Effects of pituitary-testicular axis suppression in utero and during the early neonatal period with a long-acting luteinizing hormone-releasing hormone analog on genital development, somatic growth, and bone density in male cynomolgus monkeys in the first 6 months of life.

The specific role of late fetal and early neonatal gonadotropins and/or sex steroids on genital development, linear growth, and bone mass accretion remains unclear. To investigate this, we attempted to selectively suppress pituitary-testicular activation from midgestation through early infancy with a long-acting LHRH agonist (LHRHA), D-Trp6,Pro9-NEt-LHRH, in microspheres. The agonist was injected sc on days 72-81 in utero, on day 1 of life, and 3 months postnatally in male cynomolgus monkeys. Control animals were treated with placebo. We then examined the consequences of such an intervention in the first 6 months of life. In the LHRHA-treated animals, marked suppression of plasma testosterone and gonadotropin levels were evident in the first 3 months of life compared to control values. The mean testicular volumes of the LHRHA group were significantly lower at birth and in the first 2 months of life than those of the placebo group (P less than 0.05). However, by 4 months of age, the mean testicular volumes of the two groups were comparable. Similarly, the mean stretched phallic lengths of the LHRH approximately A group were significantly lower than those of the placebo group throughout the first 6 months of life (P less than 0.05). By contrast, LHRHA treatment had no effect on somatic growth, as mean body weights, total body lengths, and trunk lengths of the two groups were similar over the first 6 months of life. Mean bone widths and densities of the distal third of the left radius and the left midfemur were similar in the two groups at 1 and 6 months of life. We conclude that pituitary-testicular axis suppression with a long-acting LHRHA in utero and during early infancy results in markedly stunted penile and testicular growth without affecting general somatic growth and bone density of appendicular cortical bone in the cynomolgus monkey in the first 6 months of life. Thus, an intact fetal and neonatal pituitary-testicular axis is critical for normal genital growth. However, the sex steroid requirement for maintenance of bone mineral content of appendicular cortical bone may be lower than that necessary for normal genital development.

Failure of insulin treatment in obese patients with non-insulin-dependent diabetes mellitus.

A number of experts recommend the use of insulin for patients with non-insulin-dependent diabetes mellitus (NIDDM) who fail to respond to diet, exercise, and oral hypoglycemics, even when the patient is morbidly obese. This article describes the use of insulin in two obese patients with NIDDM whose obesity worsened following the institution of insulin therapy. In some cases the risk for increased obesity and its complications following the institution of insulin may offset the potential benefits of insulin therapy itself. There are two main drawbacks associated with insulin therapy in these patients. First, from a medical point of view, insulin has a lipogenic effect and may actually contribute to weight gain, hyperinsulinemia, and increased insulin resistance in obese patients with NIDDM. Second, from a behavioral point of view, the institution of insulin therapy may shift the patient's and physician's focus from the preferred lifestyle adjustments to the numerous details associated with insulin use and monitoring. Since weight gain and sedentary activity are themselves risk factors for coronary artery disease, the benefits of decreased blood glucose levels should be balanced against the risk of increased weight gain in these patients.