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In this study we tested the effectiveness of the combined administration of cyproterone acetate (CPA) and testosterone enanthate (TE) in suppressing spermatogenesis. After a control phase of 3 months, 15 normal men were randomized to receive TE (100 mg/week) plus CPA at a dose of 100 mg/day (CPA-100; n = 5) or 50 mg/day (CPA-50; n = 5) or TE (100 mg/week) alone (n = 5) for 16 weeks. Semen analysis was performed every 2 weeks. Every 4 weeks, fasting blood samples were drawn for the measurement of LH, FSH, testosterone, estradiol, and biochemical and hematological parameters; subjects underwent a physical examination; and they and their partners filled in a sexual and behavioral questionnaire. Regardless of the dose, each of the 10 subjects receiving CPA plus TE became azoospermic, whereas only 3 of 5 subjects treated with TE alone achieved azoospermia. Times to azoospermia were 6.8 +/- 0.5, 8.4 +/- 1.0, and 14.0 +/- 1.2 weeks in groups CPA-100, CPA-50, and TE alone, respectively (P = NS). Throughout treatment, both gonadotropins tended to be higher in the TE alone group than in the other groups. This difference was mostly due to the higher gonadotropin levels present in the 2 men treated with TE alone that remained oligospermic. No difference in testosterone or estradiol levels was found among the groups. No significant change in lipoprotein levels or liver function tests could be detected. In the CPA-100 and CPA-50 groups, hemoglobin, hematocrit, and red blood cells were lower at the end of the treatment phase, whereas no change was detected in TE alone group. A tendency for a decrease in body weight was detected in subjects treated with CPA, whereas there was no change in subjects receiving TE alone. At the end of the treatment phase, a decrease in testis size was present in all groups. There was no significant change in sexual function, aggressive behavior, mood states, or satisfaction with relationship in any group. These results suggest that the combined administration of CPA and TE is very effective in suppressing spermatogenesis and may represent a promising regimen for reversible contraception in males.

Objective: To determine whether there has been a decline in semen quality in a group of healthy men during the past 21 years., Design: Retrospective analysis of the relationship between time and changes in semen parameters over 21 years using regression analysis., Setting: A tertiary university center., Patients: Five hundred ten healthy, normal men who donated multiple semen samples as participants in clinical studies between 1972 and 1993., Main Outcome Measures: Sperm concentration, semen volume, total numbers of sperm per ejaculate, and percent spermatozoa with normal morphology., Results: There was no decrease in sperm concentration, semen volume, total number of sperm per ejaculate, and percent normal sperm morphology in 510 healthy men studied between 1972 and 1993., Conclusion: We conclude that in this population of healthy young men there has not been any decline in semen quality in the past 21 years.

Insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) is produced by prostate epithelial and stromal cells and either enhances or inhibits the effects of IGF on prostate epithelial cells. The levels of this protein in the male reproductive tract may be determined in part by proteases, including prostate-specific antigen (PSA), produced by the prostate epithelium. In this study we examined the proteolytic activity of human seminal fluid on IGFBP-3. Seminal fluid and prostate massage fluid (PF) were examined for IGFBP-3 or its fragments by use of an IGFBP-3 RIA that detects intact IGFBP-3 as well as fragments, a two-site immunoradiometric assay (IRMA) that detects intact IGFBP-3 and the larger fragments, Western ligand blots (WLB), and immunoblots (WIB). In seminal fluid, IGFBP-3 was readily detectable by RIA, but was detected in only 50% of the samples assayed by IRMA. No detectable IGFBP-3 was observed by WLB with [125I]IGF-I as the ligand, but with IGF-II as the ligand, IGFBP-3 fragments at 16-17 kDa were noted. On WIB, the 16-kDa fragment of IGFBP-3 was most abundant, with a smaller amount of the 29-kDa fragment, but no intact IGFBP-3. These results indicated that most of the IGFBP-3 detected in seminal fluid was in small (< or = 16-kDa) fragments. When three or more seminal fluid samples collected 1 month apart were available from the same individual, the coefficient of variation was 10.0 +/- 1.26% (+/- SE) for IGFBP-3 by RIA vs. 73.3 +/- 11.2% for sperm counts in the same samples. In a group of 42 PF samples, the IGFBP-3 levels measured by either RIA or IRMA were approximately 3-fold higher than those in seminal fluid. Intact IGFBP-3 was detected by both WLB and WIB. There was a significant inverse correlation between PSA and IGFBP-3, measured by IRMA, in PF (r = -0.526; P < or = 0.004). Finally, in the PF of African-American men, PSA was significantly lower, and IGFBP-3 determined by IRMA was significantly higher compared to those in Caucasian men.

