Testosterone Deficiency and Changes in Body Composition in Men Living with HIV

Influence of Baseline Serum Testosterone on Changes in Body Composition in Response to Testosterone Therapy

Background: Common changes with menopause and aging include an increase in visceral adiposity and loss of lean body mass. Declines in sex steroid hormones contribute to these body composition changes, but emerging evidence also implicates increased pituitary production of follicle stimulating hormone (FSH). Blocking FSH action with an FSH-β subunit antibody reduced adiposity and increased lean body mass in ovariectomized female mice, and both male and female intact mice (Liu Nature 2017). Some, but not all, clinical observational studies have demonstrated positive associations between FSH and measures of adiposity (Zaidi Endocrinology 2018). Objective: To investigate the associations between endogenous FSH levels and measures of body composition in older adults from the AGES-Reykjavik cohort, independent of sex steroid hormones. Methods/Results: Participants were recruited from the AGES-R study, excluding those using sex steroid hormone agonists or antagonists. FSH (ELISA), total estradiol and total testosterone (GC/MS) were measured from fasting serum. Total body fat (kg), total body lean mass (kg), and appendicular lean mass (kg) were measured with total body DXA. Appendicular lean mass index (ALMI) was calculated as appendicular lean mass/height2 (kg/m2). Visceral adipose tissue (VAT) area (cm2) and subcutaneous adipose tissue (SAT) area (cm2) were measured with abdominal CT. Linear regression analyses of FSH in association with body composition parameters were performed, stratified by gender, both unadjusted and adjusted for age, visit window, BMI, total estradiol and total testosterone levels. Among the 245 men, the mean age was 82.4 (SD 4.0) years, mean BMI was 26.7 (SD 3.6) kg/m2 and mean FSH 19.0 (SD 16.9) IU/L . Among the 238 women, the mean age was 80.6 (SD 4.0) years, mean BMI 27.4 (SD 4.1) kg/m2 and mean FSH 71.6 (SD 23.2) IU/L. In models adjusted for age, visit window, BMI, estradiol and testosterone, there were no significant associations between FSH and any measure of body composition in men. In adjusted models in women, each SD increase in FSH was associated with a 2.67% greater SAT area (p=0.03) but no significant difference in VAT area or total body fat. Conversely, each SD increase in FSH was associated with a1.62% lower total body lean mass (p=0.005) in women, but no significant difference in ALMI. Conclusion: Consistent with preclinical models, we found higher FSH to be associated with greater subcutaneous adiposity and lower lean body mass in older women. We found no associations between FSH and measures of body composition in older men. Further research is needed to determine whether FSH-directed therapy may be an effective means of combatting the body composition changes associated with menopause.

Testosterone, the predominant sex hormone in men, is produced by the testes under stimulation by the gonadotrophs in the pituitary, which in turn are controlled by gonadotropin-releasing hormone neurons in the hypothalamus. A young adult man generally produces 3 to 10 mg of testosterone daily, which translates into serum values of 300 to 1000 ng/dL. The consequences of classical male hypogonadism (primary or secondary) have been long known to physicians and patients alike and include decreased libido, erectile dysfunction, osteoporosis, reduced sexual hair, and changes in body habitus. Recently, we have come to appreciate that reductions in serum testosterone resulting from aging or chronic disease have signs and symptoms similar to those seen in classical male hypogonadism, along with increased fat mass, decreased lean body mass, decreased muscle strength, and diminished quality of life.1 During the past decade, reports have been trickling in, mainly from laboratory and epidemiological studies (and a few clinical studies), linking differences in serum testosterone levels to various cardiovascular risk factors and also directly to cardiovascular disease and death. The article by Khaw et al2 in this issue of Circulation is another link to this growing chain. Article p 2694 Thirteen years ago, Phillips et al3 reported that low total and free testosterone levels were inversely linked to coronary artery disease, even after adjusting for age and adiposity. This observation still holds true, as was recently supported by a study showing that men with angiographically proven coronary artery disease had lower levels of testosterone than those of controls.4 Furthermore, testosterone levels were negatively correlated to the degree of coronary involvement. A few population-based studies have been published that relate low serum testosterone level with risk of death. A study of male veterans showed that low testosterone was associated with increased risk of …

