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The Roles of Estradiol and Progesterone in Decreasing Luteinizing Hormone Pulse Frequency in the Luteal Phase of the Menstrual Cycle^*

TODD B. NIPPOLDT, NANCY E. REAME, ROBERT P. KELCH and JOHN C. MARSHALL

Division of Endocrinology and Metabolism, University of Michigan Ann Arbor, Michigan 48109
Department of Internal Medicine, University of Michigan Ann Arbor, Michigan 48109
Department of Pediatrics, University of Michigan Ann Arbor, Michigan 48109

Address requests for reprints to: John C. Marshall, M.D., University of Michigan Hospitals, Department of Internal Medicine/Endocrinology and Metabolism, 1500 East Medical Center Drive, 3920 Taubman Center, Box 0354, Ann Arbor, Michigan 48109–0354.

During the luteal phase of the menstrual cycle, plasma progesterone (P) and estradiol (E₂) concentrations are elevated, and LH (and by inference GnRH) pulse frequency is slow. In contrast, LH pulse frequency increases during the early follicular phase when plasma E₂ and P are lower. To examine the mechanism(s) responsible for the slower GnRH pulse frequency in the luteal phase, we maintained plasma P, E₂, or both at midluteal concentrations from the midluteal phase to the time of the next early follicular phase and measured the effects on LH secretion.

Thirteen normal women with regular menstrual cycles were studied during two or three cycles. Blood was obtained every 10 min during 10-h studies. Control cycle luteal and early follicular studies were followed by a second control study in the luteal phase of the treatment cycle. P (six women), E₂ (seven women), or both (five women) then were given twice daily by im injection for 6–12 days until the day corresponding to the early follicular study of the control cycle (EF + P, EF + E₂, or EF + E₂ + P). A final study was performed 1 week after the injections were discontinued (F).

LH pulse frequency was low in the midluteal phase [3.2 ± 0.2 (±SE) pulses/10 h] and increased by the early follicular phase (8.0 ± 0.8 pulses/10 h) in the control cycles. The increase in LH pulse frequency was not significantly inhibited by administration of P (6.7 ± 0.7 pulses/10 h; EF + P). However, during both E₂ alone and E₂ + P, LH pulse frequency remained low (EF + E₂, 3.6 ± 0.8; EF + E₂ + P, 2.0 ± 0.7 pulses/10 h). The mean plasma FSH concentrations paralleled changes in LH pulse frequency, increasing from the luteal to the early follicular phase in the control cycles and during P injections and remaining low during E₂ and E₂ + P injections. We conclude that continued exposure to P alone does not maintain GnRH pulse frequency at midluteal phase values and that any effect of P requires the presence of E₂. As E₂ alone maintained lower LH pulse frequency, E₂ may act directly to decrease the pulsatile GnRH secretion or it may potentiate the effects of low (<3.2 nmol/L) P concentrations.

^* Presented in part at the 69th Annual Meeting of The Endocrine Society, Indianapolis, IN, June 1987. This work was supported by NIH Grant RO1-HD-1600-05 and Clinical Research Center Grant 5M01-RR-42.

Current address: Division of Endocrinology and Metabolism, Mayo Clinic, Rochester, Minnesota 55905. Recipient of National Research Scientist Award 1-F32-HD-7029-01 from the NICHHD.

Received October 14, 1988.

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