B. Hudson

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.

HORMONAL STUDIES IN KLINEFELTER'S SYNDROME

Some aspects of the hormonal abnormalities of Klinefelters syndrome have been studied in nineteen patients. As a group the plasma production rate, the total and free levels of testosterone, and the metabolic clearance rates of testosterone and oestradiol were low. Plasma oestradiol, LH and FSH levels were elevated and there was increased peripheral conversion of testosterone to oestradiol. The production rates of oestradiol and the binding capacities of the sex steroid binding globulin were normal. There were fluctuations in the blood levels of LH, FSH, testosterone and oestradiol, but these appeared to be less marked than in healthy men. Both LH and FSH levels were suppressed by acute or prolonged testosterone administration and there was no evidence for a differential effect on LH. It is suggested that the threshold for suppression of LH and FSH is increased in hyper‐gonadotrophic states. Although no statistically significant relationships were found between the hormonal and clinical abnormalities of the syndrome it is probable that the hyperoestrogenism and androgen deficiency are linked to the development of the signs of feminization and hypogonadism.

REVERSIBLE MALE INFERTILITY DUE TO CONGENITAL ADRENAL HYPERPLASIA

We have studied a patient who was azoospermic and infertile. The cause of his infertility was unusual and curable: untreated congenital adrenal hyperplasia resulting from a partial 21‐hydroxylase deficiency. The diagnosis was suggested by the combination of small testes, elevated levels of testosterone and suppressed levels of gonadotrophins.

EFFECTS OF SYNTHETIC ORAL OESTROGENS IN NORMAL MEN AND PATIENTS WITH PROSTATIC CARCINOMA: LACK OF GONADOTROPHIN SUPPRESSION BY CHLOROTRIANISENE

The effects of the oral synthetic oestrogens, diethylstiboestrol and chlorotrianisene, have been studied in healthy male volunteers and in patients with prostatic carcinoma. The plasma levels of follicle stimulating hormone, luteinizing hormone and testosterone decreased significantly during treatment with diethylstilboestrol. Although plasma levels of testosterone decreased during treatment with chlorotrianisene, levels of follicle stimulating and luteinizing hormones were not significantly suppressed. This pattern of response was observed both in healthy males and in patients with prostatic carcinoma, regardless of whether chlorotrianisene was used as the primary therapy in the latter group or following therapy with diethylstilboestrol or orchidectomy. The capacity of the sex steroid binding globulin for testosterone was increased following prolonged administration of both agents. It is concluded that suppression of plasma testosterone levels observed during chlorotrianisene therapy is the result of a direct effect on the testis and that this agent may be of value in studies of gonadotrophin physiology.

SUPPRESSION OF ŒSTRADIOL SECRETION AND LUTEINISING-HORMONE RELEASE DURING ŒSTROGEN-PROGESTAGEN ORAL CONTRACEPTIVE THERAPY

Abstract Plasma-œstradiol and luteinising-hormone levels were measured in women during the normal menstrual cycle and during combined oral contraceptive treatment. During normal cycles, the plasma levels of cestradiol consistently reached peak values and began to fall immediately prior to the peak of plasma-luteinising hormone. This finding, together with the known action of oestrogen on stimulation of luteinising-hormone secretion, indicates that feedback from the ovary via œstradiol secretion is an essential component of the physiological mechanism for cyclic luteinising-hormone release and

Alterations in spermatogenic activity and hormonal status in a seasonally breeding rat rattus fuscipes

Abstract The changes in the levels of serum FSH, LH, and testosterone have been studied during the seasonal reproductive cycle in males of the species Rattus fuscipes. In males captured in winter the seminiferous tubules were small, spermatogenesis was arrested at the primary spermatocyte stage, and the Sertoli cells contained increased numbers of lipid inclusions. The Leydig cells were atrophic and contained large crystalloids. The aspermatic state was accompanied by low levels of serum FSH, LH, and androgen. Reactivation of spermatogenesis occurred in spring and was accompanied by a rise in the levels of FSH, LH, and androgen. These hormonal changes were associated with a depletion of lipid inclusions from the Sertoli cells which paralleled the activation of spermatogenesis. The rising androgen levels were accompanied by the enlargement of Leydig cells and the disappearance of the crystalloids. In summer the fully active testes were associated with further increments of serum FSH and androgen levels above those seen during spring. It is concluded that the environmental cues controlling the seasonal reproductive cycle exert their influence on the testis through changes in gonadotrophin secretion by the pituitary gland.

Testosterone Plasma Levels in Normal and Pathological Conditions

The purpose of this paper is to review what is now a fairly substantial body of knowledge about the concentration of testosterone in human plasma both in normal and abnormal conditions. For the most part, this review will be directed to testosterone in the male; however, other closely related steroids such as andros-tenedione and dehydroepiandrosterone (DHEA) will be discussed in so far as these are relevant; likewise, plasma levels of all these steroids in the female will be discussed particularly when it may be appropriate to compare and contrast them between the two sexes. This presentation will thus aim to synthesize this knowledge, and will draw upon many contributions from different laboratories, including our own.

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.