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PubMed2002

Testosterone recovery following prolonged adjuvant androgen ablation for prostate carcinoma.

BACKGROUND: This study was conducted to describe the rate and completeness of the recovery of testosterone production following prolonged temporary androgen ablative therapy in men with prostate carcinoma undergoing curative radiation therapy. METHODS: Two-hundred and sixty-seven men treated with between 3 months and 3 years of adjuvant androgen ablation (AA) were followed at 6-month intervals following cessation of their androgen deprivation therapy. A comparative group of 518 men not undergoing AA were also followed. RESULTS: Drugs used included low dose cyproterone/stilboestrol (CPA/DES) in combination (56%) and 1 month depot (18%) and 3 month depot (25%) leutinizing hormone releasing hormone agonist (LHRHa). Seventy-nine percent of men in the current study recovered normal testosterone levels (10nmol/L), and 93% recovered levels of at least 5nmol/L. In comparison, men who had never received androgen ablative therapy showed a fall of testosterone, with 17% having sub-normal levels after 3 years. Median time to testosterone recovery was 10 months. Factors associated on multivariate analysis with delayed testosterone recovery included advanced age (P = 0.008), low pre-therapy testosterone (P = 0.04), and the use of 3 month LHRHa preparations as compared with CPA/DES (P = 0.002) or 1 month LHRHa preparations (P = 0.015). The duration of drug use was not significantly associated with time to testosterone recovery. CONCLUSIONS: Long-acting LHRHa preparations appear to have a more prolonged action than previously supposed. Most men treated for up to 2 years recover normal testosterone levels after cessation of adjuvant androgen ablation, and the limited data available in the current study on patients treated for 3 years also suggests most will recover.

Adenocarcinoma↗

PubMed1991

Effects of testosterone on a selected neuronal population within the preoptic sexually dimorphic nucleus of the Japanese quail.

The effects of testosterone on the volume and cytoarchitecture of the sexually dimorphic nucleus of the preoptic area (POM) were investigated in male and female Japanese quail. It was confirmed that castration decreases the POM volume in males and that, in gonadectomized birds of both sexes, testosterone increases this volume to values similar to those observed in intact sexually mature males. This suggests that the sex difference in POM volume results from a differential activation by T so that this brain morphological characteristic is not truly differentiated in the organizational sense. This conclusion was extended here by demonstrating that males exposed to a photoperiod simulating long days and that are known to have high plasma levels of testosterone have a larger POM than short-day males that have inactive testes. Detailed morphometric studies of POM neurons revealed a structural heterogeneity within the nucleus. A population of large neurons (cross-sectional area larger than 70-80 microns2) was well represented in the dorsolateral but was almost absent in the medial part of POM. This lateral population of neurons was sensitive to variations of testosterone levels in males but not in females. The cross-sectional area, diameter, and perimeter of the dorsolateral neurons were significantly increased in males exposed to high testosterone levels (intact birds exposed to long days or castrated birds treated with the steroid). These changes were not observed in the medial part of the nucleus. Interestingly, the size of the dorsolateral neurons was not affected by testosterone treatments in females. These results suggest that the swelling of neurons in the lateral POM of males might be responsible for the increase in total volume of the nucleus, which is observed in physiological situations associated with a high testosteronemia. In addition, the sensitivity to testosterone of the dorsolateral neurons in the POM appears to be sexually differentiated. This differential response to testosterone might represent a truly dimorphic feature in the organizational sense and additional studies manipulating the early steroid environment should be performed to test this possibility.

Animals↗

PubMed1997

Testosterone pharmacokinetics after application of an investigational transdermal system in hypogonadal men.

This open-label, randomized, placebo lead-in, three-treatment crossover study in 19 hypogonadal men (27-82 years of age) evaluated dose proportionality of serum testosterone concentrations with application of one or two investigational transdermal testosterone systems for application to the arm or torso. Testosterone in vivo kinetics profiles were determined using DeMonS, a recently developed numerical deconvolution method that estimates drug absorption at different time intervals and/or drug disposition model parameters. After application of the investigational transdermal systems, the mean serum testosterone, dihydrotestosterone, estradiol, and free testosterone concentrations were elevated to normal levels. Treatment allowed approximation of the normal circadian pattern of endogenous testosterone secretion, and the increase in serum testosterone concentrations was proportional to the surface area of systems applied. The investigational transdermal system provided effective testosterone replacement therapy as judged by pharmacokinetic parameters.

