Shannon K. Laughlin-Tommaso

Epidemiology of Uterine Fibroids: From Menarche to Menopause.

Uterine leiomyomata (UL) have a substantial impact on womens health, but relatively few studies have identified opportunities for primary prevention of these neoplasms. Most established risk factors are not modifiable, including premenopausal age, African ancestry, age at menarche, and childbearing history. The main challenge in studying UL is that a large proportion of tumors are asymptomatic. Herein, we review the epidemiology of UL from published studies to date. We highlight the advantages of ultrasound screening studies and the ways in which their innovative methods have helped clarify the etiology of disease. We conclude with a discussion of promising new hypotheses.

Unilateral oophorectomy results in compensatory follicular recruitment in the remaining ovary at time of ovarian stimulation for in vitro fertilization.

OBJECTIVE To assess the effect of unilateral oophorectomy (UO) by assessing ovarian reserve (OVR) and the response to gonadotropin stimulation in women with UO undergoing in vitro fertilization (IVF) compared with the response of the ipsilateral ovary of women without UO. DESIGN Historical cohort study. SETTING Academic fertility clinic. PATIENT(S) Fifty-one women with single ovary compared with a referent group with both ovaries in a 1:2 fashion. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Day-3 follicle-stimulating hormone (FSH), estradiol, and antral follicle counts as measures of OVR, and IVF outcomes including number of follicles aspirated and oocytes retrieved. RESULT(S) The baseline demographics and serum markers of OVR were not different. Referent women had greater follicular yield and oocyte numbers when compared with women with UO; however, when compared with the ipsilateral ovary of the referents, women with UO had a higher antral follicle count and greater follicle and oocyte numbers. In multivariate analyses, the ovary from women with UO was more likely to yield more than the median number of follicles and oocytes than the ipsilateral ovary in referent women. Live-birth rates in both groups were similar. CONCLUSION(S) Our results suggest that the remaining ovary appears to compensate in follicular yield after UO in women, confirming the animal data. Women with UO can be reassured and appropriately counseled regarding IVF.

Cardiovascular risk factors and diseases in women undergoing hysterectomy with ovarian conservation

Objective:This study aims to determine the association of preexisting cardiovascular risk factors and cardiovascular diseases with hysterectomy with bilateral ovarian conservation using a case-central design. Methods:Using the Rochester Epidemiology Project records-linkage system, we identified all Olmsted County, MN women who underwent hysterectomy with ovarian conservation between January 1, 1965 and December 31, 2002 (cases). Each case was age-matched (±1 y) with a randomly selected woman who resided in the county and did not undergo hysterectomy or oophorectomy before the index date (date of hysterectomy in her matched case). Using electronic codes, we identified cardiovascular risk factors (diabetes, hypertension, hyperlipidemia, obesity, metabolic syndrome, and polycystic ovary syndrome) and cardiovascular diseases (coronary artery disease, congestive heart failure, myocardial infarction, and stroke) that occurred before the index date. Analyses were stratified by age at hysterectomy and indication for surgical operation. Results:During the study period, 3,816 women underwent hysterectomy with ovarian conservation for a benign indication. Preexisting hyperlipidemia, obesity, and metabolic syndrome were significantly more frequent in cases than in controls in univariable analyses. In multivariable analyses, obesity remained significantly associated overall, for nearly all age groups, and across all indications. Stroke was significantly more frequent in cases than in controls among women younger than 36 years. Congestive heart failure and stroke were significantly less common in cases than in controls among women older than 50 years. Conclusions:Hysterectomy with ovarian conservation is associated with cardiovascular risk factors, particularly obesity. Obesity may contribute to underlying gynecologic conditions leading to hysterectomy; however, surgical selection may also play a role.

Combined endometrial ablation and levonorgestrel intrauterine system use in women with dysmenorrhea and heavy menstrual bleeding: Novel approach for challenging cases

STUDY OBJECTIVE To evaluate the feasibility and impact of levonorgestrel intrauterine system (LNG-IUS) on treatment failure after endometrial ablation (EA) in women with heavy menstrual bleeding (HMB) and dysmenorrhea at 4 years. DESIGN Cohort study (Canadian Task Force II-2). SETTING An academic institution in the upper Midwest. PATIENTS All women with HMB and dysmenorrhea who underwent EA with combined placement of LNG-IUS (EA/LNG-IUS cohort, 23 women) after 2005 and an historic reference group from women who had EA alone (EA cohort, 65 women) from 1998 through the end of 2005. INTERVENTION Radiofrequency EA, thermal balloon ablation, and LNG-IUS. MEASUREMENTS AND MAIN RESULTS The primary outcome was treatment failure defined as persistent pain, bleeding, and hysterectomy after EA at 4 years. The combined treatment failure outcome was documented in 2 patients (8.7%) in the EA/LNG-IUS group and 19 patients (29.2%) in the EA group with an unadjusted OR of .23 (95% CI, .05-1.08). After adjusting for known risk factors of failure, the adjusted OR was .19 (95% CI, .26-.88). None of the women who underwent EA/LNG-IUS had hysterectomy for treatment failure compared with 16 (24%) in the EA group (p = .009); postablation pelvic pain was documented in 1 woman (4.3%) in the EA/LNG-IUS group compared with 8 women (12.3%) in the EA group (p = .24). One woman in the EA/LNG-IUS group (4.3%) presented with persistent bleeding compared with 15 (23.1%) in the EA group (p = .059). Office removal of the intrauterine device was performed in 4 women with no complications. CONCLUSION LNG-IUS insertion at the time of EA is feasible and can provide added benefit after EA in women with dysmenorrhea and HMB.

