Expression of estrogen receptors in non-malignant mammary tissue modifies the association between insulin-like growth factor 1 and breast cancer risk.

BACKGROUND: Several studies have reported that the insulin-like growth factor 1 (IGF-1) is positively associated with estrogen receptor-positive [ER(+)] breast cancer risk, whereas there is little or no association with respect to ER(-) breast cancer. All comparisons of ER(+) breast cancer cases, however, have been made versus healthy controls, for whom there is no information about the ER expression in their mammary gland. PATIENTS AND METHODS: In the context of a case-control investigation conducted in Athens, Greece, we studied 102 women with incident ERα(+) breast cancer and compared their IGF-1 blood levels with those of 178 ERα(+) and 83 ERα(-) women with benign breast disease (BBD) who underwent biopsies in the context of their standard medical care. Data were analysed using multiple logistic regression and controlling for potential confounding variables. RESULTS: ERα(+) breast cancer patients had higher IGF-1 levels compared with women with BBD [odds ratio (OR) 1.36, 95% confidence interval (CI): 0.95-1.94, per 1 standard deviation (SD) increase in IGF-1 levels]. When ERα status of women with BBD was taken into account, the difference in IGF-1 levels between ERα(+) breast cancer patients and women with BBD was clearly driven by the comparison with BBD women who were ERα(+) (OR = 1.95, 95% CI: 1.31-2.89 per 1 SD increase in IGF-1 levels), whereas there was essentially no association with IGF-1 levels when ERα(+) breast cancer patients were compared with ERα(-) BBD women. These contrasts were particularly evident among post/peri-menopausal women. CONCLUSIONS: We found evidence in support of an interaction of IGF-1 with the expression of ERα in the non-malignant mammary tissue in the context of breast cancer pathogenesis. This is in line with previous evidence suggesting that IGF-1 increases the risk of ER(+) breast cancer.

A comparison of hormonal profiles between breast cancer and benign breast disease: a case-control study.

BACKGROUND: Benign breast disease (BBD), particularly proliferative BBD, is an established breast cancer risk factor. However, there has been no systematic attempt to compare the hormonal profiles of the two conditions. In a case-control investigation in Athens, Greece, we compared levels of estrogens, testosterone and insulin-like growth factor-1 (IGF-1), as well as their principal binding proteins, between breast cancer patients, women with BBD by histological type (proliferative and nonproliferative) and women with no breast pathology. PATIENTS AND METHODS: We studied 466 women with incident breast cancer, 704 women with BBD and 244 healthy women. We used multiple regression to compare log-transformed serum hormone levels of breast cancer patients with those of healthy women and women with BBD by histological type (proliferative and nonproliferative BBD). RESULTS: The hormonal profile of breast cancer in our study was in line with the generally accepted hormonal profile of this disease, as reported from large cohort studies. Compared with healthy women, breast cancer patients tended to have higher levels of steroid hormones. The evidence was strong for estrone (difference 21.5%, P < 0.001), weaker for testosterone (difference 15.8%, P = 0.07) and weaker still for estradiol (difference 12.0%, P = 0.18). Also compared with healthy women, breast cancer patients had barely higher levels of IGF-1 (difference 2.0%, P = 0.51), but had significantly lower levels of IGF binding protein 3 (IGFBP-3) (difference -6.7%, P = 0.001). Compared with women with BBD, breast cancer patients had nonstatistically significantly lower levels of steroid hormones, but they had higher levels of IGF-1 [difference 5.5%, 95% confidence interval (CI) 0.7% to 10.6%] and lower levels of IGFBP-3 (difference -3.7%, 95% CI -6.7% to -0.7%). Differences were more pronounced when breast cancer patients were contrasted to women with proliferative BBD. CONCLUSIONS: Our findings suggest that high levels of IGF-1 may be an important factor toward the evolution of BBD to breast cancer.

The hormonal profile of benign breast disease.

