The binding constants of the alpha(1)-foetoprotein of the rat embryo serum for oestrone and oestradiol-17beta have similar values, i.e. 1 x 10(8) M(-1) in average at 25 degrees. There is probably one binding site per mole of binding protein. The high alpha(1)-foetoprotein concentration in the rat embryo serum at 17-19 days of pregnancy explains the exceptionally high levels of fixation of the phenolsteroids by this serum.

A double-blind trial of piperazine oestrone sulphate was performed over a period of 14 months on 55 menopausal women complaining of depressiona and hot flushes. Depression was not affected but the hot flushes were significantly lessened by the oestrogen treatment. After three months of piperazine oestrone sulphate there were no significant accelerations of prothrombin time or increases in factors VII or X but, after six months, there was an acceleration in the prothrombin time. After 14 months those who received piperazine oestrone sulphate for the first six months showed a significant increase in alpha 1-antitrypsin and factor VIIR:AG. Oestrone piperazine sulphate appears to produce less marked changes in coagulation than oestrogen-containing oral contraceptives or conjugated equine oestrogens.

Serum FSH and LH and total urinary oestrogens were measured in 20 mature onset postmenopausal diabetic women and compared to 20 nondiabetic women matched for age, years since menopause, surface area and per cent ideal weight. Significantly higher levels of urinary oestrone, oestradiol and oestriol and significantly lower levels of FSH and LH were found in the diabetic women. Closer analysis of these findings showed that the differences were maintained for the diabetics who required insulin for adequate control, whereas diabetics controlled on diet alone or diet and oral hypoglycaemic drugs were not significantly different from control subjects except in urinary oestrone excretion.

17Beta-hydroxysteroid dehydrogenases (17beta-HSDs) are a family of enzymes that regulate steroid availability within a tissue by catalysing the interconversion of active and inactive forms. Type 1 is up-regulated in many breast tumours, and is responsible for the reduction of oestrone to active oestradiol which stimulates cell proliferation within the tumour. Type 2 oxidises many active steroids to their inactive forms, including oestradiol to oestrone. In this study, we have compared the mRNA expression and enzyme activities of Type 1 and Type 2 in MCF-7, MDA-MB-231, T47D, JEG3 and 293-EBNA cell lines. Also studied were two cell lines stably expressing transfected Type 1 cDNA. RT-PCR indicated that little Type 1 mRNA is expressed in two of the breast cancer cell lines, MCF-7 and MDA-MB-231, and in 293-EBNA cells, but that expression is much higher in the T47D breast cancer cell line, and in the choriocarcinoma cell line, JEG3. However, a higher level of expression of Type 1 is seen in the transfected cell lines MCF-7.8H and 293-EBNA[His617beta-HSD1]. Activity assays show that there is high association between mRNA expression and enzyme activity. Assays indicate that, with the exception of MDA-MB-231 cells, Type 2 activity is low in these lines. The study of the basal activities of these enzymes will be used in future studies investigating the regulation of the enzymes by endogenous and exogenous factors. An understanding of their regulation in both healthy and malignant tissues may lead to future therapeutic intervention at the regulatory level.

Platelet serotonin content was measured by high pressure liquid chromatography in 56 peri- and postmenopausal women, in order to study variations of this parameter with hormonal status and depressive mood symptoms. Clinical symptoms were assessed by a self-report depression symptom scale (CES-D of NIMH). Thirty-eight women with a score of 16 or more were considered as presenting depressive symptoms (mean score +/- SD = 28.8 +/- 10.5), while the others formed the control group (n = 18, score = 4.4 +/- 4.2). Platelet serotonin contents were significantly lower in the 'depressed' group (0.302 +/- 0.010 vs. 0.366 +/- 0.020 nmol 10(-8) platelets, means + SEM, P less than 0.001 by Mann-Whitney U-test). In 'depressed' women who had been treated for one or more depressive episodes, platelet 5-HT contents (0.283 +/- 0.023, n = 18, P less than 0.01) were significantly lower with respect to controls. In patients without previous episodes of depression, serotonin expressed in nmol 10(-8) platelets did not differ significantly from controls but serotonin expressed in nmol ml-1 of blood was slightly lower than control values (0.890 +/- 0.085, n = 20 vs. 1.088 +/- 0.090 nmol ml-1, n = 18, P less than 0.02). Platelet serotonin content was positively correlated to plasma oestrone and oestradiol concentrations among the control group but not in the 'depressed' group.(ABSTRACT TRUNCATED AT 250 WORDS)

