Biomedical subjects
C A Paulsen
Publications and source records attributed to C A Paulsen.
Selection biases in semen study?
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Annual patterns of luteinizing hormone, follicle stimulating hormone, testosterone and inhibin in normal men.
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.
Proteolysis of insulin-like growth factor-binding protein-3 in the male reproductive tract.
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.
Combined administration of levonorgestrel and testosterone induces more rapid and effective suppression of spermatogenesis than testosterone alone: a promising male contraceptive approach.
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.
A combined regimen of cyproterone acetate and testosterone enanthate as a potentially highly effective male contraceptive.
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.
Data from men in greater Seattle area reveals no downward trend in semen quality: further evidence that deterioration of semen quality is not geographically uniform.
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.
Tibial intramedullary alignment in total knee arthroplasty.
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.
Testosterone enanthate at a dose of 200 mg/week decreases HDL-cholesterol levels in healthy men.
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.
Preservation of fertility despite subnormal gonadotropin and testosterone levels after cessation of pulsatile gonadotropin-releasing hormone therapy in a man with Kallmann's syndrome.
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.
Stroke after pituitary irradiation.
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.
Relationship of serum inhibin levels to serum follicle stimulating hormone and sperm production in normal men and men with varicoceles.
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.
A double-blind, placebo-controlled trial of the effect of chronically administered oral acyclovir on sperm production in men with frequently recurrent genital herpes.
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The use of sperm penetration assay in evaluation of men with varicocele.
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.
Comparison of gonadal function between fertile and infertile men with varicoceles.
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.
Transient reduction in serum HDL-cholesterol following medroxyprogesterone acetate and testosterone cypionate administration to healthy men.
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.
Gonadotropin control of spermatogenesis in man: studies of gonadotropin administration in spontaneous and experimentally induced hypogonadotropic states.
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Stimulation of sperm production by human luteinizing hormone in gonadotropin-suppressed normal men.
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)