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Biomedical subjects

J K Amory

Publications and source records attributed to J K Amory.

At least 19 recordsLinked to original sources
PubMed2006

Characterization of verbal and spatial memory changes from moderate to supraphysiological increases in serum testosterone in healthy older men.

BACKGROUND: It has been suggested that cognitive changes in response to T supplementation may occur within an ideal range. The objective of this study was to compare the cognitive responses of older, eugonadal men in whom moderate or large increases in serum testosterone levels was induced by exogenous testosterone supplementation. DESIGN: Randomized, double-blind, placebo-controlled study with subsequent grouping of participants according to average increase in circulating T from baseline. SETTING: Community dwelling participants. PARTICIPANTS: Fifty-seven healthy, eugonadal, community dwelling male volunteers, mean age 67 years (+/-11 years). INTERVENTIONS: Participants were randomized to receive weekly intramuscular (i.m.) injections of either 50, 100 or 300 mg T enanthate or placebo (saline) injection for 6 weeks. Cognitive evaluations using a battery of neuropsychological tests were conducted at baseline, weeks 3 and 6 of treatment and after 6 weeks of wash-out. MAIN OUTCOME MEASURES: Performance on cognitive tests of verbal and spatial memory. RESULTS: Men with moderate increases in serum T and/or its metabolites demonstrated significant improvements in verbal and spatial memory. In contrast, men with large or low increases in circulating T levels, failed to demonstrate significant changes in memory. CONCLUSION: These results suggest that in healthy older men, beneficial changes in cognitive function induced by T supplementation are most evident with moderate changes in cognition from moderate to high T supplementation increases in T levels. Large or no to low increases in T levels do not appear to appreciably effect cognition.

Aged↗
PubMed2006

Miglustat has no apparent effect on spermatogenesis in normal men.

BACKGROUND: In mice, administration of the glycosphingolipid biosynthesis inhibitor miglustat results in reversible infertility, characterized by impaired sperm motility and markedly abnormal sperm morphology. This observation suggested that miglustat might have utility for fertility control in man. To ascertain the impact of miglustat on human spermatogenesis, we conducted a pilot study of miglustat administration in normal men. METHODS: After a 2-week baseline period, seven normal men were administered miglustat 100 mg, orally, twice daily for 6 weeks. During treatment, subjects had frequent seminal fluid analyses to assess the impact of treatment on sperm concentration, motility and morphology and the ability to undergo the acrosome reaction by in vitro assays. RESULTS: Five subjects completed all aspects of the study. In these subjects, there was no apparent effect of miglustat on sperm concentration, motility or sperm morphology after 6 weeks of therapy. In addition, no changes in acrosome structure or function were observed with treatment, despite therapeutic concentrations of miglustat in the serum and seminal plasma. All subjects experienced gastrointestinal upset, diarrhoea and mild weight loss during treatment. No other abnormalities in blood counts, serum chemistries, vision or overall health were observed. CONCLUSION: In contrast to the observations in mice, the oral administration of miglustat does not appear to affect human spermatogenesis. Further elucidation of the mechanism underlying the species specificity of miglustat may improve our understanding of the role of glycosphingolipids in spermatogenesis and result in alternative approaches to male fertility control.

1-Deoxynojirimycin↗
PubMed2006

Male hormonal contraceptives.

