Influence of gender and menopause on gastric emptying and motility

The aims of this study were to determine (a) if there are differences in gastric emptying rates of a mixed liquid and solid meal between men and women, (b) if menopausal status affects gastric emptying, and (c) whether differences in solid emptying rates are associated with alterations in postprandial antral motility parameters. A dual-isotope technique was used to measure gastric emptying in 20 men, 18 premenopausal women, 14 postmenopausal women, and 8 postmenopausal women taking estrogen and progesterone hormone replacement. A multilumen perfusion catheter was used to measure antral motility in 6 men and 6 premenopausal women. Premenopausal women, postmenopausal women, and postmenopausal women taking oral estrogen and progesterone had slower gastric emptying of liquids than did men (p less than 0.025, less than 0.05, and less than 0.025, respectively). Both premenopausal women and postmenopausal women taking sex hormone replacement therapy had slower emptying of solids than did men (p less than 0.025 and less than 0.05) but, in contrast to liquids, postmenopausal women not on hormone replacement emptied solids at a rate similar to that of men. There were no differences in postprandial antral motility parameters between men and premenopausal women. These findings support the hypothesis that sex steroid hormones have variable inhibitory effects on gastric emptying of a mixed meal and this should be considered when studying gastric emptying in disorders that occur predominantly in premenopausal women.     

Sex hormones in postmenopausal women with primary biliary cirrhosis.

To evaluate serum sex hormone profiles in nonalcoholic postmenopausal women with liver disease, 25 women with primary biliary cirrhosis (11 in cirrhotic stage) and 46 healthy controls were studied. The patients had significantly (p less than 0.05) elevated serum concentrations of estrone and androstenedione and significantly (p less than 0.05) lower concentrations of estrone sulfate, dehydroepiandrosterone sulfate and 5 alpha-dihydrotestosterone compared with the 46 controls. Serum concentrations of sex hormone binding globulin, testosterone, non-sex hormone binding globulin-bound testosterone and non-protein-bound testosterone did not differ significantly (p greater than 0.05) between primary biliary cirrhosis patients and controls. Patients in the cirrhotic stage had significantly (p less than 0.05) higher concentrations of sex hormone binding globulin than did controls. Patients in the cirrhotic stage had significantly (p less than 0.05) higher sex hormone binding globulin and estrone sulfate levels compared with noncirrhotic patients with primary biliary cirrhosis. Otherwise, no significant differences were observed between cirrhotic and noncirrhotic patients. The observed changes in steroid concentrations may be a consequence of hepatic dysfunction.     

Menopausal age and sex hormones in postmenopausal women with alcoholic and non-alcoholic liver disease.

In order to evaluate age at menopause and serum sex hormone profiles in postmenopausal women with stable chronic liver disease, six non-cirrhotic alcoholics, 13 with alcoholic cirrhosis, eight with non-alcoholic cirrhosis, and 46 healthy controls were studied. In all three groups, patients were significantly (p less than 0.05) younger at the time of natural menopause than controls. Compared to controls, non-cirrhotic alcoholic women had significantly (p less than 0.05) reduced levels of DHAS, significantly (p less than 0.05) more alcoholic cirrhotic women had detectable oestradiol concentrations, elevated concentrations of oestrone and sex hormone binding globulin (SHBG) and reduced levels of 5 alpha-dihydrotestosterone (DHT), while women with non-alcoholic cirrhosis had significantly elevated concentrations of SHBG and reduced levels of oestrone sulphate, DHT, androstenedione and dehydroepiandrosterone sulphate (DHAS) (p less than 0.05). The observed changes may be a consequence of liver disease since similar changes were observed in patients with alcoholic and non-alcoholic liver disease, but an additional effect of alcohol cannot be excluded.     

Sex hormones and bone metabolism in postmenopausal rheumatoid arthritis treated with two different glucocorticoids.

