Pamela Taxel

Oral estrogen improves serum lipids, homocysteine and fibrinolysis in elderly men

The effects of estrogen on cardiovascular risk factors have been less well defined in men than in women. We measured lipid and lipoprotein concentrations, lipoprotein particle size distributions, lipoprotein (a), homocysteine, and markers of thrombosis and fibrinolysis in 18 [corrected] healthy elderly men (age 74 +/- 3 years, mean +/- S.D.) before and after 9 weeks of treatment with 0.5, 1 or 2 mg/day of oral micronized 17beta-estradiol. LDL-C (-6%), apo B (-9%), triglyceride (-5%), and homocysteine (-11%) concentrations decreased with estradiol, whereas HDL-C (+14%) increased. Intermediate-size VLDL subclass concentrations were lowered and LDL and HDL subclass levels altered in such a way as to cause average LDL and HDL particle size to increase. Lipoprotein (a) did not change. Fibrinogen (-13%) and plasminogen activator inhibitor-1 (PAI-1) concentrations (-26%) decreased, but there were no changes in thrombotic markers including thrombin-antithrombin III complex, prothrombin fragment 1.2, D-dimer, antithrombin activity, protein-C and S and von Willebrand factor antigen. Breast tenderness occurred in four men and heartburn in five but did not require discontinuation of treatment. We conclude that oral estrogen in men reduces homocysteine, fibrinogen, and PAI-1 concentrations and favorably influences VLDL, LDL and HDL subclass levels without increasing markers of thrombotic risk.

The effect of 6 months of androgen deprivation therapy on muscle and fat mass in older men with localized prostate cancer

Objective. To evaluate body composition changes, specifically skeletal muscle mass, in men receiving androgen deprivation with luteinizing-hormone releasing hormone-agonist (LHRH-A) for prostate cancer (PCa) in comparison with healthy controls. Design. Retrospective analysis of body composition changes in men with prostate cancer receiving LHRH-A therapy from 2 clinical trials compared to men without prostate cancer serving as a placebo-control in another clinical trial. Setting. Clinical Research Center in Connecticut. Participants. Thirty men (> 60 years) receiving 6 months of LHRH-A therapy for PCa were compared to a healthy group of 25 men without PCa. Measurements. Appendicular skeletal muscle/height2 (ASM/ht2), lean and fat mass were assessed by dual energy x-ray absorptiometry. Total testosterone levels were assessed by enzyme immunoassay. Results. At baseline, 12/30 (40%) of the treatment group and 7/25 (28%) of the control group (p = 0.11) met criteria for sarcopenia. There were no differences between control groups in ASM/ht2 or lean mass. The LHRH-A group had a higher percent body fat than the control group, 29.8 ± 6.3 versus 26.3 ± 4.6 (p = 0.02). ASM/ht2 and lean mass decreased in the LHRH-A group from 7.5 ± 0.9 kg to 7.3 ± 0.9 kg (−2.3% ± 0.03; p ⩽ 0.001) and 53.5 ± 5.4 kg to 52.3 ± 5.3 kg (−2.1% ± 0.03; p ⩽ 0.001), respectively. There was no muscle loss in the control group. At 6 months, the LHRH-A group had increased percent body fat from 29.8 ± 6.4 to 32.2 ± 5.8 (9.5% ± 0.13; p ⩽ 0.001), whereas the control group had decreased in percent body fat from 26.6 ± 4.6 to 25.3 ± 5.0 (−3.8% ± 0.08; p = 0.02). Conclusions. Men undergoing LHRH-A treatment for PCa decreased appendicular skeletal muscle and lean tissue and increased body fat within 6 months of initiation of therapy. Lifestyle changes or medical interventions to minimize the effects of androgen deprivation therapy for PCa deserve investigation.

