ABM Clinical Protocol #9: Use of Galactogogues in Initiating or Augmenting the Rate of Maternal Milk Secretion (First Revision January 2011)

Abstract

A central goal of The Academy of Breastfeeding Medicine is the development of clinical protocols for managing common medical problems that may impact breastfeeding success. These protocols serve only as guidelines for the care of breastfeeding mothers and infants and do not delineate an exclusive course of treatment or serve as standards of medical care. Variations in treatment may be appropriate according to the needs of an individual patient. These guidelines are not intended to be all-inclusive, but to provide a basic framework for physician education regarding breastfeeding.

Background

Galactogogues (or lactogogues) are medications or other substances believed to assist initiation, maintenance, or augmentation of the rate of maternal milk synthesis. Because perceived or actual low milk supply is one of the most common reasons given for discontinuing breastfeeding,^1–8 both mothers and health professionals have sought medication(s) to address this concern. Evaluation of evidence-based studies and emerging information regarding more serious potential side effects of some galactogogues have resulted in a recent shift in the Academy of Breastfeeding Medicine's recommendations regarding these drugs and herbs. In 2004, the previous version of this protocol used existing evidence that prescription galactogogues were effective and described when and how to use them. ⁹ Emerging data suggest that we should exercise more caution in recommending these drugs to induce or increase the rate of milk secretion in lactating women, particularly in women without specific risk factors for insufficient milk supply.

Human milk production is a complex physiologic process involving physical and emotional factors and the interaction of multiple hormones, the most important of which is believed to be prolactin. Despite the fact that prolactin is required for lactation, there has been no evidence for direct correlation of serum prolactin levels (baseline or percentage increase after suckling) with the volume of milk production in lactating women.^10–12

Lactation is initiated with parturition, expulsion of the placenta, and falling progesterone levels in the presence of very high prolactin levels. Systemic endocrine control of other supporting hormones (estrogen, progesterone, oxytocin, growth hormone, glucocorticoids, and insulin) is also important. ¹³ These hormonal changes trigger secretory activation (lactogenesis II) of the mammary secretory epithelial cells, also called lactocytes. Prolactin secretion functions in a negative feedback system in which dopamine serves as an inhibitor. Therefore, when dopamine concentration decreases, prolactin secretion from the anterior pituitary increases. The theory behind pharmaceutical galactogogues is that dopamine antagonists increase prolactin secretion ¹⁴ and subsequently increase the overall rate of milk synthesis. However, as mentioned above, no correlation exists between serum prolactin and increased milk volume.^10–12

After secretory activation, the rate of milk synthesis is controlled locally in the mammary gland by autocrine control. Lactating breasts are never completely “empty” of milk, so the terms “drain, drainage, draining,” etc., are more appropriate. If the breasts are not drained regularly and thoroughly, milk production declines. Alternatively, more frequent and thorough drainage of the breasts typically results in an increased rate of milk secretion, with both a rapid (per feeding) effect and a delayed (several days) effect. ¹² Even though the rate of milk synthesis is controlled locally at this stage of lactation, suckling-induced peaks of prolactin continue throughout the entire course of breastfeeding.

Potential Indications for Galactogogues

Galactogogues commonly have been used to increase a faltering rate of milk production, often due to the effects of maternal or infant illness and hospitalization or because of regular separation such as work or school. One very common area of use has been the neonatal intensive care unit, where the aim has been to stimulate initial secretory activation or augment declining milk secretion in these mothers. Mothers who are not breastfeeding but are expressing milk by hand or with a pump often experience a decline in milk production after several weeks. Galactogogues have also been used for adoptive breastfeeding (induction of lactation in a woman who was not pregnant with the current child) and relactation (reestablishing milk secretion after weaning).

Many breastfeeding medicine specialists and lactation consultants have recommended these drugs and herbs, usually as a last resort when other non-pharmacological measures have not resulted in an increase in milk volumes. However, some providers may inappropriately recommend galactogogues prior to emphasizing the primary means of increasing the overall rate of milk synthesis (i.e., frequent feeding and complete milk removal at regular intervals) or evaluating other medical factors that potentially may be involved.

