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Biomedical subjects

Joel S Finkelstein

Publications and source records attributed to Joel S Finkelstein.

At least 19 recordsLinked to original sources
PubMed2006

Effects of teriparatide, alendronate, or both on bone turnover in osteoporotic men.

CONTEXT: We have previously demonstrated that alendronate reduces the ability of teriparatide to increase bone mineral density (BMD) in osteoporotic men. The underlying basis for this observation is poorly understood. OBJECTIVE: The primary aim of this study was to determine whether teriparatide increases osteoblast activity when the ability of teriparatide to increase osteoclast activity is suppressed by alendronate. DESIGN: This was a nonblinded, randomized, controlled trial. SETTING: The study was conducted at the General Clinical Research Center of a teaching hospital. PATIENTS: We studied 63 men, age 46-85, with low spine and/or hip BMD. INTERVENTIONS: Subjects received alendronate 10 mg daily (group 1), teriparatide 37 microg sc daily (group 2), or both (group 3) for 30 months. Teriparatide was begun at month 6. MAIN OUTCOME MEASURES: The primary endpoint was the change in serum N-telopeptide, osteocalcin, and amino-terminal propeptide of type 1 procollagen. RESULTS: In men receiving teriparatide monotherapy (group 2), levels of all bone turnover markers increased markedly during the first 6 months of teriparatide administration and then declined toward baseline during the next 18 months. In men who received combination therapy (group 3), bone turnover marker levels declined in the first 6 months (while receiving alendronate alone) and then returned to baseline levels (N-telopeptide) or above (osteocalcin and amino-terminal propeptide of type 1 procollagen) after teriparatide was added. Changes in each marker were significantly different between groups 1 and 2 (all P values < 0.001), groups 1 and 3 (all P values < 0.001), and groups 2 and 3 (all P values < 0.03). CONCLUSIONS: As with BMD, alendronate impairs the action of teriparatide to increase bone turnover in men.

Aged↗
PubMed2006

Hormone predictors of bone mineral density changes during the menopausal transition.

UNLABELLED: OBJECTIVE AND CONTEXT: Our objective was to examine predictability of reproductive hormone concentrations for bone mineral density (BMD) loss during the menopausal transition. DESIGN: We conducted a longitudinal (five annual examinations), multiple-site (n = 5) cohort study, the Study of Women's Health Across the Nation (SWAN). PARTICIPANTS: Participants included, at baseline, 2311 premenopausal or early perimenopausal African-American, Caucasian, Chinese, and Japanese women. MAIN OUTCOME MEASURES: We assessed annual dual-energy x-ray absorptiometry lumbar spine and total hip BMD measures, with endogenous estradiol (E2), FSH, androgens, and self-reported menstrual bleeding patterns. RESULTS: Over the 4-yr period, lumbar spine BMD loss was 5.6% in natural postmenopause, 3.9% in surgical postmenopause, or 3.2% in late perimenopause. Baseline FSH concentrations, subsequent FSH levels, and their interaction predicted 4-yr BMD loss. If baseline FSH was less than 25 mIU/ml, higher follow-up FSH (>70 mIU/ml) predicted a 4-yr spine BMD loss of -0.05 g/cm(2). If baseline FSH values were more than 35-45 mIU/ml, lower follow-up FSH (i.e. 40-50 mIU/ml) predicted a -0.05 g/cm(2) 4-yr spine BMD loss. Charts show amounts of predicted BMD losses with combinations of baseline FSH values and FSH levels over time. E2 concentrations less than 35 pg/ml were associated with lower BMD, but annual E2 measures and changes did not predict BMD loss. Testosterone, free androgen index, and dehydroepiandrosterone sulfate concentrations were not significantly associated with BMD loss. CONCLUSIONS: Spine and hip BMD losses during the menopause transition were most strongly related to the interaction between initial FSH levels and longitudinal FSH changes and not to E2 or androgen levels or changes.

