Abstract
Background:
Quality of life (QOL) and psychological health has been reported to be decreased among women with gynecological conditions such as uterine fibroids (UFs).
Materials and Methods:
Women enrolled in the Comparing Options for Management: PAtient-centered REsults for Uterine Fibroids (COMPARE-UF) registry, receiving procedural therapy for symptomatic UFs, were eligible for this analysis if they completed a series of health-related QOL surveys administered at three time points (baseline, 6–12 weeks postprocedure, and 1 year postprocedure; n = 1486). Ethical approval for this study was obtained at each recruiting site and the coordinating center (NCT02260752, clinicaltrials.gov).
Results:
More than 26% (n = 393) of women reported moderate anxiety/depression on the baseline anxiety/depression domain of the Euro-QOL 5-dimension instrument. At both the 6–12 weeks and 1-year postprocedural follow-up, there was significant improvement in the UF QOL symptom severity score (p < 0.001, p < 0.001), the total UF symptom QOL score (p < 0.001, p < 0.001), and the Euro-QOL 5-dimension visual analog scale (p < 0.001, p = 0.004) compared with the preprocedural baseline scores. The reporting of anxiety/depression decreased by 66.4% among women who were at baseline, whereas 5.6% of women previously reporting no anxiety/depression reported anxiety/depression at the 1-year follow-up.
Conclusion:
UF symptoms were more severe among women reporting anxiety/depression at baseline. At the 1-year follow-up, health-related QOL scores improved among all women and the prevalence of anxiety/depression decreased in most, but not all women, whereas severity of anxiety/depression worsened in a small percentage of women (5.6%). Overall, these results suggest that UF treatment improves symptoms of anxiety/depression associated with symptomatic UFs.
Keywords: abnormal, bleeding, endometrial, ablation, hysterectomy, leiomyoma
Introduction
Uterine fibroids (UFs) are benign smooth muscle tumors in the uterus that can affect up to 80% of women during their lifetime.1 For women with symptomatic UFs the physical symptoms can include heavy and/or prolonged menstrual bleeding, menstrual pain, pelvic pressure, abdominal bloating, and fatigue.2,3 Studies have reported that women with UFs report lower quality of life (QOL), higher health care costs, and a negative life impact because of UFs.4–7 In addition to physical and financial hardships, psychological distress and increased anxiety and/or depression has been reported to be common among women affected by UFs and more common compared with those without UFs.8–12 Shen et al. found that women with UFs had an increased risk for developing depression compared with women without UFs.11
Possibly contributing to the anxiety and depression among women with symptomatic UFs are the limitations in treatment options.10 Some studies have evaluated the effects of UF surgical treatment with anxiety and depression. Although these studies have primarily reported positive associations between surgical treatment for UFs and decreased anxiety and/or depression,11,13 these studies did not assess how physical symptoms accompanying UFs are associated with feelings of anxiety/depression. To address this question, we evaluated the relationship between UFs and anxiety and/or depression as measured with a generic QOL instrument, and the extent to which UF symptoms mediated this relationship among women undergoing therapeutic procedures for UFs.
Materials and Methods
Comparing Options for Management: PAtient-centered REsults for Uterine Fibroids (COMPARE-UF) registry (NCT02260752, clinicaltrials.gov) is a multi-institutional prospective observational registry that enrolled premenopausal women undergoing procedural therapy for UF at one of nine clinical sites located throughout the continental United States. Between November 11, 2015 and August 29, 2019, women were enrolled in COMPARE-UF and were eligible for the current analysis if they were at least 1 year past a UF procedure.14 Procedures included myomectomy, hysterectomy, endometrial ablation, uterine arterial embolization, magnetic resonance-guided focused ultrasound, and progestin-releasing intrauterine device (IUD) insertion. Exclusions for this analysis were women who were actively trying to become pregnant or had a confirmed pregnancy after UF surgery.
Women younger than 31 years were found to have only received myomectomies versus any of the other procedures. To ensure there was no procedural bias among women younger than 31 years, we excluded this group of women. Women who received a diagnosis of cancer were also excluded. We excluded 91 women with missing baseline (within 45 days of surgery or 31 days of IUD insertion), short-term (6–12 weeks postprocedure), or 1-year (11–18 months postprocedure) survey data, resulting in 1486 women eligible for analysis (Fig. 1).
FIG. 1.
Flowchart of Inclusion/Exclusion criteria and final study population.
Sociodemographic and Health-related Quality-of-Life questionnaires
At baseline demographic information was collected and participants completed a series of sociodemographic and Health-related Quality-of-Life (HRQOL) questionnaires.14 Menstrual, UF, medical, and reproductive history were also collected. At the short-term and 1-year postprocedure follow-up participants again completed all questionnaires.15–17 Women also completed sociodemographic, menstrual, medical, and reproductive surveys at the 1-year follow-up. For each time period and for each questionnaire participants had the option of completing the questionnaires through a secure, password-protected web-based study portal (SignalPath, LLC, Durham, NC) or through paper or through a phone interview with the Duke Clinical Research Institute (DCRI) staff members or clinical site study coordinator(s).
The Uterine Fibroid Symptom Quality-of-Life questionnaire (UFS-QOL) is a 37-item questionnaire that includes six subscales (concern, activities, energy/mood, control, self-conscious, and sexual function) that has been validated to assess health in women with UFs.9 The sum of these subscales is the total UFS-QOL in which a higher value is indicative of better HRQOL. Symptom severity is assessed from the UFS-QOL by using the sum of the first eight questions; a higher symptom severity score is indicative of worse UF symptoms. The Menopause Rating Scale HRQOL scale (MRS-HRQOL) is an 11-item questionnaire designed to assess HRQOL or severity of complaints among women.18 Responses to the MRS-HRQOL are as follows: none, mild, moderate, severe, and very severe.
