I. What is adenomyosis?
Adenomyosis is a benign lesion caused by the invasion of the basal layer of the endometrium into the myometrium. It used to be called intrinsic endometriosis, while non-myometrial endometriosis was called extrinsic endometriosis to show the difference. Adenomyosis occurs mostly in menstruating mothers aged 30 to 50 years. About half of the patients have a combination of uterine fibroids at the same time, and about 15% have a combination of endometriosis. The latter is also known as adenomyoma, which is not easily distinguished from fibroids. The depth of infiltration of the lesions can be divided into three categories: lesions infiltrating only the superficial myometrium, lesions infiltrating the middle myometrium, and lesions infiltrating more than the middle myometrium.
In layman’s terms, this means that the muscles and glands of the uterus are faulty. The uterus is composed of three layers of tissue: the endometrium on the inside, the muscle in the middle, and a plasma membrane on the outside, like the peritoneum. Normally, the endometrium should be below the muscle layer and there is a boundary between them. If the endometrium and the superficial muscle layer are damaged, such as by childbirth, multiple abortions and scraping, the endometrium will take advantage of the situation. They grow and develop in the uterine muscle and stimulate the surrounding myocytes to proliferate, and adenomyosis develops. The endometrium in the muscle can, like the normal endometrium, become periodically congested, edematous or even bleeding in response to changes in the menstrual cycle, which can cause intense lower abdominal pain due to strong uterine contractions. Sometimes, adenomyosis appears only in one part of the uterus, causing localized myometrial cells to proliferate significantly to form a mass, which is then called adenomyoma. However, it is actually not a real tumor and does not contain tumor cells, and there is no obvious boundary with the surrounding area.
Why do I get adenomyosis?
The real pathogenic mechanism is not clear. Most scholars believe that it is related to genetics, injury (such as curettage and cesarean section), hyperestrogenemia, and viral infection. Serial sections of adenomyosis specimens have revealed that some of the endometrial lesions in the myometrium are directly connected to the endometrium on the uterine cavity surface, so it is generally believed that trauma to the uterine wall during multiple pregnancies and deliveries and chronic endometritis may be the main causes of this disease. In addition, because of the lack of submucosal layer under the basal lining of the endometrium, and because adenomyosis is often combined with fibroids and hyperplasia of the endometrium, it is thought that the invasion of the basal endometrium into the myometrium may be related to high estrogen stimulation.
Observation of the surgically removed hypertrophied uterus by incision reveals fresh or old myometrial bleeding, which is a manifestation of ectopic endometrial tissue in the myometrium. Some ectopic endometrial tissues in the myometrium may even have proliferation, secretion, metaplasia, and other changes similar to the menstrual cycle. Although serial sectioning of autopsies and specimens of uterus removed for disease reveals endometrial tissue in the myometrium in 10-47% of cases, only 70% of them have clinical symptoms.
What are the clinical manifestations of adenomyosis?
The main manifestations are excessive menstruation and progressive dysmenorrhea. The degree of dysmenorrhea is severe, manifested as persistent lower abdominal pain, lumbago, anal swelling with nausea and vomiting. It often leads to infertility or anemia.
Secondary dysmenorrhea occurs in older women, i.e., when they approach 40 years of age, and is progressively worse, often spasmodic. It manifests as small abdominal pains during menstruation that begin several years after the birth of a child and usually get worse. Pain medication is usually required, and many patients need pain relief injections. Some women are in so much pain that they roll around on the floor, and the pain relief injections do not completely stop the pain. Over time, the pain relief injections become less and less effective, so that they cannot hold on to their daily routine. Dysmenorrhea is caused by edema of the ectopic endometrium during menstruation, bleeding, and stimulation of spasmodic contraction of the muscle wall.
The menstrual flow increases, the period lengthens, and anemia easily occurs, and a few may have spotting bleeding before and after menstruation. This is due to the increase in the size of the uterus, the increase in the area of the endometrium of the uterine cavity, and the ectopic endometrium between the myometrium walls affecting the contraction of the myometrial fibers.
The uterus is enlarged on gynecological examination, mostly uniformly, but adenomyosis may also be present in those with a normal or even smaller than normal uterus. The uterus is hard and there is pressure pain. A few patients may have nodular protrusions or surface irregularities. During menstruation, the uterus may be enlarged, softer than usual, and the pain may be more pronounced. A few patients have pain during sexual intercourse, facial growth of acne, chloasma, etc.
4. How to diagnose adenomyosis?
Adenomyosis should be considered in middle-aged fertile women with secondary, gradually increasing dysmenorrhea. Ultrasound examination is best performed during menstruation or just after menstruation, which typically shows a uniformly enlarged uterus with many small scattered cystic reflections between the muscles. Uterine iodine oil imaging can be seen in one or several places into the muscle wall, forming diverticulum-like shadows, but its positive rate is only about 20% and should be differentiated from uterine fibroids. In some patients, pelvic magnetic resonance examination can be done to understand the myometrium and lesions. The final diagnosis also relies on the gross and pathological histological examination of the uterus.
