Metabolic effects of tibolone in postmenopausal women with non-insulin dependent diabetes mellitus.

OBJECTIVE: Postmenopausal women with non-insulin dependent diabetes (NIDDM) are frequently obese, hypertensive and hyperlipidaemic and hence at particular risk of coronary heart disease (CHD). They might therefore benefit from menopausal therapy. In view of the improvement in insulin sensitivity and the reduction in triglyceride levels induced by tibolone in healthy postmenopausal women we evaluated the effects of 12 months of tibolone on glycaemic control, serum insulin and lipid levels in postmenopausal women with NIDDM. DESIGN: A prospective 12 months before/after intervention study. PATIENTS: Fourteen postmenopausal women (mean age 58.14 +/- 1.25 years; mean duration of menopause 121.21 +/- 13.42 months; mean BMI: 26.55 +/- 0.97) with NIDDM (mean duration of diabetes 113.79 +/- 13.89 months). MEASUREMENTS: Fasting and postprandial blood glucose levels were assessed monthly, serum fructosamine, fasting and postprandial insulin every 3 months and serum lipids (total cholesterol, triglyceride, HDL-cholesterol and LDL-cholesterol) every 6 months. RESULTS: Changes in blood glucose, both fasting and postprandial, were not statistically significant during the treatment period. Serum fructosamine concentration increased significantly after 9 months. A significant decrease in fasting and postprandial insulin concentrations was observed after 9 months. A non-significant decrease was observed in total cholesterol, LDL cholesterol and triglyceride but no change in HDL cholesterol. Body weight did not change during the period of observation. CONCLUSION: A slight deterioration in glycaemic control, a fall in insulin concentration and no change in serum lipids were observed in women with NIDDM during 12 months treatment with tibolone.

Thyroid C cells of middle-aged rats treated with estradiol or calcium.

The structure and function of C cells of middle-aged female rats (14-months old) treated with estradiol dipropionate (EDP), calcium (Ca) or a combination of EDP+Ca were studied. A stereological method was used to determine the volume of calcitonin (CT)-immunoreactive C cells and their nuclei, and the relative volume density and mean number of the C cells per section were calculated. Serum levels of CT, osteocalcin, parathyroid hormone (PTH), and beta-estradiol were also measured. A significant decrease in body weight of the rats treated with EDP or EDP+Ca was observed. These treatments led to a significant decrease in cellular and nuclear volumes, relative volume density, and mean number of C cells per section, in comparison with the corresponding controls. A reduction of the serum level of CT, PTH, and osteocalcin was also recorded in EDP- and EDP+Ca-treated animals. No statistically significant differences between Ca- and vehicle-injected rats, with regard to all morphometric C cell parameters and biochemical values determined, were seen. However, a conspicuous degranulation of the C cells and decreased immunoreactivity for CT in the Ca-receiving group, which could be interpreted as the signs of increased activity of these cells, were noticed. This effect of Ca was also observed in rats injected with EDP and Ca in combination, when the inhibitory effect of EDP on C cell function was less noticeable than in the group treated with EDP alone.

Changes in prolactin levels with the menopause: the effects of estrogen/androgen and calcitonin treatment.

Prolactin levels were evaluated over a 2-year period in three groups of postmenopausal women: group A consisted of 35 untreated women distributed according to time since the menopause; group B consisted of 17 women on a combined estrogen/androgen preparation (Gynodian depot) intramuscularly at monthly intervals; and group C consisted of 12 women on 100 units of salmon calcitonin intranasally on alternate days and 1500 mg calcium daily. The control group (group D) consisted of 11 healthy premenopausal women. Serum prolactin, estradiol, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels were measured at the onset and at 6-month intervals over 24 months. Mean serum prolactin concentrations decreased significantly during the second postmenopausal year in untreated women p = 0.0001 and p = 0.0000 after 18 and 24 months, respectively) when compared to either the levels in premenopausal women or those at the beginning of the menopause (p = 0.0007). Neither combined estrogen/androgen nor calcitonin therapy significantly influenced prolactin levels which were similar throughout the observed period. In the group on a combined estrogen/androgen preparation, physiological estradiol concentrations together with a suppression of gonadotropins during the first 6 months of therapy were achieved. In women treated with intranasal salmon calcitonin, estradiol, FSH and LH levels were unchanged. Our results show that prolactin levels decrease significantly during the second year of the menopause. Neither combined estrogen/androgen, nor salmon calcitonin therapy had any effect on serum prolactin concentrations in postmenopausal women.

