Isolated glans insufficiency due to venous leakage.

Lack of tumescence of the glans penis during normal penile erection may represent a handicap to sexual intercourse. The pharmacodynamic spongiosography for the evaluation of venous drainage of the corpus spongiosum is described, demonstrating a pathologic venous outflow. The patient was successfully treated by resection and ligature of the deep dorsal vein. This procedure is simple to perform and could constitute a therapy for this clinical pathologic entity.

Prostaglandin E1 in erectile dysfunction. Efficiency and incidence of priapism.

Prostaglandin E1 (PGE1) was used for diagnostic and therapeutic purposes in 149 men with erectile dysfunction over a period of 20 months (February 1987-October 1988). The intracavernous application of PGE1 in varying doses resulted in an erection sufficient for sexual intercourse in 79% of cases. In order to differentiate between vascular and non-vascular impotence, 5 micrograms PGE1 were found to be a sufficiently high and safe dose for the first intracavernous injection. Local discomfort, ranging from mild to severe pain after injection, was recorded in 40% of patients. A significant difference in severe side effects was found between arterial, venous and non-vasculogenic impotence, the highest incidence of local pain occurring in non-vasculogenic patients. The most striking result was the occurrence of 4 cases of priapism, all in the non-vascular group, 1 of these occurring after the injection of only 5 micrograms PGE1.

Dose-dependent effect and side-effect of prostaglandin E1 in erectile dysfunction.

1. Recent work has demonstrated artificial penile erection after intracavernous injection of prostaglandin E1 (PGE1). A possible dose-response relationship between PGE1 and its erectile action was examined in a double-blind, cross-over designed, placebo-controlled study. 2. Twenty patients aged (mean +/- s.d.) 45 +/- 10.5 years suffering from psychogenic erectile dysfunction were tested on four occasions. Subjects received four intracavernous injections of saline containing either no other substance, preservative, 5 micrograms or 10 micrograms PGE1. 3. Investigations revealed clear dose-dependency of PGE1 in the grade and duration of erection achieved as well as in the latency between injection and achievement of erection (P less than 0.001). Saline and preservative did not induce erection. 4. Some local pain of varying grades did occur in 11/20 patients after 5 micrograms PGE1 and in 14/20 patients after 10 micrograms PGE1 injected intracavernously. This side-effect was caused by PGE1 itself and also showed a clear dose-relation (P = 0.0035). 5. Prostaglandin E1 appears to be a promising substance for diagnostic and therapeutic purposes in erectile dysfunction. Despite the discomfort observed in some patients, PGE1 is very effective even in low doses. PGE1 10 micrograms is suggested as the appropriate initial diagnostic dose for intracavernous injection to differentiate between the normal and pathological cavernous-vascular system.

Efficiency and side effects of prostaglandin E1 in the treatment of erectile dysfunction.

The efficiency and side effects of a single dose of intracorporeally applied prostaglandin E1 (20 mcg.) in inducing penile erection were examined. In addition, the effect of this dose of prostaglandin E1 was compared to the effect of 7.5 mg. papaverine plus 0.25 mg. phentolamine in a double-blind, crossover designed study. We tested twice 12 men 52.9 +/- 7.6 years old (mean +/- standard deviation) with erectile dysfunction. On 1 occasion the subjects received 20 mcg. prostaglandin E1 and on the other they received 7.5 mg. papaverine and 0.25 mg. phentolamine. At this dosage prostaglandin E1 was most effective in inducing artificial penile erection (11 of 12 patients). However, 75 per cent of the subjects reported burning sensations during the entire period of erection and in 1 prostaglandin E1 treatment resulted in a sustained erection. At the doses used, prostaglandin E1 was more effective in inducing penile erection than papaverine plus phentolamine (11 versus 6 patients). Intracavernous injection of prostaglandin E1 is a potent tool for artificial penile erection and warrants precise examination for its potential clinical use.

Alterations in nocturnal serum melatonin levels in humans with growth and aging.

The available data on potential alterations in serum melatonin (MLT) levels during a human lifetime are fragmentary and inconsistent. We, therefore, measured day- and nighttime serum MLT concentrations in 367 subjects (210 males and 157 females), aged 3 days to 90 yr. Blood samples were collected between 0730 and 1000 h and between 2300 and 0100 h. Serum MLT levels were measured by RIA. The mean nighttime serum MLT concentration was low during the first 6 months of life, i.e. 27.3 +/- 5.4 (+/- SE) pg/mL (0.12 +/- 0.02 nmol/L). It then increased to a peak value at 1-3 yr of age [329.5 +/- 42.0 pg/mL; (1.43 +/- 0.18 nmol/L)], and it was considerably lower [62.5 +/- 9.0 pg/mL; (0.27 +/- 0.04 nmol/L)] in individuals aged 15-20 yr. During the following decades serum MLT declined moderately until old age (70-90 yr of age), i.e. 29.2 +/- 6.1 pg/mL (0.13 +/- 0.03 nmol/L). This biphasic MLT decline follows 2 exponential functions with different slopes (from age 1-20 yr: r = -0.56; P less than 0.001; y = 278.7 X e -0.09x; from age 20-90 yr: r = -0.44; P less than 0.001; y = 84.8 X e -0.017x). The decrease in nocturnal serum MLT in children and adolescents (1-20 yr) correlated with the increase in body weight (r = -0.54; P less than 0.001) and body surface area (r = -0.71; P less than 0.001). At a later age (20-90 yr) there was no correlation among these variables. Daytime serum MLT levels were low and no age-related alterations were found. This study revealed major age-related alterations in nocturnal serum MLT levels. The negative correlation between serum MLT and body weight in childhood and adolescence is evidence that expansion of body size is responsible for the huge MLT decrease during that period. The moderate decline at older ages must derive from other factors.