Dexamethasone suppresses in vivo levels of bone collagen synthesis in neonatal mice

The objective of this study was to determine the acute effects of glucocorticoids on in vivo levels of bone collagen synthesis in neonatal mice. Mice were injected with vehicle or dexamethasone at the start of the experiment. At 22 h, mice were given a 10 microCi injection of [3H]proline. At 24 h, the mice were sacrificed and the incorporation of [3H]proline into collagenase-digestible CDP labeling) and noncollagen (NCP labeling) protein in calvariae were determined by digestion with bacterial collagenase. Calvarial RNA was analyzed for COL 1A1 and osteocalcin mRNA levels by Northern blotting. After 24 h, vehicle-treated mice showed a 9.8 +/- 1.0% weight gain while dexamethasone-treated mice (1 mg/kg) had a 7.4 +/- 0.8% weight loss. Dexamethasone (1 mg/kg) decreased CDP and NCP labeling in calvariae by 51 +/- 4% and 17 +/- 4%, respectively (13 experiments). The inhibitory effect on protein labeling was selective for collagen since dexamethasone decreased the percent collagen synthesis from 25.4 +/- 1.6% to 16.6 +/- 1.0% (13 experiments). Dexamethasone at 3 mg/kg also decreased CDP labeling and the percent collagen synthesis in calvariae. There was a 30% reduction in COL1A1 mRNA levels and a 67% decrease in osteocalcin mRNA levels. To determine the reversibility of the inhibition of collagen synthesis, mice were given a single injection of dexamethasone (1 mg/kg) and then injected with [3H]proline 2 h prior to sacrifice at 24, 48, or 72 h. The reduction in CDP labeling observed at 24 h was fully reversed by 48-72 h. Moreover, by 72 h, the-rate of weight gain by dexamethasone-treated mice was similar to vehicle-treated controls. These data show that administration of dexamethasone to neonatal mice leads to a selective decrease in bone collagen synthesis within 24 h that is accompanied by down-regulation of osteocalcin and COL1A1 mRNA levels. This model will be useful in determining mechanisms by which high dose glucocorticoids inhibit bone formation in vivo.

The Effect of Short-Term Estradiol Therapy on Cognitive Function in Older Men Receiving Hormonal Suppression Therapy for Prostate Cancer

Objectives: To determine the effect of estrogen (E) alone (without the influence of testosterone (T)) on cognitive function in older men, using 17‐β micronized estradiol versus placebo in older men rendered hypogonadal (low T and E) by treatment for prostate cancer.

Risedronate prevents early bone loss and increased bone turnover in the first 6 months of luteinizing hormone-releasing hormone-agonist therapy for prostate cancer

Study Type – Therapy (RCT)
Level of Evidence 1b

Osteoporosis in older men.

Historically, the focus in osteoporosis has been on postmenopausal women. In the past few years, information about osteoporosis in other populations, including men, has begun to emerge. Although less common in older men, osteoporosis nonetheless represents a major health concern. Approximately 30% of hip fractures worldwide occur in men, resulting in significant mortality and loss of independence. The incidence of osteoporotic fractures in men is increasing. The reason for this is unclear, but improvement in longevity and better management of other chronic diseases most likely play a role. Two recent studies have addressed the question of fracture risk in men past middle age and have estimated that men > 50 years of age have a 19% to 25% lifelong risk of osteoporotic fracture. Mortality is higher following hip fracture and pain is more intense in men than in women following severe vertebral fracture.

Chiasmal herniation as a complication of bromocriptine therapy.

Introduction Medical treatment of macroprolactinomas with dopamine agonists decreases tumor mass and improves visual defects. We report an unusual complication of a macroprolactinoma responding to bromocriptine: a visual field defect caused by downward herniation of the optic chiasm. Materials and Methods A 64-year-old woman was found to have a 4.5 cm macroprolactinoma with superior displacement of the optic chiasm, bitemporal hemianopia, and serum prolactin concentration (P) of 17,060 μg/L. Bromocriptine was initiated at 2.5 mg/day and increased to 7.5 mg/day over 2 months. Results After 2 months, visual fields improved significantly and tumor height decreased to 3 cm with resolution of the optic chiasm displacement. P decreased to 1,180 μg/L. After 5 months of therapy, visual fields were normal, and P was 8 μg/L. After 8 months of therapy, new bilateral visual defects were observed. Magnetic resonance imaging (MRI) revealed further decrease of the tumor height to 1.5 cm, and inferior and leftward traction of the optic chiasm as the probable mechanism for the new visual field deficit. P was <1 μg/L. Bromocriptine was decreased to 5 mg/day to allow reduced traction on the optic chiasm and its blood supply. Over the next 4 months, visual field abnormalities resolved. Conclusions We report the development of a visual field abnormally that is explained by chiasmal herniation caused by a shrinking macroprolactinoma. This complication resolved with a decrease in the bromocriptine dose. We suggest that patients undergoing bromocriptine therapy for macroprolactinomas be followed for this potential complication.