BACKGROUND: Limited information exists about the endocrine milieu of benign breast disease (BBD), a documented breast cancer risk factor. We compared blood levels of estrogens, testosterone and insulin-like growth factor-1 (IGF-1) between BBD patients by histological type and women without breast pathology. METHODS: We studied 578 BBD patients and 178 healthy women in Athens, Greece, who provided blood samples, and completed interviewer-administered questionnaires. RESULTS: Of the BBD patients, 254 had non-proliferative disease, 268 proliferative disease without atypia and 56 atypical hyperplasia. Comparing BBD patients with healthy women, the per cent differences (and 95% confidence intervals) for blood hormones, among pre-menopausal and peri/post-menopausal women, respectively, were: 22.4% (-4.0%, 56.1%) and 32.0% (5.6%, 65.1%) for estradiol; 26.2% (10.1%, 44.8%) and 30.9% (16.8%, 46.6%) for estrone; 19.5% (3.1%, 38.4%) and 16.5% (-5.0%, 42.9%) for testosterone; and -5.2% (-13.8%, 4.4%) and -12.1% (-19.8%, -3.6%) for IGF-1. Steroid hormones tended to be higher in proliferative compared with non-proliferative BBD. CONCLUSIONS: Circulating steroid hormones tend to be higher among women with BBD than women with no breast pathology and higher in proliferative than non-proliferative disease; these patterns are more evident among peri/post-menopausal women. In peri/post-menopausal women IGF-1 was lower among women with BBD compared with healthy women.

Testosterone and oestradiol in relation to tobacco smoking, body mass index, energy consumption and nutrient intake among adult men.

There is substantial evidence linking steroid hormones and diet to cancer aetiology. The evidence on lifestyle determinants of steroid hormones, however, is limited. We have conducted a study to identify dietary and other lifestyle predictors of testosterone and oestradiol among adult men. Subjects were 112 healthy Greek men, recruited as controls in a case-control study on the aetiology of liver cancer. Demographic data and detailed histories of smoking habits and alcohol consumption were recorded. Diet was assessed through an interviewer-administered validated food-frequency questionnaire. Serologic measurements of oestradiol, testosterone and sex hormone binding globulin were also conducted. We developed linear regression models to evaluate the associations of smoking and dietary factors with serum testosterone and oestradiol. The results indicate that, among men, both testosterone and oestradiol serum levels decline with age, whereas body mass index may be inversely related with testosterone and positively with oestradiol. The evidence concerning alcohol in relation to these hormones is inconclusive. Emerging evidence concerning smoking suggests positive associations with both hormones in the blood. The principal nutritional findings are a positive association of carbohydrate intake with testosterone levels and a set of inverse associations of vitamins with oestradiol.

Are dietary influences on the risk of prostate cancer mediated through the insulin-like growth factor system?

OBJECTIVES: To investigate whether dietary factors that appear to affect the risk of prostate cancer may be similarly associated with serum levels of insulin-like growth factor 1 (IGF-1). Patients and methods In the context of a case-control study, 112 men were admitted to three teaching hospitals in Athens, Greece, for disorders other than cancer. Sociodemographic data and detailed histories of smoking, alcohol and coffee consumption were recorded. A validated food-frequency questionnaire was administered by an interviewer and serological measurements of IGF-1 and its binding protein-3 conducted. RESULTS: IGF-1 declined significantly by almost 25% among men aged >75 years and there was a small reduction in IGF-1 levels with increased alcohol intake, with a mean (95% confidence interval, CI) change of -1.6 (- 2.2 to -0.9)% for an increment of one drink per day. There was no evidence for an effect of either smoking or coffee consumption on IGF-1 level. Among foods, the consumption of cooked tomatoes was substantially and significantly inversely associated with IGF-1 levels, with a mean (95% CI) change of -31.5 (- 49.1 to -7.9)% for an increment of one serving per day. CONCLUSIONS: The strongest known dietary risk factor for prostate cancer (lycopene deficit, as reflected in a reduced intake of cooked tomatoes) and an important endocrine factor in the aetiology of this disease (IGF-1) seem to be related in a way that suggests that at least one, and perhaps more, exogenous factors in the development of prostate cancer may be mediated through the IGF-1 system.

Estrogens, testosterone and sex hormone binding globulin in relation to liver cancer in men.

