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Objectives: The aim of this study was to investigate the influence of anastrozole on serum hormone levels in postmenopausal women with hormone receptor-positive breast cancer., Methods: We prospectively determined serum levels of estradiol, testosterone, dehydroepiandrosterone sulfate (DHEAS), sex hormone binding globulin (SHBG), follicle stimulating hormone (FSH) and luteinizing hormone (LH) at screening, as well as after 12 and 24 months of treatment and studied the associations with markers of bone turnover and bone mineral density (BMD)., Results: Altogether, a full set of hormone levels was available for 70 patients. Anastrozole treatment led to decreases of 92.1% for estradiol and 11.1% for LH over the observation period (p < 0.001). Conversely, FSH, DHEAS and testosterone concentrations increased by 5.9%, 33.3% and 50%, respectively (p < 0.001). SHBG levels remained stable during the 24 months of treatment (p = 0.355). There were modest associations between FSH, SHBG, CrossLaps and N-terminal propeptide of human procollagen type I (p < 0.05). Moreover, SHBG correlated positively with the BMD of femoral neck, total hip, total hip T-score, lumbar spine and the lumbar spine T-score, whereas FSH and estradiol correlated with the lumbar spine T-score (p < 0.05)., Conclusions: During the 24 months of follow-up, treatment with anastrozole decreased the serum levels of estradiol and LH. Furthermore, we found notable increases of serum levels of FSH, DHEAS and testosterone in the first 12 months of treatment, stabilizing thereafter. Additionally, we were able to correlate hormone levels with markers of bone turnover and BMD for the first time in this regard.

Objective: Coffee consumption has been inversely associated with type 2 diabetes risk, but its mechanisms are largely unknown. We aimed to examine whether plasma levels of sex hormones and sex hormone-binding globulin (SHBG) may account for the inverse association between coffee consumption and type 2 diabetes risk., Research Design and Methods: We conducted a case-control study nested in the prospective Women's Health Study (WHS). During a median follow-up of 10 years, 359 postmenopausal women with newly diagnosed type 2 diabetes were matched with 359 control subjects by age, race, duration of follow-up, and time of blood draw., Results: Caffeinated coffee was positively associated with SHBG but not with sex hormones. Multivariable-adjusted geometric mean levels of SHBG were 26.6 nmol/l among women consuming ≥4 cups/day of caffeinated coffee and 23.0 nmol/l among nondrinkers (P for trend = 0.01). In contrast, neither decaffeinated coffee nor tea was associated with SHBG or sex hormones. The multivariable-adjusted odds ratio (OR) of type 2 diabetes for women consuming ≥4 cups/day of caffeinated coffee compared with nondrinkers was 0.47 (95% CI 0.23-0.94; P for trend = 0.047). The association was largely attenuated after further adjusting for SHBG (OR 0.71 [95% CI 0.31-1.61]; P for trend = 0.47). In addition, carriers of rs6259 minor allele and noncarriers of rs6257 minor allele of SHBG gene consuming ≥2 cups/day of caffeinated coffee had lower risk of type 2 diabetes in directions corresponding to their associated SHBG., Conclusions: Our findings suggest that SHBG may account for the inverse association between coffee consumption and type 2 diabetes risk among postmenopausal women.

Objective: Exogenous sex hormone use is associated with many health effects. Current exogenous hormone use influences endogenous sex hormone levels, but little is known about longer term effects on endogenous hormones after cessation of use. The aim of this study was to examine the relationship between past hormone use and current endogenous hormone status., Design: This was a cross-sectional study of 1,983 postmenopausal women aged 55 to 81 years from the general community. The women were not currently using exogenous hormones. Past use of oral contraceptives (OCs) and hormone therapy (HT) as well as circulating endogenous sex hormones and sex hormone-binding globulin concentrations were evaluated., Results: Past OC users had significantly lower endogenous estradiol, estrone, androstenedione, testosterone, and sex hormone-binding globulin concentrations compared with never users independent of age, body mass index, smoking, physical activity, and reproductive factors. Past HT users had significantly lower testosterone and 17alpha-hydroxyprogesterone concentrations. Past OC use and HT use were both independently associated with lower testosterone concentrations: -9% (95% CI: -16% to -2%) for ever OC use compared with never OC use and -7% (95% CI: -17% to -2%) for ever HT use compared with never HT use. The magnitude of 5% to 10% differences in endogenous hormone concentrations was similar or greater for past OC use compared with past HT use, although OC use occurred earlier in the past., Conclusions: Past OC use and HT use seem to be related to long-term differences in endogenous sex hormones and sex hormone-binding globulin concentrations in postmenopausal women many years after cessation of use. These findings have implications for understanding the longer term effects of exogenous hormone exposures earlier in life with health and disease risk in later life.

