Allan R. Glass

Testicular dysfunction in untreated Hodgkin's disease

Gonadal function was examined in 19 young men with Hodgkins disease before therapy and compared with that of 11 men with other malignancies, 13 men with primary testicular failure, and 19 normal men of similar age. Total (p less than 0.01) and free (p less than 0.05) testosterone levels were decreased in Hodgkins disease. In those with advanced (stage III + IV) and symptomatic (B), Hodgkins disease serum testosterone levels were indistinguishable from those in primary testicular failure, yet serum levels of luteinizing hormone were normal. Moreover, the acute response of serum testosterone to exogenous human chorionic gonadotropin (HCG) was significantly greater in Hodgkins disease than in primary testicular failure (p less than 0.03). These data and the finding that basal serum follicle-stimulating hormone levels are significantly lower than normal in Hodgkins disease (p less than 0.05) suggest that the cause of pretreatment hypogonadism in Hodgkins disease is not simple primary testicular failure. Total sperm count was decreased in 40 percent of men with Hodgkins disease but in none of the men with other malignancies (p less than 0.05), suggesting specific seminiferous tubular dysfunction in Hodgkins disease. However, motility was abnormal in 69 percent of men with Hodgkins disease and 60 percent of those with other malignancies, suggesting that this is a nonspecific effect of cancer. Serum prolactin levels were significantly higher than normal in Hodgkins disease (p less than 0.05) but not in other malignancies. Our findings suggests that the cause of testicular dysfunction that is present before treatment of Hodgkins disease is complex, perhaps involving both pituitary and gonadal abnormalities.

Treatment of hirsute women with cimetidine.

THE treatment of hirsute women is controversial and often presents a therapeutic dilemma. Mechanical methods (such as shaving or using depilatories) are safe but often unacceptable to the patient, ...

Secondary Amenorrhea in Obesity: Etiologic Role of Weight-Related Androgen Excess*

A massively obese, amenorrheic young woman had elevated levels of plasma androgens which could be reduced either acutely by dexamethasone administration or chronically by weight loss. Normalization of plasma androgen levels in both instances led to resumption of ovulation, suggesting that weight-related hyperandrogenism is a cause of amenorrhea in obesity.

Fertility onset, spermatogenesis, and pubertal development in male rats: effect of graded underfeeding

ABSTRACT: Undernutrition has proven to be a useful model for exploring the relationship between growth and pubertal development in female rats, such as the “critical body weight” hypothesis of pubertal timing, but corresponding studies in the male have been hampered by lack of specific discrete markers of puberty similar to vaginal opening or first estrus in females. In the current study, we explored the effect of five different levels of food intake (as low as one-thrid of normal) beginning at weaning on pubertal development and timing in male rats, using the date of the initial successful conception with normal females as a discrete marker for puberty in males. In underfed males, there was a weak inverse correlation (r=–0.31, P<0.05) between the age at puberty and the growth rate, the latter being used as an index of the degree of underfeeding. In contrast, there was a strong direct correlation (r=0.78, P<0.001) between body weight at puberty and growth rate. In the most severely underfed groups, the Lee index of body fat remained subnormal before and after puberty. Initial litter size also tended to be reduced when the males were underfed. At age 51 days (prior to puberty), graded underfeeding led to progressive reductions in serum luteinizing hormone and follicle-stimulating hormone levels as well as in parameters of androgen status (serum and testicular testosterone, prostate, and seminal vesicle weights). Testicular size was also reduced, but daily sperm production rate was not greatly affected by underfeeding. Testicular histology at age 51 days revealed mature step 19 spermatids in all groups, with some reduction in seminiferous tubular diameter in the most severely underfed group. The effect of underfeeding on testicular testosterone and spermatogenesis appeared to decrease as underfeeding was continued for an additional 70 days. We conclude that graded underfeeding beginning at weaning leads to major reductions in gonadotropins and androgens but has less effect on spermatogenesis or the timing of puberty. Therefore, in normal rats, the timing of puberty is closely related to spermatogenic development, which can proceed once initiated despite low gonadotropin and androgen levels. Underfed male rats have low body weights and low body fats at puberty, refuting the “critical body weight” and “critical body fat” hypotheses of pubertal timing.

Androgen receptor abnormalities in identical twins with oligospermia: Clinical and biochemical studies

Abstract Identical twin brothers presented with oligospermia, small testes, normal male phenotypes, elevated serum luteinizing hormone levels, and normal or elevated serum testosterone levels. Both men had low to low-normal cytosol androgen receptor binding capacity in cultured fibroblasts from pubic skin biopsy specimens. Qualitative abnormalities of cellular androgen receptors were suggested by low-normal or low nuclear androgen uptake in fibroblasts from both brothers as well as abnormal thermolability and subnormal molybdate stabilization of androgen receptors from one brother. In vivo androgen sensitivity was assessed in one twin following administration of testosterone or the non-aromatizable androgen fluoxymesterone. Fluoxymesterone suppressed serum luteinizing hormone and serum testosterone/estradiol-binding globulin, and although testosterone suppressed both serum luteinizing hormone and serum follicle-stimulating hormone, the suppression of serum luteinizing hormone by testosterone was subnormal. Both subjects showed marked exaggeration of the serum 17-hydroxyprogesterone increase after administration of human chorionic gonadotropin, despite normal serum testosterone increases, suggesting a block in testicular 17,20-desmolase, which converts 17-hydroxyprogesterone to testosterone. These studies suggest that oligospermia and block of the enzyme 17,20-desmolase may be the earliest manifestations of androgen resistance, and the finding of the syndrome of oligospermia, normal male phenotype, and androgen receptor abnormalities in identical twins indicates a genetic etiology of this disorder.