This clinical study has been undertaken to evaluate the usefulness of Proviron (mestero1one. Schering), which has been considered as an orally effective androgen preparation for the treatment of faulty spematogenesis in the male Prior to commencement of therapy at least two spermiograms were checked in each patient. In assessing the results, the patients were divided into two groups according to the sperm counts, as follows: group of less than 10 million per ml. (10 mill. (-) group), and group of more than 10 million per ml. but less than 40 million per ml. (10 mill. (+) group). They were also divided into two groups according to sperm motility, as follows: group of less than 30 per cent (30% (-) group) and group of more then 30 per cent (30% (+) group). Treatment scheme was as follows: Twenty to 30 mg of proviron was given by mouth daily for more than 90 days to be justified on the basis of the general assumption that spermatogenetic cycle lasts approximately 74 days. An average duration of the treatment was 90 days in this study. The results were considered to be Good if more than 20 per cent of improvement being noted either on the count or on the motility beyond the pre-treatment level; Moderate if only slight improvement on the count or motility; and Negative if no change on the count or motility. The results of this study are presented as follows: 1. Total number of subjects treated: 50 cases An average age of the husbands: 36 (29-45) An average age of their wives: 31 (24-40) An average duration of marital life: 4 years (1-17 years) An average frequency of coitus: 2 per week 2. Changes of sperm counts: 10 mill. (-) group: Good was found in 29% of total subjects Moderate in 47%, and Negative in 24%. 10mill. (+) group: Good in 62% of total subjects, Moderate in 28%, and Negative in 10%. An average of total subjects: Good in 48%, Moderate in 36%, and Negative in 16%. 3. Chenges of motility: 10 mill. (-) group: Good in 24% of total subjects Moderate in 57%, and Negative in 19%. 10 mill. (+) group: Good in 62% of total subjects Moderate in 31%, and Negatiye in 7%. An average of total subjects: Good in 48% of total subjects Moderate in 42%. and Negative in 12%. 30% (-) group: Good in 42% of total subjects Moderate in 42%, and Negative in 16%. 30% (+) group: Good in 50% of total subjects, Moderate in 42%, and Negative in 8%. An average of total subjects: Good in 46% of total subjects Moderate in 42%, and Negative in 12%. 4. Other changes: Volume of seminal fluid: increased from 2.6m1. of pre-treatment to 2,8mI. of post-treatment. Normal shape of spermatosoa: increased from 73% of pre-treatment to 78% of post-treatment. Coital frequency per week: increased from Z times of pre-treatment to 3 times of post-treatment. Body weight: gained 2kg after the treatment. The introduction of proviron an orally active androgen, has been welcomed by many andrologists. principally because it in contrast to other active androgen, does not curb pituitary activity and, therefore, has no effects on the hormonal homeostasis. It does not produce the rebound phenomenone in all the cases treated, but in a small number of cases the rebound phenomenone might be occurred. It has no adverse effect on liver function. In conclusion, the author's clinicsl experience confirmed that proviron appears to be of value particularly in the treatment of oligospermias by longterm treatment without any noticeable adverse effects.
Body Weight ; Coitus ; Homeostasis ; Humans ; Liver ; Male ; Mesterolone ; Mouth ; Oligospermia ; Sperm Count ; Sperm Motility ; Spermatogenesis* ; Spouses

A man having severe oligospermia, due to partial maturation arrest at spermatid stage, was given low dose estrogen-testosterone combination therapy for three months. His sperm count increased enormously, following which his wife conceived and delivered a healthy baby at term.
