and block the effect of endogenous progesterone. Mifepristone also antagonizes the pro-proliferative effect of estrogen on the endothelium by inhibiting its differentiation, promoting apoptosis, and reducing its growth potential through non-competitive anti-estrogenic effects. Mifepristone acts on the hypothalamic-pituitary-ovarian axis, inhibiting FSH secretion, preventing follicular development and causing ectopic endothelium to atrophy. It acts directly on adenomyotic cells, inhibiting their proliferation and differentiation and reducing their growth potential. Acts on local blood vessels and vascular-related factors to affect the angiogenesis and physiological function of endometrium, and affects the proliferation of endometrium. It inhibits the autocrine secretion of IL-6 and participates in immune regulation by inhibiting the secretion of IL-6, resulting in ectopic lesions and reduced local immune and inflammatory responses in the endometrium. Decrease the autocrine (paracrine) secretion of epidermal growth factor receptor (EGFR) in ectopic endometrial cells to inhibit the proliferation of ectopic endometrium.
Usage and dosage: ①Short course: Mifepristone 25mg, 10mg or 12.5mg, starting from the 1st~3rd sweet of menstruation, for 3~6 consecutive appointments. ②Long course: one is 25mg/d continuous dose; the other is 25mg daily for 1 month, and then changed to 10mg daily for long term use.
Treatment effect: Mifepristone for uterine adenomyosis has obvious recent efficacy, but the recurrence rate is high after stopping the drug.
Adverse effects: Mifepristone is safe and effective in the treatment of adenomyosis with few adverse effects.
Surgical treatment of adenomyosis
Indications for radical surgery: 1. Patients over 40 years of age with obvious clinical symptoms of dysmenorrhea and excessive menstruation and without fertility requirements. 2. Patients with obvious clinical symptoms, extensive lesions and ineffective drug therapy. 3. Patients who recur after conservative surgery and require reoperation should opt for hysterectomy.
Surgical indications for conservative surgery: 1. Patients with fertility requirements should try to preserve the uterus. 2. Patients without fertility requirements, but require preservation of the uterus. Sexual total hysterectomy is generally advocated. Although subtotal hysterectomy is simple and easy to perform, the preservation of the cervix may sometimes lead to recurrence due to incomplete removal of the lesion. Surgical removal of the uterus is the most effective and complete treatment for adenomyosis
Combined surgical and pharmacological treatment of adenomyosis
Limitations of conservative surgery: (1) it is only applicable to focal nodular lesions, not to patients with diffuse uterine enlargement, and its application has certain limitations; (2) conservative surgery cannot remove diffuse lesions around nodular lesions; (3) surgical treatment treats the symptoms but not the root cause, it only changes the lesions already formed by endometriosis, but does not change the pathophysiological basis of endometriosis. The above characteristics determine that the disease is very easy to recur after surgical treatment, especially conservative surgical treatment. Combined surgical and pharmacological treatment is very necessary.
Preoperative medication; GnRH-a or pseudo-menopausal medication is more commonly used. Preoperative application of GnRH-a can reduce uterine blood flow, shrink lesions, shrink the uterus, reduce pelvic adhesions and congestion, inhibit the production of ovarian physiological cysts, and correct anemia. Generally, medication is given for 3 months before conservative surgery
Postoperative medication: mainly to treat residual lesions, reduce or postpone recurrence, and restore the fertility of infertile patients. The choice of drugs for postoperative treatment of adenomyosis should take into account the age of the patient, the extent of the lesion and the socioeconomic conditions of the patient.
Interventional treatment of adenomyosis
History of interventional treatment of adenomyosis: The treatment of adenomyosis is slightly earlier in China than abroad. The treatment of adenomyosis with uterine artery embolization (UAE) was an episodic event; on June 18, 1999, a patient with 42 patients suffering from dysmenorrhea but with a desire to have children insisted on UAE treatment and bilateral uterine artery embolization was performed. The dysmenorrhea improved 1 month after UAE, decreased from grade 4 to grade 2 after 3 months and to grade 1 after 6 months and then disappeared. Menstruation also returned to normal. In foreign countries, the interventional treatment of adenomyosis started from the cases of failed interventional treatment of uterine fibroids. It is considered that the treatment of adenomyosis with action pulse embolization is ineffective.
Mechanism of interventional treatment of uterine adenomyosis: theoretically the mechanism of UAE treatment of uterine adenomyosis by embolization of the arteries from the uterus causes necrosis and absorption of endometrial lesions ectopic to the uterine body due to ischemia and hypoxia, and the volume of the uterus appears significantly large reduction leading to the closure of the channel of the smile between the muscle walls. It can cause necrosis of its ectopic endometrium to achieve therapeutic effect, or it may damage the estrogen receptors on the ectopic endometrium and inhibit the secretory function of the ectopic glands at the molecular level to achieve clinical efficacy.
Indications for interventional therapy: 1. Patients with typical clinical symptoms and signs and a clear clinical diagnosis such as ultrasound and MRI; 2. Women of all ages who are reluctant to remove the uterus because of their concerns about surgery or their fertility requirements; 3. Patients with a history of pelvic surgery or pelvic adhesions who are estimated to have difficulty in surgery; 4. Patients with lung disease, hyperthyroidism, diabetes mellitus, psychosis, and other diseases that are not suitable for open surgery, but with secondary dysmenorrhea and 5 Patients whose clinical symptoms such as dysmenorrhea and menorrhagia are severe and affect their health. 5 Patients whose medication is ineffective or whose adverse reactions are too great to continue treatment. 6 Patients with combined uterine fibroids.