Studies using high dose testosterone (T) administration in normal men as a male contraceptive have resulted in azoospermia rates of only 50-70%. Previous studies of T and progestogen combinations have shown comparable rates of azoospermia, but have been uncontrolled or used T in doses less than that associated with maximal suppression of sperm production. We conducted a randomized, placebo-controlled, single blind trial comparing 6 months of T enanthate administration (100 mg, im, weekly) with the same dose of T enanthate in conjunction with the progestogen levonorgestrel (LNG; 500 micrograms, orally, daily) in 36 normal men, aged 20-42 yr (n = 18 in each group). The primary end points were induction of azoospermia or severe oligospermia (< 3 million sperm/mL). The combination of T plus LNG was much more effective in suppressing sperm production than T alone. Sixty-seven percent of the T plus LNG group (12 of 18) and 33% of the T alone group (6 of 18) achieved azoospermia by 6 months (P = 0.06). Severe oligospermia or azoospermia developed in 94% of the T plus LNG (17 of 18) group compared to 61% of the T alone group (11 of 18; P < 0.05). T plus LNG also suppressed sperm production more rapidly than T alone. Time to azoospermia was 9.9 +/- 1.0 vs. 15.3 +/- 1.9 weeks in the T plus LNG and T alone groups, respectively (mean +/- SEM; P < 0.05). Serum high density lipoprotein cholesterol decreased 21.7 +/- 3.6% in men given T plus LNG (P < 0.05), compared to only a 1.8 +/- 3.8% decrease in men in the T alone group. Average weight gain was 5.3 +/- 0.8 kg in the T plus LNG group and 2.3 +/- 0.9 kg in the T alone group (P < 0.05). Acne and increase in hemoglobin were similar in the two groups. We conclude that combination hormonal therapy with T plus a progestogen might offer a reversible male contraceptive approach with a more rapid onset of action and more reliable induction of both azoospermia and severe oligospermia than T alone.

Reproductive functions in most animals demonstrate seasonal fluctuations that allow young to be born at a time of the year favourable for their survival. Whether there is a seasonal change in the human reproductive system is unclear. In the present study, we measured serum concentrations of luteinizing hormone, follicle stimulating hormone, testosterone and inhibin in the same 16 normal men sampled monthly for 1 year. A statistically significant increase in all four measured hormones was found in June, with a nadir in August. Our findings suggest that a circannual rhythm of gonadotrophins and testicular hormones exists in normal men. The mechanism leading to this rhythm and the importance of the rhythm in human biology are unknown.

We examined two methodological issues in the analysis of sperm concentration data using a large database of sperm concentrations in healthy men that were collected at the University of Washington. We showed that the raw data were skewed and that log transformation should be used to assure that the data meet the assumptions underlying most statistical estimation and testing procedures. We also addressed the issue of the great variability in sperm concentrations within a single individual and the necessity and utility of multiple sampling to reduce variance. We conclude that log-transformed data should be used for statistical analysis of sperm concentration and recommend that such analyses be based on the geometric mean of several samples from each subject to reduce variability, increase accuracy of estimation, and improve statistical power. This is particularly important when the objective is to detect small but important differences or subtle effects.

This article describes a study that assessed the accuracy of a tibial intramedullary alignment device in 44 adult cadaveric tibiae. The results suggest that greater accuracy is achieved if the device is inserted fully to the level of the distal epiphyseal scar and if used in the nonvalgus tibia. When seating of the tibial guide rod is incomplete or when the tibia has a valgus anatomic bow, cross-checking with extramedullary alignment devices is recommended to maximize accuracy of tibial component position.

The concept that androgen alone can provide an effective male contraceptive has been tested in a multicentre, multiphase trial by the World Health Organization. Results from this trial showed that an ester of testosterone, testosterone enanthate (TE), administered at a dose of 200 mg/week, has a very high contraceptive efficacy, and suggested that, at least in some populations, androgen alone might provide a viable option for the control of male fertility. It has been claimed that testosterone represents one of the gender-related risk factors for coronary artery disease (CAD) in men. Epidemiological and interventional studies have failed to establish a convincing relationship between testosterone and high density lipoprotein cholesterol (HDL-C). Therefore, there is concern about possible negative effects on lipoprotein asset of an androgen-alone male contraceptive. In this study we analysed the effects of long-term (12 months) administration of TE (200 mg/week) in normal healthy men. Blood samples (six men > 10 h fast = Group 1; 30 men > 4 h fast = Group 2) were drawn from 36 men, monthly before the beginning of the injections (control), every 3 months throughout the study period (treatment), and 1 month after stopping TE injections (recovery). Total cholesterol (chol), triglycerides, HDL-C and LDL-C levels were measured in these samples. Biochemical parameters were also monitored. TE administration induced a significant decrease (15-20%) in HDL-C levels that was of comparable magnitude in men from both groups (fasting and non-fasting) and occurred regardless of basal HDL-C levels. No statistically significant effect on other lipoproteins was detected. Considering all men together, HDL-C levels were decreased in 78% of the men by month 3, 83% by month 6, 94% by month 9 and 97% by month 12 of treatment. In all men the HDL-C decrease was reversible within 1 month of stopping TE administration. It is concluded that: (1) injection of 200 mg TE/week causes a 15-20% decrease in HDL-C in normal men with no effect on other lipoproteins, (2) the suppressive effect of TE is maintained throughout the 1-year-injection period, and a direct relationship between the duration of TE administration and the proportion of men showing decreased HDL-C levels, was observed. (3) The HDL-C decrease was reversible within 1 month of stopping TE administration. These data will be important in designing further studies on male contraception, and in interpreting the relationship between testosterone levels, HDL-C levels and potential cardiovascular risk.

