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Franks S, Hamilton-Fairley D, Sagle M, et al., 1993, Low-dose gonadotropin therapy in polycystic ovarian syndrome., Ann N Y Acad Sci, Vol: 687, Pages: 301-304, ISSN: 0077-8923
MASON HD, MARGARA R, WINSTON RML, et al., 1993, INSULIN-LIKE GROWTH FACTOR-I (IGF-I) INHIBITS PRODUCTION OF IGF-BINDING PROTEIN-1 WHILE STIMULATING ESTRADIOL SECRETION IN GRANULOSA-CELLS FROM NORMAL AND POLYCYSTIC HUMAN OVARIES, JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, Vol: 76, Pages: 1275-1279, ISSN: 0021-972X
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- Citations: 54
BONNEY RC, BEESLEY JS, RAHMAN C, et al., 1993, ARACHIDONIC-ACID RELEASE AND INOSITOL LIPID-METABOLISM IN RESPONSE TO BRADYKININ AND RELATED PEPTIDES IN HUMAN ENDOMETRIAL CELLS-INVITRO, PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS, Vol: 48, Pages: 253-260, ISSN: 0952-3278
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- Citations: 15
MASON HD, WILLIS D, HOLLY JMP, et al., 1992, INHIBITORY EFFECTS OF INSULIN-LIKE GROWTH FACTOR-BINDING PROTEINS ON STEROIDOGENESIS BY HUMAN GRANULOSA-CELLS IN CULTURE, MOLECULAR AND CELLULAR ENDOCRINOLOGY, Vol: 89, Pages: R1-R4, ISSN: 0303-7207
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- Citations: 58
Robinson S, Chan SP, Spacey S, et al., 1992, Postprandial thermogenesis is reduced in polycystic ovary syndrome and is associated with increased insulin resistance., Clin Endocrinol (Oxf), Vol: 36, Pages: 537-543, ISSN: 0300-0664
OBJECTIVE: In order to investigate the possible causes and effects of obesity in polycystic ovary syndrome resting energy expenditure, postprandial thermogenesis and insulin resistance were measured in 14 polycystic ovary syndrome subjects and in 14 controls. DESIGN: A cross-sectional study of a selected group of patients was performed. PATIENTS: Seven of the PCOS subjects were obese and seven lean. Controls were individually matched for age, race, weight, body mass index (BMI) lean body mass and percentage fat. The obese, but not lean, polycystic ovary syndrome subjects had a greater waist:hip ratio than controls (median (range) obese PCOS 0.865 (0.823-0.960) vs obese control 0.804 (0.823-0.940), P less than 0.025). MEASUREMENTS: Metabolic rate was measured by continuous indirect calorimetry and insulin sensitivity was assessed by a short insulin tolerance test. RESULTS: The resting energy expenditure (REE) was similar in PCOS subjects and controls (median (range), 6796 (5489-7774) vs 6833 (4893-8492) kJ/day). REE correlated with LBM in the PCOS group (r = 0.83, P less than 0.00) and the control group (r = 0.82, P less than 0.001). Postprandial thermogenesis was reduced in polycystic ovary syndrome (obese: median 45.4 (range 33.6-100.0) vs 86.5 (67.2-109.2) kJ (P less than 0.05); lean: 79.4 (73.5-108.4) vs 89.9 (76.0-109.2) kJ (P less than 0.05). Fasting insulin (9.7 +/- 3.6 vs 4.4 +/- 0.8 mU/l, P less than 0.05) and postprandial incremental insulin rise (163 +/- 31 vs 116 +/- 15 mU/l, P less than 0.025) were higher in polycystic ovary syndrome. Insulin sensitivity was reduced in polycystic ovary syndrome (obese: median 136 (range 92-169) vs 173 (109-225) mumol/l/min (P less than 0.05); lean: 161 (138-225) vs 194 (161-253) mumol/l/min (P less than 0.05)). The reduction in insulin sensitivity correlated with the reduced postprandial thermogenesis in the polycystic ovary syndrome group (r = 0.75, P less than 0.01). CONCLUSION: These results confirm previous reports o
BONNEY RC, WATSON H, BEESLEY JS, et al., 1992, ENDOMETRIAL PHOSPHOLIPASE-A2, POLYCYSTIC OVARIES AND PELVIC PAIN, BRITISH JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Vol: 99, Pages: 486-491, ISSN: 0306-5456
