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Biomedical subjects

L E Atkinson

Publications and source records attributed to L E Atkinson.

At least 19 recordsLinked to original sources
PubMed2000

Effects of testosterone replacement in hypogonadal men.

Treatment of hypogonadal men with testosterone has been shown to ameliorate the effects of testosterone deficiency on bone, muscle, erythropoiesis, and the prostate. Most previous studies, however, have employed somewhat pharmacological doses of testosterone esters, which could result in exaggerated effects, and/or have been of relatively short duration or employed previously treated men, which could result in dampened effects. The goal of this study was to determine the magnitude and time course of the effects of physiological testosterone replacement for 3 yr on bone density, muscle mass and strength, erythropoiesis, prostate volume, energy, sexual function, and lipids in previously untreated hypogonadal men. We selected 18 men who were hypogonadal (mean serum testosterone +/- SD, 78 +/- 77 ng/dL; 2.7 +/- 2.7 nmol/L) due to organic disease and had never previously been treated for hypogonadism. We treated them with testosterone transdermally for 3 yr. Sixteen men completed 12 months of the protocol, and 14 men completed 36 months. The mean serum testosterone concentration reached the normal range by 3 months of treatment and remained there for the duration of treatment. Bone mineral density of the lumbar spine (L2-L4) increased by 7.7 +/- 7.6% (P < 0.001), and that of the femoral trochanter increased by 4.0 +/- 5.4% (P = 0.02); both reached maximum values by 24 months. Fat-free mass increased 3.1 kg (P = 0.004), and fat-free mass of the arms and legs individually increased, principally within the first 6 months. The decrease in fat mass was not statistically significant. Strength of knee flexion and extension did not change. Hematocrit increased dramatically, from mildly anemic (38.0 +/- 3.0%) to midnormal (43.1 +/- 4.0%; P = 0.002) within 3 months, and remained at that level for the duration of treatment. Prostate volume also increased dramatically, from subnormal (12.0 +/- 6.0 mL) before treatment to normal (22.4 +/- 8.4 mL; P = 0.004), principally during the first 6 months. Self-reported sense of energy (49 +/- 19% to 66 +/- 24%; P = 0.01) and sexual function (24 +/- 20% to 66 +/- 24%; P < 0.001) also increased, principally within the first 3 months. Lipids did not change. We conclude from this study that replacing testosterone in hypogonadal men increases bone mineral density of the spine and hip, fat-free mass, prostate volume, erythropoiesis, energy, and sexual function. The full effect of testosterone on bone mineral density took 24 months, but the full effects on the other tissues took only 3-6 months. These results provide the basis for monitoring the magnitude and the time course of the effects of testosterone replacement in hypogonadal men.

Administration, Cutaneous↗
PubMed1997

Transdermal testosterone administration in hypogonadal men: comparison of pharmacokinetics at different sites of application and at the first and fifth days of application.

In this study of 13 hypogonadal men (25-69 years of age), three open-label, randomized treatments were administered to determine the pharmacokinetics of serum testosterone after application of an investigational testosterone transdermal system to the upper buttocks, upper arm, and back. Testosterone in vivo input kinetics profiles were estimated by DeMonS, a recently developed numerical deconvolution method for estimating drug absorption at different time intervals and/or drug disposition model parameters, and compared on the first and fifth days of system application. Area under the concentration-time curve from 0 to 27 hours (AUC0-27) values for testosterone after one-day applications to the upper buttocks, upper arm, and back were 9,560 ng.hr/dL, 8,651 ng.hr/dL, and 8,988 ng.hr/dL, respectively. Maximum observed concentration (Cmax) values were 482 ng/dL, 462 ng/dL, and 499 ng/dL, respectively. Serum testosterone concentrations were equivalent to each other, and Cmax values fell within the normal range. No drug accumulation was seen with repeated dosing over 5 days.

Administration, Cutaneous↗
PubMed1997

Testosterone pharmacokinetics after application of an investigational transdermal system in hypogonadal men.

This open-label, randomized, placebo lead-in, three-treatment crossover study in 19 hypogonadal men (27-82 years of age) evaluated dose proportionality of serum testosterone concentrations with application of one or two investigational transdermal testosterone systems for application to the arm or torso. Testosterone in vivo kinetics profiles were determined using DeMonS, a recently developed numerical deconvolution method that estimates drug absorption at different time intervals and/or drug disposition model parameters. After application of the investigational transdermal systems, the mean serum testosterone, dihydrotestosterone, estradiol, and free testosterone concentrations were elevated to normal levels. Treatment allowed approximation of the normal circadian pattern of endogenous testosterone secretion, and the increase in serum testosterone concentrations was proportional to the surface area of systems applied. The investigational transdermal system provided effective testosterone replacement therapy as judged by pharmacokinetic parameters.

