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Biomedical subjects

M J Wheeler

Publications and source records attributed to M J Wheeler.

At least 19 recordsLinked to original sources
PubMed1995

Raised serum 11-deoxycortisol in men with persistent acne vulgaris.

OBJECTIVE: Acne vulgaris is androgen dependent but the hormonal mechanisms are unclear. Although there have been many studies of serum hormones in women with acne there are few studies in men and the results are conflicting. We have therefore carried out a further study in men. DESIGN AND PATIENTS: Fifty men with acne vulgaris were age-matched against 50 normal men. MEASUREMENTS: Serum levels of dehydroepiandrosterone sulphate (DHEAS), 17 alpha-hydroxyprogesterone, 11-deoxycortisol, androstenedione and testosterone were measured by radioimmunoassay, sex hormone binding globulin (SHBG) by immunoradiometric assay and LH, FSH and oestradiol by automated ELISA. RESULTS: The acne patients had higher levels of androstenedione, median 7.35 nmol/l, (interquartile range 2-7) vs 6.05 (2.3), P = 0.004; testosterone, 21.7 nmol/l (7.5) vs 17.55 (7.7), P = 0.04; and free androgen index (FAI) 78.26 (40) vs 65.06 (20), P = 0.007, but also had higher levels of 11-deoxycortisol, 13.65 nmol/l (4.3) vs 12.0 (4.3), P = 0.022. The LH, FSH, 17 alpha-hydroxyprogesterone, DHEAS, oestradiol and SHBG levels were not significantly different. Examination of the Spearman rank correlation coefficient matrices for the serum levels of 17 alpha-hydroxyprogesterone, androstenedione and 11-deoxycortisol showed that the strongest correlation was between androstenedione and 11-deoxycortisol. CONCLUSION: Although there was overlap between the results of the acne patients and controls the acne patients tended to have higher levels of androstenedione, testosterone, free androgen index and 11-deoxycortisol. The higher levels of 11-deoxycortisol are suggestive of 11 beta-hydroyxlase dysfunction which could be due to a primary adrenal defect or a consequence of raised androgens. Also, a pathway between androstenedione and 11-deoxycortisol has been described in sheep and, although unsubstantiated in man, requires consideration.

17-alpha-Hydroxyprogesterone↗
PubMed1992

Dose-related effects of oestradiol on rat thymic and splenic T-lymphocyte responsiveness to mitogens.

The dose-related effects of oestradiol on responses of thymic and splenic lymphocytes to mitogenic stimulation were studied in immature female Wistar rats. An attempt was made to relate responses not merely to dose but also to the circulating levels of the steroid. Lymphocytes were prepared from thymus and spleen and stimulated with phytohaemagglutinin (PHA) and concanavalin A (Con A) prior to measurement of 3H-thymidine incorporation. Oestradiol suppressed lymphoid tissue weight and cell number in a dose-related manner, but it was found, unexpectedly, that the dose of oestradiol used actually stimulated responsiveness of lymphocytes to mitogenic stimulation. Log dose-response curves indicate that the effects of oestradiol on responsiveness are complex, and the results suggest that the atrophic effects of oestradiol on lymphoid tissue and its enhancement of response to mitogens might be mediated by different mechanisms. Since the stimulant effects of the steroid were observed with serum levels of oestradiol attained both physiologically and pharmacologically, the results suggest a possible mechanism of action of oestradiol in abnormal cell proliferation, as occurs in neoplastic tissues, and might also help to explain certain sex-linked immune-related disorders.

Animals↗
PubMed1992

Which hormone tests for the diagnosis of polycystic ovary syndrome?

