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TheUseofGalactogoguesintheBreastfeedingMother

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DOI:10.1345/aph.1R167·Source:PubMed

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1392 n The Annals of Pharmacotherapy n 2012 October, Volume 46 theannals.com

Breastfeeding is considered the opti-mal source of nutrition for infants

from birth to 1 year and is supported bythe American Academy of Pediatrics(AAP) and the World Health Organiza-tion.1,2 The 2012 AAP Policy on Breast-feeding recommends exclusive breast-feeding for 6 months, with continuationup to 1 year or longer. Breastfeeding hasbeen associated with both short- andlong-term benefits over formula feeding.In 2007, the Agency for Healthcare Re-search and Quality prepared a reportsummarizing the literature concerningthe relationship between breastfeedingand its impact on infant and maternaloutcomes.3 A total of 9000 abstractswere reviewed; 43 studies focused on in-fant health outcomes, 43 studies on ma-ternal health outcomes, and 29 systemat-ic reviews or meta-analyses of more than400 trials. Results of these studies indi-cated that exclusive breastfeeding for aminimum of 3 months decreased the riskof the infant developing acute otitis me-dia and/or atopic dermatitis and, if thechild were exclusively breastfed forgreater than 4 months, the result was adecrease in hospitalizations secondary tolower respiratory tract infection. Addi-tionally, if breastfeeding continued for greater than 6months, there was a potential decrease in the occurrence ofacute lymphocytic leukemia and acute myeloid leukemia.Studies have also shown a potential decrease in death fromsudden infant death syndrome and the development of

asthma, diabetes mellitus, and obesity. The Agency forHealthcare Research and Quality report also notes the po-tential benefits to the mother, including reduced risk ofbreast and ovarian cancers as well as decreased risk of dia-betes mellitus type 2 as long as the mother did not havegestational diabetes.

Despite the AAP recommendations and perceived bene-fits, breastfeeding rates in the US continue to be low.4 At

The Use of Galactogogues in the Breastfeeding Mother

Alicia B Forinash, Abigail M Yancey, Kylie N Barnes, and Thomas D Myles

Obstetrics/Gynecology

Author information provided at end of text.

OBJECTIVE: To review data regarding the efficacy of galactogogues available inthe US to increase breast milk production in postpartum mothers.

DATA SOURCES: Literature was sought using PubMed (1966-June 2012) andEMBASE (1973-June 2012). Search terms included breastfeeding, breast milk,lactation, galactogogue, metoclopramide, oxytocin, fenugreek, milk thistle, silymarin,growth hormone, thyroid releasing hormone, medroxyprogesterone, domperidone,goat’s rue, beer, Asparagus racemosus, shatavari, Medicago sativa, alfalfa, Onicusbenedictus, blessed thistle, Galega officinalis, brewer’s yeast, and herbals.

STUDY SELECTION AND DATA EXTRACTION: All studies including humans and pub-lished in English with data assessing the efficacy of galactogogues for increasingbreast milk production were evaluated.

DATA SYNTHESIS: Breast milk is considered the optimal food source for newbornsthrough 1 year of age. Many factors influence overall maternal production, includingmaternal pain, illness, balance of time when returning to work, anxiety, or emo-tional stress. Although a variety of herbal and pharmaceutical options haveanecdotal evidence of their ability to improve breast milk production, peer-reviewed studies proving their efficacy are lacking. Metoclopramide, oxytocin,fenugreek, and milk thistle have shown mixed results in improving milk produc-tion; however, the trials were small and had a variety of limitations.

CONCLUSIONS: Nonpharmacologic recommendations should be exhaustedbefore adding therapy. Although anecdotal evidence encourages the use ofmetoclopramide, fenugreek, asparagus, and milk thistle for their galactogogueproperties, efficacy and safety data in the literature are lacking. Oxytocin anddomperidone are potentially available for compounding purposes, but safety dataare limited. More studies are needed to evaluate the effects of availablegalactogogues on breast milk production.

KEY WORDS: breastfeeding, breast milk, fenugreek, galactogogue, herbals,lactation, metoclopramide, milk thistle, oxytocin, silymarin.

Ann Pharmacother 2012;46:1392-404.