The Euro-Quality-of-Life-5 Dimension (EQ-5D) is an 8-item questionnaire used to assess health level based on mobility, self care, usual activities, pain/discomfort, and anxiety/depression.19 Responses to these dimensions are: no, slight, moderate, severe, and confined/extreme/unable to perform. Participants were also asked to rate their current health level on the visual analog score (VAS), a vertical 20 cm scale where higher values are indicative of better health. In the absence of formal psychological examination or specific instruments, the anxiety/depression domain of the EQ-5D has been used to define psychological distress.20,21
Statistical analysis
Sociodemographic characteristics, UF symptoms, planned procedure, and reproductive history were summarized by anxiety/depression status at baseline. Mean values and standard deviations were used for continuous variables and frequencies and percentages for categorical variables. The two groups were compared with t-tests and chi-square tests as appropriate. HRQOL metrics by anxiety/depression status at baseline, short-term, and 1-year follow-up and change in HRQOL metrics from baseline to short and 1-year follow-up was summarized with means and 95% confidence intervals (CIs).
Multivariable logistic regression was used to identify baseline characteristics independently associated with reporting anxiety or depression. Baseline characteristics associated with anxiety/depression were considered as candidate variables and backward selection was used to trim the set of variables. The significance level to stay in the model was set to 5%. Results are presented as odds ratios with 95% CIs.
To address missing data (range of 0%–3.6% at baseline), covariates with missing data at baseline were imputed using the full-conditional specification method in SAS PROC MI.22 In conducting imputation, all important confounders and additional variables available in the COMPARE-UF data set were included. These were used to predict missing data, per the full-conditional methods to ensure no one was excluded for missing covariate data. To improve the accuracy of imputation and subsequent results, the 1-year QOL outcomes were used in the imputation process. All analyses were conducted using SAS System TS1M6 (SAS, Cary, NC).
Results
Characterization of anxiety/depression among women with UFs
Based on the anxiety/depression domain in the EQ-5D,20,21 we categorized women as nonanxious (no and slight anxiety, n = 1093, 73.6%) versus anxious/depressed (moderate and severe anxiety, n = 393, 26.4%). Women who reported feelings of anxiety/depression were more likely to have been told by a doctor or health care provider that they had anxiety (58.7% vs. 16.4%, p < 0.001) or depression (54.9% vs. 17.1%, p < 0.001) compared with women without anxiety/depression. Women in the anxious/depressed cohort were more likely to respond as having little interest or pleasure in doing things over the past 2 weeks and more feelings of depression and hopelessness (p < 0.001) (Supplementary Fig. S1) compared with women without anxiety/depression. On the MRS-HRQOL women reporting anxiety/depression were more likely to have responses ranging from moderate to very severe on the four psychological questions of the MRS-HRQOL (p < 0.001) (Supplementary Fig. S2) compared with women without anxiety/depression.
UF symptoms and QOL among women with and without anxiety/depression
Thirty percent of participants were under the age of 40, 47% white and 40% black (Table 1). There was a significant difference in distribution by both age (p = 0.02) and race (p = 0.02) with younger women and black women more likely to have anxiety/depression at baseline. Women with anxiety/depression tended to have higher body mass index compared with women without anxiety/depression (32.7 ± 9.6 vs. 29.8 ± 7.6 kg/m2, p < 0.001). There were few differences between women with and without depression/anxiety at baseline regarding prior UF surgical treatment (p = 0.67) or planned UF intervention (p = 0.83).
Table 1.
Baseline Characteristics Between Women Reporting No Anxiety/Depression Versus Anxiety/Depression on the Euro-Quality-of-Life-5 Dimension Anxiety/Depression Domain at Baseline
| Characteristic | No/slightly anxious or depressed (n = 1093) | ≥ Moderately anxious or depressed (n = 393) | Total (N = 1486) | p |
|---|---|---|---|---|
| Age (years) | 43.4 (5.5) | 42.7 (5.8) | 43.2 (5.6) | 0.02 |
| 31–39 | 255 (23.3%) | 109 (27.7%) | 364 (24.5%) | |
| 40–44 | 337 (30.8%) | 118 (30.0%) | 455 (30.6%) | |