Absorptiometry, Photon↗
PubMed2006

Regulation of C-terminal and intact FGF-23 by dietary phosphate in men and women.

UNLABELLED: FGF-23 is a novel regulator of phosphate metabolism. We studied the regulation of FGF-23 by dietary phosphate in 66 men and women using two assays. Dietary phosphate restriction decreased FGF-23 and loading increased FGF-23 significantly. An assay that measured intact FGF-23 showed the effects of dietary phosphate much more clearly than an assay that also measures presumed biologically inactive fragments. Dietary phosphate is a key regulator of circulating FGF-23; choice of assay is critical when studying FGF-23 physiology. INTRODUCTION: Fibroblast growth factor 23 (FGF-23) is a novel phosphaturic factor discovered through genetic studies of patients with renal phosphate wasting disorders. Ablation of the FGF-23 gene in mice reduces renal phosphate excretion and increases serum phosphate, suggesting that FGF-23 is critical for normal phosphate homeostasis. We examined the role of dietary phosphate in the regulation of FGF-23 in humans. MATERIALS AND METHODS: Sixty-six healthy males and females were randomized to either phosphate-depleted or -loaded diets for 5 days, after a 4-day run-in diet. FGF-23 was measured using an "intact" assay that only detects intact FGF-23 peptide and with a "C-terminal" assay that measures both intact FGF-23 peptide and presumed biologically inactive carboxyl terminal fragments. The main outcome was the within group change in FGF-23 with either phosphate depletion or loading. RESULTS: Using the intact FGF-23 assay, mean FGF-23 area under the curve (AUC) decreased by 9 +/- 16% with phosphate depletion (p = 0.0041) and increased by 35 +/- 29% with loading (p < 0.0001). Using the C-terminal FGF-23 assay, mean FGF-23 AUC decreased by 8 +/- 12% with phosphate depletion (p = 0.0003) and increased by 13 +/- 20% with loading (p = 0.0016). Increases in FGF-23 with phosphate loading were greater with the intact assay than with the C-terminal assay (p = 0.0003). Using the intact assay only, FGF-23 was significantly associated with serum phosphate (r = 0.39, p < 0.01), 24-h urinary phosphate (r = 0.47, p < 0.01), fractional excretion of phosphate (r = 0.29, p < 0.01), and 1,25-dihydroxyvitamin D (r = -0.30, p < 0.01). The association between the assays was weak (r = 0.26, p < 0.01). CONCLUSIONS: Dietary phosphate is a key regulator of circulating FGF-23 levels in humans. Additionally, choice of assay is critical when performing physiologic investigations of FGF-23.

Adolescent↗
PubMed2005

Effects of selective testosterone and estradiol withdrawal on skeletal sensitivity to parathyroid hormone in men.