PurposeSex steroids play a key role on male bone homeostasis and body composition (BC), their role in men living with HIV (MLWH) is less recognized. This study aimed at investigating the prevalence of low BMD, sarcopenia, and sarcopenic obesity (SO) and their relationship with sex steroids in MLWH aged < 50.MethodsProspective, cross-sectional, observational study on MLWH younger than 50 (median age 47.0 years). BC and BMD were evaluated with DXA. Two different definitions of sarcopenia were applied: appendicular lean mass/height2 (ALMI) < 7.26 kg/m2 or appendicular lean mass/body weight (ALM/W) < 28.27%. Low BMD was defined for Z-score < −2.0. Sarcopenia coupled with obesity identified SO. Serum total testosterone (T) and estradiol (E2) were measured by LC–MS/MS; free testosterone (cFT) was calculated by Vermeulen equation.ResultsSarcopenia was detected in 107 (34.9%) and 44 (14.3%) out of 307 MLWH according to ALMI and ALM/W, respectively. The prevalence of SO was similar by using both ALMI (11.4%) and ALM/W (12.4%). Sarcopenic and SO MLWH had lower total T and cFT in both the definition for sarcopenia. BMD was reduced in 43/307 (14.0%). Serum E2 < 18 pg/mL was an independent contributing factor for sarcopenia, SO, and low BMD.ConclusionsT and E2 are important determinants of BC even in MLWH. This is among the first studies investigating the distribution of obesity phenotypes and the prevalence of SO among MLWH showing that SO is present in 11–12% of enrolled MLWH regardless of the definition used. However, deep differences emerged using two different diagnostic definitions.

The health benefits of caloric restriction, including decreasing body fat and blood glucose, differ between males and females and this difference depends on the age at which caloric restriction begins.

Testosterone treatment in obese dieting men augments the diet-associated loss of fat mass, but protects against loss of lean mass. We assessed whether body composition changes are maintained following withdrawal of testosterone treatment. We conducted a prespecified double-blind randomized placebo-controlled observational follow-up study of a randomized controlled trial (RCT). Participants were men with baseline obesity (body mass index >30kg/m2 ) and a repeated total testosterone level <12nmol/L, previously enrolled in a 56-week testosterone treatment trial combined with a weight loss programme. Main outcome measures were mean adjusted differences (MAD) (95% confidence interval), in body composition between testosterone- and placebo-treated men at the end of the observation period. Of the 100 randomized men, 82 completed the RCT and 64 the subsequent observational study. Median [IQR] observation time after completion of the RCT was 82weeks [74; 90] in men previously receiving testosterone (cases) and 81weeks [67;91] in men previously receiving placebo (controls), P=.51. At the end of the RCT, while losing similar amounts of weight, cases had, compared to controls, lost more fat mass, MAD -2.9kg (-5.7, -0.2), P=.04, but had lost less lean mass MAD 3.4kg (1.3, 5.5), P=.002. At the end of the observation period, the former between-group differences in fat mass, MAD -0.8kg (-3.6, 2.0), P=1.0, in lean mass, MAD -1.3kg (-3.0, 0.5), P=.39, and in appendicular lean mass, MAD -0.1kg/m2 (-0.3, 0.1), P=.45, were no longer apparent. During observation, cases lost more lean mass, MAD -3.7kg (-5.5, -1.9), P=.0005, and appendicular lean mass, MAD -0.5kg/m2 (-0.8, -0.3), P<.0001 compared to controls. The favourable effects of testosterone on body composition in men subjected to a concomitant weight loss programme were not maintained at 82weeks after testosterone treatment cessation.

