The impact of fibroid treatments on quality of life and mental health: a systematic review

Abstract

Fibroids significantly impact the quality of life (QOL) and mental health of affected women. However, there are limited comparative data on QOL measures after medical, surgical, and radiologic interventions in women with fibroids. This study aimed to assess the current literature evaluating the impact of fibroids on QOL measures using several validated questionnaires for radiologic, medical, or surgical interventions or a combination of interventions before and after treatment. PubMed, PsycINFO, ClinicalTrials.gov, Embase, and Cochrane Library were searched from January 1990 to October 2023 to evaluate the available evidence, and the risk of bias was assessed using Cochrane RoB 2.0 or the Newcastle-Ottawa Scale. The review criteria included randomized controlled trials (RCTs) and observational cohort studies that included premenopausal women with symptomatic uterine fibroids, confirmed by imaging, who underwent an intervention to target fibroid disease. Only reports using validated questionnaires with a numerical baseline (pretreatment) and post-treatment scores were included. The exclusion criteria included perimenopausal or postmenopausal patients, conditions in addition to uterine fibroids that share similar symptoms, or studies that did not focus on QOL assessment. Abstracts were screened, and full texts were reviewed to determine whether studies met the inclusion criteria. A total of 67 studies were included after final review: 18 RCTs and 49 observational studies. All interventions were associated with a significant improvement in uterine fibroid–specific QOL measures, mental health metrics, and a reduction in symptom severity scores after treatment. These data reveal a substantial impact of uterine fibroids on the QOL and mental health of women with fibroids and indicate the metrics that can be used to compare the effectiveness of fibroid treatment options.

Uterine fibroids, or leiomyomas, are the most common benign tumors in women worldwide (1). Fibroids affect 70%–80% of women by the age of 50 years (2–7). Fibroids cause symptoms in up to 50% of women, including heavy and prolonged bleeding, bulk symptoms (pelvic pain or pressure and bladder and bowel dysfunction) low back pain, and dyspareunia (8–12). However, this percentage is likely underestimated because there is a substantial delay in the proper diagnosis even in women with severe symptoms (13). Risk factors include African American race, older age, premenopausal state, a strong family history, diet, and hypertension (3, 10). Fibroids are the leading indication for hysterectomy and the second most common surgery for women after cesarean section (14). As a result, approximately 200,000 hysterectomies and 30,000 myomectomies are performed for fibroid disease annually (15). When adjusted to 2023 USD, the economic burden is estimated to be $44 billion USD annually to the US healthcare system (16). In addition to healthcare costs, indirect costs due to disability and time taken off from work were estimated to be 1.55–17.2 billion 2010 USD annually (16).

Quality of life (QOL) measures are important because they represent a holistic approach to assess patient well-being and satisfaction (17). The inclusion of QOL variables in clinical care was shown to improve outcomes in cardiovascular disease, chronic kidney disease, and chronic obstructive pulmonary disease (18–20). Notably, the QOL scores for uterine fibroids were similar to, or worse than, those associated with a diagnosis of diabetes mellitus, heart disease, or breast cancer (21). This reduction in the QOL in women with fibroids adversely impacts their mental health. Uterine fibroids are reported to be among the greatest psychological stressors for women, adversely affecting emotional and mental health determined by QOL measures, surveys, and semistructured interviews (21–24). Women affected with fibroids have 1.12-fold higher rates of depression and anxiety (22). Shen et al. (23) found that the incidence of depression in women with uterine leiomyomas was 7.48 per 1,000 women vs. 4.88 per 1,000 without fibroids (23). Glover et al. (25) conducted a survey in 200 women with fibroids in London and found that 35% of women scored in the borderline or clinical range for depression and 61% scored in the borderline or clinical range for anxiety. After adjusting for confounders, including a diagnosis of cancer, mental health condition, prescription for antidepressant medication, and age of <18 or >50 years before hysterectomy, patients with fibroids had higher rates of depression, anxiety, and self-directed violence (22). However, there are limited data on QOL measures in women with fibroids evaluating QOL scores before and after treatment (21). Determining how QOL and mental health metrics respond to available treatments could inform clinical decisions regarding interventions to optimize the health of affected women. Thus, there is a critical need to compare QOL outcomes that assess mental health among current interventions in women with fibroids. To accomplish this objective, we conducted a systematic review of the available literature to assess the impact of fibroids on the QOL scores and mental health before and after therapeutic interventions for fibroids.

MATERIALS AND METHODS

Information Sources

PubMed, PsycINFO, ClinicalTrials.gov, Embase, and Cochrane Library were searched from January 1990 to October 2023. The identified articles are reported with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.

Search Strategy

A literature search was performed with a detailed list of terms using the aforementioned information sources. An example of the terms used in search is as follows: ‘‘Surveys and Questionnaires’’ OR ‘‘Checklist’’ OR ‘‘checklists’’ OR ‘‘Interview’’ OR ‘‘interviews’’ OR ‘‘interviewed’’ OR ‘‘Inventory’’ OR ‘‘Likert scales’’ OR ‘‘Questionnaire’’ OR ‘‘questionnaires’’ OR ‘‘Recall’’ OR ‘‘recalled’’ OR ‘‘Survey’’ OR ‘‘surveys’’ OR ‘‘surveyed’’ OR ‘‘Quality of Life’’ OR ‘‘quality of life’’ OR ‘‘QOL’’ AND ‘‘Leiomyoma’’ OR ‘‘leiomyoma’’ OR ‘‘leiomyomas’’ OR ‘‘leiomyomata’’ OR ‘‘leiomyomatas’’ OR ‘‘fibroid’’ OR ‘‘fibroids’’ OR ‘‘fibromyoma’’ OR ‘‘fibromyomas’’ OR ‘‘myoma’’ OR ‘‘myomas’’ OR ‘‘myomatosis’’ AND ‘‘uterus’’ OR ‘‘uterine’’ OR ‘‘uteri’’ OR ‘‘myometrium.’’ A detailed search strategy is shown in Appendix 1 (available online).

Eligibility Criteria

Peer-reviewed, English-speaking articles published between January 1990 and October 2023 were included in this study. The inclusion criteria included premenopausal women with symptomatic uterine fibroids confirmed by imaging and results from a validated questionnaire that included a numerical baseline (pretreatment) and posttreatment scores. Only RCTs and observational studies were included. Case studies, case reports, and literature reviews were excluded. Literature reviews were used to cross-reference but were not included (detailed eligibility criteria are shown in Appendix 2). This is an extension of the study previously published in 2022 (21). In addition to studies previously reported, 10 studies were included.

Study Selection and Instruments

The aforementioned search engines were used with a detailed search strategy to evaluate the available evidence investigating the association of uterine fibroids on QOL. Two reviewers worked independently to screen each abstract and title (B.N., B.S.). Any discrepancies were resolved with senior reviewer (J.S.). If the abstract met the review criteria, the text was reviewed in further detail to determine whether the study met all inclusion criteria. The two reviewers collaborated, and the collected data were combined. Appendix 2 includes the specific inclusion and exclusion criteria. If included, studies were divided by fibroid-specific QOL scores, the general QOL scores, and instruments using other QOL measures. The QOL scores were categorized and reported according to fibroid treatment including medical, surgical, or radiologic intervention. Fibroid-specific QOL and general QOL measures were included in this study. The uterine fibroid symptom and quality of life questionnaire (UFS-QOL) is a fibroid-specific 37-item score that evaluates the severity of symptoms and health-related QOL with six subscales: concern; activities; energy/mood; control; self-consciousness; and sexual function (17). An increase in the score indicates an improvement in QOL. A decrease in the symptom severity score indicates an improvement in symptom severity. The short form survey, 36-Item Short Form Health Survey (SF-36), is a 36-generalitem questionnaire with nine domains including physical function, physical role, bodily pain, general health, vitality, social function, emotional role, and mental health (26). Emotional role includes 3 questions, and mental health includes 5 questions assessing anxiety, depression, and loss of behavioral or emotional control and psychological well-being (27, 28). The Short Form-12 is a general questionnaire that includes 12 items with a mental component and physical component summary (29). The European Quality of Life Five-Dimension Scale Summary Index (EQ-5D) is a 5-item study that evaluates mobility, self-care, daily activities, pain/discomfort, and anxiety/depression (30). The second part of the scale is the EQ Visual Analogue Scale (EQ-VAS), which is a 1-item scale assessing the patient’s own assessment of health (30). The World Health Organization Quality of Life-BREF questionnaire is a general 26-item questionnaire with physical health, psychological health, social relationships, and environment (31). The Female Sexual Function Index (FSFI) is a 19-item symptom-specific questionnaire evaluating desire, arousal, lubrication, orgasm, satisfaction, and pain (32). The Urogenital Distress Inventory is a 19-item symptom-specific questionnaire evaluating health-related QOL, symptom distress and distinguishing among different types of established urinary incontinence (33). The Prolapse and Incontinence Sexual Questionnaire is a 12-item symptom-specific survey with behavioral-emotive and physical partner-related domains (34). Sexual activity questionnaire is a 23-item symptom-specific survey assessing hormonal status, reasons for sexual inactivity, and sexual functioning (35). Symptom checklist 90 is a 90-item symptom-specific checklist with several domains including somatization, obsessive compulsive, interpersonal sensitivity, depression, anxiety, hostility, phobic anxiety, paranoid ideation, psychoticism, and a category of additional items (36). The questionnaire for screening sexual dysfunctions is a variable item symptom-specific survey evaluating the frequency of sexual problems, experiences distressed with these problems, and sexual satisfaction. The Brief Index of Sexual Functioning is a 22-item symptom-specific survey assessing thoughts/desires, arousal, frequency of sexual activity, receptivity/initiation, please/orgasm, relationship satisfaction, and problems affecting sexual function (37).

