Cardiovascular health in transgender people

This review examines the relationship between exogenous sex steroids and cardiovascular events and surrogate markers in trans (transgender) people. Data from trans populations is compared to data from postmenopausal women and hypogonadal men when appropriate. In an age-adjusted comparison with cisgender people, trans people appear to have an increased risk for myocardial infarction and death due to cardiovascular disease. It is uncertain whether hormone therapy in trans people affects their risk of stroke. In studies that followed trans people on hormone therapy, the rates of myocardial infarction and stroke were consistently higher in trans women than trans men. There is strong evidence that estrogen therapy for trans women increases their risk for venous thromboembolism over 5 fold. Extrapolating from studies of hormone therapy in postmenopausal women, transdermal estrogen likely carries a lower risk for venous thromboembolism than oral estrogen. Regarding red blood cells, testosterone therapy increases hemoglobin in trans men, and lowering testosterone in trans women has the opposite effect. Regarding blood pressure, the effects of hormone therapy on systolic blood pressure in trans women are inconsistent, with most studies showing an increase. In trans men, testosterone therapy consistently increases systolic blood pressure and may increase diastolic blood pressure. For lipids, hormone therapy may increase triglycerides in both trans women and men. In trans men, testosterone therapy also may increase LDL-cholesterol and decrease HDL-cholesterol.     

Clinical review: Controversies regarding transdermal androgen therapy in postmenopausal women

CONTEXT: Recently, the field of androgen therapy in postmenopausal women has received much attention and press. Although the ovary ceases to produce follicles and estrogen at menopause, it continues to produce androgens. Hence, many oophorectomized women complain of sexual dysfunction (despite adequate estrogenization). Previous studies of nontransdermal testosterone replacement have shown an improvement in libido and sexual frequency, although at the cost of supraphysiological testosterone levels. Transdermal testosterone patch (Intrinsa) was developed to deliver a physiological amount of testosterone. In 2004, the Food and Drug Administration voted not to approve Intrinsa until long-term safety data are available. EVIDENCE ACQUISITION: Recent trials of Intrinsa in postmenopausal women were included. A MEDLINE search was conducted for articles published over the last 40 yr based on the key words androgen therapy/replacement and postmenopausal women. Relevant placebo-controlled trials of nontransdermal androgen therapy in postmenopausal women were also reviewed. EVIDENCE SYNTHESIS: Early results from industry-funded trials show that transdermal testosterone therapy results in only moderate (although statistically significant) improvement in libido in surgically menopausal women (on estrogen). However, the published data are of short duration (24 wk). Hence, long-term safety in these women remains unclear. CONCLUSION: We recommend a short-term trial (not to exceed 24 wk) of transdermal testosterone therapy (once approved) in surgically menopausal (estrogenized) women with distressful sexual dysfunction. Until the patch gets approval, a short trial of oral methyltestosterone in deserving estrogenized women may be justified.     

Clinical Review: Sex steroids and the periosteum--reconsidering the roles of androgens and estrogens in periosteal expansion

CONTEXT: Traditionally, differences in periosteal bone formation between men and women have been assumed to reflect two diverging endocrine effects: stimulatory effects of androgens in men and inhibitory effects of estrogens in women. In line with this concept, it is tempting to speculate that men experience more periosteal bone expansion than women because they are exposed to more endogenous androgens and less estradiol. However, recent data challenge this traditional concept. EVIDENCE ACQUISITION: A PubMed search was conducted for relevant most recent findings in both humans and animals in the context of an intriguing observation of ongoing periosteal expansion after estrogen treatment in an aromatase-deficient boy. EVIDENCE SYNTHESIS: Human experiments of nature have provided evidence that androgens and estrogens are both required for the process of pubertal periosteal bone expansion typically associated with the male bone phenotype. Androgens alone appear insufficient to drive male periosteal bone formation. In both sexes, androgens may stimulate periosteal bone formation, but low levels of estrogen may increase the mechanical sensitivity of the periosteum. Higher concentrations of endogenous estrogen, however, inhibit periosteal bone apposition and/or its interaction with mechanical loading. This biphasic action of estrogen on the periosteum may result from a direct effect on its receptor, either alpha or beta, but may also depend on changes in serum IGF-I. CONCLUSIONS: Simple concepts of the roles of sex steroids in periosteal apposition have to be reconsidered in the context of these recent findings.     

Direct inhibition of Leydig cell function by estradiol.

