Pulsatile secretory characteristics of allopregnanolone, a neuroactive steroid, during the menstrual cycle and in amenorrheic subjects

Objective: To investigate whether allopregnanolone, a neuroactive steroid involved in modulating behavioural and neuroendocrine functions, shows episodic secretion in eumenorrheic women, during the follicular and luteal phases of the menstrual cycle, and in women with stress-induced amenorrhea. Patients: Six eumenorrheic women and 14 women with hypothalamic amenorrhea were enrolled for the present study. Methods: All subjects underwent hormonal evaluation in baseline conditions and a pulsatility study to determine LH, cortisol and allopregnanolone episodic release. Eumenorrheic subjects were investigated twice, in the follicular phase (days 3 - 7) and in the luteal phase (days 18 - 22) of the menstrual cycle. LH, FSH, prolactin, estradiol, phosphate, DREA, allopregnanolone and cortisol levels were evaluated in each case. Results: In healthy women, serum gonadotropin and gonadal steroid levels were significantly lower (P < 0.01 and P < 0.05 respectively) than those in amenorrheic subjects. Allopregnanolone was higher in amenorrheic subjects and during the luteal phase, compared with the follicular phase, of cumenorrheic subjects (P < 0.01). Pulse analysis revealed a significant episodic discharge of allopregnanolone in all subjects (follicular phase 6.5+/-0.3 peaks/6 h and luteal phase 5.5+/-0.4 peaks/6 h, hypothalamic amenorrhea 7.0+/-0.7 peaks/6 h) with higher pulse amplitude in amenorrheic subjects and during the luteal phase compared with the follicular phase of the cumenorrheic subjects (P < 0.05). Moreover, the specific concordance index demonstrated that allopregnanolone is coupled with LH only during the luteal phase of the cycle and with cortisol during both phases. Allopregnanolone-cortisol coupling was also observed in amenorrheic subjects. Conclusions: Allopregnanolone is secreted episodically. Both the ovary and adrenal glands release this steroid hormone and it shows temporal coupling with LH only during the luteal phase, with cortisol during both the studied phases of the menstrual cycle in eumenorrheic women and again with cortisol in hypothalamic amenorrheic patients.