Adult ; Anabolic Agents ; therapeutic use ; Clomiphene ; therapeutic use ; Drug Therapy, Combination ; Female ; Fertility Agents, Female ; therapeutic use ; Humans ; Male ; Mesterolone ; therapeutic use ; Oligospermia ; drug therapy ; etiology ; Pregnancy ; Pregnancy Outcome ; Sexual Maturation ; Sperm Count ; Testis ; drug effects ; pathology ; Testosterone ; therapeutic use

Medical therapy was attempted on 210 idiopathic infertile males with spermatogenic disturbances During the past 7 years (1972-1978). and the clinical results obtained were summarized as follows: 1. The subjects were composed of 166 cases of oligospermias with sperm counts of less than 30* 106/ml, and motility of less than 40% and 44 cases of testicular azoospermias. Patients with small testis, with high FSH, with Sertoli cell only syndrome, and with tubular hyalinization were excluded in this study(Table 1). 2. The clinical characteristics of the subjects: An average age of the patients was 33 (22-45), and that of their sexual partners, 29 (21-38). An average duration of infertile marital life was 3 years (1-16 years). An average frequency of sexual intercourse was 3 per week (1-6/week). An average volume (size) of testis was 15ml (5-25ml). Testicular biopsies which had been performed on 44 azoospermias revealed that germinal cell arrest in 27%, peritubular fibrosis in 34%, and hypospermatogenesis in 39%. Mean value of plasma FSH was 5.2IU/L (1.O-13.0IU/L) ; LH, 4.9IU/L (0.8- 13.8IU/L) ; and testosterone, 540ng/dl (290-845ng/dl). Seminal fructose was 283mg/dl (125-405mg/ dl) (Table 1). 3. Medical therapy was continued for at least 3 months (1 treatment unit) since complete cycle from spermatogonium to mature sperm is estimated to require 70+/-4 days. An average duration of treatment was 6 months (2 units) in this series. At least 3 semen samples were analyzed before instituting regimens for standardization of baseline levels of each patient, and a similar number of ejaculates monthly during and after the therapy to ascertain the usefulness of the therapy. 4. In order to assess the efficacy of the medical therapy for faulty spermatogenesis, the following tentative criteria were used: Improved represents fertility index unit (sperm count(1000000/ml) Xsperm motility(%) / 100000000) before the treatment improved more than 10 units after the treatment. ""Unchanged"", no remarkable changes before and after the therapy. ""Deteriorated"", spermiogramme of post-treatment decreased after the therapy. Pregnancy achievement was also evaluated. 5. Treatment groups and regimens used were as follows(Table 2): 1) Oligospermia group: (1) Liothyronine group . Triiodothyronine (Thyronamine. Takeda. Japan), 25-50mcg daily by mouth, was administered to 13 cases. Improvement was found in 15%, while deterioration was noted in 23% of the 13. Pregnancy resulted in 1 case. (2) Vitamins group : Vitamedin composed of biotin, 100mg; vitamin B6, 100mg; vitamin B12, 1mg; and vitamin E, 300mg (Sankyo Zoki. Japan). 1gm/day orally. was given to 5 cases. Improvement was found in 20% of the 5.(3) L-Arginine group: L-Arginine monohydrochloride, amino acid (Rikagaku, Japan), 500mg/day. was administered by mouth to 20 cases. Improvement was noted in 30% of the 20. Pregnancy occurred in 2 cases. (4) AICAMIN group: AICAMIN, 4-amino-5-imidazole carbotamide orotate, nucleic acid precursor (Fujizawa, Japan), 600mg/dey, was given by mouth to 18 cases. Improvement was found in 33% of the 18. Pregnancy induced in 2 cases. (5) ATP group: Adenosin triphosphate (ATP, Adephos, Kowa. Japan), 300mg/day orally, was given to 6 cases. Improvement was noted in 33% of the 6. Pregnancy took place in 1 case. (6) Clomiphene group: Clomiphene citrate, l-(p-B-diethyl amino-ethoxyl phepyl) 1-2 diphenyl-2- thloroethylene (Samsung, Korea), 75mg/day, was administertd by mouth to 7 cases. Improvement was found in 29% of the 7. Pregnancy resulted in 1 case. (7) Mesterolone group: Oral androgen, Mesterolone (l a-metbyI-5 a-androstane-17B-o1-3-one) (UpJohn. Korea). 50-75mg/day orally, was given to 17 cases. Improvement was noted in 29% of the 17. Pregnancy achieved in 2 cases. (8) Testosterone rebound group: Depot testosterone cypionate (Schering, Korea), 250mg thrice a month, was administered intramuscularly to 15 cases. Improvement was shown in 27%. while deterioration was found in 33% of the 15. Pregnancy occurred in 2 cases. (9) HCG group , Human chorionic gonadotropin, (Puberogen, Sankyo Zoki, Japan; Tong-A, Korea), 3. 