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Biomedical subjects

W R Butt

Publications and source records attributed to W R Butt.

At least 37 records · Page 2Linked to original sources
PubMed1981

Treatment of hyperprolactinaemia with pergolide mesylate: acute effects and preliminary evaluation of long-term treatment.

The acute and long-term effects of oral pergolide mesylate, a new potent, long-acting dopamine agonist, were investigated in 10 hyperprolactinaemic patients. After a single 50 micrograms dose of pergolide mesylate, serum prolactin concentrations fell steadily to reach a mean minimum value at 6 h of 20% of baseline values; this degree of suppression was maintained throughout the 24 h study period. In one patient serum prolactin was measured for 2 days after a single dose and remained suppressed for 45 h. There were no acute changes in the serum concentration of luteinising hormone, follicle-stimulating hormone and growth hormone. Preliminary evaluation of longer term treatment with pergolide indicates that this drug at a once-daily dose of 50-150 micrograms is a safe, well tolerated, and effective new treatment for hyperprolactinaemia.

Administration, Oral↗
PubMed1981

Oestrogen-gonadotrophin feedback mechanisms in the puerperium.

The effect of oestradiol benzoate on serum gonadotrophin concentrations before and after LHRH administration was studied in lactating and non-lactating women at 3 and 6 weeks post-partum. Except in the non-lactating women at 6 weeks, basal serum FSH concentrations were suppressed by oestrogen. There were no significant changes in basal concentrations of LH after oestrogen in the lactating women in either the 3- or 6-week studies. Individual increases in the basal LH concentrations in two out of six non-lactating subjects in the 6-week study occurred but overall there were no significant changes. In the 6-week study amplification of the LH response to LHRH was found in both groups, the effect being significantly greater in the non-lactating women. Overall FSH responses were also significantly different in the two groups, being suppression in those lactating ad amplification in those not lactating. The LH/FSH ratios following LHRH administration in the 6-week non-lactating study were similar to those seen in the early follicular phase in regularly menstruating subjects. The basal ratios in the lactating subjects were, however, significantly less than those seen in the non-lactating subjects both at 3 and 6 weeks. This difference was associated with the relative enhancement of LH release in non-lactating subjects and enhancement of FSH release in those lactating. Taken together the results indicate the presence of an intact negative feedback of oestrogen on gonadotrophin release in both groups being enhanced at 6 weeks post-partum in the lactating subjects; also in the lactating subjects at 6 weeks there was less amplification by oestrogen of the responsiveness of the anterior pituitary to LHRH. At 6 weeks, however, in the non-lactating group these responses were similar to those seen in normal regularly menstruating subjects. These dynamic endocrine studies suggest a possible hypothalamic-pituitary mechanism which may help to explain the delayed return of ovulatory cycles in lactating women.

Estradiol↗
PubMed1981

Oestrogen stimulated neurophysin in pregnancy and lactation.

Serum concentrations of oestrogen stimulated neurophysin (ESN) were measured throughout pregnancy in thirty-one women and until 6 weeks post-partum in a further twenty-three. During pregnancy ESN rose progressively and values during labour were similar to those immediately before delivery. There were significant correlations (P less than 0.05) between serum ESN and oestradiol values measured in samples from four patients. After delivery the concentration of ESN fell rapidly to the range for non-pregnant women by 5 days post-partum, whether the mothers lactated or not, and remained fairly constant for the next 6 weeks. Bromocriptine or metoclopramide, drugs which affect prolactin secretion, were without effect on ESN values. At 8 days post-partum in sixteen of the eighteen patients studied there was an increase in ESN concentration 30 min after suckling commenced. At 6 weeks similar changes occurred in five of the ten subjects studied. In contrast, at 8 days there was no significant change in ESN in four mothers who bottle fed their babies over the 90 min studied. The relationship between ESN and hormonal changes during pregnancy and lactation is discussed in the light of these results.

Estradiol↗
PubMed1981

Failure of 2-hydroxyoestrone to lower prolactin concentrations in hyperprolactinaemic women.

The catechol oestrogen 2-hydroxyoestrone has been reported to lower serum prolactin concentrations acutely in normal women and it has been proposed that it may be effective in suppressing prolactin secretion in hyperprolactinaemic patients. Five women with hyperprolactinaemia and anovulation were studied. Following a control infusion, 2-hydroxyoestrone was given at a rate of 80 micrograms/h for 4 h. In no patient was there a fall in prolactin levels and no changes were observed in gonadotrophin concentrations. We conclude that a short-term infusion of 2-hydroxyoestrone, at a dose which will produce high blood levels of the steroid, does not affect prolactin or gonadotrophin secretion in hyperprolactinaemic states.