To investigate the effect of low doses of 2 different glucocorticoids on bone mass, sex hormone status and bone metabolic indices, a study was undertaken in 16 postmenopausal women with rheumatoid arthritis (RA) receiving < 15 mg/day of deflazacort and in 16 patients with RA matched for age, years postmenopause and disease duration, receiving < 10 mg/day of prednisone. Sixteen healthy postmenopausal women and 16 nonsteroid treated patients with RA were also studied as control groups. Vertebral bone density (vBMD) was lower (mean +/- SD: 0.65 +/- 0.07 vs 0.73 +/- 0.09 g/cm2; p < 0.02) in prednisone treated patients than in deflazacort treated patients, whose vBMD values were similar to those of nonsteroid treated RA. No significant difference was found as for radial bone mineral content. Circulating levels of estradiol, dehydroepiandrosterone sulfate, androstenedione and progesterone were low in all patient groups with RA when compared with healthy controls. The prednisone treated patients showed significantly lower values of all sex hormones with respect to deflazacort treated patients. Osteocalcin values were also lower (3.0 +/- 1.4 vs 3.9 +/- 1.6 ng/ml; p < 0.05) in prednisone treated patients with respect to deflazacort treated group. Glucocorticoid treated patients showed a direct correlation (r2 = 0.39) between vBMD and plasma estradiol levels, while no correlation was found with osteocalcin values. In conclusion, our postmenopausal patients with RA treated with low dose prednisone had reduced levels of sex hormones and osteocalcin and reduced vertebral bone mass. Comparable doses of deflazacort showed only a mild inhibitory effect on sex hormones and osteocalcin, and did not show any detectable effect on bone mass.     

Transdermal 17 beta-estradiol combined with oral progestogen increases plasma levels of insulin-like growth factor-I in postmenopausal women.

In order to evaluate the effect of postmenopausal estrogen replacement therapy on the plasma levels of the insulin-like growth factor-I (IGF-I) 12 postmenopausal women aged 44 to 59 years were studied. The control group consisted of 15 healthy premenopausal women aged 20-44 years. In the postmenopausal women the plasma levels of IGF-I, gonadotrophins and sex hormones were determined before and after 3 and 6 months cyclic replacement therapy with transdermal 17 beta-estradiol (E2 100 micrograms patches applied twice weekly) combined with oral chlormadinone acetate (2 mg daily for 7 days in each cycle). Basal levels of estradiol (E2), IGF-I, dehydroepiandrosterone sulphate (DHEA-S), testosterone and androstenedione were lower, but gonadotropin levels were higher in postmenopausal than in premenopausal women. In all the women studied age was inversely correlated with IGF-I levels (r = -0.793, p less than 0.001) and with DHEA-S concentrations (r = -0.435, p less than 0.02). In postmenopausal women transdermal estradiol administration restored the circulating E2 levels to the early follicular range and increased the IGF-I levels (from 76.4 +/- 9.2 micrograms/l to 141.8 +/- 20.8 micrograms/l; p less than 0.01). Transdermal estradiol decreased gonadotrophin levels without changes in concentration of DHEA-S, testosterone, androstenedione and SHBG. In postmenopausal women before and during replacement therapy a positive correlation was found between estradiol and IGF-I concentrations (r = -0.439, p less than 0.01). These results suggest that cyclic replacement therapy with transdermal 17 beta-estradiol in combination with chlormadinone acetate given orally increase the plasma levels of IGF-I in postmenopausal women.     

Dyslipoproteinemia in patients with active rheumatoid arthritis: effects of disease activity, sex, and menopausal status on lipid profiles

OBJECTIVE: To investigate the lipid profiles in patients with active rheumatoid arthritis (RA) and to assess the relationship of inflammatory disease activity markers, sex, and menopausal status with lipid profiles. METHODS: Three groups of patients with active RA (n = 184) were studied: men (n = 61, mean age 50.8 +/- 4.81 yrs), premenopausal women (n = 58, mean age 39.2 +/- 2.44 yrs), and postmenopausal women (n = 65, mean age 60.4 +/- 2.14 yrs), and healthy controls (n = 161): men (n = 65, mean age 50.9 +/- 3.42 yrs), premenopausal women (n = 47, mean age 40.3 +/- 1.66 yrs), and postmenopausal women (n = 49, mean age 61.3 +/- 3.16 yrs). We measured fasting plasma levels of total cholesterol (TC), triglyceride (TG), HDL-cholesterol (HDL-C), LDL-cholesterol (LDL-C), lipoprotein (a) [LP(a)], apolipoprotein A1 (apo A1), apolipoprotein B (apo B), and erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). RESULTS: Male RA patients had significantly higher apo B/apo A1 and LP(a) and lower HDL-C than male controls. Female RA patients had significantly higher TC, LDL-C, and LP(a) than female controls. Premenopausal RA patients had significantly higher LDL-C, TC/HDL-C, LDL-C/HDL-C, and apo B/apo A1 and lower TG and HDL-C than premenopausal controls. Postmenopausal RA women had significantly higher TG and LP(a) and lower TC than postmenopausal controls. Female RA patients had higher HDL-C, apo A1, and TC/HDL-C and lower apo B/apo A1 than male RA patients. Postmenopausal RA patients had significantly higher TC, TG, TC/HDL-C, apo B, LP(a), and LDL-C/HDL-C than premenopausal RA patients. CRP correlated positively with TC/HDL-C, LDL-C/HDL-C, and apo B/apo A1 and negatively with HDL-C in male RA patients. In female RA patients CRP had positive correlation with TC/HDL-C and LDL-C/HDL-C and negative correlation with HDL-C. CONCLUSION: These findings suggest that patients with active RA have altered lipid profiles and that disease activity, sex, and menopausal status affect lipid profiles, and these would be expected to change the pattern of atherosclerotic events in RA.     