Sulphation is an important conjugation pathway in drug metabolism that has been studied in several species including humans. However, few studies have been performed using the dog as a subject. In this report we describe the cloning and characterization of a canine cytosolic sulphotransferase (SULT). The overall primary structure of this enzyme is very similar to that of a rat phenol-sulphating enzyme found in the EMBL Database and to a mouse SULT termed amine-N-sulphotransferase (81% identity). The expressed canine SULT conjugates small phenols and aromatic amines such as dopamine, minoxidil, p-nitrophenol and 5-hydroxytryptamine, but not dehydroepiandrosterone or beta-oestradiol. These results are in agreement with the results reported for the mouse SULT. In contrast with the mouse enzyme, the canine SULT does not conjugate eicosanoid compounds, i.e. prostaglandins, thromboxane B(2) or leukotriene E(4). The canine SULT is expressed at high levels in the colon of both genders; it is also expressed in the small intestine, kidney and liver. Furthermore, because the canine, mouse and rat SULT forms exhibit significant sequence identity (more than 80%), they seem to represent a distinct group in the SULT family tree. This suggestion is strengthened by the low identity with other SULTs. The subfamily that is most similar to this new group is SULT1A, with approx. 60% similarity. However, the mouse and canine enzymes are not characterized by the efficient sulphation of p-nitrophenol, dopamine, beta-oestradiol or oestrone. Thus these results seem to exclude them from the SULT1A subfamily. We therefore propose a new subfamily in the phenol SULT family, designated SULT1D, and consequently the canine enzyme is termed SULT1D1.

An oestrogen sulphotransferase, active towards both oestrone and oestradiol, and of high specific activity, is present in cytosol prepared from adrenal glands of both sexes of English Shorthair and Hartley guinea pigs. The ovarian and testicular cytosolic activities of this enzyme are markedly low in comparison with the adrenal activity. The adrenal enzyme is distinct from an accompanying pregnenolone sulphotransferase as judged by f.p.l.c. gel filtration, chromatofocusing, and differences in activation brought about by the addition of thiol groups. The oestrogen sulphotransferase behaved as a 67 kDa protein on a Sephadex G100 column and as a 48 kDa protein on f.p.l.c. gel-filtration columns. Two forms of the enzyme with apparent pI values of 6.1 and 5.5 were eluted during f.p.l.c. chromatofocusing. Sequential salt fractionation, f.p.l.c. gel filtration and elution from an agarose-hexane-adenosine-3',5'-diphosphate affinity gel has resulted in a preparation which, when resubmitted to f.p.l.c. gel filtration, yields a considerably purified oestrogen sulphotransferase. When submitted to SDS/polyacrylamide-gel electrophoresis under reducing conditions, a main protein band of 34-36 kDa is observed. It is suggested that the enzyme may exist as a dimer in the cytosol.

Exhaled nitric oxide (NO), early morning urinary nitrites/nitrates and urinary female sex steroid conjugates were measured daily to investigate whether there was a variation in NO generation during the menstrual cycle. Exhaled NO concentrations and early morning urine samples were taken for 30 consecutive days in five healthy normotensive women with proven ovulation. The urine samples were analysed for nitrite-nitrate creatinine ratios, oestrone-3-glucuronide (EG) and pregnanediol-3-alpha glucuronide (PG). The mean (95% CI) exhaled NO concentration was 52 ng g-1 in the 150 readings and the mean molar urinary nitrate-creatinine ratio was 0.18. There was no temporal relationship between the measurement of NO production and urinary sex steroid conjugates within the menstrual cycle. These findings suggest that oestrogens do not modulate exhaled NO concentration and appear not to increase the production of the early morning urinary nitrates in healthy premenopausal women. There was also no sex difference in exhaled NO generation.

