Fran E. Kaiser

Longitudinal changes in testosterone, luteinizing hormone, and follicle-stimulating hormone in healthy older men

Cross-sectional studies have demonstrated a decline in testosterone and free and bioavailable testosterone with age. This occurs in a majority of older persons without an increase in luteinizing hormone (LH), suggesting that a component of the testosterone decrease is due to secondary hypogonadism. To determine whether these findings could be duplicated in a longitudinal study, we measured testosterone, LH, follicle-stimulating hormone (FSH), and sex hormone-binding globulin (SHBG) levels in 77 men participating in the New Mexico Aging Process Study who had sera available in 1980 or 1981 and two or more serial samples in 1982, 1984, 1989, and/or 1994. Thirty-nine subjects had samples available from both 1980 and 1994. The age at entry into the study ranged from 61 to 87 years. Testosterone levels decreased over the 15 years of the study. In persons who were alive for the duration of the study, testosterone levels were significantly lower 5 years before termination of the study (P < .05). Testosterone levels did not differ at entry into the study among those who died and those who were alive at the end of the study period. Eight of 77 subjects (10%) had LH levels above the normal range at some time during the study. In contrast, 43% of subjects had elevated FSH levels. Both LH and FSH increased significantly with age. SHBG levels were measured in 1980 and 1994 and increased significantly with age (P < .0001). LH and FSH were highly correlated with one another, but neither correlated with testosterone. This study demonstrated a longitudinal decline in testosterone and an increase in LH and FSH in older men. The average rate of decrement in testosterone concentration was 110 ng/dL every decade.

Effects of Testosterone Replacement Therapy in Old Hypogonadal Males: A Preliminary Study

To examine the effects of testosterone administration to older hypogonadal males (bioavailable testosterone less than 70 ng/dL).

Impotence and Aging: Clinical and Hormonal Factors

A cross‐sectional study of 216 impotent men aged 40 to 79 years (mean age 60.9 years) was conducted to determine if there are age‐related changes in clinical and hormonal parameters in an impotent population. There was a slight increase in the degree of sexual dysfunction with age, with complete erectile failure occurring in a larger percent of the 60‐ and 70‐year‐olds than in the younger patients (41% vs 27% for the 40 year olds, P < .05). No patient above the age of 70 years reported any full erections, even of short duration. In contrast, reported levels of libido did not vary significantly with age. Abnormal penile Doppler studies diagnostic of vasculogenic impotence were found in 17.8% of the patients tested, and an additional 17.8% were found to have evidence suggestive of a vascular etiology. These abnormal vascular findings were associated with an extremely high prevalence of clinically apparent atherosclerosis in this population. In 22.9% of the subjects, an abnormal vascular response was found only on exercise, ie, a “pelvic steal”, which only occurred above the age of 50 years. There was a marked age‐related alteration in the concentration of testosterone CD and bioavailable testosterone (BT), but no statistically significant change in the levels of gonadotropins with age. An increase in the prevalence of eugonadotropic hypogonadism with age was found, which suggested an increasing prevalence of hypothalamic pituitary dysfunction in this patient group. For both vascular and hormonal changes (such as low T and BT), the greatest changes appear to occur after the age of 50.

The Effect of Recombinant Human Growth Hormone on Malnourished Older Individuals

Malnutrition in the elderly is often unrecognized and untreated. Reduced secretion of growth hormone (GH) has been suggested as a cause of decreased muscle and bone mass with aging. This pilot study characterized the nutritional response of elderly malnourished subjects to recombinant human GH (rhGH). Subjects were included if they were over 60 years of age, if weight was more than 20% below average body weight (ABW), and if serum albumin concentration was less than 3.8 g/dL. Subjects were divided into two groups: one received 100 Hg/kg rhGH (Protropin®, Genentech) intramuscularly (IM) daily for 21 days; the other received a daily control injection of normal saline (Controls ‐ C) (0.1 mL/kg IM) for the same period of time.

Age-related decrease of plasma testosterone in SAMP8 mice: Replacement improves age-related impairment of learning and memory

Corticosterone increases with aging but pregnenolone, dehydroepiandrosterone, and testosterone decrease. The marked decrease in hormones that occurs with aging may contribute to the age-related deficit in learning and memory. Administration of these hormones after training was found to improve long-term memory processing in normal young mice. SAMP8 (P8) mice show an age-related loss of learning and memory for a variety of tasks whereas age-matched control mice of the closely related SAMR1 (R1) strain do not. In this study, we found an age-related decrease in serum testosterone levels of 71% between P8 mice 4 and 12 months of age, but only a 26% decrease between R1 mice of the same ages. The difference between the P8 mice was significant (p < 0.01) and the difference between the R1 mice was not. The decrease in testosterone in 12-month-old P8 mice was not accompanied by gross morphological change in the testes. A SC testosterone implant, sufficient to increase plasma testosterone levels to 414 +/- 25 ng/dl, alleviated impaired learning and memory of a foot shock avoidance task in P8 mice. Castration of 4-month-old P8 mice did not produce a deterioration in learning and memory, indicating that low levels of testosterone per se are not responsible for the impairment seen in 12-month-old P8 mice. This suggests that impaired cognitive functioning of the older P8 mice was due to an interaction of aging and reduced testosterone levels.

Relationship of penile brachial pressure index to myocardial infarction and cerebrovascular accidents in older men

Vascular disease is a major cause of impotence in patients over the age of 40. In a prospective study of 130 impotent patients followed for 24 to 36 months, patients with a penile brachial pressure index (PBPI) of 0.65 or less had a significantly greater risk of a myocardial infarction or a cerebrovascular accident than patients with higher PBPIs. It is concluded that impotence in association with a low PBPI should be considered an indicator of a future major vascular event.