Administration, Cutaneous↗

PubMedDate not supplied

Influence of photoperiod, ambient temperature and melatonin on testosterone synthesis and release during reproductive maturation in male deer mice.

Four experiments were designed to investigate the influence of photoperiod and other environmental factors on androgen production and reproductive maturation in deer mice. Male prairie deer mice (Peromyscus maniculatus), born in a light/dark cycle of 6L:18D, either remained in this short photoperiod or were switched to a long day regimen of 16L:8D at weaning. In a cross-sectional experiment, the deer mice were killed between 3 and 8 weeks of age for measurement of serum testosterone concentration and reproductive organ weights. In a second experiment, blood was collected from each mouse at weekly intervals between 3 and 9 weeks of age. This repeated measures design was used to reduce the high variability in testosterone values observed in the first experiment. Reproductive organs were weighed at the termination of the experiment. Testosterone concentrations and reproductive organ weights were greater in males reared in the long photoperiod in both experiments. In a third experiment, the animals were housed under five different conditions to test the influence of high ambient temperature and melatonin as well as photoperiod. At 7 weeks of age, they received an injection of hCG or saline. More testosterone was released in deer mice reared in 16L:8D and 27 C than in those reared in short days (6L:18D) or those reared in high ambient temperature (35 C) or those treated with exogenous melatonin. One week later, animals were sacrificed. The single hCG treatment caused significant reversal of the suppression of accessory sex organ weights following melatonin, short days or 35 C temperature. In a fourth experiment, the additive influence of melatonin and 35 C temperature was tested. Animals treated with 35 C or both melatonin and 35 C had lower serum testosterone at 7 weeks of age, released less testosterone after hCG, and had smaller organ weights with or without hCG than long day controls. The influence of melatonin treatment and 35 C temperature appears to be additive for testicular weight and testosterone release after hCG. Thus, the attenuation of reproductive development that accompanied short days, melatonin treatment and high ambient temperature occurred via diminished testosterone secretion, which can be overcome at least in part by gonadotropin treatment.

Animals↗

PubMed2004

Exogenous testosterone prevents motoneuron atrophy induced by contralateral motoneuron depletion.

Gonadal steroids exhibit neuroprotective and neurotherapeutic effects. The lumbar spinal cord of male rats contains a highly androgen-sensitive population of motoneurons, the spinal nucleus of the bulbocavernosus (SNB), whose morphology and function are dependent on testosterone in adulthood. Unilateral SNB motoneuron depletion induces dendritic atrophy in contralateral SNB motoneurons, but this atrophy is reversed in previously castrated males treated with testosterone. In the present experiment we test the hypothesis that the morphology of SNB motoneurons is protected from atrophy after contralateral motoneuron depletion by exogenous testosterone alone (i.e., with no delay between castration and testosterone replacement). We unilaterally depleted SNB motoneurons by intramuscular injection of cholera toxin conjugated saporin. Simultaneously, some saporin-injected rats were castrated and immediately given replacement testosterone. Four weeks later, contralateral SNB motoneurons were labeled with cholera toxin conjugated HRP, soma sizes were measured, and dendritic arbors were reconstructed. Contralateral SNB motoneuron depletion induced somal atrophy and dendritic retraction, but testosterone treatment prevented both of these effects. Thus, the presence of high-normal levels of testosterone prevents motoneuron atrophy induced by contralateral motoneuron depletion. These data support a therapeutic role for testosterone in preventing atrophy induced by motoneuron injury.

Animals↗

PubMed2002

Association between prostate cancer and serum testosterone levels.