Suppression of plasma testosterone levels from a mean of 760 ng/dl to a mean of 295 ng/dl could be induced in normal young adult men 24 h after a single injection of 2 mg aqueous 17 beta-estradiol. Maximum suppression to 123 ng/dl was noted 36 h after estradiol administration. Neither LH nor FSH levels were similarly affected. After administration of 5000 IU hCG to a similar group of subjects, daily blood samples were obtained for testosterone and estrogen. Maximum testosterone levels of 2060 ng/dl (basal, 784 ng/dl) were seen 96 h after hCG administration. Maximum estrogen levels of 13 pg/ml (basal 73 pg/ml) were seen 36 h after hCG administration. The testosterone response to hCG could be attenuated by preceding hCG administration with an injection of 17 beta-estradiol. These results can be explained by the concept of enzyme inhibition; estrogen acts directly on the Leydig cell to effect changes in the activities of certain enzymes important for testosterone synthesis. Whether endogenous estrogen production by the Leydig cell may be important in this postulated short loop feedback is as yet unclear.     

The association of sex hormone levels with poor mobility, low muscle strength and incidence of falls among older men and women

OBJECTIVE: The objective of this study was to examine whether low levels of oestradiol and testosterone are associated with impaired mobility, low muscle strength and the incidence of falls in a population-based sample of older men and women. DESIGN: Cross-sectional population-based study, based on data of the Longitudinal Ageing Study Amsterdam (LASA), including 623 men and 663 women, aged 65-88 years. MEASUREMENTS: Serum levels of oestradiol, testosterone, albumin and sex hormone-binding globulin (SHBG) were measured. Physical performance, functional limitations and muscle strength were assessed, and a follow-up on falls was performed prospectively within 3 years. RESULTS: After adjustment for age, level of education, alcohol use, physical activity, chronic disease and body mass index (BMI), men in the highest quartile of the oestradiol/SHBG ratio had significantly higher physical performance scores than men in the lowest quartile (beta = 0.103). Serum levels of total testosterone were positively associated with muscle strength (beta = 0.085). Calculated bioavailable testosterone levels were positively associated with physical performance and muscle strength (beta = 0.128 and 0.109 respectively). No associations of oestradiol levels with mobility were seen in women. Levels of oestradiol and testosterone were not associated with falls. CONCLUSIONS: It can be concluded that low levels of sex hormones were associated with impaired mobility and low muscle strength in men, but not in women. Levels of sex hormones were not associated with the incidence of falls neither in men, nor in women.     

Testosterone dose-dependently increases maximal voluntary strength and leg power,but does not affect fatigability or specific tension

Testosterone supplementation in men increases fat-free mass, but whether measures of muscle performance, such as maximal voluntary strength, power, fatigability, or specific tension, are improved has not been determined. Furthermore, the extent to which these measures of muscle performance are related to testosterone dose or circulating concentration is unknown. To examine the relationship between testosterone dose and muscle performance, 61 healthy, eugonadal young men (aged 18-35 yr) were randomized to 1 of 5 groups, each receiving a long-acting GnRH agonist to suppress endogenous testosterone production plus weekly injections of 25, 50, 125, 300, or 600 mg testosterone enanthate for 20 wk. These doses produced mean nadir testosterone concentrations of 253, 306, 542, 1345, and 2370 ng/dl, respectively. Maximal voluntary muscle strength and fatigability were determined by a seated leg press exercise. Leg power was measured using a validated leg power instrument. Specific tension was estimated by the ratio of one repetition maximum muscle strength to thigh muscle volume determined by magnetic resonance imaging. Testosterone administration was associated with a dose-dependent increase in leg press strength and leg power, but muscle fatigability did not change significantly during treatment. Changes in leg press strength were significantly correlated with total (r = 0.46; P = 0.0005) and free (r = 0.38; P = 0.006) testosterone as was leg power (total testosterone: r = 0.38; P = 0.007; free testosterone: r = 0.35; P = 0.015), but not muscle fatigability. Serum IGF-I concentrations were not significantly correlated with leg strength, power, or fatigability. Specific tension did not change significantly at any dose. We conclude that the effects of testosterone on muscle performance are specific; it increases maximal voluntary strength and leg power, but does not affect fatigability or specific tension. The changes in leg strength and power are dependent on testosterone dose and circulating testosterone concentrations and exhibit a log-linear relationship with serum total and free testosterone. Failure to observe a significant testosterone dose relationship with fatigability suggests that testosterone does not affect this component of muscle performance and that different components of muscle performance are regulated by different mechanisms.     