OBJECTIVE: Liver disease in men has been associated with an imbalance of serum estradiol and testosterone. We have evaluated whether serum estradiol and testosterone levels are altered in male liver cancer patients as a result of a specific effect of the disease or because of the associated liver damage. METHODS: We have performed a hospital-based case-control study in Greece. The study subjects were all men; 73 patients with hepatocellular carcinoma (HCC), 25 with metastatic liver cancer (MLC) patients and 111 control subjects. Serum estradiol, testosterone and sex hormone binding globulin (SHBG) levels were measured for each subject. Data were analyzed by multiple linear regression. RESULTS: Mean serum estradiol levels were significantly higher among HCC patients as well as among patients with MLC compared to controls. Mean serum testosterone levels were significantly lower among HCC patients as well as among patients with MLC compared to controls. The mean SHBG levels did not differ significantly between the groups. After controlling for the degree of liver damage, the elevated serum estradiol and reduced serum testosterone levels among HCC and MLC patients were no longer significant. CONCLUSIONS: Changes in sex steroid levels among patients with liver damage are due to the liver damage per se and not to specific disease processes.

Insulin-like growth factor binding protein-3 predicts survival from acute childhood leukemia.

OBJECTIVE: To investigate whether the three principal components of the insulin-like growth factor (IGF) system, IGF-1, IGF-2 and IGF binding protein-3 (IGFBP-3), are associated with survival from childhood leukemia. PATIENTS AND METHODS: 116 children, 0--14 years old, with newly diagnosed and bone-marrow-biopsy-confirmed acute childhood leukemia between 1993 and 1996 were followed up until death or March 31, 1998. IGF-1, IGF-2 and IGFBP-3 were measured at diagnosis and clinical data, including presence of hepatosplenomegaly and number of white blood cells, were available. RESULTS: After controlling for gender, age, indicators of clinical severity and the other measured components of the IGF system there was a statistically significant (p < 0.05) inverse association of IGFBP-3 with survival. An increment of one standard deviation in IGFBP-3 was associated with a 65% reduction of the death hazard among the children with leukemia. Neither IGF-1 nor IGF-2 was associated with survival in this data set. CONCLUSION: The presented empirical evidence in conjunction with the fact that IGFBP-3 modulates IGF-1 and IGF-2 bioavailability and is likely to have proapoptotic effects makes this compound a plausible independent predictor of survival from childhood leukemia.

Age at menarche and age at menopause in relation to hepatocellular carcinoma in women.

OBJECTIVES: To assess whether age at menarche, age at menopause, parity, and selected blood hormones are associated with risk of hepatocellular carcinoma among women. DESIGN: Case-control. SAMPLE: and setting Data collected from 50 cases of hepatocellular carcinoma among women and 62 female controls with minor trauma or surgical conditions who attended one of three hospitals in Athens, Greece between 1995 and 1998. METHODS: Researchers collected information on Reproductive variables and assayed sera samples for blood hormone levels and for chronic infection with Hepatitis B and C viruses. RESULTS Individuals with hepatocellular carcinoma had a lower mean age at menarche and a significantly higher mean age at menopause. After adjusting for potential confounding, age at menopause remained an important and significant predictor, increasing the risk of hepatocellular carcinoma 24% for each later year of menopause (P < 0.001). For each year that menarche was delayed, risk of hepatocellular carcinoma declined 21% (P = 0.100). Mean levels of insulin-like growth factor-1 and its binding protein were significantly reduced in cases compared with controls, while levels of oestradiol, testosterone and sex hormone binding globulin were somewhat higher among the cases. CONCLUSIONS: This study provides indirect, but converging evidence that steroid hormones in general, and oestrogens in particular, play an important role in the aetiology of hepatocellular carcinoma among women.

Endogenous risk factors for childhood leukemia in relation to the IGF system (Greece). The Childhood Haematologists-Oncologists Group.

OBJECTIVE: Insulin-like growth factor-1 (IGF-1) and its principal binding protein-3 (IGFBP-3) are central in the mediation of the effect of growth hormone, and the IGF system has been reported to play a role in the pathogenesis of childhood leukemia. METHODS: To further evaluate the hypothesis connecting the IGF system to this disease, we have examined whether IGF-1 and IGFBP-3 are associated with the two main endogenous risk factors for childhood leukemia, namely gender and birth weight, since boys and heavier newborns are known to be at higher risk. IGF-1 and IGFBP-3 were measured under code in the serum of 118 apparently healthy children aged 0-14 years and the values of each of these components were regressed on age, gender and birth weight. Insulin-like growth factor-2 (IGF-2), as a dependent variable, and anemia during the corresponding pregnancy, as a predictor variable, were also evaluated for exploratory purposes. RESULTS: In the total data set, IGF-1 was positively associated with birth weight (p = 0.0001), whereas girls had higher levels of IGFBP-3 (p = 0.01). CONCLUSIONS: It appears that the associations of measured components of the IGF system with the examined risk factors for childhood leukemia are largely compatible with those that would have been expected, if this system played a role in the pathogenesis of childhood leukemia.