000IU every 5 days intramuscularly, was administered to 20 cases. Improvement was found in 31% of the 20. Pregnancy resulted in 2 cases. (10) Liothyronine + L-Arginine +AICAMIN combination group : Combined use of Liothyronine, 50mcg/day; L-Arginine, 500mg/day; and AICAMIN, 600mg/day. was given by mouth to 26 cases. Improvement was noted in 35% of the 26. Pregnancy occurred in 4 cases. (11) HCG+ Testosterone combination group : Combined use of HCG (Puberogen), 3.000IU every 5 days intramuscularly, in conjunction with Depot testosterone, 250mg monthly intramuscularly. vas administered to 9 cases. Improvement was shown in 33% of the 9. Pregnancy took place in 1 case (12) Liothyronine +L-Arginine +AICAMIN+HCG+ Testosterone combination group : Combined use of Liothyronine, 50mcg/day; L-Arginine, 500mg/day; and AICAMIN, 600mg/day; and HCG, 3,000 IU every 5 days intramuscularly, and Depot testosterone, 250mg/month intramuscularly, was administered to 14 cages. Improvement was found in 13% of the 14. Pregnancy was resulted in 3 cases. In a total of 166 oligospermias, improvement was noted in 51 cases (31%). and pregnancy occurred it 21 cases (13%), Pre-treatment sperm counts of 21X 10s/ml, and motility of 34% increased to 36X 106/ml, and 48% respectively after the treatment in 51 cases of oligospermia group. That is. fertility index increased from 7 units before treatment to 17 units after treatment(Table 3). 2) Azoospermia group : (1) Clomiphene group: Clomiphene citrate, 50-75mg/day orally. was given to 4 cases. No improvement was observed in this group. (2) HCG group: HCG (Puberogen), 3, 000IU every 5 days intramuscularly, was administered to 4 cases. No improvement was observed is this group. (3) HCG +Testosterone combination group : Combined use of HCG, 3.000IU every 5 days intramuscularly with Depot testosterone, 250mg/month intramuscularly, was administered to 8 cases. No improvement was observed in this group. (4) Liothyronine +L-Arginine + AICAMIN+HCG +Testosterone combination group : Combined use of Liothyronine, 50mcg/day; L-Arginine, 500mg/day; and AICAMIN, 600mg/day orally, and HCG, 3. 000IU, every 5 days intramuscularly; and Testosterone depot, 250mg/month intramuscularly, was administered to 28 cases. Viable sperm were produced in counts of 2-40X 106/ml in 7 cases of the 28. Pregnancy resulted in 2 cases(Table 4). 3) In summary of the medical therapy on the 210 idiopathic infertile males of faulty spermatogenesis, improvement was observed in 51 cases (28%), and pregnancy occurred in 17 cases (8%). No change was found in 123 cases (59%) and pregnancy resulted in 4 cases (2%). Deterioration was noted in 29 cases (17%), and pregnancy achieved in 2 cases (1%) in the present series. 6. For evaluation of the infertile males, complete history taking, physical examination, laboratory examination were carried out(Table 5). Testicular size should be measured on infertile patients by orchidometers. Average size of testis of the 210 patients revealed 15ml in volume, while that of normal fertile Korean male is 19+/-5ml(Table 6). Usually sperm production was almost not possible in hypogonadism whose testicular volume was less than 8ml. 7. In testicular biopsy, the patients with Sertoli cell only syndrome (germinal cell aplasia), severe hypospermatogenesis, tubular hyalinization. germinal cell arrest, and Leydig cell failure were not always in response to the medical therapy. 8. There have been wide variations on reported normal range of spermiogramme(Table 7). The lower limits of spermiogramme which is necessary to impregnate have been reported that sperm count. more than 20X106/ml and 100X 106/total; motility, more than 50% ; normal morphology, more then 70%, despite patients with sperm counts less than 1X106/ml could impregnate in 11% of them (Table 8). However, the author`s experience suggested that for the successful pregnancies to take place, the following conditions must be met in the volume of 2ml of seminal fluid, the sperm count, more than 40X106/mI, 60% of motility with 3 of activity grade, and 80% of normal morphology (Tables 9 and 10). Marked fluctuations in sperm count (fluctuation range, 100X 106/ml) are observed in both normal and infertile males. therefore, at least 3 semen analyses should be carried out before the treatment. This clinical observation showed that significant improvement could be traced especially in patients with the sperm counts of pre-treatment were exceeded 10X 106/ml. 9. Plasma FSH, LH, and testosterone should be measured in cases of small testis with severe oligospermia, and azoospermia. Infertile patients with extremely high FSH Level, hypergonadotropic hypogonadism, was not responded to the medical therapy(Tables 11, 12, 13, 14 and Fig. 1). 