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Cited by 4 publications
References 273 publications
Pharmacokinetics and Pharmacodynamics of a Parenteral Testosterone Microsphere Formulation in the Male Rat
This study examined the pharmacokinetics (the time course and pattern of testosterone release) and pharmacodynamics (effects on accessory sex organ weights, and serum LH and FSH levels) of a biodegradable testosterone microsphere formulation in the male rat. Two hundred seventy‐five 55‐day‐old, sexually mature male rats underwent surgical orchiectomy or sham surgery and were divided into five groups as follows, to receive placebo or testosterone microsphere systems designed to release 25, 75, or 225 μg/day testosterone: group I: intact age‐matched controls, sham operated, placebo microspheres; group II: surgically orchiectomized, placebo microspheres; group III: surgically orchiectomized, 25 μg/day testosterone microspheres; group IV: surgically orchiectomized, 75 μg/day testosterone microspheres; and group V: surgically orchiectomized, 225 μg/day testosterone microspheres.Serum testosterone levels were fairly uniform from day 2 to 85 without any significant trend. After day 100, serum testosterone levels gradually fell into the castrate range by day 196. There was a dose‐dependent increase in serum testosterone levels in groups III, IV, and V over those seen in group II (castrated rats, placebo treated). Prostate and seminal vesicle weights were significantly lower in castrated animals treated with placebo or the 25‐μg/day testosterone microsphere system (group III). Mean prostate and seminal vesicle weights in groups IV and V were not significantly different from those in intact controls (group I) in the first 85 days. After day 85–100, seminal vesicle and prostate weights declined gradually in groups III, IV, and V, approaching castrate range by day 196. Serum LH and FSH levels were higher in castrated rats treated with placebo (group II) or 25 μg/day testosterone (group III). The 75‐μg dose maintained serum LH and FSH levels in the normal male range, and the highest dose (225 μg/d) lowered serum LH levels below those seen in intact rats. After day 100, serum testosterone levels in groups III, IV, and V gradually fell into the castrate range. We conclude that this biodegradable testosterone microsphere formulation provides uniform and dose‐dependent release of testosterone for 10–14 weeks and is worthy of further evaluation as a method of testosterone replacement.
Pharmacokinetics and Pharmacodynamics of a Parenteral Testosterone Microsphere Formulation in the Male Rat
This study examined the pharmacokinetics (the time course and pattern of testosterone release) and pharmacodynamics (effects on accessory sex organ weights, and serum LH and FSH levels) of a biodegradable testosterone microsphere formulation in the male rat. Two hundred seventy‐five 55‐day‐old, sexually mature male rats underwent surgical orchiectomy or sham surgery and were divided into five groups as follows, to receive placebo or testosterone microsphere systems designed to release 25, 75, or 225 μg/day testosterone: group I: intact age‐matched controls, sham operated, placebo microspheres; group II: surgically orchiectomized, placebo microspheres; group III: surgically orchiectomized, 25 μg/day testosterone microspheres; group IV: surgically orchiectomized, 75 μg/day testosterone microspheres; and group V: surgically orchiectomized, 225 μg/day testosterone microspheres.Serum testosterone levels were fairly uniform from day 2 to 85 without any significant trend. After day 100, serum testosterone levels gradually fell into the castrate range by day 196. There was a dose‐dependent increase in serum testosterone levels in groups III, IV, and V over those seen in group II (castrated rats, placebo treated). Prostate and seminal vesicle weights were significantly lower in castrated animals treated with placebo or the 25‐μg/day testosterone microsphere system (group III). Mean prostate and seminal vesicle weights in groups IV and V were not significantly different from those in intact controls (group I) in the first 85 days. After day 85–100, seminal vesicle and prostate weights declined gradually in groups III, IV, and V, approaching castrate range by day 196. Serum LH and FSH levels were higher in castrated rats treated with placebo (group II) or 25 μg/day testosterone (group III). The 75‐μg dose maintained serum LH and FSH levels in the normal male range, and the highest dose (225 μg/d) lowered serum LH levels below those seen in intact rats. After day 100, serum testosterone levels in groups III, IV, and V gradually fell into the castrate range. We conclude that this biodegradable testosterone microsphere formulation provides uniform and dose‐dependent release of testosterone for 10–14 weeks and is worthy of further evaluation as a method of testosterone replacement.
Summary. The first theoretical reflections concerning the relation of hormone production with the ageing process stemmed from Charles Edouard Brown‐Sequard (1817–1894). At the age of 72 years he experimented on himself with an injection of animal testicular extract. The Viennese physiologist Eugen Steinach (1861–1944) gained world‐wide acknowledgement for his theory of ‘autoplastic‘ treatment of ageing. He deduced that after vasoligation, an increased incretory hormonal production would ensue following the cessation of the secretory output of the gonads. The first operation was performed in 1918 and resulted in a vasectomy boom over the next two decades. The Russian Serge Voronoff (1866–1951), working in Paris, was one of the first to transplant testicular tissue from a monkey into a human reproductive gland in 1920. Five years later he had already performed this procedure on 300 patients and attracted patients from all over the world. In America early efforts of human testicular transplantation were performed by Frank Lydston and V.D. Lespinasse. Steinach's vasoligation was taken over by many American doctors, e.g., Harry Benjamin and Charles H. Chetwood. Among the patients who underwent a rejuvenation operation according to Steinach's method were Sigmund Freud (1856–1939) and the Irish poet and Nobel Prize winner William Butler Yeats (1865–1939). Two caricatures from the German magazine Simplicissimus published in 1927, confirm that the rejuvenation operations were constantly in the limelight of the printed media. From 1935 onwards rejuvenation operations gradually lost their appeal due to the introduction of artificial androgens.
Androgen therapy has been primarily used for replacement therapy in symptomatic hypogonadal men. Other indications under clinical investigation include androgen replacement therapy for older men with age-associated decline in serum testosterone levels, muscle-wasting disease, male contraception and as adjunctive therapy to oestrogen (and progesterone) hormone replacement for postmenopausal women. Recent scientific and pharmaceutical interests led to development of new long-acting injectables, transdermal delivery systems and sublingual preparations. The benefits of androgen replacement must be weighed against the potential risks when androgens are used in conditions other than male hypogonadism. In the future, designer androgens with specific beneficial effect on sexual function, mood, bone and muscle mass but with attenuated effects on serum lipid profiles and the prostate gland may be developed.
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