Published Online, 25 Sept 2012, theannals.com, doi: 10.1345/aph.1R167

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birth, initiation of breastfeeding occurs for 75% of moth-ers; however, the rate of breastfeeding decreases to 44.6%at 6 months and 23.8% at 12 months. Exclusive breast-feeding rates are even lower at 35% and 14.8% at 3months and 6 months, respectively. Many factors can con-tribute to difficulty feeding and may lead to early cessationof breastfeeding; these include structural abnormalitiessuch as inverted nipples and oral clefts, infection, pain,poor latching, and insufficient milk production.5 Factorsthat have been associated with a reduction in breast milkproduction include preterm delivery, maternal illness, anxi-ety, fatigue, and emotional stress. Because of the manydocumented benefits of continued breastfeeding for the in-fant and mother, different measures are taken to increasebreast milk production. A variety of herbal and pharma-ceutical products have been recommended as galacto-gogues, substances that promote lactation. The purpose ofthis article is to review data regarding the efficacy of galac-togogues available in the US for increasing breast milkproduction in postpartum mothers.

Physiology of Breastfeeding

Many factors play a role in the development of breastmilk. During early pregnancy, estrogen and progesteronedevelop key components of the breast tissue for lactation;estrogen stimulates milk duct development and proges-terone forms lobules that are responsible for milk produc-tion. Prolactin is the predominant hormone that stimulatesmammary glands; however, high progesterone and estro-gen progesterone levels during pregnancy suppress pro-lactin’s action on milk production during pregnancy. Addi-tionally, prolactin and human chorionic somatomam-motropin stimulate the production of enzymes required formilk production. After delivery, estrogen and progesteronelevels significantly decrease, allowing prolactin to fullystimulate the alveoli for milk production. Cortisol, insulin,vasoactive intestinal peptide, growth hormone, and thy-roid-releasing hormone stimulate prolactin and influencethe composition of milk, whereas dopamine inhibits pro-lactin, suppressing its action.6,7 Milk secretion is primarilycontrolled by oxytocin, which stimulates the myoepithelialcells to contract and release stored milk into the ducts (ie,letdown). Milk must be ejected from the lumen of the alve-oli into the milk ducts to reach the infant. Infant sucklingstimulates production of prolactin as well as oxytocin.Milk secretion continues until suckling ends. Interestingly,even if the alveoli still contain milk, once suckling stops,no more milk can be released. It is important to allow plen-ty of time for feeding or breast pumping to empty thebreasts. When all of the milk is released, the breast stimu-lates additional milk production for the next feeding. Thisfeedback mechanism leads to an overall increase in supplyover time.6,7

Literature Selection

A search of PubMed (1966-June 2012) and EMBASE(1973-June 2012) was performed with the terms breastfeed-ing, breast milk, lactation, galactogogue, metoclopramide,oxytocin, fenugreek, milk thistle, silymarin, growth hormone,thyroid-releasing hormone, medroxyprogesterone, domperi-done, goat’s rue, beer, Asparagus racemosus, shatavari, Med-icago sativa, alfalfa, Onicus benedictus, blessed thistle, Gale-ga officinalis, brewer’s yeast, and herbals. Limits of Englishlanguage and human subjects were applied to the searches.References of all articles were reviewed to identify additionalrelevant articles. All relevant articles were included despitelimitations due to the limited supply of published data evalu-ating these therapies. These products are commonly recom-mended in practice by both maternal and pediatric health careproviders. Case reports, case series, and abstracts were ex-cluded unless they were the only published literature on thetopic. Medications that are not available in the US were ex-cluded from this review.

Herbal Products

Natural herbal medications, such as fenugreek (Trigo-nella foenum-graecum), milk thistle (silymarin; Silybummarianum), A. racemosus (shatavari), alfalfa (M. sativa),blessed thistle (O. benedictus), goat’s rue (G. officinalis),fennel (F. vulgare), and brewer’s yeast, are often recom-mended to breastfeeding mothers to increase milk produc-tion. However, data on herbal products are limited and of-ten based on anecdotal evidence. Fenugreek, milk thistle,and asparagus are frequently recommended and are theonly herbal galactogogues that have some, although mini-mal, published clinical data on use in humans.8,9

FENUGREEK

Fenugreek is a member of the pea family and is oftenused as artificial maple flavoring.10 The galactogogue prop-erty of fenugreek was first reported in the 1940s. Althoughits exact mechanism of action is unknown, there are 2 pro-posed mechanisms. The first is that it increases sweat pro-duction, leading to an increase in milk supply given thatthe breast is considered to be a modified sweat gland (Fig-ure 1).10,11 The second thought is that milk flow is increasedby fenugreek phytoestrogens and diosgenin, a steroid sa-pogenin, components.12 The recommended dose of fenu-greek is 2-3 capsules (580-610 mg per capsule) 3-4 timesper day, and it may be discontinued once milk supply hasincreased to the desired level.10,11 Many women have re-ported results within 24-72 hours.8,10,11

