Effects of cetrorelix, a GnRH-receptor antagonist, on gonadal axis in women with functional hypothalamic amenorrhea

Abstract

Background. Gonadotropin Releasing Hormone (GnRH) antagonists (GnRHa) suppress gonadotropin and sex-steroid secretion. In normal women, acute GnRHa administration induces inhibitory effect on pituitary-gonadal axis, followed by Luteinizing Hormone (LH) rebound. Functional hypothalamic amenorrhea (HA) is characterised by impaired gonadotropin secretion and hypogonadism secondary to blunted GnRH pulsatility.

Methods. We studied the effects of a GnRHa, cetrorelix (CTX 3.0 mg), in six women with HA (age 30.7 ± 3.2 years; BMI 21.5 ± 1.7 kg/m²) and six control subjects (CS, 28.2 ± 0.6 years; 22.6 ± 0.9 kg/m²) on LH, Follicle-Stimulating Hormone (FSH) and oestradiol levels over 4 h (08.00–12.00 am) before, +24 h and +96 h after CTX; LH, FSH, and oestradiol were also evaluated at +6, +8, +12, +48, +72 h after CTX.

Results. CS: CTX reduced (p < 0.05) LH, FSH, and oestradiol (nadir at +12 h, +24 h, and +24 h); LH rebounded at +96 h, FSH and oestradiol recovered at +48 h and +72 h. The 4-h evaluation showed LH and FSH reduction (p < 0.05) at +24 h, with LH rebound at +96 h. HA: CTX reduced (p < 0.05) LH, FSH, and oestradiol, (nadir at +24 h, +48 h, and +48 h, recovery at +48 h, +72 h, and +96 h). The 4-h evaluation showed gonadotropin reduction (p < 0.05) 24 h after CTX, without any rebound effect.

Conclusions. One single CTX dose still modulates gonadotropin secretion in HA. Its ‘paradoxical’ stimulatory effect on gonadotropins needs to be verified after prolonged administration.

Keywords:

• Cetrorelix
• GnRH antagonists
• hypothalamic amenorrhea
• FSH
• LH
• oestradiol

Acknowledgements

The authors thank Dr. A. Bertagna and Mrs A. Barberis for their skillful technical assistance. This study was supported by grants from the University of Turin, Italy.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.