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PubMed2006

Testosterone treatments: why, when, and how?

Testosterone treatment is controversial for men and even more so for women. Although long-term outcome data are not available, prescriptions for testosterone are becoming more common. Testosterone is used primarily to treat symptoms of sexual dysfunction in men and women and hot flashes in women. Potential benefits include improved libido, increased bone mass, and increased sense of well-being. In individuals with human immunodeficiency virus infection or other chronic diseases, testosterone has been shown to improve mood and energy levels, even in patients with normal testosterone levels. Testosterone can be administered by injection, patch, topical gel, pill, or implant. Side effects in men include polycythemia and acne. Side effects in women include acne, hepatotoxicity, and virilization and usually only occur when testosterone is used in supraphysiologic doses. Long-term studies of the effects of testosterone on prostate cancer, breast cancer, and heart disease have not been completed. Mammograms and monitoring of prostate-specific antigen, hematocrit, and lipid levels are recommended for patients taking testosterone.

Androgens↗

PubMed1991

Chronic testosterone treatment impairs vocal learning in male zebra finches during a restricted period of development.

To study the effects of chronic exposure to testosterone on song behavior development, we administered various amounts of testosterone to juvenile male zebra finches during different periods of song acquisition. We report that testosterone exposure during development profoundly impairs song learning in juvenile males. The effects of the hormone do not seem to be dose related but vary according to the period of life during which testosterone is administered. Exposure to testosterone starting before day 40 and lasting until adulthood decreases the number of syllables in the birds' repertoire and increases the number of phrases per bout of singing. In addition to these changes in the "syntactical" features of song, acoustic abnormalities are also present in the song syllables of males that begin to receive testosterone during the first month of life. Administration of testosterone during only the first 3 weeks of life produces acoustic abnormalities but has no effect on repertoire size or bout structure. Birds receiving the hormone between 20 and 40 d of age develop both acoustic abnormalities and a reduced repertoire size, but their song bouts contain a normal number of song phrases. Exposure to testosterone starting on day 40 produce no behavioral abnormalities. These results indicate that normal song development requires a period of low levels of circulating testosterone and also provide support for the idea that vocal learning entails a progressive sequence of events.

Aging↗

PubMed1990

Inhibitory effect of testosterone on gap junctional intercellular communication of human transitional cell carcinoma cell lines.

A dye transfer method was applied to investigate the effect of testosterone on gap junctional intercellular communication (IC) of two kinds of human transitional cell carcinoma cell lines, JTC-30 and JTC-32. When JTC-30 cells were cultured with testosterone at nontoxic concentrations (17-69 microM), a dose and time dependent inhibition of dye transfer was observed. More than 90% inhibition occurred after exposure to 69 microM testosterone for 96 h. The inhibition was reversed rapidly after testosterone deprivation. Similar results were obtained with JTC-32 cells. 17 beta-Estradiol showed no inhibitory effect on IC of both transitional cell carcinoma cell lines even at toxic levels. Testosterone exhibited no inhibitory effect on IC of human fibroblasts. The inhibitory effect of 5 alpha-dihydrotestosterone was almost similar to that of testosterone. At concentrations examined, cyproterone acetate influenced neither dye transfer nor the inhibitory effect of testosterone, suggesting a mechanism of testosterone action different from that of the known receptor system. Since blockage of IC has been indicated as one reliable evidence for tumor promotion, current results suggest that testosterone is a possible endogenous promoter of the bladder carcinoma and may therefore possibly play a role on the sexually different incidence of bladder carcinoma.

Carcinoma, Transitional Cell↗

PubMedDate not supplied

Testosterone treatment of men with alcoholic cirrhosis: a double-blind study. The Copenhagen Study Group for Liver Diseases.