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- Citations: 5
HAMILTONFAIRLEY D, KIDDY D, WATSON H, et al., 1992, ASSOCIATION OF MODERATE OBESITY WITH A POOR PREGNANCY OUTCOME IN WOMEN WITH POLYCYSTIC-OVARY-SYNDROME TREATED WITH LOW-DOSE GONADOTROPIN, BRITISH JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Vol: 99, Pages: 128-131, ISSN: 0306-5456
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- Citations: 198
KIDDY DS, HAMILTONFAIRLEY D, BUSH A, et al., 1992, IMPROVEMENT IN ENDOCRINE AND OVARIAN-FUNCTION DURING DIETARY-TREATMENT OF OBESE WOMEN WITH POLYCYSTIC-OVARY-SYNDROME, CLINICAL ENDOCRINOLOGY, Vol: 36, Pages: 105-111, ISSN: 0300-0664
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- Citations: 632
Bonney RC, Beesley JS, Franks S, 1991, Release of arachidonic acid from human endometrial cells in culture mediated by calcium ionophore (A23187) or fluoride., J Reprod Fertil, Vol: 93, Pages: 449-460, ISSN: 0022-4251
Primary cultures of endometrial glands and stromal cells were labelled with [14C]-arachidonic acid for 4 h before exposure to either the calcium ionophore, A23187 (which activates phospholipase A2 (PLA2) by increasing intracellular calcium concentrations) or sodium fluoride (which activates a G-protein). Calcium ionophore (0.5-50 mumol/l) stimulated a dose- and time-dependent release of arachidonic acid from endometrial glands. Incubation with ionophore (10 mumol/l) for 1 h released 22% of the incorporated arachidonic acid. There was a corresponding decrease in phospholipids and no loss from triglycerides. Stromal cells were unresponsive to ionophore. Fluoride (10 mmol/l) stimulated a release of arachidonic acid from stromal cells and endometrial glands (6.5% of the total arachidonic acid incorporated). In stromal cells, arachidonic acid was released from triglycerides in Day-1 cultures and from phospholipids in Day-2 cultures. In both Day-1 and Day-2 cultures of endometrial glands, arachidonic acid was released from phospholipids, but not from triglycerides. Among the phospholipids, phosphatidylcholine was always the major source of arachidonic acid. Arachidonic acid release from endometrial glands and stromal cells may be mediated by activation of PLA2 (or phospholipase C) via a G-protein, but in glands calcium ionophore may have a direct effect on PLA2. The response to calcium ionophore may reflect the differences in calcium requirements of the two endometrial PLA2 isoenzymes.
Franks S, Kiddy DS, Hamilton-Fairley D, et al., 1991, The role of nutrition and insulin in the regulation of sex hormone binding globulin., J Steroid Biochem Mol Biol, Vol: 39, Pages: 835-838, ISSN: 0960-0760
In an analysis of 263 women with polycystic ovary syndrome (PCOS), 91 (35%) of whom were obese (body mass index greater than 25 kg/m2), it was found that obese women with PCOS were more likely to be anovulatory and had a higher prevalence of hirsutism than the non-obese subgroup. Although serum concentrations of gonadotrophins, androstenedione and total testosterone were similar in obese and lean women with PCO, sex hormone binding globulin (SHBG) levels were significantly lower, and free testosterone correspondingly higher, in obese women. Serum concentrations of SHBG were inversely correlated with those of both fasting and glucose-stimulated insulin. A short-term, very-low-calorie diet resulted in a 2-fold increase in SHBG which was mirrored by a fall in serum insulin. Similar biochemical changes were also observed during a long-term (6-7 months) 1000 kcal diet and were associated with an improvement of menstrual function and fertility. This encourages the view that calorie restriction has an important part to play in the management of obese women with PCOS.