1. A computerized technique is described for the quantitative determination of radiometabolites from incubation studies. 2. Seven steroid substrates have been incubated with human endometrial tissue. The principal radiometabolites were identified and determined after 2hr. incubation without the addition of cofactors and after 4hr. incubation with cofactors. 3. The main products from progesterone were 20alpha-dihydroprogesterone and 5alpha-pregnanedione with lower yields of 5beta-pregnanedione and 20beta-dihydroprogesterone. There was no evidence for 17alpha-hydroxylase activity. 4. 17alpha-Hydroxyprogesterone was transformed into small yields of 17alpha,20alpha- and 17alpha,20beta-dihydroxypregn-4-en-3-one. In one incubation there was evidence for conversion into androstenedione. 5. Dehydroepiandrosterone was transformed into small amounts of androstenedione, 5alpha-androstanedione and androsterone. 6. Androstenedione and testosterone were interconvertible, the reaction favouring the formation of androstenedione. 5alpha-Androstanedione and androsterone were formed from both substrates. There was no evidence for the formation of phenolic steroids. 7. Oestrone and oestradiol-17beta were interconvertible, the reaction favouring the formation of oestrone.

Endocrine studies in girls with precocious thelarche were compared with those of normal girls of similar ages. Girls with precocious thelarche showed breast development and oestrogenised vaginal smears as the only signs of precocious sexual development. A few of the girls were tall and some had advanced bone ages but these two findings were not consistently present in the same patient. Hormones--such as serum oestradiol, oestrone, delta 4-androstenedione, progesterone, dehydroepiandrosterone (DHEA), follicle-stimulating hormone, luteinising hormone, and prolactin, and urinary 17-ketosteroids--were measured. Only DHEA was different, being higher in girls with precocious thelarche. It is suggested that the high DHEA level may serve as a precursor for conversion to oestrogens in target tissues, breast, and vagina. This mechanism for oestrogenisation had been reported in other patients.

The effects of 14 steroids at concentrations between 0.1 and 10 micrograms/ml on human spermatozoal forward migration in vitro were tested. Oestradiol-17 beta at a concentration of 0.1 microgram/ml significantly activated spermatozoal forward migration in ejaculated human semen. However, the effect of oestradiol-17 beta at concentrations of 2 and 10 micrograms/ml on ejaculated human sperm motility was not significantly different from the control where no steroid was added. Progesterone, testosterone, oestriol, oestrone, oestradiol-17d, and ethinyl oestradiol significantly inhibited human spermatozoal forward migration at concentrations of 10 micrograms/ml. Chlormadinone acetate and medroxyprogesterone acetate at concentrations of 2 and 10 micrograms/ml significantly inhibited human spermatozoal forward migration, while norethynodrel, ethynodiol diacetate, norgestrel and lynoestrenol significantly inhibited human spermatozoal forward migration at concentrations between 0.1 and 10 micrograms/ml. However, norethindrone had no demonstrable effect on human spermatozoal forward migration at the above concentrations.

The relationship between hormone levels, plasma catecholamines, and mood disturbances has been investigated in 44 patients during days 2 to 5 of the immediate post-partum period. Fifty-two per cent of the mothers showed periods of emotional lability although there was no significant correlation between plasma concentrations of FSH, prolactin, oestrone, oestradiol, cortisol, or progesterone and the incidence of post-partum blues. In contrast there was a significant reduction of circulating catecholamines which correlated with mood disturbances. Women who experienced only a single day of post-partum blues had significantly lower levels of noradrenaline and adrenaline on that day compared with preceding or subsequent days.