Efforts are underway to develop additional forms of contraception for men. The most promising approach to male contraceptive development involves the administration of exogenous testosterone (T). When administered to a man, T functions as a contraceptive by suppressing the secretion of luteinizing hormone and follicle-stimulating hormone from the pituitary, thereby depriving the testes of the signals required for spermatogenesis. After 2-3 months of treatment, low levels of these gonadotropins lead to markedly decreased sperm counts and effective contraception in a majority of men. Hormonal contraception with exogenous T has proven to be free from serious adverse effects and is well tolerated by men. In addition, sperm counts uniformly normalize when the exogenous T is discontinued. Thus, male hormonal is safe, effective and reversible; however, spermatogenesis is not suppressed to zero in all men, meaning that some diminished potential for fertility persists. Because of this recent studies have combined T with progestogens and/or gonadotropin-releasing antagonists to further suppress pituitary gonadotropins and optimize contraceptive efficacy. Current combinations of T and progestogens completely suppress spermatogenesis without severe side effects in 80-90% of men, with significant suppression in the remainder of individuals. Recent trials with newer, long-acting forms of injectable T, which can be administered every 8 weeks, combined with progestogens, administered either orally or by long-acting implant, have yielded promising results and may soon result in the marketing of a safe, reversible and effective hormonal contraceptive for men.

Contraceptive Agents, Male↗
PubMed2005

A multicentre study investigating subcutaneous etonogestrel implants with injectable testosterone decanoate as a potential long-acting male contraceptive.

BACKGROUND: The combination of etonogestrel implants with injectable testosterone decanoate was investigated as a potential male contraceptive. METHODS: One hundred and thirty subjects were randomly assigned to three treatment groups, all receiving two etonogestrel rods (204 mg etonogestrel) and 400 mg testosterone decanoate either every 4 weeks (group I, n = 42), or every 6 weeks (group II, n = 51) or 600 mg testosterone decanoate every 6 weeks (group III, n = 37) for a treatment period of 48 weeks. RESULTS: One hundred and ten men completed 48 weeks of treatment. Sperm concentrations of <1 x 10(6)/ml were achieved in 90% (group I), 82% (group II) and 89% (group III) of subjects by week 24. Suppression was slower in group II, which also demonstrated more frequent escape from gonadotrophin suppression than groups I and III. Peak testosterone concentrations remained in the normal range throughout in all groups. Mean trough testosterone concentrations were initially subphysiological but increased into the normal range during treatment. Mean haemoglobin levels increased in group I, and a non-significant increase in weight and decline in high-density lipoprotein cholesterol was observed in all groups. Fourteen subjects discontinued treatment due to adverse events. CONCLUSIONS: Subcutaneous etonogestrel implants in combination with injectable testosterone decanoate resulted in profound suppression of spermatogenesis that could be maintained for up to 1 year. Efficacy of suppression was less in group II, probably due to inadequate testosterone dosage. This combination has potential as a long-acting male hormonal contraceptive.

Administration, Cutaneous↗
PubMed2005

Testosterone improves spatial memory in men with Alzheimer disease and mild cognitive impairment.

OBJECTIVE: To determine the efficacy of testosterone (T) supplementation on cognition in a sample of men with Alzheimer disease (AD) or mild cognitive impairment (MCI). METHODS: Fifteen patients with AD and 17 patients with MCI aged 63 to 85 years completed a randomized, double-blind, placebo-controlled study. Nineteen participants received weekly intramuscular (IM) injections of 100 mg T enanthate and 13 participants received weekly injections of placebo (saline) for 6 weeks. Cognitive evaluations using a battery of neuropsychological tests were conducted at baseline, week 3, and week 6 of treatment and again after 6 weeks of washout. RESULTS: Peak serum total T levels were raised from baseline an average of 295% in the active treatment group. Improvements in spatial memory (p < 0.05) and constructional abilities (p < 0.05) and verbal memory were evident in the T group. No changes were noted for selective and divided attention or language. Prostate specific antigen did not significantly change during this brief treatment. CONCLUSION: Testosterone supplementation may benefit selective cognitive functions in men with Alzheimer disease and mild cognitive impairment.

Aged↗
PubMed2005

The role of aromatization in testosterone supplementation: effects on cognition in older men.