Prevalence of sarcopenia and predictors of skeletal muscle mass in healthy,older men and women

BACKGROUND: Sarcopenia refers to the loss of skeletal muscle mass with age. The objective of this study was to determine the prevalence of sarcopenia in a population of older, community-dwelling research volunteers. METHODS: Appendicular skeletal muscle mass was measured by dual x-ray absorptiometry in 195 women aged 64 to 93 years and 142 men aged 64 to 92 years. We defined sarcopenia as appendicular skeletal muscle mass/height(2) (square meters) less than 2 standard deviations below the mean for young, healthy reference populations. We used two different reference populations and compared prevalence in our population to that reported in previous studies. Body mass index (BMI) was calculated and physical activity and performance were measured with the Physical Activity Scale for the Elderly, the Short Physical Performance Battery, and the Physical Performance Test. We measured health-related quality of life by using the SF-36 general health survey. Serum estrone, estradiol, sex hormone-binding globulin, parathyroid hormone, and 25-hydroxy vitamin D were measured in all participants and bioavailable testosterone was measured only in men. Leg press strength and leg press power were determined in men. RESULTS: The prevalence of sarcopenia in our cohort was 22.6% in women and 26.8% in men. A subgroup analysis of women and men 80 years or older revealed prevalence rates of 31.0% and 52.9%, respectively. In women, skeletal muscle mass correlated significantly with BMI and levels of serum estrone, estradiol, and 25-hydroxy vitamin D; in men, it correlated significantly with BMI, single leg stance time, leg press strength, leg press power, SF-36 general health score, Physical Performance Test total score, and bioavailable testosterone levels. With the use of linear regression analysis, BMI was the only predictor of appendicular skeletal muscle mass in women, accounting for 47.9% of the variance (p <.05). In men, BMI accounted for 50.1%, mean strength accounted for 10.3%, mean power accounted for 4.1%, and bioavailable testosterone accounted for 2.6% of the variance in appendicular skeletal muscle mass (p <.05). CONCLUSIONS: Sarcopenia is common in adults over the age of 65 years and increases with age. BMI is a strong predictor of skeletal muscle mass in women and men. Strength, power, and bioavailable testosterone are further contributors in men. These data suggest that interventions to target nutrition, strength training, and testosterone replacement therapy should be further investigated for their role in preventing muscle loss with age.     

Prevalence of sarcopenia and predictors of skeletal muscle mass in nonobese women who are long-term users of estrogen-replacement therapy

BACKGROUND: Sarcopenia refers to the loss of skeletal muscle mass with age. We have found a prevalence of sarcopenia of 22.6% in older postmenopausal women not receiving estrogen. The objective of this study was to determine the prevalence of sarcopenia in a population of older, nonobese, community-dwelling women who had been long-term users of estrogen replacement therapy (ERT). METHODS: We measured appendicular skeletal muscle mass by dual x-ray absorptiometry (DXA) in 189 women aged 59 to 78 years old who had been using ERT for at least 2 years (mean +/- SD duration, 12.7 +/- 8.2 years). We defined sarcopenia as an adjusted appendicular skeletal muscle mass (ASM) (mass divided by height squared) more than 2 SDs below the mean for a young healthy reference population. Health and menopause history were obtained. Body mass index (BMI) was calculated, and physical activity and performance were measured using the Physical Activity Scale in the Elderly, the chair rise time, the 6-minute walk, and measures of lower extremity strength and power. Serum estrone, estradiol, testosterone, and sex hormone binding globulin were measured. RESULTS: The prevalence of sarcopenia in nonobese, community-dwelling women who were long-term ERT users was 23.8%. Skeletal muscle mass correlated significantly with BMI, age at the time of starting ERT, hand grip strength, lower extremity strength and power, and testosterone level, but not with estradiol level. In linear regression analysis, BMI, leg press strength, and testosterone level contributed to adjusted ASM, accounting for 48.7% of the variance (p <.001). CONCLUSIONS: Sarcopenia is as common in nonobese women who are long-term ERT users as in community-dwelling women not using ERT, suggesting that ERT does not protect against the muscle loss of aging. BMI, strength, and testosterone level contributed to appendicular skeletal mass in women. These data suggest that interventions to target nutrition, strength training, and testosterone replacement should be further investigated for their role in preventing muscle loss with age.     

