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Biomedical subjects

S Franks

Publications and source records attributed to S Franks.

At least 127 records · Page 7Linked to original sources
PubMed1989

Diet-induced changes in sex hormone binding globulin and free testosterone in women with normal or polycystic ovaries: correlation with serum insulin and insulin-like growth factor-I.

The purpose of this study was to investigate the effect of calorie restriction on serum concentrations of sex hormone binding globulin (SHBG) in women with normal or polycystic ovaries (PCO) and to examine the possible role of insulin and insulin-like growth factor-I (IGF-I) in mediating changes in SHBG levels. Six normal subjects with mean (SD) body mass index (BMI) 25.5 (2.2) and five subjects with PCO (BMI 36.1 (3.7)) were studied before and after 2 or (PCO only) 4 weeks of a very low calorie diet (330 kcal/day; Cambridge Diet). In both normal women and patients with PCO there was a twofold increase in SHBG concentrations after 2 weeks and this was sustained in the PCO subjects for a further 2 weeks. The rise in SHBG was accompanied by a fall in free testosterone concentrations. There were parallel changes in serum insulin and IGF-I concentrations which decreased during the diet and there were significant negative correlations of SHBG with insulin in both normal subjects (r = -0.62) and women with PCO (r = -0.60). In addition, serum concentrations of an insulin-dependent small molecular weight (34 kDa) binding protein for IGF-I (IGF-BPI) increased significantly during dieting in both groups and were negatively correlated with serum insulin (controls, r = -0.56; PCO, r = -0.68) and positively correlated with serum SHBG levels (controls, r = 0.69; PCO, r = 0.63). In summary, these data indicate that in both normal subjects and those subjects with PCO, calorie restriction results in a highly significant increase in SHBG concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Diet, Reducing↗
PubMed1989

Medroxyprogesterone acetate in the treatment of pelvic pain due to venous congestion.

Ovarian function was suppressed with 30 mg of medroxyprogesterone acetate, daily for 6 months, in 22 women with lower abdominal pain due to pelvic congestion. There was reduction in pelvic congestion demonstrated by venography in 17 of the 22 women, and in 16 this was associated with induction of amenorrhoea which suggests that effective ovarian suppression is an important component of successful treatment. In the 17 women who showed a reduction in venogram score, the median change in pain score was 75% compared with only 29% in the five women with no change in venogram score (P less than 0.01). This significant association between reduction in pelvic congestion and pain indicates that pelvic congestion is likely to be the cause of pain in these women and that treatment with medroxyprogesterone acetate could be of value.

Adult↗
PubMed1989

A randomized controlled trial of medroxyprogesterone acetate and psychotherapy for the treatment of pelvic congestion.

The value of medroxyprogesterone acetate (MPA) and of psychotherapy in the treatment of lower abdominal pain due to pelvic congestion was assessed in a randomized controlled trial. Eighty-four women with abnormal pelvic venography were assigned to one of four treatment groups: MPA alone, MPA plus psychotherapy, placebo alone, and placebo plus psychotherapy. Women were treated for 4 months and thereafter followed up regularly for 9 months with pain assessments, pelvic ultrasound scanning, and hormone measurements. During treatment, MPA showed a significant benefit in terms of a reduction in visual analogue scale pain score, with 73% of women reporting at least 50% improvement compared with 33% of those treated with placebo. At 9 months after the end of therapy there was no overall significant effect of MPA or psychotherapy, but there was an interaction between MPA and psychotherapy, with 71% of the women in this group showing a greater than or equal to 50% reduction in pain score. Therapy with MPA is a useful first-line therapy for women with pain associated with demonstrable pelvic congestion.

Adult↗
PubMed1989

Delayed puberty.

The pattern of physical development which occurs during normal puberty is described with reference to the underlying changes in hormone secretion. A summary of the causes of delayed puberty is given and the authors suggest a suitable protocol for investigation and management of this disorder.

Adolescent↗
PubMed1988

Improvement of in vitro fertilisation after treatment with buserelin, an agonist of luteinising hormone releasing hormone.