OBJECTIVE: To determine the contribution of conversion of testosterone (T) to estradiol on cognitive processing in a population of healthy older men who received T supplementation. METHODS: Sixty healthy, community-dwelling volunteers aged 50 to 90 years completed a randomized, double-blind, placebo-controlled study. Participants were randomized to receive weekly IM injections of 100 mg T enanthate plus daily oral placebo pill (T group, n = 20), 100 mg testosterone enanthate plus 1 mg daily of anastrozole, an aromatase inhibitor (oral pill), to block the conversion of T to estradiol (AT group, n = 19), or saline injection and placebo pill (placebo group, n = 21) for 6 weeks. Cognitive evaluations using a battery of neuropsychological tests were conducted at baseline, week 3 and week 6 of treatment, and after 6 weeks of washout. RESULTS: Circulating total T was increased from baseline an average of 238% in the T and AT treatment groups. Estradiol increased an average of 81% in the T group and decreased 50% in the AT group during treatment. Significant improvements in spatial memory were evident in the AT and T treatment groups. However, only the group with elevated estradiol levels (T group) demonstrated significant verbal memory improvement. CONCLUSION: In healthy older men, improvement in verbal memory induced by testosterone administration depends on aromatization of testosterone to estradiol, whereas improvement in spatial memory occurs in the absence of increases in estradiol.

Aged↗
PubMed2002

Cognitive effects of short-term manipulation of serum sex steroids in healthy young men.

We examined the effects of sex steroids on cognitive functioning by exogenously manipulating circulating T levels in a group of healthy young men. Thirty-two men were randomized to receive 8 wk of treatment including: 1) im T enanthate 100 mg/wk plus daily oral placebo (T); 2) im placebo/wk plus 125 microg daily oral levonorgestrel (LNG); 3) im T enanthate 100 mg/wk plus 125 microg daily oral LNG (T + LNG); 4) im placebo/wk plus daily oral placebo. Cognitive functions were assessed at baseline and twice during treatment. Serum T and E2 levels were significantly increased in the T and T + LNG groups compared with baseline (P < 0.01) and T levels were significantly decreased in the LNG group (P < 0.05). Verbal memory significantly decreased in the LNG group (P < 0.01) and was maintained by coadministration of T in the T + LNG group. Divided attention was unaffected in the LNG group but improved significantly in the T + LNG group. In summary, decreased serum T levels induced by LNG or direct effects of the progestin, LNG, adversely affects verbal memory in normal young men. These results suggest that short-term changes in sex steroid levels have effects on cognitive function in healthy young men.

Administration, Oral↗
PubMed2001

Endocrine regulation of testicular function in men: implications for contraceptive development.

The testicle has two important and complimentary functions in the adult male: the production of sperm and the synthesis of testosterone. Testicular function is directed by the central nervous system through its effects on the pituitary gland. Precise regulation of testicular function is accomplished by an elegant endocrine feedback loop in which the secretion of pituitary gonadotropins is stimulated by the pulsatile release of GnRH from the hypothalamus and modulated by testicular hormones. Inhibin, testosterone and its metabolites inhibit the secretion of the gonadotropins both directly at the pituitary and centrally at the level of the hypothalamus. In the testis, LH mainly stimulates testosterone production and FSH promotes spermatogenesis, but the exact details of these actions are only now being elucidated. The discovery of novel mutations in gonadotropin structure and signaling provide unique insight into the roles of these crucial hormones in the development and function of the male reproductive axis. A key goal of research into hormonal regulation of testicular function is the development of reversible, safe and effective male hormonal contraceptives. Recent promising trials of hormonal contraceptive combinations may soon bring the promise of male contraception to fruition.

Contraception↗
PubMed2001

Testosterone delivery using glutamide-based complex high axial ratio microstructures.

Complex high axial ratio microstructures (CHARMs) were evaluated for delivery of testosterone in vivo. Methods to incorporate testosterone included noncovalent mixing and covalent attachment of testosterone to the lipid to form a prodrug monomer. When prepared by covalent attachment, testosterone-loaded CHARMs were resistant to in vitro spontaneous hydrolysis; when injected into rats, testosterone was released with biphasic kinetics consisting of a burst followed by a much slower phase. Some CHARM material associated with testosterone persisted at the site of injection for at least 9 days.