Fenugreek is often prescribed to nursing mothers, basedon anecdotal reports. One physician observed the success-ful use of fenugreek in more than 1200 patients. Unfortu-

The Annals of Pharmacotherapy n 2012 October, Volume 46 n 1393theannals.com

nately, detailed information was not available in regard togestational age, time of initiation, or specific results.10 Twostudies showed that fenugreek appears to stimulate breastmilk production (Table 1).12-14 Limitations of these reportsinclude lack of reporting maternal and infant adverse ef-fects, adherence, and doses of fenugreek used. Confound-ing factors that affect breastfeeding success, includingcaloric and fluid intake of mother, other medications used,frequency and duration of breastfeeding, and stress/painlevel of the mother, were not controlled in these studies.One study evaluating 10 exclusively pumping women waspresented only in abstract form; full evaluation of the datais therefore not possible.13 The second study, a randomizedtrial, also included a small sample size and focused mainlyon birth weight, loss of birth weight, and time to regainbirth weight.12 Milk volume produced was measured onlyon the third day after delivery and the study concludedwhen the infant reached birth weight, so the full efficacy offenugreek was unable to be determined. The biggest limi-tation of this study is that the galactogogue tea includedother herbal components thought to have galactogogueproperties, including fennel and goat’s rue; thus, it is diffi-cult to conclude that benefit is solely from fenugreek.12,15

Although it appears that fenugreek may have some bene-fit, randomized clinical trials are needed to determine its spe-cific role as a galactogogue. Safety data are minimal since ad-

verse events and tolerability were not reported. Currently, theFood and Drug Administration (FDA) lists fenugreek as gen-erally regarded as safe (GRAS); however, these data are notspecifically aimed at the nursing mother and infant.10,16 Addi-tionally, no information has been published to describe thesafety or relative infant dose of fenugreek consumptionthrough breast milk. There are reports of mild gastrointestinalsymptoms in the mother, mainly diarrhea, and there is poten-tial for hypoglycemic effects.10,11 The fenugreek seed can leadto a maple-like odor that can be mistaken in infants formaple-syrup urine disease, which is a metabolism disorder inwhich the body is unable to break down certain parts of pro-teins.9,17 Women who are pregnant should not use fenugreek,as it has been shown to stimulate uterine contractions.8,16

MILK THISTLE

Another popular herbal galactogogue is milk thistle (sily-marin, St. Mary’s milk), which has been used for more than2000 years for a variety of ailments.18 It is theorized that milkthistle galactogogue effects are secondary to an increase inprolactin levels, as seen in female rats (Figure 1).19 Clinicaldata are limited to 1 placebo-controlled trial14 conducted inPeru (Table 1).12-14 Limitations of this study include a smallsample size, indirect measurement of milk production byweighing the infant before and after feeding, as well as not

1394 n The Annals of Pharmacotherapy n 2012 October, Volume 46 theannals.com

AB Forinash et al.

Figure 1. Physiology of lactation and potential medication mechanisms of action. PIH = prolactin inhibiting hormone; PRH = prolactin releasing hormone.aExact mechanism of action unknown but known to increase prolactin.

including detailed information on both the mother and in-fants, infant weight gain, adverse event data, and adherence.Randomized controlled trials evaluating the benefit of milkthistle are needed to show its benefit, safety, and potential roleas a galactogogue. As with many herbal agents, safety dataare minimal and, unlike fenugreek, milk thistle is not listed asGRAS by the FDA. No data are available describing the rela-tive infant dose of milk thistle after breast milk consump-tion.18

SHATAVARI

Shatavari is a popular galactogogue used in India. Theexact mechanism of action is unknown but could possiblybe secondary to the presence of steroidal saponins, whichpotentially increase prolactin levels.20 Two studies havebeen conducted to determine whether prolactin increasedwith shatavari; unfortunately, the results were conflict-ing.20,21 Both studies looked at milk production as a sec-ondary outcome; however, this was determined indirectlyby weighing the infant before and after treatment. Onceagain, study results were conflicting. Other limitations ofthe trials included small sample size, omission of detailedinformation on adherence, reasons for drop-outs, and in-formation about adverse events for both mother and infant.As with milk thistle, shatavari is not listed as GRAS by theFDA.22 There is also recent evidence showing teratogenicityin animal studies, thus shatavari should be avoided in preg-nant females.23 No data are available describing relative in-fant dose of shatavari after breast milk consumption.22,23

Randomized controlled trials are needed to determine thebenefit, safety, and potential role as a galactogogue.

