The pathophysiological implications of circulating androgens on bone mineral density in a normal female population

In this cross-sectional study performed on 147 healthy or osteoporotic, but otherwise normal premenopausal (n = 26 and n = 13, respectively) or postmenopausal (n = 40 and n = 68, respectively) women aged 40.1+/-9.9 and 61.9+/-8.9 years, respectively (range 20-82 years), serum ovarian and adrenal sex steroids and their relationship to bone mineral density (BMD) were evaluated. The levels of dehydroepiandrosterone sulfate (DHEAS), dehydroepiandrosterone (DHEA), androstenedione (AD), and estradiol correlated positively with BMD at the hip and spine as did serum testosterone with BMD at the spine. An inverse relationship was found between sex hormone binding globulin (SHBG) levels and BMD at the spine and hip. After adjustment for age, body mass, and sex steroid confounders, the bioavailable testosterone value (but not the DHEAS, DHEA, AD, or SHBG) values was demonstrated to be an independent determinant of BMD at the spine (beta 0.18, P<0.02) and hip (beta 0.24, P<0.02). Similarly, estradiol was found to be an independent determinant of BMD at the spine (beta 0.25, P<0.007). However, only SHBG levels (but not other steroid parameters) correlated positively with indices of bone remodeling, namely, serum osteocalcin and cross-linked telopeptide of type I collagen (ICTP). The present study suggests that a major decline in index of free testosterone (testosterone/SHBG) may influence the development of female osteoporosis. The clinical significance of circulating SHBG levels in the assessement of bone metabolic turnover remains to be established.     

Adrenal gland and bone

The adrenal gland synthesizes steroid hormones from the adrenal cortex and catecholamines from the adrenal medulla. Both cortisol and adrenal androgens can have powerful effects on bone. The overproduction of cortisol in Cushing’s disease leads to a dramatic reduction in bone density and an increase risk of fracture. Overproduction of adrenal androgens in congenital adrenal hyperplasia (CAH) leads to marked changes in bone growth and development with early growth acceleration but ultimately a significant reduction in final adult height. The role of more physiological levels of glucocorticoids and androgens on bone metabolism is less clear. Cortisol levels measured in elderly individuals show a weak correlation with measures of bone density and change in bone density over time with a high cortisol level associated with lower bone density and more rapid bone loss. Cortisol levels and the dynamics of cortisol secretion change with age which could also explain some age related changes in bone physiology. It is also now clear that adrenal steroids can be metabolized within bone tissue itself. Local synthesis of cortisol within bone from its inactive precursor cortisone has been demonstrated and the amount of cortisol produced within osteoblasts appears to increase with age. With regard to adrenal androgens there is a dramatic reduction in levels with aging and several studies have examined the impact that restoration of these levels back to those seen in younger individuals has on bone health. Most of these studies show small positive effects in women, not men, but the skeletal sites where benefits are seen varies from study to study.     

Ovarian steroidogenesis in Japanese patients with polycystic ovary syndrome

Gonadotropin and steroid hormone levels in both peripheral and ovarian venous blood were measured in samples obtained from 20 Japanese patients with polycystic ovary syndrome (PCOs) and 10 normal women in early follicular phase (normal women) by radioimmunoassay. The change in the amount of steroid hormone following intravenous human menopausal gonadotropin (HMG) or dexamethasone administration was investigated. The mean concentration in patients with PCOs was significantly higher than the concentrations found in normal women for LH (p less than 0.001), but not for FSH in peripheral blood. Significantly elevated ovarian venous steroid hormone levels in PCOs were found for 17 alpha-hydroxypregnenolone (p less than 0.05), progesterone (p less than 0.05), 17 alpha-hydroxyprogesterone (p less than 0.01), 4 delta-androstenedione (p less 0.01), testosterone (p less than 0.01), estrone (p less than 0.01) and estradiol (p less than 0.05), but not for dehydroepiandrosterone-sulfate (DHEAS). The ovarian dehydroepiandrosterone (DHEA) level was slightly elevated in PCOs. The concentration of ovarian 4 delta-androstenedione in PCOs reached twelve times as much as that in normal women. After the administration of HMG, all of the ovarian venus steroid hormone levels were elevated slightly and without significance in the short observation time for 10 min. The DHEAS level was suppressed while the ovarian DHEA level remained high in PCOs following dexamethasone administration. These findings seem to indicate there is no adrenal involvement and no adrenal-like component in the ovary of PCOs, and no evidence of 3 beta-hydroxysteroid dehydrogenase and/or aromatase deficiency in this study. The increase in the steroid hormone secretion in PCOs is explained by the increase in ovarian production in polycystic enlarged ovaries.     

