Effect of oral tamoxifen on semen characteristics and serum hormone profile in male bonnet monkeys

The effects of oral tamoxifen were studied at a dose of 0.4 mg/kg per day, on the serum hormones and semen parameters in adult male bonnet monkeys, for a period of 90 days. Honey was used as vehicle. Monkeys were treated with honey for 30 days, followed by tamoxifen from Day 30-120 (90 days). Thereafter the treatment was withdrawn until Day 150 of schedule. Blood samples were drawn at 12 and 24 clock hours at monthly intervals for the analysis of luteinizing hormone, follicle-stimulating hormone and testosterone. Semen samples were also collected for analysis once a month, from Day 0-150 of exposure. Tamoxifen treatment produced a transient but significant increase in circulating gonadotropins, at Day 90 of treatment schedule, corresponding to 60 days of treatment. Whilst serum testosterone levels were normal throughout treatment period, an increase was observed after 30 days of drug withdrawal. No effect of oral tamoxifen was evident on semen parameters, viz., volume, counts, morphology and motility. However, throughout the exposure period to honey, a significant increase was observed in sperm counts without any effect on testosterone levels. The present study suggests that oral tamoxifen has a transient antiestrogenic effect on the serum hormones and no effect on semen parameters of adult nonhuman primate males. It is concluded that bioefficacy of oral tamoxifen may have been reduced due to hepatic metabolism.     

Study of medroxyprogesterone acetate and testosterone enanthate as a male contraceptive

In an attempt to produce azoospermia while maintaining normal serum testosterone levels, injections of medroxyprogesterone acetate (100 mg or 150 mg) and testosterone enanthate (200 mg) were administered intramuscularly for 4 consecutive months to 14 normal men. This treatment caused suppression of gonadotropins and reduction of sperm counts in all subjects. Sperm concentrations fell below 5 million/ml in 10 subjects, 2 of whom attained azoospermia. A recovery phase of 16–41 weeks after the last injection was necessary for all subjects to return to pretreatment sperm concentrations. Pretreatment testosterone levels were not maintained during treatment, but there was no subjective loss of libido. Unilateral gynecomastia occurred in one subject during the treatment phase of the study. The dosage of the gestagen-androgen formulation used in this study is probably insufficient for use as a male contraceptive.     

Investigations on the use of testosterone oenanthate as a male contraceptive agent

The effect of exogenous testosterone on male gonadal function was in vestigated by applying a practical dose schedule of weekly injections of testosterone enanthate. 7 healthy young males received 22 intramuscular injections of 250 mg testosterone enanthate once a week for a period of 21 weeks. Mean sperm counts were reduced from a pretreatment value of 73 million sperm/ml to below 3 million sperm/ml within 9 weeks of testosterone administration and remained so during the whole treatment period. A marked recovery of spermatogenesis did not occur before 13 weeks after testosterone withdrawal, when the mean sperm count rose to 63 million sperm/ml. Changes of the mean sperm motility and percentage of normal sperm morphology generally paralleled those of the mean sperm concentration, whereas the mean semen volume, libido, potency, and secondary sex characteristics remained unaffected. A consistently azoospermic semen was not developed by any individual. This and the fact that sperm counts in 3 out of 7 males still showed some depression of spermatogenesis at the end of the observation period of 28 weeks after testosterone withdrawal indicate that testosterone enanthate admin istered in the described dose schedule is not a safe male contraceptive agent. However, further research on the use of hormones for the control of fertility in men seems warranted.     

Clinical evaluation of long-term treatment with levo-norgestrel and testosterone enanthate in normal men

Thirteen healthy men (25–35 years) with proven fertility were scheduled for long-term treatment (> 12 months) with levo-norgestrel (500 μg daily) and testosterone enanthate (200 mg monthly). The volunteers were regularly investigated prior to, during and after treatment. Seven volunteers withdrew from medication after 1 to 12 months of treatment; three due to psychological side effects, one because of stiffness of a finger joint, two for personal reasons and one for unspecified reasons. Sperm counts were significantly decreased during treatment and in 7 volunteers the sperm counts were <5 × 10⁶/ml. However, two of these volunteers exhibited a breakthrough in sperm counts after 12 and 13 months of a 16-month treatment period. Serum testosterone, serum LH and serum FSH were significantly decreased during treatment, but returned, as did sperm counts, to normal levels after withdrawal of treatment. No rebound effect was seen. Potency and libido remained unchanged. No toxicological side effects were observed and finally no consistent changes were seen in blood coagulation parameters.     