10. There is suggestive evidence that the combined use of 5 different regimens such as HCG, Testosterone, Liothyronine, L-Arginine, and AICAMIN in the forms of continuous medication at least for the period of 3 months, seems to be more effective than any others. However, this evidence was not conclusive since it has been noted that with some medications, the deteriorated effect was greater than the improved effect. 11. It has been reported that improvement was found in about 30% of the patients and pregnancy occurred in about 10% of the patients who were treated (Tables 15 and 16). However, pregnancy occurred in the 15 men out of the 51 patients whose spermigoranme improved with the medical therapy, whilst pregnancy resulted in the 4 men out of the 96 patients whose spermiogramme unchanged. and also pregnancy took place in the 2 men out of the 29 patients whose spermiogramme deteriorated in the oligospermia group of the present series. This pregnancy rate raises considerable doubt as to the efficacy of the empirical therapy in treating men with infertility, was medical treatment more successful than no treatment). 12. It is very difficult to judge properly the efficacy of the medical therapy without control group of men with placebo and without well controlled trials with an adequate data. A far more precise diagnosis procedures, selection of strict indications end selection of an appropriate treatment regimens should be necessary to evaluate properly the usefulness of the treatment. Further studies with increased number of patients for development of fundamentals of such medical treatment and also standardization of protocol for international comparisons.
Adenosine Triphosphate ; Arginine ; Azoospermia ; Biopsy ; Biotin ; Chorionic Gonadotropin ; Clomiphene ; Coitus ; Diagnosis ; Fertility ; Fibrosis ; Fructose ; Gonadotropins ; Humans ; Hyalin ; Hypogonadism ; Infertility ; Infertility, Male* ; Japan ; Male ; Male* ; Mesterolone ; Mouth ; Oligospermia ; Physical Examination ; Plasma ; Pregnancy ; Pregnancy Rate ; Reference Values ; Semen ; Semen Analysis ; Sertoli Cell-Only Syndrome ; Sexual Partners ; Sperm Count ; Spermatogenesis ; Spermatozoa ; Testis ; Testosterone ; Triiodothyronine ; Vitamin B 12 ; Vitamin B 6 ; Vitamin E ; Vitamins

Infertility is a world wide problem affecting up to 5% of all couples and in some communities up to 30% (WHO, l975). Although it is well known that the male factor is the main cause of the infertility in 40-50% of the cases, the appropriate drugs for treating this condition have not yet been found. Androgens have been tried at different doses, the higher ones to provoke suppression of spermatogenesis and ultimate rebound phenomenon. This has led to controversy due to the high percentage of permanent oligozoospermia reported by some authors (2-8%) and to the short-lived improvement obtained with this treatment. Mesterolone, an androgen without suppressive action upon the hypothalmic-pituitary axis. is presently used, although results are not yet conclusive. The present investigation would assess the effectiveness of mestero1one currently used in the treatment of idiopathic male infertility. To assess the effectiveness of treatment with mesterolone which is alleged to improve semen quality (sperm density, motility and morphology) in idiopathic infertile selected patients, this would be a double blind study to follow prospectively men suffering from primary idiopathic testicular failure being treated with mesterolone, Proviron, Schering, a drug which is presumed to improve this condition. Results would be assessed through several sperm parameters and pregnancy rate. Participants in the study will be men with primary idiopathic oligozoospermia and asthenozoospermia. The inclusion criteria would be as follows: a) men aged 20-40 years, whose female partners are entirely normal, b) informed volunteers with primary testicular failure, c) men having vaginal intercourse at least 2 times weekly with one partner and without known psycho-sexual problems, d) men willing to enter this study and relying only on the drug administered throughout the study, e) no history of