BACKGROUND: The purpose of the current study was to determine whether the presence of prostate cancer altered serum testosterone levels. METHODS: Initially, we evaluated both serum total and free testosterone levels in patients with either high-grade (n = 18) or moderate-grade (n = 146) prostate cancer, detected by prostate needle biopsies. Then both serum total and free testosterone levels, before and after prostatectomy, were compared in 79 of the 164 men with prostate cancer. RESULTS: In the first setting, serum total and free testosterone levels (307 +/- 24 ng/dl and 1.14 +/- 0.09 ng/dl) in patients with high-grade prostate cancer were significantly lower than those in patients with moderate-grade prostate cancer (452 +/- 12 ng/dl and 1.51 +/- 0.04 ng/dl) and those without prostate cancer (451 +/- 17 ng/dl and 1.55 +/- 0.06 ng/dl). After prostatectomy in 79 patients with prostate cancer, serum levels of both total and free testosterone (511 +/- 15 ng/dl and 1.78 +/- 0.05 ng/dl) were found significantly elevated when compared with their respective presurgical total and free testosterone levels (450 +/- 17 ng/dl and 1.60 +/- 0.06 ng/dl). CONCLUSION: Our findings show that serum total and free testosterone levels in patients with prostate cancer are altered, supporting the possibility that prostate cancer may inhibit serum testosterone levels.

Adult↗

PubMed2004

Neutralizing VEGF bioactivity with a soluble chimeric VEGF-receptor protein flt(1-3)IgG inhibits testosterone-stimulated prostate growth in castrated mice.

BACKGROUND: Recent studies show that testosterone-stimulated growth of the glandular tissue in the ventral prostate in adult castrated rats is preceded by increased epithelial VEGF synthesis, endothelial cell proliferation, vascular growth, and increased blood flow. These observations suggest that testosterone-stimulated prostate growth could be angiogenesis dependent, and that VEGF could play a central role in this process. METHODS: Adult male mice were castrated and after 1 week treated with testosterone and vehicle, or with testosterone and a soluble chimeric VEGF-receptor flt(1-3)IgG protein. RESULTS: Treatment with testosterone markedly increased endothelial cell proliferation, vascular volume, and organ weight in the ventral prostate lobe in the vehicle groups, but these responses were inhibited but not fully prevented by anti-VEGF treatment. The testosterone-stimulated increase in epithelial cell proliferation was unaffected by flt(1-3)IgG, but endothelial and epithelial cell apoptosis were increased in the anti-VEGF compared to the vehicle-treated groups. CONCLUSIONS: This study suggests that testosterone stimulates vascular growth in the ventral prostate lobe indirectly by increasing epithelial VEGF synthesis and that this is a necessary component in testosterone-stimulated prostate growth.

Animals↗

PubMed1982

Effect of inhibitors of RNA and protein synthesis on mitochondrial aspartate aminotransferase response to testosterone in rat ventral prostate.

The prostate gland is unusual in that it has a high content of citric acid compared with other soft tissues. The mechanism of citrate accumulation in prostate is unknown. One possibility is that aspartate aminotransferase (AAT) could supply an extra Krebs cycle source of oxaloacetate for citrate formation. Since testosterone regulates citrate production and secretion and strong transaminase activity exists in prostate, a relationship between AAT and citrate production could exist if testosterone also regulates AAT activity. To investigate this possibility, animals were castrated and given testosterone. After a total castration period of 72 hours, animals were sacrificed and mitochondrial AAT activity determined. Results revealed that castration decreased AAT activity and testosterone replacement stimulated activity. Neither castration nor testosterone affected malate dehydrogenase (MDH) activity. Both actinomycin D and cycloheximide blocked the testosterone stimulation of AAT activity. These studies indicate that testosterone may regulate AAT activity in rat ventral prostate. Furthermore, regulation may occur through testosterone stimulation of specific RNA and protein synthesis.

Animals↗

PubMed1994

Testosterone-induced masculinization of the rat levator ani muscle during puberty.