The interventions included radiologic, surgical, and medical interventions. Radiologic techniques included uterine artery embolization (UAE), uterine fibroid embolization, magnetic resonance-guided focused ultrasound surgery, magnetic resonance-guided high-intensity focused ultrasound, radiofrequency volumetric thermal ablation (or radiofrequency ablation [RFA]), ultrasound or percutaneous-guided microwave transcervical ablation, and ultrasound-guided high-intensity focused ultrasound. Surgical techniques included laparoscopic, robotic, or abdominal myomectomy or hysterectomy, hysteroscopic myomectomy, and transcervical fibroid ablation. Medical treatments were mifepristone, ulipristal, herbal formula guizhi fuling wan, or relugolix.

Data Extraction and Analysis

Each questionnaire per individual study was reviewed, and the mean pretreatment and posttreatment scores were calculated. Then, the mean score of each questionnaire (the scores for all studies that included that questionnaire were combined) was calculated for pretreatment and posttreatment. If there were multiple questionnaires administered after treatment, the scores from the furthest time after the intervention were included in analysis. The earliest time point document was 1 month. In the manuscript, we present the longest time point reported by the investigators. The Wilcoxon signed-rank test was performed to assess differences between the pretreatment and posttreatment scores for all uterine fibroid–specific QOL and symptom severity scores (P < .05 as significant). In addition, the Wilcoxon signed-rank analysis was performed for the uterine fibroid–specific QOL and symptom severity scores (17) according to radiologic intervention as well as medical and surgical interventions combined.

An effect size was calculated for each study’s questionnaire score to determine Cohen’s d. To calculate the effect size, the posttreatment mean was calculated subtracted by the mean of pretreatment divided by (standard deviation of posttreatment — standard deviation of posttreatment) with a 95% confidence interval. The effect sizes were compared by treatment modality including radiologic, surgical, or medical intervention. Studies reporting a combination of therapies were not included.

Assessment of the Risk of Bias

The two reviewers worked independently to determine bias. Each RCT was determined by the Cochrane RoB 2.0 tool to have low risk, some risk, or high risk of bias (38). Cohort studies were determined to have good, fair, or poor quality according to the Newcastle-Ottawa Scale (39).

RESULTS

A total of 4,020 articles were identified, including 1,463 from PubMed, 1,994 from Embase, 46 from PsycINFO, 402 from Cochrane, and 115 from ClinicalTrials.gov. After screening, 1,078 duplicates were removed, leaving 2,942 unique titles and abstracts reviewed. A total of 2,815 studies were excluded after the initial title and abstract review, leaving 127 for full review. After a full review, 60 studies were excluded for several reasons, such as study subjects not being premenopausal. Screening and identification of included studies using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines is shown in Figure 1. A total of 67 studies were included for final review: 18 RCTs and 49 observational studies (Fig. 1). Of the 49 studies reporting the UFS-QOL, 18 were of good quality, 19 of fair quality, 1 of poor quality, 6 with some risk, and 6 with low risk. OF 15 general QOL studies, 10 were of good quality, 3 of fair quality, 2 of some quality, and 1 of low quality. We included all studies because of the limited number of literature available. Because of excessive heterogeneity of data available and small sample size, a meta-analysis was not performed because it may result in biased reporting.

FIGURE 1.

Preferred Reporting Items for Systematic Reviews and Meta-Analyses flowchart of article identification, retrieval, review, and inclusion.

Uterine Fibroid–Specific QOL Assessment

The UFS-QOL has proven an essential instrument for assessment of fibroid-related symptoms (17). A total of 45 studies used the UFS-QOL scores, and 47 reported the UFS-QOL symptom severity scores (Tables 1 and 2) (40–89). Among these studies, a total of 28 publications were included in the analysis.

TABLE 1.

Mean uterine fibroid symptom and quality of life and fibroid symptom quality of life symptom severity scores categorized by treatment type. Data from the fibroid-specific instrument (UFS-QOL)

Instrument	No. of studies	Mean pretreatment score	Mean posttreatment score	Reference range	P value
UFS-QOL	36	47.2 (95% CI, 43.50–50.94)	80.4 (95% CI, 75.90–84.94)	0–100	< .0001
Radiologic	14	46.5 (95% CI, 40.09–52.88)	77.9 (95% CI, 68.85–86.96)	0–100	.0002
Surgical	12	48.5 (95% CI, of 41.78–55.23)	85.0 (95% CI, 80.55–89.37)	0–100	.0005
Medical	8	46.8 (95% CI, 37.80–55.72)	78.7 (95% CI, 68.59–88.72)	0–100	.0078
UFS-QOL symptom severity	34	53.1 (95% CI, 47.52–58.66)	21.7 (95% CI, 16.51–26.79)	0–100	< .0001
Radiologic	16	58.7 (95% CI, 50.54– 66.93)	26.6 (95% CI, 17.53–35.68)	0–100	.0002
Surgical	10	49.5 (95% CI, 39.61–59.39)	17.1 (95% CI, 10.78, 23.35)	0–100	.002
Medical	7	45.3 (95% CI, 30.41–60.21)	16.9 (95% CI, 5.411–28.35)	0–100	.0156

Note: The reference range for the UFS-QOL and UFS-QOL symptom severity scores are 0–100; however, higher numbers for the UFS-QOL denote a better quality of life, and higher numbers for the symptom severity score denote greater fibroid symptoms. The rows in gray represent a summary of the data for the UFS-QOL and UFS-QOL symptom severity scores among the included studies. Radiologic techniques included uterine artery embolization, uterine fibroid embolization, magnetic resonance-guided focused ultrasound surgery, magnetic resonance-guided high-intensity focused ultrasound, radiofrequency volumetric thermal ablation (or radiofrequency ablation), ultrasound or percutaneous-guided microwave transcervical ablation, and ultrasound-guided high-intensity focused ultrasound. Surgical techniques included laparoscopic, robotic, or abdominal myomectomy or hysterectomy, hysteroscopic myomectomy, and transcervical fibroid ablation. Medical treatments were mifepristone, ulipristal, herbal formula guizhi fuling wan, and relugolix. The Wilcoxon signed-rank test was performed to assess differences between the mean pretreatment and posttreatment scores. A P value of < .05 was considered significant. UFS-QOL = uterine fibroid symptom and quality of life questionnaire.

TABLE 2.

Results of studies that evaluated a fibroid-specific instrument.