We determined the effects of conjugated linoleic acid (CLA) supplementation during resistance training. Seventy-six subjects were randomized to receive CLA (5 g.d(-1)) or placebo (PLA) for 7 wk while resistance training 3 d.wk(-1). Seventeen subjects crossed over to the opposite group for an additional 7 wk. Measurements at baseline, 7 wk, and 14 wk (for subjects in the crossover study) included body composition, muscle thickness of the elbow flexors and knee extensors, resting metabolic rate (RMR), bench and leg press strength, knee extension torque, and urinary markers of myofibrillar degradation (3-methylhistidine (3MH) and bone resorption (cross-linked N-telopeptides (Ntx)). After 7 wk the CLA group had greater increases in lean tissue mass (LTM) (+1.4 vs +0.2 kg; P < 0.05), greater losses of fat mass (-0.8 vs +0.4 kg; P < 0.05), and a smaller increase in 3MH (-0.1 vs + 1.3 micromol.kg LTM.d(-1); P < 0.05) compared with PLA. Changes between groups were similar for all other measurements, except for a greater increase in bench press strength for males on CLA (P < 0.05). In the crossover study subjects had minimal changes in body composition, but smaller increases in 3MH (-1.2 vs +2.2 micromol.kg LTM.d(-1); P < 0.01) and NTx (-4.8 vs +7.3 nmol.kg(-1) LTM.d(-1); P < 0.01) while on CLA versus PLA. Supplementation with CLA during resistance training results in relatively small changes in body composition accompanied by a lessening of the catabolic effect of training on muscle protein.

Age-related decrease in resting energy expenditure in sedentary white women: effects of regional differences in lean and fat mass

Do women with PCOS have a unique predisposition to obesity?

37-Year-Old Man With Fatigue and Erectile Dysfunction

Both baseline cardiorespiratory fitness and adiposity predict the risk of cancer mortality. However, the effects of changes in these two factors over time have not been evaluated thoroughly. The aim of this study was to examine the independent and joint associations of changes in cardiorespiratory fitness and body composition on cancer mortality. The cohort consisted of 13,930 men (initially cancer-free) with two or more medical examinations from 1974 to 2002. Cardiorespiratory fitness was assessed by a maximal treadmill exercise test, and body composition was expressed by body mass index (BMI) and percent body fat. Changes in cardiorespiratory fitness and body composition between the baseline and the last examination were classified into loss, stable, and gain groups. There were 386 deaths from cancer during an average of 12.5 yr of follow-up. After adjusting for possible confounders and BMI, change hazard ratios (95% confidence intervals) of cancer mortality were 0.74 (0.57-0.96) for stable fitness and 0.74 (0.56-0.98) for fitness gain. Inverse dose-response relationships were observed between changes in maximal METs and cancer mortality (P for linear trend = 0.05). Neither BMI change nor percent body fat change was associated with cancer mortality after adjusting for possible confounders and maximal METs change. In the joint analyses, men who became less fit had a higher risk of cancer mortality (P for linear trend = 0.03) compared with those who became more fit, regardless of BMI change levels. Being unfit or losing cardiorespiratory fitness over time was found to predict cancer mortality in men. Improving or maintaining adequate levels of cardiorespiratory fitness appears to be important for decreasing cancer mortality in men.

