By Alexandra Morell, MD
Adjunct Instructor, Department of Obstetrics and Gynecology, University of Rochester Medical Center, Rochester, NY
SYNOPSIS: A randomized controlled trial demonstrated superior efficacy of cabergoline compared to pyridoxine (78% vs. 35%; P < 0.001) at suppression of lactation seven days after delivery.
SOURCE: Dayan-Schwartz A, Yefet E, Massalha M, et al. The efficiency of cabergoline vs pyridoxine for lactation inhibition — a randomized controlled trial. Am J Obstet Gynecol 2024;230:561.e1-561.8.
In the United States, approximately 84% of women have ever breastfeed, and 50% of women are exclusively breastfeeding at three months postpartum.1 Although breastfeeding does have several benefits for the mother and infant, some patients have contraindications to breastfeeding and others do not desire to breastfeed. Breast engorgement typically causes bilateral breast pain, firmness, and swelling related to interstitial edema and hyperemia.2 Up to 66% of patients who do not breastfeed experience moderate engorgement symptoms and up to 56% will experience severe symptoms.3 Nonpharmacologic methods, such as wearing supportive bras, fluid restriction, or use of ice packs or cold cabbage leaves, commonly are used for symptomatic management.4
Cabergoline is a dopamine agonist that stimulates pituitary lactotrophs and inhibits prolactin secretion, which previously has been shown to be well-tolerated and is a potential pharmacologic method of lactation suppression.5 Pyridoxine (vitamin B6) has a less well-known mechanism but is thought to act as a coenzyme in the conversion of dihydroxyphenylalanine into dopamine, leading to increased serum dopamine levels likely inhibiting prolactin secretion and inhibiting lactation.6
This randomized controlled trial compared the efficacy and adverse effects of cabergoline and pyridoxine for the treatment of lactation inhibition at a teaching hospital in Israel between December 2021 and September 2022. Postpartum patients not desiring to breastfeed and without contraindications to either cabergoline or pyridoxine were included. Exclusion criteria included patients with prior adverse reactions to either treatment or hypertensive disorders of pregnancy, including chronic hypertension, gestational hypertension, and preeclampsia. Participants were randomly allocated in a 1:1 ratio to receive either cabergoline (1 mg once if started within 24 hours of delivery or 0.25 mg twice a day for two days if started more than 24 hours after birth) or pyridoxine (200 mg three times a day for one week).
The participants completed questionnaires at four different time points during the first two weeks of enrollment (days 0, 2, 7, and 14). Questionnaires assessed breast engorgement and pain (scored on a five-point scale, with 0 representing no symptoms and 5 representing severe symptoms), milk leakage, adverse effects, conservative methods of lactation inhibition, mastitis, use of antibiotics, fever, and discontinuation of treatment. In addition, any new symptoms since starting the medication also were evaluated.
The primary outcome was success at inhibiting lactation or a score of 0 for both breast engorgement and pain on day 7. Secondary outcomes were to assess the efficacy of pyridoxine in treatment of lactation inhibition and evaluate other factors contributing to successful lactation inhibition. To achieve a statistical power of 90% and a two-sided alpha level of 0.05, an enrollment goal of 44 patients per group was necessary. For statistical analyses, chi-square or Fisher exact tests were used for categorical variables and Student’s t-test was used for continuous variables.
A total of 3,790 postpartum patients were screened for enrollment. Of these, 159 patients were eligible for enrollment and 70 patients declined to participate, resulting in 89 total participants randomized (n = 45 in the cabergoline group and n = 44 in the pyridoxine group). Baseline characteristics were similar between the two groups. One participant in the pyridoxine group was excluded from analysis after deciding to avoid pharmacologic management once enrolled. The analysis was performed using the intention-to-treat principle.
Cabergoline was superior to pyridoxine for lactation inhibition on day 2 and day 7. A score of 0 for breast pain or engorgement was noted in 64% of the cabergoline group vs. 31% of the pyridoxine group on day 2 (P = 0.001) and 78% in the cabergoline group vs. 35% in the pyridoxine group on day 7 (P < 0.001). No difference in score was noted on day 14 (91% in the cabergoline group vs. 92% in the pyridoxine group, P = 1).
Of note, nine patients receiving pyridoxine transitioned to or added cabergoline for symptom management secondary to treatment failure, decreasing the efficacy on day 7 to 28%. No difference in scores was observed between patients receiving different cabergoline doses on day 7 (79% for the 1-mg dose, 76% for the 0.25-mg dose; P = 1). Milk leakage was lower in the cabergoline group on day 7 and day 14 (P = 0.0003 and P = 0.02, respectively).
