Gonadotrophin-Release Upon Intravenous Administration of a Long-Acting Analogue of Luteinizing Hormone-Releasing Hormone in Females With Increased Plasma-Androgens

Abstract

D-Ser-(TBU)6-EA10-LH-RH, an analogue of luteinizing hormone-releasing hormone (LH-RH) with prolonged action evokes in normal male and female subjects a qualitatively different secretory pattern of LH, as peak levels are reached between 30 and 60 min in males and between 120 and 240 min in females. Females with increased production of adrenal androgens due to congenital adrenal hyperplasia (off substitution therapy; N = 8), idiopathic hirsutism (N = 1) and adrenocortical carcinoma (N = 2) present upon the administration of the LH-RH-analogue with a secretory pattern of LH and FSH which is qualitatively identical with that of normal female subjects, whereas the response of LH in these patients differs from that seen in normal males. Pre-treatment with dexamethasone did not induce any qualitative changes in the secretory response of LH and FSH upon the LH-RH-analogue in patients with increased endogenous production of adrenal androgens. A larger pool and/or a more pronounced de novosynthesis of LH, which apparently is not altered by increased levels of adrenal androgens, may be the cause of the more pronounced and prolonged increase of LH in female subjects following the administration of the LH-RH-analogue. Previous studies about the action of D-Ser-(TBU)C-EA10-LH-RH (König et al. 1975) in normal male (Wiegelmann el al. 1976; Vierhapper et al. 1977) and female (Friedrich et al. 1978; Dericks-Tan et al. 1977) subjects have shown a prolonged response of LH and FSH in comparison to equimolar doses of

An Adrenal Adenoma Causing Virilization of Mother and Infant

“…It would appear that normal menstrual function and fertility were maintained in the present case in the face of moderate long-term androgen excess, a phenomenon which may be explained by the relative insensitivity of the female hypothalamus to the LH-suppressive effect of androgen (Vierhapper et al, 1979). The birth of a virilized infant to a mother in whom there was only equivocal clinical evidence of virilization is an apparent paradox, but the response of the tumour to exogenous gonadotrophin suggests that androgen production may have been enhanced during pregnancy.…”

Serum concentrations of gonadotrophins in hypergonadotrophic patients following stimulation by a long-acting analogue of luteinizing hormone-releasing hormone

“…This is in contrast to the prolonged second segment of the biphasic LH release induced by prolonged infusion of natural LHR (De Kretser et al 1975). This sexual difference cannot be ex¬ plained by the prevailing sex-steroid hormone milieu, since it is maintained in women with ele¬ vated serum concentrations of androgens and in men with elevated concentrations of serum oestradiol (Vierhapper et al 1979. A qualitatively similar response of FSH upon stimulation with the LRH-analogue is seen in healthy men and women with a delayed response in both groups (Vierhapper et al 1979Vier¬ happer 8c Waldhäusl 1980).…”

“…This sexual difference cannot be ex¬ plained by the prevailing sex-steroid hormone milieu, since it is maintained in women with ele¬ vated serum concentrations of androgens and in men with elevated concentrations of serum oestradiol (Vierhapper et al 1979. A qualitatively similar response of FSH upon stimulation with the LRH-analogue is seen in healthy men and women with a delayed response in both groups (Vierhapper et al 1979Vier¬ happer 8c Waldhäusl 1980). A similar pattern of stimulated FSH secretion was also found in the various groups of hypergonadotrophic patients examined in this study.…”

“…This sexual difference in LH release is unaffected by increased serum concentra¬ tions of androgens in females and by increased serum oestradiol concentrations in males (Vierhapper et al 1979 and may be due to differences in the size of the 'second poof of LH in men and women. The object of the present study was to investigate the effect of the LRH-analogue in patients with increased gonadotrophin produc¬ tion either due to previous orchidectomy or due to Klinefelter's syndrome.…”