Potentially Available from CompoundingPharmacies

OXYTOCIN

Before oxytocin nasal spray was voluntarily removedfrom the US market in 1995 and worldwide in 1999, it wascommonly used to promote milk letdown in women withdecreased milk production. Supplemental oxytocin in-creased breast milk production because it causes contractionof the myoepithelial cells that surround areola tissue in thebreast (Figure 1).24 Three randomized, double-blind studieshave been conducted evaluating the impact of oxytocin nasalspray immediately prior to each breastfeeding session to in-crease breast milk production (Table 2).25-31 Oxytocin nasalspray 3 IU per spray prior to each feeding from birth to 5days postpartum showed significant differences in overallbreast milk production. Production increased 3- to 5-foldwith oxytocin nasal spray compared with placebo in primi-parous mothers and 2-fold in multiparous mothers.

Oxytocin appears to be generally well tolerated, but minorepistaxis was reported by 1 woman in 1 study.25 No infant ad-verse events were reported; however, safety cannot be as-sumed since only a small number of exposures occurred.Limitations of these studies include small sample size, shortduration, minimal to no information on infant weight gain re-ported, evaluated only the effects in preterm delivery, andoverall medication adherence was not verified.24-27 The firsttrial also used an indirect method for measuring productionby breast engorgement instead of actual milk production.25

Overall, oxytocin improved milk production when used inlate preterm deliveries compared with historical controls but

The Use of Galactogogues in the Breastfeeding Mother

The Annals of Pharmacotherapy n 2012 October, Volume 46 n 1395theannals.com

Table 1. Comparison of Herbal Galactogogue Clinical Trialsa

InfantAge Milk Effect on Infant

Reference Regimen Patients (FT/PT) Attainment Milk Production Weight

Turkyilmaz Fenugreek tea, Fenugreek tea (n = 22) 1 day Nursing, except day 3 Day 3 postdelivery: fenugreek Lactation 201112 ≥3 cups daily Control (n = 22) (FT) postdelivery by 73.2 ± 53.5 mL; control consultant for all

Placebo (n = 22) mechanical breast pump 38.8 ± 16.3 mL; placebo groups31.1 ± 12.9 mL (p = 0.004)7.3 ± 2.7 mL; placebo9.9 ± 3.5 mL

Swafford Fenugreek 10 Breast pump Daily average increase from 200013 3 capsules 207 to 464 mL (p = 0.004)

daily16

Di Pierro Micronized Milk thistle (n = 25) Nursing, then pumping to Milk thistle 601.92 mL (day 0),200814 milk thistle Control (n = 25) void the gland 989.76 mL (day 30), and

420 mg/day 1119.24 mL (day 60); anfor 63 days 85.95% increase

Placebo 530.36 mL (day 0),649.76 mL (day 30), 700.56 mL (day 60); a 32.09% increase

FT = full-term delivery; PT = preterm delivery.aNo data have been reported on maternal or infant adverse events.

1396 n The Annals of Pharmacotherapy n 2012 October, Volume 46 theannals.com

AB Forinash et al.

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no improvement in early preterm deliveries compared withplacebo.

Currently, oxytocin is available in intramuscular and intra-venous injection forms in the US; however, it lacks the indi-cation for lactation purposes. Oxytocin powder is still avail-able for compounding pharmacies and could potentially beused as a galactogogue. Available data do not describe therelative infant dose and theoretical infant dose in breastmilk.32

DOMPERIDONE

In addition to oxytocin, domperidone is a potential galac-togogue available in powder formulation for potential com-pounding. Domperidone is a dopamine antagonist and canincrease prolactin levels (Figure 1). Domperidone 10 mgorally every 8 hours for 2 weeks has been shown to increasemilk supply in 48 hours, and it has a low relative infant doseof 0.04% and a subtherapeutic theoretical infant dose of 0.18µg/kg/day.28-31,33 Domperidone significantly increased milkproduction in women with preterm deliveries (Table 2).25-31 Itappears to be generally well tolerated, but abdominal cramps,headaches, constipation, and depression have been reported,although rates were higher when the dose was increased to20 mg every 8 hours. No infant adverse events were reported;however, safety cannot be assumed since only a small num-ber of exposures occurred. Limitations of these domperidonestudies include small sample size; location, having been con-ducted in other countries; and potential confounders that mayhave affected milk supply, such as fluid and calorie intake,frequency of pumping, medical history, and concomitantmedications, were not provided.

