Objective
Many fibroids regress with pregnancy or postpartum involution. We sought to identify factors that might inhibit or enhance this natural regression.
Study Design
We used a prospective cohort of women with fibroids (n = 494) determined by ultrasound screening during the early first trimester identified from the Right from the Start study. Ultrasounds were repeated 3-6 months postpartum (n = 279). Logistic regression analyses were used to identify factors associated with fibroid regression (>50% reduction in volume).
Results
Postpartum progestin users had significantly less fibroid regression ( P = .01), whereas there was no association for combined estrogen-progestin use. Cesarean delivery and fever (hypothesized to inhibit regression) and breast feeding (hypothesized to enhance regression) were not associated with fibroid regression.
Conclusion
Progestin use in the postpartum period may limit regression of fibroids, consistent with prior literature on progesterone’s role in fibroid development. Research into progestin-only treatments in critical reproductive periods is needed.
Fibroids are common in pregnant women and are eliminated or decreased in size over the course of the pregnancy and/or the time of postpartum uterine involution. We previously reported that pregnancy eliminated 36% of fibroids, regardless of the initial fibroid size. This pregnancy-related fibroid regression may account for the inverse association between parity and fibroid risk seen in many epidemiologic studies.
The complex mechanical and cellular mechanisms related to birth and uterine involution may play a role in fibroid elimination and shrinking. Factors that affect the involution process may limit or enhance natural regression. For instance, breast feeding can delay the postpartum return of menstrual cycles; the resulting decrease in ovarian steroids may enhance the regression process. Delivery type (vaginal vs cesarean) may also affect involution as suggested by an ultrasound-based study that found that cesarean delivery is associated with larger uterine size than vaginal delivery at 1 and 3 months’ postpartum. Thus, we hypothesized that breastfeeding would enhance fibroid regression, and that cesarean delivery and postpartum infection would inhibit fibroid regression. We also examined other factors, including postpartum hormonal contraception and length of gestation.
Materials and Methods
This analysis was conducted as part of an ongoing prospective study of pregnancy, Right from the Start . The overall cohort study has collected data in North Carolina, Tennessee, and Texas. Methods have been described previously. Briefly, eligibility criteria included age 18 or older, enrollment before 13 completed weeks gestation by last menstrual period, intention to carry pregnancy to term, fluency in English or Spanish, and plans to remain in the study area for at least 18 months. Women were recruited from the community early in pregnancy or when planning a pregnancy. Institutional review boards at all sites gave approval, and written informed consent was obtained from each participant.
An early pregnancy endovaginal ultrasound screened systematically for uterine fibroids of at least 0.5 cm in largest diameter. Of the 494 study participants with fibroids, 294 participated in the postpartum ultrasound, which was scheduled between 3 and 6 months after delivery. Fifteen women not completing the postpartum interview were excluded, leaving 235 women who had a live birth and 44 who had a miscarriage. The primary reason for not completing a postpartum ultrasound was that the postpartum ultrasound was not added to the study until 2002, although enrollment for Right from the Start began in 2000. Systematic follow-up with incentive to attend the postpartum ultrasound began in 2005. Women who completed the postpartum ultrasound were on average 1 year older than those who did not complete it, but there was no difference in ethnicity or parity.
The data collection from ultrasounds has been described in detail. Briefly, fibroid number, type of the largest fibroid (submucous, subserous, intramural, or pedunculated), and location (fundus, corpus, cervix) were documented by sonographers. Triplicate measures of largest diameter in 3 dimensions were used to estimate fibroid volume using the prolate ellipsoid formula. For more than 1 fibroid, total fibroid volume was calculated by summing all of the individual fibroid volumes. Fibroid images were saved initially as still photos and later as digital images on CD-ROM for review by study physicians (K.H., S.L.). Body mass index (BMI) was calculated from height and weight measured at the study ultrasound.