A man with IHH and anosmia presented in 1980. He was successfully treated with various hormonal regimens; four children were conceived with hCG or pulsatile GnRH therapy. The patient discontinued GnRH after the fourth child was conceived, and testosterone enanthate injections were prescribed. However, he took the injections only briefly and 15 months later he demonstrated continuing spermatogenesis despite low serum FSH and LH levels. His wife successfully became pregnant. This case adds to the recognized range of recovery in IHH, with fertility despite stopping hormonal therapy and despite low serum gonadotropin and T levels.

Background and Purpose: Cranial irradiation may lead to accelerated atherosclerosis over several years. Stroke has been described after cranial irradiation administered for a number of conditions. However, pituitary irradiation has only rarely been associated with stroke., Case Descriptions: Two patients, 39 and 46 years of age, suffered strokes 13 and 20 years, respectively, after irradiation for pituitary tumors. Strokes were in the territories of small perforating arteries, but large vessels such as the carotid siphon and anterior cerebral arteries were also abnormal. Other risk factors for stroke were absent., Conclusions: It is suggested that pituitary irradiation increases the risk of subsequent stroke due to the known effects of ionizing radiation on vascular walls.

The purpose of this study was to examine the relationships between serum inhibin levels as measured by RIA and serum FSH and sperm concentration. Three groups of men were used for this study: group I, normal fertile men (n = 67); group II, fertile men with a varicocele (n = 57); and group III, infertile men with a varicocele (n = 21). There were no differences in mean serum inhibin levels between the three groups. The two groups of men with varicoceles exhibited higher serum FSH levels and FSH responses to GnRH than the normal men. Sperm counts in both groups II and III were significantly lower than group I. In the normal men there was an inverse correlation between baseline serum inhibin and serum FSH levels and GnRH stimulated FSH levels, r = -0.415 and 0.422, P less than 0.005, respectively. Furthermore, the normal men exhibited a positive correlation between serum inhibin measurements and sperm concentration and testicular volume, r = 0.35 and 0.26, P less than 0.01 and less than 0.05, respectively. In neither group of men with a varicocele were these relationships found. These data demonstrate that serum inhibin does correlate with FSH in a negative fashion, when the reproductive system is normal, as would be expected for a negative feedback factor. Finally, the relationship of serum inhibin levels to testicular size and sperm count in the normal men suggests that serum inhibin levels reflect to some extent the integrity of seminiferous tubule function.

Since sex hormone-binding globulin (SHBG) levels are often elevated in sera of patients with testicular insufficiency, it is important to determine whether SHBG declines into the normal range and the extent of change in free testosterone (free T) after androgen administration. Five normal men and five patients with Klinefelter's syndrome were studied before and after the administration of testosterone enanthate (200 mg, im every 2 weeks). An additional five normal men and five patients with hypogonadotropic hypogonadism (HH) were treated with hCG (2000 U, three times a week). Three months after the administration of T or hCG, serum total and free T increased in both normal men and patients. Free T increased significantly in the Klinefelter's and HH patients from 94 +/- 20 and 14 +/- 5 pg/ml, respectively, to 271 +/- 50 and 276 +/- 41 pg/ml (P less than 0.01; P less than 0.001). The increase in the normal men treated with T or hCG was also significant (from 211 +/- 52 and 220 +/- 37 pg/ml to 390 +/- 83 and 330 +/- 90 pg/ml). SHBG fell in both the T-treated normal men (from 6.5 +/- 1.2 ng dihydrotestosterone bound/ml to 4.3 +/- 0.4; P less than 0.02) and the T-treated Klinefelter's patients (from 16.4 +/- 2 to 4.3 +/- 0.5; P less than 0.01). However, it was unchanged in the hCG-treated HH patients and rose in the hCG-treated normal men (from 6.6 +/- 0.7 to 8.6 +/- 1.0; P less than 0.05). This study demonstrates that treatment of hypogonadal men with T and hCG in the doses used increased free T levels above the basal levels for normal men. However, the effects of the increase in free T, as determined by a change in SHBG, were different depending upon the type of treatment.