A pharmacological dose of melatonin increases PRL levels in males without altering those of GH, LH, FSH, TSH, testosterone or cortisol.

Since reports on the influence of melatonin (aMT) on the human endocrine system are scant and inconsistent, the effect of an acute, pharmacological dose of aMT on various hormone levels in healthy males was examined in 3 different experiments. Experiment I: 80 or 240 mg of crystalline aMT were administered per os to 8 volunteers. Before, during and after this treatment, serum levels of aMT, PRL, LH, FSH and testosterone were examined. Although aMT increased at least 1,500-fold over basal levels, only PRL was significantly and consistently elevated after aMT treatment, whereas serum levels of the other hormones were not altered. Experiment II: in 2 subjects, the pulsatile secretion pattern of LH was monitored for 6 h before and 6 h after aMT administration (240 mg p.o.). Neither the amplitude nor the frequency of LH pulses was influenced by the pineal hormone. Experiment III: in 14 volunteers, serum PRL, GH, TSH and cortisol concentrations were examined, once after oral administration of 240 mg aMT and once after placebo. Serum PRL levels were significantly higher after aMT than after placebo; GH showed a slight but not significant trend towards elevation after aMT, whereas other hormones were not altered. An acute pharmacological dose of aMT causes isolated elevation of serum PRL levels and may slightly increase GH. Hormones of the pituitary gonadal axis as well as TSH and cortisol are not altered by aMT.

Bioavailability of oral melatonin in humans.

We administered crystalline melatonin (80 mg) in gelatin capsules to 5 young male volunteers and measured serum and urinary melatonin levels at intervals. Changes in serum melatonin levels were best described by a biexponential equation with an absorption constant (ka) of 1.72 h-1 (half-life = 0.40 h) and an elimination constant (ke1) of 0.87 h-1 (half-life = 0.80 h). Peak serum melatonin levels, ranging from 350 to 10,000 times those occurring physiologically at nighttime, were observed 60-150 min after its administration, remaining stable for approximately 1.5 h. The fraction of ingested melatonin that was absorbed, estimated from the area under the curve describing serum melatonin concentrations as a function of time after melatonin administration (the concentration-time curve), varied by 25-fold among subjects. 3 additional volunteers received three melatonin-containing capsules (80 mg each) at 60-min intervals. This regimen extended the duration of elevated serum melatonin levels to 4-6 h. Melatonin excretion closely paralleled serum melatonin levels until 9 h after the hormone's administration, after which urinary levels tended to be higher than those predicted from serum levels. However, the area under the concentration-time curve for serum melatonin correlated well (r = 0.96) with the cumulative melatonin excretion during the initial 15 h after melatonin's administration, indicating that either approach can be used to estimate the absorption of orally administered melatonin.

Diminished prolactin response to thyrotropin and insulin in anorexia nervosa.

Although patients with anorexia nervosa (AN) have a variety of endocrine disturbances, it generally is believed that the PRL response to stimulation is not altered in this disorder. We measured basal serum PRL values and serum PRL values after stimulation either with TRH (200 micrograms/m2) or with insulin (4 IU/m2) in 27 women with AN and 9 normal women. Basal values in anorexic women and normal women did not differ significantly, whereas all stimulation variables (mean PRL stimulation values, maximum PRL values, sum of increments, and area under the stimulation curve) were significantly lower in AN patients than in normal women. Furthermore, after TRH stimulation most of these variables correlated positively with the percentage of ideal body wt of the patients, indicating that the diminished PRL response was wt dependent. This diminished PRL response in the patients may accompany starvation and low estradiol values. Both conditions per se are known for their association with diminished PRL responses. Hence, no hypothesis which posits hypothalamic dopamine excess as the basic disturbance in AN seems justified. Moreover, diminished PRL responses in AN are not consistent with an assumption of hypothalamic dopamine depletion in this disorder.

Fall in nocturnal serum melatonin during prepuberty and pubescence.

Morning (7:30 AM to 10:00 AM) and nighttime (11:00 PM to 1:00 AM) serum melatonin concentrations were measured in 89 children, adolescents, and young adults. Morning levels (generally 0-20 pg/ml) did not change with sexual maturation or with age. Nighttime levels decreased significantly both with sexual maturation and with age. Nighttime serum melatonin fell from 195 +/- 24 pg/ml (mean +/- SEM) in prepubertal children younger than 7 years of age, to 119 +/- 23 pg/ml in prepubertal children aged 7 years or older, to 49 +/- 4 pg/ml in young adults (puberty stage V). Similarly, nocturnal serum melatonin levels fell from 210 +/- 35 pg/ml in the youngest age group (ages 1-5) to 133 +/- 17 in children aged 5-11 years and to 46 +/- 4 in young adults. Nocturnal plasma concentrations of luteinising hormone measured at various stages of puberty tended to vary inversely with those of melatonin (r = -0.35). Past difficulties in demonstrating a relation between gonadal maturation and human pineal function may have reflected the use of insufficiently sensitive or specific melatonin assays, or serum sampling only during daytime, or the initiation of sample collection when subjects were already too old.