Total cholesterol and high density lipoprotein cholesterol as important predictors of erectile dysfunction.

Although erectile dysfunction is frequently seen in patients with manifestations of arteriosclerotic disease, the independent contribution of serum cholesterol in predicting erectile dysfunction is unclear. The aim of this study was to examine the relation between serum cholesterol and erectile dysfunction. Medical histories, physical examinations, and blood tests were obtained at Cooper Clinic, Dallas, Texas, from 3,250 men aged 26-83 years (mean, 51 years) without erectile dysfunction at their first visit, who had one more clinic visit, all between 1987 and 1991. These men were followed 6-48 months after the first clinic visit (mean, 22 months). Erectile dysfunction was reported in 71 men (2.2%) during follow-up. Every mmol/liter of increase in total cholesterol was associated with 1.32 times the risk of erectile dysfunction (95% confidence interval 1.04-1.68), while every mmol/liter of increase in high density lipoprotein cholesterol was associated with 0.38 times the risk (95% confidence interval 0.18-0.80). Men with a high density lipoprotein cholesterol measurement over 1.55 mmol/liter (60 mg/dl) had 0.30 times the risk (95% confidence interval 0.09-1.03) as did men with less than 0.78 mmol/liter (30 mg/dl). Men with total cholesterol over 6.21 mmol/liter (240 mg/dl) had 1.83 times the risk (95% confidence interval 1.00-3.37) as did men with less than 4.65 mmol/liter (180 mg/dl). Those differences remained essentially unchanged after adjustment for other potential confounders. The authors conclude that a high level of total cholesterol and a low level of high density lipoprotein cholesterol are important risk factors for erectile dysfunction.

Case report: abnormal thyroid function tests in a patient and two normal volunteers treated with salsalate.

There are only three prior reports of abnormal thyroid function tests in patients who have received salsalate, the salicylate ester of salicylic acid. The authors report an elderly clinically euthyroid man who had thyroid function tests suggestive of central hypothyroidism while taking salsalate but whose thyroid tests returned to normal after the drug was discontinued. They also studied thyroid function tests, including free thyroxine (FT4) and reverse (T3), in two normal volunteers who took salsalate 750 mg twice daily for 1 week. In the normal subjects, total T4 and FT4 began to fall within 24 hours after the first dose of salsalate, and remained suppressed for at least 24 hours after the drug was discontinued. This rapidity of effect by salsalate is previously undescribed. There was also a fall in FT4, probably due to the use of diluted serum in the equilibrium dialysis FT4 assay. Because FT4 measurement using diluted serum or equilibrium dialysis may cause falsely low FT4 measurements, the authors believe ultrafiltration may be the only reliable method of measuring FT4 in these patients.

Immobilization hypercalcemia in an adult patient with pancreatitis and sepsis: case report.

We describe an adult patient who developed persistent hypercalcemia while bedridden for more than three months with pancreatitis and sepsis. On the basis of hypercalciuria, suppressed serum intact PTH, suppressed serum 1,25-dihydroxy vitamin D3 and no clinical evidence of malignancy, the diagnosis of immobilization hypercalcemia was established His hypercalcemia improved during treatment with saline, calcitonin and/or etidronate. With active mobilization and weight-bearing exercises, serum calcium finally normalized. We discuss clinical and laboratory features as well as current modalities of treatment of this rare form of hypercalcemia in adults.

Serum cholesterol profiles during treatment of obese outpatients with a very low calorie diet. Effect of initial cholesterol levels.

We studied relative changes of serum cholesterol in obese patients during and after weight loss to determine if they depend on initial cholesterol levels as classified by the National Cholesterol Education Program. Three groups of obese free-living outpatients with desirable (normal) (less than 5.17 mmol/l, n = 26), borderline-high (5.17-6.18 mmol/l, n = 29), and high (greater than 6.21 mmol/l, n = 32) initial total cholesterol completed a 26-week program employing a very low calorie diet. The program involved 12 weeks of supplemented fasting, followed by 6 weeks of refeeding and then 7 weeks consumption of step 1 diet that maintained the new reduced weight. The groups were similar in initial clinical characteristics and they also lost comparable percentages of initial weights. Relative reduction in total cholesterol throughout the study was significantly larger in both borderline-high and high cholesterol groups compared to normal. In patients of borderline-high and high cholesterol groups favourable and significant reduction of total cholesterol, LDL cholesterol, total cholesterol/HDL cholesterol, and LDL cholesterol/HDL cholesterol ratios were maintained at the end of the study. The percent decrease in total serum cholesterol at the end of the study positively correlated with the percent of weight loss in patients of the high cholesterol group. We conclude that obese hypercholesterolemic patients have favorable changes in cholesterol profile following weight loss, and that relative reduction of cholesterol levels depend on initial levels. However, specific roles of weight loss, change in diet and/or increased physical activity in observed changes in lipid profiles cannot be determined by this study.