Pharmaceutical Galactogogues

Currently available pharmaceutical galactogogues are all dopamine antagonists and will increase prolactin levels via this mechanism. ¹² A number of older studies documented increased baseline prolactin levels in lactating women who took metoclopramide or domperidone.^15–20 However, there are only a few randomized, placebo-controlled, blinded studies on each of these agents, and these studies are small.

Domperidone

Regarding domperidone, there are two well-designed randomized, placebo-controlled, blinded studies. One of the studies, published in 2010 (n = 46), shows that domperidone is associated with significantly increased volumes of expressed milk among women with premature infants less than 31 weeks' gestation; the study concluded at 14 days, so longer-term effects cannot be evaluated. ¹¹ One very small study (n = 6) suggests that individual women may be “responders” or “non-responders” and that primiparas may respond to domperidone with higher prolactin levels than multiparas.” ²¹

Metoclopramide

For metoclopramide, only four randomized, placebo-controlled, blinded studies have been published, and they each have some problem(s) in design, small sample size, and/or patient selection.^22–25 Metoclopramide did not produce a statistically significant effect on infant weight gain in a randomized controlled trial of metoclopramide versus placebo in a 2008 study of 20 mothers who were relactating: 10 women received metoclopramide, and 10 received placebo; all received a course of standardized counseling regarding optimal breastfeeding technique. ²⁴ These results replicated an earlier study with a total of 50 mothers. ²⁵ All four of these higher-quality studies^22–25 found no differences in milk volumes and/or duration of breastfeeding between metoclopramide and placebo. Two found optimal breastfeeding instruction or counseling to be positively associated with a statistically significant increase in infant weight gain (and corresponding decrease in use of supplemental feedings).^24,25 The other two did not evaluate or assist with optimal breastfeeding routines.^22,23

Summary

Despite widespread use of these pharmaceutical galactogogues, there are important reasons for reconsideration of this practice:

• Galactogogues do increase baseline serum prolactin, but there is no direct correlation between baseline prolactin levels and rates of milk synthesis or measured volumes of milk production.

• Previous studies up through 2006 have tended to show a pattern of increased milk production, but they have generally been of poor quality,^9,10 with the following weaknesses:

• Older reviews have cited studies with positive results while minimizing or ignoring studies with negative results.^9,26,27

• A key systematic review in 2007 ¹⁰ found two main problems.

• Prescription drugs used as galactogogues constitute “off-label” use in most countries (they are not approved by regulatory agencies for this indication).

Herbals, Foods, and Beverages as Galactogogues

In non-Western cultures, postpartum women are assisted in a number of ways that are intended to ease their transition to motherhood and to optimize breastfeeding. Many cultures keep new mothers very warm and insist on a period of rest of approximately 1 month. Many also have traditional foods and herbs for postpartum women that are meant to increase the mother's strength and enhance lactation. ²⁸ Many of these herbal remedies have been used throughout history to enhance milk supply. Some herbs mentioned as galactogogues include fenugreek, goat's rue, milk thistle (Silybum marianum), oats, dandelion, millet, seaweed, anise, basil, blessed thistle, fennel seeds, marshmallow, and many others. Although beer is used in some cultures, alcohol may actually reduce milk production. A barley component of beer (even nonalcoholic beer) can increase prolactin secretion, but there are “no systematic studies” and “there is no hard evidence for causal effect.”^29,30 The mechanism(s) of action for most herbals are unknown. Most of them have not been scientifically evaluated, but traditional use suggests safety and possible efficacy. The available studies for herbs, herbal medicines, or herbal galactogogues suffer from the same deficiencies as the studies for pharmacologic agents: Small numbers of subjects, lack of information regarding breastfeeding advice, and lack of randomization, controls, or blinding (Levels of Evidence II-1, ³¹ II-3 ³² ). ^* The placebo effect may be the reason for widespread impressions (anecdotal experience) of a positive effect of fenugreek on increased milk volumes (Level of Evidence III, personal communications from K.A. Marinelli [2010], N. Wight [2010], C. Smillie [2009], and N.G. Powers [2010]). The minimal specific data regarding these herbs are presented in the Appendix.

