A long-term, prospective study of the physiologic and behavioral effects of hormone replacement in untreated hypogonadal men.

This study describes sexual activity, nocturnal penile erections, and mood states as a function of serum levels of androgens in previously untreated hypogonadal men before and during hormone replacement, selected infertile men (elevated serum follicle-stimulating hormone levels), and normal men. Nocturnal penile tumescence and rigidity were measured with a portable monitor, and sexual activity and mood were assessed by prospective, self-reported written forms. Nocturnal erections were absent or of very low amplitude and duration in the untreated hypogonadal men compared to the infertile and normal men. Nocturnal erections increased steadily during hormone replacement and were in the normal range within 6 to 12 months of treatment. In contrast, serum testosterone concentration rapidly reached the upper range of normal. During treatment, the hypogonadal men reported increases in several aspects of sexual activity, including sexual interest and the number of spontaneous erections. On mood inventories, the untreated hypogonadal men scored significantly higher in ratings of depression, anger, fatigue, and confusion than did infertile and normal men. During hormonal replacement therapy these scores decreased, although the hypogonadal men continued to score higher in "depression" than did infertile and normal men. In most instances, the men with infertility and the normal men were statistically indistinguishable in nocturnal penile tumescence and rigidity parameters, self-reported sexual activity, and mood state. These data support the hypothesis that androgen treatment increases nocturnal and spontaneous erections, and sexual interest, and has some capacity to improve mood.

Testosterone therapy is associated with reduced tactile sensitivity in human males.

Responses to vibrotactile stimuli were examined in men as a function of chronic exposure to either exogenous or endogenous androgens. Psychophysical techniques were used to evaluate thresholds to stimulus detection and perceived stimulus intensities in response to mild vibration applied to either the finger or the penis. Normal men were compared to the following groups: (a) untreated hypogonadal men, (b) androgen-replaced hypogonadal men, or (c) infertile men with androgen levels in the low normal range. Among the four groups, untreated hypogonadal men perceived vibrotactile stimuli as most intense and were slightly more sensitive to touch than were men with higher levels of androgen. Chronic treatment with testosterone enanthate was associated with a decline in the perceived intensity of vibrotactile stimuli in hypogonadal men. The lowest levels of sensitivity to tactile stimuli were observed in the infertile men.

Quantitative assessment of nocturnal penile tumescence and rigidity in normal men using a home monitor.

Current methods now permit the measurement of nocturnal penile tumescence and rigidity (NPTR) in men with erectile dysfunction. But the relationship of rigidity to tumescence and the changes in rigidity with age have not been defined in normal men. Accordingly, the authors assessed NPTR in 47 normal men using a portable, take-home monitor (Rigiscan). Penile tumescence time was found to decrease with advancing age (p less than 0.05), whereas the number of erectile episodes and penile rigidity did not significantly change with age for men in the third through sixth decades (p less than 0.05). Using area-under-the-curve as an integrated measure of amplitude and duration, significant correlations between tumescence and rigidity (p less than 0.001), and between tip and base measurements (p less than 0.001) were found. With these normative data, prospective studies should determine the sensitivity and specificity of various NPTR parameters in the diagnosis of erectile dysfunction.

Sperm motion characteristics in men with isolated hypogonadotropic hypogonadism treated with gonadotropin.

The authors compared curvilinear velocity (Vc) and linearity (L) of sperm from fertile oligospermic men with isolated hypogonadotropic hypogonadism (IHH) to Vc and L of sperm from fertile normal men in order to determine if sperm motion analysis is better than sperm density as an indicator of fertility potential. Nine fertile men with IHH treated with exogenous gonadotropins and 20 fertile normal men were studied. Sperm density was significantly lower in the men with IHH compared with normal men (15.5 +/- 4.8 x 10(6)/ml versus 92.4 +/- 9.7 x 10(6)/ml; mean +/- standard error of the mean [SEM]; P less than 0.01) as was percent motility (51.4 +/- 4.7 versus 73.4 +/- 3.1; P less than 0.01). While a small but significant difference in Vc was noted between the groups at the 40 micron/second cumulative distribution point (P less than 0.01), no difference in L was found between the two groups. When the men with IHH were subgrouped according to sperm density (greater than 20 x 10(6)/ml versus less than or equal to 20 x 10(6)/ml, no differences in Vc were found between the subsets, but for L sperm were somewhat less directional for the subgroup with a density less than or equal to 20 x 10(6)/ml (P = 0.05). Coanalysis using both Vc and L parameters indicated that sperm from IHH patients were distributed similarly to sperm from normal men. However, sperm motion characteristics in men with unexplained infertility were different from values measured in normal men and IHH patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Initial trial of slow-release testosterone microspheres in hypogonadal men.