| 45–54 | 501 (45.8%) | 166 (42.2%) | 667 (44.9%) | |
| Race | 0.02 | |||
| White | 521 (47.7%) | 178 (45.3%) | 699 (47.0%) | |
| Black | 417 (38.2%) | 177 (45.0%) | 594 (40.0%) | |
| Other | 155 (14.2%) | 38 (9.7%) | 193 (13.0%) | |
| Insurance | <0.001 | |||
| Private | 954 (87.4%) | 293 (74.9%) | 1247 (84.1%) | |
| Active military | 6 (0.5%) | 2 (0.5%) | 8 (0.5%) | |
| Other | 131 (12.0%) | 96 (24.6%) | 227 (15.3%) | |
| Medical treatment | ||||
| Currently treated for depression | 65 (6.0%) | 123 (32.1%) | 188 (12.9%) | <0.001 |
| Currently treated for anxiety | 69 (6.4%) | 145 (37.9%) | 214 (14.7%) | <0.0001 |
| Planned UF procedure | 0.83 | |||
| Myomectomy | 365 (33.4%) | 132 (33.6%) | 497 (33.4%) | |
| Hysterectomy | 516 (47.2%) | 175 (44.5%) | 691 (46.5%) | |
| Endometrial ablation | 96 (8.8%) | 37 (9.4%) | 133 (9.0%) | |
| Uterine arterial embolization | 87 (8.0%) | 37 (9.4%) | 124 (8.3%) | |
| Other | 29 (2.6%) | 12 (3.0%) | 41 (2.8%) | |
| UF symptoms at baseline | ||||
| Duration of symptoms | 5.9 (6.6) | 6.9 (7.2) | 6.1 (6.7) | 0.006 |
| Any fibroid symptoms | 1029 (94.4%) | 383 (97.5%) | 1412 (95.2%) | 0.02 |
| Bleeding symptoms | 908 (83.3%) | 352 (89.6%) | 1260 (85.0%) | 0.003 |
| Menses ≥7 days | 631 (57.9%) | 277 (70.5%) | 908 (61.2%) | <0.001 |
| Heavy menses | 840 (77.1%) | 329 (83.7%) | 1169 (78.8%) | 0.006 |
| Bleeding between periods | 509 (46.7%) | 220 (56.0%) | 729 (49.2%) | 0.002 |
| Frequent urination | 583 (53.5%) | 258 (65.6%) | 841 (56.7%) | <0.001 |
| Nocturia | 568 (52.1%) | 258 (65.6%) | 826 (55.7%) | <0.001 |
| Abdominal bloating | 762 (69.9%) | 329 (83.7%) | 1091 (73.6%) | <0.001 |
| Abdominal/pelvic pressure | 741 (68.0%) | 317 (80.7%) | 1058 (71.3%) | <0.001 |
| Pelvic pain requiring meds | 398 (36.5%) | 241 (61.3%) | 639 (43.1%) | <0.001 |
| Appear pregnant | 399 (36.6%) | 196 (49.9%) | 595 (40.1%) | <0.001 |
| Discomfort during intercourse | 412 (37.8%) | 209 (53.2%) | 621 (41.9%) | <0.001 |
| Nonmenstrual pain | 141 (12.9%) | 64 (16.3%) | 205 (13.8%) | <0.001 |
| History of anemia | 540 (50.0%) | 235 (60.4%) | 775 (52.8%) | <0.001 |
| Requiring transfusion | 85 (7.9%) | 47 (12.3%) | 132 (9.1%) | 0.010 |
| Reproductive history | ||||
| Ever pregnant | 760 (70.0%) | 278 (71.1%) | 1038 (70.3%) | 0.70 |
| Two or more pregnancies | 602 (55.1%) | 218 (55.5%) | 820 (55.2%) | 0.89 |
| Subfertility | 129 (11.8%) | 58 (14.8%) | 187 (12.6%) | 0.13 |
| Miscarriage(s) | 56 (5.1%) | 34 (8.7%) | 90 (6.1%) | 0.01 |
| Social factors | ||||
| Marital status | 0.01 | |||
| Married/living as married or with a domestic partner | 618 (57.4%) | 186 (47.9%) | 804 (54.9%) | |
| Separated | 29 (2.7%) | 15 (3.9%) | 44 (3.0%) | |
| Divorced | 106 (9.9%) | 50 (12.9%) | 156 (10.7%) | |
| Widowed | 9 (0.8%) | 7 (1.8%) | 16 (1.1%) | |
| Single, never married | 314 (29.2%) | 130 (33.5%) | 444 (30.3%) | |
| Highest education | <0.001 | |||
| Less than high school | 18 (1.7%) | 10 (2.6%) | 28 (1.9%) | |
| High school (grade 12 or general equivalency diploma) | 103 (9.5%) | 49 (12.6%) | 152 (10.3%) | |
| Some college (1- to 3-year college or technical school) | 266 (24.6%) | 133 (34.2%) | 399 (27.1%) | |
| College graduate (4-year college) | 352 (32.6%) | 98 (25.2%) | 450 (30.6%) | |
| Graduate degree (e.g., Masters, Doctorate, or professional degree) | 342 (31.6%) | 99 (25.4%) | 441 (30.0%) | |
| Employment status | <0.001 | |||
| Employed full-time | 812 (75.2%) | 244 (62.7%) | 1056 (71.9%) | |
| Employed part-time | 128 (11.9%) | 35 (9.0%) | 163 (11.1%) | |
| Homemaker | 56 (5.2%) | 24 (6.2%) | 80 (5.4%) | |
| Retired | 6 (0.6%) | 0 (0.0%) | 6 (0.4%) | |
| Disabled | 27 (2.5%) | 31 (8.0%) | 58 (3.9%) | |
| Not currently working | 51 (4.7%) | 55 (14.1%) | 106 (7.2%) | |
| Financial toxicity | 28.9 (9.6) | 21.8 (10.7) | 27.0 (10.4) | <0.001 |
“Other” variables include self-reported options that are not accounted for in that category.
UF, uterine fibroid.
In addition to a longer duration of UF symptoms (6.9 ± 7.2 vs. 5.9 ± 6.6 years, p = 0.006), women reporting anxiety/depression had more UF-related symptoms (p < 0.05) compared with women without anxiety/depression (Table 1). Frequent urination (p < 0.001), nocturia (p < 0.001), abdominal bloating (p < 0.001), and pelvic pain requiring medication (p < 0.001) were increased among women reporting anxiety/depression than women without. The proportion of women who had experienced miscarriage was higher among women with anxiety/depression compared with those without (p = 0.01).