Hamilton-Fairley D, Kiddy D, Watson H, et al., 1991, Low-dose gonadotrophin therapy for induction of ovulation in 100 women with polycystic ovary syndrome., Hum Reprod, Vol: 6, Pages: 1095-1099, ISSN: 0268-1161
Women with anovulation due to polycystic ovary syndrome are likely to develop multiple follicles during gonadotrophin therapy and therefore have a high risk of multiple pregnancy. We have developed a low-dose regimen for use in these women; 100 women with clomiphene-resistant polycystic ovary syndrome were treated. Ninety-five of the women ovulated at least once, 72% of the 401 cycles induced were ovulatory and the majority (73%) of these were uni-ovulatory. The overall cumulative conception rate was 55% at 6 months with only two multiple pregnancies. The rate of early pregnancy loss was 32%, which is similar to that reported by other groups. The prevalence of complications was low with no cases of severe hyperstimulation and less than 5% of cycles were abandoned because of development of multiple follicles. Analysis of baseline and mid-follicular luteinizing hormone levels showed that a raised baseline and/or mid-follicular luteinizing hormone level was associated with a poor response to treatment, i.e. anovulation, ovulation but no conception, or early pregnancy loss. There were no successful pregnancies in the women whose luteinizing hormone levels were persistently raised during ovulatory cycles. Low-dose gonadotrophin therapy is a safe and effective method of inducing ovulation; it is associated with a high incidence of single follicular development and a very low multiple pregnancy rate.
SHARP PS, KIDDY DS, REED MJ, et al., 1991, CORRELATION OF PLASMA-INSULIN AND INSULIN-LIKE GROWTH FACTOR-I WITH INDEXES OF ANDROGEN TRANSPORT AND METABOLISM IN WOMEN WITH POLYCYSTIC-OVARY-SYNDROME, CLINICAL ENDOCRINOLOGY, Vol: 35, Pages: 253-257, ISSN: 0300-0664
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- Citations: 61
Franks S, 1991, The ubiquitous polycystic ovary., J Endocrinol, Vol: 129, Pages: 317-319, ISSN: 0022-0795
BONNEY RC, HIGHAM JM, WATSON H, et al., 1991, PHOSPHOLIPASE-ACTIVITY IN THE ENDOMETRIUM OF WOMEN WITH NORMAL MENSTRUAL BLOOD-LOSS AND WOMEN WITH PROVEN OVULATORY MENORRHAGIA, BRITISH JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Vol: 98, Pages: 363-368, ISSN: 0306-5456
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- Citations: 6
Sagle MA, Hamilton-Fairley D, Kiddy DS, et al., 1991, A comparative, randomized study of low-dose human menopausal gonadotropin and follicle-stimulating hormone in women with polycystic ovarian syndrome., Fertil Steril, Vol: 55, Pages: 56-60, ISSN: 0015-0282
Treatment with low-dose follicle-stimulating hormone (FSH) is associated with a high rate of ovulation in anovulatory women with polycystic ovarian syndrome (PCOS), but it is not clear whether the success of treatment is because of the use of pure FSH or the low dose of gonadotropin. We undertook a randomized controlled study to compare the effects of urinary FSH and human menopausal gonadotropin (hMG) using a low-dose regimen in 30 women with PCOS. Each subject received a maximum of three cycles of either FSH or hMG. Ovulation occurred in 75% of subjects and in 77% of cycles induced with FSH and in 94% of women, 85% of cycles of those treated with hMG. A single dominant follicle developed in 70% (FSH) and 65% (hMG) of cycles, respectively. Five singleton pregnancies occurred in each group. This study shows that low-dose FSH and hMG are equally successful in inducing ovulation, suggesting that the success of treatment depends on the low dose of gonadotropin used rather than the presence or absence of luteinizing hormone in the preparation.
FRANKS S, MASON HD, 1991, POLYCYSTIC-OVARY-SYNDROME - INTERACTION OF FOLLICLE-STIMULATING-HORMONE AND POLYPEPTIDE GROWTH-FACTORS IN ESTRADIOL PRODUCTION BY HUMAN GRANULOSA-CELLS, JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY, Vol: 40, Pages: 405-409, ISSN: 0960-0760
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- Citations: 16
Franks S, Kiddy D, Sharp P, et al., 1991, Obesity and polycystic ovary syndrome., Ann N Y Acad Sci, Vol: 626, Pages: 201-206, ISSN: 0077-8923
Our studies show that obese women with polycystic ovary syndrome are more likely to have hirsutism and menstrual disturbances than are lean women with PCOS. The most obvious biochemical differences between obese and lean women with PCOS is that SHBG concentrations are much lower in women with obesity. The SHBG levels are inversely related to insulin, and insulin has been shown to have a direct inhibitory action on SHBG secretion. Other factors, however, may contribute to the mechanism of the increased prevalence of hirsutism and anovulation in obese women with PCOS, such as a direct effect of insulin or increased activity of 5 alpha-reductase in peripheral tissues. Finally we have been able to show that weight reduction of more than 5% is associated with an improved biochemical profile and, importantly, with restoration of fertility.