Treatment with buserelin, an agonist of luteinising hormone releasing hormone, and human menopausal gonadotrophin was compared with the conventional treatment of clomiphene citrate and human menopausal gonadotrophin in the outcome of in vitro fertilisation. Seventy seven infertile women had 83 cycles of treatment with buserelin and human menopausal gonadotrophin, and concurrently another 328 infertile women were treated with clomiphene citrate and human menopausal gonadotrophin. Seven (8%) cycles were cancelled owing to inadequate super-ovulation or ovarian hyperstimulation in the women receiving buserelin and 103 (31%) were cancelled because of poor follicular development in those receiving clomiphene citrate. The mean number of oocytes recovered was significantly higher with buserelin (9.5 (SD 4.5) v 5.5 (2.2)) as was the mean number of embryos obtained (4.3 (2.4) v 2.9 (1.7)). Significantly more women who had an embryo transfer became clinically pregnant after treatment with buserelin (53% (30/57) v 30% (48/159), or 36% v 14% of treatment cycles). Altogether 33% (10) of pregnancies in women treated with buserelin were multiple compared with 23% (11) in those treated conventionally. Of the 17 completed pregnancies in women treated with buserelin, 11 resulted in the birth of live babies (eight singletons, two sets of twins, and one set of triplets) and six failed, five before 12 weeks' gestation and one at 22 weeks. The 13 continuing pregnancies (32 weeks) were eight singletons, two sets of twins, and three sets of triplets. Of the 48 completed pregnancies in women treated with clomiphene citrate, 35 resulted in the birth of live babies (26 singletons, five sets of twins and four sets of triplets) and 13 failed, eleven before 12 weeks' gestation and two by 27 weeks. Buserelin increased the chance of pregnancy after in vitro fertilisation compared with conventional treatment, but the risk of multiple pregnancy may be increased.

Buserelin↗
PubMed1988

Polycystic ovaries--a common finding in normal women.

The prevalence of polycystic ovaries (PCO) in normal women of reproductive age was determined by pelvic ultrasound scanning of 257 volunteers who considered themselves to be normal and who had not sought treatment for menstrual disturbances, infertility, or hirsutism. All women had completed a menstrual history questionnaire. 99 women were on oral contraceptives at the time of the study. Of the 158 subjects who were not on oral contraceptives 18% had irregular cycles. 116 (73%) women had normal ovaries and 36 (23%) had PCO. 5 women had multifollicular ovaries and 1 had small, unstimulated ovaries. Only 1 woman with normal ovaries had an irregular menstrual cycle. Of the women with PCO, 76% had irregular cycles, and 6 of the 8 with regular cycles were hirsute. Women with and those without PCO differed in distribution of serum LH concentrations although the median values were similar. 25% of women with PCO had LH concentrations which exceeded the upper limit of the normal range. Thus PCO are common in normal women. Some of these women may have clinical and biochemical markers of PCO, which suggest that PCO in women who consider themselves to be normal is part of the same clinical spectrum as the classic Stein-Leventhal syndrome.

Adolescent↗
PubMed1988

Pulsatile infusion of gonadotrophin releasing hormone (GnRH): investigative and therapeutic applications.

Normal gonadotrophin secretion, and therefore normal ovarian function, depend on delivery to the pituitary of the hypothalamic neuropeptide gonadotrophin releasing hormone (GnRH) in a pulsatile pattern. In the mid-follicular phase of the menstrual cycle, for example, discrete pulses of luteinizing hormone (LH) can be observed at approximately 90 min intervals. Many disorders of ovulation are caused by abnormalities of this natural pulsed signal. We have developed and used a small portable infusion pump to deliver GnRH to women with hypothalamic amenorrhoea; our studies, and those of other groups, have shown that successful ovulation and pregnancy result from such treatment. The results of treatment at St Mary's Hospital show that 16 women with hypogonadotrophic amenorrhoea received a total of 31 cycles of treatment with pulsatile GnRH; 25 (81%) of these cycles were ovulatory and 11 of the 14 women who were trying to conceive became pregnant. There was only one multiple pregnancy (twins).

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↗
PubMed1988

Anti-androgens in gynaecological practice.

Hirsutism and acne in women are common distressing problems. Unwanted hair growth, acne and seborrhoea result from the action of androgens on the skin. Such effects depend not only on increased androgen production by the ovary or adrenal gland but also on the bioavailability of androgen to peripheral tissues. This in turn is related to transport of androgens in plasma by specific binding proteins and to peripheral metabolism of testosterone and androstenedione to their more potent 5 alpha-reduced derivatives. An effective anti-androgen is one which blocks the androgen receptor-mediated actions of testosterone and DHT on skin. CPA, the treatment of choice in the UK, is a potent androgen receptor-blocking steroid which also has progestational properties. When combined with ethinyloestradiol it also suppresses ovarian function, thus reducing androgen production, and provides effective contraception.

Acne Vulgaris↗
PubMed1988

Mechanism and management of ovulatory failure in women with polycystic ovary syndrome.

Polycystic ovary syndrome is the most important cause of chronic anovulation. In women who fail to respond to clomiphene, low-dose FSH given in a step-wise fashion can induce normal follicular growth and ovulation. The failure of the action of endogenous FSH in these women may be related to reduced biological activity of circulating FSH, but may also involve inhibition of its action at follicular level by polypeptide growth factors such as EGF.

