The postpartum period is characterized hormonally by elevated levels of PRL and low levels of
gonadotropins and sex
steroids. In breast feeding, this state of
postpartum amenorrhea can persist for an extended period, even though PRL levels decrease slowly. Although the action of PRL on multiple target sites has frequently been suggested as the cause of this ovarian quiescence, a suckling-induced alteration in hypothalamic
gonadotropin-releasing hormone (
GnRH) production has also been hypothesized. To test this latter hypothesis, we provided a uniform pulsatile
GnRH stimulus to eight exclusively breast-feeding women for an 8-week duration beginning at 4 weeks postpartum. Five women with functional hypothalamic
amenorrhea served as a comparison group. All women received
GnRH administered at a dose of 200 ng/kg every 90 min sc via a portable
infusion pump. Serial blood sampling for LH, FSH, and PRL was performed weekly for 5 h at 10-min intervals beginning immediately before initiation of
GnRH, during the period of
GnRH, and 1 week after the cessation of
GnRH. The women collected daily urine aliquots for
estrone-3-glucuronide,
pregnanediol-3-glucuronide, and LH determinations. Serial transvaginal sonography was used to monitor follicular development. Before
GnRH treatment the urinary
steroid and serum
gonadotropin levels of the two groups were low and similar. As expected, PRL levels were higher in the postpartum women (87 micrograms/mL vs. 4.25 micrograms/L, P < 0.05). After initiation of pulsatile
GnRH, LH values increased and FSH values decreased in both groups. The LH increase with
GnRH was significantly greater in the breast-feeding group than in the hypothalamic
amenorrhea group (19.75 mIU/mL vs. 12.34 mIU/mL, P < 0.05). Analysis of pulse frequency and amplitude revealed a nearly complete 1:1 induction of LH pulses by the exogenous
GnRH in both groups, with the breast-feeding group showing a greater amplitude (12.26 mIU/mL vs. 5.34 mIU/mL, P < 0.05). The cycle lengths, urinary
steroids, and vaginal ultrasonography demonstrated a more rapid initial ovarian responsiveness in the breast-feeding group, as determined by the length of the first follicular phase. The breast-feeding group also showed a brisker ovarian response, as evidenced by a greater number of follicles that were 12 mm or greater (2.3 vs. 1.2, P < 0.05), and a greater luteal phase peak and integrated
pregnanediol excretion, respectively (3.02 micrograms/L
creatinine and 39.87 micrograms/L
creatinine/cycle vs. 1.89 micrograms/L
creatinine and 7.69 micrograms/L
creatinine/cycle, P < 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)