Editorials4 November 2008Use of Growth Hormone Secretagogues to Prevent or Treat the Effects of Aging: Not Yet Ready for Prime TimeFREEMarc R. Blackman, MDMarc R. Blackman, MDFrom Veterans Affairs Medical Center, Washington, DC 20422.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-149-9-200811040-00010 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Aging is associated with progressive and substantial decreases in growth hormone secretion and in circulating concentrations of insulin-like growth factor I (IGF-I) (1). Increasing evidence suggests that these hormonal changes, coupled with estrogen deficiency in menopausal women and reduced total and bioavailable testosterone in men, contribute to age-related decreases in skeletal muscle mass and strength (sarcopenia), increased total and intra-abdominal fat, loss of bone mass (osteopenia), insulin resistance, dyslipidemias, and enhanced risks for type 2 diabetes mellitus and cardiovascular disease (15). Taken together, these changes in body composition and function are precursors of musculoskeletal frailty, disability and reduced physical function, falls, bone fractures and subsequent nursing home admissions, and mortality (6).Numerous reports indicate that growth hormone treatment improves body composition, muscle strength, metabolic and physical function, bone density, and quality of life in nonelderly adults with pathologic growth hormone deficiency (7). In contrast, relatively few randomized, controlled trials of recombinant human growth hormone have been conducted in older people, and the results of such studies have been equivocal or disappointing in terms of clinical benefits (8). In particular, administration of growth hormone to healthy older persons has consistently resulted in improvements in body composition (increases in lean body mass; decreases in total and abdominal fat mass; and, less frequently, augmented bone mineral density) and some metabolic parameters (lowering low-density lipoprotein cholesterol), without significantly affecting muscle strength, physical performance, or quality of life. Moreover, side effects of growth hormone treatment, such as peripheral edema, arthralgias, myalgias, glucose intolerance, and loss of insulin sensitivity, are especially common in older persons (8). Development of insulin resistance is of concern because it predisposes a patient to diabetes mellitus and vascular disease.Injections or infusions of growth hormonereleasing hormone (GHRH) and parenteral or oral administration of a ghrelin-mimetic growth hormone secretagogue (GHS) have been shown to restore levels of growth hormone and IGF-I in older persons to those of young adults (911), indicating that the aging pituitary is capable of enhanced growth hormone secretion if appropriate stimuli are supplied and suggesting that older adults with relative growth hormone deficiency might also benefit from growth hormone stimulation.Why use GHRH or a GHS in older persons? Growth hormone is released in episodic pulses by cells of the anterior pituitary gland and is an important hormone that increases muscle and bone mass and decreases body fat (1). Most circadian growth hormone release occurs at night, especially during slow-wave sleep. Growth hormone secretion is principally regulated by 2 stimulatory peptideshypothalamic GHRH and ghrelin, which is produced in the stomach, small intestine, and hypothalamusand the inhibitory peptide somatostatin. Biologically active GHRH is a 40 or 44amino acid peptide that stimulates growth hormone production via the GHRH receptor (1). Ghrelin, an octanoylated 28amino acid peptide, stimulates growth hormone secretion via a distinct, endogenous GHS receptor (12, 13). MK-677 is an orally active GHS and ghrelin mimetic that stimulates GHS-1 receptors. Ghrelin exerts considerable appetite-stimulating and growth hormonereleasing effects; thus, the clinical effects of a ghrelin mimetic might be expected to differ from those of GHRH or growth hormone (14). The availability of an orally administered GHS that enhances pulsatile release of growth hormone provides a practical opportunity to test the notion that chronic stimulation of growth hormone release can improve physical function in older adults.Evidence suggests that GHRH or a GHS, like growth hormone, can increase lean body mass and decrease fat mass in older persons, but effects on muscle strength and physical performance have been less consistent. Two studies that reported improvements in physical function (15, 16) provided no placebo comparison, were of short duration (3 months), and had small sample sizes. The former, which used the oral GHS and ghrelin mimetic MK-677, was conducted in obese participants, and the latter, which used GHRH, was conducted in healthy postmenopausal women.In this issue, Nass and colleagues (17) report the effects of MK-677 on age-associated decreases in lean body mass and increases in body fat. The investigators conducted a 2-year, double-masked, placebo-controlled, modified-crossover, General Clinical Research Centerbased clinical trial in which 65 healthy men and women (of whom some were receiving hormone replacement therapy) 60 to 81 years of age received 25 mg of MK-677 each morning. The primary outcome measures at 1 year included 24-hour growth hormone secretory profiles, morning IGF-I serum concentrations, fat-free mass (determined by a 4-compartment model), and abdominal visceral fat. The study was powered on the 12-month change comparison between the MK-677 and placebo groups and did not evaluate possible effects of sex or hormone replacement therapy. Secondary outcome measures included various other body composition, endocrinemetabolic, strength, physical performance, and quality-of-life measures. After 1 year, circadian pulsatile growth hormone secretion and morning IGF-I concentration were augmented to those of healthy young adults. Fat-free (total body and limb lean) mass and intracellular water increased significantly, the latter being a biomarker of fat-free mass. Total and abdominal fat, muscle strength and function, and quality of life did not change. Low-density lipoprotein cholesterol levels decreased slightly, whereas cortisol, fasting blood glucose, and hemoglobin A1c levels increased. The Quicki index of insulin sensitivity decreased slightly. MK-677 was generally well tolerated. Appetite and body weight increased somewhat, but peripheral edema, joint or muscle pains, newly detected malignant disease, and other adverse outcomes did not significantly increase in women or men. Analysis of the 2-year outcome data in a subset of 53 of the 65 participants revealed that the growth hormone IGF-I and fat-free mass changes persisted. In participants treated for 2 years with MK-677, fasting blood glucose values were no longer elevated. Concentrations of IGF-I returned to normal 1 month after crossover and by 6 months after study completion. Nass and colleagues concluded that long-term functional and, ultimately, pharmacoeconomic studies are indicated in older adults.Is there a role for MK-677 or another GHS in attenuating age-related alterations in body composition and losses of function that lead to disability and loss of independence? Nass and colleagues, in their rigorously conducted study, clearly found that sustained use of an oral GHS for 1 to 2 years will maintain a youthful growth hormone and IGF-I hormonal profile and augment fat-free (lean body) mass. However, as with other published studies using growth hormone, GHRH, or MK-677, no functional or quality-of-life benefits and some unwanted and worrisome adverse effects (such as increased insulin resistance and decreased glucose tolerance) were observed. Possible reasons for Nass and colleagues' findings include the relatively small number of participants studied; their general good health (questionable ceiling effect); their uncertain pretreatment growth hormone, IGF-I, and sex-steroid status; the combination of data from men and women, and from women receiving and not receiving hormonal replacement (estrogen with or without progestin); and the relatively short duration of the intervention. Given that men and women respond differently to manipulation of the growth hormoneIGF-I axis (18), and that such responsivity is further modulated by endogenous or exogenous gonadal steroids, it is important to design studies so that possible qualitative and quantitative sexual dimorphic effects can be discerned.Doseresponse relationships of MK-677 and other GHS have been characterized with regard to their effects on growth hormone secretion and IGF-I, but little knowledge exists regarding dose–response effects on body composition and other outcome measures. In a recent, preliminary series of reports of 12-month data from a multicenter study that used a different orally active GHS in older persons at risk for mild functional decline (19, 20), dose-responsive increases in IGF-I and changes in body composition were accompanied by small but significant improvements in some measures of physical function. These findings suggest that evaluating growth hormone axis manipulation may have more benefit for older persons who are at increased risk for frailty. Moreover, because ghrelin and its mimetics also act by nongrowth hormone mechanisms, such as by affecting appetite and caloric balance and the thymus and proinflammatory cytokine pathways (14), it seems prudent to investigate the effects of a GHS on multiple target tissues in addition to muscle, fat, and bone, such as the heart, brain, and immune system.Clearly, many questions about the potential utility and safety of an oral GHS in older persons remain unanswered. What might be the optimal intervention paradigm, for what clinical outcomes, and in what populations? Would long-term administration of MK-677 or other secretagogues improve physical and psychological functions and quality of life; have different effects according to age or racial or genetic predisposition; overstimulate the pituitary gland or central nervous system, with increased risk for pituitary neoplasms or neurobehavioral dysfunction; increase cancer frequency in older individuals, who are already at greater risk for malignant diseases; or supplant the less physiologic and more costly use of recombinant growth hormone or injectable GHRH or its analogues? At present, the clinical use of growth hormone axis manipulation in aged persons should be restricted to carefully controlled clinical studies and is not ready for prime time. However, Nass and colleagues' findings raise many questions that we need to address.Marc R. Blackman, MDVeterans Affairs Medical CenterWashington, DC 20422