Androgens↗
PubMed1988

Serum androstanediol glucuronide concentrations in normal and hirsute women and patients with thyroid dysfunction.

There is currently much interest in measurements of 5 alpha-androstane-3 alpha, 17 beta-diol glucuronide (AdiolG) as a marker of peripheral androgen metabolism. We have therefore developed an assay to measure serum AdiolG levels and report that mean concentrations in hirsute (2.9 +/- 1.9 nmol/l, mean +/- SD, n = 15) and non-hirsute (1.9 +/- 0.6 nmol/l, n = 7) women with polycystic ovaries do not differ significantly from concentrations in normal women (2.2 +/- 0.8 nmol/l, n = 20). However, a correlation was found between serum AdiolG levels and Body Mass Index (r = 0.48, P less than 0.05) for women with polycystic ovaries, suggesting that weight may be an important factor in determining concentrations of this steroid conjugate. Serum AdiolG levels were significantly reduced in hypothyroid women (0.6 +/- 0.4 nmol/l, n = 5) and women receiving oral contraceptive therapy (0.6 +/- 0.4 nmol/l, n = 28) but increased in hyperthyroid women (4.0 +/- 0.6 nmol/l, n = 5). The results from this study do not support the hypothesis that serum AdiolG levels provide a marker of peripheral androgen metabolism in hirsute women and show that it is essential to exclude from such investigations any women with thyroid abnormalities or receiving oral contraceptive therapy.

Adult↗
PubMed1988

Reduced frequency of luteinizing hormone pulses in women with weight loss-related amenorrhoea and multifollicular ovaries.

We have studied pulsatile secretion of LH in 10 women with secondary amenorrhoea and multifollicular ovaries (MFO). This group of patients have a history of mild to moderate, or partially recovered weight loss. They have normal basal LH concentrations but evidence of oestrogen deficiency suggesting a hypothalamic abnormality of gonadotrophin regulation. The results of gonadotrophin pulse analysis were compared with those in normal women during the early follicular phase of the cycle. The mean LH concentration during the 8 h study (5.0 +/- 0.9 [SD] U/l) was not significantly different from that in normal women (5.7 +/- 2.5). There was no difference between the groups in mean LH pulse amplitude (2.1 +/- 0.5 in MFO; 2.2 +/- 1.3 in normal women). The frequency of LH pulses was, however, significantly lower in women with MFO (2.8 +/- 1.6 vs 4.8 +/- 1.5, P less than 0.05). Two women with MFO had LH pulses of normal frequency. One subsequently developed a normal pattern of ovarian follicles. The other showed a sleep-related rise in LH concentrations during a 24 h profile which was similar to the pattern of gonadotrophin secretion normally observed during late puberty. These results show that women with MFO have a hypothalamic disturbance of gonadotrophin regulation with slowing of LH pulses without a diminution of pulse amplitude.

Amenorrhea↗
PubMed1988

Serum 11 beta-hydroxyandrostenedione as an indicator of the source of excess androgen production in women with polycystic ovaries.

Serum 11 beta-hydroxyandrostenedione levels (11-OHA) were measured in normal women and women with polycystic ovaries (PCO) to assess their value in localizing the source of excessive androgen production in women with PCO. Serum 11-OHA was undetectable (less than 1.5 nmol/L) in an adrenalectomized woman, a woman with 11-hydroxylase deficiency, and a woman receiving chronic dexamethasone therapy, confirming the specificity of the antiserum used in this study. Serum 11-OHA concentrations were similar in normal women [mean, 5.0 +/- 2.3 (+/- SD) nmol/L] and women with PCO (5.0 +/- 2.1 nmol/L); serum androstenedione concentrations were increased in women with PCO. Thus, the ratio of androstenedione to 11-OHA was significantly higher (P less than 0.001) in women with PCO (2.0 +/- 0.7) than in normal women (1.1 +/- 0.5). Serum 11-OHA levels after adrenal suppression or stimulation were similar in women with PCO who had an ovulatory response and those who failed to ovulate after clomiphene administration. Administration of dexamethasone (1 mg) and injection of ACTH (250 micrograms) were associated with marked suppression and subsequent stimulation of serum 11-OHA levels in both normal women and women with PCO, and the responses were similar in the two groups. Also, the hour to hour and diurnal variations in serum 11-OHA were similar to those of androstenedione and cortisol during a 24-h period, indicating the adrenal origin of 11-OHA. Our finding of similar serum 11-OHA levels in the presence of increased serum androstenedione levels in women with PCO supports the concept that the ovary is the major source of excess androgen production in women with PCO.

Adrenal Glands↗
PubMed1988

Hydrolysis of phosphatidylinositol by human endometrium: modulating effects of steroids on arachidonic acid and 1,2-diacylglycerol release.