Despite effectiveness, this formerly commercially avail-able product was removed from the market in 2004. TheFDA released a statement expressing concerns for dom-peridone safety in lactating women due to potential for car-diac arrhythmias and sudden cardiac death in 2004 andagain in 2009.34,35 This risk was discovered in oncology pa-tients with hypokalemia receiving intravenous domperi-done; however, the FDA issued warnings specific to lactat-ing mothers to avoid the use of domperidone.

Prescription Products

METOCLOPRAMIDE

Metoclopramide is a commonly prescribed galactogoguethat acts through dopamine antagonism to increase pro-lactin levels and stimulate increased milk production (Fig-ure 1).36-41 In one study, milk supply increased 52% after 2days of treatment.38 Metoclopramide has been studied as 10mg given orally 3 times a day for 5 days to 4 weeks, butmost commonly 7-14 days, initiated with onset of lactationor later for partial or complete lactation failure in bothpreterm and full-term infants (Table 3).36-48 Metoclopramide

The Use of Galactogogues in the Breastfeeding Mother

The Annals of Pharmacotherapy n 2012 October, Volume 46 n 1397theannals.com

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mde

liver

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1398 n The Annals of Pharmacotherapy n 2012 October, Volume 46 theannals.com

AB Forinash et al.

Tabl

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paris

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The Use of Galactogogues in the Breastfeeding Mother

The Annals of Pharmacotherapy n 2012 October, Volume 46 n 1399theannals.com

Gup

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has been studied in 13 trials with mixed results; however,the most recent, a randomized controlled trial with strongtrial design, failed to maintain power, which may have con-tributed to the lack of significant differences found betweengroups.48 Metoclopramide crosses into breast milk, but thiswould result in subtherapeutic infant exposure because of alow relative infant dose of 4.4%; the theoretical infant doseis 18.75 µg/kg/day.49 One study estimated that the maxi-mum exposure of the infant to metoclopramide would be45 µg/kg/day, whereas typical pediatric dosing is 100-500mg/kg/day for reflux.42,49 The only adverse event reported ininfants has been intestinal gas. Limitations of these studiesinclude small sample sizes, short duration, and indirectmeasurement of milk production by weighing the infant be-fore and after feeding, as well as not reporting maternal andinfant adverse events, infant weight gain, and adherence.Additionally, no data were provided about several factorsknown to influence milk supply, including length or fre-quency of breastfeeding, caloric and fluid intake, andstress/pain evaluation of the mother, nor was informationregarding adherence reported. Several studies were con-ducted in different countries, making it difficult to evaluatethe influence of culture, diet, and other differences thatmight exist. Overall, metoclopramide has been evaluated asa galactogogue in 213 mothers, with mixed results. Whencomparing various patient characteristics (preterm vs full-term), time of initiation (within 14 days postpartum vs lat-er), or trial characteristics (milk production measured byweighing the infant vs pumping; randomized controlled tri-als vs other designs), no subgroup strongly demonstratedefficacy or overall efficacy.

Metoclopramide should not be used for all patients. Thelabeling has a boxed warning for risk of tardive dyskinesiawhen the drug is used for more than 3 months.50 Womenwith a history of tardive dyskinesia or seizures or who areat risk for developing tardive dyskinesia should avoid us-ing this product. Metoclopramide may also increase therisk for serotonin syndrome when used with other medica-tions that act on serotonin. A few examples include selec-tive serotonin receptor inhibitors, serotonin-norepinephrinereceptor inhibitors, monoamine oxidase agonist inhibitors,and tramadol. Metoclopramide is renally eliminated andrequires dose reductions to 50% the normal dose when cre-atinine clearance is less than 40 mL/min. Patients withpheochromocytoma should also avoid metoclopramide be-cause of the potential for hypertensive crisis. Despite theAAP listing of metoclopramide as a drug with effects thatare unknown but that may be of concern, it received a lac-tation category of L2 (safer: been studied in a limited num-ber of breastfeeding women without an increase in adverseevents in the infant, and/or evidence of demonstrated riskin infant is remote) in Medications in Mother’s Milk and isconsidered medication with small risk in Drug Use inPregnancy and Lactation.49-51