Prolactin and growth hormone responses to hypoglycemia in patients with rheumatoid arthritis and ankylosing spondylitis

OBJECTIVE: Prolactin (PRL) and growth hormone (GH) are pituitary hormones with immunomodulating properties. Their upregulated secretion may play a role in the pathogenesis of chronic inflammatory diseases. We evaluated PRL and GH responses to secretion stimulus in patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS). METHODS: Insulin hypoglycemia (0.1 IU/kg) was induced in 15 women with RA, 18 men with AS, and healthy controls matched for age, sex and body mass index. Plasma concentrations of glucose, PRL, GH, interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF-a) were analyzed. RESULTS: RA patients had significantly lower area under the curve (AUC) of PRL (p = 0.049) compared to RA controls. During hypoglycemia double or higher increase of plasma PRL occurred in 5 RA (33%) patients and in 8 RA controls (57%). Using the General Linear Model procedure, no significant differences in PRL or GH responses were observed in patients with RA and AS. TNF-a was higher in patients with RA compared to RA controls (p < 0.05). There was no significant difference in TNF-a concentrations between AS patients and AS controls. IL-6 was higher in RA patients compared to controls (p < 0.05) and in AS patients compared to controls (p < 0.01). Significant positive correlation was found between TNF-a levels and AUC of PRL in AS patients (r = 0.46, p = 0.047), but not in the 2 control groups or in RA patients. CONCLUSION: Our results indicate no upregulated PRL or GH responses to stimulation in premenopausal women with RA or men with AS.     

A therapeutic dilemma: suppressive doses of thyroxine significantly reduce bone mineral measurements in both premenopausal and postmenopausal women with thyroid carcinoma

We measured lumbar spine, femoral neck, and forearm bone mineral (BMD) in 24 women (14 premenopausal and 10 postmenopausal) who had been treated with total thyroidectomy and 131 Iodine ablation therapy for nonanaplastic thyroid carcinoma and 24 case controls. At the time of the study, all patients were free of cancer (negative 131 Iodine whole body scan and serum thyroglobulin levels less than 0.3 micrograms/L) and all were receiving doses of T4 sufficiently high to prevent a rise in a serum thyroid-stimulating hormone concentration after an iv bolus of TRH. Femoral neck BMD were significantly reduced in both the premenopausal women (89 +/- 3.8% of case controls, 95% CI, 81 to 98) and postmenopausal women (77 +/- 3.9% of case controls; 95% CI, 68 to 86) receiving T4. Lumbar spine BMD and forearm BMD were unaffected in the premenopausal women, but significantly reduced in the postmenopausal women receiving T4 (lumbar spine BMD = 84 +/- 6.2% of case controls; 95% CI, 70 to 98 and forearm BMD = 89 +/- 5.6% of case controls; 95% CI, 76 to 101). Serum bone Gla-protein, a marker of bone turnover, was significantly increased in both the premenopausal and the postmenopausal women receiving T4 compared to case controls (P less than 0.001 for the difference between patient groups and controls). Whereas the cumulative dose of T4 was highly correlated with the femoral neck BMD in the premenopausal patients (r = 0.528; P less than 0.05); the presence of hypogonadism was the main determinant of the lumbar spine and forearm BMD. This data confirms that premenopausal and postmenopausal women receiving suppressive doses of T4 for thyroid carcinoma have diminished bone mineral measurements and are at risk for osteoporosis.     