Age-related changes of vertebral bone mineral density in Russian population]

Vertebral trabecular bone mineral density (BMD) was measured by quantitative computed tomography (QCT) in 1061 subjects (610 females and 451 males aged from 7 to 91 and from 12 to 89, respectively) with known history of diseases or taking medicines affecting bone metabolism. Peak BMD values in our patients were observed at the age of 20-29 years with further gradual decrement in men and more steep in women. Negative relationship between BMD and age was r = -0.991 for men and r = -0.968 for women. Analyzing BMD changes by decades we observed the largest decrement in men after 60 (13.1% for 60-69 and 14.1% for 70-79 years of age) and in women after 50 (22.5% for 50-59, 22.1% for 60-69 and 20.8% for 70-79 years) which was most probably due to decline in sex hormones production that is known to significantly influence bone metabolism. This was confirmed by BMD values three-phase approximation in women showing the lowest rate of calcium loss by trabecular bone in reproductive period (1.9 mg/cm3/yr) and the highest in perimenopause (3.98 mg/cm3/yr). Annual calcium loss in postmenopause was 2.22 mg/cm3.     

A cross-sectional study of dehydroepiandrosterone sulfate in prepubertal children with myelomeningocele

OBJECTIVE: To assess biochemical characteristics of adrenarche in patients with myelomeningocele (MMC), we examined serum levels of dehydroepiandrosterone sulfate (DHEAS) in prepubertal MMC patients. PATIENTS AND METHODS: The study included a total of 54 prepubertal patients with MMC and shunted hydrocephalus: 13 patients (2 m, 11 f; aged 4.6-10.1 years, mean 8.1 +/- 0.4) with isolated pubarche (Tanner stage PH 2-4, B1 or testes volume < or =3 ml) and 41 prepubertal MMC patients without pubarche (17 m, 24 f; aged 2.0-11.9 years; mean 6.8 +/- 2.5). DHEAS levels were measured directly by chemiluminescence immunoassay (Nichols, USA). Auxological data (supine length, body mass index (BMI), arm span) and bone age (BA) were recorded. RESULTS: (mean +/- SD): Basal DHEAS levels correlated with chronological age (CA) (r = 0.32, p < 0.05), BA (r = 0.65, p < 0.01; n = 23), BMI (r = 0.54, p < 0.01) and pubic hair stage (PH1 vs. PH2-4, r = 0.49, p < 0.01). 10/11 patients aged 2-4 years had DHEAS levels in the normal range, whereas 18/40 (45.0%) of the 5- to 9-year-old patients showed elevated levels (>+2 SDS). Ten patients with isolated pubarche (10/13; 2 m, 8 f; CA 8.3 +/- 1.5 years) and 9 patients without pubarche (9/41; 6 m, 3 f; CA 6.9 +/- 2.1 years) had elevated DHEAS levels (+6.34 and +4.05 SDS, respectively). The values correlated with BA/CA ratio (p < 0.05, n = 23). There was a trend to higher BMI SDS levels in patients with elevated DHEAS levels. CONCLUSION: Our data show an early and increased activation of adrenal androgen secretion in MMC patients.     

Differential effects of aging on estrogen negative and positive feedback

Recent studies have demonstrated an age-related decline in gonadotropins and a decrease in pituitary responsiveness to GnRH, indicating that aging influences the neuroendocrine components of the female reproductive axis independently of changes in ovarian function. To determine whether aging might also affect the luteinizing hormone (LH) negative and positive feedback responses to gonadal steroids, we administered a controlled, graded sex steroid infusion to 11 younger (45-56 yr) and nine older (70-80 yr) postmenopausal women (PMW) in whom endogenous ovarian steroids and peptides are uniformly low. The doses of estradiol (E(2)) and progesterone (P) were chosen to mimic levels across the normal follicular phase and have been shown previously to induce negative followed by positive feedback on LH. Similar E(2) and P levels were achieved in younger and older PMW (P = 0.4 and 0.3, respectively) and produced a biphasic LH response in all subjects. The early decline in LH to 53% of baseline was not different in older vs. younger PMW. However, the positive feedback effect was attenuated in older compared with younger PMW (peak LH 144.4 ± 19.5 vs. 226.8 ± 22.3 IU/l, respectively, P = 0.01). In conclusion, these studies in PMW demonstrate preservation of short-term steroid negative and positive feedback in response to exogenous E(2) and P with aging. Attenuation of positive feedback in older compared with younger PMW is consistent with previous reports of declining GnRH responsiveness with aging.     