The effect of monthly depot medroxyprogesterone acetate and testosterone on human spermatogenesis I. Uniform dosage levels

Depot medroxyprogesterone acetate (DMPA) was tested for suppressive effects on spermatogenesis in 29 men. DMPA was administered as a monthly injection of 100 or 150 mg; in addition, testosterone was given either in subdermal sustained release implants of testosterone propionate (TP), or as a monthly injection of 100 or 250 mg testosterone enanthate (TE). Sperm production was reduced in 28/29 subjects. In most instances, production was severely inhibited, as indicated either by sperm counts below 1 million/ml, or by testicular biopsy showing spermatogenic arrest. No changes were reported or observed in the size, consistency, or sensitivity of breasts, testicles or prostate. Some subjects reported slight initial decreases in libido, but returned to normal after the first few weeks of treatment. Metabolic parameters were measured in some subjects, and showed no significant changes. Transient weight gain occurred in a few subjects.     

A short-term evaluation of semen and accessory sex gland function in phase III trial subjects receiving intravasal contraceptive RISUG

Following the intravasal injection of a new male contraceptive RISUG (reversible inhibition of sperm under guidance) in volunteers, routine semen analysis, semen biochemistry and germ cell morphology were evaluated in comparison with the corresponding preinjection samples for a maximum period of 6 months. Sperm counts in all 25 subjects before injection varied from 45 to 120 x 10(6)/ml. Out of 25 subjects, 6 became azoospermic after 1 month, 15 after 2 months, 3 after 3 months and 1 after 4 months of contraceptive injection. The mean volume of the ejaculates was found to be less as compared to preinjection samples. Occasional sperm or sperm heads and immature germ cells were identified in only a few postinjected subjects. However, no pregnancy was reported in these subjects during the study period. Abnormal morphology found in most of the sperm, but not in the accompanying immature germ cells, may be due to a charge-related effect on the former but not on the latter cells. Neutral alpha-glucosidase, the biochemical marker for epididymis, was estimated to be significantly lower in the seminal plasma of all the postinjected subjects. On the other hand, acid phosphatase activity and fructose levels in the seminal plasma were found to be in the normal range. Based on the above findings, it is concluded that at least for the present study period, RISUG, a new male contraceptive, is effective as a partially occluding agent in the vas deferens.     

Preclinical evaluation for noninvasive reversal following long-term vas occlusion with styrene maleic anhydride in langur monkeys

A preclinical evaluation for reversal through a noninvasive approach following long-term vas occlusion with styrene maleic anhydride (SMA) has been attempted in langur monkeys at the level of semen parameters, sperm functional tests, semen biochemistry, histology and ultrastructure of reproductive organs, hematology and serum clinical biochemistry including antisperm antibodies (ASA), prostate-specific antigen (PSA) and testosterone. Noninvasive reversal through palpation, percutaneous squeezing and electrical stimulation, forced vibratory movements and suprapubic percussion in the inguinal segments and per-rectal digital massage was attempted in seven langur monkeys after 540 days following vas occlusion. The results revealed instant azoospermia reversal on the same day of reversal with impaired sperm quality, which showed gradual improvement and normospermia with normal motility and viability after 60-90 days of reversal. Sperm functional tests, including ultrastructure of spermatozoa, indicative of sterility in the initial ejaculations, reached normalcy after 90-120 days of reversal. The seminal plasma biochemistry indicative of obstructive azoospermia regained a normal pattern after 90-120 days of reversal. The morphology of testes that showed focal degeneration during 540 days of vas occlusion and that of vasa deferentia that showed exfoliation of epithelial cells resumed to normal morphology comparable with control animals after 150 days of reversal. The morphology of the epididymis, seminal vesicle and prostate did not show appreciable changes following vas occlusion and after noninvasive reversal compared with those of control animals. Hematology, serum clinical chemistry, ASA, PSA and testosterone fluctuated within control limits, indicating safety of the procedure at the level of accessory reproductive organs. The results suggest that noninvasive reversal is feasible even after long-term vas occlusion with SMA and is safe without adverse side effects.     