OBJECTIVE: To assess the frequency of abnormal values for hormone measurements commonly used in the biochemical diagnosis of polycystic ovary syndrome (PCOS). DESIGN: Hormone measurements in 63 unselected women with clinical and ultrasound diagnosis of PCOS attending gynaecological and general endocrine clinics in a District General Hospital were compared with those from a group of 20 normal ovulatory controls in the early follicular phase of their cycles. MEASUREMENTS: Serum levels of luteinizing hormone (LH), follicle stimulating hormone (FSH), LH/FSH ratio, total testosterone, derived free testosterone, sex hormone binding globulin, androstenedione, and dehydroepiandrosterone (DHEA) were measured by radioimmunoassays. LH and FSH measured by two different assays. RESULTS: The mean serum LH and LH/FSH ratio were significantly (P less than 0.01) higher in the women with PCOS compared with the normal group, but these two measurements were in the abnormal range for only 35% and 41-44%, respectively. Absolute gonadotrophin values were significantly different using the two assay methods, which employed the same reference preparation as standard. Mean serum total testosterone concentration was significantly higher in the PCOS group and was the most frequently (70%) abnormal biochemical marker for PCOS. Sex hormone binding globulin (SHBG) did not differ significantly between the two groups but showed a negative correlation with body mass index in women with PCOS. The combination of SHBG and testosterone to derive a free testosterone value did not further aid the biochemical diagnosis of PCOS. Androstenedione was significantly higher in the PCOS group than in the control group, with a frequency of 53%. There was no significant difference in DHEA-S between the two groups. CONCLUSION: When typical ovarian ultrasound appearances plus the clinical features of oligomenorrhea and/or hirsuitism were used to define PCOS total testosterone was the best single hormonal marker of the condition. Testosterone, androstenedione or LH, either alone or in combination, were raised in 86% of women with PCOS and these should be the definitive hormonal tests. Using LH/FSH ratio as a biochemical criterion for diagnosis of PCOS should be abandoned because of its low sensitivity. To be of value the normal range for all hormones should be precisely defined in a group of regularly ovulating women in the early follicular phase of the cycle for the assay used in each laboratory.

Androstenedione↗
PubMed1991

Amenorrhoea in women with non-alcoholic chronic liver disease.

Amenorrhoea is common in women with non-alcoholic chronic liver disease, but little is known about its causes or consequences. We investigated 12 young women with non-alcoholic chronic liver disease and amenorrhoea and compared them with 11 healthy age matched controls studied in the follicular phase of the menstrual cycle. None of the patients had raised serum concentrations of follicle stimulating hormone suggesting primary gonadal failure, but the variance in serum concentrations of testosterone, oestradiol, prolactin, and luteinising hormone were significantly greater in chronic liver disease patients than control subjects (p less than 0.01). Seven of the 12 chronic liver disease patients had low serum luteinising hormone concentrations, and compared with controls these patients also had significantly reduced median values of oestradiol (64 pmol/l), testosterone (1.1 nmol/l), and follicle stimulating hormone, and were significantly underweight as assessed by skinfold thickness measurements (all comparisons p less than 0.025). In the group with chronic liver disease skinfold thickness was significantly correlated with serum luteinising hormone (p less than 0.02). The five patients with normal serum luteinising hormone had higher median values of both oestradiol (237 pmol/l) and testosterone (3.0 nmol/l) than the control subjects (oestradiol: 113 pmol/l, testosterone: 1.9 nmol/l) but were not more obese or hirsute. Amenorrhoea was unrelated to the duration or severity of liver disease. The metacarpal cortical bone area (an index of bone density) was inversely related to the duration of amenorrhoea (p less than 0.02). We conclude that amenorrhoea in women with non-alcoholic chronic liver disease arises from hypothalamic-pituitary dysfunction and can occur at any stage. The hormonal findings in amenorrhoeic chronic live disease patients are not uniform. In some, hypogonadotrophic hypogonadism is related to undernutrition whereas others have normal to high values of luteinising hormone and sex steroids. Prolonged oestrogen deficiency can be a risk factor for osteoporosis in women with chronic liver disease.

Adult↗
PubMed1991

Metabolic clearance rate of testosterone in male epileptic patients on anti-convulsant therapy.