Steroid sulphatase activity in the human ovarian corpus luteum, stroma, and follicle: comparison to activity in other tissues and the placenta

Steroid sulfatase activity was measured in 89 human samples, using dehydroepiandrosterone sulfate (DHEAS) as substrate. The lowest activity was that of follicular fluid which was significantly lower than that of other tissues tested (each P less than 0.01). The steroid sulfatase activity of ovarian tissue taken collectively (corpus luteum, stroma, and follicles) was higher than that of other tissues taken collectively (abdominal skin, uterus, and fallopian tube) (P less than 0.001), and the steroid sulfatase activity of either the follicle (P less than 0.01) or the stroma (P less than 0.05) was significantly greater than that of the corpus luteum. The geometric mean steroid sulfatase activity of the placenta was significantly higher than other tissues tested (each P less than 0.01) and was 22-fold higher than that of the follicle, the tissue with the next highest activity. These data indicate that the human ovary (particularly the stroma and follicle) is capable of utilizing DHEAS, an adrenal product, as a substrate for production of other androgens such as dehydroepiandrosterone (DHEA), androstenedione, and testosterone.     

Cross sectional and longitudinal study of bone mineral content of the distal forearm in adult premenopausal women

The range of fat corrected distal forearm mineral content (FMC) (at a site which comprises approximately 75% cortical and 25% trabecular bone) and the effect of aging on FMC were determined in normal premenopausal women. In 106 women (mean age 39; range 18-56) the mean FMC was 1.184 (SD 148) g/cm; fat correction increased this to 1.239 (SD 148) g/cm. There were significant correlations between fat corrected FMC and height, weight and BMI (r greater than 0.16; P less than 0.05). In 43 of these women (mean age 35; range 18-51) repeat measurements of FMC were performed. The last measurement was separated from the first by a mean time interval of 27 +/- 3 months. There was no significant change in uncorrected FMC (baseline 1.185 +/- 0.21 g/cm compared with their final measurement 1.182 +/- .020 g/cm; P = 0.51). Fat-corrected FMC (baseline 1.229 +/- .021 g/cm compared with 1.223 +/- .020 g/cm later) tended to decrease although this change was not significant (P = 0.06). Age ranked cusum analysis demonstrated a non-significant fat-corrected rate of change in FMC of -.3% yr in those over 35 years of age (P less than 0.10). This data suggests that if there is any distal forearm bone loss before the menopause it is negligible.     

Dehydroepiandrosterone status in postmenopausal women is determined by the gene for the vitamin D receptor.

Data documenting the indirect interaction of vitamin D and bone metabolism via hormonal systems are rare. The authors analysed the predictive role of the vitamin D receptor (VDR) gene for circulating sex steroids and their precursors in postmenopausal women. Using the PCR technique, the polymorphic FokI, ApaI, TaqI and BsmI sites of the VDR gene were determined in relation to serum dehydroepiandrosterone sulphate (DHEAS), androstenedione (AD), testosterone, and estradiol levels. After adjustment to body mass and years since menopause, circulating DHEAS was higher in the Ff genotype than in ff (p < 0.001) and FF genotypes (p < 0.05, ANCOVA followed by least significant difference multiple comparison tests). The Ff genotype also contributed to the highest BMD at the hip (p < 0.01 as compared to ff genotype) and at the spine (p < 0.05). No significant associations were found between ApaI, TaqI and BsmI polymorphisms and serum DHEAS or between FokI, ApaI, TaqI or BsmI and serum androstenedione, testosterone or estradiol. The study shows that the VDR gene predicts synthesis and/or metabolism of sexual steroid preursor DHEA in parallel with bone mineral density (BMD). The results indicate that DHEA production and bone mass share a common genetic control through VDR.     

