Gonadotropin-releasing hormone antagonist for postpartum contraception: outcome for the mother and male offspring in the marmoset.
GnRH antagonists have potential for use in postpartum contraception, as it is likely that they would be effective in maintaining the inhibition of ovulation associated with lactation, but possible effects on the infant by transfer of antagonist via breast milk are unknown. The aim of this study was to establish whether chronic treatment with a GnRH antagonist would prevent ovulation throughout the period of lactation using the marmoset monkey as a model and to evaluate the effects of the presence of GnRH antagonist in breast milk on the postnatal rise in plasma testosterone concentrations in male infants. Mothers who had delivered male twins were selected. Starting within 3 days postpartum, mothers (n = 5/group) were treated with either 6.0 or 0.6 mg/kg of the GnRH antagonist antide, sc, once per week for 11 weeks. Ten postpartum lactating females acted as controls. All animals were housed in family groups with fertile males. To determine possible effects on the postnatal rise in testosterone, plasma samples were collected from the male infants of the high dose antide-treated mothers at weekly intervals for 12 weeks. Plasma progesterone concentrations were monitored in lactating mothers until establishment of pregnancy in both treated and control groups. Concentrations of antide were determined by RIA in plasma from mothers in the high dose group, in their milk, and in pooled plasma samples from their infants. Ovulation followed by pregnancy occurred in all of the control animals. No ovulations occurred during treatment with antide. Antide was present throughout treatment in plasma and breast milk in the mother. In male infants feeding from mothers receiving high dose treatment, antide was not detectable in infant plasma, and plasma testosterone concentrations were within the normal range for male neonates in our colony. These results indicate that the GnRH antagonist has potential as a method of contraception postpartum without affecting the postnatal rise in testosterone in male infants.
Fraser
H M
HM
Medical Research Council Reproductive Biology Unit, Center for Reproductive Biology, Edinburgh, United Kingdom.
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Conn
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Lunn
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D000818:Animals; D000831:Animals, Newborn / Q000033:anatomy & histology / Q000097:blood*; D001835:Body Weight / Q000187:drug effects; D002144:Callithrix; D003267:Contraception; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000037:antagonists & inhibitors*; D007774:Lactation; D008297:Male; D008892:Milk / Q000378:metabolism; D009842:Oligopeptides / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D009994:Osmolar Concentration; D010060:Ovulation / Q000187:drug effects; D049590:Postpartum Period; D011247:Pregnancy; D011256:Pregnancy Outcome; D012727:Sex Characteristics; D013739:Testosterone / Q000097:blood
D009842:Oligopeptides; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; C057022:iturelix