Hormones and hormone antagonists

Experience

There are only a few publications that discuss tolerance of hypothalamic and pituitary hormones during breastfeeding. In a series of studies on the contraceptive effect of 600 μg of buserelin, a luteinizing hormone-releasing hormone (LRH) antagonist administered nasally, a dosage of 1–2 μg was reported for the fully breastfed infant. Oral bioavailability is poor, so a toxic effect on a breastfed child is not to be expected ( ).

The thyrotropin-releasing hormone (TRH) protirelin releases prolactin. Its lactation-promoting use has been discussed ( ). Toxic effects on a breastfed infant are not to be expected; however, studies are lacking.

Desmopressin is found in the mother’s milk in only limited amounts. Oxytocin , which has long been used to induce labor and for postpartum uterine involution, promotes the milk ejection reflex, and has not been shown to be toxic for the infant.

Carbetocin is a synthetic long acting analog of oxytocin, which is used intravenously and intramuscularly. It appears in the mother’s milk in minimal amounts (0.00005% of the maternal weight-related dosage) ( ). There are no data on the use during breastfeeding of the other hypothalamic and pituitary hormones, or their synthetic analogs corticorelin , sermorelin , somatorelin , cetrorelix , chorionic gonadotrophin , gonadorelin , goserelin , leuprolide acetate , menotropin , nafarelin , triptorelin , urogonadotropin , octreotide , somatostatin , tetracosactid , somatropin (growth hormone), follitropin-α , follitropin-β , urofollitropin , argipressin , lypressin , ornipressin , lanreotide , and terlipressin . This also holds true for the oxytocin-antagonist atosiban and the somatropin-receptor antagonist pegvisomant .

Experience

With a maternal therapy of 2 × 0.125 mg methylergometrine up to 1.1 μg/L has been measured in the milk. This is a maximum of 0.16 μg/kg of the infant’s bodyweight, or 3.1% of the maternal weight-related dosage. In a more recent study on 20 women with postpartum uterine atony, either 250 μg methylergometrine or 200 μg misoprostol were applied orally (see also Section 4.11.13 ). The maximum methylergometrine concentration in milk was reached at 2 hours. It has a half-life of 1.9 hours. Considering the maximum concentration in milk, the relative dose was 2.4%. The median M/P ratio was 0.2 ( ).

A potentially negative influence on milk production due to prolactin antagonism is known. For breastfed infants themselves, the preparation seems to be tolerated in the overwhelming majority of cases. It should, however, be mentioned that TIS-Berlin has to date received 15 case descriptions involving ergotism-like symptoms in breastfed children (particularly restlessness, vomiting, and diarrhea) (Schaefer, personal communication). This cannot be explained in the light of the above-mentioned limited transfer. Experiences with accidental direct administration of methylergometrine to the newborn infant, due to a mix-up of the medication in the delivery room, also argue against a toxic risk via the mother’s milk. In such cases, ergotism-like symptoms were first observed after a dosage that was 150–200 times above that transferred through mother’s milk (Poison Control Center Berlin, unpublished observations). However, hypersensitivity, or the transfer of individual higher doses via breast milk, cannot be ruled out. In this connection, those studies on the pharmacological effects of ergotamine residue in mothers’ milk substitute conducted in the 1930s are at least of historical interest ( ).

Experience

Bromocriptine is an ergotamine derivative. As a prolactin inhibitor, it reduces the milk production and is used to treat prolactinoma. Because of the possible cardiovascular side effects in the mother, particularly the threat of cerebral angiopathy and myocardial infarction ( , ), it has been removed from the market for use in postpartum lactation suppression ( ; see also Chapter 3.7 ). Intolerance in the breastfed baby, even with prolactinoma treatment, has not been observed ( ). Even after an intake of 5 or 10 mg daily, no side effects via the mother’s milk are to be expected in the infant.

The effect of breastfeeding on the growth of the prolactinoma appears to be more limited than that of pregnancy, so an interruption of dopamine agonist treatment with bromocriptine during breastfeeding can be considered ( ).

Cabergoline is taken less often (e.g. once a week) because of its considerably longer half-life and period of effectiveness. In addition, there seem to be fewer side effects. With respect to the other prolactin inhibitors, lisuride , metergoline , and quinagolide , experience during breastfeeding is insufficient.

Experience

L-thyroxine is used as a substitute in cases of hypothyroidism (at least 1 μg/kg daily for adults) and for this reason, is not problematic. The normal thyroid content of mother’s milk is approximately 1 μg/L. An infant takes in about 0.15 μg/kg in 24 hours; this represents about 1% of a substitution dosage at this age (10 μg/kg daily). This amount does not influence the thyroid function of a healthy infant. The same applies for treatment (substitution) of maternal hypoparathyroidism.

This also implies that maternal L-thyroxine substitution has no therapeutic effect in cases of a neonatal congenital hypo- or athyroidism. This has to be taken into account in cases of extremely premature newborns with a higher risk for hypothyroidism. Neither breast milk nor formula contains enough thyroxine for substitution ( ).

The clinical use of thyroid receptor antibodies (TRAb) measurements for the diagnosis and follow-up of autoimmune thyroid diseases, remains a matter of controversy and differs geographically. TRAb can result in transient neonatal thyroid disease by transfer through milk from mothers treated for thyrotoxicosis. Serum TRAb concentration in neonates decreases gradually with time after birth. The calculated half-life for offspring-serum and breast-milk TRAb has been calculated as approximately 3 weeks and 2 months, respectively. Transient neonatal thyroid disease may be worse and more prolonged during breastfeeding as a consequence of TRAb in breast milk ( ).