Study	Study design	Treatment	Score before treatment	Score after treatment	Cochrane RoB grade or Newcastle-Ottawa Scale grade
Ahmadzade et al. (2023) (40)	Retrospective observational cohort study	Microwave ablation, n = 17	HRQOL: 61.0 ± 21.7 UFS-QOL SS: 51.1 ± 22.2	12-mo HRQOL: 95.4 ± 6.5 12-mo UFS-QOL SS: 11.5 ± 4.7	Fair
Anchan et al. (2023) (41)	Retrospective observational cohort study	Hysterectomy abdominal (HA), n = 741 Myomectomy (M), n = 446 Uterine artery embolization (UAE), n = 155	HRQOL HA: 51.0 (25.4) M: 44.3 (24.3) UAE: 40.6 (23.8) SS: HA: 50.3 (24.6) M: 59.8 (24.1) UAE: 62.3 (24.4)	12-mo HRQOL HA: 87.6 (17.3) M: 93.1 (16.5) UAE: 82.3 (21.4) 12-mo SS HA: 16.8 (15.9) M: 7.8 (14.4) UAE: 20.1 (18.0)	Fair
Berman et al. (2014)a (42)	Prospective cohort	Radiofrequency volumetric thermal ablation, N = 104	SS: 60.2 ± 18.8 HRQOL: 39.2 ± 19.2	SSb: 3 mo, 26.6 6 mo, 26.4 12 mo, 25 24 mo, 24.9 36 mo, 27.6 HRQOLb: 3 mo, 77.2 6 mo, 79.7 12 mo, 81.1 24 mo, 80.3 36 mo, 77.8 (22.9)	Good
Brolmann et al. (2016) (43)	Prospective cohort	RFA, N = 50	SS: 61.7 ± 16.9 HRQOL: 34.3 ± 19.0	SSb: 3 mo, 31.7 ± 20.1 6 mo, 25.1 ± 19.3 12 mo, 26.6 ± 24.0 HRQOLb: 3 mo, 76.4 ± 22.2 6 mo, 79.5 ± 22.7 12 mo, 80.7 ± 24.7	Good
Chen et al. (2016) (44)	Prospective cohort	Magnetic resonance-guided high-intensity focused ultrasound, n = 107	SS: 34.4 (14.70) HRQOL: 73 (18.80)	1-mo SSb: 28.1 (15.00) HRQOLb: 78.1 (18.00) 3-mo SSb: 27.2 (15.70) HRQOLb: 78.5 (19.50) 6-mo SSb: 24 (16.10) HRQOLb: 82.2 (17.30)	Fair
Chudnoff et al. (2019) (45)	Prospective cohort	Ultrasound-guided transcervical fibroid ablation, N = 147	SS: 54.9 ± 18.65 HRQOL: 40.3 ± 20.51	SSb: 3 mo, 26.9 ± 19 6 mo, 22.7 ± 17.47 12 mo, 22.6 ± 7.75 HRQOLb: 3 mo, 77.9 ± 21.9 6 mo, 84 ± 17.63 12 mo, 84.2 ± 18.96	Fair
Daniels et al. (2022) (46)	Randomized controlled trial	Uterine artery embolization (UAE), N = 127 Myomectomy (M), N = 127	UFS-QOL: UAE: 42.1 (26.4) M: 37.0 (23.9)	6-mo UFS-QOL: UAE: 73.9 (26.7) M: 80.5 (21.7) 1-y UFS-QOL: UAE: 75.7 (26.1) M: 84.7 (22.1) 2-y UFS-QOL: UAE: 80.0 (22.0) M: 84.6 (21.5)	Some risk
Duvnjak et al. (2017)a (47)	Prospective cohort	Uterine fibroid embolization, n = 26	SS: 65 HRQOL: 62	SSb: 33 HRQOLb: 81	Fair
Fasciani et al. (2022)a (48)	Prospective observational cohort study	RFA, n = 112	UFS-QOL, 74.27 (70.48 – 78.06) UFS-QOL SS 33.37 (6.25–75.00)	12-mo UFS-QOLb 88.69 (85.78 – 91.60) 12-mo UFS-QOL SS 12.39 (5.96 – 18.83) 24-mo UFS-QOL 88.75 (83.22 – 94.27) 24-mo UFS-QOL SS 11.19 (8.19–14.19) 36-mo UFS-QOLb 93.64 (87.60 – 99.70) 36-mo UFS-QOL SSb 9.41 (3.93–14.89)	Fair
Feng, et al (2010) (49)	Prospective cohort	Mifepristone, n = 43 Placebo, n = 19	HRQOL: 39.77 ± 20.46	HRQOLb: 88.86 ± 13.27	Good
Fiscella et al (2006)a (50)	Randomized controlled trial	Mifepristone (M), n = 22 Placebo (P), n = 20	M SS: 67 M HRQOL: 38	6-mo M HRQOL: 88 M SS: 50	Low risk
Fornazari et al. (2019)a (51)	Prospective cohort	Uterine fibroid embolization, n = 26	SS: 71.4 HRQOL: 39	6 mo: SS: 33.1 HRQOL: 68.4	Good
Garza-Leal et al. (2019) (52)	Retrospective cohort (VITALITY study-Fast EU)	Transcervical RFA with the Sonata System, n = 17	SS: 64.9 ± 16.9 HRQOL: 27.2 ± 22.4	57–73 mo: SSb: 27.6 ± 36.1 HRQOLb: 76 ± 32.6	Fair
Guido et al. (2013) (53)	Multicenter prospective cohort (Half)	Radiofrequency volumetric thermal ablation, n = 124	SS: 61.1 ± 18.6 HRQOL: 37.3 ± 19.1	3-mo SS: 29.1 ± 18.9 3-mo HRQOL: 75.1 ± 22.1 6-mo SS: 28.5 ± 19.3 6-mo HRQOL: 77.8 ± 20.2 12-mo SS: 26.6 ± 19 12-mo HRQOL: 79.5 ± 20.6 24-mo SSb: 25.4 ± 20.6 24-mo HRQOLb: 79.3 ± 21.7	Good
Hai et al. (2021) (54)	Retrospective cohort study	RFA with mifepristone** (M), n = 30 vs. RFA, n = 30	HRQOL M: 53.1 ± 12.6 RFA: 57.4 ± 16.3 SS: M: 32.5 ± 5.1 RFA: 31.8 ± 4.7	12-mo HRQOLb M: 89.4 ± 7.1 RFA: 82.8 ± 5.8 12-mo SSb M: 6.7 ± 5.6 RFA: 1.8 ± 4.8	Good
He et al. (2018) (55)	Retrospective cohort	Ultrasound-guided highintensity focused ultrasound, N = 81	SS: 56.3 ± 16.7 HRQOL: 41.3 ± 21.2	SS: 1 mo, 40.5 ± 17.2 3 mo, 31 ± 15.1 6 mo, 20.6 ± 14.2 HRQOL: 1 mo, 60.6 ± 19.7 3 mo, 72.3 ± 18.1 6 mo, 73.4 ± 19.2	Fair
Hu et al. (2020) (56)	Prospective cohort study	Focused ultrasound surgery (FUS), n = 39 Transcervical resection of myoma (TCRM), n = 42	SS FUS: 29.25 ± 15.27 TCRM: 26.41 ± 15.16 QOL FUS: 65.67 ± 15.73 TCRM: 68.45 ± 12.82	3-mo SS: FUS: 18.83 ± 10.79 TCRM: 14.43 ± 10.55 3-mo QOL: FUS: 76.77 ± 10.97 TCRM: 81.59 ± 12.69 6-mo SS: FUS: 11.36 ± 10.71 TCRM: 12.66 ± 9.88 6-mo QOL: FUS: 84.79 ± 12.21 TCRM: 86.48 ± 14.57 12-mo SS: FUS: 9.21 ± 11.92 TCRM: 8.35 ± 8.37 12-mo QOL: FUS: 89.70 ± 13.69 TCRM: 90.91 ± 11.70	Fair
Hudgens et al. (2019)a (57)	Prospective cohort	Transcervical fibroid ablation with Sonata, N = 147 (125 in US)	SS: 54.3 HRQOL: 40.6	SSb: 3 mo, 24.8 12-mo HRQOLb: 20.3 3 mo, 80 SSb: 86.7	Good
Ierardi et al. (2019)a (58)	Prospective cohort	Percutaneous microwave ablation, n = 14	SS: 54.3 HRQOL: 40.6	SS: 3 mo,b 29 6 mo,b 13.2 12 mo,b 0.6 HRQOLb: 3 mo,b 84.8 6 mo,b 98 SSb 100	Fair
Jacoby et al. (2020) (59)	Prospective observational cohort study	Laparoscopic RFA, N = 26	UFS-QOL score: 50.06 ± 24.10 SS: 53.73 ± 20.41	6-wk UFS-QOLb: 63.95 ± 23.12 12-wk UFS-QOLb: 27.25 ± 15.24 6-wk SSb: 42.43 ± 13.78 12-wk SSb: 73.43 ± 20.92	Fair
Keizer et al. (2022)a (60)	Multicenter prospective cohort study	Transcervical resection, n = 104	UFS-QOL 44 (33–62) UFS-QOL SS 54 (44 – 66)	3-mo UFS-QOLb 82 (57–91) 3-mo UFS-SSb 25 (12–41) 6-mo UFS-QOLb 89 (67–97) 6-mo UFS-SSb 22 (9–41)	Fair
Keserci et al. (2017) (61)	Retrospective cohort	Magnetic resonanceguided high-intensity focused ultrasound, n = 76	Scar SS: 54.7 ± 14.4 No scar SS: 51.6 ± 16.1	6-mo scar SSb: 4.2 ± 5.0 6-mo no scar SSb: 6.2 ± 7.5	Good
Kramer et al. (2016)a (62)	Interim analysis of randomized controlled trial	Radiofrequency volumetric thermal ablation (RFVTA), n = 21 Laparoscopic myomectomy (LM), n = 22	SS: RFVTA: 38.9 LM: 41.8 HRQOL: RFVTA: 77.1 LM: 70.2	SS 24 mob: RFVTAb: 16 LMb: 22.3 HRQOLb: RFVTAb: 89.4 LMb: 85.6	Low risk
Laughlin-Tommaso (2019)a (63)	Randomized controlled trial	Magnetic resonanceguided high-intensity focused ultrasound (MRgFUS), n = 43 Uterine artery embolization (UAE), N = 40	SS MRgFUS: 53.9 UAE: 53.1 HRQOL MRgFUS: 52.5 UAE: 51	SS MRgFUS: 6 mo, 31.3 12 mo, 34.1 24 mo. 32.1 UAE: 6 mo, 13.2 12 mo, 13.8 24 mo, 14.2 HRQOL MRgFUSb: 6 mo, 77 12 mo, 72.8 24 mo, 71.8 UAE: 6 mo, 91.2 12 mo, 93 24 mo, 92.4	Some risk