Characterization of serum dehydroepiandrosterone secretion in golden hamsters

Dehydroepiandrosterone (DHEA) is an adrenal androgen whose function is poorly understood. Although DHEA and DHEA sulfate (DHEAS) are secreted in relatively high quantities by the human adrenal, the laboratory rat secretes very little, thus hindering experimental studies of the hormone. In this paper, we measured the changes in serum DHEA and DHEAS under various physiological conditions in golden hamsters. Evening serum DHEAS fell from 6.30 +/- 0.78 microg/dl (mean +/- SE) before surgery to 3.03 +/- 0.23 microg/dl 12 days after bilateral adrenalectomy. Hamsters had higher levels of DHEA and DHEAS in the evening than in the morning, but removal of the gonads did not consistently decrease serum DHEA or DHEAS in males or females. Evening levels of DHEA and DHEAS reached a peak around 7 weeks of age and then gradually decreased to about one-third of these levels by one year of age. These results suggest that DHEA and DHEAS are secreted at least in part from the hamster adrenal, that they do not originate from the gonads, and that there is a daily rhythm with peak levels at a time of day just preceding the active phase. In addition, the levels of these hormones decrease with aging.     

Endogenous estradiol and testosterone levels are associated with cognitive performance in older women and men

Relatively few studies have investigated the relationship between endogenous sex steroid levels and cognition in older people and the reported results have been inconsistent. A number of experimental hormone replacement studies have suggested that estrogen replacement in older women enhances cognition, especially verbal memory. In contrast, little research has been done focusing on men. In the current study the association between endogenous sex steroids (estradiol and testosterone) and cognition was investigated in 38 healthy older women (mean age 68 years) and 30 healthy older men (mean age 69 years). Five cognitive tests measuring verbal memory, spatial memory, verbal fluency, mental rotation, and susceptibility to interference were administered. Results revealed that in women higher estradiol levels as well as testosterone levels were associated with better verbal memory (paired associates and estradiol; r =.38, P < 0.05; paired associates and testosterone; r =.33, P < 0.05;). Moreover estradiol, but not testosterone was associated with less susceptibility to interference (Stroop color word test; r = -0.34, P < 0.05). In men the only significant association was a negative correlation between testosterone and verbal fluency (r = -0.38, P < 0.05). The associations observed in this small study support the notion that estradiol is protecting verbal memory and possibly also frontal lobe mediated functions in older women. In contrast to the positive findings in women endogenous sex steroids do not appear to be closely linked to better cognition in older men.     

Relationship of fat mass and serum estradiol with lower extremity bone in persons with chronic spinal cord injury

In the spinal cord injury (SCI) population, a relationship between adiposity and leg bone has not been reported, nor one between serum estradiol and leg bone mass. A cross-sectional, comparative study of 10 male pairs of monozygotic twins discordant for SCI was performed. Relationships were determined among bone mineral density (BMD), bone mineral content (BMC), lean mass, fat mass, and serum sex steroids. In the twins with SCI, significant relationships were evident between leg BMD or BMC with total body percent fat (r2= 0.49, P < 0.05; r2= 0.45, P = 0.05), leg fat mass (r2 = 0.76, P < 0.0005; r2= 0.69, P = 0.005), and serum estradiol (r2= 0.40, P = 0.05; r2= 0.37, P = 0.05). By stepwise regression analysis, in the twins with SCI, leg fat mass was found to be the single most significant predictor of leg BMD or BMC (F = 12.01, r2= 0.76, P = 0.008; F = 50.87, r2= 0.86, P < 0.0001). In the able-bodied twins, leg lean mass correlated with leg BMD and BMC (r2= 0.58, P = 0.01; r2= 0.87, P = 0.0001). By use of within-pair differences, significant correlations were found for leg lean mass loss with leg BMD loss (r2= 0.56, P = 0.01) or leg BMC loss (r2= 0.64, P = 0.0005). In conclusion, in twins with SCI, significant correlations were observed between fat mass and leg BMD or BMC as well as between serum estradiol values and leg BMD. The magnitude of the leg muscle mass loss was correlated with the magnitude of bone loss.     

Serum Dehydroepiandrosterone Sulphate Concentration Is Not a Predictive Factor in IVF Outcomes before the First Cycle of GnRH Agonist Administration in Women with Normal Ovarian Reserve

Objective

The aim of our study was to determine whether serum dehydroepiandrosterone sulphate (DHEAS) concentration and the models incorporating it could help clinicians to predict IVF outcomes in women with normal ovarian reserve undergoing their first long protocol.