Hypercalcemia of immobilization in an adult patient with peripheral neuropathy.

A 48-year-old man developed a marked and persistent hypercalcemia 3 months after admission for paraplegia resulting from severe peripheral neuropathy most likely of alcoholic etiology. Serum ionized calcium was elevated, and parathyroid hormone levels were low normal by the two separate radioimmunoassays. Urinary calcium excretion was markedly elevated, and serum 1,25-dihydroxyvitamin D level was decreased. An extensive clinical evaluation for possible occult malignancy, myeloma, and sarcoidosis as a cause of hypercalcemia produced no positive findings. Treatment with calcitonin caused prompt normalization of serum calcium, and its discontinuation resulted in recurrence of hypercalcemia. With improvement of neuropathy, the patient started active physical therapy. We gradually discontinued calcitonin, and the patient's serum calcium remained normal during the following 11 months. We discuss difficulties in both clinical and laboratory diagnosis of hypercalcemia of immobilization in the adult patient because no specific laboratory test is available.

Interleukin-1 inhibits Leydig cell steroidogenesis in primary culture.

Inflammation and infection induce an acute phase response. The response is characterized by fever and production of interleukin-1 (IL-1). In the present study we evaluated the effects of interleukin-1 on Leydig cell function in primary culture. hCG-stimulated testosterone formation was markedly reduced by IL-1, with an ED50 of 1 U/ml. Basal testosterone production was slightly enhanced in the presence of low concentrations of IL-1, while high concentrations of IL-1 inhibited testosterone formation. Significant inhibition of hCG-stimulated testosterone formation was noted as early as 8 h after the addition of IL-1. IL-1 also inhibited hCG-stimulated cAMP formation, as well as 8-bromo-cAMP- and forskolin-stimulated testosterone synthesis. Furthermore, LH binding to Leydig cells was reduced by human IL-1. The inhibitory effects of IL-1 were reversed only partially by the addition of a cyclooxygenase inhibitor, indomethacin (0.1 mM), even though prostaglandin E2 formation was completely blocked. This indicates that the observed effects of IL-1 are not completely mediated by increased PGE2 formation. The present study suggests that IL-1 is a potent modulator of Leydig cell steroidogenesis. Decreased testosterone formation may modulate the immune response and contribute to the catabolic changes occurring during infection.

Hormone kinetics after intramuscular testosterone cypionate.

There have not been reports analyzing in detail the reproductive hormone changes in hypogonadal men after usual therapeutic injections of testosterone cypionate (TC). In 11 hypogonadal men 200 mg intramuscular TC caused a threefold rise in serum T (peak values, days 2 to 5), a 33% increase in % free T (%FT) (days 2 to 7), and a 4.5-fold rise of absolute FT (peak on days 2 to 3), a 66% increase in % nonsex hormone-binding globulin-bound T (%non-SHBG-T) (peak days 2 to 7), a sixfold increase in absolute non-SHBG-T (peak days 4 to 5), and a threefold rise of estradiol (days 2 to 7). Many of the men achieved androgen concentrations (T, FT, and non-SHBG-T) above the respective normal concentrations between days 2 and 7; then steroid values declined to basal levels by days 13 to 14. Non-SHBG-T showed the largest-fold absolute increase and on day 4 to day 5 averaged three times the mean in normal men. Five men achieved non-SHBG-T values several times the upper limit of our total normal range. Luteinizing hormone became suppressed in men receiving their first intramuscular TC injection and remained suppressed in men receiving chronic TC. Thus, in hypogonadal men, biweekly injections of 200 mg TC result in wide variations in circulating androgen levels, from high to elevated shortly after intramuscular TC declining to basal by days 13 to 14.

Group treatment of secondary erectile dysfunction.

The effects of three group treatment formats on 20 men with secondary erectile dysfunction and their partners were contrasted. After a comprehensive medical and psychological screening, each couple was assigned to one of three treatment groups (Communication Technique Training, Sexual Technique Training, Combination Treatment) or to one of two control groups (Attention-Placebo, No-Treatment). Couples in the three treatment groups and the attention-placebo group participated in their respective formats in twice-weekly sessions for a total of 20 hours. The no-treatment control group received sex education and treatment after a 5-week waiting list period. All three treatment groups fostered substantial gains so that between-format differences were not statistically significant. Subject variables which predicted success/experience ratio gains included age of the male partner, perceived level of relationship adjustment, and the male partner's success/experience ratio prior to treatment. Eighty-one percent of the treated men reached the criterion of 80% or greater success/experience ratio (successful penetration and subsequent ejaculation) at the 6-month follow-up. Good nocturnal tumescence prior to treatment was correlated with a better treatment outcome than poor tumescence.