Objective: To evaluate in a group of postmenopausal women the effects of long-term raloxifene treatment on breast density using a digitized analysis of mammograms and on insulinlike growth factor-1 (IGF-1), insulinlike growth factor binding protein-3 (IGFBP-3), and sex hormone-binding globulin (SHBG) plasma levels., Design: Seventy healthy postmenopausal women with normal body weight were enrolled in this study and were divided into two groups based on their bone status, evaluated by dual-energy x-ray at the lumbar spine (L2-4). Fifty women (chronological age 52.4 +/- 4.1 y, menopausal age 42.1 +/- 3.9 y), in whom the L2-4 T score was less than -2.5 SD, were treated with raloxifene HCl 60 mg/day orally for 2 years. The other 20 women (chronological age 53.6 +/- 3.5 y, age at menopause 43.1 +/- 3.6 y), in whom the L2-4 T score ranged between -1 and -2.5 SD, were enrolled as controls. All 70 women received calcium (1 g/d orally) and cholecalciferol (880 UI/d orally) supplementation. Moreover, all women followed a normocaloric and personalized diet. All women had mammography at baseline and after 2 years of therapy. The mammographic images on traditional support (radiography) were acquired by using a film scanner and were then elaborated by means of ad hoc software. Moreover, assessments of IGF-1, IGFBP-3, and SHBG plasma levels were obtained at baseline and after 24 months., Results: After 24 months of therapy, there was a significant variation in the raloxifene-treated group with respect to baseline in the distribution of gray classes of radiographic images. In particular, an attenuation of graphic trace with a reduction of the areas with the lowest and most elevated gray classes was observed. In the control group, no significant variations of graphic traces were observed. Moreover, raloxifene treatment significantly reduced IGF-1 and increased IGFBP-3 and SHBG plasma levels at 24 months. During follow-up, IGF-1, IGFPB-3, and SHBG levels did not change significantly in the control group., Conclusions: Long-term treatment with raloxifene in a population of postmenopausal women is able to reduce breast density. Such an effect could perhaps explain the reduction in the incidence of mammary carcinoma observed in the Multiple Outcomes of Raloxifene Evaluation study probably due to the direct antiestrogenic activity of raloxifene on mammalian tissue and/or its indirect activity increasing SHBG levels or modifying the IGF-1/IGFBP-3 ratio.

SHBG, the most important transport protein for sex steroids, is produced in the liver under the control of estrogen action. In a randomized, double-blind, prospective crossover study we compared basal levels of serum SHBG and their responses to increasing doses of oral and transdermal estradiol (E2), followed by E2 plus oral progestin (medroxyprogesterone acetate [MPA]), in 40 postmenopausal women with or without a history of intrahepatic cholestasis of pregnancy (ICP), which could affect the synthesis of SHBG. Serum samples collected at baseline, on the last day of each E2 period, and on the last day of the E2 plus MPA combination were assayed for SHBG and E2. Basal levels of SHBG showed no difference between the study groups. Oral but not transdermal E2 increased SHBG concentrations by 67-171% in the control group, but the response was smaller (42-121%) in the ICP group. Addition of MPA decreased SHBG levels by 14-18% in both groups during both treatments. In conclusion, a history of ICP is associated with blunted responses of SHBG to oral estrogen.

Objective: To compare ospemifene and raloxifene regarding their effects on hormones, lipids, genital tract, and tolerability in postmenopausal women., Design: A randomized, double-blind study in which 118 healthy postmenopausal women received 30 (n = 29), 60 (n = 30), or 90 mg (n = 30) of ospemifene or 60 mg (n = 29) of raloxifene for 3 months., Results: There were no significant differences in the baseline characteristics between study groups. In comparison with raloxifene, follicle-stimulating hormone levels decreased significantly more in the 90-mg ospemifene group and sex hormone-binding globulin levels increased more in all ospemifene groups. Total cholesterol and low-density lipoprotein cholesterol levels decreased more in raloxifene than in ospemifene groups, although the difference in low-density lipoprotein cholesterol between 90-mg ospemifene and raloxifene was not significant. Endometrial thickness did not change in any study group and endometrial biopsies showed atrophy in the majority of subjects at 3 months. All ospemifene groups demonstrated a clear estrogenic effect on the vaginal epithelium, as seen in Pap smears. This was in sharp contrast to the raloxifene group, which had no effect on the vaginal epithelium. Kupperman index decreased in all study groups during treatment. The adverse events were mild, mainly single cases, and no clustering of events was observed. There were no clinically significant abnormal findings in laboratory safety parameters., Conclusions: Ospemifene, at the dose of 90 mg/day, was more estrogenic than raloxifene, as shown by changes in serum follicle-stimulating hormone and sex hormone-binding globulin levels. Neither agent stimulated endometrium, but in contrast to raloxifene, ospemifene had a clear estrogenic effect in the vagina. Further studies with ospemifene are needed in subjects with vaginal atrophy.

