Normal Plasma Testosterone Research Articles

Endocrinological effects of single daily ketoconazole administration in male beagle dogs.

Some endocrinological effects of single daily oral administration of 150 mg ketoconazole for 15 days were investigated in 4 male beagle dogs. Plasma testosterone fell markedly within 3-4 h and then progressively returned to control concentrations by 10 h after drug administration. On the other hand, plasma 17 alpha-hydroxyprogesterone, progesterone and 17 alpha, 20 alpha-dihydroxyprogesterone increased within 3-10 h before returning to basal values after 24 h. Plasma LH did not rise significantly though some high individual levels were noted. Plasma cortisol and oestradiol-17 alpha levels were not significantly modified by the treatment. These results confirm that a high therapeutic dose of ketoconazole, given orally once a day, transiently inhibits in vivo the 17-20 lyase enzyme of the testis, without modifying basal cortisol and oestradiol-17 beta plasma concentrations and that enzymatic inhibition still occurs after daily treatment for up to 2 weeks but remains transient and parallels the resorption profile of the drug so that normal plasma testosterone levels are observed from 10 to 24 h after drug intake. However, permanent inhibition of androgen biosynthesis might be obtained by the administration of high doses of ketoconazole given several times a day.

Hirsutism and Weight Gain in a Woman with Normal Plasma Testosterone

Hirsutism and Weight Gain in a Woman with Normal Plasma Testosterone

Reproductive system of the obese male zucker rat. Reproductive capacity, artificial insemination and plasma testosterone levels.

The sexual behavior of obese and lean male Zucker rats placed with receptive lean female rats was evaluated longitudinally. At 3 to 4 months of age and at 5 to 8 months of age, obese males intromitted less consistently than lean males and fewer obese males ejaculated during the observation periods. By 9 to 12 months of age, none of the obese males were sexually active during the observation period. More obese males ejaculated if left overnight with receptive females. However, at all ages studied, the pregnancy rate for females left overnight with obese males was lower than that for females left overnight with lean males. Sperm from obese and lean male rats was used to artificially inseminate proestrous lean female rats. The pregnancy rate was similar for females artificially inseminated with sperm from obese versus lean males. Even sperm from obese males which previously had failed to naturally inseminate lean females was successfully used to artificially inseminate lean females. Furthermore, the number of implanted embryos was similar for females inseminated, naturally or artificially, with sperm from obese versus lean males. These findings support the suggestion that sperm from obese males is normal in fertilizing capability, and suggest that inadequate sexual behavior is the primary factor limiting their reproductive capacity. Plasma testosterone levels in obese and lean rats were measured by radioimmunoassay. Plasma levels were lower in obese males 8 to 12 months of age compared to lean males of comparable age, and compared to obese males 3 to 6 months of age. However, reduced plasma testosterone levels cannot account for the reproductive inadequacy of obese male Zucker rats since sexual behavior was inadequate and the natural insemination rate was reduced at 3 to 4 months of age despite normal plasma testosterone levels. Furthermore, testosterone levels in obese males are adequate to maintain normal spermatogenesis. The reproductive defect in obese male Zucker rats appears to be behavioral rather than functional.

Plasma testosterone levels in patients with cluster headache.

SYNOPSISPlasma testosterone levels were determined radio‐immunologically in 57 men, including 23 patients suffering from cluster headache where the tests were carried out during the exacerbation of the disease but between the fits, 10 patients with trigeminal nerve neuralgia, 10 with radicular pain and 14 blood donors. Only in blood donors the normal plasma testosterone level was found and in the remaining tested groups this level was lowered in a statistically significant degree, the lowest values were observed in patients suffering from radicular pain. It is suggested that during cluster headache the level of testosterone is lowered but this is associated with repetitive pain seizures and not with the processes involving hypothalamus.

The hemicastrated rat: definition of a model for the study of the regulation of testicular steroidogenesis.

