Human Reproduction, Vol. 14, No. 8, 1993-1997,
August 1999
© 1999 European Society of Human Reproduction and Embryology
Parenteral administration of progestin Nestorone® to lactating cynomolgus monkeys: an ideal hormonal contraceptive at lactation?
1 Steroid Research Laboratory, Institute of Biomedicine, 2 Department of Obstetrics and Gynecology, University of Helsinki, Finland, 3 The Population Council, Center for Biomedical Research, New York, 4 The Jones Institute for Reproductive Medicine, Eastern Virginia Medical School, Norfolk, and 5 Balance Pharmaceuticals Inc., Santa Monica, USA
Nestorone® (NES) progestin is highly effective for contraception following parenteral administration, but ineffective after oral ingestion due to rapid first-pass metabolism. Thus, NES might be ideal for lactational contraception; possible NES in milk should be metabolized by the nursing infant. We evaluated the distribution of NES, its endocrine effects and infant weight gain in five cynomolgus monkeys and their nursing infants. Nestorone® implants, releasing ~40 µg NES/day in vitro, were placed s.c. in the mothers 3–4 months following delivery, where they remained in situ for 4 weeks. Sampling (blood daily from the mother; milk and blood from the infant at 3 day intervals) was initiated at 2 weeks prior to insertion, and continued for 2 weeks following removal of the implant. NES, oestradiol, progesterone and prolactin were measured by radioimmunoassays and the infants were weighed weekly. The (mean ± SD) maternal serum and milk concentrations of NES were 337 ± 90 and 586 ± 301 pmol/l during the use of the implants. The ratio of milk/serum NES was 1.68 ± 0.12 (mean ± SE), and the serum and milk concentrations were significantly correlated (r = 0.75, P < 0.001). NES was not detectable (<13 pmol/l) in any infant serum samples. Concentrations of prolactin (mean ± SD) were 41.1 ± 32, 26.7 ± 7.6 and 26.3 ± 9.5 ng/ml before, during and after the use of the implants respectively. The (mean ± SE) infant weight increased from 643 ± 54 g 1 week prior to insertion to 713 ± 54 g 1 week following removal. These data confirm that NES in milk is rapidly metabolized by the suckling infant. Therefore, NES appears to be an ideal hormonal contraceptive for use during lactation.
Key words: distribution/lactation/pharmacokinetics/progestin-only contraception/radioimmunoassay
6 To whom correspondence should be addressed at: Steroid Research Laboratory, Institute of Biomedicine, PO Box 8, FIN-00014, University of Helsinki, Finland
Nestorone® is a registered trademark of The Population Council, New York, NY, USA