Heritability of plasma sex hormones and hormone binding globulin in adult male twins.

Plasma sex hormone concentrations have been used as biomarkers in epidemiological studies of many conditions including cancer, obesity, bone density, and coronary heart disease. The objective of this analysis was to estimate genetic and nongenetic influences on endogenous sex hormones (testosterone, estradiol, estrone, and SHBG) in a large sample of 532 adult white male twins (134 monozygotic and 132 dizygotic twin pairs) from the National Heart, Lung, and Blood Institute Twin Study. Participants were aged 59-70 yr at the time of plasma collection, and hormone concentrations were determined with RIA. Genetic models were fitted by the method of maximum likelihood. Testosterone and SHBG concentrations have substantial genetic variation, with additive genetic factors accounting for 57 and 68% of the total phenotypic variation, respectively. In contrast, variation in estrone (37% shared environmental and 63% individual specific environmental effects) and estradiol concentrations (25% genetic effect, 44% shared environmental effects, and 31% individual specific environmental effects) were largely influenced by nongenetic factors. Assessment of the relative contribution of genetic and nongenetic influences on hormone concentrations may help in the search for genes underlying variation and covariation in complex traits affected by plasma sex hormone concentrations.

Relationship of endogenous sex hormones to coronary heart disease: a twin study.

We examined the association between endogenous sex hormones (estradiol, estrone, testosterone, and SHBG) and coronary heart disease (CHD) in white male twins. Stored plasma samples were available for 566 participants of the National Heart, Lung, and Blood Institute Twin Study, a longitudinal study of cardiovascular disease in male twins. Twenty-eight of these individuals were lost to follow-up, and outcome data were missing. Of the remaining 538 participants, 78 had CHD at baseline, and 154 subsequently developed CHD over 20 yr of follow-up. We observed no differences in mean unadjusted or age- and body mass index-adjusted log-transformed sex hormone concentrations for participants with and without CHD (all P > 0.08). Quartile and median split analyses revealed no significant association between any of the sex hormones and either prevalent or incident CHD. The discordant monozygotic twins showed no significant case-control group difference in estradiol, estrone, testosterone, and SHBG (all P > 0.3). The positive and negative concordant twin pairs had similar values for each of the sex hormones (all P > 0.3). We observed no relationship between endogenous sex hormone concentrations and prevalent or incident CHD in this sample of male twins.

Long-term effects of nutrient intervention on markers of bone remodeling and calciotropic hormones in late-postmenopausal women.

BACKGROUND: Adequate intakes of calcium and vitamin D reduce bone loss and fracture risk in the elderly. Other nutrients also affect bone health, and adequate intakes may influence bone turnover and balance. OBJECTIVE: We compared the long-term effects on bone turnover markers and calciotropic hormones of a multinutrient supplement, a calcium and vitamin D supplement, and dietary instruction aimed at increasing calcium intake through foods. DESIGN: Ninety-nine healthy postmenopausal women participated in a 3-y, randomized trial, receiving either 1) supplemental calcium (1450 mg/d) and vitamin D [10 microg (400 IU)/d], 2) calcium, vitamin D, and other nutrients (multinutrient supplement), or 3) dietary instruction (dietary control group). Data are from 83 subjects who completed the trial. RESULTS: Increases over baseline in calcium intakes and serum 25-hydroxyvitamin D concentrations were sustained over 3 y in all treatment groups. Circulating parathyroid hormone concentrations were reduced at year 1 in all treatment groups but trended toward baseline thereafter. Bone turnover markers followed a similar pattern, and none of the changes in biochemical concentrations differed significantly between groups. CONCLUSIONS: All 3 interventions offer long-term feasibility for increasing calcium intake and serum 25-hydroxyvitamin D concentrations. The dietary addition of micronutrients implicated in skeletal physiology confers no obvious bone-sparing effect in healthy postmenopausal women beyond that of calcium and vitamin D alone. The attenuation over time in suppression of parathyroid hormone and bone turnover might help explain why nutrient intervention tends to have less of a bone-sparing effect than do skeletally active medications such as estrogen or bisphosphonates.

Effects of oligofructose-enriched inulin on intestinal absorption of calcium and magnesium and bone turnover markers in postmenopausal women.

Deficiency of oestrogen at menopause decreases intestinal Ca absorption, contributing to a negative Ca balance and bone loss. Mg deficiency has also been associated with bone loss. The purpose of the present investigation was to test the hypothesis that treatment with a spray-dried mixture of chicory oligofructose and long-chain inulin (Synergy1; SYN1) would increase the absorption of both Ca and Mg and alter markers of bone turnover. Fifteen postmenopausal women (72.2 (SD 6.4) years) were treated with SYN1 or placebo for 6 weeks using a double-blind, placebo-controlled, cross-over design. Fractional Ca and Mg absorption were measured using dual-tracer stable isotopes before and after treatment. Bone turnover markers were measured at baseline, 3 and 6 weeks. Fractional absorption of Ca and Mg increased following SYN1 compared with placebo (P < 0.05). Bone resorption (by urinary deoxypyridinoline cross-links) was greater than baseline at 6 weeks of active treatment (P < 0.05). Bone formation (by serum osteocalcin) showed an upward trend at 3 weeks and an increase following 6 weeks of SYN1 (P < 0.05). Closer examination revealed a variation in response, with two-thirds of the subjects showing increased absorption with SYN1. Post hoc analyses demonstrated that positive responders had significantly lower lumbar spine bone mineral density than non-responders (dual X-ray absorptiometry 0.887 +/- 0.102 v. 1.104 +/- 0.121 g/cm2; P < 0.01), and changes in bone turnover markers occurred only in responders. These results suggest that 6 weeks of SYN1 can improve mineral absorption and impact markers of bone turnover in postmenopausal women. Further research is needed to determine why a greater response was found in women with lower initial spine bone mineral density.