Cardiac flow velocity in women with the polycystic ovary syndrome.

OBJECTIVE: Women with the polycystic ovary syndrome (PCOS) often have several of the known risk factors for cardiovascular disease, including hyperinsulinaemia. We have therefore investigated variables of cardiac flow in young women with PCOS and related them to blood levels of reproductive hormones (LH, FSH, oestradiol and testosterone) and also of insulin. DESIGN: A prospective study. PATIENTS: Twenty-six young women with PCOS (mean age 22.8 +/- 0.9 years; mean BMI 23.0 +/- 0.8) and 11 healthy age matched women with regular ovulatory cycles (mean age 26.3 +/- 1.7 years; mean BMI 22.9 +/- 0.9). MEASUREMENTS: Cardiac flow was measured by pulsed wave Doppler echocardiography in the follicular phase of the cycle in controls and oligomenorrhoeic women; there was no special timing for amenorrhoeic women. The indicators assessed were: ejection fraction (EF), pre-ejection time (PEP), ejection time (ET), peak systolic flow velocity (PFV), acceleration time (AT), flow velocity integral (FVI), mean acceleration (MA), diastolic time (DT), early diastolic filling time (Ei), atrial filling time interval (Ai), peak velocity of the early diastolic filling (PE) and peak velocity of the atrial filling (PA). Serum LH, FSH, oestradiol, testosterone, SHBG and insulin concentrations were analysed by standard RIA. RESULTS: Significantly lower PFV (1.055 +/- 0.025 vs 1.242 +/- 0.054, P = 0.0006) and MA (17.06 +/- 0.57 vs 23.00 +/- 1.49, P = 0.0001) and longer AT (0.063 +/- 0.001 vs 0.056 +/- 0.004, P = 0.026) were found in women with PCOS as compared to age matched controls. Significant negative correlation between serum fasting insulin concentration and EF (r = -0.725, P = 0.002), PFV (r = -0.719, P = 0.0025), FVI (r = -0.654, P = 0.008) and MA (r = -0.757, P = 0.001) was observed in the 15 women with PCOS in whom insulin was measured. CONCLUSION: An inverse relation between serum fasting insulin level and left ventricular systolic outflow parameters suggests that insulin is associated with the decreased systolic flow velocity observed in women with PCOS.

Effect of recombinant human growth hormone treatment on insulin-like growth factor (IGF-I) levels in insulin-dependent diabetic patients.

Basal and recombinant human growth hormone (rhGH)-stimulated insulin-like growth factor (IGF-I) levels were studied in 19 insulin-dependent diabetic patients and 4 healthy subjects. Diabetic patients were divided according to glucagon test result into CpN (10 patients without residual beta cell activity) and CpP (9 patients with preserved beta-cell activity) and CpP (9 patients with preserved beta-cell activity) groups, and according to age into three groups (A = 21-30 years; B = 31-40 years; C = 41-50 years). All control subjects belonged to group B. Blood glucose and growth hormone were measured at hourly intervals and IGF-I every 6 h during 24 h before and after 7 days treatment with 4 IU of rhGH given subcutaneously at 8 p.m. The age-related decrease in basal IGF-I levels was evident in both CpN and CpP groups of diabetic patients. IGF-I net increase with rhGH treatment was variable and insignificant in comparison with basal value without age-related differences in CpN diabetics. Progressively larger, age-related increases in IGF-I concentrations were observed in CpP diabetic patients. This study indicates impairment of hepatic IGF-I generation capacity in diabetic patients without residual beta-cell activity and the importance of simultaneous actions of portal insulin and GH on hepatic IGF-I production.

