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Biomedical subjects

J K Amory

Publications and source records attributed to J K Amory.

11 recordsLinked to original sources
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↗
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↗