Men with
hypogonadism require
testosterone replacement for optimal health. In the United States,
testosterone is currently administered by daily transdermal patches, topical
gels or
intramuscular injections every 1-3 weeks. Biodegradable
polylactide-co-glycolide
microcapsules are currently used for long-term
drug delivery in humans. Such
microcapsules that contain
testosterone could provide a better means of long-term
testosterone therapy. We therefore studied the pharmacokinetics and pharmacodynamics of
testosterone release from
testosterone microcapsules in men with
hypogonadism. Fourteen men who had been treated previously with
testosterone were enrolled in an open-label, prospective study of
testosterone microcapsule administration. Subjects were enrolled if 2 consecutive serum total
testosterone levels were lower than 8.7 nmol/L after a 4-week washout from
testosterone therapy. Subjects were injected with a single dose of either 267 mg (n = 7) or 534 mg (n = 7) of (Viatrel)
testosterone microcapsule, and serum total
testosterone,
dihydrotestosterone,
estradiol,
sex-hormone binding globulin,
luteinizing hormone, and
follicle-stimulating hormone levels were determined at days -14, -7, and 0 before the injection; at days 1, 2, and 7 after the injection; and then weekly thereafter for 8-12 weeks. Mean serum total
testosterone levels peaked immediately following injection on day 1 at 25.2 +/- 2.6 nmol/L in the 267 mg group and 34.7 +/- 2.4 nmol/L in the 534 mg group. Total serum
testosterone levels declined gradually and fell below 8.7 nmol/L at 42 days after injection in the 267 mg group, and 70 days after injection in the 534 mg group.
Estradiol and
dihydrotestosterone levels followed a similar pattern. Mean serum free
testosterone also peaked immediately following injection on day 1 at 0.51 +/- 0.05 nmol/L in the 267 mg group and 0.97 +/- 0.08 nmol/L in the 534 mg group. No significant adverse reactions were seen, although 2 subjects complained of transient tenderness and fullness at their injection sites. We conclude that a single injection of 534 mg of
testosterone microcapsules to men with
hypogonadism normalizes serum
hormone levels for up to 10-11 weeks, albeit with a pronounced early peak and a relatively long period of low-normal serum total
testosterone. Subcutaneously administered
testosterone microcapsules may provide a safe and convenient method for the long-term treatment of male
hypogonadism or
testosterone replacement in
male contraceptive regimens.