Effect of mifepristone (RU486) on the pituitary response to gonadotrophin releasing hormone in women

R Kazem, L E Messinis, Paul Alfred Francois Fowler, N P Groome, P G Knight, Allan Templeton

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Mifepristone interrupts folliculogenesis in women but the mechanism is not clear, Previous studies have investigated the effect of this compound on gonadotrophin secretion and have provided conflicting results. To study further the effect of mifepristone on basal and gonadotrophin-releasing hormone (GnRH)-induced gonadotrophin secretion, 12 normally ovulating women were investigated during two consecutive menstrual cycles, comprising an untreated cycle (control) and a cycle treated with mifepristone. All women were treated with mifepristone on days 2-8 at the dose of 100 mg (group 1, eight women) or 10 mg per day (group 2, six women). Two women were treated with both regimens in two different cycles. On day 8 of both cycles, the women received two GnRH pulses of 10 mu g each 2 h apart. Blood samples in relation to the first GnRH pulse were taken at -15, 0, 30, 60, 120, 150, 180 and 240 min. In group I, the increase in luteinizing hormone (Delta LH) in response to GnRH was significantly attenuated from 30 to 180 min, while the increase in follicle stimulating hormone (Delta FSH) was attenuated only in response to the second GnRH pulse. No significant decrease in Delta LH and Delta FSH response to Gn:RH was seen during treatment with the 10 mg dose (group 2). In group 1, serum oestradiol and inhibin-A concentrations after day 8 were lower than in the control cycles and the LH peak was postponed by 7 days on average. Basal LH values increased significantly on day 8 in both groups, while FSH values did not change significantly compared with the control cycles. A significant increase in serum progesterone and cortisol values occurred during the treatment only in group 1. Mid-luteal values of inhibin-A were significantly lower in cycles treated with 100 mg mifepristone than in the control cycles. We conclude that the disruption of folliculogenesis by mifepristone cannot be explained by a decrease in basal FSH concentrations during the critical period of follicle recruitment and selection. It is possible that mifepristone exerts its effect at the level of the ovary. It is also suggested that progesterone during the follicular phase of the cycle may participate in the control of the self-priming action of GnRH on the pituitary.

Original languageEnglish
Pages (from-to)2585-2590
Number of pages6
JournalHuman Reproduction
Volume11
Issue number12
Publication statusPublished - Dec 1996

Keywords

  • folliculogenesis
  • gonadotrophin-releasing hormone
  • mifepristone
  • low-dose mifepristone
  • menstrual-cycle
  • antiprogesterone RU486
  • follicular phase
  • RU-486
  • surge
  • ovulation
  • progesterone
  • inhibition
  • estradiol

Cite this

Kazem, R., Messinis, L. E., Fowler, P. A. F., Groome, N. P., Knight, P. G., & Templeton, A. (1996). Effect of mifepristone (RU486) on the pituitary response to gonadotrophin releasing hormone in women. Human Reproduction, 11(12), 2585-2590.

Effect of mifepristone (RU486) on the pituitary response to gonadotrophin releasing hormone in women. / Kazem, R ; Messinis, L E ; Fowler, Paul Alfred Francois; Groome, N P ; Knight, P G; Templeton, Allan.

In: Human Reproduction, Vol. 11, No. 12, 12.1996, p. 2585-2590.

Research output: Contribution to journalArticle

Kazem, R, Messinis, LE, Fowler, PAF, Groome, NP, Knight, PG & Templeton, A 1996, 'Effect of mifepristone (RU486) on the pituitary response to gonadotrophin releasing hormone in women' Human Reproduction, vol. 11, no. 12, pp. 2585-2590.
Kazem R, Messinis LE, Fowler PAF, Groome NP, Knight PG, Templeton A. Effect of mifepristone (RU486) on the pituitary response to gonadotrophin releasing hormone in women. Human Reproduction. 1996 Dec;11(12):2585-2590.
Kazem, R ; Messinis, L E ; Fowler, Paul Alfred Francois ; Groome, N P ; Knight, P G ; Templeton, Allan. / Effect of mifepristone (RU486) on the pituitary response to gonadotrophin releasing hormone in women. In: Human Reproduction. 1996 ; Vol. 11, No. 12. pp. 2585-2590.
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KW - antiprogesterone RU486

KW - follicular phase

KW - RU-486

KW - surge

KW - ovulation

KW - progesterone

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