Animals↗
PubMed2001

Male hormonal contraceptives.

As the world human population continues to explode, the need for effective, safe and convenient contraceptive methods escalates. Historically, women have borne the brunt of responsibility for contraception and family planning. Except for the condom, there are no easily reversible, male-based contraceptive options. Recent surveys have confirmed that the majority of men and women would consider using a hormonal male contraceptive if a safe, effective and convenient formulation were available. Investigators have sought to develop a male hormonal contraceptive based on the observation that spermatogenesis depends on stimulation by gonadotropins, follicle-stimulating hormone (FSH) and luteinising hormone (LH). Testosterone (T) and other hormones such as progestins suppress circulating gonadotropins and spermatogenesis and have been studied as potential male contraceptives. Results from two large, multi-centre trials demonstrated that high-dosage T conferred an overall contraceptive efficacy comparable to female oral contraceptives. This regimen was also fully reversible after discontinuation. However, this regimen was not universally effective and involved weekly im. injections that could be painful and inconvenient. In addition, the high dosage of T suppressed serum high-density lipoprotein (HDL) cholesterol levels, an effect that might increase atherogenesis. Investigators have attempted to develop a hormonal regimen that did not cause androgenic suppression of HDL cholesterol and that was uniformly effective by suppressing spermatogenesis to zero in all men. Studies of combination regimens of lower-dosage T and a progestin or a gonadotropin-releasing hormone analogue have demonstrated greater suppression of spermatogenesis than the WHO trials of high-dosage T but most of these regimens cause modest weight gain and suppression of serum HDL cholesterol levels. Overall, the data suggest that we are close to developing effective male hormonal contraceptives. The focus is now on developing effective oral regimens that could be safely taken daily or long-acting depot formulations of a male hormonal contraception that could be conveniently injected every 3 - 6 months. In this article, we shall review the exciting new developments in male hormonal contraception.

Contraceptive Agents, Male↗
PubMed2001

Advances in male hormonal contraception.

New male contraceptive options are urgently needed. Safe, effective and fully reversible methods of male contraception would be useful for monogamous couples who are trying to regulate their family size. In addition, an effective male hormonal contraceptive that could be implanted or injected as a long-acting formulation every 3-6 months would be useful in countries where limiting population growth has become a public policy imperative. Male hormonal contraception is based on the same principles as traditional oestrogen-progestin female oral contraceptives. Both spermatogenesis and ovulation are dependent upon normal secretion of the pituitary gonadotropins, follicle stimulating hormone (FSH) and luteinizing hormone (LH). Exogenous gonadotropin-releasing hormone (GnRH) analogues and sex steroid hormones such as testosterone (T) and progestins suppress gonadotropins and spermatogenesis. Two large multicentre trials demonstrated that weekly administration of high-dosage T was very effective in suppressing gonadotropins and spermatogenesis and conferred an overall contraceptive efficacy comparable to female oral contraceptives. Studies of combination regimens of lower-dosage T plus a progestin or a GnRH analogue have demonstrated greater suppression of spermatogenesis than the World Health Organization trials of high-dosage T. Most of these male hormonal contraceptives have been associated with modest weight gain and suppression of serum high-density cholesterol (HDL) levels. In this article, we review the new developments in male hormonal contraception.

Anabolic Agents↗
PubMed2000

Are physicians aware of which of their patients have indwelling urinary catheters?

