Congress on New Perspectives of Andrology in Human Reproduction, 1994
This Congress took place on September 19-24, 1994 in the city of Manado, North Sulawesi, Indonesia under auspice of the Indonesian Society of Andrology, the Indonesian National Family Planning Coordination Board, the WHO Special Programme of Research, Development and Research Training in Human Reproduction, and the International Society of Andrology. Special Symposia were organized both by WHO and ISA. About 150 andrologists, mainly from Indonesia, but also from other Southeast Asia countries, participated. The following are highlights of the presentations of some of the invited speakers.
Dr. H.J. Glander (Germany) presented findings on lower expression of adhesion molecules (AM) on spermatozoa from teratozoospermic semen samples in comparison to that of the normal semen. Treatment with detergents increased the expression of AM only in normal semen, which could contribute to the pathogenesis of teratozoospermia.
Dr. N. Moeloek (Indonesia) present preliminary data from a three center study on therapeutic effects of Tribulus terrestris in idiopathic oligozooperms. About 40 volunteer infertile males were recruited to the study. No adverse effect on liver function or testis volume was noted. There was an increase in the sperm concentration after a daily dose of six tablets of purified Tribulus terrestris for about 72 days. An improvement in sperm morphology was also noted. Five pregnancies during the study were reported during these experiments. In contrast, in the control study on 9 normal volunteers (normozoospermia), the same result was also observed but no pregnancies were reported. Hence, Tribulus terrestris may enhance the sperm function by its effects in capacitation. Further studies on sperm function after treatment with Tribulus terrestris seem warranted.
Dr. N.R. Kalla (India) presented a lecture on future prospects of some plant derived chemicals as male contraceptives agents. He presented the history of the field from ancient times until the modern era. Dr. Kalla focused on the trials with gossypol as an oral male contraceptive and presented new views on its side effects. Hypokalemia is a common side effect in the Chinese studies. According to Kalla, no significant decline of potassium has been observed in studies outside China.
Zhang Gui-yuan (China) was unable to attend, and his results were reviewed by Dr. GMH Waites (WHO). Dr. Zhang referred in his introduction to the surprising report that purified crystals, assumed to be steroids, were extracted from human urine in the 11th century by Shen Kuo (1031-1095) and were used for the treatment of male and female patients. Since the 1970s, there has been collaboration between China and WHO which has taken the form of development and testing new methods of vas occlusion, conduct of large-scale clinical studies on the safety of vasectomy and study of the comparative efficacy of 3 methods of vas occlusion, i.e. no scalpel vasectomy, chemical sterilization with cyano-methacrylate, and polyurethane plug occlusion. Four Chinese centers also took part in the WHO multicenter contraceptive efficacy study on testosterone-induced azoospermia and oligozoospermia. These studies reflect the train ing and institution strengthening activities supported by WHO. The Chinese endocrinologists are producing and testing clinically their own hormonal formulations of androgens and progestogens. China is also developing institutes of molecular biology and conducting enzyme studies on androgen metabolism.
Dr. A. Aribarg (Thailand) discussed the Thai experience with a number of good leads for male contraceptive agents. He discussed the potential of the Chinese celery plant, purified Tripterygium wilfordii and other plant products. He described his research on the use of testosterone as a male contraceptive, with concern about rebound of sperm counts, possible effects on liver function and acne. The discussion emphasized the rarity of rebound of sperm counts and the belief that testosterone esters do not induce liver dysfunction.
Dr. K.M. Arsyad (Indonesia) discussed the management of the laboratory workup for male infertility. The laboratory examination is primarily done by the semen analysis, and other laboratory examinations will be carried out depending on the result of the routine semen analysis. The results of these semen analyses should serve as a guide to further andrological examination, which include advanced semen analyses and endocrinological examination such as FSH, LH, prolactin and testosterone, as well as immunological examinations.
