[The preventive effect of indeloxazine hydrochloride to the sexual dysfunction caused by anti-androgenergic agent (allylestrenol)].

Anti-androgenergic agents are usually used for patients with benign prostatic hypertrophy (BPH). However steroidal anti-androgenergic agents tend to suppress the sexual function. This side effect is very significant in middle-aged men. Therefore we studied the preventive effect of indeloxazine hydrochloride (INDX), which induces an increase of the dopamine level in the brain, on the sexual dysfunction induced by an anti-androgenergic agent (allylestrenol: ALE). Thirty-six patients with BPH were classified into two groups, one used ALE only, and the other ALE with INDX. For the subjective evaluation of the sexual function, a self assessment questionnaire method was employed before and after administration. We especially studied 3 questions, "morning erection", "erectile capacity" and "frequency of sex". For the objective evaluation of the sexual function, nocturnal penile tumescence (NPT) was measured using an erectometer. NPT occurs in healthy males as a physiological phenomenon and it shows the erectile capacity objectively. The levels of LH, total testosterone and free testosterone were also determined. In the ALE only group, sexual dysfunction was found subjectively and objectively, but in the ALE with INDX group, it was not found. Levels of LH, total testosterone and free testosterone were decreased in the both groups. There was no significant difference between the two groups. We hypothesized that the sexual dysfunction due to ALE is related with not only to the decrease of androgen, but also to suppression of the central nervous system; for example, the suppression of the area of the brain mediating sexual behavior.(ABSTRACT TRUNCATED AT 250 WORDS)

Correlation between the birth prevalence of isolated hypospadias and parental subfertility.

Factors associated with the occurrence of isolated hypospadias have been studied. We previously reported a secular trend association between hypospadias occurrence and progestagen use by the Hungarian population. Further study does not support that secular trend association. The use of progestagens for the treatment of reproductive problems is a very complex issue, and there are other factors relating to male and female fertility that differentiate the hypospadias families from the controls. It appears that families with problems of subfertility are at increased risk for the occurrence of hypospadias. Our data support more recent studies, which do not demonstrate an association between the occurrence of hypospadias and the administration of progestagens in humans.

A case-control study to evaluate the risk of congenital anomalies as a result of allylestrenol therapy during pregnancy.

The 1980-1984 data base of the Hungarian Case Control Surveillance System for Congenital Anomalies was used to evaluate possible teratogenicity of allylestrenol therapy during pregnancy. In an initial global analysis, three of the 24 congenital anomaly groups studied (ie, clubfoot, multiple anomalies, and hypospadias) had a significantly higher incidence of allylestrenol use. A case control analysis, however, excluded a pathogenetic role for allylestrenol in the etiology of clubfoot and multiple congenital anomalies. A greater use of allylestrenol in the first global evaluation was explained by a higher incidence in these groups of impending miscarriage and preterm labor, which are indications for allylestrenol therapy. The case control analysis did indicate a greater use of allylestrenol in the hypospadias group, but this difference was not statistically significant in the critical period for induction of hypospadias (ie, the third and fourth months of gestation). The causal role of subfertility in the etiology of hypospadias was an indirect factor, explaining the greater use of allylestrenol during pregnancy in this group; in Hungary, women with a history of infertility frequently receive hormonal support in the first trimester. The authors conclude that the data analyzed do not indicate any teratogenic effects of the use of allylestrenol during pregnancy.

[Clinical effects of allylestrenol on benign prostatic hypertrophy by double-blind method].