Endogenous Sex Hormones and Cholesterol Gallstones: A Case-Control Study in an Echographic Survey of Gallstones

In a population survey of gallstones, the serum levels of hormones of the pituitary-gonadal axis and the sex hormone-binding globulin (SHBG) were compared in subjects with cholesterol gallstones and in a control group. In 84 subjects who entered the survey, echo-graphic gallstones that had been identified at the survey, turned out to be radiolucent or mixed (predominantly of cholesterol) at subsequent x-ray. The controls were without gallstones at echography, matched to the cases for potential confounders of the association sex hormones-cholelithiasis. Testosterone (T) 17-β-estradiol (E2), 17-OH progesterone (P), and SHBG were dosed by radioimmunoassay; follicle-stimulating hormone (FSH), Iuteinizing hormone (LH), and prolactin (Prl) by dissociation-enhanced lanthanide fluoro immunoassay (DELFIA). Men with gallstones had lower LH than controls (n = 34, median difference = -0.62 mU/ml, 95% confidence interval (CI) -1.20 to -0.26 mU/ml, paired sign test, p = 0.003). Premenopausal women in the luteal phase of the menstrual cycle with gallstones had higher E2 than controls (n = 7, median difference: +117, pg/ml, 95% CI: +10 to +218 pg/ml, p = 0.008). Postmenopausal women had lower LH than controls (n = 35, median difference = -4.57 mU/ml, 95% CI -9.5 to -1.0 mU/ml, p = 0.04). No other hormones showed statistically significant differences between cases and controls, in either males or females. The findings of this exploratory study in subjects with radiolucent and mixed gallstones suggest that men and postmenopausal women have lower LH, and premenopausal women in the luteal phase of the cycle have higher E2, than controls.     

The effect of glucocorticoids on bone mass in rheumatoid arthritis patients. Influence of menopausal state

We studied 97 patients with definite or classic rheumatoid arthritis (RA). Fifty-four patients (19 premenopausal women, 25 postmenopausal women, and 10 men) had been treated with low-dose glucocorticoids for at least 12 months (mean dose less than 10 mg/day). The remaining 43 patients (15 premenopausal women, 17 postmenopausal women, and 11 men) had been treated with penicillamine, and served as a patient control group. The distal forearm bone mineral content (BMC) was measured in all patients by single photon absorptiometry using 125I, and the total body bone mineral (TBBM) was measured in 61 patients by dual photon absorptiometry using 153Gd. Compared with normal controls, both treatment groups had significantly decreased BMC and TBBM (0.01 less than P less than 0.001). When the patients were stratified according to pre- and postmenopausal state, we found significantly lower BMC and TBBM values in the premenopausal glucocorticoid-treated women than in penicillamine-treated women. However, no differences in BMC and TBBM values were found in the corresponding postmenopausal groups. In the premenopausal women treated with glucocorticoids, the duration of treatment and cumulative dose correlated with BMC. No such correlations were found in the postmenopausal women. We conclude that 1) RA is associated with loss of bone mass, 2) systemic glucocorticoid treatment further aggravates the bone loss, 3) in postmenopausal RA patients, the bone loss resulting from menopause and from the disease itself is not accelerated by low-dose glucocorticoids, and 4) in premenopausal RA patients, however, the bone mass is significantly affected by glucocorticoid treatment. We therefore suggest that these factors be considered when prescribing glucocorticoids, in order to minimize the bone loss.     

Premenopausal sexual dimorphism in lipopolysaccharide-stimulated production and secretion of tumor necrosis factor

OBJECTIVE: To establish whether sexual dimorphism in tumor necrosis factor (TNF) concentration in lipopolysaccharide (LPS)-stimulated whole blood culture is related to menopausal status or hormone concentrations. METHODS: Healthy volunteers (72 premenopausal female, 159 male, and 62 postmenopausal female) completed questionnaires and gave peripheral blood specimens for whole blood LPS-stimulated TNF assay and for selected hormone levels. TNFab microsatellite markers were genotyped. RESULTS: Mean LPS-stimulated TNF level in the premenopausal female group was 18% lower than the postmenopausal female mean (1579 +/- 913 pg/ml compared with 2257 +/- 881 in the men and 1965 +/- 950 in the postmenopausal women; p < 0.0003 and p 0.058, respectively). Analyzing a subset for which blood counts were obtained, mean stimulated TNF per monocyte was lower in the premenopausal female group than in the postmenopausal female group and appeared lower than in the male group (2.67 +/- 1.96 pg/ml per 10(3) monocytes vs 4.44 +/- 2.16 and 3.60 +/- 1.40; p = 0.018 and p = 0.12, respectively). Total plasma cortisol was higher in premenopausal women than men, and, in turn, higher in men than postmenopausal women (mean +/- SD 16.1 +/- 5.7, 12.2 +/- 3.6, and 10.4 +/- 4.3 microg/dl, respectively; p < 0.05 for each comparison). Using multiple linear regression to correct for covariates and TNF allelic effects, premenopausal status predicted TNF level independently from potential confounders or TNF genetic markers (covariate-adjusted decrement of 408 pg/ml; p = 0.0241). In the male group, total cortisol predicted lower TNF level (coefficient -67.5 pg/ml for each microg/dl cortisol; p = 0.0006 after stepwise selection), but total testosterone had no effect. In premenopausal women, LPS-stimulated TNF was not related to total estradiol, testosterone, or cortisol level. CONCLUSION: Premenopausal women had a lower mean whole blood LPS-stimulated TNF level than postmenopausal women, but there was no significant relation to total estradiol, testosterone, or cortisol levels in premenopausal women.     

