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Acceleration of Luteinizing Hormone Pulse Frequency in Functional Hypothalamic Amenorrhea by Dopaminergic Blockade^*

S. L. BERGA, A. B. LOUCKS, W. G. ROSSMANITH, L. M. KETTEL, G. A. LAUGHLIN and S. S. C. YEN

Department of Reproductive Medicine (T-002) and the General Clinical Research Center, University of California-San Diego School of Medicine La Jolla, California 92093

A constellation of neuroendocrine secretory aberrations, including reduced LH pulse frequency and PRL concentrations, has been documented in women with functional hypothalamic amenorrhea (FHA). As pituitary function was preserved, these aberrations were attributed to an alteration in hypothalamic neuromodulation. To investigate the participation of the dopaminergic system in the genesis of the reduced LH pulse frequency and suppressed PRL levels in FHA, we studied six women with FHA and six cyclic women in the early follicular phase by obtaining blood samples at 15-min intervals for 48 h during sequential 24-h infusions of saline and a dopamine receptor blocker, metoclopramide (MCP). A hypothalamic vs. pituitary site of action was inferred from the pulsatility characteristics. MCP consistently elicited an increase in the LH pulse frequency in the women with FHA [7.3 ± 1.2 (±SE) to 10.5 ± 1.3 pulses/24 h; P < 0.005]. In contrast, the eumenorrheic women did not show a significant change in LH pulse frequency in response to MCP (15.2 ± 1.0 to 14.3 ± 0.9 pulses/24 h). While the PRL concentrations were significantly lower in the FHA group during the infusion of saline (P < 0.001) and MCP (P < 0.005), the relative increases in PRL during MCP were similar in both groups. The acceleration of LH pulse frequency by blockade of dopamine receptors implies that there is increased hypothalamic dopaminergic inhibition of GnRH pulse frequency in women with FHA.

^* This work was supported by NIH Grants HD-21198, HD-12303–12, and GCRC RR-00827, and the American Fertility Society-Ortho Distinguished Fellowship in Reproduction, and was conducted by the Clayton Foundation for Research. Presented in part at the 36th Annual Meeting of the Society for Gynecological Investigation, San Diego, CA, 1989.

Recipient of the Bank of America-Giannini Foundation Fellowship, the American Fertility Society-Ortho Distinguished Fellowship in Reproduction, and the Clinical Associate Physician Award from the NIH. To whom all correspondence should be addressed. Current address: University of Pittsburgh, Magee-Womens Hospital, Department of Obstetrics and Gynecology, Pittsburgh, Pennsylvania 15213.

Received May 22, 1990.

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