Previous study of the development of the levator ani muscle (LA) revealed that the sex difference in muscle fiber number is under the control of testosterone during the perinatal period. In this study, the development of the LA muscle was examined in both sexes to test the hypothesis that testosterone action determines a further sex difference at the onset of puberty. This period is of key importance because plasma testosterone concentration rises sharply between Postnatal Days 40 and 60 in the male, while in the female testosterone level stays very low. In the male, a transient increase in the satellite cell number occurs between Days 42 and 47, followed by a persistent myonuclei increase. Hence, when the pubertal process has been completed, the myonuclei number is increased by about 50%. Moreover, sexual dimorphism related to the muscle fiber width becomes more marked: before puberty (Day 30), the mean cross-sectional area of muscle fibers is 2-fold higher in males than in females, while between Days 30 and 78, a further hypertrophy is observed which leads to a mean cross-sectional area about 10-fold higher in the male. In the female, during the same period, there is neither satellite cell increase nor myonuclei increase and the fiber cross-sectional area remains constant. Treatment with testosterone before the onset of puberty induces a marked but transient satellite cell increase not only in male but also in female LA muscle as early as 3 days after the time of injection. This cell proliferation is followed by a subsequent increase in the myonuclei number. Results indicate that (1) the levator ani muscle in the male exhibits high sensitivity to testosterone during the pubertal process; during this period, sexual dimorphism related to fiber width and myonuclei number is emphasized; (2) the myonuclei increase is subsequent to the testosterone-induced satellite cell proliferation; and (3) the female LA muscle presents the same sensitivity to testosterone as the male. Hence, the female muscle does not acquire specific male characteristics, owing to the very low concentration of circulating androgens.

Animals↗

PubMed2000

Changes in the metabolic elimination profile of testosterone following exposure of the crustacean Daphnia magna to tributyltin.

The biocide tributyltin has been found to cause the development of pseudohermaphroditic conditions in some neogastropod species. These abnormalities of the reproductive system have adversely affected the fecundity of some field populations of gastropods, resulting in local population declines. Current evidence suggests that tributyltin elicits these effects by interfering with the biotransformation of testosterone to other steroid derivatives, resulting in an elevation in endogenous testosterone or some of its bioactive derivatives. The purpose of the present study was to determine whether tributyltin altered testosterone metabolism in daphnids (Daphnia magna), a species commonly used in ecotoxicology testing. Exposure of daphnids to 1.2 microg (tin)/L caused a general increase in the rate of elimination of oxido-reduced, hydroxylated, and glucose-conjugated derivatives of testosterone. However, tributyltin exposure had no significant effect on the rate of elimination of the glucose-conjugated forms of the various oxido-reduced and hydroxylated derivatives of testosterone. As a result, the percentage of the oxido-reduced and hydroxylated metabolites of testosterone eliminated as glucose conjugates decreased with increasing tributyltin exposure levels. These results demonstrate that tributyltin causes alterations in testosterone metabolism in daphnids that would result in an increase in the production of oxido-reduced derivatives. These products are preferentially retained in the tissues of daphnids and are variously androgenic in vertebrates. The increased production of oxido-reduced derivatives of testosterone may be mechanically responsible for the masculinizing effects of tributyltin in some species and suggests that daphnids may be a suitable surrogate for evaluating the potential of chemicals to elicit this form of toxicity.

Androstane-3,17-diol↗

PubMed2002

Monthly patterns of testosterone and behavior in prospective fathers.

The individual time patterns of salivary testosterone of adult healthy men, self-reported sexual behavior and their co-occurrence with regular weekly or monthly intervals were studied. Twenty-seven volunteer males (mean age 33 +/- 1 years) collected daily morning saliva over a period of 90 days. Evening questionnaires provided daily information on sexual activity. From the saliva, testosterone immunoreactive substances were determined using enzyme immunoassay. To detect events in which increases of testosterone were associated with sexual activity and at the same time controlling for regular internal patterns in men, data were analyzed using Theme software. First results indicated a varying number of complex nonrandom interaction patterns of testosterone with sexual activity, but also with weekly (i.e., Saturdays) and monthly intervals (i.e., 28-day full-moon intervals). The social context of the occurrence of specific pattern combinations was elaborated using parameters from the men's self-reported general life history profiles. Peak hormone levels occurred around weekends in the majority of the males. The 28-day monthly interval coincided with testosterone peaks only in those of the paired men who reported a current wish for children ("prospective fathers"), but not in unpaired men or in those who did not wish to have children with their current partner. Rather than representing a direct regular pattern of the male testosterone per se, the observed patterns suggest that men have the facultative potential to adjust their testosterone responses to their female partner's cycle. In line with the interactions between behavior and androgens observed in vertebrates in general, this study adds an example of the mutual character of hormone-behavior interactions and, thus, for the social context of testosterone patterns in human males.

