Drugs that Suppress Lactation,Part 2

Dopaminergic Drugs

Dopaminergic drugs act by decreasing secretion of prolactin by the pituitary gland. Because lactation success is not directly related to serum prolactin, these drugs are generally not completely effective in suppressing lactation. For example, levodopa is a dopamine precursor that suppresses serum prolactin. Nevertheless, one mother taking sustained-release levodopa and carbidopa for Parkinson's disease successfully breastfed her infant.

The ergot alkaloids and their synthetic derivatives (e.g., bromocriptine) are perhaps the drugs most commonly used intentionally for lactation suppression. Bromocriptine previously had U.S. Food and Drug Administration approval for this use, but it was removed by the manufacturer in the United States because of numerous deaths from myocardial infarction and stroke. Another ergot, lisuride (available outside of the United States) is indicated for lactation suppression in some countries. One mother took bromocriptine for amenorrhea–galactorrhea syndrome while nursing successfully.

The oxytocic ergots, ergonovine and methylergonovine have been studied for their effect on lactation. Ergonovine (no longer commercially available in the United States) given in the immediate postpartum period lowers basal serum prolactin and possibly the suckling-induced prolactin response. It also appears to decrease the rate of breastfeeding. The evidence with methylergonovine is mixed, although it appears that methylergonovine can decrease serum prolactin and possibly the amount of milk production and duration of lactation, especially when used in the immediate postpartum period. The effect appears to be related to the dosage and route of administration, with injected doses having a greater impact than oral doses. A short oral course of methylergonovine immediately postpartum does not appear to markedly decrease lactation.

Cabergoline is a nonergot that is indicated for hyperprolactinemia and has been used successfully to suppress lactation. It is not known whether the cardiovascular risks to nursing mothers are similar to those of bromocriptine, but in almost 500 women reportedly treated to date with cabergoline for lactation suppression, no severe cardiovascular reactions have occurred.

Pramipexole (Mirapex^®), ropinirole (Requip^®), and rotigotine (Neupro^®) are nonergot dopaminergic drugs used for both Parkinson's disease and restless leg syndrome. All reduce serum prolactin, but no information is available concerning their effects on lactation.

Because pyridoxal phosphate is involved in the enzymatic conversion of dopa to dopamine, high dosages of pyridoxine (vitamin B₆) were used in several old studies to suppress lactation with variable results. There is no concern with the small doses of pyridoxine in multivitamins.

Despite their history of use and formal approval, a Cochrane meta-analysis concluded that evidence for efficacy of dopamine agonists for lactation suppression is weak. ¹ Nevertheless, it is best to consider dopamine agonists as drugs to avoid in mothers who wish to continue nursing, unless perhaps, the mother needs treatment for a preexisting condition.

Hormones

Estrogens in high doses either alone or with testosterone were routinely used during the 1960s and 1970s to suppress lactation postpartum. But they increased the risk of thromboembolism and pulmonary embolism and fell out of favor. Supraphysiologic serum levels of testosterone, either from a tumor or from exogenously administered testosterone, reduce serum prolactin and milk production in postpartum women.

Although the effect of estrogens on lactation appears to be dose related, the dose at which they have no effect and when the effect diminishes postpartum are not firmly established. The use of low-dose, estrogen-containing contraceptives postpartum continues to be controversial, in large part because the results of published studies are neither consistent nor of the highest quality. ² This controversy is currently manifested in the disagreement between guidelines from the U.S. Centers for Disease Control and Prevention (CDC) and those of the World Health Organization (WHO). CDC guidelines state that combined (i.e., estrogen-containing) hormonal contraceptives should not be used until after the first 4 weeks postpartum because of concerns about potential effects on blood clotting and breastfeeding performance. ³ The more conservative WHO guidelines recommend not using combined contraceptives in nursing mothers before 6 weeks postpartum and that the disadvantages of using the method generally outweigh the advantages between 6 weeks and 6 months postpartum. ⁴

Progestogen-only contraception is also controversial because of timing and study quality. Because the postpartum drop in progesterone is a trigger for lactation, the argument goes that if a synthetic progestogen is given soon after delivery, lactation will be adversely affected. A systematic review found that there is no clear evidence that early use of progestogen-only contraception has an adverse effect on nursing infants. ⁵ This is reflected in both WHO and CDC guidelines that indicate progestogen-only contraception can generally be started immediately postpartum, except WHO guidelines recommend that injectable forms (e.g., depot medroxyprogesterone acetate, Depot Provera^®) be withheld until 6 weeks postpartum, because of concerns of infant exposure via breast milk, not suppression of lactation. A recent review of four published studies estimated that there is about a 0.9% chance of lactation suppression with the etonogestrel implant (Nexplanon^®) inserted immediately postpartum. Overall, it appears that if immediate postpartum progestogen-only contraception has an adverse effect on lactation, it is a small effect. An excellent review of the impact of postpartum contraception on breastfeeding and the breastfed infant has recently been published. ⁶

Other hormonal agents such as the antiestrogens (e.g., clomiphene, tamoxifen) have been tried as postpartum lactation suppressants. Although there is some indication that they suppress lactation, the studies are limited and inconclusive. ¹

Decongestants

Pseudoephedrine is the most effective oral decongestant. In one small study, a single dose of pseudoephedrine 60 mg orally decreased milk production by 24% over the following 24 hours. There was a 13.5% decrease in serum prolactin after pseudoephedrine, but this difference did not achieve statistical significance.