At baseline, women with anxiety/depression reported lower total UFS-QOL mean scores 32.3 (95% CI: 30.1–34.6) compared with women without anxiety/depression 52.4 (95% CI: 50.8–54.0) (Fig. 2A). This was true across all domains of the UFS-QOL (p < 0.001). The UFS-QOL symptom severity score was significantly higher among anxious/depressed women 66.6 (95% CI: 64.4–68.8) compared with those without anxiety/depression 51.7 (95% CI: 50.2–53.2) (Fig. 2B). When women were asked to indicate their overall health on the EQ-5D VAS, women with anxiety/depression reported lower mean health scores 62.2 (95% CI: 60.1–64.2) compared with women without anxiety/depression 75.0 (95% CI: 74–76.1) (Fig. 2C).
FIG. 2.
Anxiety/depression and QOL measures at baseline. Survey results collected at baseline (before UF procedure) were compiled for women classified as anxious/depressed (n = 393) and women who were not anxious/depressed (n = 1093). Women with anxiety/depression also reported lower QOL (A), higher symptom severity (B), and a lower overall health (C) compared with women without anxiety/depression. QOL, quality of life; UF, uterine fibroid.
Social factors and increased anxiety/depression among women with UFs
Women with anxiety/depression were more likely to be divorced, separated, or widowed compared with women without anxiety/depression (Table 1). Women with anxiety/depression were less likely to have completed a 4-year college or graduate degree compared with women without anxiety/depression (p < 0.001) and were more often homemakers, disabled, or not working compared with women without anxiety/depression (p < 0.001). Women with anxiety/depression reported a lower financial toxicity score (lower the score the more financial toxicity) compared with women without anxiety/depression (21.8 vs. 28.9, p < 0.001). Use of tobacco (8.7% vs. 5.9%, p < 0.001) and marijuana (11% vs. 4.2%, p < 0.001) was greater among women with anxiety/depression compared with women without. However, alcohol use was lower in anxious/depressed women compared with women without anxiety/depression (80.3% vs. 87%, p = 0.003).
Medical comorbidities, increased risks, and increased anxiety/depression among women with UFs
Women with anxiety/depression were more likely to have high blood pressure (34.6% vs. 26.3%, p = 0.002), asthma (21.5% vs. 15.2%, p < 0.001), and polycystic ovary syndrome (9.8% vs. 4.3%, p < 0.001) compared with women without anxiety/depression. There were no statistical differences between the two groups of women when the prevalence of diabetes (p = 0.21), thyroid problems (p = 0.15), or blood clots (p = 0.12) were compared.
In the multivariable logistic regression analysis, five variables had a significant independent association with anxiety/depression at baseline (Supplementary Table S1). Race was associated with anxiety/depression: when compared with white women, black women and women of “other” races were 35% and 45% less likely to report anxiety/depression. The odds of self-reporting anxiety/depression increased 14% for each 10-unit increase in the UFS-QOL symptom severity score at baseline. Compared with women employed full-time, women reporting disability or who were not working were more likely to be anxious/depressed. Financial toxicity was also associated with anxiety/depression with a 24% increase in the odds of reporting anxiety/depression. Pain/discomfort was strongly associated with anxiety/depression at baseline compared with no pain/discomfort.
Black women (29.8%) were more likely to report anxiety/depression compared with white women (25.4%); however, a negative relationship was found in the multivariable logistic regression. To determine which of the other variables contributed to this negative association between anxiety and black women, the covariates were examined individually with race (black vs. white women with anxiety). When race is adjusted for either financial toxicity and/or pain/discomfort the likelihood of black women reporting as anxious/depressed decreases (Supplementary Table S2).
Changes in the EQ-5D and UFS-QOL postprocedure
Before a UF procedure, 393 women reported anxiety/depression, however this number decreased to 120 (69.5% decrease) at the short-term follow-up with a final 132 (66.4% decrease from baseline) reporting as anxious/depressed 1 year after a UF procedure (Fig. 3A). Of the 1093 women without anxiety/depression at baseline, 40 women (3.7% increase) at the short-term follow-up and 61 (5.6% increase from baseline) at the 1-year follow-up self-identified as anxious/depressed on the EQ-5D (Fig. 3B). A subanalysis of these 61 women who moved from no anxiety/depression at baseline to anxiety/depression at the 1-year follow-up showed no statistically significant difference in self-reported adverse intraoperative events surrounding UF procedures (p = 0.26; Table 2).
FIG. 3.
QOL after interventional procedures for UFs. The number of women with anxiety/depression at baseline that reported feelings of anxiety/depression after a UF procedure decreased at STFU (69.6%) and the 1Yr FU (66.4%) (A). Some women without anxiety/depression at baseline reported feelings of anxiety/depression at the STFU (3.7%) and 1Yr FU (5.6%) (B). Overall health and fibroid-related symptoms (UFS-QOL) significantly improved in both cohorts of women at both the STFU and 1Yr FU compared with their preprocedural (baseline) measurements (C). 1Yr FU, 1 year follow-up; STFU, short-term follow-up; UFS-QOL, Uterine Fibroid Symptom Quality-of-Life questionnaire.
Table 2.
One-Year Uterine Fibroid Symptom Quality-of-Life Questionnaire Symptom Severity Scores and the Number of Women Who Reported Adverse Intraoperative Events Following Their Uterine Fibroids Procedure from the 1093 Women Who Were Not Anxious/Depressed at Baseline
| Characteristics | Total (n = 1093) | Not anxious/depressed (n = 1032) | Anxious/depressed (n = 61) | p |
|---|---|---|---|---|
| UFS-QOL Symptom Severity | <0.0001 | |||
| Mean (SD) | 12.3 (16.7) | 11.6 (15.8) | 23.5 (25.1) | |
| Median (IQR) | 6.3 (0.0–18.8) | 6.3 (0.0–15.6) | 12.5 (6.3–34.4) | |
| Intraoperative adverse events | 0.2608 | |||
| No | 977 (93.6%) | 925 (93.8%) | 52 (89.7%) | |
| Yes | 67 (6.4%) | 61 (6.2%) | 6 (10.3%) |
IQR, interquartile range; SD, standard deviation; UFS-QOL, Uterine Fibroid Symptom Quality-of-Life questionnaire.