An excellent correlation was found between salivary testosterone (T) and serum T concentrations, as measured by RIA. Using polyacrylamide gel electrophoresis, we have demonstrated that sex steroid-binding globulin could not be identified in the saliva of men with serum sex steroid-binding globulin. After exogenous T administration, saliva and serum T rose abruptly and in parallel. Salivary T concentrations in male patients with thyrotoxicosis were similar to those in normal males, whereas the serum T and sex steroid-binding globulin values were significantly higher in the hyperthyroid patients. This study demonstrates that salivary T levels may be used as an index of free serum T.

Three men who volunteered as normal subjects were found to have abnormally high levels of serum follicle-stimulating hormone (FSH) despite having normal seminal fluid analyses and fertility. Two of the men had a history of previous orchitis, and one had an atrophic testis. Serum luteinizing hormone and testosterone levels were normal. These cases appear to represent compensated primary testicular disease, with normal sperm counts and fertility maintained at the expense of chronically elevated FSH levels. These results imply that in certain situations, the measurement of serum FSH levels may be a more sensitive index of testicular disease than the performance of seminal fluid analyses.

The specific roles of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in controlling human spermatogenesis are poorly understood. We studied the effect of an experimentally induced, selective LH deficiency on sperm production in normal men. After a 3-mo control period, five men received 200 mg testosterone enanthate (T) i.m./wk to suppress LH, FSH, and sperm counts. Then, while continuing T at the same dosage, human FSH (hFSH) was administered simultaneously to replace FSH activity, leaving LH activity suppressed. Four men received 100 IU hFSH s.c. daily plus T (high dosage hFSH) for 13-14 wk, while one man received 50 IU hFSH s.c. daily plus T (low dosage hFSH) for 5 mo. The effect on sperm production of the selective LH deficiency produced by hFSH plus T administration was assessed. In the four men who received the high dosage hFSH regimen, sperm counts were markedly suppressed during T administration alone (0.3+/-0.2 million/cm(3), mean+/-SE, compared with 94+/-12 million/cm(3) during the control period). Serum LH bioactivity (determined by in vitro mouse Leydig cell assay) was suppressd (140+/-7 ng/ml compared with 375+/-65 ng/ml during control period) and FSH levels (by radioimmunoassay) were reduced to undetectable levels (<25 ng/ml, compared with 98+/-21 ng/ml during control period) during T alone. With the addition of 100 IU hFSH s.c. daily to T, sperm counts increased significantly in all subjects (33+/-7 million/cm(3), P < 0.02 compared with T alone). However, no subject consistently achieved sperm counts within his control range. Sperm morphology and motility were normal in all four men and in vitro sperm penetration of hamster ova was normal in the two men tested during the hFSH-plus-T period. During high-dosage hFSH administration, serum FSH levels increased to 273+/-44 ng/ml (just above the normal range for FSH, 30-230 ng/ml). Serum LH bioactivity was not significantly changed compared with the T-alone period (147+/-9 ng/ml). After the hFSH-plus-T period, all four men continued to receive T alone after hFSH was stopped. Sperm counts were again severely suppressed (0.2+/-0.1 million/cm(3)), demonstrating the dependence of sperm production on hFSH administration. Serum T and estradiol (E(2)) levels increased two- to threefold during T administration alone compared with the control period. Both T and E(2) levels remained unchanged with the addition of hFSH to T, confirming the lack of significant LH activity in the hFSH preparation. In the one man who received low dosage hFSH treatment, sperm counts were reduced to severely oligospermic levels, serum FSH was suppressed to undetectable levels, and serum LH bioactivity was markedly lowered during the T-alone period. With the addition of 50 IU hFSH s.c. daily to T, sperm counts increased, to a mean of 11+/-3 million/cm(3). During this period, serum FSH levels increased to a mean of 105+/-11 ng/ml (slightly above this man's control range and within the normal adult range), while LH bioactivity remain suppressed. After hFSH was stopped and T alone was continued, sperm counts were again severely reduced to azoospermic levels. We conclude that FSH alone is sufficient to reinitiate sperm production in man during gonadotropin suppression induced by exogenous T administration. FSH may stimulate sperm production in this setting by increasing intratesticular T through androgenbinding protein production or by increasing the sensitivity of the spermatogenic response to the intratesticular T present during exogenous T administration.