CONTEXT: Gonadal steroid withdrawal increases bone turnover and causes bone loss in men, but the underlying mechanisms have not been defined. We previously reported that gonadal steroid deprivation increases the skeletal sensitivity to the bone resorbing properties of PTH infusion in men, but it is not known whether this effect is mediated by the absence of androgens, estrogens, or both. OBJECTIVE: The objective of the study was to determine the selective effects of testosterone and estradiol withdrawal on the skeletal sensitivity to PTH infusion in healthy adult men. DESIGN AND SETTING: We randomly assigned 58 healthy men between the ages of 20 and 45 yr to receive treatment with combinations of a GnRH analog, an aromatase inhibitor, and hormone add-back therapy to produce the following treatment groups: group 1 (testosterone and estradiol deficient, n = 16); group 2 (testosterone sufficient but estradiol deficient, n = 12); group 3 (testosterone deficient but estradiol sufficient, n = 14); and group 4 (testosterone and estradiol sufficient, n = 16). Twenty-four-hour PTH infusions were performed at baseline and after 6 wk of therapy. Serum N-telopeptide (NTX), C-telopeptide (CTX), osteocalcin (OC), and amino-terminal propeptide of type I procollagen (P1NP) were measured every 6 h during the PTH infusions. RESULTS: Serum testosterone levels fell into the castrate range in groups 1 and 3, whereas estradiol levels were similarly reduced in groups 1 and 2. Gonadal steroid levels in the replaced groups were unchanged from baseline. Serum NTX levels measured before PTH infusion did not change in group 4 (+T, +E) but increased significantly in all other groups. A similar pattern was observed in serum CTX, although the increase in group 2 (+T, -E) was not significant (P = 0.12). Preinfusion concentrations of both OC and P1NP fell in most groups, but these changes were significant in group 2 (+T, -E) for both OC and P1NP and group 4 (+T, +E) for P1NP only. Serum NTX and CTX increased during PTH infusions in all groups at all time points (P < 0.001). In the eugonadal group (group 4 +T+E), the increase in NTX was the same at wk 0 and 6, whereas in all the other groups, the PTH-induced increase in serum NTX was significantly greater at wk, 6 compared with wk 0. The same pattern emerged for CTX, although the difference in group 3 (-T,+E) was not significant (P = 0.12). Serum OC and P1NP levels fell during PTH infusions in all groups and at all time points (P < 0.001), but no significant differences were observed between wk 0 and 6 in any group. CONCLUSIONS: These results demonstrate that the selective suppression of testosterone, estradiol, or both hormones increases the skeletal responsiveness to the bone-resorbing effects of PTH in men. These findings underscore the importance of both androgens and estrogens in male skeletal homeostasis and suggest that changes in skeletal sensitivity to PTH may play an important role in the pathogenesis of hypogonadal bone loss in men.

Adult↗
PubMed2005

Compliance with osteoporosis medications.

BACKGROUND: Long-term compliance with pharmacologic treatments for many asymptomatic conditions may be suboptimal, but little is known about compliance with medications used for osteoporosis. This study was undertaken to assess the level and determinants of compliance with drugs prescribed for osteoporosis. METHODS: This retrospective cohort study used pharmacy claims data from US Medicare and filled prescriptions from a state pharmaceutical benefits program. We included persons 65 years or older who initiated use of a medication for osteoporosis (alendronate sodium, calcitonin, hormone therapy, raloxifene hydrochloride, or risedronate) from January 1, 1996, through December 31, 2002. The outcome of interest was suboptimal medication compliance, defined as equal to or less than 66% of days with medication during a 60-day period. RESULTS: One year after initiating treatment for osteoporosis, 45.2% of the 40,002 patients were not continuing to fill prescriptions. Five years after initiation, 52.1% of patients were not continuing to fill prescriptions for an osteoporosis medication. Several characteristics independently predicted compliance: female sex, younger age, fewer comorbid conditions, using fewer nonosteoporosis medications, bone mineral density testing before and after initiating a medication, a fracture before and after initiating a medication, and nursing home residence during the 12 months before initiating a medication. However, models adjusted for the significant patient variables explained only 6% of the variation in compliance. CONCLUSIONS: Most patients who initiate a medication for osteoporosis do not continue to take it as prescribed. Although several patient characteristics significantly correlated with compliance, adjusted models explained little of the variation.

Age Distribution↗
PubMed2005

Changes in bone mineral density and body composition during initial and long-term gonadotropin-releasing hormone agonist treatment for prostate carcinoma.