Differences in low density lipoprotein subfractions and apolipoproteins in premenopausal and postmenopausal women

Postmenopausal or oophorectomized women are at higher risk for the development of coronary artery disease than are premenopausal women. These differences in risk may be due to alternations in plasma lipoproteins modulated by hormonal changes. Plasma cholesterol, triglyceride, lipoprotein cholesterol, and apolipoprotein A-I and B (apoB) concentrations, as well as low density lipoprotein (LDL) particle size (LDL 1-7), as assessed by 2-16% polyacrylamide-agarose gradient gel electrophoresis, were determined in 87 premenopausal and 43 postmenopausal women. All were participants in the Framingham Offspring Study, were gynecologically normal, and were not taking any hormones. The postmenopausal women had significantly (P less than 0.05) higher plasma LDL cholesterol concentrations than did the premenopausal women. Plasma triglyceride, total cholesterol, very low density lipoprotein cholesterol, and apoB levels were higher, and apoA-I and high density lipoprotein cholesterol were lower in the postmenopausal group, but these differences were not significant at P less than 0.05. The postmenopausal women were likely to have small LDL particles compared to premenopausal women. Controlling for age and body mass index effects significantly reduced the differences in total cholesterol, LDL cholesterol, apoB, and LDL particle size and broadened the differences in apoA-I and high density lipoprotein cholesterol. These data indicate that menopause is positively correlated with LDL cholesterol (P less than 0.05) and decreased LDL particle size (P less than 0.05) after adjusting for significant covariates.     

Sex hormone concentrations in patients with rheumatoid arthritis are not normalized during 12 weeks of anti-tumor necrosis factor therapy

OBJECTIVE: Androgens such as dehydroepiandrosterone sulfate (DHEAS) and testosterone are markedly lower in postmenopausal women with rheumatoid arthritis (RA) than in controls. In contrast, compared to controls, serum levels of estrogens are normal or elevated in women with RA. Since tumor necrosis factor (TNF) alters production of these hormones, we investigated changes of these hormones during anti-TNF antibody (anti-TNF) therapy with adalimumab in longstanding RA. METHODS: In this longitudinal anti-TNF therapy study in 13 patients with long-standing RA without prior prednisolone (7 infusions of anti-TNF: Week 0, 2, 4, 6, 8, 10, and 12), we measured serum concentrations of interleukin 6 (IL-6), androstenedione, DHEA, DHEAS, free testosterone, estrone, and 17ss-estradiol. Levels of these hormones in patients were compared to serum levels of 31 age and sex matched healthy controls. RESULTS: Upon treatment with anti-TNF, there was an impressive decrease of clinical markers of inflammation, erythrocyte sedimentation rate, and serum levels of IL-6. Serum levels of DHEAS and free testosterone were markedly lower at baseline in patients compared to controls, but this did not change during anti-TNF therapy. Serum levels of DHEA and 17ss-estradiol were significantly elevated in patients compared to controls, but similarly, anti-TNF therapy did not change initially increased levels. Molar ratios of hormones, which reflect hormone shifts via converting enzymes, showed typical alterations at baseline, but did not change markedly during anti-TNF therapy. CONCLUSION: Longterm therapy with anti-TNF did not change altered serum levels of typical sex hormones in patients with RA, although baseline values were largely different. In patients with RA, this indicates that alterations of sex hormones and altered activity of respective converting enzymes are imprinted for a long-lasting period over at least 12 weeks.     