Cervical neoplasia–related factors and decreased prevalence of uterine fibroids among a cohort of African American women

OBJECTIVE To investigate whether the previously reported inverse association between cervical neoplasia and uterine fibroids is corroborated. DESIGN Cross-sectional analysis of enrollment data from an ongoing prospective study of fibroid development. SETTING Not applicable. PATIENT(S) Self-reported data on abnormal Pap smear, colposcopy, and cervical treatment were obtained from 1,008 African American women ages 23-34 with no previous fibroid diagnosis and no reported history of human papillomavirus vaccination. Presence of fibroids was assessed at a standardized ultrasound examination. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) The association between the three cervical neoplasia-related variables and the presence of fibroids was evaluated with logistic regression to estimate age-adjusted and multivariable-adjusted odds ratios (aORs). RESULT(S) Of the analysis sample, 46%, 29%, and 14% reported a prior abnormal Pap smear, colposcopy, and cervical treatment, respectively. Twenty-five percent had fibroids at ultrasound. Those reporting cervical treatment had a 39% (aOR, 0.61; 95% confidence interval [CI] [0.38-0.96]) reduction in fibroid risk. Weak nonsignificant associations were found for abnormal Pap smear and colposcopy. CONCLUSION(S) Although a protective-type association of cervical neoplasia with uterine fibroids seems counterintuitive, a causal pathway is possible, and the findings are consistent with two prior studies. Further investigation is needed on the relationship between fibroids and cervical neoplasia and human papillomavirus-related mechanisms.

Periprocedural Outcomes Comparing Fibroid Embolization and Focused Ultrasound: a Randomized Controlled Trial and Comprehensive Cohort Analysis.

BACKGROUND: Uterine fibroids are a common problem for reproductive‐aged women, yet little comparative effectiveness research is available to guide treatment choice. Uterine artery embolization and magnetic resonance imaging–guided focused ultrasound surgery are minimally invasive therapies approved by the US Food and Drug Administration for treating symptomatic uterine fibroids. The Fibroid Interventions: Reducing Symptoms Today and Tomorrow study is the first randomized controlled trial to compare these 2 fibroid treatments. OBJECTIVE: The objective of the study was to summarize treatment parameters and compare recovery trajectory and adverse events in the first 6 weeks after treatment. STUDY DESIGN: Premenopausal women with symptomatic uterine fibroids seen at 3 US academic medical centers were enrolled in the randomized controlled trial (n = 57). Women meeting identical criteria who declined randomization but agreed to study participation were enrolled in a nonrandomized parallel cohort (n = 34). The 2 treatment groups were analyzed by using a comprehensive cohort design. All women undergoing focused ultrasound and uterine artery embolization received the same postprocedure prescriptions, instructions, and symptom diaries for comparison of recovery in the first 6 weeks. Return to work and normal activities, medication use, symptoms, and adverse events were captured with postprocedure diaries. Data were analyzed using the Wilcoxon rank sum test or χ2 test. Multivariable regression was used to adjust for baseline pain levels and fibroid load when comparing opioid medication, adverse events, and recovery time between treatment groups because these factors varied at baseline between groups and could affect outcomes. Adverse events were also collected. RESULTS: Of 83 women in the comprehensive cohort design who underwent treatment, 75 completed postprocedure diaries. Focused ultrasound surgery was a longer procedure than embolization (mean [SD], 405 [146] vs 139 [44] min; P <.001). Of women undergoing focused ultrasound (n = 43), 23 (53%) underwent 2 treatment days. Immediate self‐rated postprocedure pain was higher after uterine artery embolization than focused ultrasound (median [interquartile range], 5 [1–7] vs 1 [1–4]; P = .002). Compared with those having focused ultrasound (n = 39), women undergoing embolization (n = 36) were more likely to use outpatient opioid (75% vs 21%; P < .001) and nonsteroidal antiinflammatory medications (97% vs 67%; P < .001) and to have a longer median (interquartile range) recovery time (days off work, 8 [6–14] vs 4 [2–7]; P < .001; days until return to normal, 15 [10–29] vs 10 [10–15]; P = .02). There were no significant differences in the incidence or severity of adverse events between treatment arms; 86% of adverse events (42 of 49) required only observation or nominal treatment, and no events caused permanent sequelae or death. After adjustment for baseline pain and uterine fibroid load, uterine artery embolization was still significantly associated with higher opioid use and longer time to return to work and normal activities (P < .001 for each). Results were similar when restricted to the randomized controlled trial. CONCLUSION: Women undergoing uterine artery embolization have longer recovery times and use more prescription medications, but women undergoing focused ultrasound have longer treatment times. These findings were independent of baseline pain levels and fibroid load.