Laughlin-Tommaso (2020)a (64)	Prospective cohort	Hysteroscopic myomectomy (HM), n = 338 Laparoscopic/robotic Myomectomy (LRM), n = 519 Abdominal myomectomy (AM), n = 349	SS: HM: 53.2 RLM: 49.2 AM: 52.4 HRQOL: HM: 49.1 LRM: 52.6 AM: 48.7	3-mo symptom severity: HM: 22.3 LRM: 20.0 AM: 19.5 HRQOL: HM: 73.9 LRM: 75.9 AM: 74.5	Good
Lee et al. (2010) (65)	Prospective cohort	Radiofrequency volumetric thermal ablation, n = 68	SS: 71.3 ± 7.5 HRQOL: 48.8 ± 15.4	18-mo SSb: 10.3 ± 3.3 18-mo HRQOLb: 97.5 ± 4.2	Good
Lee et al. (2020)a (66)	Prospective cohort	Transvaginal highintensity focused US therapy n=13	UFS-QOL: 66.6 HRQOL: 41.4	3-mo UFS-QOLb: 32.85 3-mo HRQOLb: 73.3	Good
Levens et al. (2008) (67)	Randomized controlled trial	Ulipristal, n = 12 Placebo, n = 6	SS: 29.3 ± 32.1	3 mo SS: 3.9 ± 9.0	Some risk
Lin et al. (2009)a (68)	Prospective cohort	Magnetic resonanceguided high-intensity focused ultrasound, n = 3	SS: 46.8	3-mo SS: 34.4	Poor
Lukes et al. (2019) (69)	Randomized controlled trial	Placebo, n = 169 Ulipristal 5 mg, n = 215 Ulipristal 10 mg, n = 205	SS: Placebo, 64.4 ± 21.7 5-mg ulipristal, 65.9 ± 1 9.3 10-mg ulipristal, 62.3 ± 22.3 HRQOL: Placebo, 33.2 ± 22 5-mg ulipristal, 32.3 ± 20.8 10-mg ulipristal, 35.3 ± 22.6	SSb: Placebo, 50.7 ± 21.9 5-mg ulipristal, 28.7 ± 24.5 10-mg ulipristal, 20.3 ± 18.1 HRQOLb: Placebo, 47.5 ± 25.9 5-mg ulipristal, 76.2 ± 25.8 10-mg ulipristal, 85.4 ± 20.9	Low risk
Lukes et al. (2020) (70)	Randomized controlled trial	Transcervical fibroid ablation, n = 147	SSS 55 ± 19 HRQOL 40 ± 21	3-y SSSb: 22 ± 21 3-y HRQOLb: 83 ± 23	Some risk
Mariara et al. (2017)a (71)	Prospective cohort	Uterine fibroid embolization, n = 80	SS: 51.6 HRQOL: 48.3	12 mo SSb: 15.6 HRQOLb: 89.7	Good
Mashiach et al. (2018) (72)	Retrospective cohort	Magnetic resonanceguided high-intensity focused ultrasound, n = 68	SS: 29.6 ± 5.6	6–42 mo, SSb: 14 ± 8.6	Fair
Meng et al. (2022) (73)	Randomized controlled trial	Herbal formula Guizhi Fuling Wan, n = 78	HRQOL: 53.45 ± 15.82 UFS-QOL SS 40.71 ± 17.16	16-wk HRQOLb: 56.87 ± 22.57 16-wk UFS-QOL SS: 28.04 ± 20.48	Low risk
Murji et al. (2016)a (74)	Prospective cohort	Ulipristal, n = 36 black women; n =52 white women	SS: black, 51.7; white, 55.9 (±25.4) HRQOL: Black: 45.4 White: 42.2	3 mo SSb: black, 54.9; white, 57.4 HRQOL: Black: 36.2 White: 57.2	Fair
Rattray et al. (2018)a (75)	Randomized noninferior controlled trial (TRUST)	Laparoscopic RFA, n=23 Myomectomy (M), n = 22	SS: RFA Baseline: 61.5 (19.8) M: 58.4 (18.8) HRQOL: RFA: 39.8 (25.5) M: 47.9 (23.9)	3-mo SSb: RFA: 34.8 (25.6) M: 32.2 (22.6) HRQObL: RFA: 63.3 (31.1) M: 69.9 (24.1)	Some risk
Roy et al. (2022) (76)	Prospective cohort study	Transcervical fibroid ablation, n = 147	UFS-QOL: 40 ± 21	1-y UFS-QOLb 84 ± 19 3-y UFS-QOLb 83 ± 23	Fair-none
Shlansky-Goldberg et al. (2014) (77)	Prospective, randomized, single-center, singleblind, parallel-group, noninferiority study	Uterine artery embolization with SPVA microspheres (SPVA), n = 30 Uterine artery embolization TAG microspheres (TAG), n = 30	SPVA SS: 64.2 ± 20.6 HRQOL: 42.1 ± 20.2 TAG SS: 65.1 ± 20.3 HRQOL: 42.0 ± 23.7	SPVA 3-mo SS: 16.3 ± 12.1 3-mo HRQOL: 90.0 ± 13.1 TAG 3-mo SS: 22.7 ± 20.5 3-mo HRQOL: 90.0 ± 11.7	Some risk
Shveiky et al. (2013)a (78)	Prospective cohort	Uterine fibroid embolization, n = 57	SS: 64 HRQOL: 46.7	SSb: 28.9 HRQOLb: 77.4	Fair
Smith et al. (2004) (79)	Prospective cohort	Uterine artery embolization, n = 64	SS: 61.61 ± 20.95 HRQOL: 44.92 ± 25.24	32 mo: SSb: 26.42 ± 23.38 HRQOLb: 80.58 ± 23.66	Good
Spies et al. (1999) (80)	Prospective cohort	Uterine fibroid embolization, n = 50	General health: 71.6 ± 24.73 Health perception: 42.5 ± 18.39 Physical functioning: 77 ± 22.43 Restricted activity: 9.76 ± 9.78 Difficulty with activity: 69 ± 25.54 Pain: 31.08 ± 22.1 Energy/vitality: 37.44 ± 23.71 Sleep: 56.75 ± 23.19 Mental health: 66.33 ± 19.95 Health distress: 39.69 ± 25.98 Self-image: 53.89 ± 29.07 Sexual functioning: 42.23 ± 22.33	6 mo General healthb: 79.83 ± 16.48 Health perceptionb: 77.42 ± 23.59 Physical functioningb: 90.59 ± 13.9 Restricted activityb: 2.55 ± 4.79 Difficulty with activityb: 86.29 ± 19.19 Painb: 19.09 ± 21.64 Energy/vitalityb: 60.97 ± 16.47 Sleepb: 67.5 ± 16.57 Mental healthb: 78.97 ± 13.58 Health distressb: 17.26 ± 21.67 Self-imageb: 75 ± 28.3 Sexual functioning: 58.73 ± 20.96	Fair
Spies et al. (2005)a (81)	Multicenter prospective cohort study	Uterine artery embolization, n = 211	SS: 58.61 HRQOL: 46.95	6-mo SSb: 19.87 6-mo HRQOLb: 85.04 12-mo SSb: 19.23 12-mo HRQOLb: 86.68	Good
Spies et al. (2010)a (82)	Multicenter nonrandomized prospective study	Uterine artery embolization (UAE), n = 107 Myomectomy (M), n = 61 Hysterectomy (H), n = 106 Normal control, n = 101	UAE HRQOL: 42.9 ± 21.6 UAE SS: 65.1 ± 19.3 M HRQOL: 37.3 ± 20.9 M SS: 63.9 ± 18.2 H HRQOL: 64.9 ± 21.8 H SS: 40.9 ± 23.1	12 mob: UAE HRQOL: 82.9 ± 20 UAE SS: 24.9 ± 18.6 M HRQOL: 81.1 ± 23.2 M SS: 23.4 ± 18.9 H HRQOL: 92.3 ± 11 H SS: 7.6 ± 8.4	Good
Stewart et al. (2019)a (83)	Prospective cohort	Magnetic resonanceguided high-intensity focused ultrasound, n = 109	SS: 61.7 (15.2) HRQOL: 47 (18.6)	SSb: 3 mo, 41.2 (21.8) 6 mo, 37.7 (21.2) HRQOLb: 3 mo, 65.9 (22.4) 6 mo, 67.9 (21.7)	Good
Stewart et al. (2023)a (84)	Randomized controlled trial	Relugolix, n = 253 Placebo, n = 256	SS: 57.8 (21.3) HRQOL: 38.1 (21.9)	Wk 12 SSb: 29.8 Wk 12 HRQOLb: 70.3 Wk 24 SS: 22.4 Wk 24 HRQOL: 76.6	Low risk
Takmaz (2018) (85)	Prospective cohort	Robotic myomectomy (RM), n = 31 Laparoscopic myomectomy (LM), n = 33	SS: RM: 44.76 ± 4.18 LM: 46.59 ± 4.32 HRQOL: RM: 60.62 ± 5.02 LM: 58.70 ± 4.63	12-mo SSb: RM 24.9 ± 2.87 LM: 23.87 ± 2.23 HRQOLb: RM: 75.33 ± 3.94 LM: 82.03 ± 2.67	Good
Turtulici et al. (2018) (86)	Prospective cohort	Transvaginal ultrasound-guided RFA with realtime virtual needle tracking system, n = 19	UFS-QOL: 68 ± 36	1-mo UFS-QOL: 70 ± 40 3-mo UFS-QOLb: 84 ± 22 6-mo UFS-QOLb: 97 ± 16	Good
Wallace et al. (2020)a (87)	Prospective observational cohort study	Hysterectomy (H), n = 630 Myomectomy (M), n = 483	HRQOL: H: 45.7 (25.8) SS: H: 57.8 (23.8) HRQOL: M: 45.9 (24.2) SS: M: 56.8 (24.2)	6-mo H:HRQOL: 93.3 (15.6) M:SS: 7.8 (14.8) M:HRQOL: 82.0 (22.6) M:SS: 20.3 (19.2)	Fair
Yadavali (2019)a (88)	Randomized controlled trial (RAGE trial)	Uterine artery embolization with Embospheres (E), n = 10 Gelfoam (G), n = 10	SS: E: 64 (18) G: 54 (15) HRQOL: E: 41 (28) Gelfoam G: 53 (19)	6-mo follow-up SSb: E: 23 (16) G: 32 (26) HRQOLb: E: 79 (20) G: 78 (21)	Low risk
Zhang et al. (2023) (89)	Prospective cohort	Uterine artery embolization, n = 15	UFS-QOL SS: 100.1 ± 9.7	1-mo UFS-QOL SSb: 74.7 ± 6.5 3-mo UFS-QOL SSb: 71.0 ± 7.2 12-mo UFS-QOL SSb: 54.3 ± 5.3	Fair