Adult↗
PubMed1980

Adrenal function in subgroups of the PCO syndrome assessed by a long ACTH test.

Fifteen patients with the polycystic ovarian (PCO) syndrome were classified into Group A (n = 6) and Group B (n = 9) based on their LH responses to LHRH before and at 44 and 92h after administration of oestradiol benzoate. Adrenal function in both groups was assessed by comparing the hormone responses to ACTH (0.5mg twice daily for 4 days) with those obtained in nine normally ovulating women during the early follicular phase of their cycles. In Group A patients there was no significant difference from normals in the serum concentration of dehydroepiandrosterone sulphate (DHAS), 17 alpha-hydroxy-progesterone (17-OHP) or androgens (testosterone and dihydrotestosterone). In contrast, the serum concentrations in Group B were significantly higher (P less than 0.01) for each of these steroids before ACTH, and remained higher at 2 and 4 days for DHAS, but not for the other two steroids. The concentration of oestrone was significantly higher (P less than 0.05) in Group B patients before, and 2 days after, ACTH, while in Group A patients higher concentrations (P less than 0.02) were found only after 2 days. The concentrations of oestradiol, on the other hand, were not different from normal in either group before ACTH and became lower than normal in both groups at 2 days and remained lower at 4 days in Group B. The concentration of cortisol was within the normal range throughout in Group A, but was lower than normal after 4 days in Group B patients (P less than 0.05). The ratios between the sums of concentrations of DHAS to cortisol on days 2 and 4 (P less than 0.001) or 17-OHP to cortisol (P less than 0.05) were elevated in Group B compared with normal subjects. LH, FSH and prolactin values were normal throughout in Group A, but in Group B patients the mean value for LH was significantly elevated before ACTH and at 4 days after ACTH (P less than 0.02).

Adrenal Glands↗
PubMed1979

Oestrogen modulation of gonadotrophin and prolactin release in women with anovulation and their responses to clomiphene.

An LHRH test was performed before and at both 44 and 92 h after the administration of 2.5 mg oestradiol benzoate in eleven patients with hyperprolactinaemia, eight with idiopathic secondary amenorrhoea and seven with oligomenorrhoea. The basal serum hormone concentrations and the responses to LHRH were compared with the same tests performed on ten normal subjects during the early follicular phase of their menstrual cycles (days 4--6). Mean basal concentrations of oestradiol in each group of patients and oestrone in those with hyperprolactinaemia were significantly lower than in the normal subjects. The mean concentration of prolactin in women with secondary amenorrhoea remained lower than in the normal women throught the tests (P less than 0.05). The LH and FSH responses to LHRH before oestrogen in patients with hyperprolactinaemia and of FSH in those with secondary amenorrhoea, were greater than in the normal subjects (P less than 0.001). After oestrogen treatment the responses were similar in all groups except in those with oligomenorrhoea where LH and FSH responses at 44 h (P less than 0.05 and P less than 0.01 respectively) and LH responses at 92 h (P less than 0.01) were lower than in normal controls. The responses at 92 h in all groups were greater than at 44 h (amplification) but the amplification at 92 h and at 44 h compared to the pre-treatment responses, tended to be lower in each group of patients compared to the normal controls. In the hyperprolactinaemic group of patients there was a negative correlation between the basal prolactin concentration and the gonadotrophin amplifications at 92 h (P less than 0.01), and a positive correlation between the basal oestrone levels and the amplifications at 92 h (P less than 0.01). The results of the oestrogen amplification test in eleven of the non-hyperprolactinaemic anovular patients were compared with the ovulatory response to 100 mg clomiphene given for 5 days. Six showed a normal oestrogen amplification and they all ovulated. Two patients failed to show greater amplification at 92 than at 44 h and required human chorionic gonadotrophin (HCG) as well as clomiphene to ovulate. The other three showed a diminished LH amplification at 92 h; they required 200 mg clomiphene and showed a prolonged follicular phase. The responses of the hyperprolactinaemic patients to clomiphene were poor and there was a negative correlation between prolactin concentration and oestrogen production (P less than 0.01). All ten hyperprolactinaemic patients treated with bromocriptine ovulated and eight conceived. The oestrogen amplification test appears to have some value in predicting the subsequent response to clomiphene in non-hyperprolactinaemic anovular women.

