THE EFFECTS OF CHRONIC TREATMENT WITH LHRH ON GONADOTROPHIN SECRETION AND PITUITARY RESPONSIVENESS TO LHRH IN WOMEN WITH SECONDARY HYPOGONADISM

Abstract

Twenty women with secondary hypogonadism and four normal women in the early follicular phase of the cycle were treated for 7 days with 10, 50 or 100 micrograms synthetic LHRH administered intramuscularly at 4 h intervals. Concentrations of pituitary and ovarian hormones in plasma were measured at intervals during the treatment period. The episodic pattern of LH secretion and the gonadotrophin responses to acute stimulation with LHRH were evaluated before and after treatment. In normal women the concentrations of gonadotrophins and the LH response to LHRH remained unchanged, whilst the FSH response to LHRH was reduced after treatment. Concentrations of oestradiol rose progressively in response to treatment, indicating follicular development. In hypogonadal subjects with unimpaired pituitary function, treatment with LHRH induced a marked but transient increase in the concentrations of LH and FSH in plasma and a progressive rise in that of oestradiol. The concentration of progesterone was increased in four of the 11 subjects. However, the amplitude of LH pulses and the responses of FSH and LH to LHRH after treatment were suppressed below pretreatment values. Women with hypogonadotrophic hypogonadism and diminished pituitary responses to LHRH exhibited a sustained increase in the concentrations of LH, FSH and oestradiol in plasma to normal follicular phase levels. The amplitude of LH pulses and the LH response to LHRH were increased after treatment but did not reach normal values. The FSH response to LHRH was further reduced after treatment. Treatment of similar subjects with 10 micrograms LHRH induced a small increase in the concentration of gonadotrophins but not of ovarian steroids. These data demonstrate that the effect of chronic treatment with LHRH on women with secondary hypogonadism depends on the level of endogenous gonadotrophins. The dose of LHRH used in hypogonadal women receiving treatment by intermittent injection may require adjusting according to the level of gonadotrophin secretion if an optimal response is to be obtained.