The effects of the somatostatin analogue octreotide on ovulatory performance in women with polycystic ovaries.

The elevated luteinizing hormone (LH) and androgen concentrations characteristic of women with polycystic ovaries (PCO) are considered crucial factors in their infertility. The somatostatin analogue octreotide lowers LH and androgen concentrations in women with PCO. The effects of octreotide given concurrently with human menopausal gonadotrophin (HMG) were therefore compared with that of HMG alone in 28 infertile women with PCO resistant to clomiphene. In 56 cycles of combined HMG and octreotide therapy there was more orderly follicular growth compared with the multiple follicular development observed in 29 cycles in which HMG was given alone (mean number of follicles > 15 mm diameter on the day of human chorionic gonadotrophin (HCG) administration: 2.5 +/- 0.2 and 3.6 +/- 0.4 respectively; P = 0.026). There was a significantly reduced number of cycles abandoned (> 4 follicles > 15 mm diameter on day of HCG) in patients treated with octreotide+HMG, so that HCG had to be withheld in only 5.4% of cycles compared to 24.1% with HMG alone (P < 0.05). The incidence of hyperstimulation was also lower on combined treatment. Octreotide therapy resulted in a more 'appropriate' hormonal milieu at the time of HCG injection, with lower LH, oestradiol, androstenedione and insulin concentrations. Although growth hormone concentration was similar on both regimens, significantly higher insulin growth factor-I concentrations were observed on the day of HCG in women on combined therapy than on HMG alone.

The effect of intranasal salmon calcitonin on biochemical parameters of bone turnover in postmenopausal women.

This study aims to evaluate the effect of intranasal salmon calcitonin on variables of bone metabolism in 12 postmenopausal women during 24 months of treatment. A treatment regime of 100 U of intranasal salmon calcitonin on alternate days and 1500 mg daily of oral elementary calcium was applied. The control group consisted of 35 postmenopausal women distributed according to time since menopause. Biochemical and hormonal evaluations of calcium metabolism were performed at the start of treatment and after 6, 12, 18 and 24 months of treatment. Mean serum osteocalcin concentration was unchanged during the 1st year of treatment but was significantly elevated during the 2nd year (p = 0.03 and p = 0.005 after 18 and 24 months, respectively) when compared to levels at 12 months. Similar elevation of osteocalcin levels was observed in untreated women during the first 12 postmenopausal months. Mean 24-h hydroxyproline excretion decreased during the first 12 months of therapy but increased in the subsequent 6 months. The observed rise in serum osteocalcin concentration and urinary hydroxyproline excretion during the 2nd year of treatment with calcitonin was accompanied by a significant rise in serum calcitonin level. No significant differences in serum calcium, phosphorus, alkaline phosphatase or parathormone concentration, or urinary calcium excretion, were observed between treated and untreated women during the 24-month period. This study shows that 12 months' treatment with intranasal salmon calcitonin decreases bone resorption in early postmenopausal women, while bone formation remains unchanged. Longer treatment with intranasal salmon calcitonin, however, seems to be ineffective, most probably due to secondary resistance to calcitonin.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of two different progestins (cyproterone acetate and norgestrel), administered in a cyclical estradiol valerate regimen, on markers of bone turnover.