Leptin and insulin growth factor I in relation to breast cancer (Greece).

OBJECTIVES: Because both breast cancer and the hormone leptin are associated with obesity and reproductive phenomena in women, we have examined whether there is a relationship between leptin and breast cancer among premenopausal and postmenopausal women. We have also evaluated in this dataset the association of IGF-I with breast cancer. METHODS: Seventy-five cases, diagnosed during mammographic screening, with incident breast cancer were matched for age and type of permanent residence with seventy-five controls from those screened negative in the same study base. RESULTS: There was no evidence for an association between IGF-I and either premenopausal or postmenopausal breast cancer risk or between leptin and postmenopausal breast cancer. Among premenopausal women, however, there was a strong and statistically significant inverse association of leptin with breast cancer. CONCLUSION: We did not confirm the positive association, reported from other investigations, of IGF-I with premenopausal breast cancer risk. We have found evidence, however, that leptin may be inversely related to breast cancer risk among premenopausal women. The latter finding is not biologically implausible and deserves to be examined in additional datasets.

Insulin-like growth factor 1 in hepatocellular carcinoma and metastatic liver cancer in men.

The insulin-like growth factor (IGF) axis has important autocrine, paracrine, and endocrine roles in the promotion of growth. Alterations of the IGF system have recently been implicated in the pathogenesis of several malignancies, but the relation to hepatocellular carcinoma (HCC) risk is unclear. To address this issue, we used an immunoradiometric assay to quantify IGF-1 levels in serum samples in a hospital-based, case-control study in Greece. The study subjects were all men and included 53 patients with HCC positive for hepatitis B and/or hepatitis C virus infections, 20 virus-negative HCC patients, 25 virus-negative patients with metastatic liver cancer (MLC), and 111 virus-negative control subjects. Data were analyzed by multiple linear regression, using IGF-1 as the dependent variable. The mean value of IGF-1 was 65.9 ng/ml among virus-positive HCC patients, 79.5 ng/ml among virus-negative HCC patients, 110.8 ng/ml among patients with MLC, and 174.7 ng/ml among hospital controls. After controlling for the degree of liver damage, as assessed by prothrombin time and serum albumin level, the reduction in IGF-1 level among HCC patients was found to be more than could be attributed to liver damage alone. This finding may have both diagnostic and pathophysiological implications.

Insulin-like growth factor-I and binding protein-3 in relation to childhood leukaemia.

The aetiology of most cases of childhood leukaemia remains unknown, but several studies have indicated that increased birthweight and height are risk factors for the disease. Since insulin-like growth factor-I (IGF-I) mediates the effect of growth hormone and has been positively associated with prostate cancer, we have evaluated the role of this hormone and its principal binding protein, IGFBP-3, in the aetiology of childhood leukaemia. Incident cases of childhood leukaemia from those recorded by a national network of childhood oncologists were enrolled in our study. Controls were children hospitalised for acute conditions of no more than moderate severity with matching for gender, age and maternal place of residence. Blood measurements of IGF-I and IGFBP-3 were undertaken using commercially available radioimmunoassays. Serum IGF-I values decreased by about 1.7% per month, and the rate of decline was higher, though not significantly so, among cases (2.1% per month) than among controls (1.4%). There was no significant association between IGF-I and the likelihood of childhood leukaemia, but an increment of 1 microg/ml of IGFBP-3 was associated with a substantial and statistically significant reduction of childhood leukaemia by 28% (95% confidence interval 7% to 45%). Because IGFBP-3 is essentially a binding protein, we interpret our findings as indicating that bioavailable IGF-I may play an important role in the aetiology of childhood leukaemia. The much smaller quantities and the inherent instability of IGF-I in the blood in comparison to those of IGFBP-3 are likely to hinder documentation of an underlying positive association of IGF-I with the disease.

Clinical features and evolution of antinuclear antibody positive individuals in a rheumatology outpatient clinic.