When the symptom severity score on the UFS-QOL was assessed, women who developed anxiety/depression after their UF procedures had higher symptom severity scores compared with women with no anxiety/depression at 1-year follow-up (Table 2; p < 0.0001).
An improvement in the EQ-5D VAS score was reported in both groups of women at the short-term and the 1-year follow-up compared with their baseline scores (Fig. 3C). However, women in the anxious/depressed group had lower mean VAS scores 75.1 (95% CI: 73.3–77) at 1 year compared with women without anxiety/depression 84.3 (95% CI: 83.5–85.1). Of importance, women in the anxiety/depressed group had a mean VAS score equivalent to the mean baseline VAS score in women without anxiety/depression 75.0 (95% CI: 74–76.1).
The total UFS-QOL score improved among women with and without anxiety/depression at short-term and at 1 year (Fig. 3C). Despite the improvement in UFS-QOL, at 1 year, women originally reporting anxiety/depression at baseline still had lower mean total UFS-QOL scores, 82.4 (95% CI: 80.0–84.8) compared with women without anxiety/depression at baseline 91.0 (95% CI: 90.0–91.9). The symptom severity score also decreased between both groups of women at short-term and the 1-year follow-up (Fig. 3C). At the 1-year follow-up women in the anxious/depressed group had higher mean symptom severity scores (18 [95% CI: 16–20]) compared with women without anxiety/depression, 12.3 (95% CI: 11.3–13.3).
Discussion
Principal findings
In this study, 26.4% of women undergoing procedural treatment for UFs self-reported as anxious/depressed at baseline. Women with anxiety/depression had more severe UF symptoms compared with women without anxiety/depression; despite having few differences in planned UF procedures or UF treatment history. At 1-year follow-up, most women who originally had anxiety/depression had improvements in QOL and no longer reported feelings of anxiety/depression.
Results in the context of what is known
One year after UF procedure, QOL and symptom severity scores improved in the majority of women. Studies among women with reproductive disorders other than UFs, such as endometriosis or abnormal uterine bleeding, have also reported positive correlations between anxiety/depression and their uterine disorder, suggesting that the underlying gynecologic disease may drive the mood disorder.8,11,23,24 Although women in the anxiety/depressed group tended to have larger changes in their QOL scores, their overall health was still rated at the same level as women without anxiety/depression before a UF procedure. Similar results have been reported by others as women who underwent surgery for their UFs had a lower incidence of depression compared with women without surgical intervention (4.76 vs. 7.89 per 1000 person-years).11
Another study examining mental health and QOL in women with UF 1 year after they either had a hysterectomy or an observation/nonsurgical alternative reported significant improvement in the Mental Health Index among women receiving hysterectomies compared with no change being observed among women in the nonsurgical arm.13 Women with endometriosis who report more frequent comorbidities associated with pain were also found to be at greater risk for mental health conditions.24,25 Of interest, women with anxiety/depression at baseline were also more likely to report pain as greater than slight on the pain or discomfort scale of the EQ-5D relative to women without anxiety/depression (data not shown). The results of the current study give further proof to the link between symptom severity and mental well-being.
The majority of the women reporting anxiety/depression at baseline demonstrated resolution of these feelings after their UF procedure (decrease from 393 women at baseline to 132 at 1-year follow-up, 66.4% decrease). There was a small number of women in the nonanxious/depressed cohort who identified as anxious/depressed at the short-term 1-year follow-up. Many factors can contribute to depression and beyond UF; according to the Centers for Disease Control, 10.1%–11.5% of women at ages 20–59 years experience depression in a given year.26 The degree to which depression/anxiety after treatment is attributable to treatment, or non-UF-related factors is difficult to ascertain within our cohort, but is consistent with other findings.
Some studies have reported no change in mood or worsening of mood after surgical treatment for UFs.27,28 In this study, among the 61 women who developed anxiety/depression after their UF procedure, there were no significant differences in intraoperative events between the groups; however, newly anxious/depressed women had a significantly higher symptom severity score compared with women who remained not anxious/depressed; because higher baseline severity was also associated with anxiety/depression, it is plausible that some of the new anxiety/depression is related to recurrent or persistent UF symptoms.