The effect of monthly depot medroxyprogesterone acetate and testosterone on human spermatogenesis. II. High initial dose

The combination of depot medroxyprogesterone acetate (DMPA) and testosterone enanthate (TE) was tested for suppressive effects on spermatogenesis in 12 men. DMPA was administered in an initial injection of 1000 mg, with subsequent monthly injections of 150 mg. An injection of 250 mg TE was administered with each DMPA injection. Sperm production was inhibited in 11/12 subjects; in 10, sperm counts fell below 1 million/ml. Decreases were observed in plasma LH, FSH, testosterone. (T) and estradiol (E₂) at 4 weeks after the 1st injection. During continued treatment, LH rose to the pretreatment level, while FSH, T and E₂ remained at least partially reduced. No changes were reported or observed in the size, consistency or sensitivity of testicles, prostate or breasts. Two subjects reported slight decreases in libido, but returned to normal after the first month of treatment. Metabolic parameters showed no significant changes. No weight gain occurred.     

Changes in the biochemical composition of semen following danazol plus testosterone enanthate administration to the langur monkey

Changes in the biochemical composition of semen, which reflect the accessory sex organ functions, following danazol (100 mg/day; orally) plus testosterone enanthate (50 mg/month; i.m.) administration have been investigated in langur monkey. The levels of acid phosphatase, lactic dehydrogenase and glycerylphosphorylcholine in the semen decreased significantly; whereas fructose, citric acid, magnesium and semen volume did not show any significant changes. A gradual decrease in the motility and count of spermatozoa was observed. At 60 days of treatment all animals became azoospermic. No drug related hematological changes were observed. The combination therapy impaired the epididymal and prostatic functions along with suppression of spermatogenesis.     

Cyproterone acetate affects protamine gene expression in the testis of adult male rat

The temporal effects of oral administration of cyproterone acetate (CPA), a progestational androgen receptor blocker, were studied on the fertility of adult male rat sires, at a dose of 20 mg kg-1 day-1 after 15 days of gavage. The treatment reduced the fertility and weights of accessory sex glands, without altering the serum levels of luteinizing hormone, follicle-stimulating hormone (FSH) and testosterone (T). Sperm counts were significantly reduced after treatment. Several changes were evident in caput epididymal sperm chromatin in treated rats. The in vitro decondensation rates of sperm chromatin and total fluorescent acridine orange (AO) dye uptake were enhanced. The fluorescent AO dye uptake by the double- and single-stranded sperm chromatin increased. The uptake of thiol-specific monobromobimane fluorescent dye by sperm chromatin was significantly reduced. Sperm of treated rats exhibited hypoprotamination. Protamine levels in the testis were significantly reduced after treatment. Androgen-binding protein (ABP) expression was significantly reduced in testis after treatment. A slight but significant increase was observed in cyclic AMP immunoexpression in testis after treatment. The expression and levels of transition proteins 1 (TP1) and 2 (TP2) as well as cyclic AMP response element modulator protein-tau were maintained at control levels in the testis of treated rats. The present study reports that androgen receptor occupation by CPA preferentially reduces the levels of spermatidal protamine in testis and spermatozoa involved in nuclear chromatin condensation. It is inferred that ABP could be mediating the effects of T in modulating the sequential expression of TPs and protamines during nuclear chromatin condensation. It is likely that indirect effects of T involve its aromatization in spermatids.     

禁欲时间与精液参数的相关性研究

目的:探讨禁欲时间与精液参数的关系。方法:接纳在孕前检查中要求精液检查的620例为对象,分析禁欲时间与精液参数之间的关系。结果:禁欲1～3d精液量无明显增加,为2.2～2.9ml;禁欲4d精液量增加到3.4ml,显著高于禁欲1d;禁欲4d与禁欲7d的精液量无差异。精子密度从禁欲1d的26.3×106/ml上升到3d的64.6×106/ml,增量明显(P<0.05);禁欲4d与6d的精子密度无明显增加;不同禁欲时间a级、b级和(a+b)级精子的比例无明显的变化。结论:在本研究范围内,精液的量、精子密度和总精子数随着禁欲时间延长而增加,精子的活力保持不变。     

超生理剂量11-酸睾酮对人精液中脱落生殖细胞的影响

为研究大剂量睾酮对生精细胞的影响,对53例志愿接受11-酸睾酮的成年男性在给药前后及恢复期的精液进行分析,用瑞-姬氏染色进行脱落生殖细胞观察。结果为给药后30,60天脱落生殖细胞计数随精子计数减少而减少,初级精母细胞、次级精母细胞比例增多,精子细胞减少。细胞增多了凋亡脱落生殖细胞的各种形态变化,包括凋亡的初级、次级精母细胞和精子细胞。恢复期随精子计数的恢复,生精细胞的计数和形态也相应恢复。提示11-酸睾酮主要干扰了初级、次级精母细胞和精子细胞的正常分化发育。     