A comprehensive study has been made of the hemicastrated rat from 2 to 12 months of age in order to define what might represent an ideal model in which to study testicular regulation. Although there was no compensatory hypertrophy in the remaining testis of the mature hemicastrated rat, levels of plasma testosterone fell significantly within 4 h after surgery in all age groups older than 3 months, and were restored to normal levels almost immediately, usually within 8 h. There were no significant changes in LH and prolactin, and the significant rise in FSH was sufficiently delayed (2 days or more) to suggest that none of these three hormones was implicated in any obvious way in the compensatory restoration of plasma testosterone levels. Although a single testis was capable of maintaining normal plasma testosterone concentrations, its response to human chorionic gonadotrophin at 24 h after hemicastration was significantly less than that of intact animals, suggesting that the single testis was functioning at near-maximal capacity. The hormonal responses to repetitive blood sampling and to sham-surgery simulated the response to hemicastration remarkably. However, these responses were never statistically significant in within-group analysis, and therefore did not obscure the significant fall of plasma testosterone levels in response to hemicastration. The basic mechanism by which plasma testosterone is restored in the hemicastrated rat is still unknown, but the options have been narrowed.

Adult height and fertility in men with congenital virilizing adrenal hyperplasia.

The effects of congenital adrenal hyperplasia on adult height and fertility were studied in 30 afflicted men. The patients' heights ranged from 150.0 to 178.6 cm (mean +/- 1 S.D. of 164.0 +/- 7.6), which is significantly lower than both the mean adult height for American men and that of the patients' parents (P less than 0.005). There was no correlation between adult height and the age at which therapy was begun, possibly because the patients treated before one year of age had the salt-losing form of the syndrome. Therapeutic compliance may also have been involved. Apparently normal fertility, indicated by paternity and normal sperm counts, was found in 18 out of 20 patients evaluated. This group included five untreated patients who were found to be fertile and to have normal plasma testosterone and gonadotropin but elevated androstenedione levels.

Effects of an LH-RH analogue in male rats pretreated with oestradiol benzoate

Treatment of adult male rats with oestradiol benzoate (OB) for 21 days significantly decreased the body, testicular and accessory sex organ weights but increased anterior pituitary weight. OB treatment also significantly suppressed circulating FSH and LH levels as well as plasma and testicular concentrations of testosterone. The seminiferous tubules and interstitial cells were partly atrophied, and there was some effect on spermatogenesis, with step 14 to 19 spermatids being fewer than normal. Rats treated with OB for 21 days were then treated daily with LH-RH analogue ((D-Leu6, des-Gly-NH2(10))-LH-RH-ethylamide), to see if testicular function could be recovered. Circulating gonadotrophins were significantly elevated, testicular histology was normal and testicular and plasma testosterone concentrations and the accessory sex organ weights remained suppressed. These results suggest possible extra-pituitary effects of the LH-RH analogue, including a direct action on the testes and/or accessory sex organs.

Suppressive Effect of 1,2-Dibromo-3-Chloropropane on Human Spermatogenesis

Azoospermia was diagnosed in six factory workers who had been chronically exposed to 1,2-dibromo-3-chloropropane. Infertility was the presenting symptom in two patients and a decrease in libido or impotence characterized the others. Hormone studies revealed elevated plasma follicle-stimulating hormone levels and normal plasma luteinizing hormone and testosterone concentrations. Testicular biopsy showed selective atrophy of the germinal epithelium, intact Sertoli cells, and a normal appearance of a relatively increased number of Leydig cells.

Suppression and Recovery of Sperm Production in Men Treated with Testosterone Enanthate for One Year. A Study of a Possible Reversible Male Contraceptive

A group of 21 subjects was recruited among men requesting surgical sterilization to conduct a study on the efficacy of testosterone enanthate (TE) as a possible male contraceptive. Sixteen men completed the study. Administration of 200 mg TE (im) every 10 to 12 days maintained azoospermia. Less frequent injections (every 2 or 3 weeks) resulted in break‐through of sperm production. The azoospermia was associated with normal plasma testosterone levels, suppressed circulating FSH and undetectable LH. No untoward clinical side effects were noted. In 11 of the 16 subjects observations on recovery of sperm production were made. In all cases resumption of sperm production was noted. In two cases pregnancy occurred (5 to 7 weeks and 11 to 13 weeks after discontinuation of treatment). Since in most subjects long‐term recovery data were not available, observations on the quantitative aspects of recovery and relationship to the time interval after cessation of treatment could not be made.

