Results of recent trials highlight the risks of hormone therapy, increasing the importance of identifying preventive lifestyle factors related to menopausal symptoms. The authors examined the relation of such factors to vasomotor symptoms in the multiethnic sample of 3,302 women, aged 42-52 years at baseline (1995-1997), in the Study of Women's Health Across the Nation (SWAN). All lifestyle factors and symptoms were self-reported. Serum hormone and gonadotropin concentrations were measured once in days 2-7 of the menstrual cycle. After adjustment for covariates using multiple logistic regression, significantly more African-American and Hispanic and fewer Chinese and Japanese than Caucasian women reported vasomotor symptoms. Fewer women with postgraduate education reported vasomotor symptoms. Passive exposure to smoke, but not active smoking, higher body mass index, premenstrual symptoms, perceived stress, and age were also significantly associated with vasomotor symptoms, although a dose-response relation with hours of smoke exposure was not observed. No dietary nutrients were significantly associated with vasomotor symptoms. These cross-sectional findings require further longitudinal exploration to identify lifestyle changes for women that may help prevent vasomotor symptoms.

ORMONAL AGENTS HAVE BEEN the predominant therapy for menopausal hot flashes, but their use decreased substantially following the shifts in riskbenefit ratios that were identified in the Women's Health Initiative Estrogen plus Progestin randomized controlled trial. 1,2 However, no other treatments have US Food and Drug Administration approval for menopausal hot flashes, and the efficacy of alternative pharmacologic and nonpharmacologic agents is inconclusive. [3][4][5] Selective serotonin and serotonin norepinephrine reuptake inhibitors (SSRIs and SNRIs) have been investigated for hot flash treatment with mixed results [6][7][8][9][10][11] ; a pooled analysis of 7 SSRI and SNRI studies showed that decreases in hot flash scores ranged from 3% to 41% compared with placebo. 6 Differences among the serotonergic antidepressants, 11 study popu-

The effects of age, sex, renal function, and seasonal variation on serum parameters within the vitamin D endocrine system were studied cross-sectionally in a healthy population of 167 men and 114 women, aged 20-94 yr. Serum 25-hydroxy- and 1,25-dihydroxyvitamin D [25OHD and 1,25-(OH)2D] did not decline with age in either sex. Nonlinear regression using a sine function showed a significant seasonal variation in 25OHD and 1,25-(OH)2D in both sexes (P less than 0.005). Serum intact PTH increased significantly by 35% over the age span in both sexes (P less than 0.005). In women, serum phosphorus and total and ionized calcium remained constant with age. In sharp contrast, males had a marked 25% fall in phosphorus across the age span (r = -0.564; P less than 0.0001) and a slight but significant 4% decline in total and ionized calcium. Creatinine clearance declined markedly with age, but was not related to 1,25-(OH)2D in either sex. Only in men was there a significant but modest inverse relationship between creatinine clearance and PTH (r = -0.212; P less than 0.05), which was multicollinear with age. We conclude that in healthy individuals 1) compromised vitamin D status or serum 1,25-(OH)2D levels are not a normal concomitant of aging; 2) declining glomerular filtration does not appear to be the principle cause of the age-related rise in PTH; and 3) there are marked male-female differences in phosphorus metabolism across the age span.

