Endorphins and the Regulation of the Human Menstrual Cycle

Abstract

In order to assess a possible influence of endogenous opioids upon gonadotrophin secretion in women, we examined the effects of i.v. administration of 10 mg naloxone, a specific opiate antagonist, in ten normal menstruating women, in thirteen women with amenorrhoea and/or hyperprolactinaemia and in two women with putative deficiency of gonadotrophin-releasing hormone (GnRH). In thirteen subjects, a saline vehicle control study (randomized order of administration) was also performed. In the normal women, naloxone failed to elicit changes in serum gonadotrophin levels when administered during the early follicular phase of the menstrual cycle. However, significant increments of LH were observed from 30 to 165 min following naloxone administration during the late follicular phase. Similar LH responses occurred in the amenorrhoeic and hyperprolactinaemic women. There was a tendency towards a concomitant increment in FSH levels, which reached statistical significance variably from 60 to 105 min post-naloxone. The LH response to naloxone in individual subjects showed a significant (P less than 0.01) quadratic (U-shaped) relationship to the log basal oestradiol concentration. No response to naloxone was observed in the two patients with GnRH deficiency despite a brisk response to an exogenous GnRH bolus. Taken together, these data suggest that central nervous system inhibitory opioid pathways may be involved in the regulation of LH secretion in normal women and that excessive production of endogenous opioids may play a role in the pathophysiology of some amenorrhoeic conditions.

The Effects of Opiate Antagonism on Gonadotropin Secretion in Children and in Women with Hypothalamic Amenorrhea

“…This effect has been reported in patients with hypothalamic amenorrhea (3,21). These findings indicate a role of endogenous opioid peptides in suppression of LH secretion in some women with secondary amenorrhea of unknown etiology.…”

Investigations with the Specific μ-Opiate Receptor Agonist Fentanyl in Depressive Patients: Growth Hormone, Prolactin, Cortisol, Noradrenaline and Euphoric Responses

“…It is well known that estrogens influence PRL secre tion [review seeTuomisto and Männisto, 1985] and that endorphins influence human menstrual cycle [Blankstein et al, 1981], Remarkably higher PRL responses to FE were noted in females, moreover a menstrual-cyclerelated variation of these opiate-induced PRL responses was observed [Hoehe, 1988]. Thus, disturbance of the menstrual cycle, such as amenorrhea, phase of menstrual cycle, inclusion of postmenopausal females, and a diver gent number of males and females in patients and con trols may, if not carefully considered and controlled, have influenced analysis of PRL responses of patients and controls.…”

Hypothalamic versus Pituitary Stimulation of Luteinizing Hormone Secretion in the Prepubertal Female Lamb

“…The opioid peptides are also inhibitory to GnRH re lease in the prepubertal and adult sheep [34][35][36], as well as in other species [37][38][39]. Thus, activation of this inhibi tory pathway may prevent a consistent LH response to NMA in the prepubertal lamb.…”