The duration of hormone release from testosterone-loaded poly(DL-lactide-co-glycolide) microspheres was assessed in eight hypogonadal men. Eight weeks before receiving testosterone (T) microspheres, patients were withdrawn from their prior androgen therapy in order to minimize the contribution of that therapy to hormone levels measured following microsphere injection. Blood was obtained for hormone measurements immediately before and weekly for 14 weeks after the administration of the T microspheres. A biphasic release of hormone was observed; a significant increase in total T and free T concentration (compared to preinjection values) was observed during week 1 (P less than 0.01) and between weeks 6 and 11 after injection (P less than 0.05). A similar pattern was detected in estradiol and dihydrotestosterone concentrations, whereas T-binding globulin levels showed a small, reciprocal fall after the injection of microspheres (P = not significant [NS]). After receiving the T microspheres, seven of eight hypogonadal men reported the return of normal sexual function; the eight patient withdrew from the study after 5 weeks. It was concluded that T microspheres are a promising new method of androgen replacement therapy for hypogonadal men.

A low sperm concentration does not preclude fertility in men with isolated hypogonadotropic hypogonadism after gonadotropin therapy.

In order to define the minimal number of sperm needed for conception, we studied semen characteristics of men with isolated hypogonadotropic hypogonadism (IHH) who became sperm-positive during gonadotropin therapy. Twenty-two of 24 men (92%) proved fertile, initiating a total of 40 pregnancies. The mean (+/- standard error of the mean) sperm concentration at the time of conception was 16.7 +/- 4.0 X 10(6)/ml. However, 71% of pregnancies were conceived when the mean sperm concentration was less than 20 X 10(6)/ml; in 16%, the mean sperm concentration was less than 1 X 10(6)/ml. Mean total sperm count correlated highly with sperm concentration (r = 0.67, P less than 0.001). We conclude that men with IHH can initiate conception even when their sperm concentration is well below the conventional lower limit of 20 X 10(6)/ml.

Gonadotropin therapy in men with isolated hypogonadotropic hypogonadism: the response to human chorionic gonadotropin is predicted by initial testicular size.

This study was designed to determine whether exogenous hCG alone can complete spermiogenesis in men with isolated hypogonadotropic hypogonadism (IHH). hCG was administered to 22 men with IHH until maximal testicular growth was achieved. Their mean testicular volume increased from 5.5 +/- 1.1 (+/- SE) mL (pretreatment) to 10.8 +/- 1.6 mL (maximum) during treatment (P less than 10(-6)). The maximum mean testicular volume was highly positively correlated with initial volume (r = 0.84; P less than 10(-6)). All men attained normal serum testosterone levels, and 7 of 22 men achieved supraphysiological serum estradiol levels. During hCG treatment, 14 of the 22 men had sperm appear in their semen. Six of 11 men with complete gonadotropin deficiency, defined as an initial mean testicular volume less than 4 mL, became sperm positive during hCG treatment. In contrast, 9 of 11 men with partial gonadotropin deficiency (initial mean testicular volume of 4 mL or more) produced sperm during treatment (P less than 0.001). Sperm concentration was highly positively correlated with both pretreatment (r = 0.65; P less than 0.01) and final testicular volume (r = 0.73; P less than 0.0001). Of 13 men attempting to impregnate their partners, 7 were successful in initiating conception; a total of 8 pregnancies ensued. The sperm concentration at the time of conception was less than 10 million/mL in all but 1 man. Our study demonstrates that hCG, in the absence of exogenous FSH, can complete spermiogenesis in men with partial gonadotropin deficiency. The response to hCG in men with IHH is predicted by the initial testicular volume.

Leukemoid reaction associated with severe diabetic ketoacidosis.

A 30-year-old man had severe diabetic ketoacidosis and a leukemoid reaction, which promptly resolved after therapy with intravenous fluids and insulin. There was no evidence of an underlying malignancy or infection. Although a mild leukocytosis may accompany DKA, a leukemoid reaction has not been previously reported to occur with uncomplicated diabetic ketoacidosis.