A double-blind, placebo-controlled multicenter trial was conducted to determine the efficacy of oral testosterone treatment (200 mg three times daily) in men with alcoholic cirrhosis. By skewed randomization (3:2), 134 patients received testosterone and 87 placebo. Patients were followed from 8 to 62 months (median = 28 months). In the testosterone group, 33 patients died (25%; 95% confidence limits = 18 to 33%) as compared to 18 (21%; 95% confidence limits = 13 to 31%) in the placebo group. Taking age and significant prognostic variables into consideration, this corresponds with a relative mortality risk of 1.17 (95% confidence limits = 0.65 to 2.15) in the testosterone group vs. the placebo group. Testosterone treatment did not significantly affect liver biochemistry, prevalence of complications to cirrhosis or causes of death. Patients treated with testosterone developed significantly (p less than 0.05) higher serum testosterone and blood hemoglobin concentrations and significantly (p less than 0.05) lower plasma IgM concentrations as compared to the placebo group. The prevalence of gynecomastia decreased significantly (p less than 0.05) in the testosterone group as compared to the placebo group. We conclude that oral testosterone treatment has no beneficial effect on survival and liver biochemistry in men with alcoholic cirrhosis, and adverse effects cannot be excluded.

Adult↗

PubMed1985

[Influence of the concentration of precursors on the biosynthesis of testosterone by the chick embryo testis].

The aim of this study was to determine whether substrate concentration was of crucial importance in the formation of testosterone by the chick embryo testis. Testes from 15 to 18-day old chick embryos were cultured in medium 199 with dehydroepiandrosterone 1, 2, 6, 7-3H or androstenedione-4-14C added at different concentrations. Testosterone was identified and measured by crystallization to constant specific activity or by gas chromatography-mass spectrometry. The formation of testosterone could not be demonstrated at a substrate concentration of 76 nM. Concentrations in the micromolar range yielded measurable quantities of testosterone which increased to about 10% of the added substrate when the concentration was 70 microM. However, the capacity to form testosterone was shared by other organs such as the ovary or the mesonephros. These results should settle definitively the question concerning the formation of testosterone by the chick embryo testis. When exposed to high substrate concentrations, the testis can form testosterone, but under physiological conditions there is no such testosterone formation. This conclusion is in agreement with the absence of any physiological role of testosterone in the chick embryo.

Androstenedione↗

PubMed1979

Effect of sexual experience, location, malnutrition, and repeated sampling on concentrations of testosterone in blood plasma of Gallus domesticus roosters.

Five studies were conducted with mature White Leghorn roosters to study variables associated with concentrations of testosterone in blood sampled from a wing vein. Testosterone in blood plasma was unchanged 15, 30, or 45 min after collection of semen artificially whether or not roosters were trained for collection of semen. Likewise, cohabitation with hens for 7 to 8 hr was without effect. However, trained roosters had higher (P less than .05) plasma testosterone concentrations after 7 to 8 hr in a new location than untrained roosters. Furthermore, both groups in the new location had higher testosterone concentrations than the controls not translocated. Plasma testosterone was decreased (P less than .01) about 50% within 2 weeks by feeding a diet low in crude protein (2%) which decreased feed intake 33% and caused weight loss; those fed 12% crude proteins were unchanged. Variations in concentrations of testosterone among sequential samples of blood collected at 45 min intervals for 3 hr indicated random pulsatile releases of testosterone as reported for mammals. Sequential sampling at 15 min intervals for 1 to 2 hr revealed that the testosterone increases (up to 10 ng/ml) lasted for about 1 hr and that the returns to basal concentrations required about 1 to 1.5 hr. The interval between pulsatile releases may be as long as 3 hr in some roosters. These results indicate that roosters have spontaneous and pulsatile releases of testosterone as expected, because roosters release luteinizing hormone episodically during both light and dark cycles of the day.

Animals↗

PubMed1983

Elevated free testosterone levels in women with acne.

Female patients with varying grades of acne were examined to determine whether free testosterone levels were a more sensitive indicator of hyperandrogenism than total testosterone values. Of 24 women with acne studied, four were found to have elevated total testosterone levels, whereas 11 had elevated free testosterone levels. Twenty-four age-matched female control subjects without acne, hirsutism, or irregular menstrual cycles all had normal free and total testosterone values. The mean concentration of free testosterone in the patients with acne was 1.035 ng/dL, while in the control subjects it was 0.54 ng/dL. Other than hirsutism in three patients with acne with elevated free testosterone levels, there were no morphologic clues identified to determine which patients with acne are more likely to have abnormal free testosterone levels. The free testosterone level did not correlate with the type, distribution, or severity of the acne present in the patients.

