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At least 19 recordsLinked to original sources

Seminal analysis after orchiectomy in stage I teratoma.

Seminal analysis was performed within 2 months of orchiectomy on 97 patients with clinical Stage I malignant testicular teratoma managed by surveillance following orchiectomy. Relapse of malignant disease occurred in 28% of 47 patients with a sperm count less than 10 X 10(6)/ml and in 32% of 50 patients with a sperm count greater than or equal to 10 X 10(6)/ml. Of 11 patients with azoospermia, 4 relapsed and 1 developed contralateral testicular germ cell tumour. Of 35 patients with malignant teratoma undifferentiated the relapse rate was 68% in 16 patients with a sperm count less than 10 X 10(6)/ml and 42% in 19 patients with a sperm count greater than or equal to 10 X 10(6)/ml. It was concluded that sperm count analysis is non-contributory in estimating the risk of relapse in clinical Stage I teratoma.

Humans

The combined use of oral medroxyprogesterone acetate and methyltestosterone in a male contraceptive trial programme.

A male contraceptive trial was undertaken in 23 men using a combination of oral medroxyprogesterone acetate (MPA) and oral methyltestosterone (MeT). The men were divided into four groups according to varying drug dosages and were followed for 15 months (control - 3 months, treatment - 6 months, follow-up - 6 months). The parameters assessed included sperm count and motility, serum gonadotropins and sex steroids, and several biochemical and hematological tests. A questionnaire dealing with side-effects and changes in sexual function was administered intermittently. Although sperm count was suppressed (most dramatically at the highest drug doses, MPA 20mg,MeT 20mg), it was not suppressed to infertile levels. Sperm motility was unaltered; LH was modestly suppressed, FSH was not suppressed; testosterone was suppressed even at low doses; dihydrotestosterone responses were inconsistent. No significant biochemical abnormalities or side-effects occurred although some men experienced mild transient acne, gynecomastia and decreased testicular size. We conclude that in the doses used in this trial, the combination of MPA and MeT is not effective for male contraceptive, purposes and that higher doses may induce severe and undesirable side-effects.

Clinical Trials as Topic

Antispermatogenic action of gossypol in men.

Twelve Brazilian men were treated with gossypol for 1 year. The treatment schedule consisted of oral administration of 20 mg gossypol daily for 4 months, followed by a maintenance dose of 20 mg on alternate days (3 days a week), totaling 60 mg weekly for 8 months. Ten men became azoospermic at the end of the fourth month of treatment, and the two others developed marked oligospermia with necrospermia. Except for one man who complained of transient listlessness and fatigue, the subjects reported no side effects during treatment. No changes in libido or potency were reported, and plasma testosterone remained unchanged. Blood chemistry values, which included complete blood cell count, cholesterol, glucose, triglycerides, acid phosphatase, urea, transaminases, sodium, and potassium, were not changed significantly during treatment. The response of the pituitary to gonadotropin-releasing hormone stimulation and the response of the testis to gonadotropin stimulation appeared normal in men treated with gossypol. After treatment, the sperm counts reverted to essentially normal levels in 8 of 12 men. In four men, azoospermia continued 1 year after discontinuation of gossypol treatment. Retrograde phlebography carried out in three of the four men who remained azoospermic after discontinuation of therapy revealed subclinical varicocele.

Adult

A fifteen-year study of alterations in semen quality occurring after vasectomy reversal.

Semen quality was evaluated in 256 men at 2, 4, 6, and 12 months after vasectomy reversal. Total sperm counts were normal and averaged 91 X 10(6) sperm per ejaculate. The percentage of live sperm was decreased below normal to 36% and hypo-osmolarity values indicated only 41% of the sperm with normal membranes. Progressive motility and the total progressively motile sperm count were reduced and averaged 25% and 27 million, respectively. Approximately 50% of the patients had positive titers of sperm agglutinating and/or sperm immobilizing antibodies. Sperm morphology indicated tail and head shape defects with increases in both tapered and immature sperm. A fertility score combining several sperm parameters averaged only 37% of normal. All of these values remained constant with time after reversal except for progressive motility (increased), oval head shapes (increased), and tapered sperm (decreased). This study has demonstrated that characteristic defects occur in sperm (decreased). This study has demonstrated that characteristic defects occur in sperm motility, sperm membrane function and morphology, in addition to specimen fertility scores, after a vasectomy reversal and need to be taken into consideration when advising and treating these patients for subsequent fertility difficulties.