Note: The score that is the furthest time point measured posttreatment (used in calculations) is underlined. UFS-QOL = uterine fibroid symptom and quality of life questionnaire; RFA = radiofrequency ablation; SS: Symptom Severity; HRQOL: health-related quality of life.

^aIndicates study not used to calculate effect size because the standard deviation was not available.

^bIndicates statistically significant change from baseline.

Radiologic Treatment

After a radiologic treatment (14 studies), the pretreatment and posttreatment UFS-QOL scores were 46.5 ± 21.8 and 77.9 ± 19.3, respectively (P < .0001). UFS-QOL symptom severity decreased from 58.7 ± 16.1 to 26.6 ± 14.9 (P < .0001) in a total of 16 studies that used radiologic techniques. Radiologic treatment had the largest change in QOL scores.

Surgical Treatment

After a surgical intervention (12 studies), the pretreatment UFS-QOL scores increased from 48.5 ± 20.8 to 85.0 ± 17.7 (P = .0005). After surgical intervention (10 studies), the symptom severity scores decreased from 49.5 ± 19.5 to 17.1 ± 15.6 (P = .002).

Medical Treatment

Medical intervention (8 studies) increased the UFS-QOL scores from 46.8 ± 20.8 to 78.7 ± 18.8 (P = .125). After a medical treatment (7 studies), the symptom severity scores decreased from 45.3 ± 19.3 to 16.9 ± 15.4 (P = .125).

The effect of treatment is displayed in Figure 2, subdivided by intervention: surgical techniques; medical intervention; and radiologic intervention. Treatment-dependent changes ranged from −11.3 to 5.0. Patients reported meaningful differences in the UFS-QOL symptom severity as evidenced by the negative effect size, with the study by Lee et al. (65) having the largest change in QOL (Cohen’s d = −11.3). The largest change in the UFS-QOL scores was noted in the study by Lee et al. (65), showing the largest effect size (Cohen’s d = 5.0), indicating a meaningful relationship between the pretreatment and posttreatment scores. Figure 3A shows a graphical representation of the treatment-dependent effects on QOL measures on the uterine fibroid–specific QOL scores (Fig. 3A) (P < .0001) and uterine fibroid–specific QOL symptom severity scores (Fig. 3B) (P < .0001). Figure 4 shows the treatment-dependent effects on the UFS-QOL symptom severity score for radiologic intervention (Fig. 4A) (P = .0002), UFS-QOL score for radiologic treatment (Fig. 4B) (P = .0002), UFS-QOL symptom severity score for medical and surgical treatment combined (Fig. 4C) (P < .0001), and UFS-QOL score for medical and surgical treatment combined (Fig. 4D) (P < .0001).

FIGURE 2.

Effects of intervention on the fibroid-specific quality of life scores. (A) Treatment effects for studies of surgical interventions. Surgical interventions assessed included laparoscopic, robotic, or abdominal myomectomy or hysterectomy, hysteroscopic myomectomy, and transcervical fibroid ablation. (B) Treatment effects for studies of medical interventions. Medical treatments included mifepristone, ulipristal, ulipristal acetate, herbal formula guizhi fuling wan, and relugolix. (C) Treatment effects for studies of radiologic interventions. Radiologic techniques included uterine artery embolization, uterine fibroid embolization, magnetic resonance-guided focused ultrasound surgery, magnetic resonance-guided high-intensity focused ultrasound, radiofrequency volumetric thermal ablation (or radiofrequency ablation), ultrasound or percutaneous-guided microwave transcervical ablation, and ultrasound-guided high-intensity focused ultrasound. The x-axis represents the change in score from baseline, and the y-axis represents the study. The uterine fibroid symptom and quality of life questionnaire (UFS-QOL is a 37-item questionnaire that is used to measure health-related quality of life and is shown as blue bars, right panels. The rine fibroid symptom and quality of life questionnaire severity of symptoms score is a subscale of this questionnaire with eight items assessing fibroid symptoms (reference range, 0–100) and is shown in orange, left panels.

FIGURE 3.