Acne Vulgaris↗

PubMed1984

Effects of ethanol and enzyme-inducing agents on the monooxygenation of testosterone and xenobiotics in rat liver microsomes.

The simultaneous production of multiple testosterone oxidation products in hepatic microsomal incubations was monitored after injection of a post-trichloroacetic acid supernatant directly onto a reverse-phase high-performance liquid chromatography column. Twelve testosterone-derived metabolite peaks were detected on the chromatogram and the relative proportions of these products were changed distinctively after pretreatment of rats with phenobarbitone, beta-naphthoflavone and pregnenolone 16 alpha-carbonitrile. Chronic ingestion of ethanol (35% of total energy in a nutritionally adequate liquid diet) modified oxidative testosterone metabolism differently from the other enzyme inducers and reduced plasma testosterone levels relative to values in animals pair-fed the control liquid diet. Modifications to the metabolism of xenobiotic substrates after ethanol treatment confirmed that ethanol had changed the types and amounts of cytochrome P-450 in microsomal preparations. Differences in testosterone metabolite profiles between control and ethanol-treated male and female rats suggested that these results were not a consequence of ethanol-induced decreases in circulating levels of testosterone influencing the constitutive cytochrome P-450 isoenzymes. These experiments confirm that analysis of testosterone metabolites by high-performance liquid chromatography is a useful approach for detecting and discriminating between the metabolic capacity of cytochrome P-450 in microsomal preparations. In addition, increases in the rates of some testosterone hydroxylations after ethanol ingestion, in conjunction with known effects of alcohol on testosterone homeostasis, may contribute to the hypogonadism seen in male chronic alcoholics.

Androstenedione↗

PubMedDate not supplied

Testosterone regulation of proto-oncogene c-myc expression in primary Sertoli cell cultures from prepubertal rats.

The expression of c-myc has been associated with cell proliferation through changes of nuclear function. To evaluate the possibility that the proto-oncogene c-myc plays a role in testosterone-dependent gene regulation, the effects of testosterone on the expression of c-myc have been investigated in primary Sertoli cell cultures. Testosterone increased c-myc mRNA levels, with maximal stimulation reached in 16 hours. The induction of c-myc mRNA was dependent on the concentration of testosterone. Testosterone-induced c-myc mRNA levels were also increased in cells after addition of cycloheximide but reduced by actinomycin-D pretreatment. Even in the absence of hormone in culture medium, c-myc mRNA was clearly detectable in Sertoli cells from 8-day-old rats but hardly detectable in cells from 14 and 28 days of age. Testosterone stimulated c-myc mRNA expression in the Sertoli cells from only 8-/and 14-day-old rats. These results suggest that testosterone induces c-myc mRNA levels in the primary Sertoli cells from prepubertal rats, and then transient expression of c-myc may be responsible for some of the regulatory roles of testosterone-dependent genes in the Sertoli cells. The biological significance of testosterone-dependent c-myc induction is not known.

Animals↗

PubMed1995

Illness stage, concurrent medications, and other correlates of low testosterone in men with HIV illness.

Our objective was to assess whether illness stage, markers of illness progression, and use of medications believed to lower testosterone are associated with low serum testosterone in HIV+ men. Data were available for 234 HIV+ men screened for eligibility for a study of testosterone replacement therapy and/or an antidepressant trial. A screening interview was used to elicit demographic and medical information. Blood was drawn to measure markers of immunodeficiency and serum testosterone. Thirty-eight percent of the sample had testosterone levels below the normal range. Low testosterone was associated with lower CD4 cell count, later stage of illness, use of megestrol, and older age. Regression analysis showed that only age and use of such medications as megestrol were significant predictors of low testosterone. Given the prevalence of low testosterone in HIV+ men and its link to sexual dysfunction, more research is needed on treatments aimed at correcting or compensating for this hormonal deficiency as well as the study of the impact of such medications as megestrol on testosterone levels in older men.