OBJECTIVE: To identify individuals with antinuclear antibodies (ANA) not fulfilling criteria for systemic lupus erythematosus (SLE) or other connective tissue diseases (CTD); to describe their clinical and serological features, to identify factors indicating evolution to SLE. METHODS: A case-control study, based on retrospective evaluation of clinical files. The cases were ANA positive individuals (n = 50) examined in a medical outpatient setting, for symptoms compatible with SLE, but not fulfilling SLE classification criteria. Two patients with SLE were matched to each case in terms of age at initial symptom onset and sex. Thyroid autoimmunity was assessed by detecting antithyroid antibodies. Fisher's exact test and conditional logistic regression were used to evaluate the predictive ability of initial findings for SLE development. RESULTS: ANA positive individuals suspected of having a CTD present a wide variety of symptoms and findings, usually at the 4th to 5th decade of life. Antibodies to Sm and U1RNP were absent; anti-Ro(SSA) and anti-La(SSB) occurred in 6%, while anti-dsDNA occurred in less than 10% of the cases. Arthritis, butterfly and discoid rash, Raynaud's phenomenon, and anti-Ro/SSA antibodies are the initial findings indicating evolution to SLE. Hematological abnormalities such as leukopenia and thrombocytopenia as well as constitutional symptoms such as easy fatigue and arthralgias are not associated with evolution to SLE. Antithyroid antibodies were detected in 16% of the cases and 2.3% of controls. CONCLUSION: ANA may connote a form of systemic autoimmunity that is expressed as a wide variety of complaints, even in the absence of a definite diagnosis of CTD. Arthritis, rash, Raynaud's phenomenon, and anti-Ro/SSA antibodies indicate evolution to SLE. Autoimmune thyroid disease occurs in ANA positive individuals not fulfilling SLE classification criteria rather than in patients with SLE.

Azoospermia: clinical, hormonal, and biochemical investigation.

The aim of this study was to evaluate the clinical, hormonal and biochemical characteristics of infertile men with azoospermia. A total of 187 azoospermic out of 2610 infertile men (7.2%) were studied. Mean testicular volume and basal plasma levels of FSH were the most useful parameters concerning the evaluation of azoospermia. Basal plasma levels of LH and T were useful only in azoospermic men with hypogonadism, whereas plasma PRL levels, semen volume, and seminal plasma fructose levels were not found to be of common use except in selected cases.

The prognostic value of basal luteinizing hormone:follicle-stimulating hormone ratio in the treatment of patients with polycystic ovarian syndrome by assisted reproduction techniques.

One of the main endocrinological disturbances in patients with polycystic ovarian syndrome (PCOS) is the increased baseline concentrations of luteinizing hormone (LH) and consequently a high LH:follicle-stimulating hormone (FSH) ratio. The aim of this study was to assess the relationship between the baseline LH:FSH ratio with the stimulation response and the miscarriage risk in PCOS women stimulated for assisted reproduction techniques (ART) with and without gonadotrophin-releasing hormone analogue (GnRHa). Two groups of PCOS patients were analysed retrospectively. Group A (n = 20, 20 cycles) consisted of women stimulated with human menopausal gonadotrophin (HMG), and group B (n = 128, 162 cycles) comprised women stimulated with buserelin-long/HMG. LH and FSH concentrations were measured during the early follicular phase (days 4-6) in a preceding spontaneous or progestin-induced cycle. The following parameters were assessed: number of follicles developed, number of oocytes obtained and percentage of mature oocytes, as well as number of abortions and live births. In group A, the baseline LH:FSH ratio was correlated inversely with the number of follicles developed (P < 0.05), the number of oocytes obtained (P < 0.05) and the percentage of mature oocytes (P < 0.05). In group B, no correlation was found between the LH:FSH ratio and the number of follicles and oocytes, because their numbers were relatively constant irrespective of the baseline LH:FSH ratio, but a significant inverse correlation was noted with the percentage of mature oocytes (P < 0.001). However, a comparison of the slopes of the curve indicated a better correlation between the LH:FSH ratio and the percentage of mature oocytes in group A than in group B (P < 0.05). These findings were also confirmed when patients were subdivided according to the LH:FSH ratio (< 3 or > or = 3). Furthermore, in women who miscarried, the mean LH:FSH ratio was significantly higher than in women having a live birth. In conclusion, in PCOS patients stimulated with HMG, a high basal LH:FSH ratio appears to have an adverse effect on the number of follicles and oocytes, as well as on oocyte maturity. On the other hand, the administration of GnRHa in the long protocol seems to reverse this detrimental effect on follicle and oocyte development. Furthermore, a higher LH:FSH ratio seems to predict a greater possibility for miscarriage, despite the use of GnRHa.