Alternatives to Hysterectomy : Management of Uterine Fibroids

Uterine fibroids are a common condition that can be debilitating and are the leading benign cause of hysterectomy. Women often live with the symptoms rather than choose hysterectomy, but survey studies have shown that work, social life, and physical activities are hindered by fibroid symptoms. Offering alternative therapies tailored to a womans symptoms will allow her to choose a treatment that fits her needs and to preserve her uterus and fertility. The minimally invasive treatment options have a faster recovery and lower surgical risk than hysterectomy, but may require reintervention. One pharmacologic treatment offers short-term, intermittent therapy with lasting effects.

Association between patient characteristics and treatment procedure among patients with uterine leiomyomas

OBJECTIVE: To analyze the association between patient characteristics and the probability of undergoing any uterine-sparing procedure (endometrial ablation, myomectomy, and uterine artery embolization) compared with hysterectomy as the first uterine leiomyoma (index) procedure and the probability of undergoing a specific uterine-sparing procedure. METHODS: We conducted a retrospective analysis using a commercial insurance claims database containing more than 13 million enrollees annually. Based on the index procedure performed 2004–2009, women were classified into one of the four procedure cohorts. Eligible women were aged 25–54 years on the index date, continuously insured through 1-year baseline and 1-year follow-up, and had a baseline uterine leiomyoma diagnosis. Logistic regression was used to assess the association between patient characteristics and leiomyoma procedure. RESULTS: The study sample comprised 96,852 patients (endometrial ablation=12,169; myomectomy=7,039; uterine artery embolization=3,835; and hysterectomy=73,809). Patient characteristics associated with undergoing any uterine-sparing procedure compared with hysterectomy included health maintenance organization health plan enrollment, Northeast region residence, the highest income and education quintiles based on zip code, an age–race interaction, and baseline diagnoses including menstrual disorders, pelvic pain, anemia, endometriosis, genital prolapse, and infertility. Among those who had a uterine-sparing procedure, characteristics associated with undergoing uterine artery embolization or endometrial ablation compared with myomectomy included increasing age, being from the Midwest relative to the Northeast, and certain baseline conditions including menstrual disorder, pelvic pain, endometriosis, and infertility. CONCLUSION: Both clinical and nonclinical factors were associated with the receipt of alternatives to hysterectomy for uterine leiomyomas in commercially insured women.

Asymptomatic Thickened Endometrium in Postmenopausal Women: Malignancy Risk

STUDY OBJECTIVE To assess the diagnostic findings and determine the frequency of malignancy in postmenopausal women evaluated by office hysteroscopy for a thickened endometrium without bleeding. DESIGN Retrospective cohort (Canadian Task Force classification II-B). SETTING Academic medical center in the Midwestern United States. PATIENTS Over 3600 women underwent an office hysteroscopy between January 1, 2007, and October 20, 2011, for abnormal uterine bleeding or an abnormal ultrasound. Of these, 154 postmenopausal women had a thickened endometrium (>4 mm) and no bleeding. INTERVENTIONS Flexible office hysteroscopy using a 3.1-mm scope with saline as the distending media was performed for clinical reasons, and results were captured within a research database. MEASUREMENTS AND MAIN RESULTS For the 154 women, the range of endometrial measurements was 4.2 to 28 mm (mean = 10.0 mm). Hysteroscopy diagnoses included 93 patients with polyps, 19 with myomas or uterine synechiae, and 34 with benign-appearing endometrium. Nine hysteroscopies were inadequate because of poor visualization (n = 1), cervical stenosis (n = 6), or patient discomfort (n = 2). Endometrial biopsies (EMBs) were performed in 109 patients, and none were found to have cancer or an atypical endometrium. Six had simple hyperplasia without atypia, and their endometrial measurements were within the range of the patients in our study who had a benign endometrium (5-15 mm, mean = 10.3). Of the women with a polyp, 73 (78.4%) subsequently underwent polypectomy. On final pathology, 1 had cancer (endometrial measurement = 24 mm), and 1 had complex hyperplasia with atypia (endometrial measurement = 17 mm). EMBs performed in the office for these 2 patients showed an insufficient endometrium and inactive endometrium, respectively. CONCLUSION Cancer and atypia can occur in asymptomatic women. Endometrial thickness was 17 mm or greater in 2 cases, and EMBs performed in the office were inconsistent with the final diagnosis. Hysteroscopy is important when ultrasound and EMB do not agree. Polypectomy may be indicated even in asymptomatic women, but further studies regarding an endometrial measurement threshold or polyp size are warranted.

Disparities in Fibroid Incidence, Prognosis, and Management

Health disparities in fibroid prevalence, prognosis, and treatment exist for underserved women. Access to fibroid treatment alternatives can have significant effect on choices and outcomes of fibroid disease.