Fibroid regression was common with over 70% of women with live births having fibroids shrink more than 50% in volume between early gestation and 3–6 months postpartum. We found an association between fibroid regression and postpartum progestin use, with users showing significantly less regression, but no associations were found between fibroid regression and use of other hormonal contraceptives, cesarean delivery, fever, or breastfeeding. We also found that miscarriages were associated with a decrease in fibroid regression, and the later the miscarriage the greater the regression. Gestational age was not important among live births.
Our study has the advantage of systematic ultrasound screening for fibroids that was conducted very early in pregnancy; studies based on self-reported fibroid status have too much misclassification of case status to assess fibroid regression. Once the protocol was fully implemented, we also had a high retention rate for women into the postpartum period, including women returning after miscarriage, so that selection issues are less likely to bias our results. Timing of the ultrasound in early pregnancy and postpartum period did not differ between contraceptive groups nor affect the outcome of regression. As the first large prospective study to follow fibroids through pregnancy, our findings provide an investigation of factors that may affect the inverse relationship between parity and fibroids that has been reported for decades.3–5
We had small numbers for examining some of the postpartum factors. Additionally, while we collected infection data proximal to the events, more severe infections around delivery (chorioamnionitis and endometritis) are subject to poor recall during a stressful time. Ideally, we would capture infections around the time of birth either prospectively or through medical record review.
The timing of fibroid regression (during pregnancy, at birth, or during the postpartum period) and the mechanisms involved are not known. Fibroid shrinkage during pregnancy is difficult to study. As the fetus develops, it is more difficult to measure fibroids. Burbank suggested that birth and placental delivery, with its associated hypoxia, would induce regression.6
Mechanical changes during the delivery and the following three months may also play a role. Negishi found a difference in the amount of uterine involution between cesarean and vaginal deliveries.7
Thus, we anticipated differences in fibroid regression between those with cesarean and those with vaginal delivery, but we did not see any. Marginally fewer of those with cesarean deliveries exhibited fibroid regression compared with those having vaginal deliveries (68% vs 74%), but this difference is not significant.
Baird and Dunson (2003) suggested that the postpartum processes involved with uterine involution would induce fibroid regression. Many mechanisms are involved in uterine involution including mechanical forces, vascular changes, hormonal changes, hypoxia, apoptosis, and tissue development. The factors we examined were possible modulators of these biological processes. However, only progestin use was significantly associated with fibroid regression.
Both biochemical and clinical evidence support a role of progesterone in fibroid growth outside of pregnancy.11
High cellularity and mitotic activity were seen in women treated with progestin agents and during the secretory phase of the menstrual cycle when progesterone is highest. Inhibiting progesterone with agents such as RU-486 has shown reduction in size. Thus, inhibition of fibroid regression by progestin-only medication in the postpartum period is plausible. Progestin-only contraception can be used during breastfeeding, so most users also reported breastfeeding. However, a progestin effect remained regardless of breastfeeding level. On the other hand, the breastfeeding results could have been influenced by progestin-only contraceptive effects. However, estimates for fibroid shrinking associated with breast-feeding changed little after excluding the progestin users.
We were surprised that duration of breast feeding, with its suppression of ovarian steroid production, was not associated with fibroid regression and that the direction of effect was opposite of that predicted. However, a lack of protective effect from breastfeeding is consistent with existing epidemiologic data. Studies that have sought to evaluate the effect of breastfeeding on fibroid risk to explain the inverse relationship of parity with fibroids, do not show significant protective effects of breastfeeding.3 12
One explanation may be that a recent study demonstrated oxytocin induced fibroid growth, which may counteract the hormonal suppression during breastfeeding.13
Our other null findings do not support hypotheses based on analogy with the literature. One study reported that uterine involution was not as complete by 3 months postpartum in women with cesarean deliveries compared to those with vaginal delivery, but as noted above, we found no effect of cesarean delivery on fibroid regression. Similarly, animal studies have shown a delay in uterine involution secondary to subclinical infection and severe endometritis (but not mild endometritis);14–15
we found no association with fibroid regression for infections or antibiotic use, while fever appeared to be marginally important. Our infection data was not limited to nor specified endometritis, so more detailed future study is needed. Early onset of ovulation increased involution time in animal studies, but we did not see associations with early return of menses.15
Small sample size may play a role in our findings.
Among those with live births, post-date delivery was associated with inhibition of fibroid shrinking, but there was no trend across gestational age. However, later miscarriage was associated with greater regression which may indicate greater shift from pregnancy hormone levels to non-pregnancy state when compared with earlier loss. Whether the mechanical changes from a longer, and usually larger, pregnancy directly affect the fibroid regression process or there is a common cause is unknown. Further data would be needed.
There is much we need to learn about the natural history of fibroids, as they are dynamic tumors that grow and shrink in response to events in the reproductive years. The postpartum events hypothesized to affect fibroid regression were not found except for progestin use. The current understanding of progesterone's effects on fibroids support our findings. Further research needs to determine the effect of all progestin treatments, whether for contraception or menorrhagia, on fibroid growth. Given the importance of contraception during the postpartum period, our findings regarding progestin contraception need to be replicated and the length of a vulnerable window elucidated before formal recommendations are formulated.