Graphical representation of treatment-dependent effects on quality of life (QOL) measures. The uterine fibroid–specific QOL symptom severity scores according to pretreatment shown in black and posttreatment scores shown in gray. The x-axis represents the pretreatment or posttreatment scores, and the y-axis represents the uterine fibroid–specific QOL scores. The error bars represent the standard deviation. ****P < .0001. (A) displays uterine fibroid–specific QOL scores (P < .0001). The uterine fibroid symptom and quality of life questionnaire is a 37-item questionnaire that is used to measure health-related QOL. (B) Uterine fibroid–specific QOL symptom severity scores (P < .0001). The uterine fibroid symptom and quality of life questionnaire severity of symptoms score is a subscale of this questionnaire with eight items assessing fibroid symptoms (reference range, 0–100).

FIGURE 4.

Graphical representation of treatment-dependent effects on quality of life (QOL) measures. The pretreatment uterine fibroid–specific QOL scores are shown in black, and the posttreatment scores shown in gray. The x-axis represents the pretreatment or posttreatment scores, and the y-axis represents the uterine fibroid–specific QOL scores. The error bars represent the standard deviation. The uterine fibroid symptom and quality of life questionnaire (UFS-QOL) is a 37-item questionnaire that is used to measure health-related quality of life. The UFS-QOL severity of symptoms score is a subscale of this questionnaire with eight items assessing fibroid symptoms (reference range, 0–100). ***P = .0002; ****P < .0001. (A) UFS-QOL symptom severity score that included radiologic intervention (P = .0002). (B) UFS-QOL score that included radiologic treatment (P = .0002). (C) UFS-QOL symptom severity score that included medical or surgical treatment (P < .0001). (D) UFS-QOL score that included medical or surgical treatment (P < .0001).

General QOL

A total of 15 studies were included (42, 52, 53, 57, 62, 65, 69, 75, 82, 90–95) that used general QOL instruments (Table 3). Five studies reported the SF-36 scores with mean pretreatment and posttreatment scores of 67.3 ± 17.6 and 82.1 ± 15.3 (reference range, 0–100), respectively (P > .05). The Short Form-12 scores (1 study) reported the mean pretreatment and posttreatment scores of 46.6 and 51.2 (reference range, 0–100), respectively (P = nonsignificant). Four studies included the EQ-5D scores with mean pretreatment and post-treatment scores of 0.8 ± 0.2 and of 0.9 ± 0.2 (reference range, 0–1), respectively (P > .05). The EQ Visual Analogue Scale questionnaire (4 studies), which is part of the EQ-5D questionnaire, reported an increased score from 71.2 ± 15.9 to 82.1 ± 15.5 (P = nonsignificant). Only one study that met the criteria used the World Health Organization Quality of Life-BREF questionnaire with mean pretreatment and post-treatment scores of 12.2 ± 1.6 and 13.5 ± 2.6 (reference range, 0–100), respectively (P = nonsignificant). According to intervention, six studies used a radiologic treatment, three used a surgical treatment, and one used a medical treatment (Supplemental Figure 1 [available online] shows the effect size, noting that some of the outcome data were not reported and, therefore, were not included in the figure as indicated by an asterisk in Table 3).

Table 3.

Summary of studies that evaluated general quality of life instruments.

Study	Study design	Instrument	Treatment	Score before treatment	Score after treatment	Cochrane RoB grade or Newcastle-Ottawa Scale grade
Berman et al. (2014)a (42)	Prospective cohort	European Quality of Life Five-Dimension Scale Visual Analog Scale	Radiofrequency volumetric thermal ablation (RFVTA), N = 104	71	3 mo, 85.3b 6 mo, 84.9b 12 mo, 85.2b 24 mo. 85.1b 36mo 86.2b	Good
Dilek et al. (2010) (90)	Prospective cohort	36-Item Short Form Survey	Myomectomy, n = 72 Normal control, n = 75	Physical function: 73.4 ± 6.4 Physical role: 47.3 ± 3.7 Bodily pain: 52.2 ± 2.9 General health: 60.7 ± 2.9 Vitality: 43.8 ± 3.1 Social function: 62.6 ± 4.9 Emotional role: 55.5 ± 4.6 Mental health: 63.0 ± 4.3	6 mo: Physical function: 80.0 ± 5.4 Physical roleb: 69.0 ± 5.1 Bodily painb: 68.5 ± 4.6 General healthb: 71.2 ± 2.6 Vitalityb: 58.6 ± 5.5 Social functionb: 80.3 ± 4.1 Emotional roleb: 77.0 ± 6.1 Mental health: 71.5 ± 5.0	Good
Garza-Leal et al. (2019) (52)	Retrospective cohort (VITALITY study-Fast EU)	European Quality of Life Five-Dimension Summary Index	Transcervical radiofrequency ablation with Sonata, N = 17	0.79 ± 0.23	57–73 mo: 0.83 ± 0.26	Fair
Garza-Leal et al. (2019) (52)	Retrospective cohort (VITALITY study-Fast EU)	European Quality of Life Five-Dimension Scale Visual Analog Scale	Transcervical radiofrequency ablation with Sonata, N = 17	70.3 ± 22.2	79.8 ± 25.5b	Fair
Guido et al. (2013)a (53)	Multicenter prospective cohort (Halt)	European Quality of Life Five-Dimension Scale Visual Analog Scale	Radiofrequency volumetric thermal ablation, n = 124	EQ-5D: 39	3mob: 71.1 6 mob: 85 12 mob: 84.8 24 mob: 85.8	Good
Hudgens et al. (2019)a (57)	Prospective cohort	European Quality of Life Five-Dimension Summary Index	Transcervical fibroid ablation with Sonata, N = 147 (125 in US)	0.73	3 mob 0.88 12 mob 0.90	Good
Kramer et al. (2015) (62)	Randomized noninferior controlled trial (TRUST)	European Quality of Life Five-Dimension Scale Visual Analog Scale	Radiofrequency volumetric thermal ablation (RFVTA), n = 21 Laparoscopic myomectomy, n = 22	RFVTA: 81.7 ± 11.2 Laparoscopic myomectomy: 72.3 ± 18.2	24 mo: RFVTA: 86.4 ± 9.7 Laparoscopic myomectomy: 79.3 ± 25.2	Low risk
Lee et al. (2010) (65)	Prospective cohort	36-Item Short Form Survey	Radiofrequency ablation (RFA), n = 68	115.1 ± 7.5	115.1 ± 9.4	Good
Liu et al. (2011) (91)	Prospective cohort	World Health Organization Quality of Life-BREF	Laparoscopic uterine artery occlusion myomectomy (LUAO + M), n = 158 Classic intrafascial supracervical hysterectomy (CISH), n = 174	LUAO + M: 12.24 ± 1.52 CISH: 12.11 ± 1.72	24 mo: LUAO + Mb: 14.49 ± 2.81 CISHb: 12.49 ± 2.39	Good
Lukes et al. (2020) (69)	Randomized controlled trial	European Quality of Life Five-Dimension Summary Index	Transcervical fibroid ablation, n = 147	0.72 ± 0.21	3 yb: 0.88 ± 0.16	Some risk
Neri et al. (2019) (92)	Prospective cohort	36-Item Short Form Survey	Ulipristal, n = 22	Physical function: 71.9 ± 21.7 Physical role: 53.8 ± 27.9 Bodily pain: 52 ± 26.8 General health: 53.5 ± 17.6 Vitality: 45.7 ± 14.8 Social function: 59.3 ± 18.4 Emotional role: 46 ± 26 Mental health: 56.3 ± 11.9	3 mo after 1st tx cycleb/3 mo after 2nd tx cycleb Physical function: 83 ± 21/86 ± 12.6 Physical role: 78.8 ± 29/75 ± 25.6 Bodily pain: 64 ± 19/70 ± 20.7 General health: 61.6 ± 20.6/63.6 ± 19.6 Vitality: 57.7 ± 16/63.8 ± 21.6 Social function: 68 ± 14.8/70.8 ± 19 Emotional role: 76.6 ± 28.6/66.4 ± 28.5 Mental health: 65.5 ± 16/68 ± 16.6	Fair
Radosa et al. (2016)a (93)	Prospective cohort	European Quality of Life Five-Dimension Summary Index	Myomectomy, n = 88	0.9 (0.2–1)	1 (0.61–1)b	Good
Rattray et al. (2018) (75)	Randomized noninferior controlled trial (TRUST)	European Quality of Life Five-Dimension Scale Visual Analog Scale	Laparoscopic-radiofrequency ablation (RFA), n = 23 Myomectomy, n = 22	Lap-RFA 58.9 (22.8) Myomectomy 71.8 (11.5)	Lap-RFAb 77.1 (20.2) Myomectomyb 82.7 (8.1)	Some risk
Spies et al. (2001)a (94)	Prospective cohort	Short Form-12	Uterine artery embolization trisacryl gelatin, n = 29	MCS: 47 PCS: 46.1	3-mo MCS: 49.5 3-mo PCSb: 51 6-mo MCS: 50.2 6-mo PCSb: 52.2	Good
Spies et al. (2010) (82)	Multicenter nonrandomized prospective study	36-Item Short Form Survey	Uterine artery embolization (UAE), n = 107 Myomectomy, n = 61 Hysterectomy, n = 106 Normal control, n = 101	Physical function: 75.1 ± 26.0 Physical role: 47.9 ± 41.9 Bodily pain: 48.5 ± 24.3 General health: 67.5 ± 20.4 Vitality: 36.1 ± 21.5 Social function: 62.4 ± 28.1 Emotional role: 57.2 ± 42.8 Mental health: 62.9 ± 19.8	12 mo: Physical function: 91 ± 16.7 Physical role: 83.7 ± 32.0 Bodily pain: 77 ± 22.1 General health: 75.5 ± 19.3 Vitality: 61.7 ± 20.3 Social function: 83.7 ± 22.3 Emotional role: 80.3 ± 35.1 Mental health: 76 ± 17	Good
Taran et al. (2009) (95)	Prospective cohort	36-Item Short Form Survey	Magnetic resonance-guided focused ultrasound (MRgFUS), n = 109 Hysterectomy n = 83	Physical function MRgFUS: 72.8 ± 23.9 Hysterectomy: 56.1 ± 30.0 Physical role MRgFUS: 45.2 ± 41.5 Hysterectomy: 33.4 ± 39.1 Bodily pain MRgFUS: 52.0 ± 22.4 Hysterectomy: 40.1 ± 26.9 General health: MRgFUS 66.0 ± 19.7 Hysterectomy: 58.1 ± 22.8 Vitality MRgFUS: 41.3 ± 20.8 Hysterectomy: 37.2 ± 20.2 Social function MRgFUS: 61.5 ± 27.6 Hysterectomy: 54.2 ± 29.2 Emotional role MRgFUS: 57.8 ± 40.2 Hysterectomy: 39.4 ± 42.9 Mental health MRgFUS: 63.0 ± 16.9 Hysterectomy: 55.1 ± 21.6	6-mo follow-up Physical function MRgFUS: 82.5 ± 15.9 Hysterectomy: 86.9 ± 19.2 Physical roleb: MRgFUSb 68.3 ± 31.0 Hysterectomy 80.0 ± 37.6 Bodily painb MRgFUS 69.1 ± 19.2 Hysterectomy: 79.5 ± 22.6 General healthb: MRgFUS 69.3 ± 15.1 Hysterectomy: 75.3 ± 18.4 Vitalityb: MRgFUS: 59.1 ± 15.1 Hysterectomy 65.6 ± 20.1 Social function MRgFUS 79.5 ± 18.4 Hysterectomy 84.8 ± 22.6 Emotional role MRgFUS: 75.0 ± 30.1 Hysterectomy: 78.1 ± 36.8 Mental healthb MRgFUS: 73.3 ± 11.7 Hysterectomy: 79.6 ± 15.1	Good

