The role of testosterone measurement in the investigation of androgen disorders.
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Biomedical subjects
Publications and source records attributed to M J Wheeler.
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An evaluation has been carried out of 13 commercial testosterone kits. The within- and between-assay imprecision was found to be unsatisfactory for some kits. Sensitivity and linearity were acceptable for all the kits but several showed concentration-dependent biases to the ALTM or GCMS values. The occurrence of anomalous results and changing performance characteristics of some of the direct kits is also presented.
The effect of chronic oral administration of cimetidine (1 g per day) and ranitidine (300 mg per day) on plasma levels of prolactin (PRL), testosterone, dihydrotestosterone (DHT), luteinizing hormone (LH), follicle stimulating hormone (FSH), sex hormone binding globulin (SHBG) and human growth hormone was compared in 2 groups of male patients who presented with dyspeptic symptoms. Eight were treated with ranitidine and 9 with cimetidine for 4 weeks. The glucose and insulin response to a 100 g oral glucose load was also assessed. Cimetidine treatment resulted in a significant increase in plasma testosterone levels which was not found in the ranitidine group. No significant change occurred in PRL, LH, FSH, SHBG, DHT and growth hormone. There was no evidence of a significant alteration in carbohydrate metabolism.
The thymus is a critically important organ during development, but atrophies progressively during the ageing process after puberty and is often considered to be unimportant in adult life. We have found that the thymus, which is grossly atrophied in 12- to 15-month-old male rats, is markedly restored in size 30 days after orchidectomy. The organ then appears normal histologically, having a well-defined cortex and medulla, is vascularized and filled with thymocytes. The regeneration of the thymus after orchidectomy was inhibited in a dose-related fashion by testosterone implants which produced serum concentrations of testosterone within the physiological range. The thymus was also increased in size after orchidectomy of 10-week-old rats, and testosterone inhibited the enlargement of the thymus. These results have important implications for the possible enhancement of the immune system with associated improvement of health during ageing and disease. They also point to an important physiological link between the endocrine and immune systems.
Serum high-density lipoprotein (HDL) cholesterol, testosterone and sex-hormone-binding globulin (SHBG) were measured in 300 men, aged 35-64 years, of African and Indian descent who represented a 40% sample of participants in a community survey of coronary heart disease in Trinidad. Free testosterone was calculated from total testosterone and SHBG. In 113 men, HDL2 and HDL3 cholesterol were measured by a precipitation technique. Indian men had a significantly lower HDL-cholesterol concentration than African men (P = 0.003), which is known to be due to a reduction in the HDL3 fraction (demonstrable only in younger men in the subsample drawn for this study). Testosterone did not differ with ethnic group, but SHBG was reduced in Indians (P = 0.03). After allowance for age, ethnic group, alcohol consumption and smoking habit, HDL cholesterol was associated positively with SHBG (P = 0.025) but was not related significantly to either total testosterone or its free and bound components. Serum HDL2 cholesterol was associated positively and independently with SHBG (P = 0.001) and total and bound testosterone (P = 0.002), whereas HDL3 cholesterol showed no significant associations with these factors. Neither SHBG or testosterone afforded an explanation for the relatively low HDL and HDL3 cholesterol concentrations in Indian men.
Cortisol (F) and dehydroepiandrosterone (DHA) were measured following each 5 kg gain in weight in a group of 16 patients with anorexia nervosa admitted to hospital for refeeding. The mean percentage of standard weight on admission was 65% and that on discharge was 92%. Basal plasma cortisol fell gradually throughout the inpatient period, the correlation coefficient of the regression line relating percentage of standard weight to plasma cortisol in all patients was -0.559 (p less than 0.001). Adrenal androgen production, however, increased with weight gain and the correlation coefficient of the regression line of androgen production against percentage of standard weight was +0.303 (p less than 0.01). The DHA/F ratio increased with weight gain. This suggests that weight gain in the patient with anorexia nervosa could be associated with increased activity in the adrenal 17,20-lyase enzymes and a decrease in the activity of the 3-beta hydroxysteroid dehydrogenase. The possibility that these adrenal enzyme changes are controlled by pituitary proopiocortin peptides [the putative cortical androgen stimulating hormone (CASH)] is discussed as is the relationship between normal adrenarche and the weight related changes in adrenal function in anorexia nervosa.
The sexual behaviour and hormonal profiles in 97 patients with chronic epilepsy from an epilepsy centre were studied. Sexual behaviour relating to numbers of sexual contacts, orgasms, spontaneous erections, and early morning erections, whether there was difficulty in obtaining or maintaining an erection, or in ejaculation, was assessed at interview. Hormonal profiles consisted of LH, FSH, prolactin, total testosterone, free testosterone, and SHBG. Information was obtained relating to type of seizure, seizure frequency, age of onset, likely pathology, IQ, and medication. The study showed that this patient group was profoundly hyposexual and had a high level of sexual dysfunction. Serum free testosterone levels were low, and it is suggested that the high level of sexual dysfunction and lack of sexual interest may well have a hormonal basis. The reasons for this are discussed.
A method is described for measuring the percentage of free testosterone in serum using steady-state gel filtration on micro-columns of Sephadex G50 (fine). The method has a coefficient of variation of 4.0% and up to 20 samples can be processed in a day. Reference ranges have been established for normal women at different stages of their menstrual cycles and for normal men; there is good agreement with values published by workers using other methods. This method combined with a specific and precise method for measuring total testosterone opens up the possibility for the routine measurement of free testosterone concentration in serum.