Previous reports concerning isolated follicle stimulating hormone (FSH) deficiency and its possible pathogenesis have been conflicting. Both "normal" and "abnormal" FSH response to luteinizing hormone releasing hormone (LHRH) infusion have been described. We studied a 22-year-old man with normal basal serum testosterone and luteinizing hormone (LH) levels but undetectable levels of serum FSH. His serum LH titers showed one secretory spike during a 40-hour sampling at 20-minute intervals, whereas his serum FSH titers remained undetectable (less than 0.4 IU/l). Infusion of LHRH, 0.2 microgram/minute for 4 hours, induced the expected rise in the serum LH levels, but serum FSH levels remained low and only at one point reached 0.9 IU/l (normal adult male basal range 0.9-10.3 IU/l). The patient received LHRH, 100 micrograms/day, for three days. A second LHRH infusion, 0.2 microgram/minute for 4 hours, induced a normal rise in both the serum LH and FSH titers. The serum sex steroid binding globulin level was 10.3 ng DHT bound/ml (normal adult male level 8.0 +/- 0.3 ng DHT bound/ml). Presence of circulating auto-antibodies to the serum FSH was excluded by determining the binding of [125I] FSH with the patient's serum and comparing it with sera obtained from two normal male adult volunteers. Pituitary function tests were otherwise intact. Presence of a pituitary tumor was excluded by computerized axial tomography and x-ray studies of the pituitary fossa and normal visual fields. Clinically, the patient demonstrated cryptorchidism, hypospadias, surgically repaired omphalocele, and bilateral hearing loss.(ABSTRACT TRUNCATED AT 250 WORDS)

The clinical features and hormonal abnormalities were surveyed in 117 men with cirrhosis of the liver. Compared with healthy men of similar ages, the patients had significantly lower metabolic clearance rates, plasma production rates and total and free levels of testosterone, reduced testosterone responses to human chorionic gonadotrophin stimulation, higher oestradiol, luteinizing hormone and follicle stimulating hormone levels and higher binding capacities of sex steroid binding globulin. The peripheral conversion of testosterone to oestradiol was also found to be significantly increased. However, the metabolic clearance and plasma production rates of oestradiol were not significantly different from those of healthy men. Patients who were severely ill with liver failure and one with haemochromatosis had low levels of luteinizing hormone and follicle stimulating hormone and sub-normal responses to clomiphene and luteinizing hormone-releasing hormone. Higher plasma oestradiol levels were found in patients with gynaecomastia and spider naevi than in those without these signs. However, the clinical features of androgen deficiency--that is, testicular atrophy, impotence and loss of secondary sex hair--were only poorly related to the low testosterone levels, and production rates and longtitudinal studies indicated that the hormonal levels, endocrine features and severity of the liver disease could change independently. It is concluded that the clearance of oestradiol from plasma is not limited by liver disease in all patients, and that reduced degradation of oestrogens is not the initial event in the sequence leading to the hormonal abnormalities of cirrhosis. While gonadotrophin deficiency occurs with liver failure and in some patients with haemochromatosis, the more usual findings are of elevated gonadotrophin levels and a poor Leydig cell response to chorionic gonadotrophin. These suggest that the hypogonadism is primary in most patients with cirrhosis. The causes of the high oestradiol levels were not discovered. Increased peripheral conversion of precursors to oestradiol or increased testicular secretion of oestradiol are possibilities. The high binding capacities of sex steroid binding globulin were not significantly correlated with either the low testosterone or high oestradiol level and the cause of this abnormality remains uncertain. The low metabolic clearance rates of testosterone appeared to result from the increased plasma protein binding of testosterone. The discrepancies in the expected relationships between the hormone and clinical changes suggest that factors other than those studied are also involved in the genesis of the endocrine features of hepatic cirrhosis.

Nineteen vasectomized men were followed for 21 to 42 months after surgery, and their sera were tested for the presence of HL-A lymphocytoxic antibodies. In a previous study, the sera of two of these men had shown a definite increase in serum reactivity 6 to 12 months after surgery. Only one of the nineteen tested in the study demonstrated, a single, weakly positive, reaction 24 months after surgery. It was considered that the initial stimulus for lymphocytotoxic antibody production was related to surgery. There was no evidence of antibody stimulation 21 to 44 months postoperatively.