BACKGROUND: Initial treatment with a gonadotropin-releasing hormone (GnRH) agonist increases fat mass, decreases lean body mass, and decreases bone mineral density (BMD) in men with prostate carcinoma. To the authors' knowledge, little is known regarding either the long-term effects of treatment or predictors of treatment-related changes in BMD and body composition. METHODS: The authors analyzed prospective 12-month data from 65 men during initial and long-term GnRH agonist treatment for prostate carcinoma. Relationships between baseline characteristics (age, treatment duration, body mass index, and baseline values for outcome of interest) and changes in lean mass, fat mass, and BMD were assessed using univariate and multivariate regression models. RESULTS: Mean BMD of total hip decreased by 1.9 +/- 2.7%, lean body mass decreased by 2.0 +/- 3.3%, and fat mass increased by 6.6 +/- 9.4% at 12 months (P < 0.001 for each comparison). Twenty-three men (35%) had received treatment with a GnRH agonist before study entry, and the mean (+/- standard deviation) duration of previous treatment was 35 +/- 41 months. Longer duration of previous GnRH agonist treatment was found to independently predict less fat accumulation and less loss of lean body mass in multivariate models. In contrast, the duration of GnRH agonist treatment did not significantly predict changes in BMD. Other covariates did not appear to predict changes in body composition or BMD consistently. CONCLUSIONS: The results of the current study showed that fat mass increased and lean body mass decreased mostly during initial GnRH agonist therapy whereas BMD decreased steadily during initial and long-term treatment.

Aged↗
PubMed2005

Effect of aromatase inhibition on bone metabolism in elderly hypogonadal men.

Both estrogens and androgens play important roles in skeletal development and maintenance in men. The relative importance of estrogens and androgens in male bone metabolism, however, remains undefined. Anastrozole is an oral aromatase inhibitor that decreases estrogen production and increases androgen production in men. Currently, anastrozole is being investigated as a potential agent for the treatment of hypogonadism in aging men. Because anastrozole lowers estrogen levels and raises androgen levels, its effect on bone metabolism is difficult to predict. To assess the effects of anastrozole on bone turnover, we randomized 37 elderly (ages 62-74) mildly hypogonadal men (serum testosterone <350 ng/dl) to receive either anastrozole 1 mg daily (n=12), anastrozole 1 mg twice weekly (n=11), or daily placebo (n=14) for 12 weeks. Serum gonadal steroid levels, serum and urine biochemical markers of bone turnover, serum osteoprotegerin, and total body bone mineral density were measured at baseline and week 12. Mean serum levels of total and bioavailable testosterone increased substantially in both treated groups. Specifically, mean +/- SD bioavailable testosterone levels increased from 99+/-31 ng/dl to 207+/-65 ng/dl in the group receiving 1 mg of anastrozole daily and from 115+/-37 ng/dl to 178+/-55 ng/dl in the subjects receiving 1 mg of anastrozole twice weekly ( p <0.001 vs placebo for both groups). Serum estradiol levels decreased modestly in both treated groups (from 26+/-8 pg/ml to 17+/-6 pg/ml in the daily treatment group and from 27+/-8 pg/ml to 17+/-5 pg/ml in the twice-weekly treatment group, p <0.001 vs placebo for both groups). Despite these hormonal changes, no increases in biochemical markers of bone resorption were observed. Specifically, mean serum N-telopeptide and urinary deoxypyridinoline concentrations remained stable in both treated groups over the 12-week treatment period. Similarly, serum biochemical markers of bone formation (osteocalcin and amino-terminal propeptide of type 1 collagen), serum osteoprotegerin, and total body bone mineral density did not change. These data demonstrate that although short-term administration of anastrozole decreases serum estradiol levels in elderly men with mild hypogonadism, this intervention does not adversely affect bone metabolism over a 12-week period. This lack of an effect may be due to the concomitant increase in testosterone production, the relative modest effect on estradiol production, or a combination of both factors. These results suggest that anastrozole therapy is unlikely to have an adverse effect on bone metabolism when taken over extended periods and may prove to be a valuable method of normalizing testosterone production in older men.

Aged↗
PubMed2005

Correlates of circulating androgens in mid-life women: the study of women's health across the nation.