Animal studies with epinephrine and norepinephrine indicate that these drugs decrease serum oxytocin, which is consistent with anxiety in nursing mothers interfering with letdown. Pseudoephedrine works by releasing epinephrine and norepinephrine from nerve endings, so it is reasonable to assume that oxytocin is also lowered by pseudoephedrine. Since restrictions on pseudoephedrine went into effect, many over-the-counter products have substituted phenylephrine for pseudoephedrine. Although intravenous phenylephrine decreases milk yield in animals, oral phenylephrine has poor oral bioavailability and a very brief duration of action, so it is unlikely to affect milk supply. However, no human studies are available on phenylephrine and lactation.

Anticholinergics and Antihistamines

Anticholinergics (e.g., atropine) inhibit lactation in animals, apparently by decreasing growth hormone and oxytocin secretion. Anticholinergic drugs also reduce serum prolactin in non-nursing women and cases of lactation suppression have been reported with the anticholinergic drug oxybutynin in postmarketing surveillance. The concern with anticholinergic drugs does not extend to inhaled anticholinergics (e.g., tiotropium) used for asthma and other breathing disorders, because they are very poorly absorbed from the respiratory tract.

First-generation antihistamines (e.g., diphenhydramine, chlorpheniramine) have anticholinergic properties that might contribute to diminution of lactation. In relatively high doses given by injection, these drugs can decrease basal serum prolactin in nonlactating women and in early postpartum women. However, suckling-induced prolactin secretion is not affected by antihistamine pretreatment of postpartum mothers. Whether lower oral doses of antihistamines have the same effect on serum prolactin or whether the effects on prolactin have any consequences on breastfeeding success have not been studied. Some combination products for colds and allergies contain both an older antihistamine and pseudoephedrine, so they might affect lactation more than either alone. Newer, nonsedating antihistamines (e.g., fexofenadine, loratadine) have little or no anticholinergic activity and are preferred during breastfeeding.

Diuretics

Diuretics have been studied as postpartum lactation suppressants, including thiazide-type agents (e.g., chlorthalidone, hydrochlorthiazide), and loop diuretics (e.g., ethacrynic acid, furosemide). These small trials have been performed in the immediate postpartum period using high doses of the drugs combined with breast binding and/or fluid restriction. No evidence indicates that the typical low doses of diuretics used to treat hypertension in nursing mothers would have a lactation inhibiting effect.

Antipsychotics

Most antipsychotic agents have some dopamine antagonist activity, thereby increasing serum prolactin. Nonpuerperal lactation or galactorrhea in patients of both sexes is an occasional side effect of these drugs. However, aripiprazole and promethazine, which are virtually devoid of dopamine antagonism, can sometimes decrease serum prolactin. They have interfered with lactation in a few cases. In one case, aripiprazole, combined with other psychotropic drugs, appeared to cause a decreased milk supply and consequent severe hypernatremic dehydration in the breastfed infant.

Herbals

Several herbal products have been purported to suppress lactation, but data range from poor to nonexistent. Jasmine is perhaps the best studied. Evidence for its possible efficacy is a study of nonlactating women with elevated serum prolactin values caused by antipsychotic drug therapy. Only 10 of the 35 women given an extract of jasmine flowers had a drop in serum prolactin of 25 mcg/L or greater and the overall average decrease in prolactin was not statistically significant. A recent study compared the daily topical application of jasmine flowers to the breasts with oral bromocriptine for lactation suppression in postpartum women. At the end of 72 hours, almost all women in both groups had lactation suppressed, although the women in the bromocriptine group had lower serum prolactin levels than those in the jasmine group.

Licorice extracts in high doses can suppress basal and stimulated serum prolactin, although actual lactation suppression has not been reported. Curiously, licorice is a component of numerous combination herbal galactagogue products. Parsley and sage are also said to suppress lactation, but their use is anecdotal and no human lactation studies have been found on these herbs.

Individual Reports

A few drugs have been reported to suppress lactation in individual cases, although these cannot be considered definitive. The most widely cited is a single case of a mother whose lactation stopped after passing a roundworm following mebendazole treatment. Subsequent studies have debunked any detrimental effect of mebendazole on lactation, so it should not be considered a risky drug to use during lactation.

Three cases of lactation suppression have been reported after local injection of a high-dose corticosteroid. In one mother, 80–120 mg of triamcinolone was injected epidurally into her cervical and thoracic spine and the facets. Three days later, she noticed a decrease in milk supply and a reduced ejection reflex that continued to worsen over the next 5 days. The second mother had 24 mg of depot methylprednisolone plus 15 mg of lidocaine injected intralesionally for tenosynovitis of the wrist. Thirty hours after the injection, lactation ceased. Her breasts were soft and not engorged at that time. Thirty-six hours later, lactation resumed slowly, reaching normal milk production 24 hours later. In the third case, a nursing mother had triamcinolone 40 mg injected into her wrist for tenosynovitis. Twenty-four hours after the injection, her milk supply dropped by 90%. Within 1 week, her milk supply increased by 50% and by 1 month after the injection, she was able to meet her infant's breast milk needs. Typical oral doses of corticosteroids do not suppress lactation.