Administration, Cutaneous↗
PubMed1978

Medroxyprogesterone acetate: peripheral serum levels and its effects on pituitary and ovarian functions in the rhesus monkey.

17 alpha-Acetoxy-6 alpha-methylprogesterone (medroxy-progesterone acetate, MPA) in doses of 50 mg followed 4 weeks later by an additional 100 mg was i.m. injected in 5 adult normal female monkeys. Serum levels of MPA, progesterone, estradiol-17-beta and LH were determined every other day for a period of 8 weeks then weekly for 8 months. Peak values of serum MPA were detected 2 weeks postinjection followed by a gradual decline to undetectable levels after variable periods ranging from 125 to 225 days. The drug, in the doses used, caused inhibition of LH and estradiol surges and suppression of progesterone for more than 6 months. The return of menstrual cyclicity preceded the return of ovulatory cyclicity. Menstrual cyclicity occurred while the drug was still detectable in the blood. The probable site of action of the drug is discussed.

Animals↗
PubMed1976

An approach to the analysis of menstrual patterns in the critical evaluation of contraceptives.

An approach to a standardized analysis of menstrual bleeding patterns is presented. The method utilizes a prospective bleeding record and characterizes the menstrual pattern of a woman according to bleeding and nonbleeding events without imposing definitions of cycle or intermenstrual bleeding. Further, the analysis is done within a time reference period similar to life-table analysis, with the experience of each woman having equal value. The method is thus applicable to the study of menstrual patterns of both normal, untreated women, and women on experimental contraceptive regimens in which expected bleeding patterns are disrupted. The methodology is aided by computer programs to process the data and by the use of standard statistical packages for comparison of output data of different groups.

Computers↗
PubMedDate not supplied

Comparison of the skin irritation potential of two testosterone transdermal systems: an investigational system and a marketed product.

Effective transdermal therapy provides controlled release of the appropriate amount of a therapeutic agent while minimizing local irritation. Transdermal administration of testosterone has the potential to produce skin irritation. This open-label, randomized, 14-day, outpatient study compared the skin irritation of an investigational testosterone transdermal system (System I) with that of a marketed testosterone transdermal system (System II) in healthy men. In Part 1 of the study. System I was applied 10 times over 14 days to the same skin site on the backs of 26 healthy men. In Part 2, the skin irritation resulting from daily application of Systems I and II was assessed over 14 days in 17 men less than 65 years of age and 16 men 65 years of age or older. At the end of Part I of the study, 65.4% of the subjects experienced no erythema, 15.4% of subjects had faint erythema, and 19.2% had moderately intense erythema immediately after System I removal. At the completion of Part 2, none of the System I application sites were assessed as having moderately intense erythema, whereas one third (33.3%) of System II application sites demonstrated moderately intense erythema. There were no differences in erythema rates between younger and older subjects with either transdermal system. During this study, repeated application of System I to the same skin site resulted in acceptable noncumulative irritation, suggesting that application-site rotation may not be necessary. A comparison of the two systems demonstrates that System I results in significantly less application-site irritation than does System II and that older men do not have a higher rate of skin reactions.

Administration, Cutaneous↗
PubMedDate not supplied

The next contraceptive revolution.

The availability of modern birth control methods has wrought a veritable contraceptive revolution in both developed and developing countries over the past two decades. But concerns about safety, costly lawsuits involving current methods, as well as diverse and changing life-styles, have left the current array of contraceptives grossly inadequate to meet growing world-wide needs. Steroid implants and improved injectables, IUDs, barrier methods and sterilization devices should be widely available in the next few years. But the long-sought-after radically new methods that will constitute the next contraceptive revolution--like vaccines, a male contraceptive and a once-a-month pill--will not be developed in the foreseeable future without a massive infusion of new funds. The eight contraceptive research and development (R&D) programs that are responsible for more than half of all current product development efforts now spend about $30 million a year on contraceptive research. With an additional $23 million annually, they could considerably accelerate current research efforts and begin new ones on products that have become possible only as the result of recent scientific discoveries. Even this level of investment--representing a 75 percent increase over current expenditures by the eight groups--would probably not be sufficient to make optimum progress in the development of radically new methods. Since the pharmaceutical industry can no longer be depended upon to take the leading role that it did 20 years ago, current public-sector R&D organizations may need to expand their efforts to include most aspects of the process of contraceptive development and introduction, and new dedicated R&D centers will probably have to be established.(ABSTRACT TRUNCATED AT 250 WORDS)

Contraception↗