Endocrine response to pregnanolone

Neuroendocrine effects of the neurosteroids, pregnanolone and allopregnanolone have been demonstrated in rats. The endocrine effects of pregnanolone in humans have so far not been fully elucidated. This study has evaluated the effects of pregnanolone administration on part of the hypothalamus-pituitary-gonadal (HPG) axis throughout the menstrual cycle in control subjects and patients with premenstrual syndrome (PMS). Intravenous pregnanolone and vehicle were given to eight women with, and eight women without, PMS during the mid-follicular and late luteal phase. Following the drug administrations, progesterone, estradiol, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and prolactin plasma levels were measured. Intravenous pregnanolone induced a rise in progesterone levels in the follicular phase. In the luteal phase progesterone levels decreased in response to pregnanolone provocation. Pregnanolone did not induce any changes in estradiol, LH, FSH or prolactin plasma levels in either cycle phase. PMS patients and control subjects did not differ with respect to the endocrine effects of pregnanolone. In conclusion, our data show that pregnanolone, in moderate doses, appears not to have any adverse effects on the HPG axis, irrespective of cycle phase.