Can a patient with adenomyosis get pregnant?
Adenomyosis often affects women between 30 and 50 years old, especially those who are approaching menopause. Usually, these patients have completed their reproductive tasks and do not have to worry about infertility. However, in recent years, with the increase in the number of patients who have had multiple abortions and scrapings, it is not uncommon for young people in their twenties and women over 30 who have not yet had children to suffer from adenomyosis.
For these patients, once they get adenomyosis, the most important concern is whether it will affect fertility and lead to infertility? It is generally accepted that severe adenomyosis, especially when combined with endometriosis, can lead to infertility. This type of patient has a thick uterus and is prone to pelvic adhesions, which are not conducive to ovulation and embryo implantation, resulting in a low pregnancy rate. Fortunately, it is uncommon for young women to have severe adenomyosis. In cases of mild adenomyosis, there is still a chance of pregnancy. In addition, if the adenoma is limited, the tumor can be surgically removed to preserve the uterus and there is still a chance for future pregnancy.
So, if a patient with adenomyoma gets pregnant, is there a risk of miscarriage during pregnancy? There is not enough literature to prove whether a pregnancy with a limited adenoma increases the rate of miscarriage. In the case of diffuse adenomyosis, the chance of miscarriage may be higher.
VI. How is adenomyosis treated?
The treatment of adenomyosis can be divided into two categories: conservative treatment and surgical treatment.
1.Conservative treatment
For young patients who still need to have children and for women who are close to menopause, conservative treatment is the first priority to try to save the uterus from total removal. Recently, the levonorgestrel intrauterine device (IUD) (trade name: Manuel), which is used in clinical practice, can significantly improve the symptoms of dysmenorrhea, pelvic pain and excessive menstruation in patients with adenomyosis, thus providing an additional treatment option for these patients. However, pharmacological treatment remains the mainstay of treatment and includes.
(1) Non-steroidal anti-inflammatory drugs can provide symptomatic relief, such as anti-inflammatory painkillers and fenpropathrin.
(2) Oral contraceptives are also effective. Periodic use not only inhibits ovulation and has a contraceptive effect, but also causes the endometrium and ectopic lining to atrophy, resulting in less menstrual flow and disappearance of dysmenorrhea. However, long-term use is not appropriate for menopausal women. Side effects include nausea, vomiting, breast swelling, breakthrough bleeding and weight gain. Currently, it is mostly used for unmarried or mild patients who have no need to have children for the time being and have significant dysmenorrhea. However, dysmenorrhea often recurs after discontinuation of the drug.
(3) Danazol can block the aromatase activity of adenomyosis tissue, inhibit the hypothalamus and pituitary gland, and act directly on the ovaries to reduce FSH, LH and E and P levels, and can also directly bind to estrogen and progesterone receptors in the endometrium, leading to endometrial atrophy and causing amenorrhea, which is called pseudo-menopause therapy. Recent studies have also demonstrated that Danazol can inhibit endometrial cell proliferation through immunomodulatory effects. Menstruation is suspended while taking the drug, so no more dysmenorrhea. Three to six months of continued use of the drug results in a thinning of the myometrium and a smaller uterus. Side effects include hypoestrogenic symptoms such as smaller breasts, vaginal dryness, sweating, and hot flashes. This drug is an androgen derivative, and long-term use may cause side effects such as low voice, acne, and beard growth. In addition, it may cause abnormal lipid metabolism and impaired liver function, so it is prohibited for people with cardiac, hepatic and renal insufficiency; during treatment, liver-protective drugs should be taken at the same time and liver function should be monitored.
(4) Mifepristone, a synthetic 19-nortestosterone derivative, has strong anti-progesterone effects due to its strong binding to progesterone receptors, causing amenorrhea and relieving pain. In earlier years, it was widely used as an anti-pregnancy drug, and in recent years, some authors have tried it in the treatment of endometriosis and proved to have some clinical efficacy. Normal menstruation resumes after 3-6 weeks of menopause, with a high recurrence rate. Some scholars reported that 100mg/d×3 months, the symptoms improved, but the lesions remained; 50mg/d×6 months, the symptoms and lesions both improved. In China, a low amount and long course of treatment, starting from the second day of menstruation, 10mg/d for 6 months, is still in the exploratory stage.
(5) Progesterone (endometrium), whose mechanism of action is to inhibit pituitary FSH and LH secretion, has strong binding ability with progesterone receptors and weak binding ability with estrogen receptors, so it has strong anti-progesterone and moderate anti-estrogen effect. It is suitable for all types of endometriosis as it can have good effects with small doses. Since the drug has a plasma half-life of 24h, it should be taken twice a week at 2.5mg on the first and fourth day of menstruation, and then at the same weekly dosing schedule for 6 months. Endometrium is better than Danazol in the treatment of endometriosis, with lighter side effects than Danazol, lower recurrence rate, higher pregnancy rate, and easier administration. However, it is more expensive.