Medical and reproductive conditions (i.e., hypertension and diabetes) are greater among women with UF and are independently associated with anxiety/depression.29–32 The incidence of depression is higher among women with UFs who have hypertension,11 which is consistent with our study findings. In the current analysis, women with anxiety/depression were more likely to also have hypertension and polycystic ovarian syndrome compared with women who were not anxious or depressed. In addition to medical conditions, psychosocial, demographic, and sociodemographic factors have been reported to have a large impact on mental health.33 In univariate analysis, black women (29.7%) were more likely to identify as anxious/depressed, compared with women in the white (25.5%) or “other” (19.7%) race categories who also responded as anxious/depressed, consistent with other studies.34,35 However, this association disappeared between black and white women after controlling for pain/discomfort and financial toxicity (an independent QOL metric that measures the degree to which costs associated with symptoms and treatment of a condition affect QOL among black women).36
The positive association between certain sociodemographic characteristics (i.e., educational attainment and increased financial toxicity) and anxiety/depression among women with UFs that was seen in this study agrees with previous studies. Knudsen et al. reported that women with UFs who had less educational attainment reported more fear/anxiety compared with women with more educational attainment.37 A positive association was found in a cross-sectional study evaluating the relationship between UF prevalence, the number of major life events, and stress.38 Marijuana and smoking, both of which are coping strategies for anxiety and/or depression, were also greater among women with anxiety/depression cohort, although alcohol consumption was lower.39
Clinical implications
These results further emphasize the importance of the provider considering the impact of psychosocial stress and mental health in women with UFs and how procedural intervention can help improve feelings of anxiety and/or depression in most women. These findings emphasize the psychological effects of UF and how feelings of anxiety/depression improve in the majority of women regardless of their procedural intervention
Strengths and limitations
The strengths of this study include a large sample size and the use of several validated questionnaires, which allowed us to evaluate physical symptoms associated with UFs, as well as sociodemographic, psychosocial, medical, and reproductive factors. In addition, analyses including the baseline measure (i.e., before UF intervention) of the outcome measures were performed. Another strength is the variety of interventional procedures among study participants. With the number of women and interventions, we were able to demonstrate that women with anxiety/depression were not on average planning certain UF interventions compared with women without anxiety/depression.
A study limitation is that we did not use a clinical diagnosis of anxiety/depression or a standardized anxiety/depression questionnaire, whereas to date all other UF studies reporting changes in anxiety/depression have done so. QOL questionnaires such as the EQ-5D and 36-Item Short Form Survey (SF-36) have been examined for construct validity to determine their generalizability among patients with diagnosed mental health problems. Both were found to be capable of distinguishing anxiety and depression among individuals with clinical anxiety or depression.40,41 However, the sensitivity of the EQ-5D decreases among patients with severe depression.41 Despite this limitation, we do believe the utilization of the anxiety/depression domain of the EQ-5D adequately assesses potentially clinically important changes in the mental wellbeing of study participants. In addition, in this study more women in the anxiety/depressed group received and were treated for a medical diagnosis of anxiety or depression compared with women in the no anxiety/depression group. Likewise women with anxiety/depression on the EQ-5D reported similar results on the MRS-HRQOL.
We also did not assess if there was a relationship between anxiety/depression and the number or size of UF. However it has previously been reported that UF location and size are not related to impairments in QOL,28 and it seems likely that any such association would be mediated through effects on type and severity of symptoms.
It should be mentioned that the majority of the recruiting sites in COMPARE-UF are well-known academic medical centers that have specialty UF clinics. These centers are more than likely able to provide a larger variety of procedures than what may be available in rural or community clinics and thus attract a different population of women. For that reason, women enrolled in COMPARE-UF may not be representative of the average UF patient in the United States. However even if this is the case, this study is unique in that the recruiting sites were geographically diverse within the continental United States. Finally, we did not follow-up with women who chose not to participate in this registry. Future registries consider following up with this population to determine if there are any barriers to participation that are preventing participation.
Conclusion
We found that at baseline, women with anxiety/depression had more severe UF symptoms, which was reflected in their HRQOL symptom severity score and VAS. Our data suggest that procedural intervention for UFs improves QOL, perception of overall health, and decreases feelings of anxiety/depression in most women with symptomatic UFs beginning 6–12 weeks after their procedure. The magnitude of improvement in QOL was slightly greater for women with anxiety/depression than for women without anxiety/depression at baseline. The results from this study provide useful information for both providers and patients alike regarding the improvement in anxiety/depression after procedural treatment for UF.
Supplementary Material
Acknowledgments
The authors acknowledge Serene S. Srouji, MD, Antonio R. Gargiulo, MD at Brigham and Women's, John C. Petrozza MD at Massachusetts General Hospital, and Olga Brooks MD at Beth Israel Deaconess Medical Center. Ram Parvataneni, MD, MPH, Erica Oberman, MD, Naghmeh Salamat Saberi, MD, Shira Varon, MD and L. Elaine Waetjen, MD at the University of California Fibroid Network. Bijan Borah, PhD, Joyce Balls-Berry, PhD, Jennifer Bantz, MD, Paul Matigbay, MD, Gokhan Anil, MD, and Jason Dewitt, MD at Mayo Clinic. Andrea Knittel, MD, Anissa Vines, PhD, Lauren Schiff, MD and Stephen Loehr, MD at UNC-Chapel Hill and Abbas Shoberi, MD at Inova Health for their help with enrolling participants in COMPARE-UF. Barbara Lytle at DCRI, Laine Thomas, PhD at Duke University, William Catherino, MD, PhD at the Uniformed Services University of the Health Sciences, Ryan Heitling, DO, LTC, MC at Madigan Army Medical Center and Gary Levy, MD, LTC, MC at Tripler Army Medical Center for their contributions to the study design for COMPARE-UF. The content of this article is solely the responsibility of the authors and readers should not interpret any statement in this product as an official position or the views of Agency for Healthcare Research and Quality (AHRQ), the U.S. Department of Health and Human Services, or Patient-Centered Outcomes Research Institute (PCORI).
Authors' Contributions
Conceptualization, K.W., E.A.S., W.K.N., V.J., and S.V.; methodology, K.W., E.A.S., W.K.N., S.Z., V.J., D.W., E.R.M., and E.M.; investigation, K.W., E.A.S., S.L.-T., W.K.N., J.P.P., V.J., R.M.A., A.S., G.R.W., G.M.L., and E.M.; writing—original draft, K.W., E.R.M., and E.M.; writing—review and editing, K.W., E.A.S., L.A.W., W.K.N., J.P.P., S.Z., S.L.-T., V.J., R.M.A., M.P.D., S.V., A.S., G.R.W., G.M.L., D.W., E.R.M., and E.M.; funding acquisition, E.R.M.; supervision, E.R.M.; statistics, S.Z. and D.W.