Plasma gonadotropins and gonadal steroids in children treated with cyclophosphamide

Twelve boys (4.7 to 15.4 years) and five girls (4.3 to 14.1 years) treated with cyclophosphamide, 50 to 100 mg/day for periods of two to 12 months were studied. Plasma follicle-stimulating hormone, luteinizing hormone, Δ 4 -androstenedione, testosterone, 17β-estradiol, 17-hydroxyprogesterone, and progesterone were determined by radioimmunoassay in four to six samples from each patient. At time of the study, cyclophosphamide had not been given for 1.0 to 5.3 years. Results were compared to age-matched healthy boys and girls. Four boys treated when prepubertal had a normal hormonal profile. Three out of seven boys treated during stage II of puberty had elevated FSH and LH levels, low Δ 4 -androstenedione levels, but normal plasma testosterone (0.9 to 2.7 years after therapy). Follow-up studies in two of these three boys (4.0 and 6.1 years, respectively, after therapy) disclosed azzospermia in one and severe oligospermia in the other; each had elevated plasma FSH concentrations. In the remaining four boys of this group with previously normal hormonal profiles, follow-up studies in three of them (4.0 to 7.9 years after cyclophosphamide therapy) disclosed normal sperm counts and plasma FSH in one boy and mild oligospermia with normal plasma concentration in two. No evidence of primary ovarian failure was detected in any of the girls. It is suggested that caution should be maintained not only in the total dose and duration of cyclophosphamide therapy, but also in the degree of pubertal development at time of initial therapy.

Effect Of Chronic Administration Of Testosterone Enanthate On Sperm Production And Plasma Testosterone, Follicle-Stimulating Hormone, And Luteinizing Hormone Levels: A Preliminary Evaluation Of A Possible Male Contraceptive

Sixteen healthy adult male volunteers were studied to determine whether it would be possible to maintain azoospermia with testosterone enanthate (TE) administered at a dose level which would not result in plasma testosterone elevation above the pretreatment range. The study was divided into two phases: induction and maintenance. During the induction phase TE (200 mg/ml) was administered twice weekly for the first 2 weeks, weekly for 2 weeks, and once every other week for 1 month. This schedule of injections resulted in suppression of gonadotropins to undetectable levels and sperm production to azoospermia or less than 100,000 sperm/ml. During the first 3 to 4 weeks, elevation of plasma testosterone levels up to 100% of base line were noted. During the maintenance phase three different schedules of injections were investigated. Administration of TE every 3 weeks resulted in a partial release of gonadotropin blockade and the reappearance of spermatozoa in the ejaculate. Plasma testosterone levels remained within the pretreatment range. Administration of TE every 2 weeks maintained sperm production below 3 million/ml and was associated with normal plasma testosterone levels. Administration ofTE every 10 to 12 days maintained complete suppression of luteinizing hormone (LH) and azoospermia or severe (<100,000/ml) oligospermia. Testosterone levels remained within the normal range. Complete suppression of LH in the presence of detectable follicle-stimulating hormone levels was essential to induce azoospermia. The data reported here suggest that investigation of testosterone as a potential male contraceptive is a promising approach to the development of a relatively simple and probably safe male contraceptive.

Correlation between blood level of androgens and sexual behavior in male leopard frogs, Rana pipiens

Blood levels of androgens in male leopard frogs ( Rana pipiens) were measured by radioimmunoassay during a period of successive injections of whole pituitary tissue which eventually evoked mating behavior, including calling and clasping. In June, one injection induced a surge from a lower level of plasma testosterone, and this higher level was sustained. The mating calling and clasping increased in frequency and intnsity while the pituitary injections were continued. Blood levels of dihydrotestosterone were similar in pattern to those of testosterone. In a second experiment, in October, normal plasma testosterone levels were higher than those associated with experimentally stimulated sex behavior in June, but little or no spontaneous sexual behavior was observed. During a period of pituitary treatment, however, sexual behavior appeared and increased progressively during treatment. Thus, although increased blood levels of androgens, as well as evoked male sex behavior both are consequences of pituitary treatment of frogs, a particular blood androgen level alone is not responsible for initiation of the behavior. Since earlier work with castrates of the same species has sshown that testosterone treatment will not evoke male behavior, but implants of testes from pituitary-stimulated frogs will do so, the present data are consistent with a hypothetical second testicular factor which, acting with testosterone, regulates male sex behavior.