It has been suggested that some progestogens could have a stimulating effect on bone formation. This study was therefore undertaken in order to compare the influence of cyproterone acetate and norgestrel on bone metabolism when administered in a discontinuous, sequentially combined regimen with estradiol valerate. Twenty healthy early postmenopausal women were randomly assigned to treatment with either Cyclo-Progynova, containing 0.5 mg of norgestrel, or Climen, containing 1 mg of cyproterone acetate (CPA), over two 28-day cycles. Markers of bone resorption-fasting urinary hydroxyproline/creatinine and calcium/creatinine ratios - and of bone formation-serum alkaline phosphatase and osteocalcin-were determined initially, before the start of treatment and thereafter twice weekly (a total of 17 assessments for each women) during the 8-week treatment period. Serum osteocalcin concentrations were slightly but not significantly higher throughout the study period in women receiving Climen, compared to those taking Cyclo-Progynova. Cyclical fluctuation of serum osteocalcin levels were more pronounced in women with a high baseline level of osteocalcin. During the period of progestogen administration, osteocalcin concentrations were either similar to or even lower than those in the phase of administration of estradiol valerate alone. Serum calcium and alkaline phosphatase concentrations were relatively stable during the study period with both treatment regimens. Urinary excretion of calcium and hydroxyproline varied during the cycle but the variation was unrelated to either type or time of progestogen administration. Mean urinary hydroxyproline excretion during the 8-week study period was similar for both preparations, although the mean decrease in the urinary hydroxyproline/creatinine ratio was insignificantly higher for the CPA-containing preparation.(ABSTRACT TRUNCATED AT 250 WORDS)

24-hour serum cortisol profiles in women with polycystic ovary syndrome.

We studied the 24-h blood profiles of cortisol in obese and non-obese women with polycystic ovary syndrome (PCOS), for comparison with the levels in healthy women (controls). The levels of other hormones, such as androgens, which are known to be disturbed in PCOS, were also compared. Luteinizing hormone (LH) and androgen (testosterone, androstenedione and dehydroepiandrosterone sulfate (DHEAS)) concentrations were significantly (p < 0.005) raised in patients with PCOS, compared to those in control women. Sex hormone binding globulin (SHBG) concentration was significantly lower in women with PCOS, particularly in those who were overweight. There was a significant negative correlation between body mass index (BMI) and SHBG concentrations (r = -0.59; p = 0.006). Mean 24-h cortisol concentrations were similar in women with PCOS and controls, as well as in the obese and non-obese PCOS patients. However, the 24-h blood cortisol profile pattern was significantly different in women with PCOS as compared to the controls (p = 0.0039). Significantly lower cortisol levels were observed during the night (levels were determined between 20.00 and 04.00 and are expressed as the area under the curve) in subjects with PCOS, compared to the control women (p = 0.02). These changes were most marked in the non-obese women with PCOS who had lower blood cortisol levels during the night than either the controls or the obese PCOS subjects. Our finding of significantly lower cortisol concentrations during the night could reflect a subtle abnormality of adrenal steroid secretion in women with PCOS.

The effect of recombinant human growth hormone on regulation of growth hormone secretion and blood glucose in insulin-dependent diabetes.

GH hypersecretion in insulin-dependent diabetes (IDDM) is well documented. Although it has recently been shown that residual insulin secretion determines the magnitude of this GH hypersecretion, the underlying mechanisms of the disorder have not yet been clarified. The 24-h GH and blood glucose profiles, insulin-like growth factor I (IGF-I) concentrations and GH responses to GRF were analyzed in 21 insulin-dependent diabetics and 4 healthy subjects before and after 7 days treatment with recombinant human GH (rhGH) (4 IU given sc at 0800 h). According to C-peptide response to glucagon IDDM patients were subdivided into C-peptide negative (CpN, n = 12) patients without endogenous pancreatic beta-cell activity and C-peptide positive (CpP, (n = 9) patients with endogenous insulin secretion. No significant difference could be observed between the mean 24-h blood glucose profile before and after rhGH treatment in any treated group. Before and on rhGH treatment the highest 24-h GH values were observed in CpN patients when compared to CpP and controls. The rhGH treatment induced a similar increase in the mean 24-h GH concentrations in all groups studied which was statistically significant only in CpP diabetics. Mean pretreatment serum IGF-I concentrations were not significantly different between CpN, CpP patients and controls. The net increase in IGF-I concentrations after rhGH treatment was however, significantly lower in CpN patients than in CpP and control subjects. GRF-induced GH response before and after rhGH treatment was significantly greater in diabetics than in controls. The response of GH to GRF in CpN diabetics was however, almost unchanged after treatment whereas it became lower in CpP diabetics and controls. The dose of 4 IU of rhGH increased significantly GH levels in diabetics with preserved beta-cell function with consequent increase in IGF-I levels and attenuation of GRF induced GH response. In contrast, the same dose of rhGH failed to induce significant increase in GH levels in diabetics without residual beta-cell activity, most probably due to already high pretreatment levels. In addition, neither increase in IGF-I levels nor suppression of GH response to GRF on rhGH treatment was observed in CpN diabetics. The results are in keeping with an important role of portal insulin in GH-induced hepatic IGF-I secretion.