There are several reports which state that male epileptics on anti-convulsant therapy have reduced sexual activity. We and others have shown that, although total testosterone is raised, the free testosterone concentration is reduced in this patient population. This could be a result of an increased metabolic clearance rate (MCR) of testosterone, inadequate secretion of LH to stimulate testosterone synthesis or inappropriately low testosterone production by the Leydig cells. We have examined these possibilities by measuring the MCR of testosterone in 15 male epileptics on anti-convulsant therapy. In this group of patients, the mean LH (9.3 +/- 5.9 IU/l) and sex-hormone binding globulin (SHBG) (54.5 +/- 22.9 nmol/l) concentrations were significantly greater than those of five normal control subjects (4.7 +/- 1.11 IU/l and 26.0 +/- 7.0 nmol/l respectively). Mean total testosterone concentrations of the two groups were not significantly different but the mean percentage of free testosterone and free testosterone concentration were significantly lower in the patient population (2.06 +/- 0.43 vs 2.98 +/- 0.27 and 0.56 +/- 1.1 vs 0.79 +/- 0.07 pmol/l). The MCR of testosterone was significantly lower in the patients (773 +/- 322 vs 1354 +/- 443 l/day) and showed a positive correlation with the percentage of free testosterone. Therefore, our results suggest that the lowered free testosterone in male epileptics on anti-convulsant therapy is not due to an increased MCR of testosterone. The increased LH concentration suggests primary hypogonadism. This, in turn, could be responsible for low free testosterone levels in the presence of normal testosterone.

Adult↗
PubMed1991

Effect of administration of human chorionic gonadotrophin on criteria used to assess testosterone administration in athletes.

Abnormal ratios of testosterone to epitestosterone (T/E) and testosterone to LH (T/LH) in the urine of male athletes are indicative of testosterone administration. The T/E ratio has been adopted by the International Olympic Committee as the sole criterion used in the detection of testosterone administration. An athlete is usually considered to have failed a drug test if the urinary T/E ratio is greater than 6. Human chorionic gonadotrophin (hCG) has been used by some male athletes to stimulate testicular secretion of testosterone. The purpose of this investigation was to examine whether the urinary T/E ratio can remain unaffected by administration of hCG to normal adult males. Administration of hCG resulted in large increases in serum testosterone concentrations and urinary T/LH ratios but small changes in urinary T/E ratios of two subjects (maximum T/E values observed were 0.8 and 1.2 respectively). These observations suggest that the urinary T/LH ratio is a valuable indicator of hCG as well as of testosterone administration. This study is the first to measure urinary T/LH ratios using the technique of gas chromatography-mass spectrometry for quantification of testosterone, and highly specific monoclonal antibodies for the measurement of LH. An ultrafiltration method is proposed as part of a confirmatory procedure to be adopted in the measurement of urinary gonadotrophins for drug control in sport.

Chorionic Gonadotropin↗
PubMed1990

Criteria to indicate testosterone administration.

A detection method for testosterone administration was developed using radioimmunoassay to measure the urinary ratios of testosterone (T) to epitestosterone (E) and to luteinizing hormone (LH). A comparative study of the effect on these ratios of a single intramuscular injection of testosterone heptanoate followed by stimulation with human chorionic gonadotrophin (HCG) in three normal men was undertaken. To allow immediate investigation, a commercially supplied epitestosterone antiserum was used. This study showed that both T/E and T/LH ratios could be used to detect testosterone administration, the latter also being an indicator of HCG use due to cross-reactivity with the LH antiserum. Subsequently, an epitestosterone antiserum of superior specificity was raised and used in a study to demonstrate the insignificant effect of exercise on these ratios. Finally, an intramuscular injection of a combined preparation of testosterone/epitestosterone heptanoates resulted in raised ratios of T/LH but not of T/E. This demonstrated the importance of the T/LH ratio in circumstances where the T/E ratio can be easily circumvented.

Adult↗
PubMed1990

Effect of long-term inhibition of gonadotrophin secretion by the gonadotrophin-releasing hormone agonist, buserelin, on sex steroid secretion and ovarian morphology in polycystic ovary syndrome.

In order to investigate the effect of long-term suppression of the gonadotrophin axis in polycystic ovary syndrome, eight affected subjects were given s.c. infusions of gonadotrophin-releasing hormone (GnRH) agonist buserelin for 12 weeks. Hormone measurement and ultrasound studies were carried out weekly, from 6 weeks before to 12 weeks after administration of buserelin. An overnight dexamethasone-suppression test was carried out before and after treatment. Maximal suppression of LH to below the lower limit of that in normal subjects occurred after 6 weeks of treatment with buserelin. Plasma testosterone and androstenedione fell to normal levels during the infusion but reached pretreatment levels during the follow-up period. There was no effect of buserelin on plasma dehydroepiandrosterone sulphate or sex hormone-binding globulin. Ovarian size decreased significantly during the infusion with the disappearance of cysts in six subjects. After cessation of buserelin therapy, there was rapid and spontaneous ovulation which occurred within 3 weeks in all subjects. The results suggest that treatment with this GnRH agonist facilitates ovulation in this condition.