Increased BMI ‘alone’ does not negatively influence sperm function - a retrospective analysis of men attending fertility treatment with corresponding liver function results

Does increased body mass index (BMI) without an underlying metabolic issue negatively influence semen quality? Proof of concept we conducted retrospective data analysis of men (N = 84) undergoing assisted reproductive technology, who had liver function testing with fasted glucose concentrations and corresponding hormone profile (testosterone, LH, FSH and prolactin) and semen analysis. Sperm count and total concentration were only reduced in metabolically unhealthy overweight/obese men. Serum GTT was the biggest predictor of Normozoospermia and Oligospermia, with BMI having no effect. Increased BMI without an underlying metabolic condition (in particular signs of NAFLD) has no influence on semen quality.     

Exposure to environmental ozone alters semen quality

Idiopathic male infertility may be due to exposure to environmental toxicants that alter spermatogenesis or sperm function. We studied the relationship between air pollutant levels and semen quality over a 2-year period in Los Angeles, California, by analyzing repeated semen samples collected by sperm donors. Semen analysis data derived from 5,134 semen samples from a sperm donor bank were correlated with air pollutant levels (ozone, nitrogen dioxide, carbon monoxide, and particulate matter < 10 microm in aerodynamic diameter) measured 0-9, 10-14, and 70-90 days before semen collection dates in Los Angeles between January 1996 and December 1998. A linear mixed-effects model was used to model average sperm concentration and total motile sperm count for the donation from each subject. Changes were analyzed in relationship to biologically relevant time points during spermatogenesis, 0-9, 10-14, and 70-90 days before the day of semen collection. We estimated temperature and seasonality effects after adjusting for a base model, which included donor's date of birth and age at donation. Forty-eight donors from Los Angeles were included as subjects. Donors were included if they collected repeated semen samples over a 12-month period between January 1996 and December 1998. There was a significant negative correlation between ozone levels at 0-9, 10-14, and 70-90 days before donation and average sperm concentration, which was maintained after correction for donor's birth date, age at donation, temperature, and seasonality (p < 0.01). No other pollutant measures were significantly associated with sperm quality outcomes. Exposure to ambient ozone levels adversely affects semen quality.     

Treatment of Oligoasthenozoospermia with Tranilast,a Mast Cell Blocker,After Long-Term Administration

The authors retrospectively examined whether long-term administration of tranilast improves semen parameters in severe oligoasthenozoospermia. Fifty-two patients presenting with sperm concentration of less than 10 &#50 10 6 sperm/mL were enrolled. Subjects were partitioned into 3 groups as follows: patients displaying an atrophic testis with elevated (FSH) (group 1), patients exhibiting normal testicular volume with elevated FSH (group 2), and patients with normal testicular volume and normal FSH levels (group 3). Tranilast (300mg/day) was administered until pregnancy was achieved or for a period of up to 12 months. Sperm concentration was significantly increased at 3 months in 16 subjects (44%) in groups 1 and 3. In group 2, sperm concentration was increased at 12 months (5 of 16 subjects; 31%). Total sperm count was obviously elevated at 3 months in groups 1 and 2, and at 6 months in group 3. Six pregnancies were achieved via natural intercourse. Tranilast, a mast cell blocker, demonstrates a certain clinical benefit in terms of improvement of semen parameters involving severe oligoasthenozoospermia, but it does not appear to afford clinical benefit in long-term administration.     

Semen collection, characterisation and artificial insemination in the beluga (Delphinapterus leucas) using liquid-stored spermatozoa

Ejaculates were collected from a beluga (Delphinapterus leucas) to gain an understanding of sperm biology and develop a short-term sperm preservation method for use in artificial insemination (AI). Ejaculate parameters and biochemistry, semen production and serum testosterone concentrations of an adult male were characterised for 21 months. Sperm viability, acrosome integrity and morphology did not change (P > 0.05) but ejaculate volume, sperm concentration and total spermatozoa per ejaculate were higher (P < 0.05) from January to June than from July to December. Peak testosterone concentrations (P < 0.05) were observed from October to April (8.0 +/- 1.6 ng mL(-1)). The effects of hyaluronic acid (HA), antioxidants, storage temperature and time on in vitro sperm characteristics were examined. Motility parameters and viability were improved (P < 0.05) when semen was stored at 5 degrees C compared with 21 degrees C. During the first 24 h of storage sperm agglutination was absent only at 5 degrees C in the presence of HA. A nulliparous 28-year-old female was inseminated endoscopically with liquid-stored semen. A pregnancy and birth of a calf was achieved following AI for the first time in this species, thereby validating both the AI technique and the fertility of beluga spermatozoa after chilled storage in a specialised diluent.     