Prolactin, human placental lactogen (HPL), oestrone, oestradiol and progesterone levels in plasma were measured before and during the first seven days after delivery in women who did not breast feed. The results confirmed the rapid clearance of placental steroids from the circulation after delivery. Plasma prolactin levels remained elevated during the early puerperium and the range of values were the same in non breast-feeding women and a group of breast feeding women. Of the 25 women studied, six developed breast engorgement. No difference in hormonal profiles were found leading to the conclusion that there is no endocrine basis for breast engorgement in non-breast feeding women.

Intraperitoneal, intravenous or oral administration of sodium oestrone [(35)S]-sulphate to male and female Medical Research Council hooded rats is followed by the rapid excretion of the bulk of the radioactivity in urine in the form of inorganic [(35)S]sulphate. Pre-treatment of rats with an antibiotic regimen does not affect the results except in the case of oral administration, when relatively large amounts of the dose are recovered as ester [(35)S]sulphate in faeces. Intravenous administration of the labelled ester to male and female rats with cannulae in bile duct and ureter gave results similar to those obtained with free-range animals. Only small amounts of radioactivity appeared in bile and this was mainly in the form of ester sulphate, including both oestrone [(35)S]sulphate and oestradiol-17beta 3[(35)S]-sulphate. Whole-body radioautography pinpointed the liver as the probable site of the desulphation of the sulphate ester and this was confirmed by liver and kidney perfusion experiments and by studies with rats in which kidney function had been eliminated by ligation of the renal pedicles.

The effects of a combination of aminoglutethimide (AG) 1,000 mg daily and 4-hydroxy-androstenedione (4OHA) 500 mg i.m. weekly on peripheral aromatase activity as measured by in vivo radioisotopic tracer methodology and serum oestrogen suppression were investigated in ten post-menopausal women with advanced breast cancer. Patients were treated for a minimum of 4 weeks with 4OHA before addition of AG for a minimum of 6 weeks. Aromatase inhibition was found to be nearly identical in the two treatment situations (92.5 +/- 4.7% and 93.8 +/- 3.8% respectively). There was no further significant suppression of plasma oestradiol or plasma oestrone levels when AG was added to 4OHA treatment (mean decrease of 7.6 +/- 12.1% and 2.8 +/- 12.0% respectively). In contrast, adding AG caused a further suppression of plasma oestrone sulphate (Oe1S) compared with 4OHA monotherapy (mean suppression of 35.2 +/- 9.1%, P < 0.025). This effect on Oe1S may be due to an influence of AG on oestrogen metabolism.

The effect of anastrozole on peripheral and tumour aromatase activity and oestrogen levels in postmenopausal patients with oestrogen receptor-rich breast tumours was investigated. Twenty-six patients were randomly allocated to treatment with anastrozole 1 mg (n=13) or 10 mg (n=13), once daily. Before and after 12 weeks' treatment, patients were infused with 3H-Delta4 androstenedione (20 MBq) and 14C-oestrone (E1) (1 MBq) for 18 h. Oestrogens were purified from excised tumours and plasma samples taken after each infusion. Peripheral and tumour aromatase activity and tumour E1 uptake were calculated from levels of 3H and 14C in purified E1 fractions from tumour and plasma. Endogenous tumour oestrogens were measured by radioimmunoassay. Twenty-three patients were available for analysis (1 mg group, n=12; 10 mg group, n=11). Following treatment, anastrozole (1 and 10 mg) markedly inhibited peripheral aromatase in all patients (the difference between pre- and on-treatment values being highly significant P<0.0001). In situ aromatase activity was also profoundly decreased by anastrozole treatment in 16 of 19 tumours (the difference with treatment also being highly significant P=0.0009). Most tumours were able to concentrate E1 beyond levels in the circulation; anastrozole treatment had no consistent effect on uptake of E1. Endogenous tumour levels of both E1 and oestradiol (E2) were significantly reduced with therapy (P=0.028 for E1 and P=0.0019 for E2). Anastrozole (1 and 10 mg daily) effectively suppresses aromatase activity, and subsequently oestrogen levels, within the breast tissue of postmenopausal women with large or locally advanced, operable, oestrogen receptor-rich breast cancers.