Adult↗
PubMed1979

Oestrogen-gonadotrophin feedback abnormalities in hyperprolactinaemic amenorrhoea demonstrated by the response to clomiphene administration.

Clomiphene was administered to 16 patients with elevated serum prolactin levels in doses of 100, 200 and 300 mg/day for five days in succeeding months and total urinary oestrogens estimated on days 0, 5, 8, 12 and 15 following commencement of treatment. The responses were compared with six patients who were amenorrhoeic but had normal serum prolactin levels and absent positive feedback to oestrogen. The increased outputs of oestrogens were similar in the two groups. In the hyperprolactinaemic group 5 out of 16 subjects showed evidence of ovulation whilst the remainder showed a secondary failure of response. Six subjects who failed to ovulate were treated with clomiphene and human chorionic gonadotrophin (HCG) and ovulations were induced in 31 out of 34 treatment cycles but no pregnancies were achieved. The responses to clomiphene therapy in the hyperprolactinaemic subjects were compared to the assessment of positive feedback mechanisms by means of oestrogen provocation and oestrogen amplification tests and good correlation was obtained. Only those with evidence of positive feedback to these tests were likely to ovulate on clomiphene.

Amenorrhea↗
PubMed1978

Oestrogen amplification of LH-RH response in the polycystic ovary syndrome and response to clomiphene.

An LH-RH test was performed before and 44 and 92 h after treatment with 2.5 mg oestradiol benzoate in 17 patients with a diagnosis of polycystic ovarian (PCO) disease. The responses were compared with the same tests performed on ten normal subjects during the early follicular phase of their menstrual cycles (days 4--6). Patients were divided into two groups on the basis of their LH responses to LH-RH. In Group A (seven patients) the response at 92 h was greater than at 44 h as in the normal subjects, but in Group B (ten patients) the response at 44 h was greater than at 92 h. Basal serum hormone values were similar in the two groups except for androgens and oestrone, which were significantly (P less than 0.01) higher in Group B patients. There was a negative correlation between the basal androgen and oestrone concentrations and the LH and FSH amplifications at 92 h in all PCO patients. The ratios of the basal concentrations of LH to FSH and the ratios of the highest levels of each achieved during the basal LH-RH test, were significantly higher in the two groups of patients when compared to controls (P less than 0.01). The test is of value in predicting the subsequent responsiveness to clomiphene. All patients in Group A showed evidence of ovulation following treatment with 100 mg clomiphene for 5 days, but only one of Group B responded in this way.

Adult↗
PubMed1978

Sex hormone levels and gonadotrophin release in premature ovarian failure.

Premature ovarian failure was studied in ten women under the age of 30; eight had an ovarian biopsy and five of these showed primordial follicles. Plasma levels of oestradiol and progesterone were similar to the follicular phase of a normal menstrual cycle, but in eight patients cervical smears showed a cornification index of less than one per cent. Levels of both androgens and of sex hormone binding globulin capacity were generally normal. Administration of LH-RH caused a release of FSH which was similar to post menopausal women and higher than both. Two patients were treated with exogenous gonadotrophins without effect.

Adolescent↗
PubMed1978

Response of acromegaly to long term bromocriptine therapy: a biochemical and clinical assessment.

The long term effects of bromocriptine in 12 acromegalics treated for a mean duration of 10.2 months are reported. Seven showed a significant (P less than 0.05) and sustained fall in serum immunoreactive growth hormone (GH) levels throughout 24 h, 6 of whom had a 50% or greater reduction in mean circulating GH during glucose tolerance testing. Only one patient had mean serum GH levels throughout the day suppressed to normal (less than 5 mIU/l) but 3 had suppression of mean serum GH during GTT to normal or very near normal (less than 10 mIU/l). The effective dose was 20 mg daily. Only 4 patients reported any improvement in soft tissue swelling and acral features, which was unrelated to the GH response. Possible reasons for the discrepancy between clinical and biochemical responses are discussed. In 9 of the 12 patients bromocriptine was discontinued and pituitary ablative therapy offered. Three out of 4 patients who underwent trans-sphenoidal hypophysectomy had mean GH levels during GTT reduced to less than 7 mIU/l. In the three who continued bromocriptine treatment GH suppression was maintained at less than 10 mIU/l for up to 3 years but with little change in acral features. Although bromocriptine is safe and was well tolerated it is not as effective as existing forms of pituitary ablative therapy and should be reserved for those cases where ablation is contraindicated or unsuccessful.