Mineral metabolism in postmenopausal women with active rheumatoid arthritis

Serum and urinary variables of bone mineral metabolism were studied in 49 postmenopausal women with rheumatoid arthritis (RA). Results were compared to those in a sex, age and menopausal age matched control group. No patient took corticosteroids, or had any disease other than RA which might affect bone. Total serum calcium was low in patients with RA compared to controls (9.0 +/- 0.5 mg% vs 9.3 +/- 0.3 mg%, p less than 0.005), but was normal when corrected for albumin (9.5 +/- 0.6 mg% vs 9.3 +/- 0.4 mg%, NS). Serum phosphorus was significantly higher in patients with RA than in controls (3.6 +/- 0.3 mg% vs 3.3 +/- 0.4 mg%, p less than 0.001) as well as serum alkaline phosphatase activity (107.6 +/- 27.2 IU/l vs. 9.6 +/- 28.91 IU/l). Serum creatinine, vitamin D and parathyroid hormone levels were comparable in both groups. Urinary hydroxyproline and mucopolysaccharide excretions were higher in patients with RA than controls, both for fasting (respectively 0.089 +/- 0.028 vs 0.039 +/- 0.023, p less than 0.001 and 0.072 +/- 0.027 vs 0.047 +/- 0.019, p less than 0.001) and for 24 h values (50.3 +/- 17.9 mg vs 36.2 +/- 15.4 mg, p less than 0.001 and 54.6 +/- 26.0 mg vs 41.7 +/- 16.5 mg, p less than 0.05). Urinary calcium excretion was comparable in the 2 groups. Our findings of raised serum phosphorus and alkaline phosphatase activity, raised urinary hydroxyproline and mucopolysaccharides excretion suggest that in patients with RA there is a higher metabolic activity of bone. In none of the patients could any indication of osteomalacia or of parathyroid overactivity be found.     

REDUCED FOREARM BONE MINERAL CONTENT AND BIOCHEMICAL EVIDENCE OF INCREASED BONE TURNOVER IN WOMEN WITH EUTHYROID GOITRE TREATED WITH THYROID HORMONE

We used single-photon absorptiometry to assess forearm bone mineral content (BMC/BW) (arbitrary units normalized for bone width) at a proximal site (PBMC/BW) and at a more distal site (DBMC/BW) in 60 women treated with 25-50 micrograms T3 or 50-100 micrograms T4 for euthyroid goitre, in 13 untreated goitre patients, and in 2 controls matched for age and menopausal state for each goitre patient. BMC/BW was not significantly different between untreated goitre patients and controls. In 36 premenopausal patients, treated for 5.8 +/- 5.4 years (mean +/- SD) a slight decrease in PBMC/BW of about 5% compared to controls to controls was observed (PBMC/BW 1.42 +/- 0.19 vs 1.49 +/- 0.13, P less than 0.05). In 24 postmenopausal patients, treated for 10.0 +/- 5.8 year, a 20% deficit in BMC/BW compared to controls was found (DBMC/BW 0.80 +/- 0.18 vs 1.06 +/- 0.20, P less than 0.001 and PBMC/BW 1.14 +/- 0.20 vs 1.42 +/- 0.19, P less than 0.001). Biochemical indices of bone metabolism in 43 pre and post-menopausal patients and 43 controls showed in the patients a higher serum alkaline phosphatase activity (AP) (P less than 0.01 and P less than 0.05 and serum osteocalcin (NS and P less than 0.05). AP was negatively correlated with TSH levels and, in postmenopausal patients, with DBMC/BW and PBMC/BW. Our results suggest that treatment of euthyroid women with moderate doses of thyroid hormone increases bone turnover with clear adverse effects on bone mineral status in postmenopausal patients.     

Interrelationships between weight loss, body fat distribution and sex hormones in pre- and postmenopausal obese women