Demographics including race/ethnicity, age, parity, education, income, and smoking status were gathered during a screening interview and first trimester computer-assisted telephone interview. Pregnancy and postpartum factors were assessed by postpartum computer-assisted telephone interview performed between 3 and 6 months’ postpartum. Variables, such as menses, gestational age, and breastfeeding duration were categorized for analysis so that extremes of the distribution could be included.
Gestational age at the time of delivery was categorized into 4 levels (<37 weeks, 37-39 weeks, 39-41 weeks, and 41+ weeks), calculated from last menstrual period adjusted by early ultrasound if dates were inconsistent. Delivery route (cesarean or vaginal) was self-reported. Intrapartum or postpartum fever was assessed by self-report on postpartum questionnaire. Antibiotic use at the time of delivery or in the postpartum period was asked as 2 separate questions and combined for data analysis.
The participants were asked about the duration of regular breastfeeding defined as suckling or pumping at least 4 times per day. A 3-level variable was created (0-29 days, 30-89 days, and ≥90 days). Women who were breastfeeding at 90 days but less than 4 times per day were put into the second category. The information on timing of the return of menses was categorized into ≤60 days postpartum, 61-90 days and >90 days. Lastly, participants were asked about up to 3 types of contraception they used postpartum. We created mutually exclusive variables for progestin-only use (including mini-pill, levonorgestrel intrauterine system, and depot medroxyprogesterone), estrogen-progestin combined (including the contraceptive ring and patch), and nonhormonal contraception. The reference group for all 3 was no contraception. Eleven percent of women had more than 1 type of contraception within the first 90 days. For users of both nonhormonal and hormonal agents (n = 23), the contraceptive method assigned was the hormonal one. If both progestin and combined hormone use were used (n = 2), the category assigned was progestin use because it was used first, and dropping those 2 had little effect on results.
The outcome variable was defined by a >50% decrease in total fibroid volume. This cutoff was chosen because it is above expected measurement error or likely first trimester growth. Fibroids that were no longer detectable on the postpartum ultrasound contributed zero postpartum volume giving a 100% decrease in volume. Volume reduction of ≤50% or volume increase at the postpartum ultrasound were combined as the referent.
Data analysis was performed using Stata 10.0 (StataCorp, College Park, TX). Logistic regression models were used to evaluate the associations of demographic, fibroid, pregnancy, and postpartum factors of interest with fibroid regression. Each pregnancy and postpartum factor of interest was examined separately controlling for black ethnicity and presence of any submucosal fibroid (the only demographic or fibroid characteristic significantly related to fibroid regression). We used 2-sided P values with an alpha equal to .05. The primary analysis was based on the 235 women with live births. An additional analysis also included the 44 women who had an ultrasound 3-6 months after a miscarriage to compare fibroid regression for miscarriages to live births.
Results
Live birth cohort
The majority of the cohort was white; 31% were black. Nearly half were between 30 and 35 years old and just under half were nulliparous ( Table 1 ). Most had only 1 fibroid (n = 166, 71%). Seventy-two percent of the women (n = 168) showed fibroid regression >50%. Twelve percent (n = 29) had fibroid volume changes of 50% or less. The rest (n = 38) showed an increase in fibroid volume with 10% showing more than a 50% increase.