A double blind comparative clinical trial was performed with allylestrenol (AE) and chlormadinone acetate (CMA) to investigate the clinical efficacy of AE on prostatic hypertrophy. Both drugs were administered orally for 12-16 weeks in a daily dose of 50 mg. With both drugs marked improvement of disorders of micturition and a slight decrease in the size of the hypertrophied prostatic node were observed. No significant difference was observed between the two drugs in the overall efficacy of the treatments. Significant improvement of practically all parameters used for evaluation of results was observed with both drugs following treatment. Ultrasonotomographic examination revealed diminution of the size of the prostatic node and x-ray examination of the ureter showed improvement in elevation of the fundus of the bladder. These improvements were better after CMA treatment than after AE treatment. With all other parameters used no significant difference was observed between the two drugs. Mild adverse effects such as loss of sexual desire and potency were observed in a few cases. The incidence of side-effects was lower following AE treatment, and the incidence of loss of sexual desire and potency was significantly lower after AE than after CMA. Taking into consideration efficacy and safety of the treatments, no significant difference was observed in usefulness between the two drugs, and we were able to confirm the usefulness of AE for the conservative treatment of prostatic hypertrophy.

[Clinical study of allylestrenol (Org AL-25) on patients with prostatic hypertrophy--transrectal ultrasonography and urodynamic examination].

Seventeen patients with benign prostatic hypertrophy were treated with 50 mg allylestrenol per day for a long period of time (mean: 37.7 weeks), and subjective and objective findings, transrectal ultrasonotomography, urodynamics, serum lipids and hormone levels were examined. Improvement rates of subjective and objective findings were 42.9-92.9%. A significant decrease in weight and diameter (antero-posterior, lateral) of the prostate was observed, but the difference in the height of the prostate was not significant. Increase in intravesical pressure was observed in 9 out of 14 cases (64.3%) and the decrease in area under the urethral pressure curve at functional profile length was observed in 6 out of 11 cases (54.5%). Slight increase of the serum lipid levels was observed in a few cases, but in many cases the fluctuation was within normal range. Although clear decrease in the testosterone levels was seen, decrease of libido and potency was observed in only one case (5.9%). No other side-effect was found. The overall efficacy rate was 58.8%, and clinical usefulness of Allylestrenol on benign prostatic hypertrophy was confirmed.

[Clinical effects of allylestrenol on prostatic hypertrophy].

Clinical effects of allylestrenol were studied on 26 patients with benign prostatic hypertrophy with urinary disturbances. Allylestrenol was administered at the dose of 50 mg/day given twice a day for more than 10 weeks. Evaluation of the drug efficacy was made based on urodynamic and ultrasonographic findings. One of the 26 cases dropped due to a side-effect (vertigo) and another due to defusal of treatment. The efficacy rate was 50%. Side-effects were observed in 2 cases (1 with decrease of potency and the other with vertigo) but were mild. It was concluded that allylestrenol is useful for treatment of urinary disturbances caused by prostatic hypertrophy.

A case of suspected teratogenic holoprosencephaly.

A case of holoprosencephaly is reported in which the mother was prescribed high doses of oestroprogestins during the first 5 months of the pregnancy. Investigation of the family failed to reveal any sign of physical abnormality. A normal karyotype was detected in the proband. The authors suggest that this case may shed some light on the normal and abnormal way in which embryonic fields develop.

[The incidence of congenital abnormalities following gestagen administration in early pregnancy (author's transl)]. / Zur Frage der Fehlbildungsraten nach Gestagenmedikation in der Frühschwangerschaft.

198 women who had been trying for years to have a baby were submitted to a trial of prophylactic allyloestrenol therapy in an attempt to lower the incidence of spontaneous abortion. Allyloestrenol (Gestanon) was given at a dosage of 10 mg daily until the 8th week of pregnancy; the dosage was then stepped up to 15 to 20 mg daily until the 12th week of pregnancy and then rapidly tailed off. A decrease in the miscarriage rate was seen only in the group of women in whom treatment had been commenced immediately following ovulation (27 women: 1 miscarriage). If therapy was initiated only after the first missed period then it was without effect (161 women: 23 miscarriages). There were 4 cases of severe congenital abnormality; 3 of these cases arose in the group given allyloestrenol immediately after ovulation (with a drastic reduction in miscarriage rate). The results are discussed. They speak against a cytotoxic effect of the gestagen. It appears likely that the lowering in miscarriage rate occurs at the expense of a failure to prevent the nidation of abnormal fetuses who would normally be aborted.