The boar produces considerable amounts of oestrogens in the Leydig-cells also occurring in semen. Very high oestrogen concentrations are measurable in the fluid of the tubuli, which contribute the main part of seminal oestrogens. Additionally, the accessory sex glands add 22% of the unconjugated oestrogens and 12% of conjugated oestrogens to the ejaculate. Concentrations vary considerably according to season and individuals. So far a maximum of 15.3 micrograms was measured in one ejaculate. Infusion of oestrogens (simulation of the oestrogen content of an ejaculate) at oestrus through a catheter into the uterus lumen leads to an increase of the myometrial contraction-frequency for 3 h. Additionally "inseminations" with oestradiol-17 beta (Oe 2), oestrone (Oe 1), and oestrone-sulfate (Oe 1-S) (naturally occurring in the ejaculate) in 10-micrograms amounts at oestrus may lead to an increase of PGF2 alpha concentrations in the uterine veins within a few minutes. This increase may be found after "insemination" with each of the three steroids but not after saline. A parallel rise of the "inseminated" oestrogen is measurable in the uterine vein plasma and may reach concentrations up to several thousand pg/ml. This rise also leads to significantly increased concentrations in peripheral plasma for about 30 min after the "insemination" of Oe 2 (increase of Oe 2 and Oe 1-S) and Oe 1 (Oe 1 and Oe 1-S). Consequences of seminal oestrogens for sperm transport and the timing of ovulation are discussed.

Steroid sulfatase (STS) is an important new therapeutic target in oncology. Attempts to design nonsteroidal STS inhibitors, because of the oestrogenicity of the original lead oestrone 3-O-sulfamate in rodents, have led to the discovery of benzophenone-4,4'-O,O-bis-sulfamate (BENZOMATE, 3). The nonfused bicyclic BENZOMATE is a highly potent STS inhibitor in vitro, inhibiting STS activity in intact MCF-7 breast cancer cells by>> 70% at 0.1 microM and in placental microsomes by>> 98% at 10 microM. When MCF-7 cells were pre-treated with 3 at 1 microM and then washed to remove unbound inhibitor, the initial 94% inhibition was reduced to 89% suggesting that 3, like other sulfamate-based STS inhibitors, inhibits the enzyme irreversibly. This agent also inhibits rat liver STS activity by 84% and 93% respectively 24 h after a single dose of 1 or 10 mg/kg, demonstrating that BENZOMATE possesses similar in vivo potency to the established potent nonsteroidal inhibitor 667COUMATE. Several modifications were made to BENZOMATE structurally and effects on in vitro activity were examined. These structure-activity relationship studies show that its carbonyl and bis-sulfamate groups are pivotal for activity, although conformational flexibility is not required. Two rigid anthraquinone-based sulfamate derivatives however showed inhibitory activity significantly better than BENZOMATE in the MCF-7 cell assay. BENZOMATE and related analogues therefore represent an important class of non-steroidal STS inhibitor and lead compounds for future drug design.

Breast cancer is a major cause of mortality in Western countries and there is an urgent requirement for novel treatment strategies. The nonsteroidal sulphatase inhibitor 667 COUMATE inhibits hepatic steroid sulphatase and growth of oestrone sulphate stimulated tumours in the nitrosomethylurea-induced rat mammary model. Other compounds that contain an aryl sulphamate moiety, for example, oestrone-3-O-sulphamate, are sequestered into red blood cells (RBCs). The aims of this study were to determine the pharmacokinetics of 667 COUMATE and to investigate its sequestration into RBCs. We administered a single p.o. or i.v. dose (10 mg kg(-1)) of 667 COUMATE to rats and used a high-performance liquid chromatography method to measure the levels of the agent and its putative metabolites in plasma. 667 COUMATE had a bioavailability of 95% and could be detected in plasma for up to 8 h. Using two independent analytical methods, we demonstrated that 667 COUMATE is sequestered by RBCs both ex vivo and in vivo. Previous investigations have revealed that 667 COUMATE is rapidly degraded in plasma ex vivo. In this study, we demonstrate that 667 COUMATE is stabilised due to its sequestration into RBCs. In conclusion, the pharmacological efficacy and high oral bioavailability of 667 COUMATE may be partly a consequence of the ability of RBCs to both protect the agent from metabolic degradation and facilitate its transport to tissues. These data support the further clinical evaluation of this novel endocrine therapeutic agent.