CONTEXT: Androgens influence sexual differentiation and behavior, body composition, and physical functioning in men, but their role in women is less well understood. Because circulating androgens decline with age, the use of androgen supplementation for women to improve health and well-being has been increasing. OBJECTIVE: The aim of this study was to assess the association between androgens and a variety of end points thought to be affected by androgens. DESIGN: In a community-based baseline cohort of women aged 42-52 yr from the Study of Women's Health Across the Nation, we measured circulating testosterone (T), dehydroepiandrosterone sulfate, and SHBG, and calculated a free androgen index (FAI) in 2961 women. MAIN OUTCOME MEASURES: Correlations of androgen measures with each other and with body mass index, waist circumference, and waist-hip ratio were computed, and odds ratios (OR) were estimated for the categorical outcomes of functional limitations, functional status, self-reported health, scores indicative of depressed mood, quality of life, sexual desire and arousal, and the presence of the metabolic syndrome. RESULTS: Androgens, and particularly SHBG, were associated most strongly with body mass index, waist circumference, and waist-hip ratio. SHBG was associated prominently inversely with the metabolic syndrome (OR = 0.32; 95% confidence interval = 0.26-0.39), which was present in 17% of women at baseline. Dehydroepiandrosterone sulfate was associated modestly with functional status and self-reported health. T was associated minimally with increased sexual desire (OR = 1.09; 95% confidence interval = 1.00-1.18). The association of FAI with self-reported health and depressive symptomatology based on the Center for Epidemiologic Studies Depression Scale score was explained more by T than by SHBG, whereas the association of FAI with sexual arousal and metabolic syndrome was due more to SHBG than to T. CONCLUSIONS: Circulating SHBG and androgens are most strongly associated with physical characteristics and the metabolic syndrome in women in this community-based cohort. Androgens are related weakly to physical functioning and other symptoms to which they commonly are attributed, such as sexual desire, sexual arousal, and well-being.

Adult↗
PubMed2005

Statin lipid-lowering drugs and bone mineral density.

BACKGROUND: HMG Co-A reductase inhibitors (statin lipid-lowering drugs) have been associated with a reduced rate of fractures in some studies, but not in others. We examined the relationship between statin use and bone density among postmenopausal women. METHODS: We conducted a cross-sectional survey at one academic medical center. Postmenopausal women who underwent bone densitometry and agreed to a telephone interview were surveyed about osteoporosis risk factors, use of hormone replacement therapy and osteoporosis medications and statin exposure. We then developed linear regression models adjusting for known counfounders to assess the relationship between statin use and bone mineral density (BMD). RESULTS: Of 339 women studied, 162 were current or past users of statins, and 177 were not. Statin users and non-users were similar with respect to age, race, prior fracture history, the presence of medical conditions associated with osteoporosis, use of medications for osteoporosis, use of tobacco and use of oral glucocorticoids. Statin users had significantly higher body mass index (BMI) and rates of thiazide use, and were more likely to abstain from alcohol. After adjusting for important confounders, we found that statin use was associated with a significantly higher t-score at the total hip (-0.53 +/- 0.17) compared with non-users (-0.83 +/- 0.18; p = 0.02). At the lumbar spine, there was a trend toward higher t-scores in statin users (-0.91 +/- 0.24) compared with non-users (-1.21 +/- 0.23; p = 0.08). CONCLUSIONS: These results support the hypothesis that statin use is associated with higher BMD. While it is unclear whether their relationship is causal, further controlled studies examining bone formation and resorption would help determine the clinical implications of these findings.

Bone Density↗
PubMed2005

Medication use patterns for osteoporosis: an assessment of guidelines, treatment rates, and quality improvement interventions.

