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Effect of mifepristone (RU486) on the pituitary response to gonadotrophin releasing hormone in women.
Hum Reprod. 1996 Dec; 11(12):2585-90.HR

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 micrograms 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 1, 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 GnRH 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.

Authors+Show Affiliations

Department of Obstetrics and Gynaecology, University of Aberdeen, UK.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

9021355

Citation

Kazem, R, et al. "Effect of Mifepristone (RU486) On the Pituitary Response to Gonadotrophin Releasing Hormone in Women." Human Reproduction (Oxford, England), vol. 11, no. 12, 1996, pp. 2585-90.
Kazem R, Messinis LE, Fowler P, et al. Effect of mifepristone (RU486) on the pituitary response to gonadotrophin releasing hormone in women. Hum Reprod. 1996;11(12):2585-90.
Kazem, R., Messinis, L. E., Fowler, P., Groome, N. P., Knight, P. G., & Templeton, A. A. (1996). Effect of mifepristone (RU486) on the pituitary response to gonadotrophin releasing hormone in women. Human Reproduction (Oxford, England), 11(12), 2585-90.
Kazem R, et al. Effect of Mifepristone (RU486) On the Pituitary Response to Gonadotrophin Releasing Hormone in Women. Hum Reprod. 1996;11(12):2585-90. PubMed PMID: 9021355.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of mifepristone (RU486) on the pituitary response to gonadotrophin releasing hormone in women. AU - Kazem,R, AU - Messinis,L E, AU - Fowler,P, AU - Groome,N P, AU - Knight,P G, AU - Templeton,A A, PY - 1996/12/1/pubmed PY - 1996/12/1/medline PY - 1996/12/1/entrez KW - Biology KW - Case Control Studies KW - Developed Countries KW - Endocrine Effects KW - Endocrine System KW - Europe KW - Follicle Stimulating Hormone KW - Gonadotropins KW - Gonadotropins, Pituitary KW - Greece KW - Hormone Antagonists KW - Hormones KW - Luteinizing Hormone KW - Mediterranean Countries KW - Northern Europe KW - Physiology KW - Pituitary Gland KW - Pituitary Hormone Releasing Hormones KW - Research Methodology KW - Research Report KW - Ru-486--administraction and dosage KW - Southern Europe KW - Studies KW - United Kingdom SP - 2585 EP - 90 JF - Human reproduction (Oxford, England) JO - Hum Reprod VL - 11 IS - 12 N2 - 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 micrograms 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 1, 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 GnRH 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. SN - 0268-1161 UR - https://www.unboundmedicine.com/medline/citation/9021355/Effect_of_mifepristone__RU486__on_the_pituitary_response_to_gonadotrophin_releasing_hormone_in_women_ L2 - https://academic.oup.com/humrep/article-lookup/doi/10.1093/oxfordjournals.humrep.a019174 DB - PRIME DP - Unbound Medicine ER -