In contrast to the numerous studies of men, very few studies have been concerned with sex hormone disturbances in women with chronic alcoholic and non-alcoholic liver diseases. The aim of the study was, to evaluate the effect of ethanol and liver dysfunction on menstrual cycle, serum sex hormone concentrations and hepatic oestrogen receptors in women. In premenopausal female alcoholics ethanol consumption increase the frequency of menstrual disturbances, abortions, and miscarriages, while infertility is not frequent. Acute ethanol intoxication has only minor effects on pituitary-gonadal hormones in premenopausal women, while chronic ethanol abuse lead to reduced concentrations of sulphated steroids, and these changes may be seen before severe liver dysfunction has appeared. In women liver dysfunction lead to earlier occurrence of menopause in comparison with normal controls, while information is insufficient or lacking regarding the influence upon fertility, pregnancy outcome and sexual behavior in women. In postmenopausal women with alcoholic and non-alcoholic liver disease, the main disturbances of sex hormone metabolism consist of elevated oestrone and sex hormone binding globulin (SHBG) concentrations, while serum concentrations of steroid sulphates and 5 alpha-dihydrotestosterone (DHT) are reduced, and the degree of liver dysfunction is a major determinant for the observed disturbances. The presence of high affinity, low capacity, specific oestrogen receptors (ER) in the liver is confirmed using a ligand binding assay (DCC), specificity analyses, and sucrose gradient centrifugation. Furthermore, the sensitivity of an enzyme immunoassay has been improved enabling the quantitative measurement of hepatic ER in 102 small liver biopsies from patients with alcoholic and non-alcoholic liver diseases. The method is suitable for quantitative assessment and ER in small tissue samples, and can be applied to other tissues than the liver. Patients with chronic liver diseases have significantly lower hepatic ER concentrations, and this reduction is determined by the degree of liver dysfunction, while the degree of alcoholic hepatitis or active ethanol consumption are less important factors. The importance of this observation for hepatic physiology and pathophysiology remains to be determined.

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

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

BACKGROUND

Obesity is an independent adverse prognostic factor in early breast cancer patients, but it is still controversial whether obesity may affect adjuvant endocrine therapy efficacy. The aim of our study (ancillary to the two clinical trials Gruppo Italiano Mammella (GIM)4 and GIM5) was to investigate whether the circulating oestrogen levels during treatment with the aromatase inhibitor letrozole are related to body mass index (BMI) in postmenopausal women with breast cancer.

METHODS

Plasma concentration of oestrone sulphate (ES) was evaluated by radioimmunoassay in 370 patients. Plasma samples were obtained after at least 6 weeks of letrozole therapy (steady-state time). Patients were divided into four groups according to BMI. Differences among the geometric means (by ANOVA and ANCOVA) and correlation (by Spearman's rho) between the ES levels and BMI were assessed.

RESULTS

Picomolar geometric mean values (95% confidence interval, n=patients) of circulating ES during letrozole were 58.6 (51.0-67.2, n=150) when BMI was <25.0 kg m(-2); 65.6 (57.8-74.6, n=154) when 25.0-29.9 kg m(-2); 59.3 (47.1-74.6, n=50) when 30.0-34.9 kg m(-2); and 43.3 (23.0-81.7, n=16) when ≥35.0 kg m(-2). No statistically significant difference in terms of ES levels among groups and no correlation with BMI were observed.

CONCLUSIONS

Body mass index does not seem to affect circulating oestrogen levels in letrozole-treated patients.