⁺indicates statistically significant change from baseline

Note: The score that is the furthest time point measured posttreatment (used in calculations) is underlined. MCS = mental component score; PCS = physical component score.

^aNot included in effect size because the standard deviation was not available.

^bIndicates statistical significance in change of quality of life score.

Mental and Emotional Health

Mental health and emotional health are components included in the SF-36 questionnaire. Four studies reported the specific mental and emotional health scores before and after treatment (Table 4). On average, emotional health improved by 40.4%, and mental health improved by 13.9% after treatment. ‘‘Low’’ mental health scores indicate feelings of nervousness and depression all of the time; high scores indicate feelings of peacefulness, happiness and calmness all of the time past 4 weeks. Low emotional health scores mean problems with work or other daily activities as a result of emotional problems, whereas high scores indicate no problems with work or other daily activities as a result of emotional problems past 4 weeks (27).

Table 4.

Results of studies that evaluated mental and emotional health.

Study	Emotional health pretreatment	Emotional health posttreatment	Percentage change	Mental health pretreatment	Mental health posttreatment	Percentage change
Dilek et al. (2010) (90)	55.5 (4.6)	77 (6.1)	38.7 ↑	63.0 (4.3)	71.5 (5)	13.5 ↑
Neri et al. (2019) (92)	46 (26)	71.5 (28.6)	55.4 ↑	56.3 (11.9)	66.8 (16.3)	18.6 ↑
Spies et al. (2010) (82)	57.2 (42.8)	62.9 (19.8)	10.0 ↑	62.9 (19.8)	76 (17)	20.8 ↑
Taran et al. (2009) (95)	48.6 (41.6)	76.6 (33.5)	57.5 ↑	59.1 (19.3)	76.5 (13.4)	29.5 ↑

Note: Data for emotional health from questions 24–26, 28, 30 in the SF-36 and data for mental health from questions 11–24. Values in parenthesis represent standard deviation. The up arrow represented an improvement in emotional or mental health scores, and the down arrow indicated a reduction in mental emotional or mental health scores.

Other QOL Measures

A total of nine studies were included that used other QOL questionnaires (78, 93, 96–99). These nine studies used only one questionnaire, except for the FSFI, which included three studies (Table 5). Because most of these instruments only included one study, statistical comparisons among the studies were not performed. The Symptom Checklist 90 scores decreased from 133 ± 41 to 116 ± 31 (P = nonsignificant) (reference range, positive if >160). The FSFI scores increased from 39.0 to 42.3 (P > .05) (reference range, 0–36). The Sexual Activity Questionnaire scores increased from a baseline of 20.3 to 22.7 (P = nonsignificant) (reference range, 0–27). The Prolapse and Incontinence Sexual Questionnaire baseline scores increased from 35.1 to 37.7 after treatment (P = nonsignificant). The Brief Index of Sexual Functioning scores increased from 24.8 ± 6.6 to 26.8 ± 5.5 (P = nonsignificant) (reference range, 0–36). Lastly, the Urogenital Distress Inventory score decreased from 44.6 to 21.4 (P = nonsignificant; reference range, 0–100). Supplemental Figure 2 shows the treatment-dependent effect noting that some of the outcome data for calculation were not reported and, therefore, not included in the figure as indicated by an asterisk in Table 5. Not all standard deviations were reported in all included studies.

Table 5.

Summary of instruments using other quality of life measures pre and post treatment for uterine fibroids.

Study	Study design	Instrument	Treatment	Score before treatment	Score after treatment	P value	Cochrane RoB grade or Newcastle-Ottawa Scale grade
Radosa et al. (2016)a (93)	Prospective cohort	Female Sexual Function Index	Myomectomy, n = 88	21.1 (5.2–33.5)	6 mo: 28 (18.7–35.2)	.001	Good
Shveiky et al. (2013)a (78)	Prospective cohort	Urogenital Distress Inventory	Uterine fibroid embolization, n = 57	44.7	3 mo: 21.4	<.0001	Fair
Shveiky et al. (2013)a (78)	Prospective cohort	Prolapse and Incontinence Sexual Questionnaire	Uterine fibroid embolization, n = 57	35.1	3 mo: 37.7	.0018	Fair
Tuschy et al. (2018)a (96)	Prospective cohort	Sexual Activity Questionnaire	Ulipristal acetate, n = 73	Pleasure: 14 (8–18) Discomfort: 1 (0–5) Habit: 1 (0–3)	3 mo: Pleasure: 15 (5–18) Discomfort: 0 (0–4) Habit: 2 (0–3)	Pleasure: .3609 Discomfort: .1441 Habit: <.0001	Fair
Tuschy et al. (2018)a (96)	Prospective cohort	Female Sexual Function Index	Ulipristal acetate, n = 73	26.6 (17.6–35.6)	3 mo: 27.4 (17.9–36.9)	.0008	Fair
Voogt et al. (2009) (97)	Prospective cohort	Symptom Checklist 90	Uterine artery embolization, n = 141	133 ± 41	3 mo: 116 ± 31	<.0005	Fair
Voogt et al. (2009) (97)	Prospective cohort	Questionnaire for Screening Sexual Dysfunctions	Uterine artery embolization, N = 141	20.3 ± 4.8	3 mo: 22.7 ± 4.1	<.0005	Fair
Wang et al. (2013) (98)	Randomized controlled trial	Brief Index of Sexual Functioning	HIFU myomectomy, n = 48	HIFU: 24.6 ± 6.6 Myomectomy: 24.91 ± 6.5	6 mo: HIFU: 26.7 ± 5.2 Myomectomy: 26.8 ± 5.7	HIFU: <.05 Myomectomy: <.05	Some risk
Zhang et al. (2018)a (99)	Prospective cohort	Female Sexual Function Index	LM, n = 120 TCRM, n = 120	LM: 69.41 TCRM: 69.4 Mean: 69.4	6 mo: LM: 71.71 TCRM: 71.4 Mean: 71.6	>.05	Fair

Note: HIFU = high-intensity focused ultrasound; LM = laparoscopic myomectomy; TCRM = transcervical resection of myoma.