Growth hormone levels in patients with type 1 diabetes are age related.

Possible effects of age on the growth hormone (GH) levels in Type 1 diabetes were examined. The study was performed in 71 patients with Type 1 diabetes (40 C-peptide negative (CpN), without residual beta cell activity; 31 C-peptide positive (CpP), with preserved beta cell activity) and 11 healthy subjects. The patients and controls were divided into three age groups (A = 21-30; B = 31-40; C = 41-50 years). Blood glucose and growth hormone (GH) were measured at hourly intervals during 24 h in all subjects in hospital conditions. GH levels decreased significantly with age in patients with Type 1 diabetes (mean 24-h GH group A: 7.3 +/- 1.0, group B:5.3 +/- 0.6, group C: 3.7 +/- 0.4 mU 1(-1); A vs C: p = 0.0007; B vs C: p = 0.03). In all age groups GH levels were significantly higher in CpN than either in CpP diabetic patients or controls (group A CpN: 8.3 +/- 1.2, CpP: 4.7 +/- 1.0, controls: 2.2 +/- 0.3 mU 1(-1); p < 0.001; group B CpN: 7.3 +/- 0.8, CpP: 3.2 +/- 0.5, controls: 1.6 +/- 1.0 mU 1(-1); p < 0.0002; group C CpN: 5.2 +/- 0.5, CpP: 2.5 +/- 0.4, controls: 1.4 +/- 0.4 mU 1(-1); p < 0.001). Mean GH levels were significantly higher in C-peptide positive patients than in controls in all age groups (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of somatostatin analog octreotide (Sandostatin) on luteinizing hormone and ovarian steroids in insulin-dependent diabetic women without residual insulin secretion.

In order to determine whether the inhibitory effect of octreotide on luteinizing hormone (LH) secretion and ovarian steroids observed in women with polycystic ovaries (PCO) is a direct or indirect action of the analog, we have investigated the effect of 7 days of octreotide on LH, follicle stimulating hormone (FSH) and ovarian steroids in nine insulin-dependent diabetic women without residual insulin secreting, as in these patients a possibly confusing inhibitory effect of octreotide on endogenous insulin production is excluded. LH and FSH pulsatility over 4 h and hormonal responses (LH, FSH, estradiol, testosterone and androstenedione) to a single subcutaneous injection of buserelin were measured before and after 7 days' treatment with octreotide 100 micrograms subcutaneously twice a day. Octreotide failed to induce a significant reduction in either serum gonadotropin or ovarian steroid levels, although there was a general tendency of hormonal responses to buserelin to be lower with the analog. The effect of octreotide on LH secretion seems to be in correlation with the pretreatment levels which are, in turn, at least determined partly by endogenous insulin secretion. Thus, the results of the present study support the view that insulin has an important influence on LH secretion.

Effects of the somatostatin analogue, octreotide, in polycystic ovary syndrome.