PURPOSE: Although infections associated with indwelling urinary catheters are common, costly, and morbid, the use of these catheters is unnecessary in more than one-third of patients. We sought to assess whether attending physicians, medical residents, and medical students are aware if their hospitalized patients have an indwelling urinary catheter, and whether physician awareness is associated with appropriate use of these catheters. METHODS: The physicians and medical students responsible for patients admitted to the medical services at four university-affiliated hospitals were given a list of the patients on their service. For each patient, the provider was asked: "As of yesterday afternoon, did this patient have an indwelling urethral catheter?" Respondents' answers were compared with the results of examining the patient. RESULTS: Among 288 physicians and students on 56 medical teams, 256 (89%) completed the survey. Of 469 patients, 117 (25%) had an indwelling catheter. There were a total of 319 provider-patient observations among these 117 patients. Overall, providers were unaware of catheterization for 88 (28%) of the 319 provider-patient observations. Unawareness rates by level of training were 21% for students, 22% for interns, 27% for residents, and 38% for attending physicians (P = 0.06). Catheter use was inappropriate in 36 (31%) of the 117 patients with a catheter. Providers were unaware of catheter use for 44 (41%) of the 108 provider-patient observations of patients who were inappropriately catheterized. Catheterization was more likely to be appropriate if respondents were aware of the catheter (odds ratio = 3.7; 95% confidence interval, 2.1 to 6.7, P <0.001). CONCLUSION: Physicians are commonly unaware that their patients have an indwelling urinary catheter. Inappropriate catheters are more often "forgotten" than appropriate ones. System-wide interventions aimed at discontinuing unnecessary catheterization seem warranted.

Aged↗
PubMed2000

The efficacy of medical abortion: a meta-analysis.

Multiple clinical studies demonstrate the efficacy of medical abortion with mifepristone or methotrexate followed by a prostaglandin analogue. However, assessing predictors of success, including regimen, is difficult because of regimen variability and a lack of direct comparisons. This meta-analysis estimates rates of primary clinical outcomes of medical abortion (successful abortion, incomplete abortion, and viable pregnancy) and compares them by regimen and gestational age. We identified 54 studies published from 1991 to 1998 using mifepristone with misoprostol (18), mifepristone with other prostaglandin analogues (23), and methotrexate with misoprostol (13). Data abstracted from studies included regimen details and clinical outcomes by gestational age. We found that efficacy decreases with increasing gestational age (p<0.001), and differences by regimen are not statistically significant except at gestational age > or =57 days. For gestations < or =49 days, mean rates of complete abortion were 94-96%, incomplete abortion 2-4%, and ongoing (viable) pregnancy 1-3%. For gestations of 50-56 days, the mean rate of complete abortion was 91% (same for all regimens), incomplete abortion 5-8%, and ongoing pregnancy 3-5%. For > or =57 days, success was lower for mifepristone/misoprostol (85%, 95% confidence interval 78-91%) than for mifepristone/other prostaglandin analogues 95% (CI 91-98%, p = 0.006). For mifepristone/misoprostol, using > or =2 prostaglandin analogue doses seems to be better than a single dose for certain outcomes and gestational ages. We conclude that both mifepristone and methotrexate, when administered with misoprostol, have high levels of success at < or =49 days gestation but may have lower efficacy at longer gestation.

Abortifacient Agents↗
PubMed2000

Newer agents for hormonal contraception in the male.

Efforts to create a hormonal contraceptive for men use testosterone to suppress the production of pituitary gonadotropins and, hence, spermatogenesis. However, conventional testosterone must be administered by frequent injection, and when given alone, is not 100% effective. Therefore, newer androgens and agents that synergistically suppress gonadotropin production are being studied to create an effective and commercially viable contraceptive.

Androgens↗
PubMed1998

The use of testosterone as a male contraceptive.

Testosterone functions as a contraceptive by suppressing secretion of the pituitary gonadotropins luteinizing hormone and follicle stimulating hormone. Low levels of these hormones decrease endogenous testosterone secretion from the testis and deprive developing sperm of the signals required for normal maturation. Interference with sperm maturation causes a decline in sperm production and can lead to reversible infertility in men, raising the possibility that testosterone could be utilized in a commercially available contraceptive. To this end, testosterone has been studied alone and in combination with either gonadotropin releasing hormone analogues or progestins in efforts to improve its contraceptive efficacy. In this chapter, we will review efforts to use testosterone to create a safe, convenient, efficacious contraceptive method for men.

