To test the effects of antiandrogen treatment on the endocrine system 20 normal young men were treated with 750 mg/day flutamide [4-nitro 3'-trifluoromethylisobutyranilide (FLU)] or 100 mg/day cyproterone acetate (CPA) for 14 days followed or preceded by a placebo treatment of the same duration 4 weeks apart. Allocation of both drugs and sequence of active and placebo substance was by random number in a double blind design. On days 1 and 14 two basal blood samples were obtained 15 min apart followed by an iv injection of 25 micrograms GnRH and 10 mg metoclopramide (MTCL). Subsequently blood samples were taken after 25, 45, 60, and 90 min. On day 8 the GnRH/MTCL test was performed after 13 basal blood samples were obtained to establish a baseline for PRL concentrations unbiased by short term stress. After 14 days of FLU treatment, serum testosterone (T) increased significantly [17.4 +/- 1.4 (SE) vs. 26.9 +/- 1.5 nmol/liter, as well as estradiol (E2) concentrations (144 +/- 12 vs. 177 +/- 20 pmol/liter). Dihydrotestosterone increased slightly after 14 days of FLU administration (1.59 +/- 0.14 vs. 1.98 +/- 0.30 nmol/liter). At the same time basal LH concentrations were significantly elevated (5.9 +/- 0.5 vs. 8.6 +/- 0.6 ng/ml), whereas FSH levels were not affected (2.8 +/- 0.6 vs. 2.8 +/- 0.6 ng/ml). No changes in PRL values were detected throughout treatment with FLU. The effect of CPA was quite different. At the end of the treatment phase, serum T levels were reduced considerably (14.6 +/- 1.8 vs. 3.3 +/- 0.4 nmol/liter). Serum E2 decreased similarly (95 +/- 13 vs. 35 +/- 6 pmol/liter). Conversion of T to dihydrotestosterone was also diminished significantly (1.72 +/- 0.33 vs. 1.14 +/- 0.33 nmol/liter). Both gonadotropins were significantly depressed after 14 days of CPA administration (LH, 5.6 +/- 0.7 vs. 2.8 +/- 0.4 ng/ml; FSH, 2.4 +/- 0.3 vs. 1.4 +/- 0.2 ng/ml). Basal PRL levels were not affected, although the response of MTCL was reduced at the end of the treatment phase. Both drugs reduced the response of LH and FSH to GnRH administration.

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In order to evaluate the prognostic value of the heterologous ovum penetration test (HOP-test) the results of this test were compared with the fertilization rate of human ova in a programme for in vitro fertilization and embryo transfer (IVF/ET). Sperm from 29 husbands (23 normozoospermic and 6 with an abnormal semen profile) were exposed on one occasion to approximately 30 hamster ova in the HOP-test and on 1 to 3 occasions to 1 to 4 preovulatory oocytes obtained from the respective wives. The mean penetration rate (+/- SEM) of the hamster ova was 43 +/- 4% (range: 0-62%) for the normozoospermic men, and 23 +/- 6% (range: 0-47%) for the men with abnormal semen profiles. In 20 out of 23 couples in which the husbands were normozoospermic, sperm penetrated the hamster ova as well as they fertilized human ova; however, in one couple, a false-positive result was obtained (penetration of the hamster ova and no fertilization of the human oocytes) and in one couple a false-negative result occurred. One negative IVF result was correctly predicted by the HOP-test. In the 6 patients with disturbed sperm motility no correct positive or negative results were obtained, whilst 4 false-positive and 2 false-negative results occurred using the HOP-test. Although the number of patients with disturbed sperm motility was small, the data suggest that the HOP-test is of limited value in predicting fertility in an IVF program for couples with reduced fertility.