In view of the association of hyperinsulinemia with elevated luteinizing hormone (LH) levels and hyperandrogenism in polycystic ovary syndrome (PCOS), the effect of octreotide was investigated in women with PCOS. Twelve amenorrheic women were treated with 100 micrograms octreotide twice a day for 7 days; 13 infertile women unresponsive to clomiphene citrate were treated either with octreotide (100 micrograms twice a day from day 1 of the menstrual cycle until corpus luteum formation) in addition to human menopausal gonadotropins (HMG) or with HMG alone. Octreotide significantly reduced the 4-hour integrated LH concentrations. LH pulse amplitude and nadir concentrations, and LH, testosterone, androstenedione, and estradiol responses to a gonadotropin-releasing hormone (GnRH) analogue in amenorrheic PCOS women. Octreotide treatment also resulted in a more "appropriate" hormonal milieu at the time of human chorionic gonadotropin (HCG) injection in the infertile women, with LH and testosterone levels being reduced while follicle-stimulating hormone (FSH) levels increased. Orderly follicular growth occurred, with one or two mature follicles being present at the time of HCG injection in cycles in which octreotide was given together with HMG. There were no cases of hyperstimulation, even in women who had previously hyperstimulated after HMG alone. Octreotide thus inhibits LH and androgen secretion and may improve ovulatory performance in infertile women with PCOS.

The effect of the somatostatin analogue octreotide on growth hormone secretion in insulin-dependent diabetics without residual insulin secretion.

Growth hormone (GH) hypersecretion is well documented in insulin-dependent diabetes mellitus (IDDM). Somatostatin inhibits GH in acromegalics and healthy subjects although data on its inhibitory effects on high GH levels in IDDM patients are controversial. The effect of treatment with the somatostatin analogue octreotide ("Sandostatin") on GH secretion, IGF1 levels and metabolic control was investigated in insulin-dependent diabetics. Growth hormone and blood glucose were measured at hourly intervals whilst IGF-I was measured every 6 hours during the 24-h period before and after 7 days' treatment with octreotide (200 micrograms subcutaneously three times daily) in 10 C-peptide negative diabetics. Octreotide significantly reduced mean 24 h GH profile (7.2 +/- 0.7 mU/L before; 5.2 +/- 0.5 mU/L on octreotide, p less than 0.01), IGF-I levels (0.62 +/- 0.06 before; 0.47 +/- 0.05 on octreotide, p less than 0.005) mean 24 h blood glucose (14.4 +/- 0.5 mmol/L before; 12.6 +/- 0.4 mmol/L on octreotide, p less than 0.001) and daily insulin requirements (44.8 +/- 3.0 IU before; 37.2 +/- 3.0 IU on octreotide, p less than 0.02). The shape of 24 h GH profile curve changed significantly on octreotide treatment (p less than 0.05) when it consisted of three nadirs and three peaks closely linked with the time of octreotide administration. Moderate (abdominal discomfort) to severe hypoglycaemia) transient side effects have been observed in all treated patients. The results of this study showed that short-term treatment with octreotide given s. c. every eight hours modulates the pattern of GH secretion in C-peptide negative insulin-dependent patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Twenty-four-hour serum growth hormone, insulin, C-peptide and blood glucose profiles and serum insulin-like growth factor-I concentrations in women with polycystic ovaries.