Study Design

We performed a retrospective analysis of 459 women undergoing cycles of intracytoplasmic sperm injection (ICSI) for the first time in a long GnRH agonist protocol.

Results

Embryo transfer was performed in 407 women (88.7%). The fertilisation rate was 78.6%. The clinical pregnancy rate was 44.8% per started cycle and 50.6% per embryo transfer. Our univariate model revealed that the best predictors of clinical pregnancy were the number of mature oocytes, the number of embryos transferred and the number of good quality embryos, account for the clinical parameters that reflect ovarian reserve the best being AMH level and AFC. DHEAS did not predict clinical pregnancy (OR 1.001, 95% CI, 0.999–1.004). After adjusting for the number of embryos transferred and class of embryos in a multivariate model, the best predictors were age (OR 0.918, 95% CI, 0.867–0.972) and AFC (OR 1.022, 95% CI, 0.992–1.053). Serum DHEAS levels were positively correlated with AFC (r = 0.098, P<0.039) and testosterone levels (r = 0.371, P<0.001), as well as the number of mature oocytes (r = 0.109, P<0.019); serum DHEAS levels were negatively correlated with age (r = -0.220, P<0.001), follicle-stimulating hormone (FSH), (r = -0.116, P<0.015) and sex hormone-binding globulin (SHBG), (r = -0.193, P<0.001).

Conclusions

DHEAS concentration (in addition to the known factors of ovarian reserve) does not predict clinical pregnancy in women with normal ovarian reserve who are undergoing ICSI.     

Gemfibrozil treatment is associated with elevated adrenal androgen, androstanediol glucuronide and cortisol levels in dyslipidemic men

We have investigated the role of steroid hormones as coronary risk factors in Helsinki Heart Study population of dyslipidemic middle-aged men. We compare here the effects of gemfibrozil and placebo on the serum levels of dehydroepiandrosterone (DHEA), its sulfate (DHEAS), their metabolite androstanediol glucuronide (3-AdiolG), androstenedione, cortisol, testosterone, and sex-hormone binding globulin (SHBG) in non-smokers. We also examined the associations between steroid and lipoprotein levels in both treatment groups. Compared with placebo gemfibrozil treatment was associated with significant elevations of the mean levels of DHEA 10.2 vs 8.0 nmol/1; P<0.005, of DHEAS 8.0 vs 5.8 μmol/1; P<0.001, of 3AdiolG 18.3 vs 8.4 nmol/1; P<0.001, of androstenedione 5.7 vs 5.1 nmol/1; P<0.02, and of cortisol 426 vs 358 nmol/1; P<0.001. The mean SHBG levels decreased from 46.4 to 41.7 nmol/1; P=0.03 with gemfibrozil treatment. No difference was found in testosterone levels 17.7 vs 18.8 nmol/1; P=0.11, or the ratio of testosterone/SHBG 0.45 vs 0.43; P=0.23. Positive correlations were found between high density lipoprotein-cholesterol and DHEAS (r=0.267; P<0.01) and DHEA (r=0.282; P<0.01) levels and negative correlations between low density lipoprotein-cholesterol and 3-AdiolG (r=−0.400; P<0.001) and cortisol (r=−0.281; P<0.01) levels in the gemfibozil group. Our results indicate that gemfibrozil treatment increases the production and turnover of adrenal androgens and cortisol, and suggest that activation of the adrenocorticol function and increased metabolism of androgens are related to the improved lipoprotein pattern during gemfibrozil treatment.     

Female reproductive system and bone

The female reproductive system plays a major role in regulating the acquisition and loss of bone by the skeleton from menarche through senescence. Onset of gonadal sex steroid secretion at puberty is the major factor responsible for skeletal longitudinal and radial growth, as well as significant gain in bone density, until peak bone density is achieved in third decade of life. Gonadal sex steroids then help maintain peak bone density until menopause, including during the transient changes in skeletal mineral content associated with pregnancy and lactation. At menopause, decreased gonadal sex steroid production normally leads to rapid bone loss. The most rapid bone loss associated with decreased estrogen levels occurs in the first 8-10 years after menopause, with slower age-related bone loss occurring during later life. Age-related bone loss in women after the early menopausal phase of bone loss is caused by ongoing gonadal sex steroid deficiency, vitamin D deficiency, and secondary hyperparathyroidism. Other factors also contribute to age-related bone loss, including intrinsic defects in osteoblast function, impairment of the GH/IGF axis, reduced peak bone mass, age-associated sarcopenia, and various sporadic secondary causes. Further understanding of the relative contributions of the female reproductive system and each of the other factors to development and maintenance of the female skeleton, bone loss, and fracture risk will lead to improved approaches for prevention and treatment of osteoporosis.     