In order to study the ability of the sperm penetration assay (SPA) to correctly classify the fertility status of men, we prospectively examined the results of the SPA performed on the semen of three groups of men of known fertility status. The groups included 67 normal men without varicoceles whose wives were pregnant (VARN), 51 men with a palpable varicocele whose wives were pregnant (VARF), and 30 infertile men with varicoceles (VARI). Two SPAs were done on each subject. Ninety-seven percent of the VARIs showed less than 15% penetration on a single test, and 91% showed less than 15% on both tests. On a single test 61% of the VARNs and 68% of the VARFs were less than 15%. If 0 penetration were used as the criteria of infertility, then 40% of the VARIs, 27% of the VARFs, and 12% of the VARNs would be classified as being infertile. These data suggest that the SPA cannot independently define male fertility status and should be used in conjunction with the standard semen analysis and clinical evaluation of the couple to assess male fertility potential.

There were 50 patients with acute epididymitis who were evaluated prospectively by history, examination and microbiologic studies, including cultures for aerobes, anaerobes, Neisseria gonorrhoeae, Chlamydia trachomatis and Ureaplasma urealyticum. Escherichia coli was the predominant pathogen isolated from the urine of men more than 35 years old, while Chlamydia trachomatis and Neisseria gonorrhoeae were the predominant pathogens isolated from the urethra of men less than 35 years old. The etiologic role of Escherichia coli and Chlamydia trachomatis was confirmed by isolation from epididymal aspirates from a high proportion of men with positive urine or urethral cultures for these agents. Chlamydia trachomatis epididymitis accounted for two-thirds of idiopathic epididymitis in young men and often was associated with oligospermia. Of 9 female sexual partners of men with Chlamydia trachomatis infection 6 had antibody to Chlamydia trachomatis, of whom 2 had positive cervical cultures for this organism and 2 others had non-gonococcal pelvic inflammatory disease. Antibiotic therapy with tetracycline was effective for the treatment of men with Chlamydia trachomatis epididymitis and should be offered to the female sex partners.

Five normal men received constant intravenous infusions of luteinizing hormone-releasing hormone (LH-RH), 0.2 mug/min, for 14-19 hours. Serum levels ofluteizining hormone (LH) revealed a biphasic pattern of increase, reaching maximal values by 4 hours after the infusions began, then remained near that level until the infusions ceased. Serum follicle stimulating hormone (FSH) levels rose gradually to maximal values by 6-13 hours and maintained this level until the end of the infusions. Testosterone (T) levels revealed gradual increases throughout the infusions. These results confirm an increase in serum T levels with prolonged endogenous gonadotrophin stimulation. This is in contrast to the inability of several previous studies to demonstrate an increase in T levels following the relatively short gonadotrophin elevation produced by single-shot LH-RH administration. The T increases produced, however, were quantitatively much less than those reported during prolonged LH-RH infusions in rams, suggesting that the human testis is less responsive to endogenous gonadotrophin stimulation than is that of the ram. In addition, prolonged LH-RH stimulation did not cause pituitary refractoriness in men as has been described in animals.

The relative roles of FSH and LH in the control of human spermatogenesis are not well established. We previously reported that supraphysiological doses of hCG can stimulate sperm production in gonadotropin-suppressed normal men despite prepubertal FSH levels. To determine whether more nearly physiological levels of human LH (hLH) also can stimulate spermatogenesis when FSH levels are suppressed, we administered hLH to normal men whose endogenous gonadotropin levels and sperm production were suppressed by exogenous testosterone enanthate (T). After a 3-month control period, 11 normal men received 200 mg T, im, weekly to suppress LH and FSH. T administration alone was continued for 3-4 months until 3 successive sperm concentrations (performed twice monthly) revealed azoospermia or severe oligospermia (sperm concentrations, less than 4 million/ml). Then, while continuing T, 4 of the 11 men (experimental subjects) simultaneously received 1100 IU hLH, sc, daily for 4-6 months to replace LH activity, leaving FSH activity suppressed. The effect on sperm production of the selective FSH deficiency produced by hLH plus T administration was determined. The remaining 7 men (control subjects) continued to receive T alone at the same dosage, without gonadotropin replacement, for an additional 6 months. In the four experimental subjects, sperm concentrations increased significantly from 0.7 +/- 0.7 million/ml (mean +/- SEM) during T treatment alone to 19 +/- 4 million/ml during hLH plus T administration (P less than 0.001). However, none of the men achieved sperm concentrations consistently in their own pretreatment range. Sperm motilities and morphologies were normal in all four subjects by the end of hLH plus T administration. In contrast, sperm concentrations in the seven control subjects remained suppressed (less than 3 million/ml) throughout the entire period of prolonged T administration alone. Serum LH bioactivity, determined monthly by in vitro mouse Leydig cell bioassay in all four experimental subjects, was markedly suppressed during T administration alone (120 +/- 10 ng/ml) compared to that during the control period (390 +/- 20 ng/ml; P less than 0.001). With the addition of hLH to T, LH bioactivity returned to control levels (400 +/- 40 ng/ml; P = NS compared to control value). Serum FSH levels determined monthly by RIA were reduced from 98 +/- 12 ng/ml during the control period to undetectable levels (less than 25 ng/ml) during the T alone and the hLH plus T periods (P less than 0.01).(ABSTRACT TRUNCATED AT 400 WORDS)