Adult↗

PubMed1994

[Effects of cutaneous mechanical stimulation on plasma corticosterone, luteinizing hormone (LH), and testosterone levels in anesthetized male rats].

Effects of cutaneous mechanical stimulation on plasma corticosterone, luteinizing hormone (LH), and testosterone levels were examined in young adult (13-22 weeks old) and aged (24-27 months old) male Wistar rats anesthetized with pentobarbital. Under the resting condition without somatic sensory stimulation, neither plasma corticosterone measured every 15 min between 1430 h and 1630 h nor plasma LH and testosterone measured every 30 min between 1400 h and 1730 h revealed any significant fluctuations. Nociceptive mechanical stimulation of both hindpaws by pinching for 10 min significantly increased plasma corticosterone, LH, and testosterone, in young adult rats. Plasma corticosterone was increased for one hour following the stimulation. On the other hand, plasma LH was increased 30 and 60 min after the cessation of stimulation, while plasma testosterone was increased 60-150 min after stimulation. However, innocuous mechanical stimulation of both hindlimbs by brushing for 10 min did not significantly change either plasma corticosterone, LH, or testosterone. These findings indicate that, nociceptive information from skin lead to the increased secretion of corticosterone from the adrenal cortex and the increased secretion of LH from the anterior pituitary, resulting in an increase in testosterone secretion from the testes into the plasma, after emotional factors are eliminated by anesthetizing the subjects. In aged rats, the same nociceptive mechanical stimulation by pinching significantly increased the plasma corticosterone levels. The magnitude and time-course of the response in aged rats were equivalent to those in young adult rats. On the other hand, in aged rats, neither plasma LH nor testosterone levels were changed by the same nociceptive mechanical stimulation. This is in sharp contrast to the increase in both plasma LH and testosterone caused by the stimulation of young adult rats. These findings indicate a functional dissociation induced by aging between the secretory responses of the anterior pituitary, testes on the one hand and the adrenal cortex on the other hand, to nociceptive somatic sensory stimulation. Aging does not alter corticosterone release from the adrenal cortex to nociceptive somatic sensory stimulation, but LH secretion from the anterior pituitary and testosterone secretion from the testes to nociceptive somatic sensory stimulation are subject to dysfunction with aging.

Aging↗

PubMed1996

Salivary testosterone levels in male adolescents with cystic fibrosis.

PURPOSE: Salivary testosterone concentrations have been used for monitoring testosterone levels in male adolescents and have been found to correlate closely with serum values. Data are lacking on such measurements in male adolescents with cystic fibrosis (CF), in which salivary gland abnormalities are commonly seen. Delayed sexual maturation occurs in many patients with CF, particularly those with severe disease. We examined the usefulness of salivary testosterone collection and measurement in male adolescents with CF. METHODS: Forty boys with CF and 35 healthy control boys participated in the study. All boys were Tanner staged and had serum and salivary testosterone concentrations measured. Testosterone assays were performed using standard radioimmunoassay techniques. RESULTS: The boys with CF were slight older, lighter in body weight, and shorter. Serum and salivary testosterone concentrations were lower in the CF group than in the control group. A significant correlation was found between serum and salivary testosterone levels for boys with CF (r = .84) and for the control boys (r = .86). Mean salivary testosterone increased as age progressed and as Tanner stage advanced. CONCLUSIONS: These results demonstrate that salivary testosterone measurements correlate well with serum values in male adolescents with CF and can be used in the monitoring of pubertal status.

Adolescent↗

PubMed1996

Occult prostate cancer in men with low serum testosterone levels.