Tomographical description of tennis-loaded radius: reciprocal relation between bone size and volumetric BMD.

Effects of long-term tennis loading on volumetric bone mineral density (vBMD) and geometric properties of playing-arm radius were examined. Paired forearms of 16 tennis players (10 women) and 12 healthy controls (7 women), aged 18-24 yr, were scanned at mid and distal site by using peripheral quantitative computerized tomography. Tomographic data at midradius showed that tennis playing led to a slight decrease in cortical vBMD (-0.8% vs. nonplaying arm, P < 0. 05) and increase both in periosteal and endocoritcal bone area (+15. 2% for periosteal bone, P < 0.001; and +18.8% for endocortical bone, P < 0.001). These data suggest that, together with an increase in cortical thickness (+6.4%, P < 0.01), cortical drift toward periosteal direction resulted in improvement of mechanical characteristics of the playing-arm midradius. Enlargement of periosteal bone area was also observed at distal radius (+6.8%, P < 0.01), and the relative side-to-side difference in periosteal bone area was inversely related to that in trabecular vBMD (r = -0.53, P < 0.05). We conclude that an improvement of mechanical properties of young adult bone in response to long-term exercise is related to geometric adaptation but less to changes in vBMD.     

Dehydroepiandrosterone sulfate and other possible influencing factors that modulate sex hormone-binding globulin levels in the hirsute patient.

This study was designed to investigate the most important factors affecting serum concentrations of sex hormone-binding globulin (SHBG) in women with hirsutism. We compared endocrine profiles based on biochemical measurements of LH, FSH, oestradiol, testosterone (T), prolactin, 17-hydroxy-progesterone, dehydroepiandrosterone sulphate (DHEAS), SHBG, cortisol and insulin in the follicular phase in 32 healthy women and 52 patients. The study group was subdivided according to SHBG levels into Group A (low level) and Group B (high level). Significant differences between Groups A and B were found in DHEAS and T levels, but not in body mass index or insulinaemia. There was a relationship between DHEAS and SHBG levels (r = 0.51) and between T and SHBG (r = 0.31). We conclude that DHEAS may be a significant modulator of SHBG in the female hirsute patient, an observation seldom mentioned in previous reports.     

Age, insulin, SHBG and sex steroids exert secondary influence on plasma leptin level in women

