[Abstract] Uterine hypertrophy is a disease in which the uterus is uniformly enlarged and the thickness of the myometrium exceeds 2.5 cm or more, accompanied by varying degrees of uterine bleeding. It is easily confused with uterine fibroids, adenomyosis, dysfunctional uterine bleeding and endometrial cancer. Because of its high rate of clinical misdiagnosis, this article reviews the progress of diagnosis and treatment of this disease.
Uterine hypertrophy (also known as diffuse uterine hypertrophy (DUMH)) is a condition in which the uterus is uniformly enlarged and the thickness of the myometrium exceeds 2.5 cm, accompanied by varying degrees of uterine bleeding. The condition was first studied by Von Scanzoni in 1861 [1]. It is easily confused with fibroids, adenomyosis, dysfunctional uterine bleeding and endometrial cancer, and has not been uniformly recognized for more than 100 years. Because of its high clinical misdiagnosis rate, this paper reviews the progress of diagnosis and treatment of this disease.
1.Incidence
Uterine hypertrophy is clinically rare, and its incidence accounts for between 4.9% and 5.7% of all hysterectomy specimens [2, 3]. 5.7% of total hysterectomy specimens were reported by Lewis to have uterine weight greater than 120 g. In China, Qi Guohua [2] reported 4.9%, Zhang Xiaoyan [4] reported 31 cases of uterine hypertrophy in 735 hysterectomy specimens, accounting for 4%, and Wang Fang et al [5] reported 660 cases of uterine hypertrophy in 660 hysterectomy specimens. Among the hysterectomy specimens, 41 cases of uterine hypertrophy were reported, accounting for 6.2%, and Xiong Xiaoyan [6] reported 61 cases of uterine hypertrophy among 4265 hysterectomy specimens, accounting for 1.4%.
2. Etiology
The etiology of this disease is not well understood, and clinical studies have found that the age of onset of this disease is mostly between 30-45 years old, with multiple pregnancies and births as common features of this group of patients, with a history of at least 1-2 full-term deliveries, and some patients have a history of pelvic or uterine operations such as abortion, sterilization, and IUDs [1, 2, 3-11]. However, uterine hypertrophy has also been reported in infertile women [12], and its etiology needs further study.
3, Pathogenesis
The size and weight of the normal uterus are related to the age of the patient and the number of births. The weight of the uterus in normal women of childbearing age is 46-137 g and can reach 243 g in women who have given birth, which is a histologically normal uterus with normal endometrium and myometrium. If the weight exceeds 250 g, the patient can have excessive menstruation with anemia and often undergo hysterectomy due to uterine bleeding. In the past, the basic pathological changes of uterine hypertrophy were thought to be due to pelvic stasis, resulting in chronic swelling of the uterus and hyperplasia of the uterine coarctation tissue, or ovarian dysfunction and continuous elevation of estrogen concentration, resulting in hypertrophy of the uterine base, or hyperplasia of the elastic fiber tissue between smooth muscles and around blood vessels in the myometrium of multiple mothers, or chronic adnexitis, pelvic coarctation tissue inflammation and inflammation of the uterine parenchyma, resulting in Uterine fibrosis, etc. All of these changes can occur individually or concurrently in one patient [1].
Some authors now believe that the main cause of myometrial thickening is caused by hypertrophy of each myocyte without hyperplasia of junctional tissue, thickening of the myometrium makes the endometrial area increase and abnormal contraction of the myometrium leads to bleeding. From the clinical data, 96.7% of the patients had a history of childbirth, suggesting that pregnancy is related to the occurrence of the disease. 15.2% had multiple births, and 55.9% had only one full-term birth. However, 84.7% had a history of abortion, suggesting that intrauterine surgery may be a predisposing factor for the disease. Intrauterine surgery may damage the superficial myometrium of the endometrium, or episodic infection during surgery can cause endometritis and the onset of the disease. In addition, in 80.3% of patients aged 49 years or older, 51.7% of preoperative scalpel pathology was endometrial hyperplasia or polyp formation, suggesting high estrogen levels, and women of this age are in a period of transformation of ovarian function, i.e., continuous secretion of estrogen but lack of progesterone to act as a counteracting agent, and excessive estrogen myocytes proliferate and induce morbidity [8].