Evaluation of different ovarian stimulation protocols for in vitro fertilization.

In this study we evaluated retrospectively the efficacy of five different ovarian stimulation protocols in an in vitro fertilization program, in which 512 women were involved. Ovulation was induced by the following protocols: group I (271 cycles): buserelin short protocol (1 mg/day, intranasally) with human menopausal gonadotropin/human chorionic gonadotropin (hMG/hCG); group II (45 cycles): buserelin (short protocol) with pure follicle stimulating hormone (p-FSH)/hMG/hCG; group III (24 cycles): clomiphene citrate (100 mg/day) with hMG/hCG; group IV (122 cycles): hMG (3 ampules/day) and hCG; group V (113 cycles): hMG/hCG and prednisolone (7.5 mg/day) after cycle programming with oral contraceptives. The lowest cancellation rate (3.3%) was noted in group I, followed by group V (9.7%). The highest number of follicles was observed in groups I (8.3 +/- 0.3; mean +/- SEM) and V (7.8 +/- 0.5). Also, more oocytes were retrieved in group I (7.2 +/- 0.3, p < 0.001), which were of good quality based on oocyte maturity as well as on the fertilization rate, and more embryos (4.5 +/- 0.3, p < 0.05) were developed. The correlation between estradiol and the total follicular volume on the day of hCG administration was also examined in the five groups. The best correlation (r = 0.6502) was found in group I, followed by group V (r = 0.5810). Significant differences were observed in the five groups with regard to the number of hMG ampules administered (p < 0.0001, F = 15.393) and the stimulation days (p < 0.0001, F = 35.32). Sixty-six clinical pregnancies were achieved: 37 (17.5%) in group I, seven (25.9%) in group II, one (10%) in group III, ten (15.6%) in group IV and 11 (15.5%) in group V (differences were not statistically significant). In conclusion, all five protocols were satisfactory in ovarian stimulation for in vitro fertilization, and gonadotropin releasing hormone (GnRH) analogs seemed to be more advantageous by reducing the cancellation rate, enhancing the number of oocytes retrieved and embryos developed and by improving the pregnancy rates.

Growth hormone, oestradiol, progesterone and testosterone concentrations in follicular fluid after ovarian stimulation with various regimes for assisted reproduction.

Follicular fluid samples and oocytes were obtained from 75 women (87 cycles), who participated in an assisted conception programme. Determinations of the concentration of oestradiol, progesterone, testosterone and growth hormone were performed in all follicular fluid samples. Patients were stimulated with the following regimes: group A (24 cycles, 94 samples), human menopausal gonadotrophin (HMG) (three ampoules/day) and human chorionic gonadotrophin (HCG); group B (23 cycles, 53 samples), HMG/HCG with prednisolone (7.5 mg/day) after cycle programming with oral contraceptives; group C (40 cycles, 60 samples), buserelin with HMG/HCG. Oestradiol concentrations (mean +/- SEM) were significantly higher (P < 0.05) in group A (320.1 +/- 27.3 ng/ml) and those of growth hormone in both groups A and C (3.8 +/- 0.2 and 3.2 +/- 0.15 ng/ml, respectively), as compared to the other groups, whereas progesterone and testosterone concentrations were similar in all groups. The mean concentrations of oestradiol, progesterone, testosterone and growth hormone were significantly higher (P < 0.01) in follicular fluid with oocytes of intermediate maturity than with mature oocytes (382.5 ng/ml, 7847.5 ng/ml, 1704.5 ng/dl and 3.7 ng/ml versus 217.8 ng/ml, 5488.4 ng/ml, 1313.6 ng/dl and 2.7 ng/ml, respectively). On the other hand, only oestradiol concentrations were significantly higher in follicular fluid of fertilized compared to non-fertilized oocytes. Concentrations of the other hormones analysed, except growth hormone, were similar in follicular fluid from pregnant and non-pregnant women after assisted reproduction. Growth hormone, on the other hand, was significantly lower (P < 0.05) in follicular fluid from pregnant compared to non-pregnant women (2.8 versus 3.5 ng/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

Ovarian stimulation with buserelin/HMG/HCG: prospective randomized study of short versus long protocol.