Change in body composition, specifically loss of lean and gain in fat mass in older adults is a major pathway leading to the onset of functional decline. Energy expenditure during daily activity may help preserve body weight and composition among older adults. PURPOSE: To determine the association of activity-related energy expenditure and change in body weight and composition among older adults. METHODS: Total energy expenditure (TEE) was assessed over two weeks using doubly-labeled water in 302 community dwelling older adults (aged 70 to 82 years). Resting metabolic rate (RMR) was measured using indirect calorimetry and the thermic effect of meals was estimated at 10% of TEE. Activity energy expenditure (AEE) was calculated as: [TEE(0.9)-RMR] and categorized into gender specific equal thirds (tertiles). Total body mass, lean mass and fat mass were assessed by dual-energy x-ray absorptiometry annually over an average of 4.8 years. RESULTS: At baseline, individuals in the highest tertile of AEE were heavier (79.6 ± 16.5 kg) than those in the lowest tertile (72.8 ± 15.3 kg), but not the middle tertile (76.6 ± 14.4 kg). Consequently, higher levels of AEE were also associated with greater lean (r = 0.13, p = 0.02) and fat mass (r = 0.12, p = 0.03). In longitudinal analyses, person-specific paths of the change in body weight estimated from a random-effects model demonstrated a significant decline in body weight (−0.38 kg/yr, p<0.001) that was consistent across all AEE tertiles (tertile 1: −0.42 ± 0.62; tertile 2: −0.29 ± 0.60; tertile 3: −0.42 ± 0.70 kg/yr). Similarly, lean mass declined by 0.28 kg per year (p<0.001) regardless of AEE levels (tertile 1: −0.28 ± 0.31; tertile 2: −0.27 ± 0.26; tertile 3: −0.31 ± 0.31 kg/yr). Total fat mass remained stable over the follow-up (β = −0.035 kg/yr, p = 0.43) and AEE levels did not affect this trajectory (p>0.20). Results were similar when values were adjusted for baseline and longitudinal changes in total body weight. CONCLUSIONS: These data suggest that although AEE has a concurrent association with body weight and composition in late life, higher levels of AEE does not appear to impact the trajectory of change. Supported by N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106 and in part by the Intramural Research Program of the NIH, National Institute on Aging.