Cerebrospinal fluid (CSF) concentrations of corticotropin, growth hormone, thyrotropin, prolactin, luteinizing hormone, and follicle stimulating hormone were measured in 28 patients with various neurologic disorders, in 49 patients with pituitary tumors of whom 22 had suprasellar extension, and in 6 patients with craniopharyngiomas. With the exception of 1 patient with pseudotumor cerebri, CSF adenohypophyseal hormone concentrations were low in patients with neurologic disease and in patients with pituitary tumor without suprasellar extension. In marked contrast, 21 to 22 patients with suprasellar extension of a pituitary tumor and 2 of 6 patients with a craniopharyngioma had elevations of one or more CSF adenohypophyseal hormones. Posttreatment CSF adenohypophyseal hormone levels fell from previously elevated levels in 4 of 5 patients. These data suggest that an elevated CSF adenohypophyseal hormone concentration is a sensitive indicator of suprasellar extension of a pituitary tumor, and posttreatment measurements are useful in determining efficacy of therapy.

A new staining method for differentiating WBCs from immature germ cells in seminal fluid has been studied. It is a combination of Bryan's sperm stain, which particulary stains the acrosomal cap of the spermatozoa and the spermatid, and Leishman's blood stain which stains the WBCs in the same way as found in blood smears. The peroxidase positive granules in the cytoplasm of the PMN leukocytes are seen clearly. Thus, it is possible to differentiate PMN leukocytes from non-separated spermatids when they are present in a common cytoplasm. The staining of acrosomal cap permits differentiation between spermatids and lymphocytes.

The role of follicle-stimulating hormone (FSH) in the control of spermatogenesis is not well established in any species, including man. We studied the effect of an experimentally-induced, selective FSH deficiency on sperm production in normal men. After a 3-mo control period, five normal men received testosterone enanthate (T) 200 mg i. m. weekly to suppress luteinizing hormone (LH) and FSH, until three successive sperm counts revealed azoospermia or severe oligospermia (sperm counts <3 million/ml). Then, while continuing T, human chorionic gonadotropin (hCG) 5,000 IU i. m. three times weekly was administered simultaneously to replace LH activity, leaving FSH activity suppressed. The effect of the selective FSH deficiency produced by hCG plus T administration on sperm production was determined. Sperm counts (performed twice monthly throughout the study) were markedly suppressed during T administration alone (1.0+/-1.0 million/ml mean+/-SE, compared with 106+/-28 million/ml during the control period, P < 0.001). With the addition of hCG to T, sperm counts returned toward normal (46+/-16 million/ml, P < 0.001 compared with T alone). In two subjects, sperm counts during hCG plus T returned into the individual's control range. Sperm motility and morphology were consistently normal in all men during hCG plus T. Serum FSH levels by RIA were normal (110+/-10 ng/ml) in the control period and were suppressed to undetectable levels (<25 ng/ml) in the T alone and hCG plus T periods. Urinary FSH excretion was markedly suppressed in the T alone (60+/-15 mIU/h-2nd IRP, P < 0.01) and hCG plus T (37+/-9 mIU/h, P < 0.01) periods compared with the control period (334+/-78 mIU/h). We conclude that spermatogenesis as assessed by sperm counts, motilities, and morphologies may be reinitiated and maintained at normal levels in men with undetectable blood FSH levels and urinary excretion of FSH less than that of prepubertal children. This conclusion implies that, although FSH may exert effects on human testicular function, maintenance of normal spermatogenesis and reinitiation of sperm production after short-term suppression by exogenous steroids can occur in spite of nearly absent FSH stimulation.

The responses of circulating levels of androgens, estrogens, and their C-21 biosynthetic precursors to a 6-h constant infusion of human Lh (hLH; 2000 IU) were studied in four males with hypogonadotropic hypogonadism (HH) and compared with those in normal male controls. Although similar levels of circulating LH were achieved, the initial and secondary increases in testosterone were significantly greater in the hypogonadotropic subjects than in the normal controls. In contrast, the responses of estradiol, estrone, 17 alpha-hydroxyprogesterone, and 17 alpha-hydroxypregnenolone to exogenous hLH were significantly lower in HH than in normal controls. The data demonstrate a different pattern of testicular steroidogenic responsiveness after pharmacological doses of hLH, with increased concentrations of circulating testosterone in subjects with HH compared to a disproportionate increase in estrogen and progestin levels in normal men.