Beesley JS, Franks S, Bonney RC, 1991, The steroidal regulation of arachidonic acid uptake by human endometrial stromal cells in culture., Adv Prostaglandin Thromboxane Leukot Res, Vol: 21B, Pages: 815-818, ISSN: 0732-8141
MASON HD, MARGARA R, WINSTON RML, et al., 1990, INHIBITION OF ESTRADIOL PRODUCTION BY EPIDERMAL GROWTH-FACTOR IN HUMAN GRANULOSA-CELLS OF NORMAL AND POLYCYSTIC OVARIES, CLINICAL ENDOCRINOLOGY, Vol: 33, Pages: 511-517, ISSN: 0300-0664
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- Citations: 77
MASON HD, MARTIKAINEN H, BEARD RW, et al., 1990, DIRECT GONADOTROPIC EFFECT OF GROWTH-HORMONE ON ESTRADIOL PRODUCTION BY HUMAN GRANULOSA-CELLS INVITRO, JOURNAL OF ENDOCRINOLOGY, Vol: 126, Pages: R1-R4, ISSN: 0022-0795
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- Citations: 153
Kiddy DS, Sharp PS, White DM, et al., 1990, Differences in clinical and endocrine features between obese and non-obese subjects with polycystic ovary syndrome: an analysis of 263 consecutive cases., Clin Endocrinol (Oxf), Vol: 32, Pages: 213-220, ISSN: 0300-0664
Two hundred and sixty-three women with ultrasound-diagnosed polycystic ovary syndrome were studied of whom 91 (35%) were obese (BMI greater than 25 kg/m2). Obese women with PCOS had a greater prevalence of hirsutism (73% compared with 56%) and menstrual disorders than non-obese subjects. Total testosterone and androstenedione concentrations in serum were similar in the two subgroups but SHBG concentrations were significantly lower, and free testosterone levels higher, in obese compared with lean subjects. In addition, concentrations of androsterone glucuronide, a marker of peripheral 5 alpha-reductase activity, were higher in obese than in non-obese women with PCOS. There were no significant correlations of either SHBG or free testosterone with androsterone glucuronide suggesting that obesity has independent effects on transport and on metabolism of androgen. There were no significant differences between the subgroups in either baseline gonadotrophin concentrations or the pulsatile pattern of LH and FSH secretion studied over an 8-h period. There was, however, an inverse correlation of FSH with BMI, but only in the obese subgroup. In conclusion, the increased frequency of hirsutism in obese compared with lean women with PCOS is associated with increased bio-availability of androgens to peripheral tissues and enhanced activity of 5 alpha-reductase in obese subjects. The mechanism underlying the higher prevalence of anovulation in obese women remains unexplained.