Only about 50% of women who are clinically hirsute have a raised total plasma testosterone concentration; in those cases where the total testosterone is normal the free testosterone may, in fact, be raised. Since the measurement of free testosterone is tedious, workers have used an androgen index or a calculated free testosterone concentration from the measurements of total testosterone and sex-hormone-binding globulin. We have examined the correlation between measured free testosterone, a derived free testosterone and an androgen index in hirsute women, normally menstruating women and non-hirsute women on oral contraceptive therapy. These three measures of the free testosterone concentration in blood gave similar results in all cases.
There was no visible thymus in ageing rats of 18 months, and 7 days after orchidectomy there was still no evidence of a thymus. By 30 days after the operation, however, there was a well-defined and well developed bilobular thymus overlying the heart, although it was smaller than those observed in 10-week-old rats. Histologically, the tissue appeared normal, was well vascularized, filled with lymphocytes and several mitotic figures were also seen. When compared with sham-operated animals, blood from these animals had a significantly higher lymphocyte count. These results have important implications for the possible enhancement of the immune system with associated improvement of health during ageing.
An attempt was made to explore the reasons why men develop coronary heart disease (CHD) despite being at low risk on the basis of established risk factors. A case control study was designed to take place after the end of a longitudinal study in which both low- and high-risk men who had developed CHD over the course of 5-6 years were compared with controls who had remained CHD-free, matched for initial risk characteristics. Low-risk men who had developed CHD had significantly lower levels of high density lipoprotein (HDL) cholesterol than their controls. This difference was not seen when high-risk men were compared with their controls. Apart from a suggestion that low risk cases had lower levels of free thyroxine (seen mainly when less severe categories of CHD were examined) there were no other significant differences between cases and controls (either low- or high-risk) in the other measured variables, which included levels of total testosterone and oestradiol in plasma, packed cell volume and heart rate. It is concluded that low levels of HDL cholesterol may partly explain why men who are otherwise at low risk develop CHD. This study design may be useful to test other hypotheses, particularly where it has not been possible to make the appropriate measurements at the start of a longitudinal study.
Plasma LH, FSH, testosterone and sex-hormone-binding globulin have been measured in a total of ten male anorectics. There was no significant correlation between body weight and FSH levels or body weight and SHBG levels. Both LH and testosterone concentrations were significantly correlated with body weight. They were well below the adult normal range at low body weight and rose with weight gain although in many cases neither hormone reached normal levels at target weight. The plasma LH and FSH response to 50 micrograms LHRH was measured in five male anorectics on twelve occasions, and compared with the responses of twelve normal adult males. The anorectic patients showed a FSH response which was normal on eleven occasions and slightly raised on one occasion. The LH response was below normal at weights below 40 kg, exaggerated between 45 kg and 50 kg and within normal limits at other weight ranges. These results are compared with previous findings in female anorectics.
The stability of a preparation of lyophilised serum and its suitability for use as a reference material for routine assays of cortisol, oestradiol, and progesterone have been studied in four laboratories with a variety of assay systems. Cortisol and oestradiol were also measured by gas chromatography-mass spectrometry. The lyophilised serum was suitable for use in all routine and reference assay methods examined, with between-method variability no greater than that for frozen serum pools. The concentrations of cortisol, oestradiol, and progesterone were predicted by accelerated degradation studies to decline by 0.01% per annum if the preparations were to be stored at --20 degrees C. The testosterone content of the preparation, determined in one laboratory, provided no evidence for degradation. The preparation can be shipped for use at ambient temperature without deleterious effect.
A cross-sectional study was performed to see if the previously described association between high density lipoprotein (HDL) cholesterol and plasma total testosterone concentration reflected a relationship with free testosterone or with sex hormone binding globulin (SHBG). In 295 employed middle-aged men, measurements were made of total testosterone and SHBG in serum and of testosterone in saliva, and also of plasma total and HDL cholesterol, plasma triglycerides and other factors which might influence HDL cholesterol levels such as body mass index, alcohol and smoking habits and thyroid hormone levels. In a multiple regression analysis using the GLIM package programme total testosterone concentrations had a persistent positive association with HDL cholesterol (t = 3.5, P less than 0.001) - this association was independent of SHBG (which had a negative association with HDL: t = -1.8, P less than 0.07. The association of HDL cholesterol with testosterone was independent of and stronger than the association of HDL cholesterol with body mass index, alcohol intake and cigarette smoking. Salivary testosterone (a measure of the circulating free hormone) also had a positive independent association with HDL cholesterol. The relationship between HDL cholesterol and testosterone thus appears to reflect an association with circulating hormone levels rather than with the hormone binding globulin.
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One hundred and two Southampton general practitioners were interviewed about female breast disease. There was agreement about clinical management and the need to both teach and promote breast self-examination. The general practitioners, however, were divided as to whether any breast screening facilities were needed in Southampton. Records kept by the general practitioners of women seen with breast symptoms showed that one-quarter of all new episodes were referred to hospital at the first visit. That the general practitioners considered early diagnosis to be important was made evident from a number of the results. This attitude is encouraging in view of the evidence showing that long-term survival may be greater when delays are shorter.
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