OBJECTIVE: To determine the prevalence of occult prostate cancer in men with low serum total testosterone or free testosterone levels. DESIGN: Retrospective analysis of a consecutive series of men. SETTING: Academic teaching hospital. PATIENTS: Seventy-seven men with low total testosterone or free testosterone levels, with normal results of digital rectal examination and prostate-specific antigen (PSA) levels of 4.0 ng/mL or less. The mean age was 58 years. INTERVENTIONS: Sextant prostate needle biopsies with ultrasound guidance. MAIN OUTCOME MEASURES: Results of prostate needle biopsies, transrectal ultrasound, prostate volume, PSA level, PSA density, total and free testosterone levels. RESULTS: Prostate cancer was identified in 14% (11/77) of the entire group and in 10 men (29%) aged 60 years or older. The median age for men with cancer was 64 years. Histologic examination showed Gleason scores of 6 or 7 for all cancers. No significant differences were noted between the cancer and benign groups with regard to PSA level, PSA density, prostate volume, total testosterone level, or free testosterone level. CONCLUSIONS: A high prevalence of biopsy-detectable prostate cancer was identified in men with low total or free testosterone levels despite normal PSA levels and results of digital rectal examination. These data suggest that (1) digital rectal examination and PSA levels are insensitive indicators of prostate cancer in men with low total or free testosterone levels, and (2) PSA levels may be altered by naturally occurring reductions in serum androgen levels.

Adult↗

PubMed1998

Effects of testosterone replacement on HDL subfractions and apolipoprotein A-I containing lipoproteins.

OBJECTIVES: Gonadal steroids are important regulators of lipoprotein metabolism. The aims of this study were to determine the effects of a minimum effective dose of testosterone replacement on high density lipoprotein (HDL) subfractions and apolipoprotein (apo) A-I containing particles (lipoprotein (Lp)A-I) and LpA-I:A-II) in hypogonadal men with primary testicular failure and to investigate the underlying mechanisms of these changes. MEASUREMENTS: Eleven Chinese hypogonadal men were started on testosterone enanthate 250 mg intramuscularly at 4-weekly intervals. HDL was subfractionated by density gradient ultracentrifugation and LpA-I was analysed by electro-immunodiffusion after 3, 6 and 12 weeks of treatment. Plasma cholesteryl ester transfer protein (CETP) activity and lipolytic enzymes activities in post-heparin plasma were measured to determine the mechanisms underlying testosterone-induced changes in HDL. RESULTS: The dosage of testosterone enanthate used in the present study resulted in suboptimal trough testosterone levels. No changes were seen in plasma total cholesterol, triglyceride, low density lipoprotein cholesterol (LDL-C,) apo B and apo(a) after 12 weeks. There was a drop in HDL3-C compared to baseline (0.82 +/- 0.17 mmol/l vs. 0.93 +/- 0.13, P < 0.01) whereas a small but significant increase was seen in HDL2-C (0.21 +/- 0.13 mmol/l vs. 0.11 +/- 0.09, P < 0.05). Plasma apo A-I decreased after treatment (1.34 +/- 0.25 g/l vs. 1.50 +/- 0.29, P < 0.01), due to a reduction in LpA-I:A-II particles (0.86 +/- 0.18 g/l vs. 0.99 +/- 0.24, P < 0.01). No changes were observed in the levels of LpA-I particles. No significant changes were seen in plasma CETP and lipoprotein lipase activities after testosterone replacement but there was a transient increase in hepatic lipase (HL) activity at weeks 3 and 6. The decrease in HDL correlated with the increase in HL activity (r = 0.62, P < 0.05). CONCLUSIONS: Testosterone replacement in the form of parenteral testosterone ester given 4-weekly, although unphysiological, was not associated with unfavourable changes in lipid profiles. The reduction in HDL was mainly in HDL3-C and in LpA-I:A-II particles and not in the more anti-atherogenic HDL2 and LpA-I particles. The changes in HDL subclasses were mainly mediated through the effect of testosterone on hepatic lipase activity.

Adult↗

PubMed1997

A zinc based self setting ceramic bone substitute for local delivery of testosterone.