Other Medications

Several other medications have been suggested as galacto-gogues and/or have properties that may improve lactation.First-generation antipsychotics and risperidone produce in-creased prolactin levels and may increase milk supply. How-ever, without a diagnostic indication for their use, we do notrecommend initiating therapy for breast milk productionalone because of potential maternal and infant adverseevents.32

Beer has been recommended for nursing mothers sincethe 1800s. Beer is thought to increase milk production by in-creasing prolactin levels.52,53 However, studies have shownthat breastfeeding infants consume 20% less milk 3-4 hoursafter the ingestion of beer by the mother, which was unrelatedto the number or duration of feedings but was likely sec-ondary to decreased quantity produced.54,55 Additionally,some of the alcohol consumed by the mother is transferred toher milk and consumed by the infant. Alcohol consumptionhas detrimental effects on the infant, including disruption insleep patterns and effects on gross motor development.55

Therefore, beer is no longer recommended as a galacto-gogue.2

Although not touted as a galactogogue, depot-medrox-yprogesterone (DMPA) has been shown to have favorableeffects on milk supply in women using the drug for contra-ceptive purposes.56-58 It is speculated that galactogogueproperties may be secondary to an increase in prolactinlevels.58 To date, no studies looking at DMPA galacto-gogue effects as a primary outcome have been completed.

Human growth hormone (GH) in doses ranging from 0.1to 0.2 IU/kg/day (maximum of 16 IU/day) for 7 days has alsobeen used as a galactogogue because of its proposed ability toincrease prolactin levels.59,60 GH lacks FDA indication for useas a galactagogue and has several limitations for use. First, itis injected subcutaneously, which would require mothers toprepare and inject it multiple times per day. Second, GH isexpensive. Also, the FDA is conducting an investigation onthe safety of GH use during childhood, with specific con-cerns for increased mortality due to bone tumors and cardio-vascular events in children exposed to GH.61 Consideringthese factors, GH is not recommended for use as a galacto-gogue.

Thyroid-releasing hormone (TRH) has also been usedas a galactogogue. TRH is secreted in breast milk and, todate, 3 of 4 studies have reported no benefit to using TRHas a galactogogue. TRH dosing in these studies rangedfrom 1 mg as a nasal spray 4 times daily for 10 days, 5 mgtwice daily for 5 days, 20 mg twice daily for 2 weeks, to 20mg twice daily for 3 weeks. Each study reported an in-crease in triiodothyronine and thyroxine; however, thestudies have not reported incidences of hyperthyroidism inthe mothers or infants.62-65 Unfortunately, the study periodshave not been long enough for the effects of elevations in

1400 n The Annals of Pharmacotherapy n 2012 October, Volume 46 theannals.com

AB Forinash et al.

triiodothyronine and thyroxine to be fully evaluated, andthere is a potential for mothers and infants to develop hy-perthyroidism. Because of this risk and lack of evidenceoverall of increased breast milk production, TRH is notrecommended for use as a galactogogue at this time.

Discussion

Breast milk is considered to be the optimal food source fornewborns through 1 year of age. Although it is a natural foodsource, women often encounter difficulties when attemptingto breastfeed and turn to supplemental sources of nutrition,such as formula, for their infant prior to the infant’s first birth-day. Although there are a variety of herbal and pharmaceuti-cal options that have anecdotal evidence supporting theirability to improve breast milk production, peer-reviewedstudies proving their efficacy and safety are lacking.

When approaching lactation difficulties, health careproviders should provide recommendations in a stepwisefashion. Nonpharmacologic measures should first be used toincrease breast milk production. All mothers should receiveextensive education about proper breastfeeding techniques,including latching, positioning, and length of feeding, sincethese factors can significantly affect breastfeeding. Stresscontributes to decreased milk production by decreasing oxy-tocin release.6,7,14 Because of this, relaxation techniques, deepbreathing, gentle massages, eating or drinking enjoyablefoods and beverages, and listening to music while breastfeed-ing have been shown to initiate the milk ejection reflex as haslooking at things that remind her of the baby, such as a pic-ture or blanket, while pumping.66 Other methods that encour-age complete emptying of the breasts include massaging andwarming the breasts while pumping.67-69 Techniques to in-crease milk supply include increasing feeding/pumping time,decreasing intervals between feedings, increasing duration ofpumping, and increasing caloric and fluid intake. Some stud-ies have shown that pumping both breasts simultaneouslymay increase breast milk production as well as save themother time.66,70