Cell Survival

Acute and chronic effects of a gonadotrophin-releasing hormone antagonist on pituitary and testicular function in monkeys.

The effects of a potent gonadotrophin-releasing hormone (GnRH) antagonist, (N-Ac-D-rho-Cl-Phe1,2,D-Trp3-D-Arg6-D-Ala10)-GnRH (Org 30276), on pituitary and testicular function of adult macaque monkeys were investigated. After a study to find the correct dose in castrated monkeys, five intact adult male animals were treated with daily s.c. injections of 5 mg antagonist for 9 weeks. The treatment resulted in an immediate decline in serum LH and testosterone in three out of five animals. The two hormones remained suppressed during the 9-week treatment period. Testosterone and LH responses to a bolus injection of GnRH (50 micrograms i.v.) were blunted or abolished during the antagonist treatment. Testicular volumes decreased markedly and ejaculates obtained at the end of treatment were azoospermic or contained only few dead sperm. Histological examination of the testes showed complete disruption of seminiferous epithelium in these animals. A decrease of body weight was observed in the treated animals. When the treatment was ceased, all inhibitory effects of GnRH antagonists were reversible. In the other two animals no consistent suppression of pituitary or testicular function could be observed during this period, nor was a doubling of the treatment dose for a further 8 weeks capable of fully suppressing endocrine and seminal parameters in these monkeys. It is concluded that GnRH antagonist treatment is capable of rapidly decreasing serum LH and testosterone and disrupting spermatogenesis in this primate species. Suppression effected by antagonist treatment is more rapid than that caused by GnRH agonists. The individual responses to the tested doses, however, vary markedly.

Animals

[Enkephalin-like immunoreactivity in Leydig cell tumor].

So far, the presence of an enkephalin-like immunoreactivity has never been reported in Leydig cell tumors at our knowledge. A 39 years old man having a painful gynecomastia and an impotency changing in time has been studied. At clinical examination, he was normal, without palpable testis tumor. The sperm count analysis showed an oligoastheno-spermia. Plasma testosterone (T) was low and plasma estradiol (E2) was high, varying from day to day. T/E2 ratio was always low (20 to 72 - N:220-240) and fell after HCG administration. Plasma LH was normal and plasma FSH was low. 17 hydroxyprogesterone (17 OH-P)/T ratio was increased (0.7 - N:0.23). A small tumor was localized in the left testis by ultrasonography. The spermatic vein catheterization, which was only possible on the left side, showed a decreased T, a high E2 and a low T/E2 ratio (19 - N:304). After unilateral orchidectomy, the histological study confirmed the diagnosis of Leydig cell tumor. With antibodies raised against synthetic Met-en-kephalin, it has been possible to detect an enkephalin-like immunoreactivity in the tumoral cells as well as in the surrounding normal cells.

Adult

Reproductive history and semen analysis in prevasectomy fertile men with and without varicocele.

A group of 598 allegedly fertile men requesting vasectomy were investigated; varicocele was found in 97 (16.2%) of these men. The mean ages and age distributions of men with and without varicocele were not significantly different. Reproductive histories (number of pregnancies, living children and spontaneous abortions, as well as incidence of present pregnancy) were similar in both groups. The average seminal characteristics (semen volume, sperm count, total sperm count, percentage of motile spermatozoa, quality of motility, morphology) were not different for men with and without varicocele, except for a slight, but significantly higher incidence of oval-headed sperm in men without varicocele. However, the incidence of varicocele was significantly higher in men with sperm counts below 40 million/ml. Three important observations may be made from this study: 1) the incidence of varicocele in this prevasectomy population was similar to that reported for the general population, but lower than the incidence reported for male partners of infertile couples; 2) in this population of allegedly fertile men, the presence of a varicocele did not significantly affect reproductive performance; 3) even though the incidence of varicocele was higher in men with sperm counts below 40 million/ml, the average seminal characteristics were not different in men with and without varicocele.

Adult

Heterogeneity of sperm density profiles following 16-week therapy with continuous infusion of high-dose LHRH analog plus testosterone.