Semen Characteristics of Gossypol-Treated Langurs (Presbytis Entellus Entellus Dufresne)

Gossypol isolated from cottonseed was fed to sexually adult male langurs at 50 and 100 mg/kg body weight per day for 90 days. Semen was collected every 2 wk, and the observations made on semen characteristics showed gossypol's detrimental effect. The gossypol administration caused a significant decline in percent sperm cells motility and a significant rise in abnormalities. The semen characteristics returned to normal levels during a 180-day recovery period following the discontinuation of gossypol treatment. A clear relationship exists between the inhibition of sperm cell motility and dose as well as duration of gossypol treatment. The testicular biopsies taken from two langurs after 90 days of gossypol treatment showed normal histoarchitecture at both the dose levels.     

Use of a new drug delivery formulation of the gonadotrophin-releasing hormone analogue Deslorelin for reversible long-term contraception in male dogs

In the present study, we tested the effect of treatment with a slow-release implant containing the gonadotrophin-releasing hormone agonist Deslorelin(TM) (Peptech Animal Health Australia, North Ryde, NSW, Australia) on pituitary and testicular function in mature male dogs. Four dogs were treated with Deslorelin (6-mg implant) and four were used as controls (blank implant). In control dogs, there were no significant changes over the 12 months of the study in plasma concentrations of luteinising hormone (LH) or testosterone, or in testicular volume, semen output or semen quality. In Deslorelin-treated dogs, plasma concentrations of LH and testosterone were undetectable after 21 and 27 days, testicular volume fell to 35% of pretreatment values after 14 weeks and no ejaculates could be obtained after 6 weeks. Concentrations returned to the detectable range for testosterone after 44 weeks and for LH after 51 weeks and both were within the normal range after 52 weeks. Semen characteristics had recovered completely by 60 weeks after implantation. At this time, the testes and prostate glands were similar histologically to those of control dogs. We conclude that a single slow-release implant containing 6 mg Deslorelin has potential as a long-term, reversible antifertility agent for male dogs.     

Could zinc prevent reproductive alterations caused by cigarette smoke in male rats?

The aim of the present study was to evaluate the effects of zinc on fertility through semen parameters, testosterone level and oxidative DNA damage to spermatozoa of rats exposed to cigarette smoke. Male Wistar rats (60 days old) were divided into four groups (n = 10 per group): control, cigarette-smoking (20 cigarettes per day), zinc (zinc chloride 20 mg kg?1 day?1) and zinc plus cigarette-smoking (zinc chloride 20 mg kg?1 day?1; 20 cigarettes per day). The treatment was applied for nine weeks and the following parameters were analysed: bodyweight, wet weights of the reproductive organs and the adrenal gland, plasma testosterone concentration, testicular function (seminal analysis and daily sperm production) and sperm DNA oxidative damage. The exposure to cigarette smoke decreased testosterone concentration, the percentage of normal morphology and the motility of spermatozoa. In addition, this exposure increased sperm DNA oxidative damage. Zinc treatment protected against the toxic damage that smoking caused to spermatozoa. This study showed a correlation between smoking and possible male infertility and subfertility, and also that the majority of smoking-induced changes in spermatozoa were prevented by zinc treatment. In conclusion, zinc, an antioxidant and stimulant of cell division, can be indicated as a promising treatment in men with infertility caused by the toxic components of cigarette smoke.     

Structural and functional changes in epididymis following danazol plus testosterone enanthate administration in rabbit

Danazol in combination with testosterone enanthate was administered to adult male rabbits to assess the structural and functional activity of epididymis. Seminal, biochemical and histological studies were made throughout the experiment. Sperm motility and count decreased markedly and at the end of treatment 75% of the animals became azoospermic. Seminal plasma GPC levels decreased significantly at 45 through 75 days of treatment. At 30 days of drug exposure, phospholipid, protein and sialic acid concentrations in caput epididymides were significantly low. Epididymal weight, phospholipid and protein contents markedly dropped in all segments of epididymides after 60 days of treatment. A reduction in epithelial and stereocilia height (caput and cauda), and lumen diameter (caput and corpus) was observed. Increase in intertubular stroma was evident. Lumen was devoid of spermatozoa at 60 days of treatment. All the changes were restored to normal 75 days after cessation of treatment. The combination therapy impaired the structural and functional integrity of the epididymis.