^aIndicates study not used to calculate effect size because the standard deviation was not available.

DISCUSSION

The evidence supports an impact of treatment on the QOL and mental health of women with fibroids. Uterine fibroid–specific QOL questionnaires revealed an improvement in QOL and a reduction in symptom severity scores after interventions including medical, surgical, or radiologic treatment. Comparatively, fewer studies have reported QOL outcomes before and after medical or surgical interventions; however, these interventions were also associated with an improvement in QOL metrics. Although reports were limited, emotional and mental health measures improved after emotional and mental health measures through the SF-36 scores after treatment, which included myomectomy, hysterectomy, ulipristal, UAE, and magnetic resonance-guided focused ultrasound (67, 75, 77, 78).

Currently, the UFS-QOL scores are not routinely reported comparing treatment options for uterine fibroids (41). A systematic review by van der Kooij et al. (100) reported that myomectomy (hysteroscopic or laparoscopic) and UAE were the best studied interventions with significant improvements in the overall health-related QOL scores. Among minimally invasive treatment options, Morris et al. (101) found that RFA and ultrasound-guided sclerotherapy improved the overall QOL measures and UAE and ultrasound-guided high-intensity frequency ultrasound improved QOL measures similar to those of surgical interventions. In addition, UAE, magnetic resonance-guided high-intensity frequency ultrasound, ultrasound-guided high-intensity frequency ultrasound, RFA, and percutaneous microwave ablation resulted in significant improvement in the uterine fibroid–specific QOL symptom severity scores (101). Zhang et al. (102) performed a systematic review comparing minimally invasive uterine sparing techniques. Uterine artery embolization led to a significant reduction in fibroid-related bleeding with improvement in 79%–98.5% of patients. As was observed in patients with inflammatory bowel disease, tuberculosis, or cancer (103–105), the inclusion of QOL instruments as standard practice could foster increased patient satisfaction after fibroid procedures.

The associated burden and distress that women with fibroids experience resemble those of other chronic diseases. Questions in the SF-36 instrument assess vitality, which refers to a patient’s energy and fatigue (106). In a previous study (21), patients with fibroids had lower scores than patients with heart disease, diabetes mellitus, and breast cancer (82, 90, 92, 95). Women with fibroids also scored lower in physical function, physical role, and bodily pain areas than those with heart disease and diabetes mellitus (21). In addition, when social functioning was measured, patients with fibroids had lower scores than those with heart disease, diabetes mellitus, and breast cancer (21).

There is an association between anxiety and depression and QOL. Longitudinal and cross-sectional studies found a link between anxiety and depression and reduced QOL scores (107–114). Quality of life can also be predictive of anxiety or depression (112). In a review by Hoertel et al. (113), the QOL scores were lower in groups with anxiety and depression than in those without a mental health diagnosis. Although evidence is more limited, fibroids affect the overall mental well-being of women. A previous study (22) found that the EQ-5D scores, which evaluate mobility, self-care, usual activities, pain or discomfort, and anxiety/depression, were lower in women with fibroids than in those with heart disease and diabetes mellitus (13, 21, 65, 82, 83, 92). The emotional and mental health scores, as part of the SF-36 questionnaire, increased after treatment. Wallace et al. (115) reported that for patients affected with fibroids undergoing treatment, after 1 year, 66.4% reported a decrease in anxiety and depression from a 26.4% reported at baseline (P < .05). It is important to recognize that in the UFS-QOL, 23 of 28 questions assess the psychological well-being of the patient, addressing anxiety, depression, and body image. These questionnaires assess mental health status, and fibroid-related stress was considered in development and validation of the instrument (17). In addition, in the symptom severity score, a component of the fibroid-specific QOL score, a question asks, ‘‘how distressed were you by…’’; thus, the score reflects a metric of whether the patient was anxious or concerned by the particular symptom (e.g., heavy bleeding, frequent urinating, and feeling fatigued). Therefore, the lower scores in the UFS-QOL and higher symptom severity scores suggest a poorer mental health status.

Nicholls et al. (24) conducted semistructured interviews in 18 women affected with fibroids and found that most of the women expressed distress about the changes they were experiencing both which they perceived to have little control over. This distress significantly affected their body image, which is a finding not investigated in many studies and an area for future research (24). In a structured interview by Ghant et al. (116) including 60 women affected with fibroids, most exhibited an emotional response to their fibroids including fear, anxiety, anger, and depression. In addition, patients felt less attractive and reported a negative self-image, and this affected intimacy (116). Fifty percent of these women felt helpless and a loss of control (116). Other studies also revealed that women with fibroids often report a loss of control (24, 117). However, as stated earlier, it is reassuring that 1 year after treatment for symptomatic fibroids, the prevalence of anxiety and depression decreased in most women (13). Studies in other conditions, such as cardiac disease, end-stage renal disease, and chronic obstructive pulmonary disease, show that QOL measures improve after treatment (117–121). Hence, including these QOL instruments in general routine care could complement the assessment of the physical symptoms and laboratory consequences of fibroid disease and provide an opportunity to determine whether the intervention improves the patient’s holistic life functioning and mental well-being.

Patients with fibroids have higher reported rates of not only depression and anxiety but also self-directed violence and stress (22). The association could be exacerbated by hormonal dysregulation, psychological stressors, and racism (122–125). Wise et al. (123) conducted a study to examine the role of stress in relation to fibroids and found that the incidence rate ratios for both lifetime and everyday experiences of racism among African American women with fibroids increased (123). The release of stress hormones cortisol and epinephrine has been associated with syndromic fibroids (126). The possible role of stress is supported by studies such as those by Whirledge et al. (127) who observed that glucocorticoids may play an important role in regulating uterine fibroid gene expression and cell growth. More evidence shows that fibroids cause stress for affected women; whether stress contributes meaningfully to the pathogenesis of fibroids requires further investigation.

The strengths of this review include the strict inclusion and exclusion criteria including RCTs and prospective cohort publications of validated questionnaires with the pretreatment and posttreatment scores. The study systematically compares the effects of different interventions for fibroids on QOL and summarizes the effects on the mental well-being of affected women. This study has some limitations. Some of the studies included were not representative of the US population with uterine fibroids because the study population was restricted to a specific locale. In addition, the post-treatment scores were completed at varying times, 1 month through 3 years, and were not standardized across all studies. The thorough and detailed search strategy excluded several studies that reported changes from baseline, instead of raw scores; therefore, few studies included all other measures including general QOL and instruments using other QOL measures. Several questions in the SF-36 survey are comparable with those listed in the PHQ9 and GAD7 (29). A study by Matcham et al. (128) found that the SF-36 scores had a sensitivity and specificity of 81% and 71%, respectively, to detect anxiety and 92.6% and 73.2%, respectively, to detect depression (128). The SF-36 may not be the best tool to assess anxiety and depression, and tools such as the PHQ9 may be used to better assess the role of mental health in future studies. The investigators recognize that although high SF-36 scores suggest depressive symptoms, these could not be used to confirm a diagnosis of depression or anxiety by a mental health professional. In addition, several studies could not be included in the effect size analysis and subanalysis by intervention type because some of the outcome data for calculation were not reported. Furthermore, notable gaps remain to guide selection of treatment choice for patients and providers. For instance, whether medical or surgical interventions may better improve QOL based on fibroid location, size, or symptom remains to be elucidated.

CONCLUSION

The evidence strongly suggests that fibroids impact the QOL and mental health of women with fibroids and that treatment leads to significant improvement in these scores. The QOL instruments provide an objective assessment to measure the pre- and post-QOL status of patients, and in most studies, these have improved after the intervention. Collection of QOL information has the potential to increase patient satisfaction and elevate the experience of women undergoing treatment for uterine fibroids.