Adult↗

PubMed1996

Neonatal phenobarbital-induced persistent alterations in plasma testosterone profiles and testicular function.

Daily sc injections of phenobarbital at anticonvulsant therapeutic doses for the rat (40 mg/kg) for the first 7 days of life resulted in below normal levels of serum testosterone from around birth to before puberty, normal levels during puberty and above normal levels of the androgen after puberty and in adulthood. Cluster analysis of the plasma testosterone secretory profiles obtained at 15-min intervals from phenobarbital-treated rats at 65 and 165 days of age revealed a significant increase in both the peak amplitudes and their durations resulting in a 100% increase in the amount of hormone secreted during the peak periods. In general, most of the rats (control and experimental) secreted testosterone as two large peaks, each 3 to 4 hr in duration, during the 10-hr lights-on collection period. In addition to permanently disrupting the ultradian profiles of plasma testosterone, neonatal exposure to the barbiturate altered testicular responsiveness to steroidogenic regulatory agents. That is, neonatal exposure to phenobarbital enhanced the responsiveness to exogenous hCG as measured by an above-normal increase in testosterone concentration. Moreover, phenobarbital-induced reductions in serum testosterone levels were delayed in adult rats neonatally exposed to the barbiturate. Whereas a single challenge dose of phenobarbital (1 or 10 mg/kg) reduced serum testosterone concentrations in control animals by almost 80% within 3 hr, a decline in serum androgen levels in the neonatally phenobarbital exposed males was not observed until 12 hr after the challenge dose. These results indicate that postpartum exposure to therapeutic levels of phenobarbital can permanently disrupt testosterone secretory profiles and alter pathways regulating testicular steroidogenesis.

Aging↗

PubMed1997

The effects of continuous testosterone exposure on spontaneous and cadmium-induced tumors in the male Fischer (F344/NCr) rat: loss of testicular response.

In the rodent testes, cadmium induces severe necrosis followed by chronic degeneration. Cadmium is also an effective testicular tumorigen, and a single dose produces a high incidence of Leydig cell tumors. The mechanism of tumor formation is unknown, but pituitary feedback, i.e., increased luteinizing hormone (LH) production due to low circulating androgen, has been implicated in causation of proliferative lesions within degenerate, hypofunctioning testes. Thus, the effects of androgen replacement on the testicular toxicity of cadmium in Fischer (F344/NCr) rats was studied. Groups (n = 50) of 10-week-old rats either received testosterone implants that approximate normal circulating levels in castrated rats or were left untreated. After 2 weeks of stabilization, rats were given either 20 micromol CdCl2/kg, s.c., weekly for the next 5 weeks (total dose 100 micromol/kg) or saline for a total of four treatment groups (control, testosterone alone, testosterone + cadmium, or cadmium alone). Portions of each group were killed either 10 weeks after initiation of cadmium exposure (n = 10), for assessment of endocrine function, or over the next 2 years (n = 40), for assessment of testicular neoplastic lesions. At 10 weeks, cadmium reduced circulating testosterone in nonimplanted rats by nearly 80% and induced a marked weight loss of the testes (>70%) and sex accessory glands (reflected in a 50% reduction in prostate mass). Testosterone implantation restored circulating testosterone levels in cadmium-treated rats and prevented Cd-induced weight loss of the sex accessory glands but not of the testes. Over 2 years, cadmium alone induced a >84% incidence of Leydig cell neoplasia and a >97% incidence of chronic degeneration, both significant increases over control rates (60 and 0%, respectively). Testosterone implantation abolished both cadmium-induced and spontaneously occurring Leydig cell tumors but had no effect on cadmium-induced chronic testicular degeneration. Thus cadmium-induced hypofunction of the testes, and subsequent loss of circulating testosterone, appears to be a critical aspect in cadmium induction of tumors in the rat testes.