Postpuberal castration and prostatic carcinoma

The occurrence of prostatic carcinoma after postpuberal castration is rather unique since only one other case has been reported. However, there was no lack of androgens in the patient in this report, because the testicular ablation was compensated by nodular hyperplasia of the adrenal cortex maintaining a normal plasma testosterone.

Plasma testosterone free index: A better indicator of plasma androgen activity?

Testosterone, quantitatively the most important androgen in the circulation, must enter cells to exert an androgenic effect. It is accepted that it is that fraction of the hormone not bound to the specific, binding, beta-globulin which is available for entry into the cells. By equilibrium dialysis we obtained an in vitro measurement of the unbound fraction. The product of this fraction and the total testosterone level gave us a testosterone free index (TFI). In normal men and women, our ranges were 24.6 to 93.6 and 0.8 to 3.8 ng/100 ml, respectively. Of 54 hirsute women, 24 had an elevated TFI; 4 of these had normal plasma testosterone levels. Thirteen men with hypogonadism had a decreased TFI. Nine of ten women and two men with hyperthyroidism had a normal TFI, although there was an elevated plasma testosterone level in most instances. The calculated TFI, which reflects both the extent of binding and the total testosterone level, may therefore be a better indicator of circulating androgen activity.

Plasma LH and FSH Response to LRH in Boys with Compensatory Testicular Hypertrophy

The plasma LH, FSH and testosterone response to LRH was studied in 12 boys with compensatory testicular hypertrophy (CTH) and normal puberty and in a matched control group with normal testicular development. It was found, that the boys with CTH had normal basal plasma testosterone and LH concentrations; at the same time the basal plasma FSH level were significantly higher than in the control group. The response of plasma LH and FSH to LRH was markedly greater in the CTH group than it was in the control group. It is concluded, that the contralateral testicular hypertrophy which enables a normal pubertal process is the result of increased secretion of gonadotropins, mainly FSH.

Studies of the relation of plasma androgen levels to androgen action in women

Testosterone-estradiol-binding-globulin (TEBG) is a major determinant of androgen disposition and action. TEBG levels, but not free testosterone levels, correlate with the metabolic clearance rate (MCR) of testosterone in normal women. This suggests that the testosterone MCR reflects androgen removal by the liver, an organ which removes a large fraction of steroid on a single passage, rather than the concentration of unbound androgen. Consequently, testosterone production seems more closely related to androgen catabolism than to androgen action. In support of this concept, we have studied a hirsute woman in whom testosterone clearance and production were elevated in the presence of a normal free testosterone level; her hirsutism seems related to androgens other than testosterone. Although testosterone is of major importance, androgen action seems to result from the net effect of several free plasma 17β-hydroxysteroids, including particularly androstenediol and dihydrotestosterone. About 25% of women with moderate male-pattern hirsutism have normal total and free plasma testosterone levels. In most such cases total 17β-hydroxysteroids are also normal. However, an abnormally low fraction of all these 17β-hydroxysteroids is bound to TEBG. As a result, an increase in the plasma “total androgenicity index” is present in this group of patients. Such women do not necessarily evidence increased testosterone production. Obesity appears to be another important determinant of androgen disposition and action. The testosterone MCR correlates well with adiposity independently of the TEBG levels in normal women. In addition, hyperandrogenism is frequently present with minimal or no hirsutism in obese women. This finding suggests that obesity increases the apparent “threshold” at which hirsutism appears in response to androgen or that obesity is a result of slight hyperandrogenism.

The effect of oestrogen administration on plasma testosterone, FSH and LH levels in patients with Klinefelter's syndrome and normal men.