Objectives. Relationships between regional body fat distribution and sex hormones as well as changes in sex hormones after weight loss were evaluated. Setting. All subjects were hospitalized in the Institute of Internal Medicine of the University of Verona. Subjects. Twenty-six premenopausal (age 33.7± 10.2 years) and 15 postmenopausal (age 57.9±5.9 years) obese women. Interventions. Body weight, body-mass index, waist and hip circumferences, visceral fat by computed tomography and sex hormones were evaluated before and after 4 weeks on a very low energy diet. Results. Body-mass index was higher in pre- than in postmenopausal women, although the difference was not significant. Total and free testosterone were significantly higher in the pre- than in the postmenopausal group (P<0.001). Significant negative correlations were found between age and total testosterone (r=?0.65; P<0.001), free testosterone (r=?0.54; P<0.001), androstenedione (r=?0.46; P<0.01) and urinary cortisol excretion (r=?0.50; P<0.01). A negative correlation was found between visceral fat and total testosterone (r=?0.41; P<0.01). After adjusting for age, the negative correlation between total testosterone and visceral fat encountered both in the subject group as a whole and in premenopausal women was no longer significant, whilst a significant negative association between visceral fat and sex hormone binding globulin (SHBG) (r=?0.56; P<0.001) was always found. When step-down regression analysis was used to evaluate the joint effect of age, menopausal status, and anthropometric and metabolic variables on sex hormones, age was the most powerful independent variable for predicting total testosterone, free testosterone and androstenedione levels, whilst menopausal status was the most powerful predictor of FSH and LH levels. Changes in hormones after VLED were analysed separately in pre- and postmenopausal women. None of the hormones changed significantly after VLED in the postmenopausal group, except for FSH values. LH, free testosterone and urinary cortisol excretion values decreased significantly after VLED in the premenopausal group. Conclusions. Our data show that age, to a greater extent than visceral fat, seems to be negatively associated with steroid sex hormones. Weight loss seems to be associated with changes in sex hormones only in premenopausal women.     

Effect of postmenopause and hormone replacement therapy on serum adiponectin levels

Little is known about the effects of menopause and hormone replacement therapy (HRT) on adiponectin production. The objectives of the study were to compare levels of serum adiponectin in post- and premenopausal women, to test whether adiponectin levels are related to endogenous estradiol and sex hormone-binding globulin (SHBG) levels, to determine whether HRT influences serum adiponectin, and to investigate relationships of adiponectin levels with cardiovascular risk factors. One hundred four women matched for body mass index were enrolled in this study, and among them were 34 postmenopausal HRT nonusers, 34 postmenopausal HRT users, and 36 premenopausal healthy women with regular menstrual cycles. We evaluated waist circumference and waist-to-hip ratio (WHR) in each women. Serum was assayed for adiponectin, estradiol, SHBG, triglycerides (TGs), total cholesterol, high-density lipoprotein cholesterol, and fasting glucose levels. Post- and premenopausal women showed no significant differences in adiponectin and SHBG concentrations. There were no differences in serum adiponectin levels between postmenopusal HRT nonusers and users; however, SHBG concentrations were higher in HRT users. The simple linear regression analyses of all studied women indicated that serum adiponectin was negatively correlated with body mass index, waist circumference, WHR, and TG levels. Positive correlation was observed between adiponectin and high-density lipoprotein cholesterol as well as between adiponectin and SHBG levels. There were no relationships between adiponectin and estradiol levels in all studied women and among subgroups. Multiple regression analysis showed that WHR and TG were significant independent predictors of serum adiponectin. In conclusion, serum adiponectin levels are not influenced by menopausal status or serum estradiol levels. Exogenous estrogen treatment does not significantly affect serum adiponectin concentrations.     

Thyroid hormone deficiency and postmenopausal status independently increase serum osteoprotegerin concentrations in women

OBJECTIVE: To study the impact of thyroxine (T4) withdrawal on serum osteoprotegerin concentrations in women, using a healthy euthyroid control group matched for age and postmenopausal status as reference. Subjects and design: Nineteen women with differentiated thyroid carcinoma were studied the last day on T4 suppressive treatment, 4-7 days after withdrawal and the day before whole body scanning. Eighteen women matched for age and postmenopausal status served as controls. Serum thyroid hormones, urinary bone markers and serum osteoprotegerin concentrations were measured. Statistical methods included repeated measures analysis of variance and one-way analysis of variance. RESULTS: Patients progressed from subclinical or mild hyperthyroidism at baseline to normal free T4 and triiodothyronine levels 4-7 days later, ending in overt hypothyroidism before scanning. Serum osteoprotegerin increased, and urinary deoxypyridolines/creatinine and pyridolines/creatinine ratios decreased, with acute hypothyroidism (P = 0.026, P = 0.003, and P < 0.001 respectively). Urinary deoxypyridolines/creatinine ratio, pyridolines/creatinine ratio, and serum osteocalcin during hypothyroidism were lower compared with those of healthy controls (P = 0.023, P = 0.019, and P = 0.011 respectively). Serum osteoprotegerin concentrations were higher in postmenopausal patients when compared with premenopausal ones, irrespective of the changes in thyroid function (P = 0.001). CONCLUSION: Serum osteoprotegerin concentrations increase following acute hypothyroidism after T4 withdrawal in women with differentiated thyroid carcinoma, and also with postmenopausal status.     