OBJECTIVE: To assess current osteoporosis treatment guidelines, studies of osteoporosis treatment, and interventions to improve osteoporosis treatment. METHODS: We searched the medical literature for articles published between January 1, 1992, and December 31, 2003, and assessed all relevant articles using a structured data abstraction process. Because of substantial heterogeneity in study design, no attempt was made to summarize the data using meta-analytic techniques. RESULTS: Seventy-six articles met criteria for inclusion. Eighteen practice guidelines were studied. Most guidelines were consistent in key treatment recommendations. Among 18 studies of treatment rates in patients who had fractures, the weighted average varied from 22% for nonhormonal treatment to 19% for calcium. We found slightly higher treatment rates for patients taking oral glucocorticoids or for those older than 65 years. There were no consistent correlates of which patients received treatment. Six studies that examined treatment frequencies after bone densitometry all found that patients with lower bone mineral density were more likely to receive treatment. Most of the 8 interventions designed to improve osteoporosis treatment showed improvement in treatment rates; however, only 3 were randomized, and these showed the smallest effects. CONCLUSIONS: Frequency of treatment of osteoporosis in at-risk populations is low. However, our assessment of the literature revealed no clear and consistent predictors of undertreatment. Few carefully controlled interventions have been reported.

Adult↗
PubMed2004

Bicalutamide monotherapy versus leuprolide monotherapy for prostate cancer: effects on bone mineral density and body composition.

PURPOSE: Gonadotropin-releasing hormone agonists decrease bone mineral density, lean mass, and muscle size and increase fat mass in men with prostate cancer. Less is known about the effects of bicalutamide monotherapy on bone mineral density and body composition. PATIENTS AND METHODS: In a 12-month, open-label study, we randomly assigned 52 men with prostate cancer and no bone metastases to receive either leuprolide or bicalutamide (150 mg by mouth daily). Bone mineral density and body composition were measured by dual energy x-ray absorptiometry and quantitative computed tomography. RESULTS: Mean (+/- standard error) bone mineral density of the posterior-anterior lumbar spine decreased by 2.5% +/- 0.5% in the leuprolide group and increased by 2.5 +/- 0.5 in the bicalutamide group from baseline to 12 months (P <.001). Mean changes in bone mineral density of the total body, total hip, femoral neck, and trabecular bone of the lumbar spine also differed significantly between groups (P < or =.003 for each comparison). Fat mass increased by 11.1% +/- 1.3% in the leuprolide group and by 6.4% +/- 1.1% in the bicalutamide group (P =.01). Changes in lean mass, muscle size, and muscle strength were similar between the groups. Breast tenderness and enlargement were more common in the bicalutamide group than in the leuprolide group. Fatigue, loss of sexual interest, and vasomotor flushing were less common in the bicalutamide group than in the leuprolide group. CONCLUSION: In men with prostate cancer, bicalutamide monotherapy increases bone mineral density, lessens fat accumulation, and has fewer bothersome side effects than treatment with a gonadotropin-releasing hormone agonist.

Aged↗
PubMed2004

Patterns of bone mineral density testing: current guidelines, testing rates, and interventions.

OBJECTIVES: To identify potential obstacles to bone mineral density (BMD) testing, we performed a structured review of current osteoporosis screening guidelines, studies of BMD testing patterns, and interventions to increase BMD testing. DESIGN: We searched medline and HealthSTAR from 1992 through 2002 using appropriate search terms. Two authors examined all retrieved articles, and relevant studies were reviewed with a structured data abstraction form. MEASUREMENTS AND MAIN RESULTS: A total of 235 articles were identified, and 51 met criteria for review: 24 practice guidelines, 22 studies of screening patterns, and 5 interventions designed to increase BMD rates. Of the practice guidelines, almost one half (47%) lacked a formal description of how they were developed, and recommendations for populations to screen varied widely. Screening frequencies among at-risk patients were low, ranging from 1% to 47%. Only eight studies assessed factors associated with BMD testing. Female patient gender, glucocorticoid dose, and rheumatologist care were positively associated with BMD testing; female physicians, rheumatologists, and physicians caring for more postmenopausal patients were more likely to test patients. Five articles described interventions to increase BMD testing rates, but only two tested for statistical significance and no firm conclusions can be drawn. CONCLUSIONS: This systematic review identified several possible contributors to suboptimal BMD testing rates. Osteoporosis screening guidelines lack uniformity in their development and content. While some patient and physician characteristics were found to be associated with BMD testing, few articles carefully assessed correlates of testing. Almost no interventions to improve BMD testing to screen for osteoporosis have been rigorously evaluated.