Decreased bioavailable testosterone in aging normal and impotent men.

Tissue available (bioavailable) testosterone (T) includes circulating free T (FT) and albumin-bound T. A reasonable assessment of bioavailable T can be made by using 50% ammonium sulfate to precipitate sex hormone-binding globulin (SHBG)-bound T. The supernatant non-SHBG-bound T (non-SHBG-T) correlates well with physiological androgen activity. To assess bioavailable T in normal aging men, we analyzed serum samples from seven healthy aged men (65-83 yr old) and compared the results to samples from 13 young men (22-39 yr old). Mean serum T, FT, and LH concentrations were not significantly different in the 2 groups. However, the mean absolute non-SHBG-T level was significantly lower (P less than 0.005) in the older group. In a separate population of 20 impotent but otherwise healthy men (5 27-37 yr old, 10 48-64 yr old, and 5 66-69 yr old), the mean absolute non-SHBG-T concentration was lower in middle-aged (P less than .01) and elderly men (P less than 0.001) than in young men. The absolute FT was lower only in the elderly group (P less than 0.05), while mean LH and T levels were similar in all 3 age groups. These data suggest that serum concentrations of tissue available T are decreased in aged men and that non-SHBG-T measurement is a more sensitive indicator of this decrease than are serum T or serum FT measurements. These changes appear to begin by middle age.

Chronic testosterone cypionate therapy in men with secondary impotence.

There have not been studies assessing the effects of chronic testosterone cypionate (TC) therapy on circulating levels of testosterone (T), estradiol (E2), free T, bioavailable T (BAT), luteinizing hormone (LH), and sexual function in impotent men with low T levels. This study was a double-blind crossover using 200 mg of TC or placebo given intramuscularly every 14 days for six injections and the other medication given for six doses. Blood was drawn before each injection. Mean concentrations of T, E2, free T, and BAT were the same on TC or on placebo, but serum LH was significantly suppressed during intramuscular TC. With TC statistically significant improvements in libido and in potency were noted. Five of the men were able to have vaginal sex while taking TC. TC injections every 14 days do not appear to maintain increased T concentrations for 2 full weeks, and other dosage/injection schedules are being evaluated, but there were improvements in libido and potency.

Fertility in aging men.

A wide variety of disorders, medications, physical factors, and trauma can alter testicular function and reproductive function in men as they age. There are no precise age limits for 'aging men', but most studies consider 50-80-yr-old subjects. Assuming we have healthy individuals, there are still changes that occur with aging. There is progressive testicular failure as evidenced by gradually increasing levels of both gonadotropins with aging. Although basal levels of male hormone remain reasonably normal in healthy older men, the ability of the Leydig cells to respond to acute stimulation with LH is reduced. There are changes in the penis, prostate, and seminal vesicle which occur with aging. Potency tends to be reduced with age. Sperm production per testis falls off with aging. The amount of capsular tissue increases in the testis with advancing years. There is very limited data about men in extreme old age (80 yr and older). Of older men who produce spermatozoa in their ejaculates, sperm motility, a manifestation of viability and fertilizing capacity, tends to be reduced. The ability of men to impregnate their wives gradually reduces from age 25 onward. Using the zona pellucida-free hamster egg, penetration by spermatozoa from aged healthy men appears to be as good as that from younger fathers. This test cannot guarantee equal fertility, but it is the best test available and correlated reasonably well with fertility. Thus, if an older man can get an erection, can ejaculate, and can produce an ejaculate with a reasonable number of motile sperm, the likelihood is that he is fertile.

Two distinct insulin-related molecules in the guinea pig: immunological and biochemical characterization of insulin-like immunoactivity from extrapancreatic tissues of the guinea pig.

In this study we extracted guinea pig brain and testis with; the extract was adsorbed to and eluted from cartridges (the Sep-Pak C18 procedure). We found this procedure superior for recovering crystalline insulin added to buffers or tissues, and for recovering endogenous insulin from plasma, but inferior for recovery of insulin from tissues. However, we did find 'rat/pork' type-insulin in guinea pig brain and testis (5-50 pg/g wet weight tissue). Our results with the Sep-Pak C18 procedures were reproduced by four other laboratories (who found 4-60 pg/g wet weight of tissue) and similar findings were also obtained by an independent investigator. Thus, we conclude that extrapancreatic tissues of guinea pigs have a second type of insulin-related material that is more typical of other mammalian insulins, but that the amount recovered is dependent upon the extraction procedure utilized.

The aging Leydig cell. VIII. Protein kinase activity.