Skeletal integrity in premenopausal and postmenopausal women receiving long-term L-thyroxine therapy.

PURPOSE: The impact of long-term L-thyroxine replacement therapy on skeletal integrity is a growing concern because of the large number of women receiving thyroid hormone therapy. The purpose of this study was to examine the hypothesis that long-term L-thyroxine therapy in which the free thyroxine index (FT4I) is maintained within a physiologic range has minimal impact on vertebral or femoral bone mineral density in both premenopausal and postmenopausal women. PATIENTS AND METHODS: We measured hip integral and spinal trabecular and integral bone densities in 28 premenopausal and 28 postmenopausal women who had been receiving L-thyroxine therapy for a median of 12 and 15 years, respectively, and in whom therapy was titrated to keep the FT4I within the normal range. The relationship between bone density parameters and thyroid hormone status was examined using univariate and multivariate statistical methods. RESULTS: Seventy-nine percent of the premenopausal women and 86% of the postmenopausal women had FT4I values in the normal range at the time of bone density determination. Moreover, throughout the study's duration, the majority of annually measured values were in the normal range for more than 80% of subjects. Premenopausal women had slightly lower bone density than would be expected for age: -6.7% (z = -0.39 +/- 0.74 [mean +/- SD], p less than 0.01), -3.1% (z = -0.22 +/- 0.78, p = 0.15), and -5.1% (z = -0.36 +/- 0.74, p less than 0.02) for spinal trabecular, spinal integral, and hip integral bone density, respectively. Postmenopausal women likewise had slightly lower bone density values that were significant only at the hip: -0.2% (z = -0.01 +/- 1.01, p = 0.95), -1.0% (z = -0.05 +/- 1.11, p = 0.80), and -6.2% (z = -0.39 +/- 0.80, p less than 0.02) for spinal trabecular, spinal integral, and hip integral bone density, respectively. When patients with previously treated Graves' disease (n = 4 in each group) were eliminated, the differences in bone density at the hip were no longer seen. Correlation analysis revealed only weak and generally nonsignificant relationships between parameters of thyroid hormone status and bone density at any site in either subgroup. Results of multiple regression analysis among the pooled data of all subjects showed that age provided a consistently significant contribution (R2 = 0.18 to 0.66) to the variability in bone density at the spine and the hip, but parameters of thyroid hormone status did not. CONCLUSION: These data provide the first supportive evidence that long-term L-thyroxine therapy that maintains the FT4I in the physiologic range is associated with a statistically significant, but clinically minimal, decrement in spinal and hip bone density in both premenopausal and postmenopausal women. The decrement at the hip was entirely due to the inclusion of patients with treated Graves' diseases. Thus, the changes in bone density in women receiving long-term L-thyroxine therapy are minimal at most and should not be a contraindication to therapy.     

Sex hormones in obese premenopausal women and their relationships to body fat mass and distribution, B cell function and diet composition

We examined sex hormone blood concentrations in a group of 33 obese non-hirsute premenopausal women with normal menses and in 14 age-matched normal-weight controls, and evaluated their relationship with anthropometric parameters, dietary habits and insulin levels. Obese women showed lower than control sex hormone-binding globulin (24.9 +/- 14.6 vs 38.6 +/- 12.5 nmol/l; p less than 0.005) and 5 alpha-dihydrotestosterone (13.7 +/- 5.4 vs 18.2 +/- 4.8 ng/dl; p less than 0.005) values. Despite their consensual behavior, the correlation coefficient between 5 alpha-dihydrotestosterone and sex hormone-binding globulin was not significant in the obese while in controls it was 0.68 (p less than 0.01). This suggests that mechanisms operating to lower the plasma levels of these compounds may be regulated differently in obesity. Body Mass Index, per cent body fat and its distribution showed a highly significant negative correlation with sex-hormone binding-globulin and 5 alpha-dihydrotestosterone values. Insulin levels did not appear to be correlated with sex hormone values. On the contrary, in the obese women we found a highly significant correlation between dietary lipids and sex-hormone-binding-globulin levels (r = -0.54; p less than 0.005) and between dietary carbohydrates and estrone values (r = 0.47; p less than 0.005); all these relationships were independent of body weight. These results confirm that in premenopausal women obesity may be characterized by detectable changes in sex steroid metabolism and suggest a possible causal role not only of the excessive quantity of metabolically active adipose tissue but also of specific dietary factors.