It is important to note that caution is required for the use of herbal preparations because of the lack of standardized dosing preparations (other than research settings), possible contaminants, allergic potential, and drug interactions. Several herbs, taken orally, will increase patient blood levels of warfarin, heparin, and other anticoagulants. There are several reports of severe maternal allergic reactions to fenugreek. ³³

Practice Recommendations

The following recommendations, based upon current evidence, apply to women experiencing difficulties with a low rate of milk production (e.g., the baby is not gaining weight normally or supplementation is being used because of low milk production, during either the initiation or maintenance of milk supply).

Specific information about individual drugs and herbs is summarized at the end of these recommendations in the Appendix.

1. Evaluate and augment the frequency and thoroughness of milk removal. Use non-pharmacologic measures to increase the overall rate of breastmilk synthesis.

2. Evaluate the mother for “medical” causes of hypogalactia: Pregnancy, medications, primary mammary glandular insufficiency, breast surgery, polycystic ovary syndrome, hypothyroidism, retained placenta, theca lutein cyst, loss of prolactin secretion following postpartum hemorrhage, heavy smoking or alcohol use, or other pertinent conditions. Treat the condition as indicated, if treatment is available ¹² (Level of Evidence II-2, II-3, and III).

3. Because current research of all galactogogues is relatively inconclusive and all of the agents have potential adverse effects, ABM cannot recommend any specific pharmacologic or herbal galactogogues at this time.

4. The healthcare provider who weighs the potential risks versus the potential benefits of these agents and chooses to prescribe a galactogogue should follow the guidelines below (Level of Evidence III) (see Appendix regarding details of prescribing specific galactogogues).

5. Inform women about available data concerning efficacy, timing of use, and duration of therapy of galactogogues (Level of Evidence I). ¹⁰ (Specific information is presented in the Appendix.)

6. Inform women about available data concerning potential adverse effects of galactogogues (see Appendix regarding details of specific galactogogues):

Conclusions

Prior to the use of a galactogogue, thorough evaluation should be performed of the entire feeding process by a lactation expert. Reassurance may be offered, if appropriate. When intervention is indicated for the dyad, modifiable factors should be addressed: comfort and relaxation for the mother, frequency and thoroughness of milk removal, and underlying medical conditions. Medication should never replace evaluation and counseling on modifiable factors. As new evidence has emerged regarding various interventions to increase milk secretion in lactating women, the case for using pharmaceutical galactogogues has grown weaker. There remain selected indications for which some of these agents may be useful, but the data are insufficient to make definitive recommendations. One high-quality study has found domperidone useful in mothers of babies less than 31 weeks' gestation in the neonatal intensive care unit (see the Appendix). Herbal galactogogues are problematic because of lack of regulation of preparations and insufficient evidence of efficacy and safety. Clinicians should prescribe galactogogues with appropriate caution in regards to drug-to-drug (or drug-to-herb) interactions as well as an overall risk-to-benefit approach and complete informed consent. Close follow-up of both mother and baby is essential to monitor the status of lactation as well as any adverse effects of the drug(s) on mother or infant.

Recommendations for Further Research

Existing studies in this area cannot be considered conclusive, and many of the recommendations are based primarily on expert opinion, small studies, and studies in which non-pharmacologic breastfeeding support was suboptimal. Most studies have been done in mothers of preterm infants using mechanical breast pumps rather than in mothers of term infants whose problems usually arise in the first few days to weeks postpartum. There is a clear need for well-designed, adequately powered, randomized, controlled trials using adequate doses of galactogogues in populations of women in which both the experimental and control groups receive modern, appropriate lactation support. These studies need to be done in mothers of both term and preterm infants and need to measure clinically relevant outcomes such as infant weight gain, need for artificial feeding (supplements other than mother's own milk), quantification of maternal milk synthesis, and adverse drug effects.