Testosterone has been shown to stimulate bone healing. However, large doses of testosterone are associated with liver damage and prostate enlargement. Continuous release of testosterone at the traumatized bone site could enhance healing without inducing systemic side effects. In this investigation a self-setting zinc sulfate calcium phosphate (ZSCAP) ceramic with and without testosterone was used to fill experimentally induced bone defects in rats. Each treatment group consisted of six albino, Holtzman rats. Groups I and II consisted of non-operated and sham-operated animals. Rats in Group III, IV, V, and VI were implanted with ZSCAP particulate ceramic powders (63-75 microns) containing 0.0, 0.5, 1.0, or 1.5 mg testosterone in a 2.3 mm defect in the femur of each rat. Radiographic and morphologic examination of the implant site at four, eight, and twelve weeks post surgery showed integration of the implant in the femur of each rat. Serum testosterone of all rats was assayed at four, eight, and twelve weeks post surgery. Differences in the serum testosterone levels of rats in the six groups were not significant. Results of this study suggest that a ZSCAP-testosterone composite can be used to repair traumatized bone without increasing the levels of testosterone in the systemic circulation.

Animals↗

PubMed1981

Detection of estrus with cows administered testosterone via injections and/or silastic implants.

Over a three year period 8 cows and 2 heifers were administered testosterone via injections and/or silastic implants. During and subsequent to treatments, blood samples were collected for determination of testosterone and cows were observed for male sex behavior. Male sex behavior was induced by administering 200 mg of testosterone propionate every other day for 20 days, and once induced, male sex behavior was maintained by injections of 200 mg of testosterone propionate every 10 days or by two 15 cm silastic implants containing testosterone propionate. Male sex behavior was also induced and maintained by administering an injection of testosterone enanthate (1 gm) and testosterone propionate (200 mg) and two 15 cm silastic implants containing testosterone propionate at the same time. Cows which are administered testosterone in this manner detected 94% of 231 females that were in estrus 342 times.

Journal Article↗

PubMed1983

Induction of male sex behavior in pony mares with testosterone propionate.

Two pony mares were administered 150 mg of testosterone propionate every other day for 20 days (ten injections) and every ten days there-after. An additional two mares and one stallion were not treated and served as controls. Testosterone propionate was dissolved in absolute ethanol and administered subcutaneously. Sex behavior tests were conducted 26 and 40 days after the first injection. Control mares exhibited very little male sex behavior. Both testosterone propionatetreated mares, however, exhibited mounting, sniffing, flehmen, biting and vocalization behavior in the presence of an estrous mare. The testosterone propionate-treated mares mounted and bit estrous mares more frequently than the stallion but exhibited less sniffing, flehmen and vocalization behavior in the presence of an estrous mare than the stallion. Testosterone propionate-treated mares and the stallion mounted an estrous mare 23.3 +/- 9.7 seconds and 172.5 +/- 22.5 seconds, respectively, after being introduced into the pen. Mares in estrus were mounted by the testosterone propionate-treated mares and the stallion an average of 4.0 +/- 1.3 and 1.0 +/- 0 times, respectively, during a ten-minute test. None of the non-estrous mares was ever mounted by the testosterone propionate-treated mares. In summary, testosterone propionate induced male sex behavior in intact mares and the testosterone propionate-treated mares effectively detected estrous mares.

Journal Article↗

PubMed1984

Variation in testosterone production among boards and its relationship to sexual interest and breeding performance.

Variation in ability to produce testosterone in response to both GnRH and ACTH administration and quatitative relationships between GnRH-stimulated testosterone levels, ACTH-stimulated testosterone levels, sexual interest and breeding performance were assessed in a group of 31 Duroc boars (115.4 +/- 2.5 kg body weight and 212.2 +/- 3.0 days of age). Mean area beneath the testosterone response curve increased (P<0.01) after GnRH and ACTH but the magnitude of response was variable among boars. Post-GnRH testosterone area varied from 7.44 to 50.86 ng/ml X h with a CV = 52.41% while post-ACTH testosterone area varied from 4.99 to 28.78 ng/ml X h with a CV = 45.46%. Mean sexual interest and mean breeding performance scores were correlated (r = 0.67, P<0.01); however, correlations of either variable with testosterone areas were low and nonsignificant. These results indicate that the testosterone-producing ability of boars of similar age and breeding is highly variable and suggest that peripheral testosterone concentrations may not be good indicators of either libido or breeding performance.

Journal Article↗