Author Disclosure Statement
E.A.S. reports personal fees from Bayer, AbbVie, ObsEva, Myovant, UpToDate, Med Learning Group, PeerView, and PER outside the submitted work and an issued patent “Methods and Compounds for Treatment of Abnormal Uterine Bleeding” 6440445. S.L.-T. reports grants from Bayer and personal fees from Allergan Pharma and UpToDate outside the submitted work. V.J. reports grants from Acessa Health outside the submitted work. M.P.D. reports grants from AbbVie, Bayer, and ObsEva outside the submitted work. E.R.M. reports personal fees from AbbVie, Merck, Allergan, and Bayer outside the submitted work. E.M. reports consultant work for Allergan outside the submitted work. All other authors have nothing to disclose.
Funding Information
Grant number P50HS023418 from the AHRQ supported this study with funding provided by the PCORI under a memorandum of understanding number 2013-001.
Supplementary Material
References
- 1. Sohn G, Cho S, Kim Y, Cho C, Kim M, Lee S. Current medical treatment of uterine fibroids. Obstet Gynecol Sci 2018;61:192–201. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2. Laughlin S, Stewart E. Uterine leiomyomas: Individualizing the approach to a heterogeneous condition. Obstet Gynecol 2011;117:396–403. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3. Wegienka G, Baird D, Hertz-Picciotto I, et al. Self-reported heavy bleeding associated with uterine leiomyomata. Obstet Gynecol 2003;101:431–437. [DOI] [PubMed] [Google Scholar]
- 4. Zimmerman A, Bernuit D, Gerlinger C, Schaefers M, Geppert K. Prevalence, symptoms and management of uterine fibroids: An international internet-based survey of 21,746 women. BMC Womens Health 2012;12:1–11. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5. Fuldeore M, Yang H, Soliman A, Winkel C. Healthcare utilization and costs among women diagnosed with uterine fibroids: A longitudinal evaluation for 5 years pre- and post-diagnosis. Curr Med Res Opin 2015;31:1719–1731. [DOI] [PubMed] [Google Scholar]
- 6. Herve F, Katty A, Queval I, Solignac C. Impact of uterine fibroids on quality of life: A national cross-sectional survey. Eur J Obstet Gynecol Reprod Biol 2018;229:32–37. [DOI] [PubMed] [Google Scholar]
- 7. Soliman A, Margolis M, Castelli-Haley J, Fuldeore M, Owens C, Coyne K. Impact of uterine fibroid symptoms on health-related quality of life of US women: Evidence from a cross-sectional survey. Curr Med Res Opin 2017;33:1971–1978. [DOI] [PubMed] [Google Scholar]
- 8. Ghant M, Sengoba K, Recht H, Cameron K, Lawson A, Marsh E. Beyond the physical: A qualitative assessment of the burden of symptomatic uterine fibroids on women's emotional and psychosocial health. J Psychosom Res 2015;78:499–503. [DOI] [PubMed] [Google Scholar]
- 9. Spies J, Coyne K, Guaou Guaou N, Boyle D, Skyrnarz-Murphy K, Gonzalves S. The UFS-QOL, a new disease-specific symptom and health-related quality of life questionnaire for leiomyomata. Obstet Gynecol 2002;99:290–300. [DOI] [PubMed] [Google Scholar]
- 10. Borah B, Nicholson W, Bradley L, Stewart E. The impact of uterine leiomyomas: A National Survey of Affected Women. Am J Obstet Gynecol 2013;209:319..e1–319.e20. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11. Shen T, Yang C, Huang Y, Lin C, Sung F. Risk of depression in patients with uterine leiomyoma: A nationwide population-based cohort study. J Affect Disord 2017;213:126–130. [DOI] [PubMed] [Google Scholar]
- 12. Diaz O, Guendelman S, Kuppermann M. Subjective social status and depression symptoms: A propsective study of women with noncancerous pelvic problems. Womens Health Issues 2014;24:649–655. [DOI] [PubMed] [Google Scholar]
- 13. Carlson K, Miller B, Fowler FJ. The Main Women's Health Study: II. Outcomes of nonsurgical management of leiomyomas, abnormal bleeding, and chronic pelvic pain. Obstet Gynecol 1994;83:566–572. [DOI] [PubMed] [Google Scholar]
- 14. Stewart E, Lytle B, Thomas L, et al. The Comparing Options for Management: PAtient-centered REsults for Uterine Fibroids (COMPARE-UF) registry: Rationale and design. Am J Obstet Gynecol 2018;219:e1–e10. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15. Wallace K, Zhang S, Thomas L, et al. Comparative effectiveness of hysterectomy versus myomectomy on 1-year health-related quality of life in women with uterine fibroids. Fertil Steril 2020;113:615–623. [DOI] [PubMed] [Google Scholar]
- 16. Nicholson W, Wegienka G, Zhang S, et al. Short-term health-related quality of life after hysterectomy versus myomectomy for symptomatic fibroids. Obstet Gynecol 2019;134:261–269. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17. Laughlin-Tommaso S, Lu D, Thomas L, et al. Short-term quality of life after myomectomy for uterine fibroids from the COMPARE-UF Fibroid Registry. Am J Obstet Gynecol 2020;222:345..e1–345.e22. [DOI] [PubMed] [Google Scholar]
- 18. Hauser G, Huber I, Keller P, Lauritzen C, Schneider H. Evaluation of climacteric symptoms (Menopause Rating Scale [MRS]). Zentralbl Gynakol 1994;116:16–23. [PubMed] [Google Scholar]
- 19. EuroQol Group. EuroQol—A new facility for the measurement of health-related quality of life. Health Policy 1990;16:199–208. [DOI] [PubMed] [Google Scholar]