Contraception↗
PubMed1998

The therapeutic potential of testosterone patches.

In the last decade, transdermal delivery of testosterone (T) has been shown to be a safe and effective means of treating male hypogonadism. Transdermal T patches can provide for physiologic androgen replacement in over 90% of men with hypogonadism. In addition, T patches have been shown to be equivalent to im. T esters in restoring normal male libido,sexual function and bone mineral density without harmful side-effects.Furthermore, in sharp contrast to periodic im. injections of T, transdermal T patches, when used daily, restore the normal circadian rhythm of T levels. The physiological and clinical importance of these circadian patterns,however, is presently unknown. The first transdermal patch to be marketed is applied to shaved scrotal skin. Newer patches can be applied to non-scrotal skin; however, these patches are associated with a significant rate of skin reactions that may require discontinuation. The main drawback to transdermal T delivery is cost, ten to twenty times the monthly cost of im. T, the method currently used to treat most hypogonadal men.Nevertheless, transdermal T patches constitute a major advance in the therapy of male hypogonadism as they allow for safe, non-invasive administration of T.

Journal Article↗
PubMedDate not supplied

Daily testosterone and gonadotropin levels are similar in azoospermic and nonazoospermic normal men administered weekly testosterone: implications for male contraceptive development.

Weekly intramuscular administration of testosterone esters such as testosterone enanthate (TE) suppresses gonadotropins and spermatogenesis and has been studied as a male contraceptive. For unknown reasons, however, some men fail to achieve azoospermia with such regimens. We hypothesized that either 1) daily circulating serum fluoroimmunoreactive gonadotropins were higher or testosterone levels were lower during the weekly injection interval, or 2) monthly circulating bioactive gonadotropin levels were higher in nonazoospermic men. We therefore analyzed daily testosterone and fluoroimmunoreactive gonadotropin levels as well as pooled monthly bioactive and fluoroimmunoreactive gonadotropin levels in normal men receiving chronic TE injections and correlated these levels with sperm production. After a 3-month control period, 51 normal men were randomly assigned to receive intramuscular TE at 25 mg (n = 10), 50 mg (n = 9), 100 mg (n = 10), 300 mg (n = 10), or placebo (n = 12) weekly for 6 months. After 5 months of testosterone administration, morning testosterone and fluoroimmunoreactive follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels were measured daily for a 1-week period between TE injections. In addition, fluoroimmunoreactive and bioactive FSH and LH levels were measured in pooled monthly blood samples drawn just before the next TE injection. In the 100-mg and 300-mg TE groups, mean monthly fluoroimmunoreactive FSH and LH levels were suppressed by 86%-97%, bioactive FSH and LH levels by 62%-80%, and roughly half the subjects became azoospermic. In the 1-week period of month 6, daily testosterone levels between TE injections were within the normal range in men receiving placebo, or 25 or 50 mg of weekly TE, but were significantly elevated in men receiving 100 or 300 mg of weekly TE. At no point during treatment, however, were there significant differences in daily testosterone or fluoroimmunoreactive gonadotropin levels, or monthly bioactive gonadotropin levels between men achieving azoospermia and those with persistent spermatogenesis. This study, therefore, demonstrates that neither monthly nor daily differences in serum testosterone, or fluoroimmunoreactive or bioactive gonadotropins explain why some men fail to completely suppress their sperm counts to zero with weekly TE administration. Innate differences in the testicle's ability to maintain spermatogenesis in a low-gonadotropin environment may explain persistent spermatogenesis in some men treated with androgen-based contraceptive regimens.

Adult↗