Hormonal effects on blood vessels

The incidence of cardiovascular disease (CVD) is lower in younger women than in men of the same age, but it increases after menopause, implicating the atheroprotective action of endogenous estrogen. Although observational studies have suggested the efficacy of estrogen therapy in postmenopausal women, placebo-controlled, randomized trials, such as the Women's Health Initiative, have not confirmed effects of estrogen therapy on CVD. Conversely, basic, experimental research has progressed and provided mechanistic insight into estrogen's action on blood vessels. By contrast, the vascular effects of androgens remain poorly understood and have been controversial for a long time. In recent years, an increasing body of evidence has suggested that androgens may exert protective effects against the development of atherosclerosis, at least in elderly men. Epidemiological studies have shown that the incidence of and mortality due to CVD were increased in elderly men with low testosterone levels, although the efficacy of androgen therapy remains unknown. Furthermore, recent experimental studies have demonstrated the direct action of androgens on the vasculature. In this review, we illustrate the effects of sex steroids on the cardiovascular system, focusing on the action of testosterone on the blood vessels.     

Testosterone supplementation for aging-associated sarcopenia

Aging of humans is associated with a loss of muscle mass and function, and an increase in fat mass. Epidemiologic studies have demonstrated a correlation between bioavailable testosterone concentrations and fat-free mass and muscle strength. Testosterone replacement in older men with low testosterone levels increases fat-free mass and muscle strength, and decreases fat mass. However, we do not know whether testosterone replacement improves physical function and other health-related outcomes, or reduces the risk of disability, falls, or fractures in older men with low testosterone levels. The long-term risks and benefits of testosterone supplementation in older men are not known.     

Androgen supplementation in older women: too much hype,not enough data

Androgen supplementation in women has received enormous attention in the scientific and lay communities. That it enhances some aspects of cognitive function, sexual function, muscle mass, strength, and sense of well-being is not in question. What is not known is whether physiological testosterone replacement can improve health-related outcome in older women without its virilizing side effects. Although it is assumed that the testosterone dose-response relationship is different in women than in men and that clinically relevant outcomes on the above-mentioned effects can be achieved at lower testosterone doses, these assumptions have not been tested rigorously. Androgen deficiency has no clear-cut definition. Clinical features may include impaired sexual function, low energy, depression, and a total testosterone level of less than 15 ng/dL, the lower end of the normal range. Measurement of free testosterone is ideal, because it provides a better estimate of the biologically relevant fraction. It is not widely used in clinical practice, because some methods of measuring free testosterone assay are hampered by methodological difficulties. In marked contrast to the abrupt decline in estrogen and progesterone production at menopause, serum testosterone is lower in older women than in menstruating women, with the decline becoming apparent a decade before menopause. This article reviews testosterone's effects on sexual function, cognitive function, muscle mass, body composition, and immune function in postmenopausal women.     

The endocrinology of gonadal involution: menopause and andropause

Most aging individuals die from atherosclerosis, cancer or dementia. In the oldest old also loss of muscle strength resulting in frailty becomes the limiting factor for an individual's chances of living an independent life until death. Two hormonal changes mark the aging process in man. In women an acute drop in estrogen production by the ovaries around the age of 50 initiates a symptom complex called menopause. In men a more subtle drop of testosterone bioactivity from 40 yrs onwards might be accompanied by more difficulty to recognize symptomatology (andropause). Hormone replacement strategies in elderly women and males with estrogens or androgens, respectively, has some clear advantages, but is currently controversial, because of the occurrence of adverse effects.     

Oral testosterone supplementation increases muscle and decreases fat mass in healthy elderly males with low-normal gonadal status

BACKGROUND: Loss of muscle mass (sarcopenia) leads to frailty in older men. The decline in testosterone over the life span may contribute to this muscle loss. We studied the ability of oral testosterone to prevent muscle loss in older men over a 12-month period. METHODS: A standard dose (80 mg twice daily) of testosterone undecanoate or placebo was administered for 1 year to 76 healthy men aged 60 years or older. All men had a free testosterone index of 0.3-0.5, which represents a value below the normal lower limit for young men (19-30 years), but remains within the overall normal male range. Measurements of body composition, muscle strength, hormones, and safety parameters were obtained at 0, 6, and 12 months. RESULTS: Lean body mass increased (p =.0001) and fat mass decreased (p =.02) in the testosterone as compared with the placebo-treated group. There were no significant effects on muscle strength. There was a significant increase in hematocrit (0.02%) in the testosterone-treated group (p =.03). Plasma triglycerides, total cholesterol, and low-density lipoprotein cholesterol levels were similar in both groups, but there was a decrease in high-density lipoprotein cholesterol (-0.1 mmol/L) at 12 months in the testosterone group as compared to the placebo group (p = 0.026). There were no differences in prostate-specific antigen or systolic or diastolic blood pressure between the groups. CONCLUSION: Oral testosterone administration to older relatively hypogonadal men results in an increase in muscle mass and a decrease in body fat.     