If nonpharmacologic interventions fail to improve sup-ply, the health care provider could consider recommendingmetoclopramide or fenugreek; however, both medicationslack strong evidence to support efficacy. Metoclopramide andfenugreek have some clinical evidence of their usefulness inincreasing breast milk production in lactating women andthey appear to be safe for the breastfeeding infant. Althoughfenugreek is rated as GRAS, it is important for the health careprovider to remember that it has minimal safety data whenused as a galactogogue. As for safety, metoclopramide is con-sidered by AAP to be a medication with unknown effects,but its use may be of concern; however, other breastfeedingsources have granted it category L2 status, medication withsmall risk.49,51

Studies focused on breastfeeding are limited and oftenlack the rigor and design that are expected in medical re-search. Limitations of lactation studies often include smallsample sizes, short duration, and indirect measurement ofmilk production by weighing the infant before and afterfeeding. Additionally, trials commonly lack control for fac-tors known to influence milk supply, including length orfrequency of breastfeeding, caloric and fluid intake, warm-ing and massaging of breasts, and evaluation of maternallevels of stress/pain. Currently, there are no available dataevaluating repeat courses or effects on lactation after medi-cation discontinuation for any medication.

Summary

Although anecdotal evidence encourages the use of meto-clopramide, fenugreek, asparagus, and milk thistle for theirgalactogogue properties, efficacy and safety data in the litera-ture are lacking. When examining the limited reported dataon potentially subtherapeutic exposure to the infant, it is like-ly that metoclopramide and fenugreek can be used; however,exposed infants should be monitored for any adverse events.Oxytocin and domperidone are potentially available for com-pounding purposes, but safety data are limited. Unfortunately,at this time there is not enough efficacy and/or safety evi-dence to support using other proposed galactogogues such asmilk thistle, goat’s rue, beer, brewer’s yeast, alfalfa, aspara-gus, domperidone, oxytocin, GH, TRH, or DMPA. Addition-ally, potential risk for maternal and/or infant harm has notbeen fully elucidated. More studies are needed to evaluate theeffects of available galactogogues on breast milk production.

Alicia B Forinash PharmD BCPS BCACP, Associate Professor ofPharmacy Practice, Department of Pharmacy Practice, St. LouisCollege of Pharmacy, St. Louis, MO Abigail M Yancey PharmD BCPS, Associate Professor of Phar-macy Practice, St. Louis College of PharmacyKylie N Barnes PharmD BCPS, PGY-2 Ambulatory Care Phar-macy Resident, St. Louis College of PharmacyThomas D Myles MD, Professor, Obstetrics/Gynecology, Depart-ment of Obstetrics, Gynecology, and Women’s Health, School ofMedicine, St. Louis UniversityCorrespondence: Dr. Forinash, aforinash@stlcop.eduReprints/Online Access: www.theannals.com/cgi/reprint/aph.1R167

Conflict of interest: Authors reported none

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EXTRACTO

Uso de Estimulantes de Producción de Leche Materna en Madresque Amamantan

AB Forinash, AM Yancey, KN Barnes, y TD Myles

Ann Pharmacother 2012;46:1392-404.

OBJETIVO: Revisar los datos existentes sobre la eficacia de productosdisponibles en los Estados Unidos y utilizados para estimular laproducción de leche materna.

FUENTE DE DATOS: Se realizó una búsqueda en PubMed (1966–junio2012) y EMBASE (1973–junio 2012) utilizando los términos

amamantar, leche materna, lactancia, metoclopramida, oxitocina,hormona de crecimiento, hormona estimulante de la tiroides,medroxiprogesterona, domperidona, hierbas, galactogogue, fenugreek,milk thistle, silymarin, goat’s rue, beer, asparagus racemosus, shatavari,medicago sativa, alfalfa, onicus benedictus, blessed thistle, galegaofficinalis, y brewer’s yeast.

SELECCIÓN DE ESTUDIOS Y EXTRACCIÓN DE DATOS: Se evaluaron todos losestudios que incluyeran humanos, publicados en el idioma inglés y queevaluaran la eficacia de productos utilizados para estimular laproducción de leche materna.

