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

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Abstract
Summary: The effects of opiate antagonism [naloxone infusion, 1 mg/(m2–h)] on gonadotropin secretion were examined in four children (one female and three males: two late prepubertal and two pubertal; chronologic age, range 11.8-15.9 yr, bone age, range 8.5-13.5 yr) and in four women with hypothalamic amenorrhea (two at normal body weight and two at low body weight). Naloxone had no effect on daytime gonadotropin secretion in three children who were biologically the youngest in the group, two late prepubertal and one early pubertal [plasma luteinizing hormone (LH) x ± SE: control day, 1.2 ± 0.1; control night, 4.5 ± 0.4; and naloxone day, 1.3 ± 0.1 mlU/ml). In contrast, opiate blockade produced a slight but discernible increase in plasma LH in the child whose hypothalamic-pituitary-gonadal axis was the most mature, a boy at mid-puberty. Naloxone produced a striking increase in plasma LH in the amenorrheic women at normal body weight (LH, x ± SE: control day, 3.4 ± 03; control night, 7.0 ± 1.0; and naloxone day, 7.4 ± 0.7 mlU/ml) as well as in those at low body weight (LH, x ± SE: control day, 3.5 ± 0.3; control night, 2.8 ± 0.2; naloxone day, 4.9 ± 0.4; and naloxone night, 6.7 ± 0.5 mlU/ml). Antagonism of endogenous opiate activity increased LH pulse frequency in all four women. These findings suggest the following conclusions: 1) the mechanisms responsible for the reduced LH secretion in some women with hypothalamic amenorrhea differ from those in late prepubertal and early pubertal children, and 2) endogenous opiates affect LH pulse frequency by actins at the hypothalamic level to change gonadotropin-releasing hormone pulse frequency.