Osteoporosis: gender differences and similarities.

Although osteoporosis has traditionally been considered a disease of women, men also incur substantial bone loss with aging, and elderly men have age-specific hip fracture incidence rates and vertebral fracture prevalence rates that are at least half those in women. Early postmenopausal bone loss (which results in the syndrome of type I osteoporosis) is due to the direct skeletal consequences of estrogen deficiency, manifested by an increase in bone resorption without an adequate increase in bone formation. Recent evidence indicates that even late postmenopausal bone loss (type II or 'smile' osteoporosis) in women may be due to estrogen deficiency. In particular, the late consequences of estrogen deficiency in elderly women result in abnormalities in calcium homeostasis and increases in parathyroid hormone secretion, leading to increased bone resorption and bone loss. The etiology of bone loss in aging men has remained relatively unclear. Recent evidence from a male deficient in estrogen receptor-alpha and in two males with aromatase deficiency indicate that estrogen may play a significant role in bone metabolism in men. Moreover, several large epidemiologic studies have found that bone mineral density correlates better with serum estrogen than testosterone in aging men. Thus estrogen deficiency may lead to bone loss in men.     

Inability to demonstrate an ultrashort loop feedback mechanism for luteinizing hormone in humans

hCG has biological properties similar to those of LH, but can be measured separately from LH by current radioimmunometric assays. To investigate the possible existence of an autoregulatory mechanism for LH in humans, we compared the basal LH concentrations and the LH response to a GnRH stimulus with and without prior administration of hCG. On two separate occasions, at least 1 week apart, six normal (eugonadal) males and six normal postmenopausal females were given, in random order, either 10,000 IU hCG or saline followed by iv injection of a 200-micrograms bolus of GnRH. Blood samples were then taken 30, 60, 90, 120, 180, 240, and 300 min after GnRH. Serum concentrations of LH and hCG were measured at each time by two monoclonal antibody sandwich assays developed in our laboratory. After exogenous hCG, serum hCG concentrations rose rapidly to 200-500 IU/L (15,000-35,000 pg/mL) in both the men and women, remaining at this high level throughout the study. In the men, sex steroid concentrations did not change in response to the hCG during the 9 study hours. Compared to saline-treated controls, hCG had no significant effect in either men or postmenopausal women on the basal LH concentration or the response to a GnRH bolus, as determined by peak response and area under the LH/time curve between 0-300 min after GnRH. We conclude that an ultrashort loop feedback mechanism for LH on its own secretion does not exist in humans, as assessed by the present protocol.     

Changes in muscle mass, muscle strength, and power but not physical function are related to testosterone dose in healthy older men

OBJECTIVES: To examine the effect of graded doses of testosterone on physical function and muscle performance in healthy, older men. DESIGN: Randomized, double‐blind, placebo‐controlled clinical trial. SETTING: General clinical research center. PARTICIPANTS: Community‐dwelling healthy men aged 60 to 75 (N=44). INTERVENTION: Monthly treatment with a gonadotropin‐releasing hormone agonist plus 25, 50, 125, or 300 mg/wk of intramuscular injections of testosterone enanthate for 20 weeks. MEASUREMENTS: Skeletal muscle mass (SMM) was estimated using dual‐energy X‐ray absorptiometry. Leg press strength was measured by one repetition maximum, leg power by Nottingham Leg Rig, and muscle fatigability by repetitions to failure in the leg press exercise. Stair climbing, 6‐meter and 400‐meter walking speed, and a timed‐up‐and‐go (TUG) test were used to assess physical function. RESULTS: Significant testosterone dose‐ and concentration‐dependent increases were observed in SMM (P<.001) and maximal strength (P=.001) but not muscle fatigability. Leg power also increased dose‐dependently (P=.048). In contrast, changes in self‐selected normal and fast walking speed over 6 or 400 meters, stair climbing power, and time for the TUG were not significantly related to testosterone dose, testosterone concentrations, or changes in muscle strength or power, or SMM. CONCLUSION: Testosterone administration was associated with dose‐dependent increases in SMM, leg strength, and power but did not improve muscle fatigability or physical function. The observation that physical function scores did not improve linearly with strength suggests that these high‐functioning older men were already in the asymptotic region of the curve describing the relationship between physical function and strength.     