LHRH agonist analogs have been investigated as potential male contraceptives. It has been shown that the LHRH agonistic analog [D-Trp6,Pro9-NEt] LHRH (LHRHA) given to men in single doses up to 500 micrograms daily for up to 20 weeks with the coadministration of testosterone enanthate produces reversible oligozoospermia. Individual responses to the treatment, however, were variable. In this study, we gave the same analog to eight normal male volunteers as a continuous infusion of 500 micrograms daily for 16 weeks. Testosterone enanthate, 100 mg, was given by injection every second week. Six of the subjects became oligozoospermic but the other two retained sperm counts that were greater than 20 million/ml, although their treatment continued for 20 weeks. The reasons for this variability of response are not clear. Serum immunoreactive LH values increased during the infusion period whereas testosterone declined. FSH values fell during treatment in all subjects except the two non-responders. The acute pituitary response to LHRHA during the treatment or shortly thereafter (48 h) was completely abolished, and bioactive LH values were suppressed totally. FSH, LH, testosterone and sperm counts returned to normal in all subjects following discontinuation of LHRHA infusion. Continuous infusion of 500 micrograms of LHRHA daily for 16 weeks with 100 mg of testosterone enanthate every 2 weeks induced desensitization of the pituitary, loss of LH bioactivity, and decreases of FSH and testosterone. This mode of administration, however, did not improve sperm density results obtained earlier by single daily injections of the analog. Heterogeneity of sperm density profiles still persists for reasons that are not yet clear.

Adult

The interpretation and significance of the fractional postcoital test.

The investigation was designed to objectively determine the clinical usefulness of the fractional postcoital test. Forty-three normal subjects had midcycle cervical mucus collection at various times after insemination. There was a significant correlation between the number of motile sperm at the internal os level and the total sperm count within the cervical mucus. The median internal os count was 15 motile sperm per high-power field with a lower 95% confidence limit of five motile sperm per high-power field. Therefore, the fractional postcoital test is useful clinically as it is a physiologic indication of sperm transport in cervical mucus.

Adult

Effect of intra-epididymal injection of copper particles on fertility, spermatogenesis, and tissue copper levels in rats.

In male rats, a single injection of 10 mg metallic copper particles in oil into each caput epididymidis induced infertility, whilst leaving mating behaviour and blood testosterone levels unchanged. Fertility tended to recover 5.5 months after the copper treatment. Although the copper content of the caput epididymidis reached a level of around 100 times higher than control values, the serum copper concentration did not rise significantly. This finding and the observation that treated animals gained weight as fast as the controls suggest a low systemic toxicity of this method. The testicular copper concentration was significantly higher than that in controls and different degrees of damage, including vacuolation, karyorrhexis, pyknosis, and cytolysis, were seen mainly in pachytene spermatocytes and early spermatids. Clumps of foreign particles, apparently metallic copper, were found in the interstices of the caput epididymidis together with degenerative changes in the epithelial cells of the caput, suggesting a possible effect of copper on the epididymal epithelium. The viability of epididymal sperm decreased more markedly than the decrease in sperm density. It is therefore most likely that the major cause of infertility after copper injection into the caput epididymidis is a direct inhibitory effect of copper on the sperm, whilst damage to the seminiferous and epididymal epithelial may contribute.

Animals

Relationship between hormone profiles and the restoration of spermatogenesis in men treated with gossypol.

Gossypol acetic acid was administered orally to 35 male volunteers at a dose of 20 mg once a day for 52-70 days in the loading phase and twice a week for 22 months in the maintenance phase. Sperm counts and the serum concentrations of LH, FSH, prolactin, testosterone and oestradiol were monitored regularly during treatment and for a follow-up period of 12 months. At around 90 days after treatment, all treated participants approached or attained azoospermia and remained at this level throughout the maintenance phase. By the end of the follow-up phase, eight treated men were still azoospermic, while sperm counts in the other 27 men were restored to normal levels. The only hormone that changed significantly during and after the treatment was FSH. From the 6th month of the treatment to the end of the follow-up phase, serum concentrations of FSH in the eight participants that reached irreversible azoospermia were significantly higher than in the other 27 men or in controls. It is suggested that monitoring of FSH levels might be of diagnostic use for identifying those participants with irreversible azoospermia during gossypol treatment.

Administration, Oral

Improvement of semen and pregnancy rate after ligation and division of the internal spermatic vein: fact or fiction?

Male partners with left-sided varicoceles of 96 infertile couples were studied. Fifty-one patients were submitted to ligation of the testicular veins and 45 individuals were randomised as controls. During an observation period of 53 months (range 36 to 74 months) we found no statiscally significant improvement in the semen crude variables, the morphology or the progressive motility in the series of men submitted to surgery. The pregnancy rate was lower in those who had an excision of varicocelle.

Adult

Why does vasectomy reversal fail?