Adult↗
PubMed1988

Uterine growth in the follicular phase of spontaneous ovulatory cycles and during luteinizing hormone-releasing hormone-induced cycles in women with normal or polycystic ovaries.

The uterine response to follicular growth in luteinizing hormone-releasing hormone (LH-RH)-induced ovulatory cycles was assessed by serial ultrasound measurement of uterine cross-sectional area and endometrial thickness in 23 cycles in women with normal ovaries and 24 cycles in women with polycystic ovaries. Nine women with spontaneous ovulatory cycles also were studied. The authors correlated uterine cross-sectional area and endometrial thickness with follicle diameter (FD) and serum estradiol-17 (E2). In women with either normal or polycystic ovaries, there was an E2-related increase in uterine cross-sectional area and endometrial thickness, but both uterine area and endometrial thickness were greater in the late follicular phase of women with polycystic ovaries compared with those with normal ovaries.

Endometrium↗
PubMed1987

Zinc status in polycythaemia.

Zinc and iron status have been measured in three groups of polycythaemic patients managed by venesection: polycythaemia rubra vera, secondary polycythaemia and idiopathic erythrocytosis. Zinc status was assessed from the concentration of zinc in polymorphonuclear cells (PMN) and plasma. The mean PMN zinc value was lower than that of age-matched controls (polycythaemics 57.5 +/- 2.3 micrograms/10(10) PMN, n = 26; controls 68.9 +/- 5.2 micrograms/10(10) PMN, n = 9; means +/- SEM, p less than 0.05). The difference was most marked in polycythaemia rubra vera; the patients were iron-deficient. The reduced PMN zinc levels may indicate that polycythaemic patients managed by repeated venesection are zinc-deficient. This may contribute to some nonspecific symptoms of polycythaemia and to recurrent infections in the hypoxic patients.

Aged↗
PubMed1987

Regeneration of the thymus in old male rats treated with a stable analogue of LHRH.

It has been shown that the thymus can be regenerated in intact old rats by implanting s.c. a stable analogue of LHRH. Old male rats were given s.c. implants of osmotic pumps containing a solution in citrate buffer of the analogue which was given at a rate of 1 microgram/h for 28 days. Some animals were given pumps containing buffer alone, and another group of rats was orchidectomized. The animals were killed after 28 days and the tissues weighed and taken for histology. Serum testosterone was measured by radioimmunoassay. Sham-treated rats had small fatty thymuses, which were poorly organized with a very narrow band of cortex. Animals treated with the analogue of LHRH and those which had been orchidectomized had relatively large thymuses which were multi-lobed in drug-treated rats, and atrophied accessory sex organs. The testes were grossly atrophied in analogue-treated rats. Histologically, the thymus looked healthy, having a wide, thymocyte-filled cortex and a clearly defined corticomedullary junction. Serum testosterone concentrations were similar in orchidectomized and analogue-treated rats. It is concluded that it is possible to regenerate the thymus in old rats treated with an analogue of LHRH, but the effect is accompanied by chemical castration. It is also clear that the old pituitary gland is susceptible to the desensitizing action of an LHRH analogue.

Animals↗
PubMed1986

Mild androgen insensitivity presenting with sexual dysfunction.

A man presented with sexual dysfunction and was found to have elevated serum levels of both gonadotropins and T, suggesting AIS. Small external genitalia were the only phenotypic abnormality. Serum T levels increased appropriately in response to hCG and CC, but the patient was severely oligospermic, and testicular biopsy study revealed profoundly impaired spermatogenesis. Studied on androgen receptors in genital skin fibroblasts were normal. PAIS with a virtually normal male phenotype can present in adulthood with sexual dysfunction as well as infertility. As with the syndrome of complete AIS, androgen receptor studies indicate that this is a heterogeneous group of disorders.

Adult↗