- 20. Chotai S, Khan I, Nian H, et al. Utility of anxiety/depression domain of EQ-5D to define psychological distress in spine surgery. World Neurosurg 2019;126:e1075–e1080. [DOI] [PubMed] [Google Scholar]
- 21. Crick K, Al Sayah F, Ohinmaa A, Johnson A. Responsiveness of the anxiety/depression dimension of the 3- and 5-level versions of the EQ-5D in assessing mental health. Qual Life Res 2018;27:1625–1633. [DOI] [PubMed] [Google Scholar]
- 22. Seaman S, Hughes R. Relative efficiency of joint-model and full-conditional-specification multiple imputation when conditional models are compatible: The general location model. Stat Methods Med Res 2018;27:1603–1614. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23. Kayhan F, Alptekin H, Kayhan A. Mood and anxiety disorders in patients with abnormal uterine bleeding. Eur J Obstet Gynecol Reprod Biol 2016;199:192–197. [DOI] [PubMed] [Google Scholar]
- 24. Estes S, Huisingh C, Chiuve S, Petruski-Ivleva N, Missmer S. Depression, anxiety, and self-directed violence in women with endometriosis: A retrospective matched cohort study. Am J Epidemiol 2021;190:843–852. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25. Facchin F, Barbara G, Saita E, et al. Impact of endometriosis on quality of life and mental health: Pelvic pain makes the difference. J Psychosom Obstet Gynaecol 2015;36:135–141. [DOI] [PubMed] [Google Scholar]
- 26. Brody DJ, Pratt LA, Hughes JP. Prevalence of depression among adults aged 20 and over: United States, 2013–2016. NCHS Data Brief 2018;303:1–8. [PubMed] [Google Scholar]
- 27. Lee H, Kim S, Park E. Psychiatric outcomes after hysterctomy in women with uterine myoma: A population-based retrospective study. Arch Womens Ment Health 2017;20:487–494. [DOI] [PubMed] [Google Scholar]
- 28. Dilek S, Ertunc D, Tok E, Cimen R, Doruk A. The effect of myomectomy on health-related quality of life of women with myoma uteri. J Obstet Gynaecol Res 2010;36:364–369. [DOI] [PubMed] [Google Scholar]
- 29. Haan Y, Diemer F, Van Der Woude L, Van Montfrans G, Oehlers G, Brewster L. The risk of hypertension and cardiovascular disease in women with uterine fibroids. J Clin Hypertens 2018;20:718–726. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 30. Wise L, Palmer J, Stewart E, Rosenberg L. Polycystic ovary syndrome and risk of uterine leiomyomata. Fertil Steril 2007;87:1108–1115. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 31. Jackson C, Pathirana T, Gardiner P. Depression, anxiety and risk of hypertension in mid-aged women: A prospective longitudinal study. J Hypertens 2016;34:1959–1966. [DOI] [PubMed] [Google Scholar]
- 32. Hart R, Doherty D. The potential implications of a PCOS diagnosis on a woman's long-term health using data linkage. J Clin Endocrinol Metab 2015;100:911–919. [DOI] [PubMed] [Google Scholar]
- 33. Sahle B, Chen W, Melaku Y, Akombi B, Rawal L, Renzaho A. Association of psychosocial factors with risk of chronic diseases: A nationwide longitudinal study. Am J Prev Med 2020;58:e39–e50. [DOI] [PubMed] [Google Scholar]
- 34. Wise L, Li S, Plamer J, Rosenberg L. Depressive symptoms and risk of uterine leiomyomata. Am J Obstet Gynecol 2015;212:617..e1–617.e10. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 35. Mutambudzi M. Association between workplace psychosocial factors and mental health in Black, Hispanic and White women: Cross-sectional findings from the National Health Interview survey. Womens Health 2017;57:1129–1144. [DOI] [PubMed] [Google Scholar]
- 36. Souza JD, Yap B, Wroblewski K, et al. Measuring financial toxicity as a clinically relevant patient-reported outcome: The Validation of the Comprehensive Score for Financial Toxicity (COST). Cancer 2017;123:476–484. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 37. Knudsen N, Wernecke K, Siedentopf F, David M. Fears and concerns of patients with uterien fibroids—A survey of 807 women. Geburtshilfe Frauenheilkd 2017;77:976–983. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 38. Vines A, Ta M, Esserman D. The association between self-reported major life events and the presence of uterine fibroids. Womens Health Issues 2010;20:294–298. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 39. Azcarate P, Zhang A, Keyhani S, Steigerwald S, Ishida J, Cohen B. Medical reasons for marijuana use, forms of use, and patient perception of physician attitudes among the US population. J Gen Intern Med 2020;35:1979–1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 40. Brazier J, Connell J, Papajoannou D, et al. A systematic review, psychometric analysis and qualitative assessment of Generic Preference-Based Measures of Health in Mental Health Populations and the estimation of mapping functions from widely used specific measures. Health Technol Assess 2014;18:vii–viii, xiii–xxv, 1–188. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 41. Connell J, O'Cathain A, Brazier J. Measuring quality of life in mental health: Are we asking the right questions? Soc Sci Med 2014;120:12–20. [DOI] [PMC free article] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.