Estrogen deficiency and declining calcium absorption due to reduced calcitriol levels or intestinal resistance to calcitriol, are important factors in the pathogenesis of age-related bone loss. The main objective of this study was to examine the effect of estrogen and 1,25-dihydroxyvitamin D therapy given individually or in combination on bone loss in elderly women. Four hundred eighty-nine elderly women with normal bone density for their age, aged 65-77 yr, were entered into a randomized double blind, placebo-controlled trial. Women were randomized to one of four groups: conjugated estrogens (0.625 mg, daily) to women without a uterus (estrogen replacement therapy) plus medroxyprogesterone acetate (2.5 mg, daily) to women with a uterus (hormone replacement therapy), calcitriol (0.25 microg twice daily), a combination of hormone replacement therapy/estrogen replacement therapy plus calcitriol, or placebos for 3 yr. The primary outcome was the change in bone mineral density of the femoral neck and spine. In the intent to treat analysis, hormone therapy (hormone replacement therapy/estrogen replacement therapy) produced a mean (+/-1 SD) increase in bone mineral density of 2.98% (+/-5.45%) at the femoral neck (P < 0.0001) and 4.36% (+/-6.42%) at the spine (P < 0.0001). There were parallel increases in total hip and trochanter bone mineral density. Calcitriol increased bone mineral density 0.10% (+/- 4.27%) at the femoral neck (P = 0.57) and 1.65% (+/- 4.83%) at the spine (P < 0.0124). The combination of hormone replacement therapy/estrogen replacement therapy + calcitriol increased bone mineral density 3.80% (+/-4.95%) at the femoral neck (P < 0.001), 4.91% (+/-6.0%) at the spine (P < 0.0001), and parallel changes at the total hip and trochanter. All three treatment groups differed significantly from placebo at the spine and for the hormone replacement therapy/estrogen replacement therapy groups at the femoral neck, spine, total hip and trochanter. There were no significant differences between combination therapy and hormone replacement therapy/estrogen replacement therapy alone on bone mineral density at any site in the intent to treat analysis. In a secondary analysis of the effect in women who were adherent to treatment, calcitriol had a more significant effect on spine (P = 0.003) and total hip (P = 0.004). The increase in bone mineral density in the adherent groups of women was always higher compared with the intent to treat groups. Combination therapy compared with hormone replacement therapy/estrogen replacement therapy alone produced a significantly greater response in trochanter (P = 0.007) and total hip bone mineral density (P = 0.0017). In summary, hormone replacement therapy/estrogen replacement therapy alone and in combination with calcitriol therapy was highly effective in reducing bone resorption and increasing bone mineral density at the hip and other clinically relevant sites in a group of elderly women, with normal bone density for their age. Calcitriol was effective in increasing spine bone minera...

Advancing age, rather than declining serum levels of IGF-I, appears to be a major determinant of life-time changes in body composition and BMD in women and men.

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Objective This report describes the "Menopausal Strategies: Finding Lasting Answers to Symptoms and Health” (MsFLASH) network and methodological issues addressed in designing and implementing vasomotor symptom trials. Methods Established in response to a National Institute of Health request for applications, the network was charged with conducting rapid throughput randomized trials of novel and understudied available interventions postulated to alleviate vasomotor and other menopausal symptoms. Included are descriptions of and rationale for criteria used for interventions and study selection, common eligibility and exclusion criteria, common primary and secondary outcome measures, consideration of placebo response, establishment of a biorepository, trial duration, screening and recruitment, statistical methods, and quality control. All trial designs are presented including: 1) a randomized, double-blind, placebo-controlled clinical trial designed to evaluate effectiveness of the selective serotonin reuptake inhibitor escitalopram in reducing vasomotor symptom frequency and severity; 2) a 2×3 factorial design trial to test three different interventions (yoga, exercise, and omega-3 supplementation) for improvement of vasomotor symptom frequency and bother; and 3) a three-arm comparative efficacy trial of the serotonin-norepinephrine reuptake inhibitor venlafaxine and low-dose oral estradiol versus placebo for reducing vasomotor symptom frequency compared to placebo. The network’s structure and governance are also discussed. Conclusions The methods used and lessons learned in the MsFLASH trials are shared to encourage and support the conduct of similar trials and encourage collaborations with other researchers.

A population of sunlight-deprived elderly was studied to determine the daily intake of vitamin D and whether dietary intake was sufficient to maintain a normal vitamin D status. Twenty-two subjects over 65 years old with serum creatinine less than 180 mumols/L and confined indoors for more than 6 months were chosen from the community and a nursing home in Southeast Baltimore. Three-day food records were obtained along with serum levels of 25-hydroxyvitamin D (25-OHD), 1,25-dihydroxyvitamin D (1,25-(OH)2 D), and intact parathyroid hormone (PTH). The mean daily vitamin D intake was over twofold greater than the adult Recommended Daily Allowance (RDA) of 200 IU. The mean 25-OHD level was 40 nmol/L (normal 25-138 nmol/L) with seven patients less than 25 nmol/L. Of these participants with 25-OHD values less than 25 nmol/L, the mean vitamin D intake was 467 IU (range 36-1096 IU). We conclude that the current RDA seems inadequate for many older individuals who do not get sun exposure. This particular population of elderly is at risk to develop vitamin D deficiency and the associated complications.