4, Pathology
4.1 Gross specimen: the uterus shows varying degrees of homogeneous enlargement, myometrial hypertrophy up to 2.5 cm or more, and weight over 250 g . A few may be combined with endometrial polyps.
4.2 Microscopic examination: hypertrophy of smooth muscle cells in the myometrium, hyperplasia of elastic fibers around blood vessels in the myometrium, chronic myometritis, hyperplasia of endometrium, hyperplastic endometrium or secretory endometrium may be combined.
5.Clinical manifestations
5.1 Symptoms: Most of them have different degrees of menstrual changes, manifested as menstrual disorders, shortened cycles, increased menstrual volume, prolonged periods, occasional sudden vaginal hemorrhage, dysmenorrhea, lower abdominal pain or discomfort, incomplete vaginal bleeding, dizziness, weakness and other secondary anemia symptoms.
5.2 Physical signs: Gynecological examination suggests that the uterus is uniformly enlarged about the size of a 2-3 month pregnancy, and the uterine body is hard in texture.
5.3 Auxiliary examination: routine blood tests suggested decreased hematocrit, mostly accompanied by varying degrees of anemia. ultrasound examination showed normal uterine section morphology on sonogram, which showed homogeneous enlargement with clear marginal contours, no surface protrusion, no deformation of the uterine cavity, no nodular hypoechoic areas or light clusters in the uterine section, and the sum of the three diameters was greater than 15 cm [14]. Diagnostic scraping revealed proliferative and secretory endometrium, excessive endometrial hyperplasia or endometrial polyps. It suggests that it may be related to high estrogen content in the body.
6, Diagnosis
6.1 Analysis of the causes of misdiagnosis
The misdiagnosis rate of uterine hypertrophy is extremely high, and it is mostly diagnosed by pathological examination after hysterectomy for uterine enlargement with menstrual changes. Zhang Xiaoyan reported that only 1 case of uterine hypertrophy was diagnosed before surgery, with a misdiagnosis rate of 96%, including 17 cases of uterine fibroids, 8 cases of dysfunctional uterine bleeding, 3 cases of ovarian cysts, and 1 case of adnexal inflammatory mass. Wang Fang reported that all 41 cases of uterine hypertrophy were misdiagnosed preoperatively, including 29 cases of uterine fibroids, 7 cases of adenomyosis and 5 cases of gonorrhea, and Chen Xiuling et al. reported that all 20 cases of uterine hypertrophy were misdiagnosed preoperatively as uterine fibroids. Regarding the reasons for misdiagnosis, it was concluded that ① uterine hypertrophy mostly occurs at the age of 30-50 years, uterine fibroids tend to occur at the age of 40-50 years, and the peak incidence of uterine adenomyosis is 30-40 years, and there is an obvious crossover in the age of onset of the three;
The main clinical symptoms of this disease are excessive menstrual flow and prolonged duration, and the uterus is uniformly enlarged in gynecological examination, such as the size of 6-8 weeks of pregnancy, while uterine fibroids, especially submucosal fibroids and adenomyosis, can also make the uterus uniformly enlarged, accompanied by increased menstrual flow.
③In addition, the relaxation of surgical guidelines to meet the patient’s eagerness to solve the psychology of abnormal menstruation is also a cause of misdiagnosis.
6.2 Diagnostic criteria and precautions in diagnosis
Diagnostic criteria.
①History of vaginal bleeding of varying degrees, manifested by increased menstrual flow, prolonged menstruation, shortened cycles, and occasionally a sudden heavy bleeding or dripping vaginal bleeding;
②The uterus is uniformly enlarged as the size of 6-8 weeks of pregnancy, hard, with smooth surface and no bumpiness;
③B ultrasound examination suggests normal uterine section morphology, uniform enlargement as pregnant, clear edge contour, surface as raised, no deformation of uterine cavity, no nodular hypoechoic areas or light clusters in uterine section, thickness of myometrium ≥2.5cm, sum of three diameters ≥15cm;
④ Diagnostic scraping: the uterine cavity was explored with a large cavity, no unevenness in the uterus during diagnostic scraping, some normal and some hypertrophic endometrial tissues were scraped out, and most of the pathological examinations were normal endometrium, a few showed proliferative and secretory phase changes or endometrial hyperplasia overgrowth and endometrial polyp-like changes, all without malignant changes [13].