| Variable | n | Percent | Unadjusted OR (95% CI) | Adjusted OR a (95% CI) | P (adj) |
|---|---|---|---|---|---|
| Ethnicity b | |||||
| White | 134 | 57.3 | Referent | Referent | Ref |
| Black | 72 | 30.8 | 0.50 (0.27–0.93) | 0.47 (0.25–0.88) | .02 |
| Hispanic | 12 | 5.1 | 1.70 (0.35–8.15) | 1.75 (0.36–8.45) | .5 |
| Other | 16 | 6.8 | 4.76 (0.60–37.6) | 5.00 (0.63–39.5) | .1 |
| Missing | 1 | ||||
| Age | |||||
| <30 | 68 | 28.9 | Referent | Referent | Ref |
| 30-35 | 108 | 46.0 | 0.72 (0.36–1.42) | 0.67 (0.33–1.35) | .3 |
| ≥35 | 59 | 25.1 | 0.98 (0.44–2.18) | 0.93 (0.41–2.15) | .9 |
| Missing | 0 | ||||
| Parity c | |||||
| Nulliparous | 112 | 47.9 | Referent | Referent | Ref |
| Primiparous | 86 | 36.8 | 0.95 (0.51–1.76) | 1.00 (0.53–1.87) | > .99 |
| Multiparous | 36 | 15.4 | 1.01 (0.44–2.33) | 1.17 (0.49–2.78) | .7 |
| Missing | 1 | ||||
| Body mass index | |||||
| Under or normal | 125 | 53.2 | Referent | Referent | Ref |
| Overweight | 43 | 18.3 | 0.52 (0.24–1.09) | 0.60 (0.28–1.29) | .2 |
| Obese | 67 | 28.5 | 0.67 (0.35–1.30) | 0.87 (0.43–1.78) | .7 |
| Missing | 0 | ||||
| Education | |||||
| ≤ High school | 20 | 8.5 | Referent | Referent | Ref |
| Some college | 39 | 16.6 | 0.67 (0.20–2.24) | 0.85 (0.24–3.02) | .8 |
| ≥4 y college | 176 | 74.9 | 0.88 (0.30–2.56) | 0.83 (0.27–2.58) | .7 |
| Missing | 0 | ||||
| Income | |||||
| ≤$40,000 | 47 | 20.6 | Referent | Referent | Ref |
| $40,001–80,000 | 90 | 39.5 | 1.15 (0.53–2.51) | 0.90 (0.39–2.06) | .8 |
| >$80,000 | 91 | 39.9 | 1.06 (0.49–2.30) | 0.85 (0.37–1.94) | .7 |
| Missing | 7 | ||||
| Smoking status | |||||
| Never | 182 | 77.8 | Referent | Referent | Ref |
| Quit >4 mo prior | 38 | 16.2 | 1.30 (0.58–2.93) | 1.13 (0.49–2.61) | .7 |
| Current/quit within 4 mo | 14 | 6.0 | 0.73 (0.23–2.27) | 0.68 (0.21–2.25) | .5 |
| Missing | 1 | ||||
| Total fibroid number | |||||
| 1 | 166 | 70.6 | Referent | Referent | Ref |
| 2+ | 69 | 29.4 | 0.58 (0.32–1.07) | 0.75 (0.40–1.42) | .4 |
| Missing | 0 | ||||
| Total fibroid volume | |||||
| ≤10 cm 3 | 37 | 15.9 | Referent | Referent | Ref |
| 10–30 cm 3 | 117 | 50.2 | 1.23 (0.54–2.78) | 1.31 (0.56–3.04) | .5 |
| >30 cm 3 | 79 | 33.9 | 0.91 (0.39–2.14) | 0.95 (0.39–2.33) | .9 |
| Missing | 2 | ||||
| Fibroid type d | |||||
| Submucous | 29 | 12.6 | 2.71 (0.86–8.47) | 3.13 (0.98–10.0) | .05 |
| Intramural | 93 | 40.4 | 1.06 (0.57–1.98) | 1.06 (0.56–2.01) | .9 |
| Subserous | 96 | 41.7 | Ref | Ref | Ref |
| Pedunculated | 12 | 5.2 | 0.61 (0.18–2.07) | 0.67 (0.19–2.35) | .5 |
| Missing | 5 | ||||
| Fibroid location | |||||
| Cervix | 33 | 14.2 | 1.86 (0.71–4.89) | 1.84 (0.69–4.94) | .2 |
| Corpus | 123 | 52.8 | Ref | Ref | Ref |
| Fundus | 77 | 33.1 | 0.91 (0.49–1.70) | 0.98 (0.52–1.85) | .9 |
| Missing | 2 |
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