Bone Density↗
PubMed2004

Body size and ethnicity are associated with menstrual cycle alterations in women in the early menopausal transition: The Study of Women's Health across the Nation (SWAN) Daily Hormone Study.

The dynamics of reproductive hormones that characterize the menopausal transition (perimenopause) are incompletely understood, particularly in non-Caucasian women. The Study of Women's Health across the Nation (SWAN) is a multiethnic cohort study of 3302 women at seven sites who were aged 42-52 yr at baseline. All participants are seen annually to assess a variety of endpoints. A subcohort of 848 women undergoes further investigation of their daily patterns of reproductive hormones in the Daily Hormone Study (DHS). DHS enrollees annually complete a daily collection of first morning voided urine for an entire menstrual cycle or up to 50 d (whichever comes first). Chemiluminescent assays measured urinary LH and FSH, as well as metabolites of estradiol [estrone conjugates (E1c)] and progesterone [pregnanediol glucuronide (Pdg)]. Cycles were assessed for evidence of luteal activity and day of luteal transition using previously developed algorithms. Midreproductive-aged women who underwent similar daily urinary analyses served as historical controls. Correlates of cycle features were identified. Eight hundred thirty-three cycles were evaluable and had complete data on covariates. Six hundred seventy-four (80.9%) cycles had evidence of luteal activity, and 159 (19.1%) did not. Women who were at least 49 yr old were less likely to have cycles with luteal activity and had more variable cycle length, higher total-cycle FSH, and lower total-cycle Pdg. Compared with heavier women, those with body mass index less than 25 kg/m2 had shorter cycles and higher total-cycle LH, FSH, and Pdg but not E1c. Chinese- and Japanese-American women had overall lower adjusted total-cycle E1c excretion. Smoking was not significantly associated with cycle length or hormones. When compared with cycles of younger control women, the cycles of the SWAN DHS participants had higher gonadotropins, lower total integrated Pdg, and E1c levels that were not different, which suggests that the ovary retains sensitivity to elevated FSH in the early menopausal transition. In this cross-sectional study of women over age 42 who are premenopausal or in the early menopausal transition, there were important differences in the characteristics of cycles related to age, body mass index, and ethnicity. Comparisons to younger women indirectly support the inhibin hypothesis, which proposes that the initiating event in the menopausal transition is the loss of inhibin negative feedback on FSH secondary to a diminished follicular reserve.

Adult↗
PubMed2004

Raloxifene to prevent gonadotropin-releasing hormone agonist-induced bone loss in men with prostate cancer: a randomized controlled trial.

GnRH agonists decrease bone mineral density and increase fracture risk in men with prostate cancer. Raloxifene increases bone mineral density in postmenopausal women, but its efficacy in hypogonadal men is not known. In a 12-month open-label study, men with nonmetastatic prostate cancer (n = 48) who were receiving a GnRH agonist were assigned randomly to raloxifene (60 mg/d) or no raloxifene. Bone mineral densities of the posteroanterior lumbar spine and proximal femur were measured by dual energy x-ray absorptiometry. Mean (+/-se) bone mineral density of the posteroanterior lumbar spine increased by 1.0 +/- 0.9% in men treated with raloxifene and decreased by 1.0 +/- 0.6% in men who did not receive raloxifene (P = 0.07). Bone mineral density of the total hip increased by 1.1 +/- 0.4% in men treated with raloxifene and decreased by 2.6 +/- 0.7% in men who did not receive raloxifene (P < 0.001). Similar between-group differences were observed in the femoral neck (P = 0.06) and trochanter (P < 0.001). In men receiving a GnRH agonist, raloxifene significantly increases bone mineral density of the hip and tends to increase bone mineral density of the spine.