Body weight and composition change after treatment for breast cancer are important considerations when investigating factors affecting risk of disease-free survival. Concurrent loss of lean body mass (LBM) and increase in body fat is common after treatment for breast cancer and are related to the development of metabolic disease. Shorter observational studies have reported significant associations between body composition changes, inflammation, cardiac death and increased risk of metabolic syndrome. Thus, studies that aim to increase the understanding of how body composition change affects outcomes in this population are required. Numerous studies have investigated the mechanisms and quantity of body fat change, however, quantity and causes of LBM loss after treatment are not fully understood.Exercise interventions have been shown to improve body composition (LBM and body fat%), waist girth, aerobic fitness and other risk factors for metabolic syndrome without reducing body weight. Nutrition interventions have been shown to reduce body weight and body fat% that is accompanied with an improvement in metabolic health. However, the reduction in weight includes potentially detrimental reductions in LBM and significantly increased risk of sarcopenia. The combination of nutrition plus exercise seems to maintain LBM and elicit concurrent body fat and/or body weight reductions. Long chain omega-3 fatty acids (LCn-3) have been associated with improved cardiometabolic health, have a theoretical yet inconsistent effect on adiposity, are associated with decreased inflammation, and more recently have been shown to improve the response of LBM to an anabolic stimulus. Thus, they present as a relevant clinical option for this population, yet no evidence currently exists after treatment for breast cancer. Therefore, this PhD research had two aims: the primary aim was to examine the independent and combined effects of an exercise and nutrition program and LCn-3 supplementation on LBM change, QOL and chronic inflammation soon after completion of treatment for breast cancer. This was done by conducting a 6-month 3-arm randomised controlled trial that compared three conditions: 1) LCn3 supplementation only (N-3); 2) LCn-3 supplementation plus a 12-week group exercise and nutrition lifestyle program (Ex+N-3); and, 3) the lifestyle program plus placebo - olive oil (Ex+OO). The secondary aim was to explore baseline cross-sectional associations between body composition (in particular LBM) and LCn-3 intake, treatment, demographical and lifestyle factors after completion of treatment for breast cancer. For the scope of this PhD thesis, the investigation targeted women who had completed treatment of breast cancer within the last 12 months, and were considered ‘disease free’ at entry to the trial. The thesis is presented as both unpublished work, and a series of published and submitted manuscripts. Due to slower than expected recruitment, 49 participants were included in the trial, and were generally representative of women who have been diagnosed with breast cancer in Australia. In the six month randomised controlled trial, all three groups experienced maintenance of LBM, with no significant differences between groups after 24 weeks. Compared to women who consumed LCn-3 supplements or participated in the lifestyle program separately, those exposed to both interventions were more likely to experience a greater amount of body weight and waist and hip girth reduction. Quality of life (QOL) improved for all groups, while C-reactive protein (CRP) levels did not change throughout the intervention. Secondary analyses indicated that LCn-3 supplementation was associated with improved physical function and maintenance of grip strength independent of exercise and nutrition. Limitations of the intervention were lower than expected recruitment rate, and the effectiveness of the resistance training program may have been reduced as a result of the use of elastic resistance equipment. In terms of the secondary aim (cross-section at baseline), after adjusting for weight and age, the major determinants of LBM after treatment were higher levels of aerobic fitness and the ability to perform a greater number of push ups. Erythrocyte levels of LCn-3, energy and protein intake, CRP and treatment related variables were not associated with body composition after treatment for breast cancer. This thesis provides new insight into the synergy of LCn-3 and an exercise and nutrition lifestyle program in a population of women who have been treated for breast cancer. Combining LCn-3 supplementation with best practice nutrition and exercise advice is a consideration for clinicians aiming to prevent and improve adverse body composition change after treatment. Longer-term research investigating the preventive effect of LCn-3 and exercise on development of metabolic syndrome and breast cancer related morbidity and mortality should be undertaken. Finally, our novel findings indicate that muscle function is strongly associated with weight adjusted LBM after treatment, and its use as a measure of health warrants further investigation in determining the overall health of breast cancer survivors.