This morphological diagnosis is still controversial, and some authors believe that in addition to the above diagnostic criteria, the diagnosis can be confirmed pathologically if the uterus weighs ≥ 200 g and the thickness of the myometrium is ≥ 2.0 cm [13].
7, Differential diagnosis
Since the clinical features of uterine hypertrophy are non-specific, it needs to be differentiated from uterine fibroids, adenomyosis, dysfunctional uterine bleeding and endometrial cancer.
7.1 Differentiation from uterine fibroids: Patients with uterine fibroids often do not have a history of multiple births, but some patients have a history of combined infertility or miscarriage. Although both interstitial fibroids and submucosal fibroids can show excessive menstruation or incomplete menstruation, vaginal examination of the uterus shows heterogeneous enlargement, the interstitial fibroids are hard, and the surface of the fibroids seems to be uneven when they are large. The ultrasound may show partial separation of the uterine cavity line (non-myoma area) and curvature. Iodine oil hysterosalpingography can show filling defects, and hysteroscopy and hysteroscopic exploration or curettage can help in the diagnosis. In contrast, hypertrophy of the uterus has a history of multiple and prolific births, and the uterus is uniformly enlarged on gynecological examination and vaginal examination.
7.2 Differentiation from adenomyosis and adenomyoma: Adenomyosis and adenomyoma have a history of infertility, dysmenorrhea, especially progressive dysmenorrhea, and hard, painful or non-painful nodules in the posterior vault, and ultrasound may show uneven echogenicity of the enlarged uterus, with varying intensity, sometimes with small echogenic areas. Hysterosalpingography with iodine oil is helpful in the diagnosis of this disease. The uterine cavity is seen to be enlarged and iodine oil can enter the myometrium from the uterine cavity to form diverticulum-like protrusions.
7.3 Differentiation from dysfunctional uterine bleeding: Dysfunctional uterine bleeding mostly occurs in adolescence after menarche or during menopause near menopause, followed by heavy bleeding during menopause. In addition, ultrasound is also helpful for diagnosis.
7.4 Differentiation from endometrial cancer; this disease is commonly seen in women before and after menopause, and diagnostic scraping can help to differentiate.
For uterine hypertrophy in the clinical differential diagnosis has some difficulties, so for
① history of multiple births, previous history of pelvic inflammatory disease;
②The uterus is homogeneously enlarged and tough, and ultrasound shows a homogeneous muscle wall without obvious occupying lesions;
③ small uterine fibroids difficult to explain excessive menstruation and severe anemia;
For patients with suspected uterine hypertrophy, we should focus on previous menstrual history, history of gynecological inflammation, history of dysmenorrhea, history of childbirth and puerperium for comprehensive analysis to reduce the rate of misdiagnosis.
8.Treatment
8.1 General treatment: supplement nutrition and correct anemia.
8.2 Hemostatic treatment: symptomatic, diagnostic scraping, application of hemostatic agents, such as Yunnan Baiyao, uterine hemorrhage, hemostasis, etc.
8.3 Anti-infection treatment: moderate application of antibiotics or Chinese medicine such as gynostemma granules, gynostemma nin, etc.
8.4 Moderate application of hormone therapy: such as testosterone propionate 25mg intramuscularly, once a day for 3 days during the bleeding period, then 2-3 times a week, not more than 300mg per month. or methyltestosterone 5-10mg sublingually once or twice a day, from the 6th day of menstruation, for 14-20d.
8.5 Hysterectomy can be considered if conservative treatment is ineffective and fertility preservation is not required.
9. Prevention
The causes of uterine hypertrophy are multiple, some of which can be prevented. Propaganda for less births, attention to aseptic operation during delivery and abortion, infection during the puerperium and after induction of labor and abortion and incomplete uterine regeneration should be given high priority. If poor contraction of the uterus is detected, uterine contraction agents should be applied promptly; try to implement effective contraceptive measures, reduce and avoid intrauterine surgery; prevent the occurrence of cervicitis, endometritis or myometritis, and can avoid uterine hypertrophy.