Phospholipase C and 1,2-diacylglycerol lipase activities were demonstrated in human endometrium using 1-stearoyl-2-[1-14C]arachidonyl phosphatidylinositol as substrate. Phosphatidylinositol is hydrolysed by phospholipase C to inositol phosphates and to 1,2-diacylglycerol which is then further metabolized by 1,2-diacylglycerol lipase to release free arachidonic acid. In the present study the radiolabelled products formed (1,2-diacylglycerol and arachidonic acid) were measured following chloroform/methanol extraction and thin-layer chromatography. Phospholipase C activity was calcium dependent and optimal at pH 5.0-5.5 and 7.5; 1,2-diacylglycerol lipase activity was also calcium dependent, with an optimum pH of 5.5. A significant increase in 1,2-diacylglycerol production was stimulated by steroid sulphates. Pregnenolone sulphate, oestrone sulphate, testosterone sulphate and dehydroepiandrosterone sulphate stimulated 4, 3.2-, 1.8- and 2.6-fold increases in release respectively. Oestradiol sulphate stimulated a 25% increase in diacylglycerol release which was not significantly different from the control value. Progesterone stimulated a fourfold increase but other free steroids had no effect. Arachidonic acid release was increased in the presence of oestradiol sulphate, oestrone and oestradiol but reduced by oestrone sulphate, dehydroepiandrosterone sulphate, progesterone, dehydroepiandrosterone and, to a lesser extent, by pregnenolone sulphate and testosterone sulphate. 5-Androstene-3 beta,17 beta-diol had no effect on the liberation of either product. This study demonstrates a potential route for the liberation of arachidonic acid from phosphatidylinositol in human endometrium. The opposing effects of steroids on phospholipase C and 1,2-diacylglycerol lipase activity could be important in regulating the release of arachidonic acid by this pathway.

Arachidonic Acids↗
PubMed1988

Inhibition of phospholipase A2 isoenzymes in human endometrium by mefenamic acid and indomethacin: modulation by calcium ions.

The inhibition of endometrial phospholipase A2 activity by the non-steroidal anti-inflammatory agents mefenamic acid and indomethacin was studied over the concentration range 1 mmol/1-0.1 mumol/l. Both phospholipase A2 type 1 (a calcium-dependent enzyme) and phospholipase A2 type 2 (a calcium-independent enzyme) were inhibited by mefenamic acid, but the magnitude of the inhibition was dependent on calcium concentration. Phospholipase A2 type 1 was inhibited 50% by 10 mumol mefenamic acid/l in the presence of 1.25-5 mmol calcium/l, but a concentration of 2.2 mmol mefenamic acid/l was required for 50% inhibition in the absence of calcium. On the other hand, phospholipase A2 type 2 was inhibited 50% by 22 mumol mefenamic acid/l in the absence of calcium and by 100 mumol mefenamic acid/l in the presence of calcium (2.5 mmol/l). Although indomethacin was a less effective inhibitor of phospholipase A2 activity, a similar relationship with calcium was demonstrated. However, indomethacin also had a stimulatory effect on phospholipase A2 type 1 activity in the absence of calcium. Our findings suggest that the two endometrial enzymes may be inhibited by different mechanisms and that the dependence of the enzyme on calcium for activation may be a contributing factor.

Calcium↗
PubMed1988

The activity of calcium dependent and calcium independent phospholipase A2 in normal endometrium and in endometrium from women suffering from menorrhagia and polycystic ovary syndrome.

The activity of 2 phospholipase A2 enzymes, PLA2(i) and PLA2(ii) was measured in endometrium in women with regular menstrual cycles without evidence of pathology and in those complaining of menstrual disturbances. There was a significant 4-fold increase in PLA2(i) activity in secretory phase endometrium (mean +/- SD: 32.7 +/- 9.5 pmol per mg protein/minute) compared to that of the proliferative and menstrual phases (9.5 +/- 4.9 and 6.1 +/- 2.6 pmol per mg protein/minute, respectively) but PLA2(ii) activity was variable and not related to the stage of the cycle (range: 4.0-97.0, 18.7-110.3 and 0.1-85.5 pmol per mg protein/minute for proliferative, secretory and menstrual phases, respectively). There was no significant difference between normal subjects and those with menorrhagia with respect to the mean activities of either isoenzyme at any stage of the cycle. Women with polycystic ovary syndrome (PCO) had markedly higher endometrial PLA2(ii) activity than normal subjects. The evidence of this study suggests that PLA2(ii) is not implicated in unexplained menorrhagia, but our preliminary findings indicate that the high level of PLA2(ii) activity found in the endometrium of women with PCO might be a marker of abnormal endometrial function.

Adult↗