Raised insulin levels are now recognized as a characteristic feature of women with polycystic ovaries (PCO), and hyperinsulinism has been shown to stimulate androgen production in such women. We have, however, recently shown that hyperinsulinaemia is present only in the obese subjects with PCO in whom insulin concentrations correlate with those of luteinizing hormone. We therefore studied 24-hour blood profiles of growth hormone (GH) and insulin-like growth factor-I (IGF-I) in obese and non-obese women with PCO, for comparison with their levels of insulin, C-peptide and other hormones, such as androgens which are known to be disturbed in PCO. Mean 24-hour GH levels were higher overall in PCO than in control subjects, although the difference was not significant. When, however, a separate analysis was made in obese as compared with non-obese PCO patients, GH concentrations were significantly higher in the non-obese group than in the obese (p = 0.0005). There was a significant negative correlation between body mass index and mean 24-hour GH concentrations (r = -0.641; p = 0.0006). IGF-I concentrations were however similar in the PCO group overall and in controls, as well as in the obese and non-obese PCO patients. The 24-hour blood glucose profile pattern was significantly different in PCO women from controls (p = 0.009), with absence of post-prandial peaks in blood glucose concentrations. These changes were most marked in the non-obese PCO group, who also had significantly lower blood glucose levels than either controls or obese PCO subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Ovarian enlargement as a possible marker of androgen activity in polycystic ovary syndrome.

This study has been carried out in an attempt to analyze clinical, hormonal and ultrasonography data and to evaluate their possible interrelationships in a group of 72 women with polycystic ovary syndrome (PCOS). Seventeen (23.6%) PCO women were found to have ovarian volume within normal range, while 72.2% had enlarged ovaries. Serum testosterone, androstenedione and DHEAS levels were higher in PCO women with enlarged ovaries when compared to patients who had ovarian volume within normal range, although the difference was not significant. However, when PCO patients were divided into subgroups according to the degree of ovarian enlargement, it was found that patients with the most enlarged ovaries had significantly higher serum androstenedione levels than those with normal ovarian volume (p = 0.039). Significant positive correlation was established between serum androstenedione concentration and ovarian volume (r = + 0.23, p less than 0.05). Hirsutism was found to be equally present in patients with normal ovarian volume (70.6%) and in patients with enlarged ovaries (71.2%) while oligomenorrhea was present more frequently among PCO women who had ovarian volume within normal range (64.7% vs. 40.4%). The results of our study allow us to suggest ovarian enlargement as a marker of excessive androgen production and disturbances of menstrual cycle in polycystic ovary syndrome.

Inhibitory effect of sandostatin on secretion of luteinising hormone and ovarian steroids in polycystic ovary syndrome.

Hyperinsulinism accompanies the raised luteinising hormone (LH) concentrations in women with the polycystic ovary syndrome (PCOS). Somatostatin inhibits insulin and LH secretion in healthy adults, so the effect of treatment with a long-acting somatostatin analogue ('Sandostatin') on gonadotropin and androgen secretion in PCOS was investigated. LH pulsatility, androgen concentrations, and hormonal responses to an oral glucose load and to administration of a GnRH agonist (buserelin) were measured before and after 7 days' treatment with sandostatin 100 micrograms subcutaneously twice a day in 10 amenorrhoeic women with classic features of PCOS. Sandostatin significantly reduced integrated LH concentrations and LH pulse amplitudes, oestradiol, testosterone, and androstenedione concentrations, and LH responses to buserelin; it also suppressed insulin and C-peptide responses to an oral glucose load. Thus sandostatin inhibits pituitary and ovarian hormonal responses in part by a direct influence on pituitary activity, and the possibility of an indirect effect mediated by changes in insulin concentrations requires investigation. These findings have implications for the treatment of infertility in women with PCOS.

Effects of a low-dose estrogen-antiandrogen combination (Diane-35) on lipid and carbohydrate metabolism in patients with polycystic ovary syndrome.

