THE EFFECT OF DANAZOL AND THE LHRH AGONIST ANALOG GOSERELIN (ZOLADEX) ON THE BIOLOGICAL-ACTIVITY OF LUTEINIZING-HORMONE IN WOMEN WITH ENDOMETRIOSIS

In an attempt to determine whether the suppression in oestradiol levels caused by danazol is due to an effect on the hypothalamic‐pituitary axis, we compared the endocrine effects of danazol with those of the LHRH (GnRH) agonist analogue goserelin. Serum levels of immunoreactive LH (I‐LH), FSH, 17β‐oestradiol (E2) and bioactive LH (B‐LH) (using a mouse Leydig cell bioassay), were measured in ten and 20 women with endometriosis treated with danazol and goserelin, respectively. I‐LH was measured both by radioimmunoassay (RIA) and immunoradiometric assay (IRMA). During 6 months of treatment with 600 mg of danazol daily, mean serum E2 decreased (P <0.05) to levels near the upper limit of the post‐menopausal range (to a mean (and 95% confidence interval of the mean) of 117 (65–169) pmol/1) whereas FSH, I‐LH (both by RIA and IRMA) and B‐LH levels were not significantly altered. During 6 months of treatment with monthly depot injections of 3–6 mg goserelin, mean serum E2 decreased (P<0.001) to well within the post‐menopausal range (to 23 (18–28) pmol/1). The mean FSH, I‐LH and B‐LH levels also decreased (P <0.05) during therapy with goserelin (from 3.9 (3–1–4.7) to 2.0 (1.6‐2.4) IU/1 for FSH, from 5.3 (4.5–6.1) to 1.9 (1.7–2.1) IU/1 for RIA‐LH, from 2.9 (2.5–3.3) to <0.5 (<0.5) IU/1 for IRMA‐LH and from 9.1 (7.1–11.1) to 2.9 (2.6–3.2) IU/1 for B‐LH). The bioactive to immunoreactive (B:I) RIA LH ratio was altered during the first month of treatment with both drugs, increasing with danazol from 1.6(1.3.1.9) to 2.0(1.7‐2.3) (P<0.05) and decreasing with goserelin from 1.7 (1.5‐1–9) to 1.4 (1.2–1.6) (P<0.05). The data indicate that danazol causes a relatively hypo‐oestrogenic state which cannot be attributed to a decrease in the immunoreactive gonadotrophin levels or to a decrease in the biological activity of LH and is associated with an increase in B: ILH ratio. In contrast, goserelin acts on the pituitary to produce suppression of gonadotrophin levels and effective down‐regulation of the pituitary. © 1990 Blackwell Scientific Publications Ltd.