ABSTRACT In 6 eugonadal males and 6 patients with Klinefelter's syndrome the effect of increasing amounts of ethinyloestradiol (EE) (15, 30 and 150 μg daily for 7 days) on plasma levels of LH, FSH and testosterone was studied. Control levels of LH and FSH in the Klinefelter patients were significantly higher than in the normal males, whereas plasma testosterone levels were significantly lower. In 3 of the 6 Klinefelter patients plasma gonadotrophin levels were clearly elevated despite normal plasma testosterone concentrations. After EE administration a dose-dependent decrease of plasma FSH and testosterone levels was observed in both the control subjects and the Klinefelter patients, whereas the LH decrease was dose-dependent in the Klinefelter patients, but not however, in the eugonadal males. Despite significant testosterone suppression plasma LH and FSH levels in the Klinefelter patients remained supranormal when compared with the levels of the control subjects. Amounts of EE, roughly equivalent to the physiological oestrogen production (15 μg of EE daily) in men, decreased plasma LH and testosterone levels in the normal males, not however, in the Klinefelter patients. The suppression of plasma testosterone by EE in both the normal subjects and the Klinefelter patients could readily be overcome by exogenous gonadotrophin administration, favouring the concept that the EE induced testosterone decrease is predominantly gonadotrophin mediated. It is concluded that small amounts of oestrogens play a role in the pituitary-gonadal axis in normal males. Although higher doses are needed to modulate this axis in Klinefelter's syndrome, the hypothalamic-pituitary-gonadal feedback in this disorder is still operative, though at a higher setting.

Blood levels of gonadotropins and gonadal hormones in gynecomastia associated with chronic hemodialysis.

Five adult men who developed gynecomastia or tender breasts while undergoing chronic hemodialysis for chronic renal failure all had elevated serum luteinizing hormone (LH) and normal plasma testosterone (T). Four had elevated serum follicle-stimulating hormone (FSH) but only one had an elevated serum prolactin. In no case was plasma estradiol (E2) elevated. One year later, when the gynecomastia had largely disappeared, the level of LH was lower in 2 of 4 patients but remained slightly elevated in all four, while the level of FSH had fallen to normal in 3 of 4 patients. The cause of the gynecomastia is not clear but it is not due to elevated levels of E2 or prolactin or to an elevated ratio of E2 to T; it may be related to elevated FSH, LH, or both.

Plasma testosterone stimulation-suppression dynamics in hirsute women: Correlation with long-term therapy

Clinical response and changes in plasma testosterone were measured in 22 hirsute women during the administration of dexamethasone, ethinyl estradiol-medroxyprogesterone, or both. The response of plasma testosterone to the administration of adrenocorticotropic hormone (ACTH), human chorionic gonadotropin (HCG) and dexamethasone was measured before treatment in 16 patients, and six additional patients were treated without initial testing. Patients were treated with three month courses of each therapy, regardless of their test results. Results of short-term testing did not correlate with those of long-term treatment. Previously elevated testosterone levels were suppressed in 80 per cent of the patients treated with dexamethasone and in all the patients treated with ethinyl estradiol-medroxyprogesterone (EE-MP). Hirsutism diminished in a third of the patients treated with dexamethasone and in half of the patients treated with EE-MP. Acne diminished in half of the patients with either therapy. There was good correlation between normalization of plasma testosterone levels and clinical improvement. Normal plasma testosterone levels were maintained for several months after dexamethasone treatment was discontinued. Recommendations are given for the approach to diagnosis and treatment of the female patient with hirsutism.

Studies of endocrine function in "isolated" gonadotropin deficiency.

Six chromatin-negative young men, ages 16–24 yr, with hypogonadotropic hypogonadism were studied in an attempt to clarify and define the endocrine abnormalities responsible for this disorder. Five of the six patients had associated congenital anomalies involving the skeletal system or midline facial structures. Pituitary function studies showed normal thyroid and adrenal function. Two of 6 patients showed subnormal growth hormone responses to arginine infusion and insulin hypoglycemia, and 4 tested showed subnormal sleep mediated growth hormone release. Evaluation of pituitary-gonadal function showed normal prepubertal concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH) and testosterone. The plasma testosterone response to acute stimulation with human chorionic gonadotropin (hCG) (5000 units daily × 4 days) was subnormal in 3 of 6 patients; however, these 3 patients achieved normal plasma testosterone concentrations after more prolonged hCG administration (5000 units twice weekl...