G. C. Rennie

CHANGES IN THE PITUITARY-TESTICULAR SYSTEM WITH AGE

In order to provide a comprehensive account of pituitary‐testicular function in man, 466 subjects, ranging in age from 2 to 101 years, were studied to examine blood levels of the pituitary gonadotrophins (LH and FSH), the sex steroids testosterone and oestradiol, the binding capacity of the sex hormone binding globulin (SHBG), the free testosterone and oestradiol fractions, and the transfer constant for the peripheral conversion of testosterone to oestradiol. The results were compared with clinical indices of testicular size, sexual function and secondary sex hair distribution. Serum LH and FSH were low before puberty, increased in pubertal adolescents to levels somewhat above those of adults and subsequently increased progressively over the age of 40 years. Testosterone levels fell slowly after the age of 40, while there was a slight rise in plasma oestradiol with increasing age. FSH and testosterone showed small seasonal variations in young adult men, the lowest values being seen in winter. SHBG binding capacity was high in two prepubertal boys, fell in adult men, but increased in old age. Free testosterone and oestradiol levels fell in old age. The metabolic clearance rates (MCR) of testosterone and oestradiol also fell in old age, while the conversion of testosterone to oestradiol was increased. Many correlations were observed between various hormonal and clinical measurements. The evidence is consistent with a primary decrease in testicular function over the age of 40 years.

Testicular control of follicle-stimulating hormone secretion.

Publisher Summary This chapter provides an overview of the testicular control of follicle-stimulating hormone (FSH) secretion. Castration is followed by an increase in circulating levels of FSH than of luteinizing hormone (LH). This suggests the possibility that the mechanisms of gonadotropin secretion either have different thresholds to steroid hormones or a feedback influence associated with the germinal epithelium. The chapter analyzes the factors that control the secretion of gonadotropins in the male and the effect of testicular disorders on the secretion. These disorders are frequently associated with characteristic abnormalities of gonadotropin secretion, observations that are valuable both in diagnosis and treatment of patients with problems of hypogonadism or infertility. All the work reported in the chapter is concerned with the testicular effects on the gonadotropins. The possibility that ovaries can produce a similar or identical substance stems from the fact that postmenopausal FSH levels are raised disproportionately, i.e., more than LH levels and there are many analogies between the functions of the testis and the ovary. There is a significant inverse correlation between the absence of ovarian follicles and the plasma levels of FSH in women with primary or secondary amenorrhea. One compelling stimulus in this field is the possibility of obtaining a substance for contraceptive use that could selectively suppress the secretion of FSH while preserving libido and potency in the male.

Testicular vein ligation and fertility in men with varicoceles.

A 44 year old white contract worker attended the Sheffield department of genitouriary medicine one week after his return from Zambia, where he had worked for three months. He gave a two week history of a urethral discharge and genital ulcers. Clnical examination and laboratory investigation confirmed that he was suffering from gonorrhoea and genital herpes, for which he received treatment. His most recent sexual contact, which occurred after the appearance of genital ulcers, was with a Zambian girl. This was his sole sexual contact there and he had had a reguar relationship with her for several weeks. He denied any homosexual exposure. His general health had been excellent and he had not received any intramuscular injections or blood transfusions while in Zambia. An initial serological test for HTLV-III antibody was negative. Eight weeks after his return he had a transient flui like illness associated with a generalised non-irritant macular rash. This settled spontaneously. A repeat serological test showed HTLV-III antibody and this was confirmed on retesting. He remains an asymptomatic carrier.Pregnancy rates in 651 subfertile couples in which the man had a varicocele were analysed by life table methods and were not found to be significantly different before and after testicular vein ligation performed in 283 patients. Estimated proportions of couples conceiving were roughly 30% by one year and 45% by two years in both groups. The operation was also not associated with improvement in results of semen analysis. These findings suggest that testicular vein ligation for varicoceles does not improve fertility.

The Assessment of Results Following Endocrine Therapy for Prostatic Cancer

Generally, recent reports on the side effects of estrogen therapy for prostatic cancer have concerned mortality statistics, relatively little attention having been paid to the quality of life of individual patients. We herein propose an assessment of treatment regimens based on the concept of the time during which a patient remains free of tumor progression or serious side effects. A particular regimen has been examined in relation to the hormonal effects of endocrine ablation, and to the dosage and type of estrogen therapy used in 59 men with prostatic cancer. Although no significant difference among treatment methods has emerged in this small group (except for the more frequent occurrence of fluid retention with the stilbestrol dosage, 30 versus 15 mg. per day) and no correlation between the degree of testosterone suppression and length of remission has emerged so far, this method of assessment proved useful and should be applicable widely. It was confirmed that gonadotropin levels remained in the normal range in patients whose testosterone levels were suppressed with chlorotrianisene.

Factors Affecting the Variability of Semen Analysis Results in Infertile Men

UNLABELLED Infertile men who had 3 or more semen analyses performed in one laboratory were placed in 2 groups (I) oligozoospermic group (n = 106), mean sperm concentration between 1 and 20 million/ml (II) asthenozoospermic group (n = 71), mean sperm concentration greater than 20 million/ml, and mean motility less than 60%. With increasing durations of abstinence from ejaculation before the tests there were significant increases in semen volume and sperm concentration. Semen volume increased over the first 4 days to a similar extent in both groups. Sperm concentrations increased over 15 days, but the effect of abstinence was much greater in the asthenozoospermic group than in the oligozoospermic group (14% compared with 1.4% of the within subject variation). Significant changes in results accompanied repeated testing, notably rises in sperm concentration and motility. Sperm motility was lower in winter and higher in summer in both groups and also, but to a lesser extent, in artificial insemination donors who collected semen in the laboratory. CONCLUSIONS duration of abstinence, the elapse of time and seasonal temperature changes affect semen analysis results, and therefore controls for these variables must be incorporated in any therapeutic trial for male infertility. On the other hand, they only account for a small proportion of the total variability and thus routine correction of results would not greatly improve the value of semen analysis in the prediction of fertility. Furthermore because differences in the duration of abstinence have only a small effect on sperm concentration in oligozoospermic men, restricting sexual intercourse to the time of ovulation may not enhance fertility.

SELECTIVE SUPPRESSION OF FSH BY TESTICULAR EXTRACTS

Studies were undertaken to determine the effects of intravenous infusions of bovine testicular extracts on plasma levels of FSH and LH in castrate male sheep. Decapsulated bovine testes were homogenized with phosphate buffer, the homogenates centrifuged at 30,000 X g for 30 min, and the supernatants extracted with diethyl ether. The aqueous extracts were filtered using Diaflo XM-100 membranes and the ultra-filtrates lyophilized. The extracts were infused over 24 hours, and plasma FSH and LH were measured prior to, during, and after the infusion. Control studies using infusions of saline and liver extracts demonstrated no decrease in FSH levels in 6 out of 7 controls, while LH levels tended to rise. Following infusions with the testicular extracts, the levels of FSH were selectively decreased to between 42% and 85% of baseline levels, and they subsequently remained suppressed for at least 24 hours. These results suggest that the testis is the site of production of a water-soluble, non-steroidal substance which exerts an inhibitory effect on the production and/or release of FSH.