Adverse effects were more common in the cabergoline group compared to the pyridoxine group (31% vs. 9%, respectively; P = 0.01). Headache (n = 6) and constipation (n = 7) were the most common adverse symptoms associated with cabergoline. Similar rates of mastitis and fever were observed in each of the two treatment groups (P = 0.67). Regarding factors contributing to lactation inhibition success, traumatic birth (based on patient self-report) was associated with lactation inhibition failure (P = 0.02). Age, body mass index, ethnicity, parity, gestational age at delivery, cesarean delivery, breastfeeding prior to medication use, breastfeeding in a prior pregnancy, lactation inhibition in previous pregnancy, and time of medication administration after delivery were not found to contribute to success.
COMMENTARY
Cabergoline traditionally has been the drug of choice for lactation inhibition in other countries and has shown efficacy for this indication, although many of the studies were conducted more than 30 years ago.7-9 This recent study demonstrated the superiority of cabergoline compared to pyridoxine for this indication and reaffirmed its efficacy, with 78% of patients having no breast symptoms within seven days of delivery.
Cabergoline currently is not approved by the U.S. Food and Drug Administration for lactation suppression. In addition, there are very few organizations with policies or protocols for lactation suppression. The U.S Department of Health and Human Services Panel on Treatment of Pregnant Women with HIV (Human Immunodeficiency Virus) Infection and Preventions of Perinatal Transmission does support the use of cabergoline for patients with HIV who choose not to breastfeed.10
There are a few clinical scenarios where lactation suppression may be useful:
• patients who have absolute contraindications to breastfeeding, including infant galactosemia, maternal infections such HIV, human T-cell lymphotrophic virus type I or II, untreated brucellosis, active Ebola, and substance use disorder with active cocaine, phencyclidine, or opioid use (stable maintenance therapy with methadone or buprenorphine is not a contraindication), and wanting to avoid engorgement symptoms;11
• any patient who chooses not to breastfeed and wants to suppress lactation;
• patients who have second-trimester terminations or pregnancy loss in the second or third trimester may desire lactation inhibition. A recent randomized controlled trial in California demonstrated the efficacy and tolerability of cabergoline for patients after second-trimester abortions or pregnancy loss.12
Cabergoline could be considered for lactation suppression if patients desire to avoid bothersome breast symptoms, although patients should be informed about the off-label use of the medication. In addition, one limitation of use is that it is contraindicated in patients with hypertensive disorders of pregnancy. Overall, the medication was well-tolerated in this study, although one-third of patients did have mild adverse symptoms, such as headache or constipation.
REFERENCES
- [No authors listed]. Barriers to breastfeeding: Supporting initiation and continuation of breastfeeding: ACOG Committee Opinion Summary, Number 821. Obstet Gynecol 2021;137:396-397.
- Mitchell KB, Johnson HM, Rodríguez JM, et al. Academy of Breastfeeding Medicine Clinical Protocol #36: The Mastitis Spectrum, Revised 2022. Breastfeed Med 2022;17:360-376.
- Spitz AM, Lee NC, Peterson HB. Treatment for lactation suppression: Little progress in one hundred years. Am J Obstet Gynecol 1998;179:1485-1490.
- Oladapo OT, Fawole B. Treatments for suppression of lactation. Cochrane Database Syst Rev 2012;2012:CD005937.
- Harris K, Yudin M, Horn D, Murphy K. Safety of cabergoline in reproductive aged women for postpartum lactation inhibition or suppression: A systematic review. J Obstet Gynaecol Can 2018;40:837.
- AlSaad D, Awaisu A, Elsalem S, et al. Is pyridoxine effective and safe for post-partum lactation inhibition? A systematic review. J Clin Pharm Ther 2017;42:373-382.
- [No authors listed]. Single dose cabergoline versus bromocriptine in inhibition of puerperal lactation: Randomised, double blind, multicentre study. European Multicentre Study Group for Cabergoline in Lactation Inhibition. BMJ 1991;302:1367-1371.
- Giorda G, De Vincentis S, Motta T, et al. Cabergoline versus bromocriptine in suppresion of lactation after cesarean delivery. Gynecol Obstet Invest 1991;31:93-96.
- Melis GB, Mais V, Paoletti AM, et al. Prevention of puerperal lactation by a single oral administration of the new prolactin-inhibiting drug, cabergoline. Obstet Gynecol 1988;71:311-314.
- Clinicalinfo.HIV.gov. Recommendations for the use of antiretroviral drugs during pregnancy and interventions to reduce perinatal HIV transmission in the United States. Updated Jan. 31, 2024. https://clinicalinfo.hiv.gov/en/guidelines/perinatal/whats-new-guidelines
- Meek JY, Noble L. Policy statement: Breastfeeding and the use of human milk. Pediatrics 2022;150:e2022057988.
- Henkel A, Johnson SA, Reeves MF, et al. Cabergoline for lactation inhibition after second-trimester abortion or pregnancy loss: A randomized controlled trial. Obstet Gynecol 2023;141:1115-1123.
A randomized controlled trial demonstrated superior efficacy of cabergoline compared to pyridoxine (78% vs. 35%; P < 0.001) at suppression of lactation seven days after delivery.
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