This study was undertaken in order to evaluate the effect of an oral contraceptive containing 35 micrograms of ethinyl estradiol and 2 mg of cyproterone acetate (Diane-35) on carbohydrate and lipid metabolism in patients with polycystic ovary syndrome (PCOS). Twenty three patients with PCOS were treated with Diane-35 for between 9 and 18 cycles without interruption (a total of 318 treated cycles). Metabolic evaluations, which included measurements of fasting blood glucose, insulin, C-peptide, total cholesterol, triglyceride, total lipids, HDL-cholesterol, LDL-cholesterol and apolipoproteins (Apo A1, Apo A2 and Apo B), were performed before treatment and every 3rd cycle during the treatment period. In the case of 5 women an oral glucose tolerance test (oGTT) was performed before and after the 12th cycle of Diane-35 treatment, with blood samples taken for glucose, insulin and C-peptide measurements. Total cholesterol showed a significant increase after the 6th cycle (p less than 0.001) and reached the mean maximal value after the 9th cycle. A similar increasing trend was observed with LDL-cholesterol, which also reached the maximal mean level after the 9th cycle of treatment (p less than 0.05). There were no significant changes in HDL-cholesterol levels. Significant increases in serum triglyceride (p less than 0.01) and total lipids (p less than 0.001) were observed after the 3rd cycle. Apo A2 concentrations increased significantly after the 6th cycle (p less than 0.001) and showed an increasing trend thereafter. A significant increase was also observed in Apo B concentrations after the 6th cycle but these decreased after the 12th cycle. In spite of these observed increases in serum lipids and lipoproteins, the mean levels remained within the normal range throughout the treatment period. Fasting serum glucose, insulin and C-peptide concentrations did not show any significant changes during the study. Higher insulin and C-peptide responses during the oGTT were observed after the 12th cycle but the differences in the areas under the curve before and after treatment were not significant. A deterioration of blood glucose was observed after treatment with Diane-35, a significant difference in mean values being noted 150 minutes after the glucose overload (p less than 0.005). However, the areas under the curve in blood glucose response before (34.92 +/- 4.12) and after (43.45 +/- 3.61) treatment were not significantly different.(ABSTRACT TRUNCATED AT 400 WORDS)

LH pulsatility and response to a single s.c. injection of buserelin in polycystic ovary syndrome.

The present study was undertaken in order to determine whether patients with polycystic ovary syndrome (PCOS) have LH pulse frequency and/or amplitude higher than those in normal cycling women during the follicular phase, and, if so, to establish possible factors which might influence LH secretion in PCOS. The study was conducted on 14 PCO patients (aged 19-30 years), who were subdivided according to the data on their cycle abnormality into 2 groups: amenorrheic (Am-PCOS, n = 9) and oligomenorrheic (O-PCOS, n = 5). LH pulsatility was assessed in the early follicular phase in controls (n = 5) and O-PCOS and at any time in Am-PCOS. Blood samples were taken every 10 minutes for 4 hours. Pulse analyses of LH data were performed using the Munro program. The buserelin test was performed on the same day by injection of 40 micrograms of buserelin (blood samples were taken every 60 minutes for the following 10 hours). Eleven PCO patients and 12 control subjects had an oral glucose tolerance test (oGTT) (blood samples were taken every 60 minutes for glucose, insulin and C-peptide measurements). Both mean LH pulse frequency and mean pulse intervals were not distinguishably different in PCO women (Am and O) and controls. In contrast, the mean pulse amplitude was significantly higher in the Am-PCOS group than in O-PCOS women and controls (p less than 0.02 and p less than 0.001, respectively). A significant positive correlation was established between nadir LH concentrations and LH pulse amplitude (r = +0.966, p less than 0.001). The LH response to buserelin stimulation was significantly higher in Am-PCOS than in O-PCOS (p less than 0.004). A highly significant positive correlation was observed between LH pulse amplitude and insulin response during oGTT (p less than 0.001) in PCO subjects. Basal (prebuserelin) LH concentrations correlated significantly with fasting insulin levels (p less than 0.008) and insulin and C-peptide responses to oGTT. These results allow us to conclude the following: 1. An increased LH pulse amplitude and an exaggerated LH response to buserelin observed in amenorrheic PCO subjects compared to those in oligomenorrheic PCO subjects fail to support the hypothesis of an intrinsic hypothalamo-pituitary abnormality. 2. The relationship between fasting and glucose-stimulated insulin levels with LH nadir concentrations, pulse amplitude and response to buserelin suggests an etiological role of insulin in the pathogenesis of PCOS.