The effects of aging on cyclic AMP (cAMP) dependent protein kinase activity of purified Leydig cells were evaluated. Purified Leydig cells from 20-day-, 40-day-, 60-day- and 30-month-old rats were incubated with or without hCG for 1 hour. At the end of incubation, tubes were centrifuged and supernatants were saved for cAMP and testosterone determinations, and the pellets were prepared for protein kinase assay. Basal cAMP levels of Leydig cells from 20-day- and 40-day-old rats were lower than those of 60-day- and 30-month-old rats. In response to hCG stimulation, Leydig cells of 40-day-old rats produced the highest amounts of cAMP, while 30-month-old had the lowest levels. Testosterone responses of 30-month-old rates were also significantly lower than those of 60-day-old mature rats. When cAMP-dependent protein kinase activities were measured, 30-month-old rats had the lowest total kinase activity. These results suggest that reduced protein kinase activity might contribute to the decreased testosterone synthesis of aged rats.

Stimulation of ornithine decarboxylase activity by luteinizing hormone in rat testicular interstitial cells in vitro is age dependent.

The developmental pattern of ornithine decarboxylase (ODC) responsiveness to luteinizing hormone (LH) in isolated rat testicular interstitial cells in vitro was examined and correlated with testosterone production by the same cells. LH caused a 60-100% stimulation of ODC activity in cells from 60-day-old rats but produced no response in cells from 30, 37, 41, 50 and 55-day-old animals. Interstitial cells from 25-day-old rats responded with a moderate (40%) but statistically significant enhancement of ODC activity to the highest LH dose (100.0 ng/ml) only. Testosterone production by control cells was low until day 41 (0.15-0.30 ng/10(6) cells per 4 h), and then markedly increased to adult levels (2.12 +/- 0.03 10(6) cells per 4 h). LH in all concentrations (0.1 - 100.0 ng/ml) employed caused a consistent 4 to 7-fold stimulation of testosterone production in interstitial cells at all ages studied. This study shows age-dependent stimulation by LH of ODC activity in rat testicular interstitial cells in vitro and no apparent correlation with testosterone production by the same cells.

Regulation of testicular ornithine decarboxylase in vitro. Effect of age, follicle-stimulating hormone, and luteinizing hormone.

We have examined hormonal regulation of ornithine decarboxylase (ODC) activity in decapsulated rat testis, isolated testicular interstitial cells, and purified Leydig cells under defined conditions in vitro. Both immature (15 to 26 days old) and adult (60 to 90 days old) rat testes were employed. Basal (fresh tissue) ODC activity varied widely among rats of the same age but was similar (less than 5% difference) in pairs of testes from the same animal. For this reason, pairs of testes were compared in subsequent in vitro studies. ODC activity of decapsulated testes of adult rats declined (to 25 to 30% of basal) during 4 hours of incubation in Medium 199 + 0.1% bovine serum albumin + 0.1 mM 3-isobutyl-1-methylxanthine at 34 C. The addition of FSH, LH, prolactin, prostaglandin E2, epidermal growth factor, insulin, or 10% fetal calf serum singly or in combination failed to prevent this decline in ODC activity. In contrast, ODC activity of decapsulated testes of immature rats remained stable (versus fresh tissue) during 4 hours of incubation. The addition of FSH (100 ng/ml) caused a small but statistically significant (P less than 0.005) stimulation of the enzyme activity, and 8-bromo cyclic AMP (0.5 mM) mimicked the effect of FSH. In isolated interstitial cells from adult rats, LH stimulated ODC activity in a dose- (10 pg-200 ng/ml) and time-dependent fashion. 8-Bromo cyclic AMP mimicked the effect of LH. Prolactin, FSH, estradiol, insulin, prostaglandin E2, and epidermal growth factor did not alter the enzyme activity. LH also stimulated ODC activity of purified Leydig cells. This study demonstrates for the first time direct in vitro stimulation of rodent testicular ODC activity by gonadotropins and reveals marked age-dependent differences in regulation of this enzyme in vitro.

Discordant regulation by luteinizing hormone of ornithine decarboxylase activity and testosterone production in isolated rat testicular cells in vitro.

Possible functional relationship between luteinizing hormone-stimulated ornithine decarboxylase and testosterone production was examined in rat testicular interstitial cells in vitro. Although luteinizing hormone enhanced both ornithine decarboxylase activity and testosterone production at a similar physiological dose range, we found dissociation in the two responses in terms of their temporal aspect and the way they were affected by an irreversible inhibitor of ornithine decarboxylase, alpha-difluoromethylornithine, and protein synthesis inhibitor cycloheximide. The results suggest that there appears to be no causal coupling between luteinizing hormone-stimulated enzyme activity and testicular steroidogenesis.