Dr. W. Pangkahila and 5 other centers from Indonesia studied the contraceptive effects of testosterone enanthate (TE) alone and in combination with dimedroxyprogesterone acetate (DMPA) as well as DMPA + 19 nortestosterone (NT). Also cimetidine in rats was found to decrease spermatogonia and pachytene spermatocytes. Aspirin or prostaglandin E and Papaya seed extract decreased spermatocytes in rats. Other plant extracts tested were less effective. On non-scalpel vasectomy, 12-month efficacy data were presented (96%) with only minor adverse reactions. Studies on heat applied to mouse testis were also reported. It was the conclusion that hormonal methods and vas occlusion show the best promise for effective regulation of male fertility.
Dr. I. Huhtaniemi (Finland) presented data on transgenic mice in studies of the pituitary-testicular function. Ablation of gonadotropins was achieved using ÒsuicideÓ genes, such as herpes simplex virus thymidine kinase. In another study, a viral oncogene (SV40 T-antigen) was inserted into gonadal somatic cells to produce gonadal tumors. The toxic gene approach resulted in decreased FSH secretion especially in fetal and neonatal mice. Interestingly, an FSHb promoter-driven tk transgene was also observed to express in spermatogenic cells and treatment with gancyclovir resulted in severe damage of spermatogenesis. The oncogene studies created ovarian and testicular tumors. The testis tumors were of Sertoli cell or Leydig cell origin. These tumors metastasized and retained their gonadotropin responsiveness and steroidogenesis.
Dr. L.J.G. Gooren (The Netherlands) reviewed his long-term experience on clinical use of testosterone undecanoate (TU). He described the pharmacology and pharmacokinetics of this testosterone ester, and described the ten-year safety data. He emphasized its effectiveness in sexual dysfunction and discussed the experience in treatment of delayed sexual maturation. In this study, low dose TU (40 mg/day) accelerated maturation without decreasing final height. The discussion brought out the possible occurrence of 5a-reductase activity in the intestine. Dr. Gooren believed that there is no advantage of non-androgenic anabolic agents over testosterone esters as anabolic agents.
Dr. C. Wang (USA) described the role of the WHO Male Reproduction Task Force in encouraging male contraceptive approaches. She described the importance of male contraception in attempting to limit the global population explosion, and emphasized the importance of research carried out in developing countries.
Dr. D. Handlesman (Australia) discussed the different strategies of male hormonal contraceptive approaches. He discussed the past experience with testosterone, GnRH analogs and other hormonal approaches. He presented the WHO multicenter trial on testosterone enanthate which showed that azoospermia could be produced in many men with TE dosage of 200 mg/week; only 1 pregnancy occurred in over 1,400 partners so far studied. When efficacy trials were done with the subjects during severe oligozoospermia (sperm count smaller than 3 million/ml) or azoospermia, the preliminary data showed that most men reached these low levels and the fertility rate was less than that expected from female oral birth control pills. Dr. Handlesman also discussed the Indonesian experience with TE + DMPA and TE+19 NT. These results were exceptionally good in terms of suppression of sperm counts. He reviewed his data on the use of testosterone implants (pellets) in suppressing sperm counts. The pellets resulted in levels of testosterone in the physiological range for up to 4 months with good suppression of gonadotropins. Unfortunately, azoospermia or oligozoospermia rates were not quite as good as during treatment with 200 mg/week of TE.
Dr. R. Swerdloff (USA) discussed the importance of understanding the effect of androgen on the brain. He discussed the organizational effects of testosterone during fetal and perinatal period on masculinizing the brain in the rat, non-human primates and human. The importance of aromatization of testosterone to estradiol in the CNS was presented. Testosterone treatment of neonatal female rats resulted in dimorphic changes in CNS and correlated with male-like behavior. Human studies also show anatomical differences in the brain between the two sexes. Although men and women have marked overlap in cognitive and behavioral functions, men tend to score better in spatial and mathematical skills while women score better in verbal skills. While the role of learning bias must be considered, the data presented by Dr. Gooren during discussion showed that decreasing or increasing androgen level in transsexuals may partially influence the spatial skills and decrease verbal skills in adulthood. Dr. Swerdloff reviewed the correlative data on serum and salivary testosterone on occupation, aggressive behavior, learning and IQ. The discussion reflected the interest in the relation of behavior and androgen. Dr. Handlesman pointed out that the large WHO testosterone studies failed to show serious adverse effect on behavior, but all agreed that more information is needed to identify more subtle effects.
Arif Adimoelja, Indonesia