The scrotum was explored in 32 patients who had vasectomy reversal which failed to restore their fertility. Twenty-three patients were azoospermic and nine had severe or persistent oligozoospermia. Amongst the 23 azoospermic cases, the vasa were found to be blocked in 12; following repeat vaso-vasostomy, normal sperm counts were produced in 10 patients; 8 of these patients followed up for 6 months or more successfully impregnated their wives. In four cases there was a secondary epididymal block: following epididymo-vasostomy, three of four patients obtained normal sperm counts and two wives became pregnant. In seven patients there was a very high antisperm antibody titre (greater than 1024 by tray agglutination test) and despite reparative surgery and prednisolone therapy, no pregnancies were obtained. The overall pregnancy rate for this group was 7 of 19 (37%). Amongst nine oligozoospermic cases, unilateral obstruction was found in eight. The block was found in the vas in five and in the epididymis in two, and in two there were very high antisperm antibody titres. After reconstructive surgery, four patients had normal sperm counts and one pregnancy has been obtained.

Adult

Influence of testosterone substitution on sperm suppression by LHRH agonists.

To investigate the effect of LHRH (GnRH) agonists on sperm suppression, we studied the effect of a depot preparation of D-Trp6 LHRH in 10 normal men for 30 weeks. In addition, to determine the role of androgenic substitution on sperm suppression, the volunteers were divided into two groups: group 1 (n = 5) received a low dose T substitution (125 mg of T enanthate every month), while group 2 (n = 5) received a normal T substitution (120 mg of T undecanoate every day). Four men became azoospermic in group 1 and none in group 2. Moreover, administration of additional T injections in 1 volunteer of group 1 resulted in the reappearance of spermatozoa in the ejaculate. Return to the low dose therapy produced azoospermia. These results suggest that testosterone supplementation supports spermatogenesis.

Contraceptive Agents, Male

Drug-induced infertility.

Primary infertility may result from the use of various drugs. This phenomenon may be the result of an effect on the hypothalamic-pituitary-gonadal axis or a direct toxic effect on the gonads. Some of the drugs considered in this article demonstrate sex-related differences in their ability to cause infertility; there also may be age-related differences. The drugs described in this review, in regard to their association with the development of infertility, include various individual antineoplastic agents (cyclophosphamide, chlorambucil, busulphan, and methotrexate) and combinations of these chemotherapeutic drugs, glucocorticosteroids, hormonal steroids (diethylstilbestrol, medroxyprogesterone acetate, estrogen, and the constituents of oral contraceptives), antibiotics (sulfasalazine and co-trimoxazole), thyroid supplements, spironolactone, cimetidine, colchicine, marihuana, opiates, and neuroleptic agents.

Adolescent

Reversible inhibition of sperm production and gonadotrophin secretion in men following combined oral medroxyprogesterone acetate and percutaneous testosterone treatment.

Six men requesting male contraception received a daily oral dose of 20 mg medroxyprogesterone acetate (MPA) in combination with 50 or 100 mg percutaneous testosterone for 1 year. From the third month the sperm concentration was less than 10(6)/ml for all the men at one time or another during treatment, and usually less than 5 X 10(6)/ml, with an average reduction of 95% with respect to pre-treatment values. The sperm count returned to previous values 3-6 months after cessation of the treatment. While FSH and LH secretion was inhibited throughout the treatment period, plasma testosterone levels were not reduced. Oestradiol levels were unaffected while dihydrotestosterone was elevated. The secretory activity of the prostate and seminal vesicles was not appreciably affected; seminal carnitine concentration was reduced during the treatment with a subsequent return to pretreatment values. No pregnancies occurred during treatment. There was no impairment of libido in the subjects, nor any incidence of gynaecomastia, or increase in average body weight. The only observed metabolic side-effect was a moderate increase in glycaemia. A synergistic action of MPA and testosterone is proposed to explain the inhibition of gonadotrophin secretion.

Adult

Endocrinological and physiological features after steroid treatment of male rats.

The effects of medroxyprogesterone acetate (Provera), testosterone propionate (TP), ethinyl estradiol (EE), and ethynodiol diacetate (ED) treatments on sperm population in different segments of the male rat reproductive tract, reproductive organ weights, circulating androgens and fertility were studied. Ten microgram TP given for five days reduced the sperm population and organ weights. A marked reduction in the number of sperm and reproductive organ weights was observed in males orally treated with estrogens. Only long-term (20 days) treatment with Provera (1 mg/day) significantly reduced sperm population and reproductive organ weights. Combination of TP and Provera resulted in a more pronounced reduction in sperm counts and organ weights. Among steroids studied, estrogen was the only compound which suppressed fertility and circulating steroid levels.

Androgens