SINGH A, HAMILTONFAIRLEY D, KOISTINEN R, et al., 1990, EFFECT OF INSULIN-LIKE GROWTH FACTOR-TYPE-I (IGF-I) AND INSULIN ON THE SECRETION OF SEX-HORMONE BINDING GLOBULIN AND IGF-I BINDING-PROTEIN (IBP-I) BY HUMAN HEPATOMA-CELLS, JOURNAL OF ENDOCRINOLOGY, Vol: 124, Pages: R1-R3, ISSN: 0022-0795
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- Citations: 133
Bonney RC, Samih A, Franks S, 1990, Uptake, distribution and release of 3H-arachidonic acid from human endometrium., Prostaglandins Leukot Essent Fatty Acids, Vol: 39, Pages: 111-117, ISSN: 0952-3278
The lysophosphatide acyltransferase blocking agent ethylmercurisalicylate (merthiolate) was used to investigate the uptake and release of arachidonic acid from explants of human endometrium in short term tissue culture. Tissue explants were (a) incubated with 3H-arachidonic acid for 1-24 h in the presence or absence of 0.5-50 microM merthiolate, and (b) prelabelled with 3H-arachidonic acid for 18 h followed by incubation with or without 50 microM merthiolate for 1-24 h. Neutral lipids, phospholipids and arachidonic acid were separated by thin layer chromatography and uptake and release of 3H-arachidonic acid expressed as % total uptake. The triglyceride pool was the main target for arachidonic acid uptake. Incorporation increased from 9.1% at 1 h to 56.6% at 24 h. Uptake into phospholipids increased from 8.1% at 1 h to 19.6% at 24 h with phosphatidylcholine accounting for 3.8% and 8.8% respectively. Incubation with 50 microM merthiolate rapidly reduced uptake into triglycerides (to 1.8% at 1 h and 0.9% at 24 h), whereas the effect on uptake into phospholipids (5.9% at 1 h, 3.4% at 24 h) was much less marked. There was a dose related inhibition of arachidonic acid incorporation into both triglycerides and phospholipids, but a lower dose of merthiolate (1 microM) was required to reduce uptake into triglycerides than into phospholipids (5 microM). Uptake into mono- and diglycerides was low and unaffected by merthiolate. Incubation of prelabelled tissue with 50 microM merthiolate resulted in a 20% increase in the release of arachidonic acid from triglycerides and a corresponding accumulation of labelled monoglyceride.(ABSTRACT TRUNCATED AT 250 WORDS)
BONNEY RC, HIGHAM J, BEESLEY JS, et al., 1990, PHOSPHOLIPASES - A ROLE IN DYSFUNCTIONAL UTERINE BLEEDING, 1ST SYMP IN REPRODUCTIVE ENDOCRINE DISORDERS, Publisher: PARTHENON PUBLISHING GROUP LTD, Pages: 43-58
KIDDY DS, HAMILTONFAIRLEY D, SEPPALA M, et al., 1989, 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, CLINICAL ENDOCRINOLOGY, Vol: 31, Pages: 757-763, ISSN: 0300-0664
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- Citations: 166
Reginald PW, Adams J, Franks S, et al., 1989, Medroxyprogesterone acetate in the treatment of pelvic pain due to venous congestion., Br J Obstet Gynaecol, Vol: 96, Pages: 1148-1152, ISSN: 0306-5456
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.
Farquhar CM, Rogers V, Franks S, et al., 1989, A randomized controlled trial of medroxyprogesterone acetate and psychotherapy for the treatment of pelvic congestion., Br J Obstet Gynaecol, Vol: 96, Pages: 1153-1162, ISSN: 0306-5456
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.
Franks S, 1989, Polycystic ovary syndrome: a changing perspective., Clin Endocrinol (Oxf), Vol: 31, Pages: 87-120, ISSN: 0300-0664
POLSON DW, MASON HD, KIDDY DS, et al., 1989, LOW-DOSE FOLLICLE-STIMULATING-HORMONE IN THE TREATMENT OF POLYCYSTIC OVARY SYNDROME - A COMPARISON OF PULSATILE SUBCUTANEOUS WITH DAILY INTRAMUSCULAR THERAPY, BRITISH JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Vol: 96, Pages: 746-748, ISSN: 0306-5456
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- Citations: 22
Polson DW, Kiddy DS, Mason HD, et al., 1989, Induction of ovulation with clomiphene citrate in women with polycystic ovary syndrome: the difference between responders and nonresponders., Fertil Steril, Vol: 51, Pages: 30-34, ISSN: 0015-0282
To identify why some women with polycystic ovary syndrome (PCO) fail to respond to clomiphene citrate (CC), the authors have monitored the endocrine and ovarian response to CC 100 mg/day given for 5 days. Of 40 cycles studied in 27 women, 73% were ovulatory. In 8 of 9 anovulatory women, there was no follicular development despite a significant rise in serum gonadotrophin concentrations within 3 to 5 days of starting CC. There were no significant differences between the ovulatory and anovulatory groups in the peak response of either luteinizing hormone (LH) or follicle-stimulating hormone (FSH). The authors conclude that, in women with polycystic ovaries, the most common reason for the failure to ovulate is an absent ovarian response to an appropriate rise in serum FSH.
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