Animals↗

PubMed1988

Effects of alcohol on aggressive behavior in squirrel monkeys: influence of testosterone and social context.

Social status and reproductive cycle determine the effects of acute, low doses of alcohol on the social behavior of squirrel monkeys. Alcohol produces biphasic effects on the behavior of dominant but not subordinate monkeys, and only during the mating season. The change in alcohol sensitivity measured in dominant monkeys coincides with changes in plasma testosterone levels. In order to directly study the interaction between alcohol, testosterone and aggressive behavior, testosterone propionate (TP, 25 mg/kg/day, SC) was administered to either dominant or subordinate male monkeys belonging to four separate groups, resulting in significantly elevated plasma levels of testosterone (i.e., 905 +/- 43 ng/ml in subordinates; 171 +/- 19 ng/ml in dominants). Two to three weeks after the beginning of testosterone treatment, the monkeys were administered doses of alcohol (0.1-1.0 g/kg). The behavior of subordinate monkeys was unaffected by TP treatment (even after the dominant monkey from each colony was removed and housed separately for 6 weeks). Testosterone treatment altered the sensitivity of subordinate monkeys to alcohol. Low doses of alcohol increased the frequency of threats, grasps, and displacements exhibited by subordinate monkeys with exogenously elevated testosterone. Daily administration of TP to dominant monkeys during the non-mating season did not affect the behavior of the treated animals in the group, although the body weight of TP-treated monkeys was similar to that measured during the mating season. Low doses of alcohol increased the frequency of threats, grasps, and displacements in dominant monkeys maintained on TP. We also tested the role of social context in maintaining high levels of plasma testosterone, and alcohol sensitivity in dominant monkeys.(ABSTRACT TRUNCATED AT 250 WORDS)

Aggression↗

PubMed1991

A mechanism for testosterone modulation of alpha-1 adrenergic receptor expression in the DDT1 MF-2 smooth muscle myocyte.

Previous reports have confirmed that steroid hormones modulate the expression of adrenergic receptors on the surface of smooth muscle myocytes. The present study was undertaken to evaluate the mechanism by which testosterone modulates alpha-1 adrenergic receptor expression in the DDT1 MF-2 transformed smooth muscle cell. Utilizing 3H-prazosin radioligand binding studies, alpha-1 adrenergic receptors were noted to increase more than 2 fold in response to incubation with 10(-8)M testosterone for 96 hours. Dihydrotestosterone similarly stimulated a significant increase in alpha-1 receptors; whereas, estradiol and hydrocortisone appeared to suppress the expression of this receptor in DDT myocytes. The testosterone effect was dose related with a maximal response observed in response to 10(-7)M testosterone at both 48 and 96 hours. Kinetic experiments utilizing 10(-8)M testosterone demonstrated a peak effect on alpha-1 receptor expression at 96 hours, and maintenance of the effect for at least 168 hours (7 days). The testosterone effect was completely prevented at both 48 and 96 hours by inhibition of transcription with actinomycin-D, or inhibition of translation with cycloheximide. Consistent with the receptor binding studies, RNA blotting studies have demonstrated maximal alpha-1 receptor mRNA levels at 48-96 hours of testosterone stimulation. In conclusion, these in vitro experiments have confirmed the physiologic concentrations of testosterone stimulate the increased expression of alpha-1 receptors in the DDT1 MF-2 myocyte after a delay of 48-96 hours; and that this effect appears to be mediated by transcription, translation, and synthesis of new proteins in these genital tract myocytes.

Animals↗

PubMed1975

Excretion of urinary testosterone in Klinefelter's syndrome.