renal, liver or any other chronic physical or psychological disease, t men who can be followed up regularly, and g) men whose female partner is not using any method of family planning. The exclusion criteria would be as follows: a) azoospermic patients, b) history of recent or severe liver or renal disease, and c) history recent severe infectious disease (less than 3 months ago), d) clinically detectable chronic diseases, e) concurrent use of drugs known or suspected to interact with the drug to be administered in the study or known to affect spermatogenesis. A total of 90 subjects are divided into the fol1owing three groups: a) placebo group: consisted of 30 Korean male with 15 oligozoospermia with sperm count of less than 20 x 1,000,000/ml and 15 asthenozoospermia with sperm motility of less than 309b, b) oligozoospermia group: consisted of 30 patients with sperm counts of less than 20 x1,000,000/ml, and c) asthenozoospermia group: consisted of 30 patients with sperm motility of less than 30%. Parameters for study are as follows: history taking, physical examination (testis size), laboratory works (CBC ESR, urinalysis, fructose in seminal fluid, testicular biopsy, semen analyses (pH of semen, volume, liquefaction. density, motility, agglutination, viability, normal form, WBC), hormonal assays (FSH, LH, testosterone, prolactin). Before starting treatment, 2 semen samples will be obtained with a time interval of not less than 1 week, each preceded by 3 days of sexual abstinence. For follow-up, patients will have a semen sample taken every month each preceded by 3 days of sexual abstinence while in treatment. After treatment, and for 3 months, a monthly semen analysis will be undertaken. Treatment scheme as follows: 75mg of mesterolone (proviron) was given by mouth daily for more than 90days to be justified on the basis of general assumption that spermatogenetic cycle lasts approximately 74days. An average duration of the treatment was 6.8 months in this study. In placebo group, digestive tablets are given as mesterolone administration. Clinical characteristics of a total of 90 patients were listed in the table l. The results were considered to be effective (+), if more than 30%, of improvement being noted on the count or more than 20% of improvement being noted on motility beyond the pre-treatment level. The results of this study are presented as follows: Changes of sperm density after treatment: Oligozoospermia group: sperm counts increased in 27%, of the 15 placebo treatment patients and 37% of the 30 mesterolone treatment patients. Asthenozoospermia group: sperm counts increased in 20%, of the 15 placebo treatment patients and in 27% of the 30 mesterolone treatment patients. Changes of sperm motility after treatment: Asthenozoospermia group: sperm motility improved in 13% of placebo treatment patients and 27% of mesterolone treatment patients. Oligozoospermia group: sperm motility improved in 20%, placebo treatment patients and 30% of mesterolone treatment patients. Changes of other parameters after treatment: Volume of seminal fluid and normal shape of spermatozoa were not changed significantly before and after the treatment between placebo and mesterolone groups and also between oligozoospermia and asthenozoospermia groups. Coital frequency and body weight were tend to increase after the mesterolone treatment. Pregnancy rates after treatment: Pregnancy resulted in l3%, of placebo treatment patients and 17% of mestero1one treatment patients in oligozoospermia group. Pregnancy occurred in 7%, of placebo treatment patients and l0% of mesterolone treatment patients in asthenozoospermia group. In conclusion, the author's clinical experience confirmed that mesterolone appears to be of value particularly in the treatment of idiopathic oligozoospermia and asthenozoospermia without any noticeable adverse effects.
Agglutination ; Androgens ; Asthenozoospermia ; Axis, Cervical Vertebra ; Biopsy ; Body Weight ; Chronic Disease ; Coitus ; Communicable Diseases ; Double-Blind Method ; Family Characteristics ; Family Planning Services ; Female ; Fibrinogen ; Follow-Up Studies ; Fructose ; Humans ; Infertility ; Infertility, Male ; Liver ; Male ; Mesterolone* ; Mouth ; Oligospermia* ; Physical Examination ; Pregnancy ; Pregnancy Rate ; Prospective Studies ; Semen ; Semen Analysis ; Sexual Abstinence ; Sperm Count ; Sperm Motility ; Spermatogenesis ; Spermatozoa ; Tablets ; Testosterone ; Urinalysis ; Volunteers