Hormonal profile of Leydig cell tumors with gynecomastia

The hormonal profile of estrogen-secreting Leydig cell tumors was studied in four patients. Plasma testosterone (T) and estradiol (E2) levels varied from day-to-day whereas the T/E2 ratios were decreased (22:85, normal 170 to 440). hCG administration induced a higher estrogen response in the patients than in normal men. The finding in the spermatic venous blood of the tumor-bearing testis of a particular biochemical profile, including a low T/E2 ratio (12:27), associated with high progesterone/17-hydroxyprogesterone ratios (0.13:0.26) and high 17-hydroxyprogesterone-androstenedione ratios (26:44), allowed localization of a small testicular tumor when no testicular abnormality was found clinically. Also, the E2 level was moderately elevated in the spermatic vein of one patient compared with normal men. Spermatic venous blood also was obtained after hCG administration in two patients. Increased estrogen and reduced T responses were found in the tumoral testis in comparison with the contralateral testis. In conclusion, the hormone content of spermatic venous effluent from testes containing an interstitial cell tumor is abnormal in several respects and such abnormalities allow detection of the tumor when it is not recognizable clinically.     

Hormone replacement therapy and fractures in older adults

Estrogen deficiency in women is associated with accelerated bone loss, and estrogen replacement therapy has been proven to be effective in preventing osteoporosis and fractures in postmenopausal women. The introduction of selective estrogen receptor modulators that have an estrogen-like effect on the skeleton but have a different pattern of effects on other tissues may have an important role in the management of osteoporosis in women in the near future. In men, androgen deficiency has been shown to be associated with osteoporosis. Although androgen replacement in hypogonadal men may decrease bone resorption and increase bone mass, long-term placebo-controlled trials are needed to better define the benefits and risks of such therapy before it can be recommended. Sex hormone deficiency is linked to the development of osteoporosis in both women and men. In women, hormonal replacement by estrogen or the newly developed selective estrogen receptor modulators may prevent the development of osteoporosis and its related fractures. In men, there is early evidence that testosterone replacement therapy may enhance bone mass in hypogonadal men.     

Characteristics of muscle fiber type are predictive of skeletal muscle mass and strength in elderly men

OBJECTIVES: To investigate the relationship between skeletal muscle fiber type‐specific characteristics, circulating hormone concentrations, and skeletal muscle mass and strength in older men. DESIGN: Cross‐sectional analyses. SETTING: University research center. PARTICIPANTS: Forty‐one community dwelling elderly men (≥65). MEASUREMENTS: Leg strength (1‐repetition maximum, 1RM) and whole‐body and limb muscle mass were determined, and muscle fiber type composition, cross‐sectional area (CSA), myonuclear content, and satellite cell (SC) content were assessed in skeletal muscle biopsy samples. In addition, blood samples were collected to determine serum testosterone, sex hormone–binding globulin, insulinlike growth factor (IGF)‐1, and IGF binding protein‐3 concentrations. RESULTS: Muscle mass correlated with muscle strength (0.41 ≤ correlation coefficient (r)≤0.72; P<.01). Muscle fiber CSA, myonuclear content, and SC content were significantly lower in type II than in type I muscle fibers. Myonuclear and SC content were positively correlated with muscle fiber CSA. Furthermore, greater muscle fiber CSA (type I and II) was associated with greater thigh muscle area and muscle strength (0.30 ≤ r ≤ 0.45; P<.05). Testosterone concentration was positively correlated with muscle mass and muscle fiber CSA. Regression analysis showed that SC content, myonuclear content, and testosterone concentration are predictive of muscle fiber CSA. Furthermore, muscle mass and type II muscle fiber CSA are predictive of muscle strength. CONCLUSION: Skeletal muscle mass and strength in elderly men are positively correlated with muscle fiber type–specific CSA, myonuclear content, and SC content. These findings support the assumption that a decline in SC content plays an important role in age‐related decline in muscle mass and strength.