The combined administration of the gonadotrophin-releasing hormone (GnRH) agonist buserelin and human menopausal gonadotrophin (HMG) was evaluated in 527 cycles (428 patients) of an assisted reproduction programme. All women were randomly allocated according to the ovulation induction protocol into two groups: group I (short protocol; 318 cycles) was given buserelin (1 mg/day) intranasally from cycle day 1 and HMG (2 ampoules/day) from day 3 until human chorionic gonadotrophin (HCG) administration: group II (long protocol; 209 cycles) was given buserelin (1 mg/day) intranasally from cycle day 1 for at least 14 days and then 2 ampoules HMG/day were added, increasing progressively according to the ovarian response. The number (mean +/- SEM) of follicles developed was higher in group II than in group I (9.1 +/- 0.4 versus 7.7 +/- 0.3, respectively; P < 0.05). More oocytes were retrieved in group II (8.4 +/- 0.5) than in group I (6.5 +/- 0.3) (P < 0.001), as well as more embryos (6.3 +/- 0.5 and 4.0 +/- 0.3, respectively; P < 0.001). Moreover, in group II there was a better correlation between oestradiol and the total follicular volume (r = 0.5391) on cycle day 0 compared with group I (r = 0.458), while oestradiol values were similar between the two groups. No differences were observed in the cancellation rate, fertilization rate and maturity of the oocytes between the two groups. The pregnancy rate per transfer was slightly better in group II (25.8%) than in group I (19.4%), but this difference was not significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation of Hamilton-Thorn automated semen analysis system.

Sperm concentration and percentage motility values generated by the HT M-2030 system (CASA) were compared with those obtained by subjective semen analysis (SSA). Three calibrations arbitrarily designated as A, M, and D for gates and discriminators and three calibrations arbitrarily designated LI, MI, and HI for default pixel count (DPC) and default intensity (DI) were evaluated. The best correlation between CASA and SSA was observed utilizing M calibration (n = 114) with which sperm concentration was +0.3 x 10(6)/mL (r = .96) and motility was -6.3% (r = .89) compared to the values obtained by SSA. It was found that 35.9% of sperm concentration values and 34.2% of sperm motility values were within 10% of the values obtained by SSA. When sperm concentration was between 50 and 100 x 10(6)/mL the difference in motility was reduced (-3.2%) while the difference in sperm concentration was reversed (-2.6 x 10(6)/mL). LI calibration (DPC = 4, DI = 86) gave acceptable results with M calibration for sperm concentration (+2.1 x 10(6)/mL) and motility (-6.9%) compared to the values obtained by SSA. In the presence of sperm clumping, the difference between CASA and SSA was reversed for sperm concentration (+0.56 x 10(6)/mL for normal samples vs. -2.2 x 10(6)/mL for samples with clumping) and was reduced for sperm motility (-7.14% vs. -4.55%, respectively). HT M-2030 under proper calibration can be used as a rapid, objective, and reliable alternative to conventional semen analysis in routine and for research purposes.

Pregnancy estrogens in relation to coffee and alcohol intake.

Total estrogen (TE), estradiol (E2), estriol (E3), and human placental lactogen (hPL) levels were determined by radioimmunoassay in the blood of 141 pregnant women during their 26th and 31st weeks of pregnancy and the results were studied in relation to coffee and alcohol intake. After controlling for maternal age, maternal weight at the corresponding week of pregnancy, parity, and tobacco smoking, as well as for mutual confounding effects, coffee intake, ascertained at the 26th week, was found to be negatively related to pregnancy E2 levels (P = 0.04 during the 26th week, and P = .16 during the 31st week), whereas alcohol intake, also ascertained at the 26th week, was found to be positively related to pregnancy TE levels (P = .04 during the 26th week, and P = .18 during the 31st week). The negative relation between coffee consumption on the one hand and E2 (and possibly TE) levels on the other may be responsible for the inverse association between maternal coffee intake and birth weight; the latter association has been repeatedly confirmed in the literature, although it was neither strong nor statistically significant in the present study. The relations of maternal coffee and alcohol consumption with pregnancy estrogen levels, if confirmed, could be utilized in studies exploring the role of prenatal exposure to these hormones in the etiology of gonadal germ-cell tumors and possibly other diseases.