Aged↗
PubMed2003

The effects of parathyroid hormone, alendronate, or both in men with osteoporosis.

BACKGROUND: Because parathyroid hormone increases both bone formation and bone resorption, it is possible that combining parathyroid hormone with an antiresorptive agent will enhance its effect on bone mineral density. METHODS: We randomly assigned 83 men who were 46 to 85 years of age and had low bone density to receive alendronate (10 mg daily; 28 men), parathyroid hormone (40 microg subcutaneously daily; 27 men), or both (28 men). Alendronate therapy was given for 30 months; parathyroid hormone therapy was begun at month 6. The bone mineral density of the lumbar spine, proximal femur, radial shaft, and total body was measured every six months with the use of dual-energy x-ray absorptiometry. Trabecular bone mineral density of the lumbar spine was measured at base line and month 30 by means of quantitative computed tomography. Serum alkaline phosphatase levels were measured every six months. The primary end point was the rate of change in the bone mineral density at the posteroanterior spine. RESULTS: The bone mineral density at the lumbar spine increased significantly more in men treated with parathyroid hormone alone than in those in the other groups (P<0.001 for both comparisons). The bone mineral density at the femoral neck increased significantly more in the parathyroid hormone group than in the alendronate group (P<0.001) or the combination-therapy group (P=0.01). The bone mineral density of the lumbar spine increased significantly more in the combination-therapy group than in the alendronate group (P<0.001). At 12 months, changes in the serum alkaline phosphatase level were significantly greater in the parathyroid hormone group than in the alendronate group or the combination-therapy group (P<0.001 for both comparisons). CONCLUSIONS: Alendronate impairs the ability of parathyroid hormone to increase the bone mineral density at the lumbar spine and the femoral neck in men. This effect may be attributable to an attenuation of parathyroid hormone-induced stimulation of bone formation by alendronate.

Absorptiometry, Photon↗
PubMed2003

Reproductive hormones in the early menopausal transition: relationship to ethnicity, body size, and menopausal status.

We measured serum reproductive hormone concentrations in a community-based, multiethnic population of premenopausal and early perimenopausal women to determine whether there are ethnic differences in hormones that can be explained by host factors. We studied 2930 participants in the Study of Women's Health Across the Nation who were aged 42-52 yr and self-identified as African-American (27.6%), Caucasian (47.1%), Chinese (7.4%), Hispanic (8.8%), or Japanese (9.0%) at 7 clinical sites. Outcome measures from this baseline assessment of a longitudinal study were serum estradiol (E2), FSH, testosterone (T), dehydroepiandrosterone sulfate, and SHBG concentrations and calculated estimates of free steroid availability, free testosterone index, and free E2 index from serum collected primarily in the early follicular phase of a spontaneous menstrual cycle. The primary explanatory variables were race/ethnicity, menopausal status, age, body mass index, day of the cycle, smoking, alcohol use, and physical activity. Chinese women had lower unadjusted E2 and SHBG levels, and Hispanic women had lower unadjusted T levels than other ethnic groups. Unadjusted serum FSH levels did not differ by race/ethnicity. E2 levels adjusted for host characteristics, particularly body size, did not differ by race/ethnicity. Adjusted FSH levels were higher, and adjusted T levels were lower in African-American and Hispanic women. Serum E2 and FSH concentrations were highly variable. Serum FSH levels, but no other hormone concentrations, were positively correlated with menopausal status. Serum dehydroepiandrosterone sulfate levels were negatively correlated with age, but not menopausal status. All hormone concentrations were significantly correlated with body mass index. We conclude that serum sex steroid, FSH, and SHBG levels vary by ethnicity, but are highly confounded by ethnic disparities in body size.

Adult↗