There is growing evidence that soy isoflavones exert hormonal and antioxidant effects in postmenopausal women. In the present study, 12 postmenopausal Korean women with diabetic retinopathy consumed 2 g of genistein combined polysaccharides (GCP), containing 120 mg of genistein and 57 mg of daidzein, daily for 12 weeks. Blood was collected prior to and after 12 weeks of GCP supplementation for analysis of fasting blood glucose, insulin, lipid profiles, sex hormone-binding globulin (SHBG), estradiol, testosterone, free testosterone, and osteocalcin and activities of glutathione peroxidase (GSH-Px), catalase, and paraoxonase. After GCP supplementation, blood glucose, insulin, total cholesterol, triglyceride, high-density lipoprotein, and low-density lipoprotein cholesterols did not change significantly. However, there were significant increases in SHBG (P < .05) and testosterone (P < .05) and a decrease in estradiol (P < .01). Free testosterone levels were not significantly affected by GCP supplementation. After supplementation, osteocalcin decreased, but the difference was not statistically significant. Although activities of catalase and paraoxonase were unchanged, GSH-Px activity (P < .01) was increased significantly. These findings suggest that GCP supplementation may change the levels of some hormones and improve antioxidant status in postmenopausal Korean women with diabetic retinopathy.

Background: Fatty acid esters of 17beta-estradiol (E2) are estrogen metabolites associated with lipoproteins in blood., Aim: To study the effects of estrogen therapy on concentrations of serum E2 fatty acid esters in postmenopausal women with a history of an estrogen-related liver disorder, intrahepatic cholestasis of pregnancy (ICP), and in healthy women in a double-blind, crossover fashion., Method: ICP (n = 10) and control women (n = 10) received increasing doses of E2 valerate orally 2-4 mg/day, or transdermal E2 50-100 microg/day for 6 weeks. After a 4-week wash-out period, the subjects crossed over to the alternate E2 treatment. Concentrations of serum E2 fatty acid esters were quantified after saponification by fluoroimmunoassay., Results: Oral E2 administration increased median serum E2 fatty acid ester concentrations from 57 to 73 pmol/L in the ICP and from 56 to 74 pmol/L in the control group, in association with elevations in serum E2, estrone and sex hormone-binding globulin levels. Transdermal E2 treatment did not increase serum E2 ester levels., Conclusions: The increase in serum E2 fatty acid esters during oral E2 administration may be attributed, at least partly, to the higher estrogen dose during oral compared with transdermal therapy. A history of ICP did not affect esterification of E2 during estrogen therapy.

We reported the results of a randomized cross-over study comparing SH D 461 M (Climen) and Prempak-C in 38 postmenopausal women who were established users of hormone replacement therapy (HRT). Climen contains 11 tablets of 2 mg estradiol valerate (EV), and 10 tablets with 2 mg EV plus 1 mg of cyproterone acetate. Prempak-C, on the other hand, is a regimen consisting of 28 tablets of 0.625 mg conjugated equine estrogens (CEE); the last 12 tablets are taken together with 0.15 mg of norgestrel (NG) tablets. Patients in Sequence I started with Climen for 6 months and then crossed-over to Prempak-C, for the next 6 months. Patients in Sequence II followed the reverse order. Following Climen treatment, significantly higher levels (P < 0.05, t-test) of sex hormone binding globulin (SHBG) and estradiol, when compared to Prempak-C treated subjects, were noted. No significant differences in follicle stimulating hormone (FSH), corticosteroid binding globulin (CBG), renin angiotensinogen, angiotensin-I and aldosterone levels between the two treatment regimens were noted. While both regimens were effective in reducing menopausal symptoms, none of the regimens could eliminate all symptoms completely. Treatment with Climen appeared to result in less frequent occurrences of some symptoms. During periods of no estrogen (only true for Climen) as well as periods of maximum P and E, subjects on Climen had significantly lower incidence of some of the symptoms (backache, lack of concentration, lethargy and swelling) when compared to those on Prempak-C.(ABSTRACT TRUNCATED AT 250 WORDS)