The urinary testosterone excretion in 55 patients with Klinefelter's syndrome was determined by gas-chromatographic methods. The mean testosterone level in the group of Klinefelter patients was significantly decreased (15.7 mug/24 hrs) compared with the excretion by 30 normal men (44.1 mug/24 hrs). An age dependency of excretion levles was not obvious in chromatin-positive men when compared to healthy subjects. A correlation between testosterone excretion and configuration types seemed to be probable by reason of observations and statistical values. Average testosterone excretion increased with increasing normalization of body proportions. Gynecomastia was noticed in 56% of those examined. With increasing severity of gynecomastia the mean testosterone levels decreased. A correlation between beard and body hair, which was decreased in almost all subjects, and testosterone excreiton was not visible. With diminishing mean testosterone excretion an increase of osteoporosis seemed to be probable. A statistically significant difference was found when comparing patients who never had ejaculations with those who had regular libido and ejaculations. Klinefelter patients who had not succeeded in completing school or an occupational education showed a significantly decreased testosterone level as compared with others who had a profession.

Adult↗

PubMed1992

Testosterone and FSH have independent, synergistic and stage-dependent effects upon spermatogenesis in the rat testis.

Adult rats were hypophysectomized and treated with ethane dimethanesulphonate (EDS) selectively to eliminate the Leydig cells in the testis. By removing the source of endogenous gonadotrophins and androgens, the subsequent effects on the seminiferous epithelium were studied after 20 days of treatment with vehicle, or FSH (2 x 50 micrograms/day) or a low dose of testosterone (0.6 mg testosterone esters every 3rd day) alone or in combination. Compared to vehicle-treated hypophysectomized rats with Leydig cells, testis weight in saline-treated hypophysectomized rats treated with EDS declined by 50%, spermatogenesis was disrupted severely and only 18% of the tubules contained spermatids, these being confined to stages I-VI of the spermatogenic cycle. Treatment with either FSH or testosterone esters alone significantly (P less than 0.01) increased testis weight compared to vehicle-treated hypophysectomized rats treated with EDS and 40% of tubules contained spermatids either at stages I-VI after FSH, or at all stages I-XIV after testosterone treatment. Treatment with FSH and testosterone esters together maintained testis weights approximately 20% above vehicle-treated hypophysectomized controls; over 70% of the seminiferous tubules contained spermatids and there was a marked stimulation of spermatogenesis at all stages of the spermatogenic cycle. The results suggest, that in the absence of the pituitary gland and the Leydig cells, FSH alone partially supports spermatogenesis up to the development of round spermatids whereas testosterone is capable of maintaining spermatid development at all 14 stages of the cycle. When FSH and testosterone were administered in combination, the effects upon spermatogenesis were far greater than the response expected if their individual effects were simply additive. It is therefore concluded that FSH may play a role in normal spermatogenesis and that this role is essentially that of augmenting the response of the testis to testosterone. The biochemical mechanisms via which this might occur are discussed and hypophysectomized rats treated with EDS used in the present studies should provide a useful approach for their identification.

Animals↗

PubMed1993

Urinary testosterone as a marker of risk of recurrence in operable breast cancer.

We investigated the role of urinary testosterone levels as a marker of risk of recurrent disease in 113 operable breast cancer patients (70 premenopausal, 43 postmenopausal). Twenty-four-hour urine collections for testosterone measurement were obtained before surgical treatment, between 20-40 days thereafter, and then every 6 months for 5 years. The cutoff values to separate 'high testosterone (A+)' from 'normal testosterone (A-)' were 8.0 micrograms/24 h in premenopause and 4.9 micrograms/24 h in postmenopause. Urinary testosterone levels were considered high when they exceeded the cutoff value in at least 2 of the first 3 measurements (pretreatment, post-treatment, 6 months) of each patient. According to the aforementioned criterion, 33 patients (29.2%) had high testosterone levels, which were associated to axillary node involvement in 16 patients. Thirteen of the latter relapsed during the 5-year follow-up period (5/7 in premenopause, 8/9 in postmenopause). Relapse-free survival (RFS) curves were drawn only for node-positive patients owning to the small number of recurrences observed in the node-negative group. In premenopausal node-positive patients, RFS was significantly different for patients presenting high and normal urinary testosterone levels (77% vs 28%, respectively; logrank test, p < 0.006). In postmenopausal node-positive patients, RFS was also different between the two groups (54% vs 11% in 'high' and 'normal' excretors, respectively) but the difference was not statistically significant. The present findings suggest that urinary testosterone is a prognostic indicator of early breast cancer recurrence in node-positive patients.

Adult↗