Effect of ovarian steroids on footshock avoidance learning and retention in female mice

Mice were trained to avoid footshock in a T-maze, with retention tested one week later. Adult male CD-1 mice made their first avoidance during acquisition after fewer trials than random cycling females and with less variability. Female mice in diestrus, when plasma levels of progesterone are low, learned to avoid footshock faster than females in estrus. Ovariectomized (OVX) mice learned in fewer trials than intact random cycling mice. Similar differences, though of a smaller magnitude, were found on the retention tests (i.e. males had better retention than females, mice in diestrus showed better retention 8 days later when in the same part of the estrous cycle than those in estrus, and OVX mice had better retention than cycling females). OVX mice with estrogen implants learned faster than those with progesterone implants or progesterone plus estrogen implants. Hormonal status did not affect sensitivity to acoustic or footshock stimuli as measured by a startle reflex, nor did it affect activity. Pretraining administration of amphetamine, picrotoxin and strychnine attenuated the impairing effect of progesterone on acquisition. The possibility that progesterone may impair learning and to some extent, retention by facilitating the GABAergic activity and thereby reducing arousal level is discussed.

Body composition and age in african-american and caucasian women: Relationship to plasma leptin levels

Leptin is a recently isolated peptide hormone released from adipocytes that has been postulated to play a role in appetite regulation and energy metabolism. Aging affects both food intake and body composition. Body composition is also affected by ethnicity. We have evaluated the relationships between serum leptin levels, age, body composition (by dual-energy x-ray absorptiometry), and hormonal parameters in a cross-sectional study of 94 women, 53 African-American (AAF) and 41 Caucasian (CF). Our hypotheses were as follows: (1) changes in body composition would be related to age in a sinusoidal pattern, (2) changes in serum leptin would parallel changes in body fat, (3) serum leptin levels would be influenced by body fat distribution, and (4) serum leptin would be related to serum concentrations of sex hormones. Serum leptin paralleled changes in body fat and body mass index (BMI) with age. In the entire group, serum leptin correlated closely with measures of body fat, including BMI and total fat mass, and there was no difference in leptin levels between the two ethnic groups. In simple regression analysis, serum leptin was related to both serum estradiol and testosterone. The relationship between serum leptin and trunk fat was linear in both groups, but significantly different in AAF and CF (P = .014). Serum leptin was associated with the trunk to lower-extremity fat ratio in CF (r = .67, P = .001) but not in AAF. Body fat was increased with advancing age until about 65 years and then declined. Measures of lean body mass declined linearly with age in the entire group, as well as both subgroups. In the entire group, total lean body mass and lean body mass corrected for BMI (lean body mass/BMI) were inversely related to age. In subjects aged less than 60 years AAF were stronger (P < .05) and had both a larger BMI and fat mass (P < .05) than CF. However, the patterns of age-related changes in fat body mass, lean body mass, and BMI were similar in both groups. In the entire group, multiple regression analysis indicated that the age, free thyroxine index (FTI), and leptin concentration were predictors of the body composition and distribution of trunk to lower-body fat. These observations indicate that there is a sinusoidal relationship between body fat and age, with a decline in body fat in extreme old age in both AAF and CF, and that serum leptin concentrations are more closely related to body fat and BMI than to age or ethnicity.

Diabetes mellitus in elderly patients: Is it different?

From the Geriatric Research, Education and Clinical Center, Sepulveda Veterans Administration Medical Center, Sepulveda, California, and the Department of Medicine, University of California, Los Angeles, California. Dr. Kaiser is a John A. Hartford Faculty Development Award Fellow in Geriatric Medicine. Requests for reprints should be addressed to Dr. John E. Morley, Geriatric Research, Veterans Administration Medical Center, 16111 Plummer Street, Sepulveda, California 91343. Manuscript submitted February 2, 1987, and accepted March 3, 1987. Diabetes mellitus in elderly patients is exceedingly common, with a prevalence in the United States of 6.9 percent in men older than 65 years and 8.9 percent in women older than 65 [I]. Among persons older than 80, 16 to 20 percent have diabetes mellitus [2]. The National Nursing Home Survey estimated that 14.5 percent of nursing home residents have diabetes mellitus [3]. In the United Kingdom, two thirds of all diabetic patients who are hospitalized are older than 65 years [4]. Diabetes mellitus is often missed in the elderly, as demonstrated by a screening program in a Canadian old people’s home, where 32 percent of the residents were reclassified as diabetic over a three-year period [5]. Furthermore, diabetic residents of nursing homes have a higher rate of hospitalization for diabetic complications compared with ambulatory diabetic patients older than 65 [6]. Thus, diabetes mellitus represents one of the major chronic disorders of the growing elderly population. Despite these impressive numbers, little attention has been paid to the special needs of elderly diabetic patients [7].

Impotence in diabetic men

Studies relating to pathogenetic mechanisms resulting in impotence in diabetic subjects have been reviewed. Erectile dysfunction was reported to occur in 50 to 75 percent of diabetic patients and the prevalence appeared to increase with age. Contributions of vascular, endocrine, and neurologic system alterations result in this disturbing condition, but a detailed analysis of all the parameters was not found in any individual study. In our review of 301 veterans presenting to a sexual dysfunction clinic, the clinical and hormonal alterations in the diabetic patients closely resemble those seen in nondiabetic impotent subjects. Atherosclerotic vascular changes play an important predisposing role in the development of impotence. A difference exists between the prevalences of associated medical conditions in diabetic patients taking insulin, compared with those receiving oral agents or receiving dietary management. The high prevalence of impotence in diabetic patients seems to be due to the high prevalence of its vascular complications. Considering the availability of useful therapeutic approaches, it is mandatory to evaluate all diabetic men for the presence of impotence.