Journal of Clinical Endocrinology & Metabolism, Vol 80, 2088-2093, Copyright © 1995 by Endocrine Society

ARTICLES

Pulsatile GnRH stimulates normal cyclic ovarian function in amenorrheic lactating postpartum women

MJ Zinaman, T Cartledge, T Tomai, P Tippett and GR Merriam
Department of Obstetrics and Gynecology, Loyola University Medical Center, Maywood, Illinois 60153, USA.

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)

This article has been cited by other articles:

				A. Bachelot and N. Binart Reproductive role of prolactin Reproduction, February 1, 2007; 133(2): 361 - 369. [Abstract] [Full Text] [PDF]

				A. M. Ahmad, R. Guzder, A. M. Wallace, J. Thomas, W. D. Fraser, and J. P. Vora Circadian and Ultradian Rhythm and Leptin Pulsatility in Adult GH Deficiency: Effects of GH Replacement J. Clin. Endocrinol. Metab., August 1, 2001; 86(8): 3499 - 3506. [Abstract] [Full Text] [PDF]

				A. Perheentupa, H. O. D. Critchley, P. J. Illingworth, and A. S. McNeilly Enhanced Sensitivity to Steroid-Negative Feedback during Breast-Feeding: Low-Dose Estradiol (Transdermal Estradiol Supplementation) Suppresses Gonadotropins and Ovarian Activity Assessed by Inhibin B J. Clin. Endocrinol. Metab., November 1, 2000; 85(11): 4280 - 4286. [Abstract] [Full Text]

				G. Barnard and F. Kohen Monitoring ovarian function by the simultaneous time-resolved fluorescence immunoassay of two urinary steroid metabolites Clin. Chem., July 1, 1998; 44(7): 1520 - 1528. [Abstract] [Full Text] [PDF]

				J. M. Bowen, G. E. Dahl, N. P. Evans, L. A. Thrun, Y. Wang, M. B. Brown, and F. J. Karsch Importance of the Gonadotropin-Releasing Hormone (GnRH) Surge for Induction of the Preovulatory Luteinizing Hormone Surge of the Ewe: Dose-Response Relationship and Excess of GnRH Endocrinology, February 1, 1998; 139(2): 588 - 595. [Abstract] [Full Text] [PDF]