(6) GnRHa (Norethindrone, Daphylline, etc.), a new safe and effective drug for the treatment of endometriosis in recent years, is a synthetic natural GnRH analogue. Under normal conditions, GnRH is released from the hypothalamus in micro-pulses and binds to receptors on the surface of the pituitary gland, forming receptor-ligand complexes, which are transported to the cells via internalization to stimulate the release of LH and FSH from the pituitary gland. synthetic GnRHa has 100 times stronger affinity with pituitary gonadotropin receptors than normal GnRH. Therefore, after the drug is administered, the plasma FSH, LH and E2 increase transiently for about 1 week during the initial phase, as most of the receptors are occupied and internalized. After about 10-15 days of continuous drug action, the amount of pituitary surface receptors decreases sharply, and this phenomenon is known as receptor down-regulation, resulting in a significant decrease in LH levels, which is called pharmacological pituitary resection, and ultimately a decrease in ovarian steroid hormones. Since GnRHa is a slow-release agent that releases GnRH into the bloodstream at a constant rate, it effectively inhibits the pituitary-ovarian system, maintains serum E2 levels at postmenopausal levels (E2 <50 pg/ml 15 days after administration), and causes endometrial atrophy. GnRHa is effective in treating endometriosis, resulting in complete remission of clinical symptoms and significant reduction of lesions. the improvement rate of endometriosis with GnRHa is 85%-90%, the improvement rate of laparoscopic lesions is 50%-80%, the pregnancy rate is 40%-60%, and the recurrence rate is 16%-59%. However, the drug is expensive.
GnRHa drug has few side effects, mainly low estrogen levels causing menopausal-like syndrome manifestations and bone loss, smaller breasts, vaginal dryness, sweating, hot flashes, and vasodilatory dysfunction. The severity varies from person to person, but is generally tolerated by patients and most recover after discontinuation of the drug. The drug does not cause side effects such as weight gain, acne and liver function damage caused by Danazol and Nemeton. Severe hypoestrogenic state (E2 < 20 pg/ml) due to long-term GnRHa application may cause abnormal calcium metabolism and thus increase the risk of osteoporosis, which is recovered in most patients after discontinuation of the drug. In relapsed cases requiring repeated treatment for 12 months or longer, in order to eliminate this side effect, reverse add-on therapy can be used, i.e., the application of GnRHa can be supplemented with small doses of estrogen or estrogen and progestin replacement therapy (HRT) to maintain E2 concentrations at 30-45 pg/ml, which does not stimulate lesion growth but also maintains normal bone metabolism and keeps serum bone metabolic indexes in the normal range. Thus, the treatment can be maintained or prolonged.
These drugs are only for temporary relief of symptoms and control of the disease, but once the drugs are discontinued for a period of time, the lesions will gradually return to their original state, and no drugs can cure the disease, and they are expensive, so they are only suitable for young patients who still have the need to have children.
2.Surgical treatment
For limited fibroids, the uterus can be preserved by surgical removal of the fibroids, and in some cases, minimally invasive laparoscopic excision of the adenomyoma can be used. In the case of diffuse adenomyosis, the uterine wall can be surgically thinned and post-operative medication can be given, and there is a chance of conception, although recurrence is still possible for some time. In recent years, the use of uterine artery embolization interventions for adenomyosis has also been reported with success. These surgical methods to preserve the uterus are suitable for patients with fertility needs.
For patients over 35 years of age who have completed their reproductive life and suffer from severe dysmenorrhea or excessive menstrual bleeding that affects their quality of life, surgical removal of the uterus is the most effective and most commonly used treatment.
In recent years, scholars at home and abroad have started to treat adenomyosis with hysteroscopy. After excision of the endometrium, menstruation is greatly reduced, and in some cases, it no longer comes, and dysmenorrhea is obviously seen.
3.Pregnancy
During pregnancy, ovarian ovulation is suppressed and menstruation does not occur, which has a therapeutic effect on the adenomyosis lesion itself. For young patients who want to have children, it is best to try to conceive while the conservative treatment is still effective and has not recurred, as there is still a chance of successful pregnancy. According to some reports, the cure rate of laparoscopic excavation of the lesion + in vitro fertility assistance is 95%.
7. Can adenomyosis become cancerous?
The incidence of endometriosis (EM) malignancy was previously thought to be 0.7% to 1.0%, but recently it is thought to be ≥2.5%. It is generally believed that adenomyosis, like uterine fibroids, is rarely cancerous.
How to prevent adenomyosis?
There is a lack of effective measures for prevention of adenomyosis. However, timely detection and treatment of narrow or obstructive diseases of the reproductive tract, fewer births, and fewer abortions or curettage have the potential to reduce its chance of development.