Acromegaly↗
PubMed1977

Recurrent breast cancer treated with the antioestrogen tamoxifen: correlation between hormonal changes and clinical course.

Forty-five post-menopausal women with recurrent breast cancer were treated with the antioestrogen, tamoxifen, 20 mg twice daily. Clinical assessment after 12 weeks indicated that 18 (40%) showed some remission. Gonadotrophins were suppressed within two weeks to relatively constant concentrations within the post-menopausal range, responses to luteinising hormone-releasing hormone (LH-RH) did not change, and androgen concentrations remained within the normal range in all patients. Oestradiol concentrations rose steadily only in women in whom treatment failed. Serum prolactin concentrations were raised in 18 out of the 44 (41%) patients in whom they were measured; 13 of these did not respond to treatment. Treatment did not change the average prolactin concentration when this was within the normal range, but it significantly reduced prolactin concentrations in hyperprolactinaemic patients--within two weeks (P less than 0-01) in those who responded well and by six weeks (P less than 0-05) in those who showed no remission. Among patients with normal prolactin values the release of prolactin after thyrotrophin-releasing hormone was significantly greater in those with no remission than in those who responded to tamoxifen. Responses in those with hyperprolactinaemia were reduced to about half the control values, and again this change occurred faster in those who were successfully treated. Patients therefore seem to have a better chance of responding to anti-oestrogen treatment if prolactin secretion is low.

Androgens↗
PubMed1977

Hormonal effects of tamoxifen in oligospermic men.

The hormonal effects of tamoxifen (10 mg daily for 6 months) have been studied in nine men with oligospermia. Basal concentrations of serum LH (1-7 +/- 0-1 (S.E.M.) i.u./l) increased to a maximum of 4-1 +/- 1-3 i.u./l (P less than 0-001) after 6 months, and FSH rose from 4-9 +/- 1-0 to a maximum of 7-7 +/- 1-3 i.u./l after 4 months of treatment (P less than 0-01). The response to luteinizing hormone releasing hormone (LH-RH) was studied at monthly intervals. Sums of increments of serum LH increased from 35 +/- 4 to 92 +/- 17 i.u./l at 4 months (P less than 0-001) and of FSH from 14 +/- 3-4 to 23 +/- 3-5 i.u./l at 4 months (P less than 0-01). Basal serum androgens rose from 25 +/- 2-7 to 38 +/- 2-4 nmol/l after 4 months of treatment (P less than 0-05), and serum oestradiol-17beta increased from 185 +/- 25 to 631 +/- 90 pmol/l by 6 months (P less than 0-001). No significant changes occurred in sperm counts. Five normal men acted as controls: they were given tamoxifen for 1 week. No significant changes were observed in serum LH, FSH or release of these hormones following administration of LH-RH. Serum androgens and oestrogens however, increased significantly by day 4 of treatment (P less than 0-05).

Androgens↗
PubMed1976

A simple method for counting antibody bound labelled steroids.

A simple method is described for the counting of tritiated antibody-bound steroid after acidification and extraction into a toluene based scintillant. The resulting count rate is stable and quenching is minimal. The method give improved count rates when compared with methods employing scintillants containing methanol, dioxane, or Triton and compares favourably with methods involving pre-heating of antibody-bound steroid or extraction of free steroids after the addition of ammonium sulphate. A specific antibody for estradiol has been used to illustrate the application of the technique to antibody titration curves and standard curves.

Animals↗
PubMed1976

Modification by sex steroids of LHRH response in the polycystic ovary syndrome.

Exogenously administered oestradiol or progesterone was found to induce augmentation of LH and FSH release in response to LHRH administration in patients with the polycystic ovary (PCO) syndrome. The effect of oestradiol upon LH release in the patients was significantly less than the augmented release induced in normal women (P less than 0-02). In contrast, progesterone induced a significantly greater LH release in PCO patients than normal women studied during the early follicular phase (P less than 0-001) but less than that in normal women studied during the mid-follicular phase of the cycle (P less than 0-01). The effects on FSH release in the PCO patients were less marked but similar to those in normal women with comparable basal steroid levels. The results suggest that both oestradiol and progesterone can modify the hypothalamic-pituitary axis in the PCO syndrome in a manner similar to that observed in normal women and a failure of these 'positive feedback' mechanisms does not appear to be the cause of the ovulatory deficiency in this syndrome.

Clinical Trials as Topic↗