Cabergoline: An Effective Intervention for Unwanted Lactation After Second Trimester Uterine Evacuation

By Rebecca H. Allen, MD, MPH, Editor

SYNOPSIS: In this double-blind, randomized controlled trial among 73 patients between 18 and 28 weeks’ gestation undergoing dilation and evacuation or induction of labor for abortion or fetal demise, a one-time dose of 1 mg of cabergoline compared to placebo reduced post-delivery lactation-related breast symptoms in the treatment arm (27.8% vs. 97.0%; relative risk, 0.05; 95% confidence interval, 0.01-0.33).

SOURCE: Henkel A, Johnson SA, Reeves MF, et al. Cabergoline for lactation inhibition after second-trimester abortion or pregnancy loss. Obstet Gynecol 2023;141:1115-1123.

Lactation, breast engorgement, and breast tenderness can occur after a second-trimester pregnancy loss or induced abortion and are bothersome to patients.¹ The authors of this study sought to determine whether cabergoline, a dopamine agonist that is U.S. Food and Drug Administration (FDA)-approved to treat hyperprolactinemic disorders, could suppress lactation in this clinical scenario.

This was a double-blind, placebo-controlled, randomized trial conducted at Stanford University from April 2021 to June 2022. The authors enrolled adult English- or Spanish-speaking individuals at 18 0/7 to 28 0/7 weeks’ gestation who were admitted for treatment of fetal demise or induced abortion. Exclusion criteria were history of mastectomy, currently breastfeeding, currently receiving another dopamine agonist or antagonist, or a contraindication to cabergoline. Patients either underwent dilation and evacuation (D&E) or induction of labor. Participants were randomized to 1 mg of cabergoline or placebo within four hours of the procedure or delivery. The patients then filled out online surveys at baseline and on days 2, 3, 4, 7, and 14 concerning breast symptoms using the Breast Symptom Inventory (four domains: engorgement, milk leakage, tenderness, and need for pain relief). The primary outcome was breast symptoms on day 4, since that is when postpartum engorgement of the breast peaks after stage two of lactogenesis. A subset of participants had prolactin levels measured on days 0, 4, 7, and 14.

After screening 150 patients, 73 were enrolled, with 26 not meeting inclusion criteria and 51 declining participation. The median age of the sample was 33 years (range 20-43 years) and the median gestational age was 22 weeks (range 18-26 weeks) with about one-half of the sample (56%) being nulliparous. Baseline breast symptoms were equivalent between the two groups. On day 4, fewer individuals in the cabergoline group reported breast symptoms compared to the placebo group (27.8% vs. 97.0%; relative risk, 0.05; 95% confidence interval, 0.01-0.33), which included all domains: breast engorgement, breast tenderness, milk leakage, and requiring pain relief. Additionally, on day 4, 2.8% of those randomized to cabergoline reported significant bother from the symptoms compared to 33.3% of the placebo group (P = 0.001). On day 4, in the sub-study, serum prolactin levels were 6.5 ng/mL ± 2.2 ng/mL in the cabergoline group compared to 18.0 ng/mL ± 5.9 ng/mL in the placebo group (P = 0.49). The most common side effects of constipation, headache, fatigue, and insomnia did not differ between the two groups.

COMMENTARY

Patients can experience bothersome breast symptoms after second trimester abortion or pregnancy loss, including the initiation of lactation. Patients often do not anticipate this and it can cause emotional distress.¹ Traditional management advice has included using tight-fitting bras, cold compresses, and nonsteroidal anti-inflammatory drugs for pain as well as avoiding any milk expression so that lactation stops. Prior data from 1990 showed that the dopamine antagonist bromocriptine reduced breast symptoms after second trimester abortion.² Cabergoline is a similar dopamine agonist that is FDA-approved for the treatment of hyperprolactinemic disorders. Although it has been studied for lactation suppression at term, it has not been well studied for this indication in the second trimester.³

The authors of this study are to be commended for investigating this intervention, since it has the potential to decrease patient distress after second trimester induced abortion or pregnancy loss. As a double-blind, placebo-controlled, randomized trial, the evidence for effectiveness is very high for cabergoline. The prolactin level sub-study offers further support for the biologic plausibility of the intervention. Furthermore, as a one-time dose, this is a simple intervention that can be accomplished prior to discharge if the patient desires. Nevertheless, the study was limited by small sample sizes in different gestational age groups. For example, whether the medication works as well at 18 weeks compared to 24 weeks was not evaluated. In addition, small differences in side effects would not be able to be detected. Therefore, further research should be conducted.

While we counsel our patients who are undergoing D&E or induction of labor for induced abortion or pregnancy loss about the possibility of breast symptoms afterward, we have not had any real effective intervention to offer. Now that this study has been published, there is an evidence-based remedy. I now will be incorporating this option into patient counseling prior to admission for uterine evacuation in the second trimester. I anticipate it can be given in the recovery room prior to discharge after D&E or after delivery if the patient is admitted for induction of labor.

REFERENCES

1. Hagey JM, Truong T, Deans EI. Breast symptoms after pregnancy loss and abortion: An observational study. Obstet Gynecol 2020;135:103S.
2. Andersen AN, Damm P, Tabor A, et al. Prevention of breast pain and milk secretion with bromocriptine after second-trimester abortion. Acta Obstet Gynecol Scand 1990;69:235-238.
3. Harris K, Murphy KE, Horn D, et al. Safety of cabergoline for postpartum lactation inhibition or suppression: A systematic review. J Obstet Gynaecol Can 2020;42:308-315.e20.