Differential diagnosis and secondary causes of osteoporosis.

Secondary osteoporosis refers to osteoporosis in which an underlying cause or factor other than those attributable to the postmenopausal state or aging can be identified. Primary, or idiopathic, osteoporosis implies that a secondary cause cannot be found. Secondary osteoporosis occurs not only in postmenopausal women but also in men and premenopausal women. In series reported from specialized centers, as many as 30% of postmenopausal women and 50% to 80% of men have an identifiable secondary cause of osteoporosis, although the frequency of secondary osteoporosis is probably much lower in the general population. In assessing the patient with osteoporosis, it is important to look for secondary causes and aggravating factors that are reversible and amenable to therapy. In addition to secondary forms, 2 metabolic bone diseases, osteomalacia and primary hyperparathyroidism, can mimic or aggravate osteoporosis. This paper will summarize the differential diagnosis and management of osteoporosis, osteomalacia, and hyperparathyroidism and review the most common causes of secondary osteoporosis.

The effect of short-term treatment with micronized estradiol on bone turnover and gonadotrophins in older men.

Evidence for the role of estrogen in male bone metabolism has been confirmed by studies on a man with a genetic defect in the estrogen receptor as well as men with aromatase defects. All exhibited tall stature, delayed epiphysial closure, decreased bone density and increased bone turnover. Estrogen is likely to affect bone turnover in men throughout life; therefore, we hypothesized that older men would show decreased bone resorption in response to estrogen therapy. To test our hypothesis, fourteen community-dwelling men with osteopenia of the femoral neck were treated for 9 weeks with micronized estradiol, 1 mg/d, a dose which is effective in postmenopausal women. Each subject served as his own control. Markers of bone resorption, N-terminal collagen crosslinks (NTX) and C-terminal collagen crosslinks (CTX) and markers of bone formation, osteocalcin (OC) and bone specific alkaline phosphatase (BSAP) were measured every 3 weeks during a 9-week treatment period and 9 weeks post-treatment. Sex hormones, gonadotrophins and calciotropic hormones were measured at baseline, 9 weeks on treatment and 9 weeks post- treatment. After 9 weeks of treatment, estradiol and estrone levels increased significantly by greater than 6-fold and 15-fold, respectively. SHBG levels increased significantly by 17%. Testosterone and free testosterone levels decreased significantly by 27% and 34%, respectively. Markers of bone resorption showed wide variation at baseline and while on treatment. There was no correlation between changes in bone markers and changes in estrogen levels. During treatment, 11 patients showed a decrease of NTX or CTX, but three showed an increase. These three and one other subject had high initial levels of FSH and LH, suggesting some degree of primary gonadal failure, which decreased during estrogen therapy. Thus, the change in NTX (and CTX) after 9 weeks of E2 treatment was correlated with initial FSH (r= -.66, p= .01) and LH (r= -.73, p= .003) values. In addition, the largest decrease in free testosterone at 9 weeks was correlated with the higher values for NTX, CTX and BAP (r=-0.66, -0.68, -0.70 respectively; p≤.01 for each of the markers). Treatment was generally well tolerated. Side effects of treatment were minimal, and included breast tenderness and decreased libido which reversed after treatment. We conclude that it is feasible to give low dose estrogen to healthy older men, but that the effects on bone turnover are not consistent. Changes in central feedback and in endogenous sex hormone production may alter the response of bone turnover to exogenous estrogen in this population.

Cancer Therapy and Osteoporosis: Approach to Evaluation and Management

The incidences of osteoporosis and cancer increase with age, and these two diagnoses are often made in the same individual. Both increasing age and hypogonadism associated with aging, as well as cancer therapies, can lead to loss of bone mass and increased risk for fragility fractures. Advancing age carries an association with increased incidence of cancers. Thus, cancer and its therapies may predispose an individual to osteoporosis and its associated morbidity and mortality. Prevention of bone loss and its consequent fractures is critical in the care of aging patients. This article reviews the mechanisms of bone metabolism and the principles of management of bone health in the older population with a history of cancer.