SÍNTESIS DE DATOS: A pesar que existe evidencia anecdótica que indicaque varias opciones farmacéuticas y productos herbarios causan unaumento en la producción de leche materna, no existe suficienteevidencia en la literatura que apoye su eficacia. Estudios conmetoclopramida, oxitocina, fenugreek, y milk thistle han tenidoresultados inconsistentes relacionados con la producción de lechematerna. Las muestras estudiadas son pequeñas y sus diseños tienenvarias limitaciones.

CONCLUSIONES: La leche materna es considerada la mejor fuente dealimento para niños desde su infancia hasta el primer año de edad.Varios factores influyen la producción de leche materna, incluyendopresencia de dolor, enfermedades, tiempo disponible, ansiedad, y estrésemocional. Se deben agotar las recomendaciones no farmacológicasantes de añadir algún otro tratamiento. A pesar que existe evidenciaanecdótica que fomenta el uso de metoclopramida, fenugreek,asparagus, y milk thistle para aumentar la producción de leche materna,es necesaria evidencia científica que apoye su eficacia y seguridad. Laoxitocina y domperidona pudieran estar disponibles para la preparaciónde mezclas extemporáneas potencialmente útiles, pero los datos sobre laseguridad de su uso son limitados. Son necesarios estudios que evalúenel efecto de los productos disponibles en la producción de leche materna.

Traducido por Astrid J García-Ortiz

RÉSUMÉ

L’Usage des Galactogogues chez la Mère qui Allaite

AB Forinash, AM Yancey, KN Barnes, et TD Myles

Ann Pharmacother 2012;46:1392-404.

OBJECTIF: Revoir les données concernant l’efficacité des galactogoguesdisponibles aux États-Unis et utilisés pour favoriser une productionaccrue de lait maternel après l’accouchement.

SOURCES DE DONNÉES: Une revue de la documentation scientifique a étéeffectuée par le biais de PubMed (1966 à Juin 2012) et EMBASE (1973à Juin 2012). Les termes de recherche de langue anglaise incluaient:breastfeeding, breast milk, lactation, galactogogue, metoclopramide,oxytocin, fenugreek, milk thistle, silymarin, growth hormone, thyroidreleasing hormone, medroxyprogesterone, domperidone, goat’s rue,beer, asparagus racemosus, shatavari, medicago sativa, alfalfa, onicusbenedictus, blessed thistle, galega officinalis, brewer’s yeast, et herbals.

SÉLECTION DES ÉTUDES ET EXTRACTION DES DONNÉES: Toutes les études delangue anglaise incluant des sujets humains et des données évaluantl’efficacité des galactogogues pour augmenter la production de laitmaternel ont été évaluées.

SYNTHÈSE DES DONNÉES: De l’information anecdotique est disponiblepour une variété d’options pharmaceutiques et botaniques concernantleur utilité pour améliorer la production de lait maternel. Cependant ladocumentation scientifique démontrant leur efficacité est insuffisante.Les options tels que le métoclopramide, l’oxytocine, le fenugreek, et lemilk thistle ont démontré des résultats conflictuels en ce qui a trait à leurcapacité d’augmenter la production de lait maternel. Cependant, lesessais cliniques sont de faible envergure et présentent plusieurs limites.

CONCLUSIONS: Le lait maternel est considéré comme l’option nutritiveoptimale pour les nouveaux nés jusqu’à l’âge de 1 an. Plusieurs facteursinfluencent la production de lait maternel incluant les douleurspostpartum et subséquentes, la maladie, le temps disponible lors d’unretour au travail, l’anxiété, et le stress émotionnel. Les options nonpharmacologiques doivent être épuisées avant d’ajouter une thérapiemédicamenteuse. Bien que des données anecdotiques encouragent

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The Annals of Pharmacotherapy n 2012 October, Volume 46 n 1403theannals.com

l’utilisation de métoclopramide, de fenugreek, d’asparagus racemosus, etde milk thistle pour leurs propriétés galactogogues, les donnéesconcernant leur efficacité et leur innocuité sont insuffisantes dans ladocumentation scientifique. L’oxytocine et le dompéridone sont destraitements potentiellement disponibles pour des fins de préparationsmagistrales mais les données d’innocuité sont limitées. Des études

additionnelles sont nécessaires afin d’évaluer les effets desgalactogogues présentement disponibles sur la production de laitmaternel.

Traduit par Chantal Guévremont

1404 n The Annals of Pharmacotherapy n 2012 October, Volume 46 theannals.com

AB Forinash et al.

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