Although cross-sectional and longitudinal studies have shown age-related changes in body composition and fat distribution, they may be related to body weight changes. The aim of this study was to evaluate yearly age-related changes in body composition and fat distribution, over a two-year period, in 101 women and 60 men (age range: 68 to 78 years at baseline). Body composition was evaluated by dual energy X-ray absorptiometry (DXA), and fat distribution by waist and hip circumferences and waist-to-hip circumference ratio. Baseline free testosterone, IGF-1 and serum albumin were evaluated in all subjects, as well as physical activity. Clinical evaluation was performed at baseline and yearly in order to exclude subjects with any condition inducing pathological changes in body composition or fat distribution. Subjects with a weight change > 5% of their baseline body weight during the study period, were excluded. Significant increases occurred in Body Mass Index (BMI) (1.18% in women, 1.13% in men), waist (1.75% in women, 1.39% in men), and hip circumference (1.06% in women, 1.31% in men), whereas height decreased significantly in both men (0.42%) and women (0.55%). Significant increases in total body fat (1.31%) and percent body fat (1.27%) were observed in women but not in men. Lean body mass did not change significantly throughout the study in either sex. Significant losses in leg muscle mass and appendicular skeletal muscle mass (ASM), calculated as the sum of arm and leg fat-free soft tissue, were observed in men (respectively 3.56 and 2.77%) and women (respectively 2.41 and 1.59%). A significant decrease in ASM adjusted by stature (ASM/height2), a proposed proxy for sarcopenia, was found in men only (1.97%). The rates of loss in leg muscle mass and appendicular muscle mass were significantly higher in men than in women, even after adjusting for free testosterone, IGF-1, physical activity and serum albumin. These data demonstrate significant changes in body composition and fat distribution in independently living, weight-stable elderly men and women. These changes are dependent on sex and independent of physical activity, hormones or serum albumin.