AIM: As the link between body fat and leptin is well known, the aim of the study was to seek for secondary regulators of plasma leptin level. PATIENTS: 86 women (mean: age 47.0+/-14.3 years; estradiol 50.0+/-60.6 ng/l; FSH 52.4+/-42.9 IU/l; BMI 26.9+/-5.9) divided into three groups according to their BMI. Group A: 39 normal weight women (mean: age 44.4+/-16.0 years; estradiol 69.6+/-79.8 ng/l; FSH 50.4+/-47.7 IU/l; BMI 22.9+/-1.3). Group B: 27 overweighted women (mean: age 55.0+/-6.4 years; estradiol 25.1+/-17.2 ng/l; FSH 75.6+/-26.3 IU/l; BMI 27.7+/-1.6). Group C: 21 obese women with mean: age 48.7+/-12.2 years; estradiol 36.9+/-44.0 ng/l; FSH 42.3+/-36.6 IU/l and BMI 34.6+/-4.9. METHODS: Standard clinical evaluation and hormone evaluation (LH, FSH, prolactin, estradiol, leptin, insulin-like growth factor-I (IGF-I), human growth hormone (hGH), insulin-like growth factor binding protein-3 (IGFBP-3), insulin, dihydroepiandrosterone sulphate (DHEAS), sex hormone binding globin (SHBG) and testosterone were done in basic condition which levels of were measured by RIA kits. Statistical analysis. Shapiro-Wilk test, Mann-Whitney-Wilcoxon u test, Spearman rank correlation coefficient and stepwise multiple regression: p values of 0.05 or less were considered as significant. RESULTS: Taking all women into account (n=86) the plasma leptin level correlated directly with age (r=0.32; p<0.02), body mass (r=0.60; p<0.001), BMI (r=0.71; p<0.001) as well as inversely with estradiol (r=-0.21; p<0.05), IGF-I (r=-0.24; p<0.05), SHBG (r=-0.34; p<0.01) and DHEAS (r=-0.30; p<0.01). However only in the group B leptin/age relation remained (r=0.40; p<0.05) after the division according to BMI. In the group B the leptin /DHEAS (r=-0.40; p<0.05) and leptin/PRL (r=0.51; p<0.05) links were also present. In the group C the leptin/SHGB relation (r=-0.56; p<0.02) only remained and an association between insulin and leptin was found (r=0.48; p<0.05). The body mass and BMI relation to age were again present only in all 86 women (r=0.30; p<0.002: r=0.36; p<0.001 resp.). Having split the women into groups, these links either disappeared or became inverse (rC=-0.39; p<0.05). Taking into consideration age/leptin relation in all women, the division according to the menopausal status revealed the direct relation in premenopausal women (n=29; r=0.43; p<0.02) and a reverse one in postmenopausal women (n=38; r=-0.32; p<0.05). The plasma leptin level was the highest (p<0.001) in group C (23.2+/-10.4 microg/l) and the lowest was found in the group A (8.9+/-4.1 microg/l). That corresponded with the differences in mean body mass index and mean body mass. The stepwise multiple regression revealed that body mass index accounted for 31% (p<0.001) and plasma SHBG level accounted for 17.7% (p<0.02) of plasma leptin variance in all women. In the group A body mass and age together accounted for 61% (p<0.01) and estradiol alone accounted for 44% (p<0.02) of plasma leptin variance. In the group B insulin alone accounted for 39% (p<0.05) and together with testosterone accounted for 46% (p<0.05) of plasma leptin variance. Finally in obese women none of the evaluated parameters significantly accounted for leptin variance. CONCLUSION: The results presented in this paper confirmed the strong influence of body fat mass on serum leptin concentration. However insulin, SHBG, sex steroids as well as age may also exert secondary influence on plasma leptin level in certain groups of women.     

Association of CYP19 Gene Polymorphism with Vertebral Fractures in Japanese Postmenopausal Women

This study investigates aromatase gene polymorphism, which might influence bone strength in terms of mineral density and quality. We explored the relationship between CYP19 polymorphisms and vertebral fractures in postmenopausal Japanese women. In addition, we compared estrogen and testosterone levels in Japanese postmenopausal women with and without fractures. Osteoporotic postmenopausal women showed higher incidences of vertebral fractures than osteopenic women or women with normal lumbar bone mineral density (L2-4 BMD). Estrogen concentrations in postmenopausal women were associated with BMD; however, no association was found between sex hormone levels and the presence of fractures. The C allele rs2470152 was significantly associated with increased risk of vertebral fractures (P = 0.04), whereas none of the CYP19 polymorphisms showed differences in sex steroid levels between subjects with and without fractures. Allelic variants of aromatase genes appear to interact to influence the risk of vertebral fractures in postmenopausal Japanese women.     

Relation between body size and bone mineral density with special reference to sex hormones and calcium regulating hormones in elderly females.

We studied the relation between body size and bone mineral density in elderly females. The study included a total of 93 ambulatory females aged over 60 years. They were divided into 3 groups according to their body mass index (BMI; kg/m2): slender group with BMI less than 20 (n = 28), normal group with BMI of 20 to 24.9 (n = 43) and obese group with BMI greater than or equal to 25 (n = 22). Fracture incidence, bone mineral density, calcium regulating hormones and steroid hormones were studied in an intergroup comparative manner. The incidence of vertebral fracture was found to be negatively correlated with BMI (the incidences of vertebral fracture in slender, normal and obese were 78.6, 48.8 and 22.7%, respectively) and bone mineral density was also BMI-related (0.390 +/- 0.016, 0.456 +/- 0.015 and 0.493 +/- 0.018 g/cm2, respectively: p less than 0.01 in ANOVA; mean +/- SE). The number of years after menopause was shorter in patients with a higher BMI. There was no intergroup difference in serum levels of PTH, vitamin D and estrogens. On the other hand, serum levels of calcitonin, DHEA, DHEAS, delta-4 androstenedione and testosterone were found to be higher in subjects with a higher BMI. From the present results, it seems that bone mineral density is supported not only by weight-bearing stress upon bone, but also by serum levels of calcitonin and androgens in obese females.