Novel, high-frequency, low-strain mechanical loading for premenopausal women with low bone mass: early findings.

Universally safe and effective methods of mechanically loading the skeleton to improve strength and prevent fracture have yet to be identified. To be osteogenic, mechanical strains must either be of substantial magnitude or applied at high frequency (>15 Hz). High-magnitude loads place frail bones at risk of fracture. Active loading can rarely be achieved at a frequency faster than 2-3 Hz. A 12-month, uncontrolled, prospective, pilot intervention trial was conducted with five premenopausal Caucasian women with low bone mass. Subjects stood on a vibrating platform (Optimass model 1000 Mechanical Strain Device) and received a 0.2-g stimulus at 30 Hz, 2 x 10 min/day, for 12 months. Bone mineral density (BMD) was measured at the whole body, lumbar spine, proximal femora (PF), and distal radius at baseline and 6 and 12 months by DXA (Hologic QDR-1000/W). Blood and urine were collected at baseline and 3, 6, 9 and 12 months for markers of bone resorption and formation. A mean percent BMD increase of 2.03% +/- 0.33% (P < 0.02) was detected at the non-dominant PF after 12 months. Trends for increases were observed at all other sites with the exception of the dominant PF. No uniform trends were observed in bone resorption and formation markers. One subject, on Fosamax, increased BMD by 6% at the lumbar spine and 4.4% at the distal radius. Preliminary findings provide evidence of a possible positive response of regions of low bone mass to brief daily bouts of in-home, passive, noninvasive, low-strain, high-frequency, mechanical loading.

Endocrine responses to acute and chronic high-altitude exposure (4,300 meters): modulating effects of caloric restriction.

High-altitude anorexia leads to a hormonal response pattern modulated by both hypoxia and caloric restriction (CR). The purpose of this study was to compare altitude-induced neuroendocrine changes with or without energy imbalance and to explore how energy sufficiency alters the endocrine acclimatization process. Twenty-six normal-weight, young men were studied for 3 wk. One group [hypocaloric group (HYPO), n = 9] stayed at sea level and consumed 40% fewer calories than required to maintain body weight. Two other groups were deployed to 4,300 meters (Pikes Peak, CO), where one group (ADQ, n = 7) was adequately fed to maintain body weight and the other [deficient group (DEF), n = 10] had calories restricted as above. HYPO experienced a typical CR-induced reduction in many hormones such as insulin, testosterone, and leptin. At altitude, fasting glucose, insulin, and epinephrine exhibited a muted rise in DEF compared with ADQ. Free thyroxine, thyroid-stimulating hormone, and norepinephrine showed similar patterns between the two altitude groups. Morning cortisol initially rose higher in DEF than ADQ at 4,300 meters, but the difference disappeared by day 5. Testosterone increased in both altitude groups acutely but declined over time in DEF only. Adiponectin and leptin did not change significantly from sea level baseline values in either altitude group regardless of energy intake. These data suggest that hypoxia tends to increase blood hormone concentrations, but anorexia suppresses elements of the endocrine response. Such suppression results in the preservation of energy stores but may sacrifice the facilitation of oxygen delivery and the use of oxygen-efficient fuels.

Bone mass and turnover in women with epilepsy on antiepileptic drug monotherapy.

Antiepileptic drugs, particularly cytochrome P450 enzyme inducers, are associated with disorders of bone metabolism. We studied premenopausal women with epilepsy receiving antiepileptic drug monotherapy (phenytoin, carbamazepine, valproate, and lamotrigine). Subjects completed exercise and nutrition questionnaires and bone mineral density studies. Serum was analyzed for indices of bone metabolism including calcium, 25-hydroxyvitamin D, parathyroid hormone, insulin growth factor I, insulin binding protein III, and bone formation markers, bone-specific alkaline phosphatase, and osteocalcin. Urine was analyzed for cross-linked N-telopeptide of type I collagen, a bone resorption marker. Calcium concentrations were significantly less in subjects receiving carbamazepine, phenytoin, and valproate than in those receiving lamotrigine (p = 0.008). Insulin growth factor-I was significantly reduced in subjects receiving phenytoin compared with those receiving lamotrigine (p = 0.017). Subjects receiving phenytoin had significantly greater levels of bone-specific alkaline phosphatase (p = 0.007). Our results demonstrate that phenytoin is associated with changes in bone metabolism and increased bone turnover. The lower calcium concentrations in subjects taking carbamazepine or valproate compared with those taking other antiepileptic drugs suggest that these antiepileptic drugs may have long-term effects. Subjects receiving lamotrigine had no significant reductions in calcium or increases in markers of bone turnover, suggesting this agent is less likely to have long-term adverse effects on bone.