In summary, seventeen infertile men with varicocele in whom no other cause for infertility could be identified, were studied before and following varicocele repair. Morphologic alterations were the most common abnormality noted in the seminal fluid with all subjects demonstrating increased numbers of tapered or amorphous spermatozoa. Ligation of the varicocele resulted in improvement in one or more of the seminal fluid abnormalities in thirteen of the seventeen patients. Seven patients achieved a pregnancy. No single seminal fluid parameter was identified which was of predictive value in determining those subjects who would demonstrate improvement following varicocele repair.

The high prevalence of men with varicoceles who by history are fertile has led some to question the suggested causal relationship between a varicocele and male infertility. However, testicular function in these fertile men has not previously been studied in detail. Fifty-five normal fertile men, 42 fertile men with varicoceles, and 24 infertile men with varicoceles and normal female partners were studied. Semen analyses were done, baseline serum testosterone and gonadotropin levels tested and the gonadotropin response to luteinizing hormone-releasing hormone (LH-RH) measured. The infertile men with varicoceles exhibited lower sperm counts, abnormal sperm morphologic features, increased baseline serum gonadotropins, and increased gonadotropin responses to LH-RH, compared with the normal fertile men. The fertile men with varicoceles showed similar abnormalities, although this was not statistically significant in all cases. That semen and hormone abnormalities were observed in both the fertile and infertile men with varicoceles suggests that the presence of a varicocele is associated with some degree of primary testicular dysfunction, regardless of present fertility status.

Serum lipids were examined in thirty normal male volunteers who had received depo-medroxyprogesterone acetate (DMPA) and testosterone cypionate (TC) in a male contraceptive trial. Progestagens have been implicated in the changes in serum lipids observed in women using oral contraceptives and this has led to concern about cardiovascular health risks associated with the long-term use of some of these preparations. The following study was done to determine if similar effects occur in men. The men in this study were divided into three DMPA dose groups (50, 100, 200 mg/month) and received intramuscular injections for six months; all men received 250 mg/month TC. There was no significant change in serum high density lipoprotein-cholesterol (HDL-C) levels during the six months of drug administration when compared to levels in the control period. However, there was a marked decrease in HDL-C during the first three months after discontinuation of the drugs (p less than 0.02). This observed change was consistent in each of the three DMPA dose groups but no dose relationship was observed. There was no statistically significant change in serum concentrations of total cholesterol, low density lipoprotein-cholesterol, triglycerides or insulin in any period of the experiment. Serum testosterone (T), estradiol, and sex hormone binding globulin (SHBG), luteinizing hormone (LH), and follicle stimulating hormone (FSH) concentrations were all significantly depressed during the drug administration period. A progestagen dose relationship was observed only for the decrease in serum testosterone and LH concentrations. Serum T and SHBG levels were still significantly reduced at 4-6 months after cessation of the drug administration. These findings demonstrate that DMPA can cause a reduction in serum HDL-C levels. It is suggested that HDL-C concentrations fell only following DMPA withdrawal as a consequence of steroid hormone changes specific to this period.

Sertoli cell ultrastructure was compared in men with testicular disorders (hypospermatogenesis; germ cell aplasia) and men with normal testes to determine if any specific cytological change could be correlated with diminished feedback from the testis resulting in elevated serum FSH levels. The normal Sertoli cell contained smooth endoplasmic reticulum, mitochondria and variable numbers of lipid inclusions, lipofuscin, crystals of Charcot-Böttcher and specialised inter-Sertoli cell junctional complexes. The principal abnormalities in Sertoli cells of men with testicular disorders were: 1) dilated vesicles of smooth endoplasmic reticulum and occasional expansions of the intercellular space; 2) increased numbers of cytoplasmic filaments; and 3) with germ cell aplasia inter-Sertoli cell junctions were complexly arranged due to interdigitation of Sertoli cell processes. Occasionally, increased lipid and lipofuscin aggregations were seen and in germ cell aplasia, aggregations of cytoplasmic glycogen were often present. Although these changes were seen more consistently with germ cell aplasia they were observed frequently with hypospermatogenesis where some tubules contained Sertoli cells with normal features. No correlation was found between abnormal Sertoli cell cytology and serum FSH levels.

D-group chromosome translocations have been associated in isolated cases with infertility in males. In this study, we demonstrated the effect of a translocated D-group chromosome on spermatogenesis as it had segregated among three male members of one family. Although the father, who carried the translocation, was obviously fertile, the effects of the translocations on his sperm were noted in the morphologic examination. This study demonstrates the need for more careful evaluation of patients with chromosomal abnormalities for effects on spermatogenesis. Furthermore, it shows the possibility of autosomal chromosomal influences on testicular function.